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VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS
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Volume 1 | Issue 4 | July 2019
Circulation: Quarterly | All-India | e-Copy format
CHIEF EDITOR
Dr. Ranga Reddy
EDITOR
Dr. T V Rao
EDITOR & CONCEPT
Dr. Dhruv Mamtora
TEAM MEMBER
Sister Solbymol
SPECIAL EDITION ON MYCOBACTERIOLOGY
newsletter
INFECTION CONTROL TRENDS
VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS
2
Respected Infection Preventionist,
Hope earlier three editions of ICT had been some help to your IPC practice.
Editorial team and eminent authors have put in their best efforts to bring out yet another thematic edition
information and practical advice to deal with the ancient infectious disease TB.
WHO has called member nations to aggressively implement “END TB” program with an objective to end Global TB
epidemic by 2030. Prime Minister Modi has gone one step ahead and pledged at “Global Stop TB Summit” to eradicate
TB in India by 2025!!
TB is the top infectious killer worldwide TB is also the leading cause of deaths among people with HIV & a major
cause of antimicrobial resistance related death. The ancient disease has killed almost 200 crore people in last 200 years.
The emergence of Drug Resistant TB is becoming a major threat to global health security causing major economic costs
to individuals and nations.
As per WHO: TB treatment saved 5,4 crores lives globally between 2000 and 2017. Globally, the treatment success
rate for people newly diagnosed with TB was 82% in 2016. But one major problem for India is poor reporting of both
cases and their treatment. “Economist Intelligence” has estimated, India is losing USD 7,3 billion (730 crores) in PPP
terms due to deaths and work absence from TB which will have sizeable impact on GDP.
WHO & GOI initiatives and proclamations are laudable. But to make them real, several steps to be taken. Early
diagnosis of tuberculosis, Treatment of all people with tuberculosis, Preventive treatment of persons at high risk, and
vaccination against tuberculosis, Political commitment with adequate resources for tuberculosis care and prevention,
Engagement of communities, civil society organizations, and public and private care providers, quality and rational use
of medicines, and infection control are success mantra for WHO End TB program.
Ending the global TB epidemic is feasible with dramatic decline in TB deaths and cases, and elimination of
economic and social burden of TB. Failure to do so will carry serious individual and global public health consequences.
We, as Infection Preventionists have major role to play in “END TB” strategy.
Hope you will find this edition too valuable tool to deal with ever increasing infectious disease burden.
With this issue we complete one Golden Year. We thank all stakeholders for their part in this stupendous success.
Sincere appreciation goes to Dr Dhruv who has taken huge burden on himself to bring all four editions in time. To further
improve the standards and stay current, we shall make changes to our content delivery and design. Our editorial team
also be reconfigured to get new perspectives. Your suggestions, proposals and ideas are most welcome.
Regards,
Editorial Team,
Infection Control Trends,
E-Newsletter.
FOREWORD
VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS
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EDITORIAL TEAM
Dr. T.V. Rao is a former Professor of Microbiology from the Andhra Medical College, Visakhapatnam
(Andhra Pradesh, India). His experiences in Zambia showed him how people lose their lives to infections
and how the lack of resources was a great challenge that practically forced patients to be treated blindly.
His association with scientific microbiologists at ICMR (NICED Calcutta) taught him how all that we do
is not necessarily right and why it is essential to involve oneself in diagnostic laboratory conditions and
even bedside medicine.
His observation includes the seamless working of Darwin’s Theory in relation to microbes and
how they pose real challenges. He also believes it is time to rethink one’s role as Medical and Clinical
Microbiologists, especially during a time where it is necessary to understand that Antibiotics are not
magic bullets but soft weapons to destroy the progress of medicine. Dr. Rao has created content that
helps many in developing countries with a global following of 5 million.
Dr. Ranga Reddy Burri is Health policy enthusiast focused on public health awareness, education
and training. Dr. Reddy is Physician, Public Health specialist & Social Entrepreneur with interest in
business verticals of high social impact. He graduated from Minsk Government Medical Institute, Belarus
with MD (Physician) degree; subsequently he did his PG Diploma in management from Pondicherry
University and Advanced Management from IESE, Barcelona, Spain with specialization in Strategy &
Business Development.
Dr. Reddy is the founder trustee of Infection Control Academy of India (IFCAI). The organization is
a result of his leadership skills, knowledge and experience gained from working in both domestic and
international MNCs. Yet, the Academy’s most valuable strength lies in the strong sense of empathy for
humans and their health imparted by Dr. Reddy and his colleague trustees. His current responsibility
includes leading Sanmed Healthcare, a startup with world class manufacturing capabilities in external
preparations. He supports several non-profit organizations in the capacity of advisor including Neelam
Rajasekhar Reddy Research Center for Social Progress, e-learning center of Hyderabad Central University
& Indian Institute of Public Health. His flair for entrepreneurship has led him to mentor through
imparting knowledge to NGO’s, startups & micro-small enterprises.
Dr. Dhruv Mamtora is a clinical microbiologist and infection control officer at S. L. Raheja Hospital,
A Fortis associate, Mahim, Mumbai since 2015. Before joining in private sector, he has worked with
government sector both in Maharashtra state as assistant professor at RCSM GMC Kolhapur and GMC
Latur as assistant professor and AIIMS, Jodhpur as senior resident. He has passed out MBBS from L. T.
M. Medical College (Sion Hospital) and done MD in microbiology from Government medical college,
Miraj. He has done his healthcare administration EPGDHA from TISS, Mumbai. He is member of multiple
professional bodies like IAMM, IATP, IMA, HIS-MF (institutional), society of clinical microbiologists (SCM)
and ISID (international society of infectious diseases).
He has number of publications in peer reviewed journals, both national as well as international &
he is also faculty and speaker for various national and international, conferences. He has also organized
many training activities and a national level conferences. He is also a media subject expert. He has also
guided as well as multiple projects related to healthcare which is in field of infection control and clinical
microbiology. He has been awarded multiple times in his organization and at national level. His topics
of interest are implementing and improving quality in healthcare, hospital and laboratory accreditation,
clinical microbiology, infection control, antimicrobial stewardship & improving medical education to a
minimum basic standard which is suitable for current healthcare scenario in country and on international
level.
Sister Solbymol P S is a PICU Nurse with 19 years of experience. She has worked as In-charge PICU
Rainbow Children’s Hospital, Hyderabad and Vikrampuri, senior staff at Ernakulam Medical Centre Kochi.
She is now working as Coordinator Quality and Infection Control Nurse at Kinder Women’s Hospital and
Fertility Centre, Cherthala, Alappuzha.
Dr. Ranga Reddy
President IFCAI and Chief Editor
“Infection Control Trends”
Email: dr.rangareddy@ifcai.in
Dr. Dhruv Mamtora
Consultant Microbiologist
and Infection Control Officer
Email: dhruv_mamtora@yahoo.com
Dr. T. V. Rao
Former Professor of Microbiology
Email: doctortvrao@gmail.com
Solbymol P S
GNM, ICCP
Email: solbyps@gmail.com
VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS
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INDEX
Guest Editorial - Dr. Chugh
“End TB Strategy” : Indian Perspective 06
Guest Editorial - Dr. Ameeta Joshi
Tuberculosis Laboratory in a Resource limited setting 08
Guest Editorial - Dr. Vijaya Lakshmi Nag
Non Tuberculous Mycobacteria (Ntm): Advances In Diagnosis
10
Guest Editorial - Dr. Rakesh P S
TB Infection Prevention and Control: 2019 Update
15
The Enigma Of Tuberculosis Continues? Story of Success, Failures and Hope?
- Dr. T. V. Rao
17
Understanding Airborne Transmission From Infection Preventionists’ View
- Dr. Dhruv Mamtora
19
Role Of An Infection Control Nurse In Tuberculosis
- Dr. Ankit Gupta, Ms Prerna Rani, Mr. Prijil Innocent
21
The Need For Psychosocial Intervention In Care For Chronic Illness
- Ms. Pragya Lodha
24
Iron & Mycobacterium Tuberculosis – Is There A Hope?
- Dr. Sourav Maiti
27
Extrapulmonary Tuberculosis - Diagnostic Challenges
- Dr. Sukanya Rengaswamy
28
Paediatric Tb-Trying To Understand From Ic Perspective
- Dr. H Srinivasa
31
Recent Updates In The Management Of Drug Resistant Tuberculosis
- Dr. Aruna Shanmuganathan
33
VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS
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INDEX
Comparison Of CD4 Counts In HIV-TB Co-Infection Before And After Art
- Dr Ravikanti, Dr Sunitha.B.R. Prof, Dr. G. Vishwanath
35
Tuberculosis Prevention In Healthcare Settings
- Dr. Nazia Khan
39
Community Infection Control in The Context of Injection
- Dr. Joven Jebio Ongole, Dr. Sharon Fynn, Dr. Gregory Jagwer
44
Infection Prevention In Community Health Facilities In The Northwest And Southwest Regions
- Amungwa Athanasius Nche
50
Antibiotic Cycling and Antibiotic Mixing: Is it Time for Requiem?
- Dr. Abhijit Chaudhury
56
Objectives Of E -Newsletter On Infection Control Trends 59
Rules and Regulations 60
VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS
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Dr. Chugh
National Professor
Emeritus of National Academy of
Medical Sciences India.
Past Prof Medical College Rohtak
The World Health Organization (WHO) has launched an ambitious program of “End TB” in collaboration with
various international and national organizations. The targets are:
1. An incidence rate of less than 10 cases per 100,000 populations per year.
2. Reduce TB deaths by 95%.
3. To cut new cases of TB by 95% in 2015-35.
To achieve this goal, we need to know: Our present burden of disease and measures to be taken to achieve the
goal.
Present status of TB Burden
Worldwide, 9.6 million new TB cases and 1.5 million deaths were seen during 2014. About 3.3% new cases and 20%
retreatment cases were MDR-TB. The treatment success rate of MDR cases is 50% and only 2.2% for XDR cases. The
annual burden of TB in India is 2.2 million. However, since ~80% of cases are treated in private sector, this estimate is
under-reported. The actual number of cases is 2-3 times higher. The mathematical modeling of transmission in India
shows an annual incidence of smear positive cases 89.8 per 100,000 population. Urban TB cases infect more due to
high population density and rural cases remain infectious for a longer period due to inappropriate treatment and
poor compliance.
The Government of India in its National Strategic Plan has set an ambitious goal to achieve this target by the year
2025, five year ahead of global deadline. With the current rate of annual decline of TB cases, it seems to be an “almost
impossible” task to achieve the goal by 2025. If we wish to achieve it, the decline rate should be more than 10-15%
per year, the present rate of decline being less than 2%. There is a need to provide better diagnostics and treatment
support, improved TB surveillance and healthcare system, nutrition, higher financial allocation and health education
for airborne precautions. Early detection and treatment of patients and their follow-up with full compliance is the first
step to it. Global Fund executive director on 18/02/2019 stated: “India’s goal of ending TB by 2025 will be a tough task”.
GUEST EDITORIALS
“END TB STRATEGY”: INDIAN PERSPECTIVE
VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS
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Other Issues of Human Tuberculosis in India are:
	 1. Zoonotic tuberculosis in humans caused by bovine. Mycobacterium tuberculosis (bMTB), its epidemiology,
and appropriate treatment is imprecise and unresolved issue. The potential zoonosis, reverse zoonosis and mixed
infections in India need further studies.
	 2. Latent TB in India is seen in 40% population (and 50% of healthcare personnel). Around 10% of these
individuals develop full-fledged TB at some time of their life. There is no current policy of diagnosis and treatment of
cases of latent TB in India.
	 3. The risk of tuberculosis in patients with cancer is significantly high in India and globally.
	 4. Molecular techniques show mycobacterial DNA and RNA in 48% of sarcoid biopsy tissues in India.3
	 5. Burden of nosocomial tuberculosis in healthcare personnel in India is significant due to lack of effective
infection control policies and their implementation.4,5
	 6. The global burden of pediatric TB is ~ 1.3 million new cases with 0.5 million deaths every year. Microbio-
logical confirmation is absent in three-fourth of the cases due to paucibacillary disease and impropriate diagnostics.6
	 7. Non-tuberculosis mycobacterium (NTM) prevalence in a TB endemic country (India) is high but often
ignored.1
	 8. Mycobacterial disease, both MTB and NTM in patients with rheumatoid arthritis is 4-fold higher.
There is a need to monitor such patients.7
	 9. Tuberculosis and chronic obstructive pulmonary disease (COPD) have a statistically significant association.
With poor air quality, high COPD in a TB endemic country (Inida), there is a need for better vigilance.
India needs to take a multi-pronged approach to reach its goal of “End TB”.
References
	 1. Chugh TD. Human tuberculosis in Inida: Some neglected issues. Curr Med Res Prac 2017; 8:64-66
	 2. Singh N, Madan k, Aggarwal AN et al. Pleuropulmonary tuberculosis following chemotherapy for
lung cancer at a tertiary care centre in India, Intl J Curr Microbial 2013; 47: 177-180.
	 3. Gupta D, Agarwal R, Agarwal AN, Jindal SK. Molecular evidence for the role of mycobacterium in
sarcoidosis : a meta- analysis. Eur Resp J 2007; 30: 508-16.
	 4. Chugh TD. Burden of nosocomial tuberculosis in healthcare workers in India. Curr Med Res Prac 2017; 7:
18-19.
	 5. Basavaraj A, Chandanwale A, Patil A et al. Tuberculosis risk among medical trainers, Pune India. Emerg
Infect Dis 2016; 22: 541-543.
	 6. Chugh TD. Diagnosis of paediatric tuberculosis. Curr Med Res Prac 2016; 6: 107-108.
	 7. Liao TL, Lin CH, Shen GH et al. Risk of mycobacterial arthritis, Taiwan, 2001-2011. Emerg Infect Dis 2015; 21
(8): 1387-1395.
	 8. Lee CH, Lee MC, Shucc et al. Risk for pulmonary tuberculosis in patients with chronic pulmonary
obstructive disease in Taiwan: a nationwide cohort study. BMC Infect Dis 2013; 13: 194.
VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS
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Dr. Ameeta Joshi
Prof & Head, Microbiology,
GGMC & JJ Hospital Mumbai
Superintendent, Cama & Albless Hospital, Mumbai
Introduction
Tuberculosis (TB) continues to be India’s severest health crisis inspite of TB control activities for more than half
a decade. The National Strategic Plan (NSP) 2017-2025 talks about a vision of TB-Free India with zero deaths, disease
and poverty due to tuberculosis and a goal to achieve a rapid decline in burden of TB morbidity and mortality while
working towards elimination of TB in India by 2025. TB can be controlled in the modern era, as long as TB is diagnosed
early and treated properly and transmission thus interrupted.
The challenge facing TB control in India remains delayed diagnosis and inadequate treatment, particularly among
patients seeking care from private providers, who alone are ill-equipped to sustain their patients on prolonged, costly
treatment. The requirements for moving towards TB elimination have been integrated into the four strategic pillars of
“Detect – Treat – Prevent – Build” (DTPB).
For detection we need diagnostic tests that are not only sensitive & specific but also algorithms so that every
effort is made so as to not miss any case and for all these we need quality assured laboratories.
Laboratory
To achieve universal access to early accurate diagnosis of TB and enhance case finding efficiency, identification of
presumptive TB cases at the first point of care and linking them to the best available diagnostic tests is of paramount
importance. For all these one needs a laboratory which is designed in such a way so that there is protection of all
personnel working inside the laboratory, sample protection as well as the surrounding environment is also protected.
Whether to construct a biosafety level (BSL) 1, 2 or 3 will depend on what are the tests that the lab is going to
conduct, but whatever the BSL of the laboratory good laboratory practices is mandatory.
TUBERCULOSIS LABORATORY IN A RESOURCE LIMITED SETTING
GUEST EDITORIALS
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If low risk activities (only microscopy and or GeneXpert tests) are going to be offered then BSL1 is sufficient
wherein one has to have open bench operations, operable windows having insect screens, standard lab practices.
Biosafety Cabinets (BSCs) not required, if GeneXpert machine is there then there should be a dedicated room for
housing the GeneXpert machine, this room will require air conditioning and a Uninterrupted Power Supply (UPS) for
the machine.
If the laboratory intends to perform medium risk activities (manipulate the sputum sample, sputum concentration
or performing a Line Probe Assay (LPA) on sample) then BSL-2 lab is required, wherein all practices of BSL1 requirements
along with limited access into laboratory, BSC Class II A2, will be needed.
In case the laboratory plans to do high risk activities (culture the TB organisms or manipulate/ perform tests on
the cultures) then all requirements of BSL1 & BSL 2 plus lab design specifically for biological containment (that is BSL-3)
will be needed along with special protective clothing for staff and an autoclave.
If one is planning on opening a TB laboratory professional help of architects (who understand containment,
biosafety concepts), financers (to estimate capital and life cycle costs) have to be used. There are vendors who give
total (turnkey), infrastructural (design as well as civil structure only), equipment only, consumables only solutions. In
the public sector the microbiologists is totally involved right from the planning to the implementation and maintenance
phase, which might not be the case in case of the private sector.
While planning one need to estimate capital and life cycle costs for the laboratory operating facility, whereby the
capital cost will include design, construction, commissioning and equipment cost and the life cycle cost will include
utility expense for ventilation and electric power, filter testing / replacement, inspections, insurance etc;. HVAC (heating,
ventilation, Air Conditioning), AHU (Air Handling Unit), Refrigerated Centrifuge and BSCs are main equipment where
special focus needs to be given especially when one is planning to set up a culture facility. Location of the HVAC needs
to be as close to the BSL3, with minimum bends in the ducts in order to cut down on the cost. It is preferable to ensure
that all electrical light fixtures, switch/sockets, controls, sensors etc. are flushed with the surface, sealed with silicon
sealant, chemical resistant and able to withstand fumigation with disinfectant chemicals. All Equipments favorably to
have their own online UPS (Uninterrupted Power Supply) and battery backup of requisite hours (based on the running
time of the machine, e.g. for a refrigerated centrifuge battery backup of half an hour as the run time of centrifugation
is 20 minutes)
Before the vendor hands over the TB facility ensure that he has supplied the validation document, detailed
procedure for validation, parameters for validation along with validation schemes for architectural layout plans,
specialized systems like HVAC system, air filtration system, pressure control system etc; services & utility like power
supply and distribution system, water supply and distribution system etc;
The aim of the TB lab is not only to offer quality assured TB diagnostic tests but ensure the safety of the laboratory
workers & the safety of the environment this will help in achieving the goal of achieving universal access to quality TB
diagnosis including drug resistant TB in the Country.
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Dr. Vijaya Lakshmi Nag
Prof. & Head, Department of Microbiology,
All India Institute of Medical Sciences, Jodhpur,
Rajasthan-India
Non-tuberculous mycobacteria (NTM), defined as any mycobacterial pathogen other than Mycobacterium
tuberculosis (Mtb) or M. Leprae. More than 170 different species known to cause disease, ranging from skin ulceration
to severe pulmonary and disseminated disease. Some species like M. avium complex (MAC), M. abscessus implicated
worldwide; others like M. malmoense are regionally significant. According to the growth rate NTM classified in to rapid
and slow growing mycobacteria. These bacteria are widely isolated from environmental sources, including drinking
and natural water, as well as soil and dust. The steady increase of NTM infections is likely due to greater exposure
to large-volume aerosols, a modernization of plumbing away from antibacterial copper pipes, and lower hot water
temperatures, which may promote environmental colonization and NTM persistence.
The spectrum of disease caused by NTM include tuberculosis (TB), like pulmonary and extrapulmonary disease,
cervical lymphadenitis in young children, and visceral and disseminated disease. Pulmonary NTM infections are most
commonly due to MAC, M. kansasii, and M. abscessus, which cause often unappreciated, worldwide burden of illness.
MAC species are abundant across the Americas, Australia, Europe, and regions of Asia compared to other species
causing pulmonary disease. Other frequently cultured NTM include M. kansasii and M. abscessus, whereas less
frequent infections can occur with M. xenopi, M. fortuitum, and M. chelonae species.
Indirect transmission of the bacteria, particularly occur in immunosuppressed individuals. The aerosolized NTM
can also survive on fomites, providing another mechanism for spread, particularly for susceptible cystic fibrosis (CF)
patients. The ubiquitous presence of NTM in the environment makes them ideal candidates for opportunistic infections
and therefore warrants specific and detailed diagnostics and further evaluation for intervention against disease.
NTM may cause disease similar to Mtb, however they generally do not respond to classic TB drug regimens, and
therefore a misdiagnosis of Mtb can lead to poor treatment, particularly in resource-poor settings lacking diagnostic
infrastructure. The treatment for NTM infection in chronic cases requires lengthy, complex, and sometimes poorly
tolerated drug regimens over many months to years, and following treatment, patients can experience relapse from
incomplete treatment or reinfection.
The recent rise in interest in diseases caused by NTM attributed to increasing association of NTM with acquired
NON TUBERCULOUS MYCOBACTERIA (NTM): AD-
VANCES IN DIAGNOSIS
GUEST EDITORIALS
VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS
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immunodeficiency disease (AIDS) as well as increasing isolation in non-AIDS population. This increase in the detection
rate is a result of improved awareness and laboratory methodology, which require accurate identification of NTM
species from clinical specimens. Mycobacterial species differ in virulence and may present characteristic antimicrobial
patterns, hence, correct species identification is important as it may also aid in treatment decision.
Diagnosis:
The clinical evaluation of a patient suspected of nontuberculous mycobacterial (NTM) infection is required before
processing of the sample. Important specimens are Sputum, Broncho alveolar lavage (BAL), body fluids, aspirates
(ascitic tap, pleural tap, synovial fluid, drains, pus discharge, gastric aspirates, and cerebrospinal fluid (CSF)) and early
morning whole urine sample for three consecutive days collected in a sterile containers.
The NTM clinical disease in human are due to environmental mycobacteria, therefore, a single positive culture
from nonsterile sources including the respiratory or digestive tract does not necessarily indicate infection or disease and
makes treatment decisions less straightforward. Often, 2 positive microbiological cultures are needed to differentiate
NTM disease versus colonization; however, these criteria have not been validated with respect to progression to
disease. The clinical, radiographic, and microbiologic criteria are equally important in exclusion of other infectious
diseases like, TB, nocardiosis, fungal infection; and noninfectious diseases eg. Sarcoidosis to make a diagnosis of NTM
disease.
Microscopy:
The smear can be stained with Ziehl-Neelsen (ZN) and modified Kinyoun staining. The preferred staining procedure
is fluorochrome microscopy; studies reported that ZN and auramine staining are more sensitive than Kinyoun staining.
While in histopathological examinations, the sensitivity of fluorescence microscopy and ZN staining is low due to
negative influence by formalin fixation. Furthermore, smear sensitivity is lower in extra-pulmonary TB patients, and
persons infected with NTM as compared to M. tuberculosis cases. However, it is very clear that ZN microscopy is an
important method in detection of mycobacteria, but it alone is unable to help in identification and must be associated
with culture.
Culture:
Lowenstein-Jensen (LJ) is conventional medium for the growth of Mycobacterium tuberculosis, and inferior to
Middlebrooks agar as an all-purpose medium for both M. tuberculosis and NTM. The liquid medium culture system
BACTEC (Becton-Dickenson Diagnostics), MB Redox (Heipha Diagnostika), BacT/ALERT® MP (bioMerieux, France),
MGIT (BD Diagnostics), and Septi-check (BD Diagnostics) are commonly used. Most media require additives OADC
enrichment (mixture of Bovine albumin, Dextrose, Catalase, and Oleic acid) to increase the growth rate and PANTA
antibiotic (mixture of polymyxin B, amphotericin B, nalidixic acid, trimethoprim, and azlocillin) are often added to
inhibit the growth of contaminants. The conventional solid method for the growth of mycobacteria is time-consuming
(6–8 weeks), but considered “gold standard. Liquid-based culture has high sensitivity and the growth of M. tuberculosis
detected within 1–2 weeks. However, they always be used in combination with the conventional LJ method for NTM
culture.
NTM speciation by phenotypic method:
The rate of growth, pigmentation of colonies, and various biochemical reactions used for phenotypic identification
of NTM species. However, these tests are time consuming and tedious to perform.
Immunochromatographic test
Rapid assays include Immunochromatographic test (standard deviation [SD] MPT64 TB Ag Kit) developed by SD
Bioline, South Korea which facilitates rapid detection and differentiation of MPT 64 antigen in M. tuberculosis isolates
and NTM. MPT 64 TB Ag kit is highly sensitive and give speedy identification of MTBC, together with M. tuberculosis,
M. africanum, M. bovis, and substrains of M. bovis BCG. The sensitivity is >99%, and 100% specificity. The advantage of
VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS
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MPT64 TB Ag test are very easy to perform from direct culture positive specimens, does not require any extraordinary
equipment and can easily distinguish between MTBC and NTM.
Molecular identification: The molecular identification of different NTM species done by genomic DNA compari-
son, but this is labor intensive. The mycobacterial 16S rRNA gene is highly conserved, more accurate than phenotypic
methods for species identification. If there are differences in the sequence of 1% or greater, generally define a new
species. Studies favoring, molecular-based PCR methods are more sensitive (sensitivity >84%) as compared to phe-
notypic culture based methods (sensitivity up to78.0%); and phenotypic are methods are more time consuming. For
these reasons, 16S rRNA can be used as a standard reference when comparing detection techniques.
NTM identification done to the species level by line-probe assays, used to amplify drug-resistance -determining
regions. The GenoType NTM-DR line-probe assay (Hain Lifescience, Nehren, Germany) is one such tool used for the
identification of clinical M. abscessus subspecies (subsp.) and drug resistance. Rapid species identification can also
be determined using commercial DNA probes (MAC, M. kansasii, and M. gordonae), while group- or complex-level
identification accomplished with high-performance liquid chromatography (HPLC).
For some NTM isolates, especially rapidly growing mycobacteria (RGM; M. fortuitum, M abscessus, and M.
chelonae), extended antibiotic in vitro susceptibility testing, DNA sequencing, or polymerase chain reaction (PCR)
restriction endonuclease assay (PRA) may be necessary. Another assay available for the detection of Mycobacterium
species from clinical samples is a PCR-reverse blot hybridization assay (REBA) Myco-ID assay (YD Diagnostics, Yongin,
South Korea), in which multiple targeted oligonucleotide specific probes (Mycobacterium-species specific) are bound
to a nitrocellulose membrane strip, then hybridized with biotinylated PCR products and subsequently visualized by
colorimetric hybridization signals.
(MALDI-TOF): Rodríguez-Sánchez and colleagues assessed 125 NTM isolates using matrix-assisted laser de-
sorption ionization-time of flight (MALDI-TOF) mass spectrometry, the GenoType common mycobacteria (CM)/ad-
ditional species (AS) assay, and a 16S rRNA/hsp65 gene sequencing reference assay to determine the alignment of
these different techniques. The MALDI-TOF assay was in agreement with the reference assay in 94.4% cases, and the
GenoType CM/AS assay was in agreement in 84% cases, showing some limitations in loss of sensitivity of the Geno-
Type CM/AS assay. However the MALDI-TOF assay requires a mass spectrometer, the GenoType CM/AS assay can be
performed using either manual or automated processing, making it more accessible in resource-limited settings.
QMAP assay: Another innovative molecular assay, the Quanta matrix multiplexed assay platform (QMAP) sys-
tem recently described by Wang and colleagues, allows clinicians to discriminate between mycobacterial species. This
assay utilizes an automated magnetic-bead–based assay following similar PCR steps as used in the PCR-REBA assay,
except denatured biotinylated PCR products added to species-specific oligonucleotide probes coupled to carboxylat-
ed microdisks, followed by the addition of streptavidin R-phycoerythrin conjugate and automated reading of fluores-
cence intensity. This process has high specificity and sensitivity and very less time consuming (~3 hrs).
Experimental animal models for NTM:
Preclinicalanimalmodelscanbeusedtostudytheinfluenceofthefactors,whichaffecttheNTMdiseaseprocess.and
evaluatenoveltherapeuticdrugsandregimensfortreatmentofNTMinfections.TwomajorcategoriesofNTMdiseaseto
considerforanimalmodeldevelopmentincludepulmonarydiseaseandextrapulmonary-disseminateddisease(typically
presenting in immunocompromised). NTM are generally less virulent than Mtb, and therefore the capacity to induce a
sustained progressive infection in a mouse strain is an important criterion and current hurdle for the development of an
experimentalmousemodel.Studieshaveshownthatmostimmunocompetentmousestrainsserveasoutstandingmodels
forthemorevirulentMACspecies;demonstraterapidclearancewheninfectedwiththelessvirulentM.abscessusisolate
making model development and selection challenging. Many different mouse strains have been used to screen different
drug compounds against MAC, including CLR, RIF, rifapentine (RPT), moxifloxacin (MXF), EMB, and amikacin (AMK).
Animal models for slow-growing mycobacteria:
The Beige mouse is used as a standard model for MAC disease. This mouse model was developed in the mid-1990s
because of the increasing numbers of HIV-seropositive patients becoming coinfected with M. avium. Beige mice display
VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS
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many immune deficiencies similar to those occurring in AIDS patients, as well as a susceptibility to infection with NTM
following either intravenous or aerosol infection, providing a unique opportunity for the study of MAC infections in this
model. The Beige mouse model is also use to screen the chemotherapeutic potential of promising compounds for the
treatment of MAC disease.
CLR and rifampicin for 6 weeks, and then treatment is stopped. Twelve weeks following drug treatment, mice
are given immunosuppressants (dexamethasone or sulfasalazine) for 5 weeks to expose any remaining bacteria
post-treatment. Bacterial burden is assessed in the organs at different times after immunosuppression to measure
reactivation.Thismodelcouldalsobeusefulfordeterminingthepotentialefficacyofcombineddrugandimmunotherapy
regimens by quantifying the numbers of bacilli remaining after treatment.
Animal models for Rapid growing mycobacteria (RGM):
The most clinically important RGM to cause human lung disease belongs to M. abscessus. M. abscessus subsp.
abscessus and M. abscessus subsp. bollettii have a functional erm41 gene; therefore, resistance to macrolides may be
identified. It has been challenging to develop an animal model for screening compounds against RGMs because of gaps
in fully understanding their pathogenesis of infection and relative avirulence. A progressive aerosol infection model has
proven elusive since most mouse models with significant deficits in innate or acquired immunity are still able to clear
an infection with a high level of RGM. This highlights the need for improved understanding of the NTM pathogenesis
of infection.
The biggest challenge that remains to advance the knowledge in NTM pathogenesis and protection is to
fully understand the process of human NTM infections (environmental, nosocomial, and endogenous/exogenous
reinfection), which can be used to help in development of animal models.
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2. Jeong SH, Kim SY, Huh HJ, Ki CS, Lee NY, Kang CI, et al. Mycobacteriological characteristics and treatment
outcomes in extrapulmonary Mycobacterium abscessus complex infections. Int J Infect Dis. 2017;60:49–56.
3. Koh WJ, Jeong BH, Kim SY, Jeon K, Park KU, Jhun BW, et al. Mycobacterial characteristics and treatment
outcomes in Mycobacterium abscessus lung disease. Clin Infect Dis. 2017;64(3):309–16.
4. Koh WJ, Moon SM, Kim SY, Woo MA, Kim S, Jhun BW, et al. Outcomes of Mycobacterium avium complex lung
disease based on clinical phenotype. Eur Respir J. 2017;50(3):
5. Diel R, Nienhaus A, Ringshausen FC, Richter E, Welte T, Rabe KF, et al. Microbiologic outcome of interventions
against Mycobacterium avium Complex pulmonary disease: A systematic review. Chest. 2018;153(4):888–921.
6. Nishiuchi Y, Iwamoto T, Maruyama F. Infection sources of a common non-tuberculous mycobacterial
pathogen, Mycobacterium avium Complex. Front Med (Lausanne). 2017;4:27 10.3389/fmed.2017.00027
7. Prevots DR, Marras TK. Epidemiology of human pulmonary infection with nontuberculous mycobacteria: a
review. Clin Chest Med. 2015;36(1):13–34.
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perspectives. Tuberc Respir Dis (Seoul). 2016;79(2):74–84.
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11. Haworth CS, Banks J, Capstick T, Fisher AJ, Gorsuch T, Laurenson IF, et al. British Thoracic Society guidelines
for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD). Thorax. 2017;72(Suppl 2):ii1–
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pathogenic nontuberculous mycobacteria from sputum specimens. Diagn Microbiol Infect Dis. 2013;75(2):225–6.
13. Martiniano SL, Sontag MK, Daley CL, Nick JA, Sagel SD. Clinical significance of a first positive nontuberculous
mycobacteria culture in cystic fibrosis. Ann Am Thorac Soc. 2014;11(1):36–44.
14. Wright PW, Wallace RJ Jr., Wright NW, Brown BA, Griffith DE. Sensitivity of fluorochrome microscopy for
detection of Mycobacterium tuberculosis versus nontuberculous mycobacteria. J Clin Microbiol. 1998;36(4):1046–9.
15. Kehrmann J, Kurt N, Rueger K, Bange FC, Buer J. Genotype NTM-DR for identifying Mycobacterium abscessus
subspecies and determining molecular resistance. J Clin Microbiol. 2016;54(6):1653–5.
16. Wang HY, Kim H, Kim S, Bang H, Kim DK, Lee H. Evaluation of PCR-reverse blot hybridization assay for the
differentiation and identification of Mycobacterium species in liquid cultures. J Appl Microbiol. 2015;118(1):142–51.
17. Springer B, Stockman L, Teschner K, Roberts GD, Bottger EC. Two-laboratory collaborative study on
identification of mycobacteria: molecular versus phenotypic methods. J Clin Microbiol. 1996;34(2):296–303.
18. Tortoli E. Impact of genotypic studies on mycobacterial taxonomy: the new mycobacteria of the 1990s. Clin
Microbiol Rev. 2003;16(2):319–54.
19. Deggim-Messmer V, Bloemberg GV, Ritter C, Voit A, Homke R, Keller PM, et al. Diagnostic molecular
mycobacteriology in regions with low tuberculosis endemicity: Combining real-time PCR assays for detection of
multiple mycobacterial pathogens with line probe assays for identification of resistance mutations. EBioMedicine.
2016;9:228–37.
20. Rodriguez-Sanchez B, Ruiz-Serrano MJ, Marin M, Lopez Roa P, Rodriguez-Creixems M, Bouza E. Evaluation
of matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of nontuberculous
mycobacteria from clinical isolates. J Clin Microbiol. 2015;53(8):2737–40.
21. Wang HY, Uh Y, Kim S, Lee H. Performance of the Quantamatrix multiplexed assay platform system for the
differentiation and identification of Mycobacterium species. J Med Microbiol. 2017;66(6):777–87.
22. Jagielski T, Minias A, van Ingen J, Rastogi N, Brzostek A, Zaczek A, et al. Methodological and clinical
aspects of the molecular epidemiology of Mycobacterium tuberculosis and other mycobacteria. Clin Microbiol Rev.
2016;29(2):239–90.
23. Huh HJ, Kim SY, Jhun BW, Shin SJ, Koh WJ. Recent advances in molecular diagnostics and understanding
mechanisms of drug resistance in nontuberculous mycobacterial diseases. Infect Genet Evol. 2018. October 11
24. Wassilew N, Hoffmann H, Andrejak C, Lange C. Pulmonary disease caused by non-tuberculous mycobacteria.
Respiration. 2016;91(5):386–402.
25. Bryant JM, Grogono DM, Greaves D, Foweraker J, Roddick I, Inns T, et al. Whole-genome sequencing to
identify transmission of Mycobacterium abscessus between patients with cystic fibrosis: a retrospective cohort study.
Lancet. 2013;381(9877):1551–60.
26. Obregon-Henao A, Arnett KA, Henao-Tamayo M, Massoudi L, Creissen E, Andries K, et al. Susceptibility
of Mycobacterium abscessus to antimycobacterial drugs in preclinical models. Antimicrob Agents Chemother.
2015;59(11):6904–12.
27. Gangadharam PR. Beige mouse model for Mycobacterium avium complex disease. Antimicrob Agents
Chemother. 1995;39(8):1647–54.
28. Bermudez LE, Inderlied CB, Young LS. Mycobacterium avium complex in AIDS. Curr Clin Top Infect Dis.
1992;12:257–81.
29. Shiloh MU, Nathan CF. Reactive nitrogen intermediates and the pathogenesis of Salmonella and
mycobacteria. Curr Opin Microbiol. 2000;3(1):35–42.
30. Andrejak C, Almeida DV, Tyagi S, Converse PJ, Ammerman NC, Grosset JH. Characterization of mouse models
of Mycobacterium avium complex infection and evaluation of drug combinations. Antimicrob Agents Chemother.
2015;59(4):2129–35.
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Dr. Rakesh PS
Medical Consultant, TB Elimination,
WHO-RNTCP Technical Assistance Project,
Kerala
With a burden of disease that accounts for more than 10 million new cases per year, tuberculosis (TB) continues
to be a major global health threat (1). Although the global number of TB deaths fell by 42% between 2000 and 2017,
and the annual decline in the global TB incidence rate is currently 1.5% (1), much action is needed to accelerate
progress towards achieving global milestones to end TB (2).
Interrupting the cycle of M. tuberculosis transmission is crucial to achieving global targets to end the TB epidemic.
Thus, there is a need to implement interventions to rapidly identify source cases, and impede person-to-person
transmission by reducing the concentration of infectious particles in the air and the exposure time of susceptible
individuals. These principles form the basis for effective infection prevention and control (IPC). Also, it has to be kept
in mind that 9299 TB cases among health workers were reported in 60 countries alone, with the notification rate for
health care associated transmission of Mycobacterium tuberculosis being twice as high as the rate in the general adult
population.
The threats posed by epidemics, pandemics and AMR have become increasingly evident as ongoing universal
challenges, and they are now recognized as a top priority for action on the global health agenda. Effective IPC is the
cornerstone of such action. The International health regulations position effective IPC as a key strategy for dealing with
public health threats of international concern (2). United Nations Sustainable Development Goals (SDGs) highlighted
the importance of IPC to safe, effective, high-quality health service delivery and universal health coverage. WHO has
released the TB Infection Prevention and Control 2019 Update which is evidence-informed recommendations outlining
a public health approach to prevent M. tuberculosis transmission within the clinical and programmatic management of
TB, and to support countries in their efforts to strengthen or build reliable, resilient and effective IPC programmes to
reach the targets of the “End TB Strategy”.
The summary of recommendations for TB IPC based on 2019 updates is as follows:
Recommendation 1: Triage of people with TB signs and symptoms, or with TB disease, is recommended to reduce
M. tuberculosis transmission to health workers (including community health workers), persons attending health care
facilities or other persons in settings with a high risk of transmission. (Conditional recommendation based on very low
certainty in the estimates of effects)
TB INFECTION PREVENTION AND CONTROL: 2019 UPDATE
GUEST EDITORIALS
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Recommendation 2: Respiratory separation / isolation of people with presumed or demonstrated infectious TB
is recommended to reduce M. tuberculosis transmission to health workers or other persons attending health care
facilities. (Conditional recommendation based on very low certainty in the estimates of effects)
Recommendation 3: Prompt initiation of effective TB treatment of people with TB disease is recommended to
reduce M. tuberculosis transmission to health workers, persons attending health care facilities or other persons in
settings with a high risk of transmission. (Strong recommendation based on very low certainty in the estimates of
effects)
Recommendation 4: Respiratory hygiene (including cough etiquette) in people with presumed or confirmed TB
is recommended to reduce M. tuberculosis transmission to health workers, persons attending health care facilities
or other persons in settings with a high risk of transmission. (Strong recommendation based on low certainty in the
estimates of effects)
Recommendation5:Upper-roomgermicidalultraviolet(GUV)systemsarerecommendedtoreduceM.tuberculosis
transmission to health workers, persons attending health care facilities or other persons in settings with a high risk of
transmission. (Conditional recommendation based on moderate certainty in the estimates of effects)
Recommendation 6: Ventilation systems (including natural, mixed-mode, mechanical ventilation and recirculated
air through high-efficiency particulate air [HEPA] filters) are recommended to reduce M. tuberculosis transmission to
health workers, persons attending health care facilities or other persons in settings with a high risk of transmission.
(Conditional recommendation based on very low certainty in the estimates of effects).
Overall, the preference for ventilation systems in resource-limited settings, based on available evidence of
effectiveness and assumptions about financial constraints, was (in order of decreasing preference): (i) natural
ventilation; (ii) mixed-mode ventilation; (iii) mechanical ventilation; and (iv) recirculated air with HEPA filtration. This
order of preference may not be applicable in settings where resources are sufficient to procure and sustain more
sophisticated systems, or where climatic conditions impede the use of natural or hybrid (mixed-mode) ventilation
systems. While robust or highly specialized systems can reduce the concentration of infectious droplet nuclei in the air
and thus prevent transmission, such systems may cause a false sense of reassurance, given the challenges in installation
and maintenance, and the likelihood of human error in their implementation. In addition, in resource-limited settings,
highly specialized systems (e.g. mechanical ventilation systems and recirculated air through HEPA filters) would have
a negative impact on equity and access, because they may not be adopted nationwide, being too expensive to install
and maintain properly.
Recommendation 7: Particulate respirators, within the framework of a respiratory protection programme, are
recommended to reduce M. tuberculosis transmission to health workers, persons attending health care facilities or
other persons in settings with a high risk of transmission. (Conditional recommendation based on very low certainty in
the estimates of effects)
The interventions described under each recommendation are not intended as stand-alone interventions; rather,
they are to be implemented as a full IPC package.
References
1.	 Global tuberculosis report 2018 (WHO/ CDS/TB/2018.20). Geneva: World Health Organization
2.	 International health regulations (2005) (third edition). Geneva: World Health Organization; 2016
3.	 WHO guidelines on tuberculosis infection prevention and control, 2019 update, Geneva: World Health
Organization; 2019
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Dr. T. V. Rao
Former Professor
of Microbiology
Email: doctortvrao@gmail.com
Tuberculosis continues to be one of the most ancient diseases in human history. Skeletons of Egyptian mummies
show clear evidence of the disease dating back 6,000 years, although some scientists believe it is much older than that.
Genetic analysis of Mycobacterium seems to suggest that modern strains of M. tuberculosis originated from a common
ancestor in Africa about 15,000 to 20,000 years ago.
ROBERT KOCH - STORY OF GREATEST INVENTION AND FAILURE TOO - In 1883, Robert Koch discovered
that the cause was from a bacterium called Mycobacterium tuberculosis. A little while after, he claimed to have
discoveredthecure.AfterannouncementoftreatmentforTuberculosiswithtuberculintherapy,thescientificsocietiesand
people excited and over 2000 people congregated to Germany for treatment. Everyone thought that the new treatment
would cure the patients, but it actually did the opposite! More and more people died at faster rates than TB patients
without treatment. Although Koch tried to save thousands of people's lives but failed, however, he was identified with
the invention of the Bacteria as he discovered the cause of tuberculosis which was a major turning point in the annals
of Medicine. A panoramic view of Koch's life reveals an array of unprecedented achievements intermixed with a few
notable failures. Koch's principal failures – his belief in the therapeutic potential of tuberculin, his error regarding
bovine tuberculosis, and his acerbic treatment of opponents – do little to mar the legacy of a dedicated physician In
1905, Koch won the Nobel Prize in Physiology and Medicine for his work with tuberculosis.
TUBERCULOSIS STILL HAPHAZARDLY TREATED? Tuberculosis continues to be haphazardly treated as many
people who have become infected with tuberculosis don’t even realize that they have an active infection. One should
be aware of someone infected with TB–whether they know it or not–can spread the illness to between 10 and 15
people without even knowing it, this is where in WHO, Public health organizations and Governmental agencies stepped
in to make the screening program for detection of Acid Fast Bacilli in the sputum, to contain the spread and open
cases of tuberculosis. The programs of screening remained a success till last few years as most of the treatments in
tuberculosiscontinuestobethedecisionoftheCliniciansinstartingdrugregimes,howeverwhenweareworkingwithpoor
infrastructure and patient cannot afford many new generations of tests, it is ideal to do, at least a sputum
Microbiology with Z.N Methods. The emergence of Multidrug-Resistant Tuberculosis gives ways to find newer methods
as just finding Acid-fast bacilli sputum do not mean the routinely used drugs cure and is a concern whether we are
looking at a dead bacilli or a Atypical Mycobacterium or even as MDR - TB, and zeal to find the ways given the way for
Molecular and new innovations to diagnose and cure the patients with MDR tuberculosis.
THE ENIGMA OF TUBERCULOSIS CONTINUES?
STORY OF SUCCESS, FAILURES AND HOPE?
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CHOOSING THE RIGHT TEST TO DIAGNOSE TUBERCULOSIS - Factors in selecting which test to use include the
reason for testing, test availability, and costing. many of the developing countries we lack facilities and many times
patients are treated on assumption and not on scientific basis.
SEARCH FOR BETTER DIAGNOSTIC TESTS - yet there are no specific and sensitive tests to suit the clinical situation
and Mycobacterium continues to be the most complex and above all many times if once we are infected it lives in us
and wait for an opportunity to flare up, which created a buzz, with greater focus on HIV/AIDS patients as it will get
reactivated with progress of HIV infection turning to be AIDS.
NEW CHALLENGES WITH MDR -TB An urgent and a persistent problem is the rise of TB that does not respond
to the two most powerful antibiotics for combating the disease. Here, treatment success is much lower, and more
attention needs to be given to improving diagnostics and getting people through effective treatment, which can be
prolonged and arduous, as well as finding new medicines.
HOW TO ACHIEVE OUR GOALS the collaboration of all the health system departments in the management of TB
is significant, since the patient may seek health care either from private medical practice or national care and the main
goals are the early diagnosis and start of treatment. Furthermore, most of the clinical problems that may arise are
addressed by ISTC and these guidelines should always be taken into consideration, at least until future research
provides more promising diagnostic and therapeutic modalities for disease control.
DETECTION OF DRUG RESISTANCE A PRIORITY - CDC advises all patients, the initial M. tuberculosis isolate should
be tested for drug resistance. It is crucial to identify drug resistance as early as possible to ensure effective treatment.
Drug susceptibility patterns should be repeated for patients who do not respond adequately to treatment or who
have positive culture results despite 3 months of therapy. Susceptibility results from laboratories should be promptly
reported to the primary health care provider and the state or local TB control program
Improvements still to come
TUBERCULOSIS IN PEDIATRIC AGE GROUP AND EXTRAPULONARY TUBERCULOSIS -“Huge improvements in the
diagnosis of tuberculosis infection and disease are on the horizon, However, because most techniques are studied
only in adults, before they become available, and TB is fundamentally different in children, and extra pulmonary
involvement although it is likely that all tests will have to be considered according to how cases present clinically and
epidemiologically.
THE SAGA OF TUBERCULOSIS CONTINUES - HOWEVER THE SEARCH ON FOR BETTER SOLUTIONS?
References
1 Problems in diagnosis and treatment of tuberculosis infection Tsara, E Serasli, and P Christaki Hippokratia. 2009
Jan-Mar; 13(1): 20–22.
2 Diagnosis of Tuberculosis Disease When Should You Suspect Tuberculosis (TB)? CDC
3 Tuberculosis is curable. So why are so many people still dying from the disease? By Editorial Board September
18, 2018, The Washington post.
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Dr. Dhruv Mamtora
Consultant Microbiologist infection control officer
S. L. Raheja Hospital, A fortis associate, Mahim, Mumbai.
Co-editor and designer “Infection control trends”
Email: dhruv_mamtora@yahoo.com
Airborne infection control is given low priority in resource limited settings especially in country like India. However
there are many models which have come up in designing and planning a healthcare facility which addresses issue of
airborne transmission of infection. Some of these are adopted in development of treatment facility of tuberculosis and
designing laboratories to undertake tuberculosis culture and sensitivity work.
In the article, I am going to review various systems of ventilation which are available and scientific principles
which are related to engineering but are yet to be adopted by medical industry for better airborne isolation facility
construction.
Infection control involves multiple aspects. First is prevention of aerosolisation of particulate material. Second
is mechanism whereby a particle which has already escaped in air is killed before inhalation by susceptible host and
thirdly isolating patient harboring tuberculosis in special ward which is negative pressure isolation facility so that
transmission can be prevented or minimized.
Fortheimplementationofsame,controlfallsinthreecategories,firstisadministrativecontrolfollowedbypersonal
protection and lastly environmental and engineering controls. Administrative controls ensure that measures are taken
appropriately to prevent transmission to susceptible patients. These include appropriate seating arrangements, triage,
communication and patient education. However it is administration who also ensures that other steps which are
personal protective equipment and environmental and engineering controls are in place in any given organization at
all times. Next is role of appropriate personal protective equipment which includes use of respirator (N95 Masks) and
appropriate procedures which are followed which minimizes risk of aerosolization like closed suction methods, use
of biosafety cabinets for processing of samples, use of water resistant apron and face shield when such procedures
are taken and ensuring that appropriate quality tests e.g. fit test for respirators are performed and regular training is
given to staff for using same. Third and last important part is environmental and engineering controls. Engineering
and environmental control ensures that transmission do not happen from one patient to another. Basically ensuring
appropriate ventilation and exhaust controls. However at same time, engineering and environmental controls are
major expenditure exercise for setting up appropriate isolation facilities for hospital set ups. The designing include
clarity on various aspects which include type of ventilation systems, airflow distribution structure, air exchange rate,
temperature and humidity both of ambient air as well as climatic conditions of establishment of facility, engineering
maneuvers like filtration of air, HEPA filter installation, UV light and architectural and construction team support for
designing above mentioned all elements.
Airborne pathogens can be bacterial, viral or fungal spores which are suspended particles either solid of liquid in
air. Some of parasitic eggs can also be suspended in air. Viruses are smallest of particles which are in nanometer sizes,
bacteria are in micrometer size and fungal spores are largest which are larger than bacteria (1-30 microns).
UNDERSTANDING AIRBORNE TRANSMISSION
FROM INFECTION PREVENTIONISTS’ VIEW
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Human activities which support spread of airborne pathogens include respiratory (talking, coughing, sneezing,
breathing),showering,flushing,tapwateruse,sewageaerosolizationfromtoilets,leakageinpipeandplumbingsystems
etc. other specific hospital activities which can generate aerosols are bed making, washing of medical equipments, wet
mopping and walking on carpets which can re-suspend particles as aerosols.
Hospital procedures like intubation, suctioning, cardiopulmonary resuscitation, bronchoscopy, autopsy, surgery,
cauterization, centrifugation etc. can also form aerosols. Presently, there is no precise list which can pin point exactly
cause effect relationship between ventilation systems and hospital procedures. However this area can be of interest
for future research.
Basic and fundamental idea should be ventilation system should be appropriate for the scope of services offered
by healthcare organization. Also the systems must be equipped to remove airborne contamination through effective
ventilation system which has multiple checks of filter and UV etc. ventilation systems and ducts are regularly inspected
and filters are timely replaced so that the optimum functioning can be assured. Some cleaning measures are in place
and parameters like airflow velocity, air changes, filter efficacy and functionality, temperature. Pressure and humidity
are monitored at regular intervals. Also pressure gauges are installed at entrance of all isolation rooms and tubes
should not be blocked or worn out and must actually measure pressure differentials.
Prevention of airborne transmission in hospitals and healthcare organization is a complex subject and it revolves
around multiple key performance areas. Cross contamination by airborne infection can be significantly reduced in well
designed and ventilated operating rooms however the same can be complex subject when it comes to designing wards.
Since wards have complex interplay of multiple factors which are contact, airborne and hand related contamination
and cross contamination in multi bed general wards.
Reduced infection by airborne transmission needs robust systems which start right at point of installation of
ventilation system and architectural design of building. It is also important that the systems which are functioning are
maintained optimally to prevent cross contamination and reduce incidence of air borne infections in a given healthcare
facility. Maintenance of systems to their maximum desired efficiency is challenge of this era and also major expenditure
for tropical countries like India where the summer temperature are high and some of metro cities are coastal where
humidity is exceeding more than 60 percent most of time in a year e.g. Mumbai, Chennai, Kolkata etc.
Very little work has been done in this area of hospital starting from a scratch from designing aspect. Because many
of organizations are built on old infrastructure which is so vast that to make changes is major capital expenditure so
also maintaining and sustaining new systems is further challenge.
There are new challenges especially for developing countries like India, where population explosion and
overcrowding is major challenge to old existing infrastructure especially in general hospitals or any other places like
bus depot, railway station or airports which are ran by governmental organizations so also maintenance for optimum
functionality in existing ventilation systems which are in place ever since installation and are looked after or maintained
only after major breakdowns or major disasters.
There is need for development of common consensus and it is an area of research so also validation of existing
system to its functionality is also challenging as there are no laid standards except some given by national and
international agencies. Since the area deals with multiple complexities which want joint attention for medical and
adjoining fields of engineering, maintenance and mechanics part of ventilation, there is huge unmet need especially at
a juncture where we stand looking forward to eradicate biggest and chronic disease of tuberculosis which is rampant
in our community and has gained new sensation after evolving as MDR, XDR and XXDR forms.
Toconclude,thesocalledmodernmedicineisyettobecomemodernizedasfarasairbornediseasesandprevention
of airborne diseases is concerned but baby steps are taken especially after knowledge of diseases like swine flu, bird
flu, MDR form of tuberculosis and SARS. There is much more to learn and execute especially in field of designing,
planning and maintaining facilities where mass public gatherings and especially in hospitals where respiratory diseases
are treated. hospitals where respiratory diseases are treated.
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Dr. Ankit Gupta, Ms. Prerna Rani, Mr. Prijil Innocent
Department Of Infection Control
Max Superspeciality Hospital, Vaishali,
Ghaziabad, Uttar Pradesh
Sinceinception,tuberculosishasplaguedthemankindandintriguedtheresearchers.ThenotoriousMycobacterium
tuberculosis has witnessed revolutionary changes, from inclusion of newer bacteria in Mycobacterium tuberculosis
complex, to development of newer diagnostic modalities (culture based to NAAT based), and overwhelming drug
resistance to many antimicrobials. The bacteria continue to evolve further, with very few new antibiotic compounds
for rescue (i.e. bedaquiline, delaminid). Being a highly communicable disease, the prevention is the key to contain the
spread in community.
The infection control measures in a hospital are crucial to the management of tuberculosis. This exercise is
carried out with extreme diligence by infection control nurses. With meticulous planning, they are entrusted with a
responsibility to help in patient management by preventing the spread. With our experience, the strategy can be aptly
called as NIYANTRAN, which may be considered as an abbreviation for various processes.
NOTIFICATION
• Notification of a case of tuberculosis is mandatory so that the patient can be offered assistance for diagnosis
and treatment.
• The infection control nurses serve as a bridge between clinical laboratories and departments which need to be
notified with a case of tuberculosis.
ISOLATION
• Isolation for the control of infection is used to prevent infected patients from infecting others (source isolation),
and/or prevent susceptible patients from being infected (protective isolation).
YEARLY HEALTHCHECK UP
The infection control nurse, in collaboration with other departments can coordinate and oversee an annual
healthcheck up for all healthcare workers.
AUDIT
ROLE OF AN INFECTION CONTROL
NURSE IN TUBERCULOSIS
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NEGATIVE PRESSURE (AND TRANSMISSION BASED PRECAUTIONS)
A. This process contains two tiers of precautions:
1. Standard precautions
2. Transmission Based Precautions
B. What are STANDARD PRECAUTIONS?
STANDARD PRECAUTIONS (applicable to blood, all body fluids, secretions, and excretions, except sweat, regardless
of whether or not they contain visible blood, non-intact skin, mucous membrane)
C. What are the various modes of transmission?
TRANSMISSION BASED PRECAUTIONS
Airborne precautions include
•	 Isolation of the patient in a private room with monitored negative air pressure.
•	 The door to the room must remain closed.
•	 Always wear appropriate respiratory protection - Use of N-95 mask for certain cases like H1N1.
•	 Use required PPE.
•	 Proper disposal of Bio medical waste.
•	 Strict compliance to hand hygiene.
•	 Limit the movement and transport of the patient from the room.
•	 Terminal disinfection after discharge / transfer out.
Droplet precautions
•	 Keep the patient in a private room.
•	 The door must remain closed.
•	 Mask must be worn when entering the room and examining or transporting a patient.
•	 Use required PPE.
•	 Proper disposal of Bio medical waste.
•	 Strict compliance to hand hygiene.
•	 Limit the movement and transport of the patient from the room.
•	 Terminal disinfection after discharge / transfer out.
Contact precautions include
•	 The door must remain closed.
•	 Use required PPE such as clean gown, glove etc.
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•	 Proper disposal of Bio medical waste.
•	 Strict compliance to hand hygiene.
•	 Limit the movement and transport of the patient from the room.
•	 Limit the movement of visitors
•	 Terminal disinfection after discharge / transfer out
TRAINING
•	 Regular sessions are taken by infection control nurse to sensitize nursing and other health care workers
regarding prevention.
RESISTANCE (MDR, XDR AND TOTAL DRUG RESISTANCE) and RNTCP
•	 The infection control nurses need to train healthcare workers about the threat of drug resistance.
•	 The family members also need to educated about precautions to be observed at home and availability of
various resources under RNTCP program.
AUDIT AND SURVEILLANCE
No infection control activity is complete without a comprehensive audit, surveillance and feedback mechanism.
N-95 RESPIRATOR MASK practices for health care workers AND USE OF RESPIRATOR/Surgical Mask – For
patients while transporting for procedures to prevent spread of infection.
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Ms. Pragya Lodha
Clinical Psychologist & Research Assistant
Health can be holistically determined by a bio-psycho-social model, however, often the medical model of illnesses
overweighs in understanding, managing and treating illnesses. This is especially so for chronic illnesses as the inevitable
first line of treatment is that of pharmacological management. What this article tries to highlight is the complementary
need for psychosocial interventions for long term management of the illnesses and better quality of life for the patient.
It is essential to understand that there are various pathways implicated in the development of chronic
illnesses. The basic sciences focus on psycho-neuroendocrinology, psycho-neuroimmunology, psycho-physiology and
psycho-somatic correlations- which is an explanation of physical and mental health affect each other and can aggravate
the either conditions in terms of chronicity or symptom presentation. Treatment of patients with chronic diseases will
be one of the main challenges of medicine in the future because they are very often influenced by psychosomatic
or biopsychic factors. Though pharmacological management of chronic illnesses is an indispensable approach to
treatment, it must be remembered that medicine is not only a diagnostic discipline but it also involves other health
care workers in action, as part of the ‘health care system’. A commonly noted phenomenon is also that patients inflicted
with chronic illnesses (cancer, renal problems, diabetes, chronic pain, coronary heart disease, bronchial asthma,
rheumatoid arthritis, inflammatory bowel disease, essential hypertension, atopic dermatitis, surgical issues and other
illnesses) can develop psychological and emotional issues.
Psychosocial interventions are strategies of care that generally fall under the mental health care dimension since
it looks at psychological and emotional well-being primarily. By definition, there is no one standard definition for
psychosocial care as the nature of care varies with what the problem is, what is the nature and extent of care needed,
who provides the care and the overall context along with the illness. Psychosocial care in the health care setting
is the provision of psychological and emotional support and practical advocacy as it relates to patients adapting to
their medical condition, accessing and adhering to medical treatment and developing coping skills to incorporate their
illness successfully into their lives.
The focus of psychosocial intervention is to assess and manage aspects such as psychological symptoms,
personality traits, attitudes toward disease and life, risk behaviour and social isolation. As biological targets, the change
of autonomic imbalance and of the effects of the psycho-endocrinological or psycho-immunological stress responses
is also that is managed under psychosocial care. Psychosocial care is an aspect of treatment that works best along with
clinical management of the illness.
Straightforwardly, the psychosocial intervention is inclusive of counselling the patient, educating them about
the illness, understanding the personal factors of the patient that may be exacerbating the illness and involving the
patient and family members in better quality care at home along with managing illness in the long term. Psychosocial
intervention addresses the following:
• Adaptation to Change
THE NEED FOR PSYCHOSOCIAL INTERVENTION
IN CARE FOR CHRONIC ILLNESS
VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS
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• Grief and Loss
• Coping Skills
• Pain Management
• Communication Skills
• Stress Management
• Problem Solving
• Assertiveness Training
• Spirituality
• Rehabilitation
• Post recovery care
• Behavioural intervention (lifestyle changes)
Through education, developing of coping skills and supportive intervention, patients are capable to effectively
handle the stressors of life.
Professionals practicing psychosocial care are specifically trained to help patients adjust to illness, diagnose
and treat behavioural and emotional disorders including anxiety and depression, work with patients on behaviour
modifications to adapt to difficult situations and respond to crisis situations.
It is often believed that symptoms of an illness reduce with clinical management and the need for psychosocial
interventions is often not felt. Patient care has been built based on an understanding that many factors impact
patients’ functioning which are importantly relative to the illness. Patients need to be assessed fully for these factors
and relevant interventions need to be implemented for better management. What is quintessential to note is that the
impact of illness varies from one person to another and consequently, the treatment approach will also vary as the set
of challenges faced by every patient are different. An individualized approach must be taken in order to eradicate the
barriers and treat the patient holistically.
The importance of psychosocial intervention in chronic illnesses:
1. Addressing the patient and taking an interest to understand the patient’s personal variables increases trust
and better understanding between the doctor/therapist-patient relationship which is a very essential factor in
patient-recovery
2. Culturally, India has a paternalistic doctor/therapist-patient relationship where the doctor/therapist is almost
equivalent to god, a relationship where doctor/therapist understand patient’s cultural variables can promote great
amount of trust in the patient
VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS
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3. Sometimes, having the belief that one trusts to get well is essential as optimism is linked with physical and
mental well-being which may lead to sooner and better recovery
4.Psychosocialcarehasprovenefficacyinalleviatingdistressinpatientsmedicallytreatedforcancer,cardiovascular
diseases, HIV/AIDS.
5. Psychosocial intervention can sometimes prevent chronic illnesses like HIV
6. Psychosocial care also improves compliance to medication and adherence to treatment as education and
counselling are components of the care that allow for better patient understanding.
7. Family involvement is an essential part of illness management and sometimes identification of symptoms
beforehand in order to prevent relapse (as far as possible) and early management of illness relapse.
8. Patient and family education about the illness is important for them to recognise early signs and symptoms, to
avoid delay in treatment and also learning management at home as and when required.
9. Counselling allows for the patient to share his / her psychological and emotional baggage and get rid of it in
order to improve quality of life and better self-care.
10. Psychosocial interventions enhance the outcomes of clinical care. Along with medication, addressing the
personal variables in a patient helps reduce the need for medication for every symptom management (which can be
taken care of psychosocially and at an interpersonal level), reassures the patient as a busy clinician may not always
have the time to spend with the patient whereas the psychosocial care provider fulfils that, the queries of the illness
get resolved by the psychosocial carer.
Where to find psychosocial care?
Psychosocial support can include mental health counselling, education, spiritual support, group support, and
many other such services. These services are usually provided by mental health professionals, such as psychologists,
social workers, counsellors, specialized nurses, clergy, pastoral counsellors, and others.
Specifically, in India, one can reach out to a psychotherapist, counselling psychologist or clinical psychologist and
/ or a social worker who does counselling. Some hospitals also have psychiatric nurses who are capable of handling the
care. These professionals can be sought either on a private clinic basis or at a hospital that has a psychiatry OPD. One
may also find to join support groups that also foster psychosocial care.
Conclusion
Researchevidencetellsusthatreasonsforrelapseofillnessandre-hospitalisationincludepsychosocialissues,such
as anxiety, lack of emotional and psychological support from family, friends and caregivers and a lack of communication
and coordination of care for patients. Perhaps because there are no published guidelines for incorporating psychosocial
care into usual clinical practice, it still is largely absent from routine patient care. The approach appreciates that all
people must be treated in the context of their personal lives, beliefs and backgrounds. It is this unique context that
patientsbringtotheirdiseaseanditsmanagement.Healthcareprovidersmustunderstandthatidentifyingthecondition
or illness and recommending a treatment is only part of effective care. If illness is addressed without addressing its
complex human host, barriers to treatment will prevent best outcomes, even if best medical therapies are offered.
References
1. Deter HC. Psychosocial interventions for patients with chronic disease. BioPsychoSocial medicine, 2012;6(1), 2.
doi:10.1186/1751-0759-6-2
2. Congressional Research Service. Medicare hospital readmissions: issues, policy options and PPACA, September,
2010.
3. Wagner EH, Austin BT, Davis C, et al. Improving chronic illness care: translating evidence into action. Health Aff
(Millwood) 2001;20:64–78.
4. Kemp K, Griffiths J, Lovell K. Understanding the health and social care needs of people living with IBD:
a meta-synthesis of the evidence. World J Gastroenterol 2012;18:6240–6249.
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Dr. Sourav Maiti
Chief Consultant Clinical Microbiologist & In-Charge,
Department of Infection Prevention & Control,
Institute of Neurosciences Kolkata
Email: smaiti76@gmail.com
Electron transport is an essential biologic process required by almost all aerobic bacteria which is dependent upon
availability of optimum amount of iron. Mycobacterium tuberculosis requires iron but in mammalian host nutritional
immunity limits the amount of free iron. In addition, free iron is really scarce at physiological pH as it exists in the form
of insoluble iron oxides. It requires 10−7
M iron for growth whereas solubility of iron is only 1.4 × 10−9
M at neutral pH.
Hence for survival M. tuberculosis needs to rob off iron from transferrin in plasma and from lactoferrin in extracellular
fluids and leukocytes. It has distinct mechanism of production of siderophore for chelating the metal iron from
protein-bound as well as from the insoluble iron.
Mycobacterialcellenvelopecontainslipid-richorganizationwhichcausesdifficultyinironacquisition.Toovercome,
it produces 2 types of siderophores – hydrophobic mycobactins and hydrophilic carboxymycobactins. Gram-negative
bacteria use TonB –dependent receptor-mediated internalization of iron. Most likely mycobacteria incorporate iron
by interplay of ferricarboxymycobactins at outside and cytoplasmic membrane-bound mycobactins. HupB might be
having an important role in mediation. Exochelins are not known to be produced by Mycobacterium tuberculosis.
Since iron is an essential nutrient for survival of Mycobacterium tuberculosis, could it have some implication
in treatment? Studies show for nosocomial multi-drug resistant strains of Staphylococcus aureus and Acinetobacter
baumannii, siderophore-mediated iron uptake has important implications. Host response includes hyperproduction of
lipocalin-2 which binds to siderophore and prevents reuptake of siderophores inside bacterial cell. On the other hand,
synthetic siderophore analogues can be used as “Trojan horse” to deliver particular antibiotics like magic bullets.
Researchers have shown that a bisubstrate inhibitor of the adenylation enzyme MbtA, which is responsible for the
second step of mycobactin biosynthesis, exhibited potent antitubercular activity. Drug discovery focused its efforts on
the inhibition of MbtI also which is another enzyme involved in the mycobactin biosynthesis. Among other compounds,
MmpL3 inhibitors also demonstrated in vitro and in vivo antitubercular activity. These are still in experimental stages
but they might answer the burning question of MDR-TB and XDR-TB. Let’s hope for the future!
IRON & MYCOBACTERIUM TUBERCULOSIS – IS THERE A HOPE?
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Dr. Sukanya Rengaswamy
MD, PGDID, CIC, Bangalore
In the last few decades, though there has been a remarkable progress in the diagnosis of pulmonary TB, Extra
pulmonary TB (EPTB) poses several clinical, diagnostic and management challenges which still need to be addressed.
The common EPTB sites are TB Lymphadenopathy, Pleural TB, Abdominal TB, Genitourinary TB and Infertility settings
(IVF) and CNS TB. Diagnosis of EPTB is challenging due to several factors such as paucibacillary samples, variable
clinical presentations, need for invasive procedures to obtain appropriate samples and lack of laboratory facilities to
process such samples in resource limited settings, where many such cases present. These can be further classified as
Pre analytical and Analytical challenges. Common challenges in the pre analytical phase are Paucibacillary nature of
samples/specimens, Non uniform distribution of microorganisms in samples, Inaccessible sites for routine sampling,
feasibility and acceptability of invasive methods for sampling. Analytical phase issues are further classified as:
I. Methodological issues:
A. Direct methods:
	 a. Tissue aspirate Microscopy and staining - ZN requires more than 106 bacilli per gram of tissue to be
positive, which is a challenge in paucibacillary cases of EPTB.
The sensitivity of sputum culture varies by site of EPTB: 28%-50% for abdominal TB, 10%-11% for tuberculosis
pericarditis, 24%-29% for tuberculous meningitis, and 5%-14% for tuberculous lymphadenitis. Repeat tests improve
diagnostic performance. In patients with urinary tract TB, three to six first-void morning urine specimens can improve
the likelihood of a positive acid-fast bacilli (AFB) culture result with approximately 80%-90% (only 30%-40% of single
specimens are positive).Repeated lumbar punctures and cerebrospinal fluid (CSF) examination also increase
diagnostic yield.
	 b. Culture is regarded as the “Gold standard” in the diagnosis of EPTB, but however the decontamination
techniques of the EP samples are harmful to Mycobacteria, thereby bringing down the sensitivity.
	 c. Molecular methods - Gene expert is the only recommended Molecular assay for EPTB. However here
again the sensitivity varies widely for different EP samples. CSF, pleural, peritoneal, pericardial, synovial and pleural
samples show low sensitivities on Expert platforms. A recent meta-analysis reported that Xpert MTB/RIF has an overall
sensitivity of 83.1% and a pooled specificity of 98.7% for the diagnosis of EPTB .Others such as Real time, Nested
PCRs. NAATs (Nucleic Acid Amplification Tests), TMA (Transcription Mediated Amplification), LCR (Ligase Chain
reaction) , LPA (LINE Probe Assay) and Phage Tek MB assays are still to be evaluated for EPTB samples. Currently no
recommendationsaremadeforuseofPCRinthediagnosisofEPTB.ThisbecauseofseveraldemandingfactorssuchasDNA
concentration, size of target DNA and repetitiveness of the amplified sequence ,choice of primers used and the
expertise of personnel involved in conducting the assay. A Quality control study of seven laboratories worldwide
showed a false positivity ranging from 0-77%.
EXTRAPULMONARY TUBERCULOSIS - DIAGNOSTIC CHALLENGES
VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS
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d. Antigen detection tests:
	 1. Serological tests: can detect mycobacterial antigens in body fluids, but require a minimum of 3-20ng/ml of
antigen. The commonly detected antigens from EPTB specimens are BCG, Lipoarabinomannan (LAM), Non protein cell
wall antigen, antigen 5, 14kDa, antigen A60, 45/47kDa antigen, cord factor (trehalose-6, 6_dimycolate). However, none
of these tests have shown a good sensitivity in paucibacillary EPTB, which poses the main diagnostic challenge.
	 2. Antigen based immunostaining-IHC/ICC: Immunohistochemistry and immmunocytochemistry. Advantage
over the ZN as it can detect degraded bacteria, while ZN requires intact bacilli. These tests have high sensitivity (70-
100%) and specificity (65-100%).Perform well in atypical histology and HIV co infected samples and can be used on for-
malin fixed paraffin embedded tissues, aspirates and body fluids too. The main challenge here is invasive tissue sample
collection and good sample preparation
Due to the above challenges, the sensitivity of detection by direct methods is only 20-25%
B. Indirect Methods are Histopathology and Cytology
	 1. Histopathology: The main issues are the confusing differentials in histopathological findings of granulomas
and atypical histological features in concomitant immunosuppressive conditions like HIV.
In TB endemic countries like India, granulomas with or without caseation, having Langhans Giant cells are
diagnosed and treated as TB.
Challenges are the lack of biopsy facilities in peripheral health care and it’s invasive nature. Incision biopsy is
also associated with sinus tract and fistula formations and therefore biopsies are limited for patients with high clinical
suspicion but negative FNACs (Fine Needle Aspiration)
	 2. Cytology: FNAC is usually the first line diagnostic test for EPTB in an accessible mass. However, here again
challenge is to differentiate other granulomatous conditions, on tubercular mycobacterial infections and atypical
cytological presentations in Immunosuppressed conditions such as HIV. The definite diagnosis of TB has to be done
only with concomitant bacteriological examination which has a sensitivity of only 20-25%. The selection of the
diagnostic procedures depends on the organ of involvement in EPTB. Various methods that include needle biopsy,
excision, endoscopy, laparoscopy, and biopsies under guidance of ultrasound, computed tomography (CT), or
endoscopic ultrasound have been employed to ascertain the diagnosis. Excisional biopsy has the highest sensitivity,
whereas FNA is less invasive and may be useful. Laparoscopy with target peritoneal biopsy is the current investigation
of choice in the diagnosis of peritoneal TB. In Bone TB , CT-guided needle biopsy is the recommended first approach to
obtain tissue for assessment.
	 3. Body fluid examination:
		 3a. Tuberculous pleuritis is an exudate, with lymphocytic predominance in about 90% of cases.
However, polymorphonuclear cells may predominate in patients with symptoms of <2-week duration. CSF typically
reveals a leucocytosis (10-1000×103cells/ml; mostly lymphocytes),raised protein (0.5-3.0 g/L), and CSF: plasma glucose
<50%. Pericardial fluid assessment typically demonstrates a bloody, exudative effusion that is often predominantly
neutrophilic and not lymphocytic.
		 3b. ADA - (Adenosine deaminase enzyme) Useful in early TB detection in endemic countries. High
sensitivity in EPTB. Determination of ADA isoenzymes and ratio of the iso enzymes in body fluids, helps in differentiating
various causes especially in borderline ADA levels. ADA-2 is elevated in TB as against other causes such as malignancy.
		 3c. GLC - Tuberculostearic acid found in femtomoles can be detected using GLC on body fluids for EPTB
diagnosis. Issues are false positives and demanding infrastructure.
C. Serological tests:
	 1. Antibody tests for diagnosis of TB have been banned in India.
	 2. Cellular immunity based tests-
		 2a. Skin tests-Mantoux – it is based on delayed hypersensitivity response.
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Challenges are:
	 • inconsistencies in performance and interpretation of the test
	 • inability to differentiate between past, latent and active infection
	 • inability to differentiate between MTB and NTM infections
	 • False negatives in Immunosuppressed conditions like HIV co infections
		 2b.IGRAs (Interferon gamma release assays) - Negative recommendations from WHO to use these
assays for the diagnosis of TB and latent TB in low and middle income countries. Very few studies are available on the
use of IGRAs in EPTB diagnosis.
II. Policy issues-
National TB Control programmes in endemic countries does not include active diagnosis and reporting of EPTB
cases. Also the diagnostic work up for EPTB requires good infrastructure and expert personnel for invasive procedures,
sampling, and specialized assays with good sensitivities. These are a challenge in TB endemic countries which come
under low and middle income category.
III. Challenges in HIV co infections with TB (especially EPTB which is common)-
EPTB Presentation in HIV is usually atypical and protean. A high degree of clinical expertise and experience is
essential along with availability and accessibility of advanced tests at the primary and secondary levels healthcare
systems for the early and accurate diagnosis of EPTB in HIV.
The Future:
The cornerstone of Global TB control is rapid and accurate diagnosis of all forms of TB. The diagnostic challenges
in EPTB, HIV and TB and MDR TB have led to WHO, FIND (Foundation for Innovative and New Diagnostics) and the
GLI (Global laboratory Initiative) prioritizing quality diagnostics which are rapid, low cost, and easy to interpret with
minimum infrastructure. Decentralizing NAAT tests leads to cost savings for both patients and providers as there
are fewer investigations, shorter length of hospital stay, reduced use of antibiotics and visit costs. New diagnostic
algorithms for the diagnosis of EPTB using assays like Immunochemistry have been validated and these need to be
used as a routine diagnostic test. The availability of new guidelines and tools for such tests such as QADAS (Quality
Assessment of Diagnostics Accuracy Standards) and STARD (Standards for reporting of Diagnostics Acuracy) can
facilitate implementation of such algorithms.
Conclusions:
Extra pulmonary TB is a huge diagnostic challenge faced by low and middle income countries which are also TB
endemic countries, where advanced and sophisticated molecular tests and drug sensitivity tests are not available
widely. However, WHO has speeded up the intake of new diagnostic tests which are evidence based. The evidence
is provided by diagnostic accuracy evaluations where accuracy performance is used as surrogate marker for
patient-important outcomes. More evidence however is required to evaluate the operational efficacy of these tests at
the field level.
References:
1. Manju Purohit and Tehmina Mustafa, Laboratory Diagnosis of Extrapulmonary Tuberculosis, Journal of Clinical
and Diagnostic Research, 2015 Apr, Vol-9(4):EE01-EE06
2. Ji Yeon Lee,Diagnosis and Treatment of Extrapulmonary Tuberculosis, Tuberc Respir Dis (Seoul) 2015 Apr; 78(2):
47–55. Published online 2015 Apr 2. doi: 10.4046/trd.2015.78.2.47
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Dr. H Srinivasa
MD Microbiology
(AIIMS, New Delhi)
Freelance Consultant Microbiologist &
Infection Control Bangalore
Email: dr.srinivasa.micro@gmail.com
INTRODUCTION
Pulmonary TB continues to be most important chronic infectious communicable diseases contributing to many
deaths. More important is that is its socioeconomic impact on family.
Compounding on that the person with Pulmonary Tuberculosis can spread to family members by droplet method
that person's with weak Immunity .Is this the reason that children with weak immunity are more susceptible?
Childhood TB can manifest in infancy or in later childhood, adolescents. the source may be mother or a family
member or in nurseries/preschools, or much later in community
It is important to realize that TB infection is different from TB as disease. The former indicates only past exposure.
Children with first exposure results in primary infection which normally resolves with or without antibiotics for 1-2weeks
in most cases.
It is those who fail to contain mycobacteria, develop post primary tuberculosis. The location of disease may not be
lungs but more commonly lymphnodes, pleura, bones etc. thus Paediatric TB is Pulmonary or Extra pulmonary.Those
with malnutrition, primary TB itself will be severe resulting in miliary TB or TB meningitis
Diagnosis and epidemiology Of Paediatric TB
Recognition of Paed TB: its diagnosis, to treat or not to treat is challenging.
When to consider definite, when probable, when unlikely good review articles with IAP recommendations are
available.
I am not sure as to whether one should treat, hilar Lymphadenopathy in otherwise healthy child or wait and
watch is better.
Lab assistance in Paediatric TB careful and correct sampling is important.
Sputum is simply not possible, Hence gastric lavage is important, throat? laryngeal swab also yield positives by
ZN smear for AFB. Now says gene expert has revolutionized the diagnosis and also provide information whether the
bacteria is MDR or not.
RNTCP guidelines have included in addition to first sample for smear, detection of DNA. In place of second sample
only few cases of drug resistant TB require prolonged drug regimen.
PAEDIATRIC TB-TRYING TO UNDERSTAND FROM IC PERSPECTIVE
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In summary we need to closely look at Paediatric TB diagnosis how much is evidence based,
Whether there is missed diagnosis Or over diagnosis.
What is the impact of BCG on evolution of primary TB, its severity if it occurs.
Is TB meningitis , Miliary TB decreasing or still persisting in certain geographical areas, what is the profile of child
affected with severe TB, as well as family members,
A study done in India showed that Family members are still the major source for Paed Tb in more than 50 % of
cases.
Another Study revealed that extra pulmonary TB is overlooked and not diagnosed early in many cases
Future Perspectives
A close study audit is required to be done by all infection control practitioners to learn more about the current
situation of Paediatric Tuberculosis. Further impact of treatment Is also equally important
References
1. Paeduiatric Tuberculosis, a decade long experience
K madhava Kamath etal
Indian J child health vol 5 issue 2 2018
2. Pediatric Tuberculosis in children in India : A prospective study
Sanjay K Jain
Biomed research International volume 2013
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Dr. Aruna Shanmuganathan
MD, DNB, Professor, Department of
Respiratory Medicine
Chettinad Hospital & research Institute,
kelambakkam, Chennai - 603103
Worldwide, tuberculosis (TB) is among the top ten causes of death & the leading cause from a single infectious
agent. It is indeed disheartening to know that 2/3rds of the global TB incidence is in 8 high burden countries with India
(27%) topping the list. The “End TB” Strategy, an ambitious vision of the Sustainable Development Goals (SDG) of the
WHO to end the global TB epidemic by 2030 has a tough task to achieve.
Drug resistant TB, especially Multidrug resistant TB (MDR TB), poses a great threat in achieving the global targets
to end the TB epidemic. Around 558,000 cases of Rifampicin resistant TB have been reported with 82 % of them being
MDR TB. Again, 3 countries account for almost half the burden with India, followed by China & Russia having the largest
numbers. In India, the percentage of MDR TB in new and previously treated patients is 2.8 and 12% respectively. The
important reasons for MDR TB fuelling the TB epidemic are delay in early diagnosis & initiation of treatment, poor
compliance associated with long treatment regimens, higher drug toxicities, and the associated co-morbidities like HIV,
DM, malnutrition and alcoholism. Only 1 in 4 MDR TB patients are initiated on treatment and treatment success is a
dismal 55%. Though MDR TB initially was largely a man made problem, primary MDR TB due to transmission of drug
resistant strains is now being increasingly diagnosed.
Drug resistant TB includes RR TB (resistance to only rifampicin), MDR TB (resistance to INH & Rifampicin with/
without resistance to other first line drugs), Mono resistance, especially to INH and XDR TB (MDR TB with additional
resistance to fluoroquinolone and second line injectable). Guidelines for treatment of the same were initiated in 2000
by the WHO. In 2006, the PMDT (Programmatic Management of Drug resistant TB) guidelines replacing the erstwhile
DOTS plus services were introduced and regular updates in these guidelines have taken place till 2017. Introduction
and approval of newer drugs with the hope of shortening treatment regimens, like Bedaquiline (2012) and Delaminid
(2014) and reports of greater success with shorter treatment regimens from countries like Bangladesh, Uzbekistan
etc lead to suggestions for changes in potential areas in the current guidelines. Hence, in 2018, the WHO convened a
Guideline Development Group (GDP) to update its policy recommendations on the treatment of MDR TB/RRTB. Fresh
evidence reviews from recently completed Phase 3 trials of Bedaquiline, Individual Patient Data Meta-analysis (IPD-
MA) of patients treated with shorter MDR TB regimens of 9-12 months duration(in comparison to 24-27 months in
RECENT UPDATES IN THE MANAGEMENT
OF DRUG RESISTANT TUBERCULOSIS
VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS
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conventional MDR regimen) and pharmacokinetic data of Bedaquiline and Delaminid in patients less than 18 yrs of age
were analyzed.
These new recommendations are now available in the WHO consolidated guidelines on drug-resistant TB
treatment 2019. They include significant changes as compared to the previous ones (2011-2017). Some of the important
recommendations are discussed here.
•	 Injectable agents like Kanamycin, Capreomycin and Amikacin are no longer the priority drugs for longer MDR
regimens and thus fully oral regimens are preferred for most patients.
•	 Regrouping of drugs used in the longer MDR regimens has been done (3 groups of drugs as compared to 4
previously).
•	 Fluoroquinolones (Levofloxacin & Moxifloxacin), Bedaquiline and Linezolid (Group A drugs) are strongly
recommended for use in longer regimens.
•	 Ideally all drugs from Group A, and 1 or more from Group B are preferred. Group C drugs are listed in the order
of preferential use and are to be used only in circumstances when drugs from the above groups cannot be used.
•	 Strong recommendations are for Bedaquiline use in longer MDR regimens in patients more than 18 yr and
consideration for use in children 6-17yr. Delaminid may also be included in longer regimens for MDR/RR TB for patients
above 3 yrs.
•	 Other changes in guidelines include Ethionamide / Prothionamide which were previously recommended are
now to be considered only if drugs from groups A and B cannot be used. Clavulanic acid is not recommended for use
any more.
•	 Hence, the total duration of the longer individualized MDR regimens would be 18-20 months with at least 4
drugs for the first 6 months and 3 thereafter based on individual patient benefit and tolerance. The treatment duration
after culture conversion should be 15-17 months. The recommendations apply to children, adults and PLHIV.
The standardized shorter MDR TB regimens of 9-12 months duration are recommended for MDR TB patients who
have not been previously treated or have no resistance to fluoroquinolones and second line injectables.
Response to treatment according to the new guidelines would be by monthly culture which translates into
more frequent monitoring. The areas where there are no changes as compared to previous guidelines are, start of
Anti-retroviral therapy with MDR TB treatment, use of surgery and models of TB care.
In summary, the recent update on the management of drug resistant TB focuses on fully oral regimens avoiding
injectables, shorter treatment regimens and use of newer drugs like Bedaquiline & Delaminid.
Patient centric care and support with Universal access to rapid diagnosis and DST (Drug Susceptibility Testing)
facilities, early initiation of treatment with pre-treatment counseling, monitoring response to treatment and active
drug safety are the chief pillars in the management of drug resistant TB.
References
1. Global TB Report 2018 – WHO
2. WHO consolidated guidelines on drug resistant Tuberculosis treatment, 2019
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Ict newsletter 4th edition july 2019 1

  • 1. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 1 Volume 1 | Issue 4 | July 2019 Circulation: Quarterly | All-India | e-Copy format CHIEF EDITOR Dr. Ranga Reddy EDITOR Dr. T V Rao EDITOR & CONCEPT Dr. Dhruv Mamtora TEAM MEMBER Sister Solbymol SPECIAL EDITION ON MYCOBACTERIOLOGY newsletter INFECTION CONTROL TRENDS
  • 2. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 2 Respected Infection Preventionist, Hope earlier three editions of ICT had been some help to your IPC practice. Editorial team and eminent authors have put in their best efforts to bring out yet another thematic edition information and practical advice to deal with the ancient infectious disease TB. WHO has called member nations to aggressively implement “END TB” program with an objective to end Global TB epidemic by 2030. Prime Minister Modi has gone one step ahead and pledged at “Global Stop TB Summit” to eradicate TB in India by 2025!! TB is the top infectious killer worldwide TB is also the leading cause of deaths among people with HIV & a major cause of antimicrobial resistance related death. The ancient disease has killed almost 200 crore people in last 200 years. The emergence of Drug Resistant TB is becoming a major threat to global health security causing major economic costs to individuals and nations. As per WHO: TB treatment saved 5,4 crores lives globally between 2000 and 2017. Globally, the treatment success rate for people newly diagnosed with TB was 82% in 2016. But one major problem for India is poor reporting of both cases and their treatment. “Economist Intelligence” has estimated, India is losing USD 7,3 billion (730 crores) in PPP terms due to deaths and work absence from TB which will have sizeable impact on GDP. WHO & GOI initiatives and proclamations are laudable. But to make them real, several steps to be taken. Early diagnosis of tuberculosis, Treatment of all people with tuberculosis, Preventive treatment of persons at high risk, and vaccination against tuberculosis, Political commitment with adequate resources for tuberculosis care and prevention, Engagement of communities, civil society organizations, and public and private care providers, quality and rational use of medicines, and infection control are success mantra for WHO End TB program. Ending the global TB epidemic is feasible with dramatic decline in TB deaths and cases, and elimination of economic and social burden of TB. Failure to do so will carry serious individual and global public health consequences. We, as Infection Preventionists have major role to play in “END TB” strategy. Hope you will find this edition too valuable tool to deal with ever increasing infectious disease burden. With this issue we complete one Golden Year. We thank all stakeholders for their part in this stupendous success. Sincere appreciation goes to Dr Dhruv who has taken huge burden on himself to bring all four editions in time. To further improve the standards and stay current, we shall make changes to our content delivery and design. Our editorial team also be reconfigured to get new perspectives. Your suggestions, proposals and ideas are most welcome. Regards, Editorial Team, Infection Control Trends, E-Newsletter. FOREWORD
  • 3. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 3 EDITORIAL TEAM Dr. T.V. Rao is a former Professor of Microbiology from the Andhra Medical College, Visakhapatnam (Andhra Pradesh, India). His experiences in Zambia showed him how people lose their lives to infections and how the lack of resources was a great challenge that practically forced patients to be treated blindly. His association with scientific microbiologists at ICMR (NICED Calcutta) taught him how all that we do is not necessarily right and why it is essential to involve oneself in diagnostic laboratory conditions and even bedside medicine. His observation includes the seamless working of Darwin’s Theory in relation to microbes and how they pose real challenges. He also believes it is time to rethink one’s role as Medical and Clinical Microbiologists, especially during a time where it is necessary to understand that Antibiotics are not magic bullets but soft weapons to destroy the progress of medicine. Dr. Rao has created content that helps many in developing countries with a global following of 5 million. Dr. Ranga Reddy Burri is Health policy enthusiast focused on public health awareness, education and training. Dr. Reddy is Physician, Public Health specialist & Social Entrepreneur with interest in business verticals of high social impact. He graduated from Minsk Government Medical Institute, Belarus with MD (Physician) degree; subsequently he did his PG Diploma in management from Pondicherry University and Advanced Management from IESE, Barcelona, Spain with specialization in Strategy & Business Development. Dr. Reddy is the founder trustee of Infection Control Academy of India (IFCAI). The organization is a result of his leadership skills, knowledge and experience gained from working in both domestic and international MNCs. Yet, the Academy’s most valuable strength lies in the strong sense of empathy for humans and their health imparted by Dr. Reddy and his colleague trustees. His current responsibility includes leading Sanmed Healthcare, a startup with world class manufacturing capabilities in external preparations. He supports several non-profit organizations in the capacity of advisor including Neelam Rajasekhar Reddy Research Center for Social Progress, e-learning center of Hyderabad Central University & Indian Institute of Public Health. His flair for entrepreneurship has led him to mentor through imparting knowledge to NGO’s, startups & micro-small enterprises. Dr. Dhruv Mamtora is a clinical microbiologist and infection control officer at S. L. Raheja Hospital, A Fortis associate, Mahim, Mumbai since 2015. Before joining in private sector, he has worked with government sector both in Maharashtra state as assistant professor at RCSM GMC Kolhapur and GMC Latur as assistant professor and AIIMS, Jodhpur as senior resident. He has passed out MBBS from L. T. M. Medical College (Sion Hospital) and done MD in microbiology from Government medical college, Miraj. He has done his healthcare administration EPGDHA from TISS, Mumbai. He is member of multiple professional bodies like IAMM, IATP, IMA, HIS-MF (institutional), society of clinical microbiologists (SCM) and ISID (international society of infectious diseases). He has number of publications in peer reviewed journals, both national as well as international & he is also faculty and speaker for various national and international, conferences. He has also organized many training activities and a national level conferences. He is also a media subject expert. He has also guided as well as multiple projects related to healthcare which is in field of infection control and clinical microbiology. He has been awarded multiple times in his organization and at national level. His topics of interest are implementing and improving quality in healthcare, hospital and laboratory accreditation, clinical microbiology, infection control, antimicrobial stewardship & improving medical education to a minimum basic standard which is suitable for current healthcare scenario in country and on international level. Sister Solbymol P S is a PICU Nurse with 19 years of experience. She has worked as In-charge PICU Rainbow Children’s Hospital, Hyderabad and Vikrampuri, senior staff at Ernakulam Medical Centre Kochi. She is now working as Coordinator Quality and Infection Control Nurse at Kinder Women’s Hospital and Fertility Centre, Cherthala, Alappuzha. Dr. Ranga Reddy President IFCAI and Chief Editor “Infection Control Trends” Email: dr.rangareddy@ifcai.in Dr. Dhruv Mamtora Consultant Microbiologist and Infection Control Officer Email: dhruv_mamtora@yahoo.com Dr. T. V. Rao Former Professor of Microbiology Email: doctortvrao@gmail.com Solbymol P S GNM, ICCP Email: solbyps@gmail.com
  • 4. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 4 INDEX Guest Editorial - Dr. Chugh “End TB Strategy” : Indian Perspective 06 Guest Editorial - Dr. Ameeta Joshi Tuberculosis Laboratory in a Resource limited setting 08 Guest Editorial - Dr. Vijaya Lakshmi Nag Non Tuberculous Mycobacteria (Ntm): Advances In Diagnosis 10 Guest Editorial - Dr. Rakesh P S TB Infection Prevention and Control: 2019 Update 15 The Enigma Of Tuberculosis Continues? Story of Success, Failures and Hope? - Dr. T. V. Rao 17 Understanding Airborne Transmission From Infection Preventionists’ View - Dr. Dhruv Mamtora 19 Role Of An Infection Control Nurse In Tuberculosis - Dr. Ankit Gupta, Ms Prerna Rani, Mr. Prijil Innocent 21 The Need For Psychosocial Intervention In Care For Chronic Illness - Ms. Pragya Lodha 24 Iron & Mycobacterium Tuberculosis – Is There A Hope? - Dr. Sourav Maiti 27 Extrapulmonary Tuberculosis - Diagnostic Challenges - Dr. Sukanya Rengaswamy 28 Paediatric Tb-Trying To Understand From Ic Perspective - Dr. H Srinivasa 31 Recent Updates In The Management Of Drug Resistant Tuberculosis - Dr. Aruna Shanmuganathan 33
  • 5. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 5 INDEX Comparison Of CD4 Counts In HIV-TB Co-Infection Before And After Art - Dr Ravikanti, Dr Sunitha.B.R. Prof, Dr. G. Vishwanath 35 Tuberculosis Prevention In Healthcare Settings - Dr. Nazia Khan 39 Community Infection Control in The Context of Injection - Dr. Joven Jebio Ongole, Dr. Sharon Fynn, Dr. Gregory Jagwer 44 Infection Prevention In Community Health Facilities In The Northwest And Southwest Regions - Amungwa Athanasius Nche 50 Antibiotic Cycling and Antibiotic Mixing: Is it Time for Requiem? - Dr. Abhijit Chaudhury 56 Objectives Of E -Newsletter On Infection Control Trends 59 Rules and Regulations 60
  • 6. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 6 Dr. Chugh National Professor Emeritus of National Academy of Medical Sciences India. Past Prof Medical College Rohtak The World Health Organization (WHO) has launched an ambitious program of “End TB” in collaboration with various international and national organizations. The targets are: 1. An incidence rate of less than 10 cases per 100,000 populations per year. 2. Reduce TB deaths by 95%. 3. To cut new cases of TB by 95% in 2015-35. To achieve this goal, we need to know: Our present burden of disease and measures to be taken to achieve the goal. Present status of TB Burden Worldwide, 9.6 million new TB cases and 1.5 million deaths were seen during 2014. About 3.3% new cases and 20% retreatment cases were MDR-TB. The treatment success rate of MDR cases is 50% and only 2.2% for XDR cases. The annual burden of TB in India is 2.2 million. However, since ~80% of cases are treated in private sector, this estimate is under-reported. The actual number of cases is 2-3 times higher. The mathematical modeling of transmission in India shows an annual incidence of smear positive cases 89.8 per 100,000 population. Urban TB cases infect more due to high population density and rural cases remain infectious for a longer period due to inappropriate treatment and poor compliance. The Government of India in its National Strategic Plan has set an ambitious goal to achieve this target by the year 2025, five year ahead of global deadline. With the current rate of annual decline of TB cases, it seems to be an “almost impossible” task to achieve the goal by 2025. If we wish to achieve it, the decline rate should be more than 10-15% per year, the present rate of decline being less than 2%. There is a need to provide better diagnostics and treatment support, improved TB surveillance and healthcare system, nutrition, higher financial allocation and health education for airborne precautions. Early detection and treatment of patients and their follow-up with full compliance is the first step to it. Global Fund executive director on 18/02/2019 stated: “India’s goal of ending TB by 2025 will be a tough task”. GUEST EDITORIALS “END TB STRATEGY”: INDIAN PERSPECTIVE
  • 7. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 7 Other Issues of Human Tuberculosis in India are: 1. Zoonotic tuberculosis in humans caused by bovine. Mycobacterium tuberculosis (bMTB), its epidemiology, and appropriate treatment is imprecise and unresolved issue. The potential zoonosis, reverse zoonosis and mixed infections in India need further studies. 2. Latent TB in India is seen in 40% population (and 50% of healthcare personnel). Around 10% of these individuals develop full-fledged TB at some time of their life. There is no current policy of diagnosis and treatment of cases of latent TB in India. 3. The risk of tuberculosis in patients with cancer is significantly high in India and globally. 4. Molecular techniques show mycobacterial DNA and RNA in 48% of sarcoid biopsy tissues in India.3 5. Burden of nosocomial tuberculosis in healthcare personnel in India is significant due to lack of effective infection control policies and their implementation.4,5 6. The global burden of pediatric TB is ~ 1.3 million new cases with 0.5 million deaths every year. Microbio- logical confirmation is absent in three-fourth of the cases due to paucibacillary disease and impropriate diagnostics.6 7. Non-tuberculosis mycobacterium (NTM) prevalence in a TB endemic country (India) is high but often ignored.1 8. Mycobacterial disease, both MTB and NTM in patients with rheumatoid arthritis is 4-fold higher. There is a need to monitor such patients.7 9. Tuberculosis and chronic obstructive pulmonary disease (COPD) have a statistically significant association. With poor air quality, high COPD in a TB endemic country (Inida), there is a need for better vigilance. India needs to take a multi-pronged approach to reach its goal of “End TB”. References 1. Chugh TD. Human tuberculosis in Inida: Some neglected issues. Curr Med Res Prac 2017; 8:64-66 2. Singh N, Madan k, Aggarwal AN et al. Pleuropulmonary tuberculosis following chemotherapy for lung cancer at a tertiary care centre in India, Intl J Curr Microbial 2013; 47: 177-180. 3. Gupta D, Agarwal R, Agarwal AN, Jindal SK. Molecular evidence for the role of mycobacterium in sarcoidosis : a meta- analysis. Eur Resp J 2007; 30: 508-16. 4. Chugh TD. Burden of nosocomial tuberculosis in healthcare workers in India. Curr Med Res Prac 2017; 7: 18-19. 5. Basavaraj A, Chandanwale A, Patil A et al. Tuberculosis risk among medical trainers, Pune India. Emerg Infect Dis 2016; 22: 541-543. 6. Chugh TD. Diagnosis of paediatric tuberculosis. Curr Med Res Prac 2016; 6: 107-108. 7. Liao TL, Lin CH, Shen GH et al. Risk of mycobacterial arthritis, Taiwan, 2001-2011. Emerg Infect Dis 2015; 21 (8): 1387-1395. 8. Lee CH, Lee MC, Shucc et al. Risk for pulmonary tuberculosis in patients with chronic pulmonary obstructive disease in Taiwan: a nationwide cohort study. BMC Infect Dis 2013; 13: 194.
  • 8. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 8 Dr. Ameeta Joshi Prof & Head, Microbiology, GGMC & JJ Hospital Mumbai Superintendent, Cama & Albless Hospital, Mumbai Introduction Tuberculosis (TB) continues to be India’s severest health crisis inspite of TB control activities for more than half a decade. The National Strategic Plan (NSP) 2017-2025 talks about a vision of TB-Free India with zero deaths, disease and poverty due to tuberculosis and a goal to achieve a rapid decline in burden of TB morbidity and mortality while working towards elimination of TB in India by 2025. TB can be controlled in the modern era, as long as TB is diagnosed early and treated properly and transmission thus interrupted. The challenge facing TB control in India remains delayed diagnosis and inadequate treatment, particularly among patients seeking care from private providers, who alone are ill-equipped to sustain their patients on prolonged, costly treatment. The requirements for moving towards TB elimination have been integrated into the four strategic pillars of “Detect – Treat – Prevent – Build” (DTPB). For detection we need diagnostic tests that are not only sensitive & specific but also algorithms so that every effort is made so as to not miss any case and for all these we need quality assured laboratories. Laboratory To achieve universal access to early accurate diagnosis of TB and enhance case finding efficiency, identification of presumptive TB cases at the first point of care and linking them to the best available diagnostic tests is of paramount importance. For all these one needs a laboratory which is designed in such a way so that there is protection of all personnel working inside the laboratory, sample protection as well as the surrounding environment is also protected. Whether to construct a biosafety level (BSL) 1, 2 or 3 will depend on what are the tests that the lab is going to conduct, but whatever the BSL of the laboratory good laboratory practices is mandatory. TUBERCULOSIS LABORATORY IN A RESOURCE LIMITED SETTING GUEST EDITORIALS
  • 9. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 9 If low risk activities (only microscopy and or GeneXpert tests) are going to be offered then BSL1 is sufficient wherein one has to have open bench operations, operable windows having insect screens, standard lab practices. Biosafety Cabinets (BSCs) not required, if GeneXpert machine is there then there should be a dedicated room for housing the GeneXpert machine, this room will require air conditioning and a Uninterrupted Power Supply (UPS) for the machine. If the laboratory intends to perform medium risk activities (manipulate the sputum sample, sputum concentration or performing a Line Probe Assay (LPA) on sample) then BSL-2 lab is required, wherein all practices of BSL1 requirements along with limited access into laboratory, BSC Class II A2, will be needed. In case the laboratory plans to do high risk activities (culture the TB organisms or manipulate/ perform tests on the cultures) then all requirements of BSL1 & BSL 2 plus lab design specifically for biological containment (that is BSL-3) will be needed along with special protective clothing for staff and an autoclave. If one is planning on opening a TB laboratory professional help of architects (who understand containment, biosafety concepts), financers (to estimate capital and life cycle costs) have to be used. There are vendors who give total (turnkey), infrastructural (design as well as civil structure only), equipment only, consumables only solutions. In the public sector the microbiologists is totally involved right from the planning to the implementation and maintenance phase, which might not be the case in case of the private sector. While planning one need to estimate capital and life cycle costs for the laboratory operating facility, whereby the capital cost will include design, construction, commissioning and equipment cost and the life cycle cost will include utility expense for ventilation and electric power, filter testing / replacement, inspections, insurance etc;. HVAC (heating, ventilation, Air Conditioning), AHU (Air Handling Unit), Refrigerated Centrifuge and BSCs are main equipment where special focus needs to be given especially when one is planning to set up a culture facility. Location of the HVAC needs to be as close to the BSL3, with minimum bends in the ducts in order to cut down on the cost. It is preferable to ensure that all electrical light fixtures, switch/sockets, controls, sensors etc. are flushed with the surface, sealed with silicon sealant, chemical resistant and able to withstand fumigation with disinfectant chemicals. All Equipments favorably to have their own online UPS (Uninterrupted Power Supply) and battery backup of requisite hours (based on the running time of the machine, e.g. for a refrigerated centrifuge battery backup of half an hour as the run time of centrifugation is 20 minutes) Before the vendor hands over the TB facility ensure that he has supplied the validation document, detailed procedure for validation, parameters for validation along with validation schemes for architectural layout plans, specialized systems like HVAC system, air filtration system, pressure control system etc; services & utility like power supply and distribution system, water supply and distribution system etc; The aim of the TB lab is not only to offer quality assured TB diagnostic tests but ensure the safety of the laboratory workers & the safety of the environment this will help in achieving the goal of achieving universal access to quality TB diagnosis including drug resistant TB in the Country.
  • 10. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 10 Dr. Vijaya Lakshmi Nag Prof. & Head, Department of Microbiology, All India Institute of Medical Sciences, Jodhpur, Rajasthan-India Non-tuberculous mycobacteria (NTM), defined as any mycobacterial pathogen other than Mycobacterium tuberculosis (Mtb) or M. Leprae. More than 170 different species known to cause disease, ranging from skin ulceration to severe pulmonary and disseminated disease. Some species like M. avium complex (MAC), M. abscessus implicated worldwide; others like M. malmoense are regionally significant. According to the growth rate NTM classified in to rapid and slow growing mycobacteria. These bacteria are widely isolated from environmental sources, including drinking and natural water, as well as soil and dust. The steady increase of NTM infections is likely due to greater exposure to large-volume aerosols, a modernization of plumbing away from antibacterial copper pipes, and lower hot water temperatures, which may promote environmental colonization and NTM persistence. The spectrum of disease caused by NTM include tuberculosis (TB), like pulmonary and extrapulmonary disease, cervical lymphadenitis in young children, and visceral and disseminated disease. Pulmonary NTM infections are most commonly due to MAC, M. kansasii, and M. abscessus, which cause often unappreciated, worldwide burden of illness. MAC species are abundant across the Americas, Australia, Europe, and regions of Asia compared to other species causing pulmonary disease. Other frequently cultured NTM include M. kansasii and M. abscessus, whereas less frequent infections can occur with M. xenopi, M. fortuitum, and M. chelonae species. Indirect transmission of the bacteria, particularly occur in immunosuppressed individuals. The aerosolized NTM can also survive on fomites, providing another mechanism for spread, particularly for susceptible cystic fibrosis (CF) patients. The ubiquitous presence of NTM in the environment makes them ideal candidates for opportunistic infections and therefore warrants specific and detailed diagnostics and further evaluation for intervention against disease. NTM may cause disease similar to Mtb, however they generally do not respond to classic TB drug regimens, and therefore a misdiagnosis of Mtb can lead to poor treatment, particularly in resource-poor settings lacking diagnostic infrastructure. The treatment for NTM infection in chronic cases requires lengthy, complex, and sometimes poorly tolerated drug regimens over many months to years, and following treatment, patients can experience relapse from incomplete treatment or reinfection. The recent rise in interest in diseases caused by NTM attributed to increasing association of NTM with acquired NON TUBERCULOUS MYCOBACTERIA (NTM): AD- VANCES IN DIAGNOSIS GUEST EDITORIALS
  • 11. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 11 immunodeficiency disease (AIDS) as well as increasing isolation in non-AIDS population. This increase in the detection rate is a result of improved awareness and laboratory methodology, which require accurate identification of NTM species from clinical specimens. Mycobacterial species differ in virulence and may present characteristic antimicrobial patterns, hence, correct species identification is important as it may also aid in treatment decision. Diagnosis: The clinical evaluation of a patient suspected of nontuberculous mycobacterial (NTM) infection is required before processing of the sample. Important specimens are Sputum, Broncho alveolar lavage (BAL), body fluids, aspirates (ascitic tap, pleural tap, synovial fluid, drains, pus discharge, gastric aspirates, and cerebrospinal fluid (CSF)) and early morning whole urine sample for three consecutive days collected in a sterile containers. The NTM clinical disease in human are due to environmental mycobacteria, therefore, a single positive culture from nonsterile sources including the respiratory or digestive tract does not necessarily indicate infection or disease and makes treatment decisions less straightforward. Often, 2 positive microbiological cultures are needed to differentiate NTM disease versus colonization; however, these criteria have not been validated with respect to progression to disease. The clinical, radiographic, and microbiologic criteria are equally important in exclusion of other infectious diseases like, TB, nocardiosis, fungal infection; and noninfectious diseases eg. Sarcoidosis to make a diagnosis of NTM disease. Microscopy: The smear can be stained with Ziehl-Neelsen (ZN) and modified Kinyoun staining. The preferred staining procedure is fluorochrome microscopy; studies reported that ZN and auramine staining are more sensitive than Kinyoun staining. While in histopathological examinations, the sensitivity of fluorescence microscopy and ZN staining is low due to negative influence by formalin fixation. Furthermore, smear sensitivity is lower in extra-pulmonary TB patients, and persons infected with NTM as compared to M. tuberculosis cases. However, it is very clear that ZN microscopy is an important method in detection of mycobacteria, but it alone is unable to help in identification and must be associated with culture. Culture: Lowenstein-Jensen (LJ) is conventional medium for the growth of Mycobacterium tuberculosis, and inferior to Middlebrooks agar as an all-purpose medium for both M. tuberculosis and NTM. The liquid medium culture system BACTEC (Becton-Dickenson Diagnostics), MB Redox (Heipha Diagnostika), BacT/ALERT® MP (bioMerieux, France), MGIT (BD Diagnostics), and Septi-check (BD Diagnostics) are commonly used. Most media require additives OADC enrichment (mixture of Bovine albumin, Dextrose, Catalase, and Oleic acid) to increase the growth rate and PANTA antibiotic (mixture of polymyxin B, amphotericin B, nalidixic acid, trimethoprim, and azlocillin) are often added to inhibit the growth of contaminants. The conventional solid method for the growth of mycobacteria is time-consuming (6–8 weeks), but considered “gold standard. Liquid-based culture has high sensitivity and the growth of M. tuberculosis detected within 1–2 weeks. However, they always be used in combination with the conventional LJ method for NTM culture. NTM speciation by phenotypic method: The rate of growth, pigmentation of colonies, and various biochemical reactions used for phenotypic identification of NTM species. However, these tests are time consuming and tedious to perform. Immunochromatographic test Rapid assays include Immunochromatographic test (standard deviation [SD] MPT64 TB Ag Kit) developed by SD Bioline, South Korea which facilitates rapid detection and differentiation of MPT 64 antigen in M. tuberculosis isolates and NTM. MPT 64 TB Ag kit is highly sensitive and give speedy identification of MTBC, together with M. tuberculosis, M. africanum, M. bovis, and substrains of M. bovis BCG. The sensitivity is >99%, and 100% specificity. The advantage of
  • 12. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 12 MPT64 TB Ag test are very easy to perform from direct culture positive specimens, does not require any extraordinary equipment and can easily distinguish between MTBC and NTM. Molecular identification: The molecular identification of different NTM species done by genomic DNA compari- son, but this is labor intensive. The mycobacterial 16S rRNA gene is highly conserved, more accurate than phenotypic methods for species identification. If there are differences in the sequence of 1% or greater, generally define a new species. Studies favoring, molecular-based PCR methods are more sensitive (sensitivity >84%) as compared to phe- notypic culture based methods (sensitivity up to78.0%); and phenotypic are methods are more time consuming. For these reasons, 16S rRNA can be used as a standard reference when comparing detection techniques. NTM identification done to the species level by line-probe assays, used to amplify drug-resistance -determining regions. The GenoType NTM-DR line-probe assay (Hain Lifescience, Nehren, Germany) is one such tool used for the identification of clinical M. abscessus subspecies (subsp.) and drug resistance. Rapid species identification can also be determined using commercial DNA probes (MAC, M. kansasii, and M. gordonae), while group- or complex-level identification accomplished with high-performance liquid chromatography (HPLC). For some NTM isolates, especially rapidly growing mycobacteria (RGM; M. fortuitum, M abscessus, and M. chelonae), extended antibiotic in vitro susceptibility testing, DNA sequencing, or polymerase chain reaction (PCR) restriction endonuclease assay (PRA) may be necessary. Another assay available for the detection of Mycobacterium species from clinical samples is a PCR-reverse blot hybridization assay (REBA) Myco-ID assay (YD Diagnostics, Yongin, South Korea), in which multiple targeted oligonucleotide specific probes (Mycobacterium-species specific) are bound to a nitrocellulose membrane strip, then hybridized with biotinylated PCR products and subsequently visualized by colorimetric hybridization signals. (MALDI-TOF): Rodríguez-Sánchez and colleagues assessed 125 NTM isolates using matrix-assisted laser de- sorption ionization-time of flight (MALDI-TOF) mass spectrometry, the GenoType common mycobacteria (CM)/ad- ditional species (AS) assay, and a 16S rRNA/hsp65 gene sequencing reference assay to determine the alignment of these different techniques. The MALDI-TOF assay was in agreement with the reference assay in 94.4% cases, and the GenoType CM/AS assay was in agreement in 84% cases, showing some limitations in loss of sensitivity of the Geno- Type CM/AS assay. However the MALDI-TOF assay requires a mass spectrometer, the GenoType CM/AS assay can be performed using either manual or automated processing, making it more accessible in resource-limited settings. QMAP assay: Another innovative molecular assay, the Quanta matrix multiplexed assay platform (QMAP) sys- tem recently described by Wang and colleagues, allows clinicians to discriminate between mycobacterial species. This assay utilizes an automated magnetic-bead–based assay following similar PCR steps as used in the PCR-REBA assay, except denatured biotinylated PCR products added to species-specific oligonucleotide probes coupled to carboxylat- ed microdisks, followed by the addition of streptavidin R-phycoerythrin conjugate and automated reading of fluores- cence intensity. This process has high specificity and sensitivity and very less time consuming (~3 hrs). Experimental animal models for NTM: Preclinicalanimalmodelscanbeusedtostudytheinfluenceofthefactors,whichaffecttheNTMdiseaseprocess.and evaluatenoveltherapeuticdrugsandregimensfortreatmentofNTMinfections.TwomajorcategoriesofNTMdiseaseto considerforanimalmodeldevelopmentincludepulmonarydiseaseandextrapulmonary-disseminateddisease(typically presenting in immunocompromised). NTM are generally less virulent than Mtb, and therefore the capacity to induce a sustained progressive infection in a mouse strain is an important criterion and current hurdle for the development of an experimentalmousemodel.Studieshaveshownthatmostimmunocompetentmousestrainsserveasoutstandingmodels forthemorevirulentMACspecies;demonstraterapidclearancewheninfectedwiththelessvirulentM.abscessusisolate making model development and selection challenging. Many different mouse strains have been used to screen different drug compounds against MAC, including CLR, RIF, rifapentine (RPT), moxifloxacin (MXF), EMB, and amikacin (AMK). Animal models for slow-growing mycobacteria: The Beige mouse is used as a standard model for MAC disease. This mouse model was developed in the mid-1990s because of the increasing numbers of HIV-seropositive patients becoming coinfected with M. avium. Beige mice display
  • 13. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 13 many immune deficiencies similar to those occurring in AIDS patients, as well as a susceptibility to infection with NTM following either intravenous or aerosol infection, providing a unique opportunity for the study of MAC infections in this model. The Beige mouse model is also use to screen the chemotherapeutic potential of promising compounds for the treatment of MAC disease. CLR and rifampicin for 6 weeks, and then treatment is stopped. Twelve weeks following drug treatment, mice are given immunosuppressants (dexamethasone or sulfasalazine) for 5 weeks to expose any remaining bacteria post-treatment. Bacterial burden is assessed in the organs at different times after immunosuppression to measure reactivation.Thismodelcouldalsobeusefulfordeterminingthepotentialefficacyofcombineddrugandimmunotherapy regimens by quantifying the numbers of bacilli remaining after treatment. Animal models for Rapid growing mycobacteria (RGM): The most clinically important RGM to cause human lung disease belongs to M. abscessus. M. abscessus subsp. abscessus and M. abscessus subsp. bollettii have a functional erm41 gene; therefore, resistance to macrolides may be identified. It has been challenging to develop an animal model for screening compounds against RGMs because of gaps in fully understanding their pathogenesis of infection and relative avirulence. A progressive aerosol infection model has proven elusive since most mouse models with significant deficits in innate or acquired immunity are still able to clear an infection with a high level of RGM. This highlights the need for improved understanding of the NTM pathogenesis of infection. The biggest challenge that remains to advance the knowledge in NTM pathogenesis and protection is to fully understand the process of human NTM infections (environmental, nosocomial, and endogenous/exogenous reinfection), which can be used to help in development of animal models. 1. Falkinham JO 3rd,. Epidemiology of infection by nontuberculous mycobacteria. Clin Microbiol Rev. 1996;9(2):177–215. 2. Jeong SH, Kim SY, Huh HJ, Ki CS, Lee NY, Kang CI, et al. Mycobacteriological characteristics and treatment outcomes in extrapulmonary Mycobacterium abscessus complex infections. Int J Infect Dis. 2017;60:49–56. 3. Koh WJ, Jeong BH, Kim SY, Jeon K, Park KU, Jhun BW, et al. Mycobacterial characteristics and treatment outcomes in Mycobacterium abscessus lung disease. Clin Infect Dis. 2017;64(3):309–16. 4. Koh WJ, Moon SM, Kim SY, Woo MA, Kim S, Jhun BW, et al. Outcomes of Mycobacterium avium complex lung disease based on clinical phenotype. Eur Respir J. 2017;50(3): 5. Diel R, Nienhaus A, Ringshausen FC, Richter E, Welte T, Rabe KF, et al. Microbiologic outcome of interventions against Mycobacterium avium Complex pulmonary disease: A systematic review. Chest. 2018;153(4):888–921. 6. Nishiuchi Y, Iwamoto T, Maruyama F. Infection sources of a common non-tuberculous mycobacterial pathogen, Mycobacterium avium Complex. Front Med (Lausanne). 2017;4:27 10.3389/fmed.2017.00027 7. Prevots DR, Marras TK. Epidemiology of human pulmonary infection with nontuberculous mycobacteria: a review. Clin Chest Med. 2015;36(1):13–34. 8. Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C, Gordin F, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007;175(4):367–416. 9. Ryu YJ, Koh WJ, Daley CL. Diagnosis and treatment of nontuberculous mycobacterial lung disease: Clinicians’ perspectives. Tuberc Respir Dis (Seoul). 2016;79(2):74–84. 10. Falkinham JO 3rd,. Environmental sources of nontuberculous mycobacteria. Clin Chest Med. 2015;36(1):35– 41. 11. Haworth CS, Banks J, Capstick T, Fisher AJ, Gorsuch T, Laurenson IF, et al. British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD). Thorax. 2017;72(Suppl 2):ii1– ii64. 12. Koh WJ, Chang B, Ko Y, Jeong BH, Hong G, Park HY, et al. Clinical significance of a single isolation of
  • 14. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 14 pathogenic nontuberculous mycobacteria from sputum specimens. Diagn Microbiol Infect Dis. 2013;75(2):225–6. 13. Martiniano SL, Sontag MK, Daley CL, Nick JA, Sagel SD. Clinical significance of a first positive nontuberculous mycobacteria culture in cystic fibrosis. Ann Am Thorac Soc. 2014;11(1):36–44. 14. Wright PW, Wallace RJ Jr., Wright NW, Brown BA, Griffith DE. Sensitivity of fluorochrome microscopy for detection of Mycobacterium tuberculosis versus nontuberculous mycobacteria. J Clin Microbiol. 1998;36(4):1046–9. 15. Kehrmann J, Kurt N, Rueger K, Bange FC, Buer J. Genotype NTM-DR for identifying Mycobacterium abscessus subspecies and determining molecular resistance. J Clin Microbiol. 2016;54(6):1653–5. 16. Wang HY, Kim H, Kim S, Bang H, Kim DK, Lee H. Evaluation of PCR-reverse blot hybridization assay for the differentiation and identification of Mycobacterium species in liquid cultures. J Appl Microbiol. 2015;118(1):142–51. 17. Springer B, Stockman L, Teschner K, Roberts GD, Bottger EC. Two-laboratory collaborative study on identification of mycobacteria: molecular versus phenotypic methods. J Clin Microbiol. 1996;34(2):296–303. 18. Tortoli E. Impact of genotypic studies on mycobacterial taxonomy: the new mycobacteria of the 1990s. Clin Microbiol Rev. 2003;16(2):319–54. 19. Deggim-Messmer V, Bloemberg GV, Ritter C, Voit A, Homke R, Keller PM, et al. Diagnostic molecular mycobacteriology in regions with low tuberculosis endemicity: Combining real-time PCR assays for detection of multiple mycobacterial pathogens with line probe assays for identification of resistance mutations. EBioMedicine. 2016;9:228–37. 20. Rodriguez-Sanchez B, Ruiz-Serrano MJ, Marin M, Lopez Roa P, Rodriguez-Creixems M, Bouza E. Evaluation of matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of nontuberculous mycobacteria from clinical isolates. J Clin Microbiol. 2015;53(8):2737–40. 21. Wang HY, Uh Y, Kim S, Lee H. Performance of the Quantamatrix multiplexed assay platform system for the differentiation and identification of Mycobacterium species. J Med Microbiol. 2017;66(6):777–87. 22. Jagielski T, Minias A, van Ingen J, Rastogi N, Brzostek A, Zaczek A, et al. Methodological and clinical aspects of the molecular epidemiology of Mycobacterium tuberculosis and other mycobacteria. Clin Microbiol Rev. 2016;29(2):239–90. 23. Huh HJ, Kim SY, Jhun BW, Shin SJ, Koh WJ. Recent advances in molecular diagnostics and understanding mechanisms of drug resistance in nontuberculous mycobacterial diseases. Infect Genet Evol. 2018. October 11 24. Wassilew N, Hoffmann H, Andrejak C, Lange C. Pulmonary disease caused by non-tuberculous mycobacteria. Respiration. 2016;91(5):386–402. 25. Bryant JM, Grogono DM, Greaves D, Foweraker J, Roddick I, Inns T, et al. Whole-genome sequencing to identify transmission of Mycobacterium abscessus between patients with cystic fibrosis: a retrospective cohort study. Lancet. 2013;381(9877):1551–60. 26. Obregon-Henao A, Arnett KA, Henao-Tamayo M, Massoudi L, Creissen E, Andries K, et al. Susceptibility of Mycobacterium abscessus to antimycobacterial drugs in preclinical models. Antimicrob Agents Chemother. 2015;59(11):6904–12. 27. Gangadharam PR. Beige mouse model for Mycobacterium avium complex disease. Antimicrob Agents Chemother. 1995;39(8):1647–54. 28. Bermudez LE, Inderlied CB, Young LS. Mycobacterium avium complex in AIDS. Curr Clin Top Infect Dis. 1992;12:257–81. 29. Shiloh MU, Nathan CF. Reactive nitrogen intermediates and the pathogenesis of Salmonella and mycobacteria. Curr Opin Microbiol. 2000;3(1):35–42. 30. Andrejak C, Almeida DV, Tyagi S, Converse PJ, Ammerman NC, Grosset JH. Characterization of mouse models of Mycobacterium avium complex infection and evaluation of drug combinations. Antimicrob Agents Chemother. 2015;59(4):2129–35.
  • 15. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 15 Dr. Rakesh PS Medical Consultant, TB Elimination, WHO-RNTCP Technical Assistance Project, Kerala With a burden of disease that accounts for more than 10 million new cases per year, tuberculosis (TB) continues to be a major global health threat (1). Although the global number of TB deaths fell by 42% between 2000 and 2017, and the annual decline in the global TB incidence rate is currently 1.5% (1), much action is needed to accelerate progress towards achieving global milestones to end TB (2). Interrupting the cycle of M. tuberculosis transmission is crucial to achieving global targets to end the TB epidemic. Thus, there is a need to implement interventions to rapidly identify source cases, and impede person-to-person transmission by reducing the concentration of infectious particles in the air and the exposure time of susceptible individuals. These principles form the basis for effective infection prevention and control (IPC). Also, it has to be kept in mind that 9299 TB cases among health workers were reported in 60 countries alone, with the notification rate for health care associated transmission of Mycobacterium tuberculosis being twice as high as the rate in the general adult population. The threats posed by epidemics, pandemics and AMR have become increasingly evident as ongoing universal challenges, and they are now recognized as a top priority for action on the global health agenda. Effective IPC is the cornerstone of such action. The International health regulations position effective IPC as a key strategy for dealing with public health threats of international concern (2). United Nations Sustainable Development Goals (SDGs) highlighted the importance of IPC to safe, effective, high-quality health service delivery and universal health coverage. WHO has released the TB Infection Prevention and Control 2019 Update which is evidence-informed recommendations outlining a public health approach to prevent M. tuberculosis transmission within the clinical and programmatic management of TB, and to support countries in their efforts to strengthen or build reliable, resilient and effective IPC programmes to reach the targets of the “End TB Strategy”. The summary of recommendations for TB IPC based on 2019 updates is as follows: Recommendation 1: Triage of people with TB signs and symptoms, or with TB disease, is recommended to reduce M. tuberculosis transmission to health workers (including community health workers), persons attending health care facilities or other persons in settings with a high risk of transmission. (Conditional recommendation based on very low certainty in the estimates of effects) TB INFECTION PREVENTION AND CONTROL: 2019 UPDATE GUEST EDITORIALS
  • 16. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 16 Recommendation 2: Respiratory separation / isolation of people with presumed or demonstrated infectious TB is recommended to reduce M. tuberculosis transmission to health workers or other persons attending health care facilities. (Conditional recommendation based on very low certainty in the estimates of effects) Recommendation 3: Prompt initiation of effective TB treatment of people with TB disease is recommended to reduce M. tuberculosis transmission to health workers, persons attending health care facilities or other persons in settings with a high risk of transmission. (Strong recommendation based on very low certainty in the estimates of effects) Recommendation 4: Respiratory hygiene (including cough etiquette) in people with presumed or confirmed TB is recommended to reduce M. tuberculosis transmission to health workers, persons attending health care facilities or other persons in settings with a high risk of transmission. (Strong recommendation based on low certainty in the estimates of effects) Recommendation5:Upper-roomgermicidalultraviolet(GUV)systemsarerecommendedtoreduceM.tuberculosis transmission to health workers, persons attending health care facilities or other persons in settings with a high risk of transmission. (Conditional recommendation based on moderate certainty in the estimates of effects) Recommendation 6: Ventilation systems (including natural, mixed-mode, mechanical ventilation and recirculated air through high-efficiency particulate air [HEPA] filters) are recommended to reduce M. tuberculosis transmission to health workers, persons attending health care facilities or other persons in settings with a high risk of transmission. (Conditional recommendation based on very low certainty in the estimates of effects). Overall, the preference for ventilation systems in resource-limited settings, based on available evidence of effectiveness and assumptions about financial constraints, was (in order of decreasing preference): (i) natural ventilation; (ii) mixed-mode ventilation; (iii) mechanical ventilation; and (iv) recirculated air with HEPA filtration. This order of preference may not be applicable in settings where resources are sufficient to procure and sustain more sophisticated systems, or where climatic conditions impede the use of natural or hybrid (mixed-mode) ventilation systems. While robust or highly specialized systems can reduce the concentration of infectious droplet nuclei in the air and thus prevent transmission, such systems may cause a false sense of reassurance, given the challenges in installation and maintenance, and the likelihood of human error in their implementation. In addition, in resource-limited settings, highly specialized systems (e.g. mechanical ventilation systems and recirculated air through HEPA filters) would have a negative impact on equity and access, because they may not be adopted nationwide, being too expensive to install and maintain properly. Recommendation 7: Particulate respirators, within the framework of a respiratory protection programme, are recommended to reduce M. tuberculosis transmission to health workers, persons attending health care facilities or other persons in settings with a high risk of transmission. (Conditional recommendation based on very low certainty in the estimates of effects) The interventions described under each recommendation are not intended as stand-alone interventions; rather, they are to be implemented as a full IPC package. References 1. Global tuberculosis report 2018 (WHO/ CDS/TB/2018.20). Geneva: World Health Organization 2. International health regulations (2005) (third edition). Geneva: World Health Organization; 2016 3. WHO guidelines on tuberculosis infection prevention and control, 2019 update, Geneva: World Health Organization; 2019
  • 17. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 17 Dr. T. V. Rao Former Professor of Microbiology Email: doctortvrao@gmail.com Tuberculosis continues to be one of the most ancient diseases in human history. Skeletons of Egyptian mummies show clear evidence of the disease dating back 6,000 years, although some scientists believe it is much older than that. Genetic analysis of Mycobacterium seems to suggest that modern strains of M. tuberculosis originated from a common ancestor in Africa about 15,000 to 20,000 years ago. ROBERT KOCH - STORY OF GREATEST INVENTION AND FAILURE TOO - In 1883, Robert Koch discovered that the cause was from a bacterium called Mycobacterium tuberculosis. A little while after, he claimed to have discoveredthecure.AfterannouncementoftreatmentforTuberculosiswithtuberculintherapy,thescientificsocietiesand people excited and over 2000 people congregated to Germany for treatment. Everyone thought that the new treatment would cure the patients, but it actually did the opposite! More and more people died at faster rates than TB patients without treatment. Although Koch tried to save thousands of people's lives but failed, however, he was identified with the invention of the Bacteria as he discovered the cause of tuberculosis which was a major turning point in the annals of Medicine. A panoramic view of Koch's life reveals an array of unprecedented achievements intermixed with a few notable failures. Koch's principal failures – his belief in the therapeutic potential of tuberculin, his error regarding bovine tuberculosis, and his acerbic treatment of opponents – do little to mar the legacy of a dedicated physician In 1905, Koch won the Nobel Prize in Physiology and Medicine for his work with tuberculosis. TUBERCULOSIS STILL HAPHAZARDLY TREATED? Tuberculosis continues to be haphazardly treated as many people who have become infected with tuberculosis don’t even realize that they have an active infection. One should be aware of someone infected with TB–whether they know it or not–can spread the illness to between 10 and 15 people without even knowing it, this is where in WHO, Public health organizations and Governmental agencies stepped in to make the screening program for detection of Acid Fast Bacilli in the sputum, to contain the spread and open cases of tuberculosis. The programs of screening remained a success till last few years as most of the treatments in tuberculosiscontinuestobethedecisionoftheCliniciansinstartingdrugregimes,howeverwhenweareworkingwithpoor infrastructure and patient cannot afford many new generations of tests, it is ideal to do, at least a sputum Microbiology with Z.N Methods. The emergence of Multidrug-Resistant Tuberculosis gives ways to find newer methods as just finding Acid-fast bacilli sputum do not mean the routinely used drugs cure and is a concern whether we are looking at a dead bacilli or a Atypical Mycobacterium or even as MDR - TB, and zeal to find the ways given the way for Molecular and new innovations to diagnose and cure the patients with MDR tuberculosis. THE ENIGMA OF TUBERCULOSIS CONTINUES? STORY OF SUCCESS, FAILURES AND HOPE?
  • 18. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 18 CHOOSING THE RIGHT TEST TO DIAGNOSE TUBERCULOSIS - Factors in selecting which test to use include the reason for testing, test availability, and costing. many of the developing countries we lack facilities and many times patients are treated on assumption and not on scientific basis. SEARCH FOR BETTER DIAGNOSTIC TESTS - yet there are no specific and sensitive tests to suit the clinical situation and Mycobacterium continues to be the most complex and above all many times if once we are infected it lives in us and wait for an opportunity to flare up, which created a buzz, with greater focus on HIV/AIDS patients as it will get reactivated with progress of HIV infection turning to be AIDS. NEW CHALLENGES WITH MDR -TB An urgent and a persistent problem is the rise of TB that does not respond to the two most powerful antibiotics for combating the disease. Here, treatment success is much lower, and more attention needs to be given to improving diagnostics and getting people through effective treatment, which can be prolonged and arduous, as well as finding new medicines. HOW TO ACHIEVE OUR GOALS the collaboration of all the health system departments in the management of TB is significant, since the patient may seek health care either from private medical practice or national care and the main goals are the early diagnosis and start of treatment. Furthermore, most of the clinical problems that may arise are addressed by ISTC and these guidelines should always be taken into consideration, at least until future research provides more promising diagnostic and therapeutic modalities for disease control. DETECTION OF DRUG RESISTANCE A PRIORITY - CDC advises all patients, the initial M. tuberculosis isolate should be tested for drug resistance. It is crucial to identify drug resistance as early as possible to ensure effective treatment. Drug susceptibility patterns should be repeated for patients who do not respond adequately to treatment or who have positive culture results despite 3 months of therapy. Susceptibility results from laboratories should be promptly reported to the primary health care provider and the state or local TB control program Improvements still to come TUBERCULOSIS IN PEDIATRIC AGE GROUP AND EXTRAPULONARY TUBERCULOSIS -“Huge improvements in the diagnosis of tuberculosis infection and disease are on the horizon, However, because most techniques are studied only in adults, before they become available, and TB is fundamentally different in children, and extra pulmonary involvement although it is likely that all tests will have to be considered according to how cases present clinically and epidemiologically. THE SAGA OF TUBERCULOSIS CONTINUES - HOWEVER THE SEARCH ON FOR BETTER SOLUTIONS? References 1 Problems in diagnosis and treatment of tuberculosis infection Tsara, E Serasli, and P Christaki Hippokratia. 2009 Jan-Mar; 13(1): 20–22. 2 Diagnosis of Tuberculosis Disease When Should You Suspect Tuberculosis (TB)? CDC 3 Tuberculosis is curable. So why are so many people still dying from the disease? By Editorial Board September 18, 2018, The Washington post.
  • 19. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 19 Dr. Dhruv Mamtora Consultant Microbiologist infection control officer S. L. Raheja Hospital, A fortis associate, Mahim, Mumbai. Co-editor and designer “Infection control trends” Email: dhruv_mamtora@yahoo.com Airborne infection control is given low priority in resource limited settings especially in country like India. However there are many models which have come up in designing and planning a healthcare facility which addresses issue of airborne transmission of infection. Some of these are adopted in development of treatment facility of tuberculosis and designing laboratories to undertake tuberculosis culture and sensitivity work. In the article, I am going to review various systems of ventilation which are available and scientific principles which are related to engineering but are yet to be adopted by medical industry for better airborne isolation facility construction. Infection control involves multiple aspects. First is prevention of aerosolisation of particulate material. Second is mechanism whereby a particle which has already escaped in air is killed before inhalation by susceptible host and thirdly isolating patient harboring tuberculosis in special ward which is negative pressure isolation facility so that transmission can be prevented or minimized. Fortheimplementationofsame,controlfallsinthreecategories,firstisadministrativecontrolfollowedbypersonal protection and lastly environmental and engineering controls. Administrative controls ensure that measures are taken appropriately to prevent transmission to susceptible patients. These include appropriate seating arrangements, triage, communication and patient education. However it is administration who also ensures that other steps which are personal protective equipment and environmental and engineering controls are in place in any given organization at all times. Next is role of appropriate personal protective equipment which includes use of respirator (N95 Masks) and appropriate procedures which are followed which minimizes risk of aerosolization like closed suction methods, use of biosafety cabinets for processing of samples, use of water resistant apron and face shield when such procedures are taken and ensuring that appropriate quality tests e.g. fit test for respirators are performed and regular training is given to staff for using same. Third and last important part is environmental and engineering controls. Engineering and environmental control ensures that transmission do not happen from one patient to another. Basically ensuring appropriate ventilation and exhaust controls. However at same time, engineering and environmental controls are major expenditure exercise for setting up appropriate isolation facilities for hospital set ups. The designing include clarity on various aspects which include type of ventilation systems, airflow distribution structure, air exchange rate, temperature and humidity both of ambient air as well as climatic conditions of establishment of facility, engineering maneuvers like filtration of air, HEPA filter installation, UV light and architectural and construction team support for designing above mentioned all elements. Airborne pathogens can be bacterial, viral or fungal spores which are suspended particles either solid of liquid in air. Some of parasitic eggs can also be suspended in air. Viruses are smallest of particles which are in nanometer sizes, bacteria are in micrometer size and fungal spores are largest which are larger than bacteria (1-30 microns). UNDERSTANDING AIRBORNE TRANSMISSION FROM INFECTION PREVENTIONISTS’ VIEW
  • 20. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 20 Human activities which support spread of airborne pathogens include respiratory (talking, coughing, sneezing, breathing),showering,flushing,tapwateruse,sewageaerosolizationfromtoilets,leakageinpipeandplumbingsystems etc. other specific hospital activities which can generate aerosols are bed making, washing of medical equipments, wet mopping and walking on carpets which can re-suspend particles as aerosols. Hospital procedures like intubation, suctioning, cardiopulmonary resuscitation, bronchoscopy, autopsy, surgery, cauterization, centrifugation etc. can also form aerosols. Presently, there is no precise list which can pin point exactly cause effect relationship between ventilation systems and hospital procedures. However this area can be of interest for future research. Basic and fundamental idea should be ventilation system should be appropriate for the scope of services offered by healthcare organization. Also the systems must be equipped to remove airborne contamination through effective ventilation system which has multiple checks of filter and UV etc. ventilation systems and ducts are regularly inspected and filters are timely replaced so that the optimum functioning can be assured. Some cleaning measures are in place and parameters like airflow velocity, air changes, filter efficacy and functionality, temperature. Pressure and humidity are monitored at regular intervals. Also pressure gauges are installed at entrance of all isolation rooms and tubes should not be blocked or worn out and must actually measure pressure differentials. Prevention of airborne transmission in hospitals and healthcare organization is a complex subject and it revolves around multiple key performance areas. Cross contamination by airborne infection can be significantly reduced in well designed and ventilated operating rooms however the same can be complex subject when it comes to designing wards. Since wards have complex interplay of multiple factors which are contact, airborne and hand related contamination and cross contamination in multi bed general wards. Reduced infection by airborne transmission needs robust systems which start right at point of installation of ventilation system and architectural design of building. It is also important that the systems which are functioning are maintained optimally to prevent cross contamination and reduce incidence of air borne infections in a given healthcare facility. Maintenance of systems to their maximum desired efficiency is challenge of this era and also major expenditure for tropical countries like India where the summer temperature are high and some of metro cities are coastal where humidity is exceeding more than 60 percent most of time in a year e.g. Mumbai, Chennai, Kolkata etc. Very little work has been done in this area of hospital starting from a scratch from designing aspect. Because many of organizations are built on old infrastructure which is so vast that to make changes is major capital expenditure so also maintaining and sustaining new systems is further challenge. There are new challenges especially for developing countries like India, where population explosion and overcrowding is major challenge to old existing infrastructure especially in general hospitals or any other places like bus depot, railway station or airports which are ran by governmental organizations so also maintenance for optimum functionality in existing ventilation systems which are in place ever since installation and are looked after or maintained only after major breakdowns or major disasters. There is need for development of common consensus and it is an area of research so also validation of existing system to its functionality is also challenging as there are no laid standards except some given by national and international agencies. Since the area deals with multiple complexities which want joint attention for medical and adjoining fields of engineering, maintenance and mechanics part of ventilation, there is huge unmet need especially at a juncture where we stand looking forward to eradicate biggest and chronic disease of tuberculosis which is rampant in our community and has gained new sensation after evolving as MDR, XDR and XXDR forms. Toconclude,thesocalledmodernmedicineisyettobecomemodernizedasfarasairbornediseasesandprevention of airborne diseases is concerned but baby steps are taken especially after knowledge of diseases like swine flu, bird flu, MDR form of tuberculosis and SARS. There is much more to learn and execute especially in field of designing, planning and maintaining facilities where mass public gatherings and especially in hospitals where respiratory diseases are treated. hospitals where respiratory diseases are treated.
  • 21. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 21 Dr. Ankit Gupta, Ms. Prerna Rani, Mr. Prijil Innocent Department Of Infection Control Max Superspeciality Hospital, Vaishali, Ghaziabad, Uttar Pradesh Sinceinception,tuberculosishasplaguedthemankindandintriguedtheresearchers.ThenotoriousMycobacterium tuberculosis has witnessed revolutionary changes, from inclusion of newer bacteria in Mycobacterium tuberculosis complex, to development of newer diagnostic modalities (culture based to NAAT based), and overwhelming drug resistance to many antimicrobials. The bacteria continue to evolve further, with very few new antibiotic compounds for rescue (i.e. bedaquiline, delaminid). Being a highly communicable disease, the prevention is the key to contain the spread in community. The infection control measures in a hospital are crucial to the management of tuberculosis. This exercise is carried out with extreme diligence by infection control nurses. With meticulous planning, they are entrusted with a responsibility to help in patient management by preventing the spread. With our experience, the strategy can be aptly called as NIYANTRAN, which may be considered as an abbreviation for various processes. NOTIFICATION • Notification of a case of tuberculosis is mandatory so that the patient can be offered assistance for diagnosis and treatment. • The infection control nurses serve as a bridge between clinical laboratories and departments which need to be notified with a case of tuberculosis. ISOLATION • Isolation for the control of infection is used to prevent infected patients from infecting others (source isolation), and/or prevent susceptible patients from being infected (protective isolation). YEARLY HEALTHCHECK UP The infection control nurse, in collaboration with other departments can coordinate and oversee an annual healthcheck up for all healthcare workers. AUDIT ROLE OF AN INFECTION CONTROL NURSE IN TUBERCULOSIS
  • 22. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 22 NEGATIVE PRESSURE (AND TRANSMISSION BASED PRECAUTIONS) A. This process contains two tiers of precautions: 1. Standard precautions 2. Transmission Based Precautions B. What are STANDARD PRECAUTIONS? STANDARD PRECAUTIONS (applicable to blood, all body fluids, secretions, and excretions, except sweat, regardless of whether or not they contain visible blood, non-intact skin, mucous membrane) C. What are the various modes of transmission? TRANSMISSION BASED PRECAUTIONS Airborne precautions include • Isolation of the patient in a private room with monitored negative air pressure. • The door to the room must remain closed. • Always wear appropriate respiratory protection - Use of N-95 mask for certain cases like H1N1. • Use required PPE. • Proper disposal of Bio medical waste. • Strict compliance to hand hygiene. • Limit the movement and transport of the patient from the room. • Terminal disinfection after discharge / transfer out. Droplet precautions • Keep the patient in a private room. • The door must remain closed. • Mask must be worn when entering the room and examining or transporting a patient. • Use required PPE. • Proper disposal of Bio medical waste. • Strict compliance to hand hygiene. • Limit the movement and transport of the patient from the room. • Terminal disinfection after discharge / transfer out. Contact precautions include • The door must remain closed. • Use required PPE such as clean gown, glove etc.
  • 23. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 23 • Proper disposal of Bio medical waste. • Strict compliance to hand hygiene. • Limit the movement and transport of the patient from the room. • Limit the movement of visitors • Terminal disinfection after discharge / transfer out TRAINING • Regular sessions are taken by infection control nurse to sensitize nursing and other health care workers regarding prevention. RESISTANCE (MDR, XDR AND TOTAL DRUG RESISTANCE) and RNTCP • The infection control nurses need to train healthcare workers about the threat of drug resistance. • The family members also need to educated about precautions to be observed at home and availability of various resources under RNTCP program. AUDIT AND SURVEILLANCE No infection control activity is complete without a comprehensive audit, surveillance and feedback mechanism. N-95 RESPIRATOR MASK practices for health care workers AND USE OF RESPIRATOR/Surgical Mask – For patients while transporting for procedures to prevent spread of infection.
  • 24. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 24 Ms. Pragya Lodha Clinical Psychologist & Research Assistant Health can be holistically determined by a bio-psycho-social model, however, often the medical model of illnesses overweighs in understanding, managing and treating illnesses. This is especially so for chronic illnesses as the inevitable first line of treatment is that of pharmacological management. What this article tries to highlight is the complementary need for psychosocial interventions for long term management of the illnesses and better quality of life for the patient. It is essential to understand that there are various pathways implicated in the development of chronic illnesses. The basic sciences focus on psycho-neuroendocrinology, psycho-neuroimmunology, psycho-physiology and psycho-somatic correlations- which is an explanation of physical and mental health affect each other and can aggravate the either conditions in terms of chronicity or symptom presentation. Treatment of patients with chronic diseases will be one of the main challenges of medicine in the future because they are very often influenced by psychosomatic or biopsychic factors. Though pharmacological management of chronic illnesses is an indispensable approach to treatment, it must be remembered that medicine is not only a diagnostic discipline but it also involves other health care workers in action, as part of the ‘health care system’. A commonly noted phenomenon is also that patients inflicted with chronic illnesses (cancer, renal problems, diabetes, chronic pain, coronary heart disease, bronchial asthma, rheumatoid arthritis, inflammatory bowel disease, essential hypertension, atopic dermatitis, surgical issues and other illnesses) can develop psychological and emotional issues. Psychosocial interventions are strategies of care that generally fall under the mental health care dimension since it looks at psychological and emotional well-being primarily. By definition, there is no one standard definition for psychosocial care as the nature of care varies with what the problem is, what is the nature and extent of care needed, who provides the care and the overall context along with the illness. Psychosocial care in the health care setting is the provision of psychological and emotional support and practical advocacy as it relates to patients adapting to their medical condition, accessing and adhering to medical treatment and developing coping skills to incorporate their illness successfully into their lives. The focus of psychosocial intervention is to assess and manage aspects such as psychological symptoms, personality traits, attitudes toward disease and life, risk behaviour and social isolation. As biological targets, the change of autonomic imbalance and of the effects of the psycho-endocrinological or psycho-immunological stress responses is also that is managed under psychosocial care. Psychosocial care is an aspect of treatment that works best along with clinical management of the illness. Straightforwardly, the psychosocial intervention is inclusive of counselling the patient, educating them about the illness, understanding the personal factors of the patient that may be exacerbating the illness and involving the patient and family members in better quality care at home along with managing illness in the long term. Psychosocial intervention addresses the following: • Adaptation to Change THE NEED FOR PSYCHOSOCIAL INTERVENTION IN CARE FOR CHRONIC ILLNESS
  • 25. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 25 • Grief and Loss • Coping Skills • Pain Management • Communication Skills • Stress Management • Problem Solving • Assertiveness Training • Spirituality • Rehabilitation • Post recovery care • Behavioural intervention (lifestyle changes) Through education, developing of coping skills and supportive intervention, patients are capable to effectively handle the stressors of life. Professionals practicing psychosocial care are specifically trained to help patients adjust to illness, diagnose and treat behavioural and emotional disorders including anxiety and depression, work with patients on behaviour modifications to adapt to difficult situations and respond to crisis situations. It is often believed that symptoms of an illness reduce with clinical management and the need for psychosocial interventions is often not felt. Patient care has been built based on an understanding that many factors impact patients’ functioning which are importantly relative to the illness. Patients need to be assessed fully for these factors and relevant interventions need to be implemented for better management. What is quintessential to note is that the impact of illness varies from one person to another and consequently, the treatment approach will also vary as the set of challenges faced by every patient are different. An individualized approach must be taken in order to eradicate the barriers and treat the patient holistically. The importance of psychosocial intervention in chronic illnesses: 1. Addressing the patient and taking an interest to understand the patient’s personal variables increases trust and better understanding between the doctor/therapist-patient relationship which is a very essential factor in patient-recovery 2. Culturally, India has a paternalistic doctor/therapist-patient relationship where the doctor/therapist is almost equivalent to god, a relationship where doctor/therapist understand patient’s cultural variables can promote great amount of trust in the patient
  • 26. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 26 3. Sometimes, having the belief that one trusts to get well is essential as optimism is linked with physical and mental well-being which may lead to sooner and better recovery 4.Psychosocialcarehasprovenefficacyinalleviatingdistressinpatientsmedicallytreatedforcancer,cardiovascular diseases, HIV/AIDS. 5. Psychosocial intervention can sometimes prevent chronic illnesses like HIV 6. Psychosocial care also improves compliance to medication and adherence to treatment as education and counselling are components of the care that allow for better patient understanding. 7. Family involvement is an essential part of illness management and sometimes identification of symptoms beforehand in order to prevent relapse (as far as possible) and early management of illness relapse. 8. Patient and family education about the illness is important for them to recognise early signs and symptoms, to avoid delay in treatment and also learning management at home as and when required. 9. Counselling allows for the patient to share his / her psychological and emotional baggage and get rid of it in order to improve quality of life and better self-care. 10. Psychosocial interventions enhance the outcomes of clinical care. Along with medication, addressing the personal variables in a patient helps reduce the need for medication for every symptom management (which can be taken care of psychosocially and at an interpersonal level), reassures the patient as a busy clinician may not always have the time to spend with the patient whereas the psychosocial care provider fulfils that, the queries of the illness get resolved by the psychosocial carer. Where to find psychosocial care? Psychosocial support can include mental health counselling, education, spiritual support, group support, and many other such services. These services are usually provided by mental health professionals, such as psychologists, social workers, counsellors, specialized nurses, clergy, pastoral counsellors, and others. Specifically, in India, one can reach out to a psychotherapist, counselling psychologist or clinical psychologist and / or a social worker who does counselling. Some hospitals also have psychiatric nurses who are capable of handling the care. These professionals can be sought either on a private clinic basis or at a hospital that has a psychiatry OPD. One may also find to join support groups that also foster psychosocial care. Conclusion Researchevidencetellsusthatreasonsforrelapseofillnessandre-hospitalisationincludepsychosocialissues,such as anxiety, lack of emotional and psychological support from family, friends and caregivers and a lack of communication and coordination of care for patients. Perhaps because there are no published guidelines for incorporating psychosocial care into usual clinical practice, it still is largely absent from routine patient care. The approach appreciates that all people must be treated in the context of their personal lives, beliefs and backgrounds. It is this unique context that patientsbringtotheirdiseaseanditsmanagement.Healthcareprovidersmustunderstandthatidentifyingthecondition or illness and recommending a treatment is only part of effective care. If illness is addressed without addressing its complex human host, barriers to treatment will prevent best outcomes, even if best medical therapies are offered. References 1. Deter HC. Psychosocial interventions for patients with chronic disease. BioPsychoSocial medicine, 2012;6(1), 2. doi:10.1186/1751-0759-6-2 2. Congressional Research Service. Medicare hospital readmissions: issues, policy options and PPACA, September, 2010. 3. Wagner EH, Austin BT, Davis C, et al. Improving chronic illness care: translating evidence into action. Health Aff (Millwood) 2001;20:64–78. 4. Kemp K, Griffiths J, Lovell K. Understanding the health and social care needs of people living with IBD: a meta-synthesis of the evidence. World J Gastroenterol 2012;18:6240–6249.
  • 27. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 27 Dr. Sourav Maiti Chief Consultant Clinical Microbiologist & In-Charge, Department of Infection Prevention & Control, Institute of Neurosciences Kolkata Email: smaiti76@gmail.com Electron transport is an essential biologic process required by almost all aerobic bacteria which is dependent upon availability of optimum amount of iron. Mycobacterium tuberculosis requires iron but in mammalian host nutritional immunity limits the amount of free iron. In addition, free iron is really scarce at physiological pH as it exists in the form of insoluble iron oxides. It requires 10−7 M iron for growth whereas solubility of iron is only 1.4 × 10−9 M at neutral pH. Hence for survival M. tuberculosis needs to rob off iron from transferrin in plasma and from lactoferrin in extracellular fluids and leukocytes. It has distinct mechanism of production of siderophore for chelating the metal iron from protein-bound as well as from the insoluble iron. Mycobacterialcellenvelopecontainslipid-richorganizationwhichcausesdifficultyinironacquisition.Toovercome, it produces 2 types of siderophores – hydrophobic mycobactins and hydrophilic carboxymycobactins. Gram-negative bacteria use TonB –dependent receptor-mediated internalization of iron. Most likely mycobacteria incorporate iron by interplay of ferricarboxymycobactins at outside and cytoplasmic membrane-bound mycobactins. HupB might be having an important role in mediation. Exochelins are not known to be produced by Mycobacterium tuberculosis. Since iron is an essential nutrient for survival of Mycobacterium tuberculosis, could it have some implication in treatment? Studies show for nosocomial multi-drug resistant strains of Staphylococcus aureus and Acinetobacter baumannii, siderophore-mediated iron uptake has important implications. Host response includes hyperproduction of lipocalin-2 which binds to siderophore and prevents reuptake of siderophores inside bacterial cell. On the other hand, synthetic siderophore analogues can be used as “Trojan horse” to deliver particular antibiotics like magic bullets. Researchers have shown that a bisubstrate inhibitor of the adenylation enzyme MbtA, which is responsible for the second step of mycobactin biosynthesis, exhibited potent antitubercular activity. Drug discovery focused its efforts on the inhibition of MbtI also which is another enzyme involved in the mycobactin biosynthesis. Among other compounds, MmpL3 inhibitors also demonstrated in vitro and in vivo antitubercular activity. These are still in experimental stages but they might answer the burning question of MDR-TB and XDR-TB. Let’s hope for the future! IRON & MYCOBACTERIUM TUBERCULOSIS – IS THERE A HOPE?
  • 28. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 28 Dr. Sukanya Rengaswamy MD, PGDID, CIC, Bangalore In the last few decades, though there has been a remarkable progress in the diagnosis of pulmonary TB, Extra pulmonary TB (EPTB) poses several clinical, diagnostic and management challenges which still need to be addressed. The common EPTB sites are TB Lymphadenopathy, Pleural TB, Abdominal TB, Genitourinary TB and Infertility settings (IVF) and CNS TB. Diagnosis of EPTB is challenging due to several factors such as paucibacillary samples, variable clinical presentations, need for invasive procedures to obtain appropriate samples and lack of laboratory facilities to process such samples in resource limited settings, where many such cases present. These can be further classified as Pre analytical and Analytical challenges. Common challenges in the pre analytical phase are Paucibacillary nature of samples/specimens, Non uniform distribution of microorganisms in samples, Inaccessible sites for routine sampling, feasibility and acceptability of invasive methods for sampling. Analytical phase issues are further classified as: I. Methodological issues: A. Direct methods: a. Tissue aspirate Microscopy and staining - ZN requires more than 106 bacilli per gram of tissue to be positive, which is a challenge in paucibacillary cases of EPTB. The sensitivity of sputum culture varies by site of EPTB: 28%-50% for abdominal TB, 10%-11% for tuberculosis pericarditis, 24%-29% for tuberculous meningitis, and 5%-14% for tuberculous lymphadenitis. Repeat tests improve diagnostic performance. In patients with urinary tract TB, three to six first-void morning urine specimens can improve the likelihood of a positive acid-fast bacilli (AFB) culture result with approximately 80%-90% (only 30%-40% of single specimens are positive).Repeated lumbar punctures and cerebrospinal fluid (CSF) examination also increase diagnostic yield. b. Culture is regarded as the “Gold standard” in the diagnosis of EPTB, but however the decontamination techniques of the EP samples are harmful to Mycobacteria, thereby bringing down the sensitivity. c. Molecular methods - Gene expert is the only recommended Molecular assay for EPTB. However here again the sensitivity varies widely for different EP samples. CSF, pleural, peritoneal, pericardial, synovial and pleural samples show low sensitivities on Expert platforms. A recent meta-analysis reported that Xpert MTB/RIF has an overall sensitivity of 83.1% and a pooled specificity of 98.7% for the diagnosis of EPTB .Others such as Real time, Nested PCRs. NAATs (Nucleic Acid Amplification Tests), TMA (Transcription Mediated Amplification), LCR (Ligase Chain reaction) , LPA (LINE Probe Assay) and Phage Tek MB assays are still to be evaluated for EPTB samples. Currently no recommendationsaremadeforuseofPCRinthediagnosisofEPTB.ThisbecauseofseveraldemandingfactorssuchasDNA concentration, size of target DNA and repetitiveness of the amplified sequence ,choice of primers used and the expertise of personnel involved in conducting the assay. A Quality control study of seven laboratories worldwide showed a false positivity ranging from 0-77%. EXTRAPULMONARY TUBERCULOSIS - DIAGNOSTIC CHALLENGES
  • 29. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 29 d. Antigen detection tests: 1. Serological tests: can detect mycobacterial antigens in body fluids, but require a minimum of 3-20ng/ml of antigen. The commonly detected antigens from EPTB specimens are BCG, Lipoarabinomannan (LAM), Non protein cell wall antigen, antigen 5, 14kDa, antigen A60, 45/47kDa antigen, cord factor (trehalose-6, 6_dimycolate). However, none of these tests have shown a good sensitivity in paucibacillary EPTB, which poses the main diagnostic challenge. 2. Antigen based immunostaining-IHC/ICC: Immunohistochemistry and immmunocytochemistry. Advantage over the ZN as it can detect degraded bacteria, while ZN requires intact bacilli. These tests have high sensitivity (70- 100%) and specificity (65-100%).Perform well in atypical histology and HIV co infected samples and can be used on for- malin fixed paraffin embedded tissues, aspirates and body fluids too. The main challenge here is invasive tissue sample collection and good sample preparation Due to the above challenges, the sensitivity of detection by direct methods is only 20-25% B. Indirect Methods are Histopathology and Cytology 1. Histopathology: The main issues are the confusing differentials in histopathological findings of granulomas and atypical histological features in concomitant immunosuppressive conditions like HIV. In TB endemic countries like India, granulomas with or without caseation, having Langhans Giant cells are diagnosed and treated as TB. Challenges are the lack of biopsy facilities in peripheral health care and it’s invasive nature. Incision biopsy is also associated with sinus tract and fistula formations and therefore biopsies are limited for patients with high clinical suspicion but negative FNACs (Fine Needle Aspiration) 2. Cytology: FNAC is usually the first line diagnostic test for EPTB in an accessible mass. However, here again challenge is to differentiate other granulomatous conditions, on tubercular mycobacterial infections and atypical cytological presentations in Immunosuppressed conditions such as HIV. The definite diagnosis of TB has to be done only with concomitant bacteriological examination which has a sensitivity of only 20-25%. The selection of the diagnostic procedures depends on the organ of involvement in EPTB. Various methods that include needle biopsy, excision, endoscopy, laparoscopy, and biopsies under guidance of ultrasound, computed tomography (CT), or endoscopic ultrasound have been employed to ascertain the diagnosis. Excisional biopsy has the highest sensitivity, whereas FNA is less invasive and may be useful. Laparoscopy with target peritoneal biopsy is the current investigation of choice in the diagnosis of peritoneal TB. In Bone TB , CT-guided needle biopsy is the recommended first approach to obtain tissue for assessment. 3. Body fluid examination: 3a. Tuberculous pleuritis is an exudate, with lymphocytic predominance in about 90% of cases. However, polymorphonuclear cells may predominate in patients with symptoms of <2-week duration. CSF typically reveals a leucocytosis (10-1000×103cells/ml; mostly lymphocytes),raised protein (0.5-3.0 g/L), and CSF: plasma glucose <50%. Pericardial fluid assessment typically demonstrates a bloody, exudative effusion that is often predominantly neutrophilic and not lymphocytic. 3b. ADA - (Adenosine deaminase enzyme) Useful in early TB detection in endemic countries. High sensitivity in EPTB. Determination of ADA isoenzymes and ratio of the iso enzymes in body fluids, helps in differentiating various causes especially in borderline ADA levels. ADA-2 is elevated in TB as against other causes such as malignancy. 3c. GLC - Tuberculostearic acid found in femtomoles can be detected using GLC on body fluids for EPTB diagnosis. Issues are false positives and demanding infrastructure. C. Serological tests: 1. Antibody tests for diagnosis of TB have been banned in India. 2. Cellular immunity based tests- 2a. Skin tests-Mantoux – it is based on delayed hypersensitivity response.
  • 30. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 30 Challenges are: • inconsistencies in performance and interpretation of the test • inability to differentiate between past, latent and active infection • inability to differentiate between MTB and NTM infections • False negatives in Immunosuppressed conditions like HIV co infections 2b.IGRAs (Interferon gamma release assays) - Negative recommendations from WHO to use these assays for the diagnosis of TB and latent TB in low and middle income countries. Very few studies are available on the use of IGRAs in EPTB diagnosis. II. Policy issues- National TB Control programmes in endemic countries does not include active diagnosis and reporting of EPTB cases. Also the diagnostic work up for EPTB requires good infrastructure and expert personnel for invasive procedures, sampling, and specialized assays with good sensitivities. These are a challenge in TB endemic countries which come under low and middle income category. III. Challenges in HIV co infections with TB (especially EPTB which is common)- EPTB Presentation in HIV is usually atypical and protean. A high degree of clinical expertise and experience is essential along with availability and accessibility of advanced tests at the primary and secondary levels healthcare systems for the early and accurate diagnosis of EPTB in HIV. The Future: The cornerstone of Global TB control is rapid and accurate diagnosis of all forms of TB. The diagnostic challenges in EPTB, HIV and TB and MDR TB have led to WHO, FIND (Foundation for Innovative and New Diagnostics) and the GLI (Global laboratory Initiative) prioritizing quality diagnostics which are rapid, low cost, and easy to interpret with minimum infrastructure. Decentralizing NAAT tests leads to cost savings for both patients and providers as there are fewer investigations, shorter length of hospital stay, reduced use of antibiotics and visit costs. New diagnostic algorithms for the diagnosis of EPTB using assays like Immunochemistry have been validated and these need to be used as a routine diagnostic test. The availability of new guidelines and tools for such tests such as QADAS (Quality Assessment of Diagnostics Accuracy Standards) and STARD (Standards for reporting of Diagnostics Acuracy) can facilitate implementation of such algorithms. Conclusions: Extra pulmonary TB is a huge diagnostic challenge faced by low and middle income countries which are also TB endemic countries, where advanced and sophisticated molecular tests and drug sensitivity tests are not available widely. However, WHO has speeded up the intake of new diagnostic tests which are evidence based. The evidence is provided by diagnostic accuracy evaluations where accuracy performance is used as surrogate marker for patient-important outcomes. More evidence however is required to evaluate the operational efficacy of these tests at the field level. References: 1. Manju Purohit and Tehmina Mustafa, Laboratory Diagnosis of Extrapulmonary Tuberculosis, Journal of Clinical and Diagnostic Research, 2015 Apr, Vol-9(4):EE01-EE06 2. Ji Yeon Lee,Diagnosis and Treatment of Extrapulmonary Tuberculosis, Tuberc Respir Dis (Seoul) 2015 Apr; 78(2): 47–55. Published online 2015 Apr 2. doi: 10.4046/trd.2015.78.2.47
  • 31. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 31 Dr. H Srinivasa MD Microbiology (AIIMS, New Delhi) Freelance Consultant Microbiologist & Infection Control Bangalore Email: dr.srinivasa.micro@gmail.com INTRODUCTION Pulmonary TB continues to be most important chronic infectious communicable diseases contributing to many deaths. More important is that is its socioeconomic impact on family. Compounding on that the person with Pulmonary Tuberculosis can spread to family members by droplet method that person's with weak Immunity .Is this the reason that children with weak immunity are more susceptible? Childhood TB can manifest in infancy or in later childhood, adolescents. the source may be mother or a family member or in nurseries/preschools, or much later in community It is important to realize that TB infection is different from TB as disease. The former indicates only past exposure. Children with first exposure results in primary infection which normally resolves with or without antibiotics for 1-2weeks in most cases. It is those who fail to contain mycobacteria, develop post primary tuberculosis. The location of disease may not be lungs but more commonly lymphnodes, pleura, bones etc. thus Paediatric TB is Pulmonary or Extra pulmonary.Those with malnutrition, primary TB itself will be severe resulting in miliary TB or TB meningitis Diagnosis and epidemiology Of Paediatric TB Recognition of Paed TB: its diagnosis, to treat or not to treat is challenging. When to consider definite, when probable, when unlikely good review articles with IAP recommendations are available. I am not sure as to whether one should treat, hilar Lymphadenopathy in otherwise healthy child or wait and watch is better. Lab assistance in Paediatric TB careful and correct sampling is important. Sputum is simply not possible, Hence gastric lavage is important, throat? laryngeal swab also yield positives by ZN smear for AFB. Now says gene expert has revolutionized the diagnosis and also provide information whether the bacteria is MDR or not. RNTCP guidelines have included in addition to first sample for smear, detection of DNA. In place of second sample only few cases of drug resistant TB require prolonged drug regimen. PAEDIATRIC TB-TRYING TO UNDERSTAND FROM IC PERSPECTIVE
  • 32. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 32 In summary we need to closely look at Paediatric TB diagnosis how much is evidence based, Whether there is missed diagnosis Or over diagnosis. What is the impact of BCG on evolution of primary TB, its severity if it occurs. Is TB meningitis , Miliary TB decreasing or still persisting in certain geographical areas, what is the profile of child affected with severe TB, as well as family members, A study done in India showed that Family members are still the major source for Paed Tb in more than 50 % of cases. Another Study revealed that extra pulmonary TB is overlooked and not diagnosed early in many cases Future Perspectives A close study audit is required to be done by all infection control practitioners to learn more about the current situation of Paediatric Tuberculosis. Further impact of treatment Is also equally important References 1. Paeduiatric Tuberculosis, a decade long experience K madhava Kamath etal Indian J child health vol 5 issue 2 2018 2. Pediatric Tuberculosis in children in India : A prospective study Sanjay K Jain Biomed research International volume 2013
  • 33. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 33 Dr. Aruna Shanmuganathan MD, DNB, Professor, Department of Respiratory Medicine Chettinad Hospital & research Institute, kelambakkam, Chennai - 603103 Worldwide, tuberculosis (TB) is among the top ten causes of death & the leading cause from a single infectious agent. It is indeed disheartening to know that 2/3rds of the global TB incidence is in 8 high burden countries with India (27%) topping the list. The “End TB” Strategy, an ambitious vision of the Sustainable Development Goals (SDG) of the WHO to end the global TB epidemic by 2030 has a tough task to achieve. Drug resistant TB, especially Multidrug resistant TB (MDR TB), poses a great threat in achieving the global targets to end the TB epidemic. Around 558,000 cases of Rifampicin resistant TB have been reported with 82 % of them being MDR TB. Again, 3 countries account for almost half the burden with India, followed by China & Russia having the largest numbers. In India, the percentage of MDR TB in new and previously treated patients is 2.8 and 12% respectively. The important reasons for MDR TB fuelling the TB epidemic are delay in early diagnosis & initiation of treatment, poor compliance associated with long treatment regimens, higher drug toxicities, and the associated co-morbidities like HIV, DM, malnutrition and alcoholism. Only 1 in 4 MDR TB patients are initiated on treatment and treatment success is a dismal 55%. Though MDR TB initially was largely a man made problem, primary MDR TB due to transmission of drug resistant strains is now being increasingly diagnosed. Drug resistant TB includes RR TB (resistance to only rifampicin), MDR TB (resistance to INH & Rifampicin with/ without resistance to other first line drugs), Mono resistance, especially to INH and XDR TB (MDR TB with additional resistance to fluoroquinolone and second line injectable). Guidelines for treatment of the same were initiated in 2000 by the WHO. In 2006, the PMDT (Programmatic Management of Drug resistant TB) guidelines replacing the erstwhile DOTS plus services were introduced and regular updates in these guidelines have taken place till 2017. Introduction and approval of newer drugs with the hope of shortening treatment regimens, like Bedaquiline (2012) and Delaminid (2014) and reports of greater success with shorter treatment regimens from countries like Bangladesh, Uzbekistan etc lead to suggestions for changes in potential areas in the current guidelines. Hence, in 2018, the WHO convened a Guideline Development Group (GDP) to update its policy recommendations on the treatment of MDR TB/RRTB. Fresh evidence reviews from recently completed Phase 3 trials of Bedaquiline, Individual Patient Data Meta-analysis (IPD- MA) of patients treated with shorter MDR TB regimens of 9-12 months duration(in comparison to 24-27 months in RECENT UPDATES IN THE MANAGEMENT OF DRUG RESISTANT TUBERCULOSIS
  • 34. VOLUME 1 | ISSUE 4 | JULY 2019INFECTION CONTROL TRENDS 34 conventional MDR regimen) and pharmacokinetic data of Bedaquiline and Delaminid in patients less than 18 yrs of age were analyzed. These new recommendations are now available in the WHO consolidated guidelines on drug-resistant TB treatment 2019. They include significant changes as compared to the previous ones (2011-2017). Some of the important recommendations are discussed here. • Injectable agents like Kanamycin, Capreomycin and Amikacin are no longer the priority drugs for longer MDR regimens and thus fully oral regimens are preferred for most patients. • Regrouping of drugs used in the longer MDR regimens has been done (3 groups of drugs as compared to 4 previously). • Fluoroquinolones (Levofloxacin & Moxifloxacin), Bedaquiline and Linezolid (Group A drugs) are strongly recommended for use in longer regimens. • Ideally all drugs from Group A, and 1 or more from Group B are preferred. Group C drugs are listed in the order of preferential use and are to be used only in circumstances when drugs from the above groups cannot be used. • Strong recommendations are for Bedaquiline use in longer MDR regimens in patients more than 18 yr and consideration for use in children 6-17yr. Delaminid may also be included in longer regimens for MDR/RR TB for patients above 3 yrs. • Other changes in guidelines include Ethionamide / Prothionamide which were previously recommended are now to be considered only if drugs from groups A and B cannot be used. Clavulanic acid is not recommended for use any more. • Hence, the total duration of the longer individualized MDR regimens would be 18-20 months with at least 4 drugs for the first 6 months and 3 thereafter based on individual patient benefit and tolerance. The treatment duration after culture conversion should be 15-17 months. The recommendations apply to children, adults and PLHIV. The standardized shorter MDR TB regimens of 9-12 months duration are recommended for MDR TB patients who have not been previously treated or have no resistance to fluoroquinolones and second line injectables. Response to treatment according to the new guidelines would be by monthly culture which translates into more frequent monitoring. The areas where there are no changes as compared to previous guidelines are, start of Anti-retroviral therapy with MDR TB treatment, use of surgery and models of TB care. In summary, the recent update on the management of drug resistant TB focuses on fully oral regimens avoiding injectables, shorter treatment regimens and use of newer drugs like Bedaquiline & Delaminid. Patient centric care and support with Universal access to rapid diagnosis and DST (Drug Susceptibility Testing) facilities, early initiation of treatment with pre-treatment counseling, monitoring response to treatment and active drug safety are the chief pillars in the management of drug resistant TB. References 1. Global TB Report 2018 – WHO 2. WHO consolidated guidelines on drug resistant Tuberculosis treatment, 2019