2. MICROBIOLOGY
Tuberculosis (TB) is caused by organisms of the
Mycobacterium tuberculosis complex, which includes
M. tuberculosis, the most common and important
agent of human mycobacterial disease, and M. bovis,
which (like several other mycobacterial species) is
acquired via ingestion of unpasteurized milk. M.
tuberculosis is a thin aerobic bacillus that is neutral on
Gram’s staining but that, once stained, is acidfast; i.e., it
cannot be decolorized by acid alcohol because of the
cell wall’s high content of mycolic acids and other lipids.
3. EPIDEMIOLOGY
• An estimated 10.4 million new cases of TB occurred worldwide in
2016, with ∼1.7 million TBrelated deaths—almost entirely in
lowincome countries. Globally, TB rates are stable or falling
• Isolates of M. tuberculosis MDR and XDR are increasing in
frequency
• Disease from a pt with pulmonary TB is spread by droplet nuclei
that are aerosolized by coughing, sneezing, or speaking.
• Droplets <5–10 µm in diameter may be suspended in air for several
hours. Transmission is determined by the intimacy and duration of
contact with a pt with TB, the degree of infectiousness of the pt,
and the shared environment.
• Pts with cavitary or laryngeal disease are most infectious, with as
many as 105–107 acidfast bacilli (AFB)/mL of sputum.
• Risk factors for development of active disease after M. tuberculosis
infection include recent acquisition (i.e., within the preceding 18
months), comorbidity (e.g., HIV disease, diabetes, silicosis,
immunosuppression, gastrectomy), malnutrition, tobacco smoking,
and presence of fibrotic lesions.
4. PATHOGENESIS
• AFB that reach alveoli are ingested by macrophages. The bacilli
impair phagosome maturation, multiply, lyse the macrophages,
and spread to regional lymph nodes, from which they may
disseminate throughout the body.
• These initial stages of infection are generally asymptomatic and
induce cellular and humoral immunity.
• About 2–4 weeks after infection, a tissuedamaging response
resulting from delayedtype hypersensitivity (the basis for
tuberculin skin testing [TST]) destroys nonactivated macrophages
that contain multiplying bacilli, and a macrophageactivating
response activates cells capable of killing AFB. A granuloma forms
at the site of the primary lesion and at sites of dissemination. The
lesions can then either heal by fibrosis or undergo further
evolution. Despite “healing,” viable bacilli can remain dormant
within macrophages or in necrotic material for years.
• Cellmediated immunity confers partial protection against TB.
Cytokines secreted by alveolar macrophages contribute to disease
manifestations, granuloma formation, and mycobacterial killing.
5. CLINICAL MANIFESTATIONS
TB is classified as pulmonary, extrapulmonary, or both. Extrapulmonary TB may occur in 10–40%
of patients, with even higher rates among HIVinfected patients.
Pulmonary TB
• •:Primary disease may cause no or mild signs and symptoms (fever and occasional pleuritic chest pain) in contrast to
the prolonged disease course that is common in post primary or adulttype disease.
• Primary disease is frequently located in the middle and lower lobes. The primary lesion usually heals spontaneously,
and a calcified nodule (Ghon focus) remains.
• Transient hilar and paratracheal lymphadenopathy is common.
• In immunosuppressed patients and children, primary disease may progress rapidly to significant clinical disease, with
cavitation, pleural effusions, and hematogenous dissemination (miliary disease).
• •Postprimary (AdultType) Disease : Also referred to as reactivation or secondary TB(primary infection or reinfection).
• It is usually localized to the apical and posterior segments of the upper lobes, where the substantially higher mean
oxygen tension favors mycobacterial growth.
• The extent of lung parenchymal involvement varies greatly, from small infiltrates to extensive cavitary disease. With
cavity formation, liquefied necrotic contents are ultimately discharged into the airways and may undergo bronchogenic
spread, resulting in satellite lesions within the lungs that may in turn undergo cavitation
• Adulttype disease presents initially with nonspecific and insidious signs and symptoms, such as diurnal fever, night
sweats, weight loss, anorexia, malaise, and weakness.
• As the disease progresses, patients develop cough and purulent sputum production, often with blood streaking.
Extensive cavitation may develop, with occasional massive hemoptysis following erosion of a vessel located in the wall
of a cavity.
• Extensive disease may produce dyspnea and sometimes ARDS. Physical findings are of limited use in pulmonary TB.
Some pts might have detectable rales in the involved areas during inspiration, especially after coughing. Rhonchi due to
partial bronchial obstruction and classic amphoric breath sounds in areas with large cavities may be heard. Systemic
features include fever and wasting. In some recurrent cases and among people with low Karnofsky score, finger
clubbing has been reported.
• The most common hematologic findings are mild anemia, leukocytosis, and thrombocytosis with a slightly elevated ESR
or CRP. Hyponatremia due to the syndrome of inappropriate secretion of antidiuretic hormone has also been reported.
6. • Extrapulmonary TB
• Any site in the body can be involved, but the most commonly affected sites are the lymph nodes, pleura, genitourinary tract,
bones and joints, meninges, peritoneum, and pericardium. Up to two-thirds of HIV-infected patients with TB have
extrapulmonary disease.
• • Lymph node TB: Presents as painless swelling of the lymph nodes, most commonly at posterior cervical and supraclavicular
sites (a condition historically referred to as scrofula).
• – Lymph nodes are usually discrete in early disease but develop into a matted nontender mass over time; a fistulous tract
draining caseous material may result.
• – Fine-needle aspiration or surgical-excision biopsy of the node is required for diagnosis. Cultures are positive in 70–80% of
cases.
• –D/D includes neoplastic diseases such as lymphomas or metastatic carcinomas, and rare disorders like Kikuchi’s disease
(necrotizing histiocytic lymphadenitis), Kimura’s disease, and Castleman’s disease.
•
• •Pleural TB: ∼20% of extrapulmonary cases. Isolated pleural effusion usually reflects recent primary infection, and the
collection of fluid in the pleural space represents a hypersensitivity response to mycobacterial antigens.
• Pleural disease may also result from contiguous parenchymal spread, as in many cases of pleurisy accompanying postprimary
disease. Depending on the extent of reactivity, the effusion may be small, remain unnoticed, and resolve spontaneously or may
be sufficiently large to cause symptoms such as fever, pleuritic chest pain, and dyspnea.
• Physical findings are those of pleural effusion: dullness to percussion and absence of breath sounds. CXR reveals the effusion
and can also show a parenchymal lesion.
• Thoracentesis is required to ascertain the nature of the effusion. The fluid is straw-colored and at times hemorrhagic; it is an
exudate with a protein concentration >50% of that in serum (usually ∼4–6 g/dL), a normal to low glucose concentration, a pH of
∼7.3 , and detectable WBC(usually 500–6000/μL). Neutrophils predominance in the early stage, lymphocyte predominates in
later stage. Cultures often may be falsely negative for M.TB. Lysozyme is also present in the pleural effusion. Measurement of
IFN-γ, can be diagnostically helpful.
• Needle biopsy of the pleura is recommended over pleural fluid analysis; it reveals granulomas and/or yields a positive culture in
up to 80% of cases.
• This form of pleural TB responds rapidly to chemotherapy and may resolve spontaneously. glucocorticoid may reduce the
duration of fever and/or chest pain but is not of proven benefit.
• Tuberculous empyema is complication of pulmonary TB. It is result of the rupture of a cavity, with spillage of a large number of
organisms into the pleural space. This process may create a bronchopleural fistula with evident air in the pleural space. CXR
shows hydropneumothorax with an air-fluid level. The pleural fluid is purulent and thick and contains large numbers of
lymphocytes. Acid-fast smears and mycobacterial cultures are often positive. Surgical drainage is usually required as an adjunct
to chemotherapy. Tuberculous empyema may result in severe pleural fibrosis and restrictive lung disease. Removal of the
thickened visceral pleura (decortication) is occasionally necessary to improve lung function.
7. • TB of the Upper Airways : Always a complication of advanced cavitary
pulmonary TB, TB of the upper airways may involve the larynx, pharynx, and
epiglottis. Symptoms include hoarseness, dysphonia, and dysphagia in
addition to chronic productive cough. Findings depend on the site of
involvement, and ulcerations may be seen on laryngoscopy. Acid-fast smear
of the sputum is often positive. Carcinoma of the larynx may have similar
features but is usually painless.
• • Genitourinary TB local symptoms predominate (e.g., urinary frequency,
dysuria, hematuria, abdominal or flank pain), and up to 75% of patients
have a CXR demonstrating previous or concomitant pulmonary disease.
Disease is occasionally identified only after severe destructive lesions of
the kidneys have developed.
• In 90% of cases, urinalysis shows pyuria and hematuria with negative
bacterial cultures. Culture of three morning urine specimens yields a
definitive diagnosis in nearly 90% of cases. Mycobacterial culture of three
morning urine specimens is diagnostic in 90% of cases.
• In female patients, it affects the fallopian tubes and the endometrium and
may cause infertility, pelvic pain, and menstrual abnormalities. In male
patients, genital TB affects the epididymis, producing a tender mass that
drain externally through a fistulous tract; orchitis and prostatitis may also
develop.
• In half of cases of genitourinary TB, UTI is also present Diagnosis requires
biopsy or culture of specimens obtained by dilation and curettage..
Genitourinary TB responds well to chemotherapy.
8. • •Skeletal TB: TB of the bones and joints is responsible for ∼10% of
extrapulmonary cases.
• Pathogenesis is related to reactivation of hematogenous foci or to spread
from adjacent paravertebral lymph nodes. Weightbearing joints (spine in
40% cases,hips in 13%, knees in 10%) affected.
• Skeletal TB responds to chemotherapy, but severe cases may require
surgery
• Spinal TB (Pott’s disease or tuberculous spondylitis) involves two or more
adjacent vertebral bodies, the lower thoracic and upper lumbar vertebrae
are usually affected in adults. With advanced disease, collapse of vertebral
bodies results in kyphosis (gibbus). A paravertebral “cold” abscess may also
form. In the upper spine, this abscess may track to and penetrate the chest
wall, presenting as a soft tissue mass; in the lower spine, it may reach the
inguinal ligaments or present as a psoas abscess. CT or MRI reveals the
characteristic lesion and suggests its etiology. Aspiration of the abscess or
bone biopsy confirms the tuberculous etiology, as cultures are usually
positive and histologic findings highly typical. Complication of Pott’s disease
is paraplegia,due to abscess or a lesion compressing the spinal cord.
Paraparesis requires rapid drainage.
• TB of the hip joints, usually involving the head of the femur, causes pain; TB
of the knee produces pain and swelling. If the disease goes unrecognized,
the joints may be destroyed. Diagnosis requires examination of the synovial
fluid, which is thick in appearance, with a high protein concentration and a
variable cell count
9. • Tuberculous Meningitis and Tuberculoma :TB ofCNS is ∼5% of
extrapulmonary cases. It is seen most often in young children but also develops in adults,
especially those infected with HIV.
• Tuberculous meningitis results from the hematogenous spread of primary or postprimary
pulmonary TB or from the rupture of a subependymal tubercle into the subarachnoid space.
• A miliary pattern is found on CXR. The disease often presents subtly as headache and slight
mental changes after a prodrome of weeks of low-grade fever, malaise, anorexia, and
irritability. If not recognized, tuberculous meningitis may evolve acutely with severe
headache, confusion, lethargy, altered sensorium, and neck rigidity
• Paresis of cranial nerves (ocular nerves in particular) is a frequent finding, and the
involvement of cerebral arteries may produce focal ischemia. The ultimate evolution is
toward coma, with hydrocephalus and intracranial hypertension.
• Lumbar puncture is used for diagnosis. In general, examination of CSF reveals a high LC(up
to 1000/μL), usually with a predominance of lymphocytes but sometimes with a
predominance of neutrophils in the early stage; a protein content of 100–800 mg/dL; and a
low glucose concentration.
• Culture of CSF is diagnostic in up to 80% of cases and remains the gold standard. Real-time
automated nucleic acid amplification (the Xpert MTB/RIF assay) has a sensitivity of up to
80% and is the preferred. Imaging studies (CT and MRI) may show hydrocephalus and
abnormal enhancement of basal cisterns or ependyma.
• If unrecognized, tuberculous meningitis is uniformly fatal. This disease responds to
chemotherapy. Trials have demonstrated that patients given adjunctive glucocorticoids may
experience faster resolution of CSF abnormalities and elevated CSF pressure, resulting in
lower rates of death or severe disability and relapse. WHO now recommends that adjuvant
glucocorticoid therapy with either dexamethasone or prednisolone, tapered over 6–8 weeks,
should be used in CNS TB.
• Tuberculoma, an uncommon manifestation of TB of the CNS, presents as one or more space-
occupying lesions and usually causes seizures and focal signs.
10. • Gastrointestinal TB: disease can affect any portion of the GI
tract (with the terminal ileum and cecum most commonly
involved), causing abdominal pain, obstruction,
hematochezia, and often a palpable mass. TB peritonitis can
follow spread of the organism from ruptured lymph nodes
and intraabdominal organs; peritoneal biopsy is usually
required for diagnosis.
• Pericardial TB (Tuberculous Pericarditis) is characterized by
an acute or subacute onset of fever, dull retrosternal pain,
and sometimes a friction rub. Effusion is common. Chronic
constrictive pericarditis is a potentially fatal complication,
even in treated patients. Adjunctive glucocorticoids remain
controversial; no conclusive data demonstrate a benefit.
Mostly it is diagnosed post mortem.
• Miliary or Disseminated TB: Miliary disease arises from
hematogenous spread of M. tuberculosis throughout the
body. Symptoms are nonspecific, and small (1- to 2-mm)
granulomas may develop in many organs. Hepatomegaly,
splenomegaly, lymphadenopathy, and choroidal tubercles of
the eye may occur. Pancytopenia is seen which is rapidly fatal.
11. • Less Common Extrapulmonary Forms TB may cause chorioretinitis, uveitis,
panophthalmitis, and painful hypersensitivityrelated phlyctenular conjunctivitis.
Tuberculous otitis is rare and presents as hearing loss, otorrhea, and tympanic
membrane perforation. In the nasopharynx, TB may simulate granulomatosis with
polyangiitis. Cutaneous manifestations of TB include primary infection due to direct
inoculation, abscesses and chronic ulcers, scrofuloderma, lupus vulgaris , miliary
lesions, and erythema nodosum. Tuberculous mastitis results from retrograde
lymphatic spread, often from the axillary lymph nodes. Adrenal TB is a
manifestation of disseminated disease presenting rarely as adrenal insufficiency.
Finally, congenital TB results from transplacental spread of tubercle bacilli to the
fetus or from ingestion of contaminated amniotic fluid. This rare disease affects the
liver, spleen, lymph nodes, and various other organs.
• HIV-Associated TB: TB is most common diseases among HIV-infected persons
worldwide. TB is likely the main cause of death in this population. The
manifestations of TB vary with the stage of HIV infection. When cell-mediated
immunity is only partly compromised, pulmonary TB presents as typical upper-
lobe cavitary disease. In late HIV infection, a primary TB-like pattern may be
evident, with diffuse interstitial or miliary infiltrates, little or no cavitation, and
intrathoracic lymphadenopathy.
• –Extrapulmonary disease occurs frequently in pts of HIV; common forms include
lymphadenitis, meningitis, pleuritis, pericarditis, mycobacteremia, and
disseminated disease.
• – Immune reconstitution inflammatory syndrome (IRIS), which may occur 1–3
months after initiation of antiretroviral therapy, may exacerbate the signs and
symptoms of TB.
12. DIAGNOSIS
• Diagnosis is first evaluated when the CXR of a patient with respiratory symptoms is
abnormal. If the patient has no complicating medical conditions that cause
immunosuppression, the chest radiograph may show typical upper-lobe infiltrates with
cavitation
• Immunosuppressed patients, including those with HIV co-infection, may have “atypical”
findings on CXR—e.g., lower-zone infiltrates without cavity formation—or interstitial disease
only.
• Diagnosis at primary level through traditional AFB microscopy, Diagnosis at a secondary
level through realtime automated nucleic acid amplification technology (e.g., the Xpert
MTB/RIF assay, which also allows detection of drug resistance), At a tertiary level molecular
tests, rapid culture, and DST.
• AFB microscopy of diagnostic specimens—can provide a presumptive diagnosis. In suspected
pulmonary TB, two or three sputum samples should be examined.
• Definitive diagnosis requires growth of M. tuberculosis in culture or identification of the
organism’s DNA in clinical samples. – Liquid media and speciation by molecular methods
have decreased the time required for diagnostic confirmation to 2–3 weeks (from 4 to 8
weeks).
• Nucleic acid amplification is useful not only for rapid confirmation of TB in AFB-positive
specimens but also for diagnosis of AFB-negative pulmonary and extrapulmonary TB.
• Drug susceptibility can be assessed via indirect testing on solid media (which takes ≥8
weeks), direct testing in liquid media (which takes ∼3 weeks), or PCR (which can provide
results within hours).
• TST is the most widely used screening test for latent TB infection.
• Interferon γ release assays (IGRAs) measure the release of interferon γ by T cells after
stimulation with TB-specific antigens and are more specific for M. tuberculosis than is TST
13. • NUCLEIC ACID AMPLIFICATION TECHNOLOGY: Several test systems based
on amplification of mycobacterial nucleic acid are now the preferred first-
line diagnostic tests.
• Xpert MTB/RIF can simultaneously detect TB and rifampin resistance in less
than 2hrs. WHO recommends its use worldwide as the first-line diagnostic
test in all adults with signs or symptoms of active TB.
• The newer Xpert MTB/RIF Ultra assay (Ultra), uses the same GeneXpert
diagnostic platform (i.e., the “noise” produced by detection of DNA from
nonviable bacilli) as positive with the greatest increases among
smearnegative, culture-positive cases and among HIV-infected persons.
• In the diagnosis of extrapulmonary TB, Xpert MTB/RIF and Ultra should be
the initial test applied to CSF from patients in whom TB meningitis is
suspected.
• Truenat MTB and MTC Plus are two newly introduced rapid molecular tests.
Truenat MTB-Rif Dx detects rifampin resistance with a sensitivity of 93%
and a specificity of 95%.
• New high-throughput automated platforms for TB diagnosis and drug-
resistant variants are becoming available (Abbott RealTime MTB and
RIF/INH, FluoroType MTBDR, BD Max MDR-TB).
• The TB-LAMP assay: Another available molecular test for detection of M.
tuberculosis is based on the loop-mediated isothermal amplification (LAMP)
temperature-independent technology that amplifies DNA, is relatively
simple to use, and is interpreted through a visual display
14. • AFB MICROSCOPY: presumptive diagnosis is still commonly based
on the finding of AFB on microscopic examination of a diagnostic
specimen smear of sputum or tissue.
• In this method light microscopy of specimens stained with Ziehl-
Neelsen basic fuchsin dyes—is satisfactory, it is time consuming
and operator dependent. The use of AFB microscopy in examining
urine or gastric lavage fluid is limited by the low numbers of
organisms, which can cause false-negative results, or the presence
of commensal mycobacteria, which can cause falsepositive results.
• MYCOBACTERIAL CULTURE: Definitive diagnosis depends on the
isolation and identification of M. tuberculosis from a clinical
specimen. Commercial liquid-culture systems such as the
Mycobacterial Growth Indicator Tube (MGIT) system are
recommended by the WHO as the reference standard for culture.
MGIT cultures usually become positive after a period ranging from
10 days to 2–3 weeks. . A low-cost, rapid immunochromatographic
lateral-flow assay based on detection of MTP64 antigen may also
be used for species identification of the M. tuberculosis complex in
culture isolates
15. • DRUG SUSCEPTIBILITY TESTING: Universal DST is considered by the WHO
as the current standard of care for all TB patients and should consist of DST
to at least rifampin for all initial isolates of M. tuberculosis, as rifampin
resistance is an excellent proxy for MDR-TB diagnosis. In addition, expanded
and rapid susceptibility testing for isoniazid and key second-line anti-TB
drugs (especially the fluoroquinolones and the injectable drugs) is
mandatory when RR-TB is found.
• Susceptibility testing may be conducted directly by molecular techniques
(with the clinical specimen) or indirectly (with mycobacterial cultures) on
solid or liquid medium. Results are obtained with reporting time of 3 weeks.
• Apart from the Xpert MTB/RIF, Xpert MTB/RIF Ultra, and Truenat MTB-Rif
Dx assays, which, as mentioned above, effectively detect rifampin
resistance, the most widely used tests are molecular line probe assays
(LPAs) for all regimens of TB treatment.
• LPAs are a family of DNA stripbased tests capable of detecting bacterial DNA
and identifying drug resistance-associated mutations. After extraction of
DNA from M. tuberculosis isolates or from clinical specimens, the resistance
gene regions are amplified by polymerase chain reaction (PCR), and labeled
and probe-hybridized PCR products are detected by colorimetric
development. This assay reveals the presence of M. tuberculosis as well as
mutations in target resistance-gene regions.
16. • RADIOGRAPHIC PROCEDURES: CXR is a rapid imaging technique used as a primary tool to
detect pulmonary TB. CXR has high sensitivity but poor specificity. Suspicion of pulmonary
TB is often based on abnormal CXR findings in a patient undergoing triage for respiratory
symptoms. “classic” picture is that of upper-lobe disease with infiltrates and cavities,
• CT is useful in interpreting questionable findings on plain CXR and in diagnosing some forms
of extrapulmonary TB (e.g., intrabdominal disease, Pott’s disease).
• MRI is useful in the diagnosis of bone lesions and intracranial TB.
• DIAGNOSIS OF M. TUBERCULOSIS INFECTION: Two tests currently exist for identification of
individuals with TB infection: the TST and IGRA, both of which measure host immunological
response to TB antigens
• Tuberculin Skin Testing : Components of M. tuberculosis in a concentrated liquid-culture
medium(known as tuberculin purified protein derivative PPD) are capable of eliciting a skin
reaction when injected subcutaneously into patients with TB. The skin test with tuberculin
PPD (TST) is most widely used in screening for TB infection. It measures the response to
antigenic stimulation by T cells that reside in the skin rather than the response of
recirculating memory T cells.
• IFN-γ Release Assays : These tests mainly measure the response of recirculating memory
CD4+ T cells—normally part of a reservoir in the spleen, bone marrow, and lymph nodes—to
persisting bacilliproducing antigenic signals.
17.
18.
19. TREATMENT
First-Line Agents
• Rifampin: Rifampin is the most important and potent antituberculous agent. The standard dosage in adults is
600 mg/d. – The drug distributes well throughout body tissues, including inflamed meninges. It turns body
fluids (e.g., urine, saliva, tears) red-orange and is excreted through bile and the enterohepatic circulation
• Isoniazid: Isoniazid is a critical drug for active and latent TB disease. The usual adult dosage is 300 mg/d or 900
mg twice per week. Isoniazid is distributed well throughout the body and infected tissues, including CSF and
body cavities. The most important toxicities are hepatotoxicity and peripheral neuropathy. Because peripheral
neuropathy can result from interference with pyridoxine metabolism, pyridoxine (25–50 mg/d) should be given
to patients with other risk factors for neuropathy, such as diabetes, alcohol abuse, or malnutrition.
• Ethambutol: The least potent first-line agent, ethambutol is synergistic with the other drugs in the standard
first-line regimen given at a dosage of 15 mg/kg daily. This agent can cause dose-dependent optic neuritis,
producing central scotoma and impairing both visual acuity and the ability to see green.
• Pyrazinamide: The usual dosage is 15–30 mg/kg daily (maximum, 2 g/d). In side effects: Hyperuricemia that
can be managed conservatively is common.
Second-Line Agents
• Fluoroquinolones: Levofloxacin, gatifloxacin and moxifloxacin have solid, broad antimycobacterial activity.
• Other agents (e.g., capreomycin, clofazimine, linezolid, carbapenems, bedaquiline) are used uncommonly but
may be needed in disease caused by resistant strains of M. tuberculosis.
Other Effective Agents
• • Streptomycin: The usual adult dose is 0.75–1.0 g IM daily or 5 times per week. Streptomycin causes
ototoxicity but is less nephrotoxic than other aminoglycosides.
• • Rifabutin: Rifabutin has fewer drug interactions than rifampicin and is recommended in place of rifampicin
for HIV-infected patients who are taking protease inhibitors or non-nucleoside reverse transcriptase inhibitors.
Rifabutin reaches tissue concentrations 5–10 times higher than those in plasma and has a much longer half-life
than rifampin. Adverse effects are gastrointestinal.
• • Rifapentine: Rifapentine is similar to rifampin but can be given once or twice weekly. This drug is not
approved for treatment in HIV-infected patients because of elevated rates of relapse.
20.
21. • Under NTEP initiation and sustaining all TB patients on appropriate anti-TB treatment
wherever they seek care, with patient friendly system and social support. Provision of free
TB drugs in the form of daily fixed dose combinations (FDCs) for all TB cases is advised with
the support of directly observed treatment (DOT).
• (DOT is a specific strategy, to improve adherence by any person observing the patient taking
medications in real time. Screening of all patients for rifampicin resistance (and for
additional drugs wherever indicated) is done.
• For drug sensitive TB and For new TB cases, the treatment in intensive phase (IP) consists
of eight weeks of Isoniazid (INH), Rifampicin, Pyrazinamide and Ethambutol (HRZE) in daily
doses as per four weight band categories and in continuation phase three drug FDCs-
Rifampicin, Isoniazid, and Ethambutol (HRE) are continued for 16 weeks.
• For previously treated cases of TB: the Intensive Phase is of 12 weeks, where injection
streptomycin is given for 8 weeks along with four drugs (INH, Rifampicin, Pyrazinamide and
Ethambutol) and after 8 weeks the four drugs (INH, Rifampicin, Pyrazinamide and
Ethambutol) in daily doses as per weight bands are continued for another four weeks. In
continuation phase Rifampicin, INH, and Ethambutol are continued for another 20 weeks as
daily doses.
• The continuation phase in both new and previously treated cases may be extended by 12-24
weeks in certain forms of TB like skeletal, disseminated TB based on clinical decision.
• Patients eligible for retreatment should be referred for a rapid molecular test or drug
susceptibility testing to determine at least rifampicin resistance, and preferably also isoniazid
resistance status. On the basis of the drug susceptibility profile, a standard first-line
treatment regimen (2HRZE/4HR) can be repeated if no resistance is documented; and if
rifampicin resistance is present, shorter regimen for MDR-TB (multi drug resistant TB)
regimen should be prescribed according to WHO’s recent drug resistant TB treatment
guidelines.
22.
23. • MDR/RR-TB TREATMENT
Shorter oral Bedaquiline-containing MDR/RR-TB regimen
• This regimen is recommended for those MDR/ RR-TB patients in whom
resistance to the component drugs has been excluded or those who have
not been previously treated for more than one month with second-line
drugs used in shorter oral Bedaquiline-containing MDR/RR-TB regimen.
• Total duration of shorter oral Bedaquiline-containing MDR/RR-TB regimen is
for 9-11 months, depending on IP duration.
• IP should be given for at least 4 months. After 4th month of treatment, if
the result of sputum microscopy is negative then CP should be initiated with
Bdq continued for another 2 months.
• If sputum smear microscopy does not become negative by the 4th month of
treatment, subject the patient to FL-LPA and SL-LPA and culture & DST and
the IP should be extended. IP can be extended to 5th or 6th month based
on smear results at the end of 4th and 5th month of treatment. This will be
done for a maximum of 2 months (i.e., total duration of IP is not more than
6 months).
• If any additional resistant to Z/Cfz on C&DST of the baseline sample is
detected or to FQ/InhA & KatG mutation of the 4th month sample is
detected, the patient needs to be reassessed at N/DDR-TBC for stopping
shorter oral Bedaquiline-containing MDR/RR-TB regimen and initiation of
longer oral M/XDR-TB regimen, immediately on receiving the report.
• Duration of CP is fixed for 5 months.
24.
25. Longer oral Bedaquiline-containing MDR/RR-TB regimen
• Longer oral M/XDR-TB regimen is recommended for MDR/RR-TB
patients with H resistance detected with both KatG and InhA
mutation; and MDR/RR-TB patients with FQ resistance detected in
shorter oral Bedaquiline-containing MDR/RR-TB regimen.
• This regimen is used also for XDR-TB patients.
• Longer oral M/XDR-TB regimen is of 18-20 months with no
separate IP or CP.
• Once a patient is placed on a longer oral M/XDR-TB regimen for at
least 4 weeks, normally that patient can no longer be switched to
the shorter oral Bedaquiline-containing MDR/RRTB regimen
because this 4-weeks treatment would represent an exposure to
second-line medicines.
• NTEP guidelines are to start with all 5 drugs of Group A and B and
continue with 4 drugs in the latter part of the regimen (beyond 6-8
months) if the patient can tolerate the drugs.
• GROUP A DRUGS: Levofloxacin, Moxifloxacin, Bedaquiline,
Linezolid.
• Group B drugs: Clofazimine and Cycloserine or terizidone.
26.
27. H mono/poly DR-TB regimen
• H mono/poly DR-TB regimen (R resistance not
detected & H resistance detected)
• Under NTEP: H mono/poly DR-TB regimen is of 6 or
9 months with no separate IP/CP.
