Elliot Welford, MD
Infectious Diseases Fellow
Division of Infectious Diseases & Global Public Health
Department of Medicine
University of California, San Diego
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
10.16.20 | TB or not TB (Burmese Refugee with Brain Mass)
1. HIV & Global Health Rounds
The UC San Diego AntiViral Research Center sponsors weekly
presentations by infectious disease and global public health clinicians,
physicians, and researchers. The goal of these presentations is to
provide the most current research, clinical practices, and trends in HIV,
HBV, HCV, TB, and other infectious diseases of global significance.
The slides from the HIV & Global Health Rounds presentation that you
are about to view are intended for the educational purposes of our
audience. They may not be used for other purposes without the
presenter’s express permission.
2. TB OR NOT TB
(BURMESE REFUGEE WITH BRAIN
MASS)
Elliott Welford, MD
Pronouns: he/him/his
UCSD Infectious Diseases Fellow
Division of Infectious Diseases & Global Public Health
10/16/2020
4. OBJECTIVES
• Describe classic MRI brain findings seen in toxoplasma encephalitis, TB
meningitis, and crypto meningitis
• Define TB based on drug resistance
• List differences between WHO and IDSA/ATS MDR TB treatment
guidelines
• Describe the ATS/IDSA guideline approach for selecting treatment
regimen for MDR-TB
5. HPI
• 29 y/o M with untreated HCV, HIV(off treatment since 8/2015), previously
treated MDR TB, both diagnosed in 2008 in Burma, who presented on
5/27/2020 w/ 5 months intermittent hemoptysis, and HA.
• He says he felt weak with malaise/pain all over the body but worst is his
headache.
• He says he has had 5 months of cough with several weeks of hemoptysis
with frank blood, unable to quantify how much. Says on 5/26/2020, he had “
a little bit of blood.”
• He was treated for TB in 2008 in Burma for at least12 months. Pt denies any
fever or weight loss. No sore throat, SOB, night sweats, nausea, vomiting,
diarrhea.
6. HISTORY
• Med History: HIV, HCV, h/o TB
• Allergies: NKDA
• Surgical History: none
• FAMILY HISTORY: Mother and father in 70s and in good health, no TB
or malignancy
7. HISTORY CONTINUED
• SOCIAL HISTORY:
Tobacco: None
• Alcohol: Stopped “several years ago.” previously socially
• Recreational drugs: IVDU when in Burma, not since he left in 2013
• Sexual history: w/ women only, no sex in at least 2yrs
• Living situation: Lives w/ sister, brother-in-law and sister's 3 children,
youngest 4yr old in an apartment in SD
• Work: Sushi chef in San Diego
8. PHYSICAL EXAM
• VS: T: 98 °F, BP: 108/71 HR: 76, RR: 14, O2: 100% on RA
• GEN: NAD, A&Ox4, lying in bed
• HEENT: EOMI, sclera anicteric, MMM, OP clear w/o lesions or ulcers. No submandibular,
cervical or axillary LAD. No thrush.
• CARDIO: RRR, no m/r/g. Peripheral pulses intact
• CHEST/PULM: Normal work of breathing. CTAB w/o w/r/r
• ABD: Soft, NTND, NABS, no HSM
• EXT: WWP, no edema
• INTEG: No rashes or lesions
• NEURO: Face symmetric, PERRL, EOMI, speech fluent, moving all extremities spontaneously,
following commands w/o issue
11. IMAGING: CT CHEST WITH IV CONTRAST
• Right greater than left apical scarring/bronchiectasis in the setting of
multi-station mild thoracic lymphadenopathy could be compatible with
sequela of prior or chronic granulomatous infection. No definite
evidence of ongoing infection
• Incidentally noted prominent/tortuous bronchial arteries can be
associated with hemoptysis.
• Paraesophageal and submucosal periesophageal varices
12. IMAGING: MRI
• Extensive locoregional mass effect associated with
multiple irregular, predominantly peripherally enhancing
lesions scattered throughout the supratentorial and
infratentorial convexities.
• Ultimately, the present constellation of findings favor
stigmata of atypical intracranial infection, such as
referable to tuberculosis with associated early
tuberculous abscess in the right frontal lobe and
scattered additional tuberculomas
• toxoplasmosis given slightly eccentric nodule within the
dominant lesion in the left thalamus
14. APPROACH TO CNS LESIONS IN
HIV/AIDS
• HIV-Associated lesion
• HIV Encephalitis
• OI
• Toxoplasmosis: most common CNS infection in the AIDS (15–50%)
• Tuberculosis
• Cryptococcus
• Candidiasis
• Aspergillosis
• Coccidiomycosis
• Neoplasm
• PML
• Primary CNS Lymphoma
17. TOXO ENCEPHALITIS
• Pathologically: necrotizing abscess, organizing abscess, chronic abscess.
• Ring-like or solid nodular enhancement with edema and mass effect.
• Located in the basal ganglia (up to 75%), corticomedullar junction, and
posterior fossa
19. • Basal meningitis: meningeal enhancement in the basal cisterns (41%)
and/or hydrocephalus (51%)
• Tuberculomas are solitary or multiple ring/nodular enhancing lesions,
which are reported to be small lesions with little mass effect and/or
edema– the result of hematogenous spread
• Tuberculous abscesses are a rare form of infection. They are larger than
tuberculomas and mostly multiloculated. The ring-like enhancing
lesions cannot be differentiated radiologically from abscesses of other
causes.
• Basal meningitis:meningeal enhancement in the basal cisterns (41%) and/or
hydrocephalus (51%)
• Tuberculomas are solitary or multiple ring/nodular enhancinglesions,which are
reported to be small lesions with little mass effect and/or edema– the result of
hematogenous spread
• Tuberculous abscesses are arare form of infection. They are larger than
tuberculomas and mostly multiloculated. The ring-like enhancing lesions
cannot be differentiated radiologically from abscesses of other causes.
• Basal meningitis:meningeal enhancement in the basal cisterns (41%) and/or
hydrocephalus (51%)
• Tuberculomas are solitary or multiple ring/nodular enhancinglesions,which are
reported to be small lesions with little mass effect and/or edema– the result of
hematogenous spread
• Tuberculous abscesses are arare form of infection. They are larger than
tuberculomas and mostly multiloculated. The ring-like enhancing lesions
cannot be differentiated radiologically from abscesses of other causes.
• Basal meningitis:meningeal enhancement in the basal cisterns (41%) and/or
hydrocephalus (51%)
• Tuberculomas are solitary or multiple ring/nodular enhancinglesions,which are
reported to be small lesions with little mass effect and/or edema– the result of
hematogenous spread
• Tuberculous abscesses are arare form of infection. They are larger than
tuberculomas and mostly multiloculated. The ring-like enhancing lesions
cannot be differentiated radiologically from abscesses of other causes.
21. • Crypto Meningitis:
• 1. Meningitis with mild dilatation of the ventricular system or (rarely) nodular
meningeal enhancement
• 2. Dilated perivascular spaces (Virchow-Robin) filled with fungiformation of
cystic found predominantly symmetrically in the basal ganglia and thalamus
• 3. Cryptococcoma (extremely rare): found preferentially in the ependyma of the
choroid plexus.
CRYPTO MENINGITIS
23. ASSESSMENT
• More likely
• Toxo
• TB
• Primary CNS
Lymphoma
• Less likely
• Crypto
• Cocci
• Candida
• Aspergillus
• HIV- related
lesion
• PML
25. TB HISTORY
• Patient presented to healthcare facility in Kuala Lumpur on September
4th,2008 with a month history of cough, hemoptysis, fever, night sweats,
loss of appetite and loss of weight. His sputum AFB smear was positive.
Chest radiograph showed right upper zone consolidation and cavities.
26. • TB smears & cultures (May 30-June 1 2012 & Nov 6-8
2012): Negative
• Pre-departure smears (Jan 22-24 2013): negative
• Departed to USA on Feb 6 2013.
28. TB DEFINITIONS BASED ON DRUG
RESISTANCE
• Mono-resistant TB
• Poly-resistant TB
• more than 1 anti-TB drug (but not INH and RIF)
• MDR TB
• At least INH and RIF
• XDR TB
• at least INH, RIF, a fluoroquinolone, and 1 of 3 second-line injectable agents
(AK, KM, or CM)
29. RESISTANCE TESTING
• Xpert MTB/RIF Assay
• NAAT, detects MTB complex and rpoB gene (>95% of rif resistance)
• Pyrosequencing (PSQ)
• Genetic markers of resistance: RIF, INH, quinolones, and injectable drugs
• Performed at CADPH
38. OBJECTIVES
• Describe classic MRI brain findings seen in toxoplasma encephalitis, TB
meningitis, and crypto meningitis
• Define TB based on drug resistance
• List differences between WHO and IDSA/ATS MDR TB treatment
guidelines
• Describe the ATS/IDSA guideline approach for selecting treatment
regimen for MDR-TB
39. REFERENCES
• Levy, R. M., Bredesen, D. E., & Rosenblum, M. L. (1985). Neurological manifestations of the acquired
immunodeficiency syndrome (AIDS): Experience at UCSF and review of the literature, Journal of
Neurosurgery, 62(4), 475-495. Retrieved Oct 14, 2020, from https://thejns.org/view/journals/j-
neurosurg/62/4/article-p475.xml
• Sánchez-portocarrero J, Pérez-Cecilia E, Jiménez-Escrig A, et al. Tuberculous Meningitis: Clinical
Characteristics and Comparison With Cryptococcal Meningitis in Patients With Human
Immunodeficiency Virus Infection. Arch Neurol. 1996;53(7):671–676.
doi:10.1001/archneur.1996.00550070109018
• Curry International Tuberculosis Center and California Department of Public Health, 2016: Drug-
Resistant Tuberculosis: A Survival Guide for Clinicians, Third Edition [pp. 66-87].
• XPERT MTB/RIF For the Diagnosis of Pulmonary and Extrapumonary TB: Policy Update, WHO.
https://apps.who.int/iris/bitstream/handle/10665/112472/9789241506335_eng.pdf?sequence=1
• Nahid P, Dorman SE, Alipanah N, et al. Official American Thoracic Society/Centers for Disease
Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment
of Drug-Susceptible Tuberculosis. Clin Infect Dis. 2016;63(7):e147-e195
• Nahid P, Mase SR, Migliori GB, Sotgiu G, Bothamley GH, Brozek JL, Cattamanchi A, Cegielski JP, Chen
L, Daley CL, Dalton TL. Treatment of drug-resistant tuberculosis. An official ATS/CDC/ERS/IDSA
clinical practice guideline. American journal of respiratory and critical care medicine. 2019 Nov
15;200(10):e93-142.
• Centers for Disease Control. Chapter 2: Transmission and Pathogenesis of Tuberculosis. Core
Curriculum on Tuberculosis. 2013. <https://www.cdc.gov/tb/education/corecurr/pdf/chapter2.pdf>
Hinweis der Redaktion
in the basal ganglia,
caput nuclei caudati, and
frontal and occipital lobes.
In the series of Villoria et al. of 35 patients with AIDS
and proven intracranial tuberculosis, hydrocephalus
was the most frequent finding (51%), followed by meningeal
enhancement (41%)
Prospective study of neurologic complications of HIV carried out from 1988—1992 in Madrid
What pathogens would you empirically cover for in this patient?
https://www.polleverywhere.com/multiple_choice_polls/8O5OHLnXt7Kk60hcS6tCl?flow=Default&onscreen=persist
2/2010-8/2011: 18mos
MDR TB is defined as resistance to which of the following?
https://www.polleverywhere.com/multiple_choice_polls/2iluBnh5lNCeB69phdMGU?flow=Default&onscreen=persist
According to the 2018 American Thoracic Society Guidelines, how many medications are recommended to treat MDR TB during the intensive phase?
https://www.polleverywhere.com/multiple_choice_polls/HtbNgtVtf6FqSne01dQNk?flow=Default&onscreen=persist
ATS/IDSA prefers oral over IV/injectable. Do not recommend Capreomycin or kanamycin. Amikacin and streptomycin can be used if sensis known.
Published systematic reviews, meta-analyses, and a new individual patient data meta-analysis from 12,030 patients, in 50 studies, across 25 countries with confirmed pulmonary rifampin-resistant TB were used for this guideline.
Certainty in the evidence was judged to be very low because the data came from observational studies with significant loss to follow-up and imbalance in background regimens between comparator groups.
Of note, our recommendations for the
use of bedaquiline, moxifloxacin, and levofloxacin in the treatment of MDR-TB are strong despite very low certainty in the evidence because the writing committee viewed the large reductions in mortality, improved treatment success rates, and relatively few adverse effects of these drugs as corresponding to the notably favorable balances of benefits and harms. Despite linezolid-containing regimens showing similar large reduction in mortality and improved treatment success, the increased adverse effects noted for linezolid correspond to a balance of benefits and harms that is less favorable compared with bedaquiline and later-generation fluoroquinolones.
Bactrim 5/30- present
In a small (77 patients) randomized trial, TMP-SMX was reported to be effective and better tolerated than pyrimethamine-sulfadiazine
We did not believe this was necessarily true because patient was also on steroids
Within the necrotic debris, a rare spherical body with centralstippled basophilic material, somewhat resembling a toxoplasma bradyzoitecyst, is seen. Similar structures, as well as smaller scattered particlespossibly representing tachyzoites, are highlighted on toxoplasma gondii IHCstain, although interpretation is complicated by high-background staining