TuberculosisACTIVE VS. LATENT INFECTION & SCREENING

M ED ST UDEN T LEC T UR E SER I ES

UPDAT ED SEPT EM BER , 2019

Bacteriology of M. TuberculosisAerobic rod

Cell wall with mycolic acid ◦ Gives the acid fast quality

◦ Weakly gram positive

Source: Infected people

Other bacteria in this genus: avum, intracellulare, leprae, bovus*

*source of BCG vaccine

PathogenesisWe rely on T-cell mediated immunity against M. tuberculosis

Early in infection, M. tuberculosis replicates within macrophages (blocks phagolysosome fusion)

Around 3 weeks after infection Th1 response activates macrophages via INF-gamma and formation of granulomas (caseating granulomas) to contain disease

Any Th1 modulating therapy should have TB testing prior to administration

Infection vs Active DiseaseINFECTION

In most immunocompetent hosts, generally asymptomatic

◦ Often forms fibrocalcific pulmnodule

◦ May remain dormant (latent) and await immune insult to reactivate (active)

2-4 weeks after infection, can develop (+)PPD

ACTIVE DISEASE

Clinical tuberculosis

Primary TB◦ After exposure, develop active

disease

◦ Occurs in ~5% of cases

Secondary TB◦ Infected host with prolonged latent

infection that sustains immune insult, reactivating infection

~5%

Primary TBOften resembles acute bacterial pneumonia

◦ Lobe consolidation, hilary adenopathy, pleural effusion

◦ May have lymphohematogenous spread

Secondary TBUsually following latent infection and reactivation

◦ This is why we screen – to identify and treat latent TB before it becomes active disease

More commonly has apical lung disease

Symptoms concerning for TB infection◦ Weight loss, FTT

◦ Night sweats

◦ Fever

◦ Fatigue

◦ Hemoptysis, cough or chest pain for pulmonary TB

TB Infections by TissueMeninges

Kidneys

Bones

Adrenals

Vertebrae

Intestines

Meningitis

Renal tuberculosis

Osteomyelitis

Addison’s Disease

Pott’s Disease

Intestinal TB (more common in countries where M. bovis is in unpasturized milk)

Screening for Latent TBRisk factors

◦ Born in high risk country

◦ Immunocompromised

◦ Travel to endemic countries

◦ Housing insecurity or lives in shelter

◦ Living with someone with TB

◦ Incarceration

◦ Having contact with someone who has been exposed to TB

PPD vs IGRA (Quantiferon Gold)◦ IDSA/CDC now recommends IGRA if >/= 5yo

◦ AAP even recommends IGRA as early as 2yo if concerns for follow-up or h/o BCG vaccination

POSITIVE Tuberculin Skin Test5mm induration if:• HIV-infected• Recent TB contact• Fibrotic changes on CXR c/w prior TB• Transplant patient• Immunosuppressed

10mm induration if:• Recent immigrant (<5yrs) from high prevalence country• IV drug user• Residents and employees of high-risk congregate setting• Mycobacteriology lab personnel• Children <4yo• Pediatric patient exposed to adult in high-risk category

15mm induration for everyone, even if no known risk factors, and including previous h/o BCG vaccination

Treatment for Active TBRifampin

◦ Hepatotoxic, stains secretions

Isoniazid◦ May cause transaminitis, B6 deficiency

Pyrazinamide

Ethambutol◦ Optic toxicity

Streptomycin◦ Ototoxicity

ReferencesCDC

◦ https://www.cdc.gov/tb/default.htm

Hay, W, Levin, M, Deterding, R, & Abzug, M. (2016). Current Diagnosis & Treatment: Pediatrics (23rd ed.). Lange.

Kumar, Abbas, & Aster. (2015). Robins and Cotran Pathologic Basis of Disease (9th ed.). Elsevier.

Tuberculosis in Children. Pediatrics In Review. Apr 2019, Vol 40, Iss 4. https://pedsinreview.aappublications.org/content/40/4/168