TB Flashcards
TB Susceptible treatment
2HRZE4HR
TB Shorter treatment
Consider in milder disease - no cavitation and smear <2+ BUT stratifying treatment is difficult in a high burden setting
TB Natural history
Most infection does not lead to disease, infection is a dynamic continuum not a binary state, self-cure is probably common but we cannot test for it, active pulmonary TB is a chronic cavitatory pneumonia. TB further impoverishes the poor
TB Key clinical features of PTB
Cough, fever, weight loss, night sweats are cardinal features
TB Diagnostic approach PTB
Sputum is key sample, microscopy widely used and detects the most infectious cases but misses half. Auramine improves performance over ZN. Xpert MTB/RIF detects MTB DNA. Sputum culture is usedd less and less, mainly if concerned about drug resistance. CXR useful and automated (CAD) reading of digital imaging increases access
TB Therapeutic principles
Multidrug therapy for 6m remains standard (2HRZE4HR), shorter 4m regimens endorsed but not implemented, TRUNCATE-TB shows we can go shorter if we can find the right regimen
TB Access
TB diagnostic and treatment services are free of charge in the public sector
TB Vaccines
TB vaccine enthusiasts believe no attempt at TB control will work without a new, effective vaccine, BCG is most widely used but efficacy is limited, objective of vaccine design (and thus study population in vaccine trials) vary, particular focus on prevention of infection (POI) and prevention of disease (POD) in those already infected, major hurdle is correlate of protection - there is no Ab level or other biomarker identified that can predict a vaccine will work, so large and long trials are needed. Therapeutic vaccines aim to improve outcome of treatment of active disease (add to standard treatment) tough as standard treatment already works well
TB LTBI Diagnosis
TST and IGRA are tests of immunoreactivity (not viable latent infection). Indeterminate IGRA means no assessment of TB risk can be made - the test is not valid, the PPV ~5% (fewer than 5% with positive result will go on to develop active TB disease)
TB LTBI Treatment
6H or 3HP (weekly) or 1HP (daily) - (P=rifapentine)
TB Epidemiology
Global TB report tracks national and global data on TB diagnosis, treatment, prevention, screening, financing, social determinants and research - also tracks progress against END-TB targets - progress has been glacial, and short on intermediate milestones, 70% TB burden in 8 countries
TB WHO 2030 END-TB Targets
90% reduction in TB patients, 95% reduction in TB deaths, reduce costs that increase poverty
TB HIV and Diabetes
Predispose to active TB, relative importance of each varies in different parts of the world, HIV is major driver in sub-Saharan Africa but not in Sth America
TB 8 top countries
India 27%, Indonesia 10%, China 7%, Phillippines 7%, Pakistan 6%, Nigeria 5%, Bangladesh 4%, DRC 3%
TB Diabetes
Risk of TB is 3x higher in diabetes than non-diabetes in same population, holds true in both low and high TB burden settings. T2DM is rapidly increasing and accounts for vast majority of this effect, risk in T1DM is probably higher but much less common. People diagnosed with TB should be tested for DM as the TB might be the first manifestation of DM (as for HIV). Screening people with DM for TB is low yield and not cost effective. TB in people with DM is not substantially different to TB in people without DM, treatment is the same
TB Natural history
Some clear infection, most control infection and develop latent TB, of those with LTBI 10% will go on to develop active TB in their lifetime (90% don’t), some develop active TB (develops over weekls to months)
TB HIV coinfection
Different natural history, phenotype and diagnosis, HIV increases probability of early progression, and probability of TB reactivation to 10% per year
TB Paediatric TB
Different natural history, phenotype and diagnosis, larger number go on to active disease
TB TB control
Stop transmission, treat adults with pulmonary TB who are the infectious source
TB Empiric antibiotics
Stop giving empiric antibiotics as it does not discriminate between those with TB and those without - broad spectrum Abx are NOT a discriminator
TB Definition PTB
Involves lung parenchyma, includes miliary disease and any PTB with EP manifestations
TB Definition EPTB
Involves any other system than lung parenchyma, includes hilar lymphadenopathy and pleural disease, for EPTB think HIV
TB Median time to culture conversion
37d in fully susceptible disease
TB WHO Vaccine priorities
1 safe effective & affordable TB vaccine for adolescents and adults, 2 affordable TB vaccine for neonates and infants with improved safety & efficacy, 3 therapeutic vaccine to improve TB Rx outcomes
TB Vaccine challenges
Efficacy seems to be different, including how far people are from the equator, gender, important to consider when looking at vaccines
TB BCG
Only licenced TB vaccine, protects children from TB meningitis and miliary disease, non-specific effects, protection from pulmonary TB lowest near the equator
TB Vaccine strategy
Efficacy signals obtained by POI candidates would require a much lower sample size and a shorter duration of follow-up compared to those candidates tested in Prevention of disease (POD) trials. POI vaccine with partial efficacy would likely have an important public health impact
TB Vaccine for PLHIV
Live mycobacterial vaccines like BCG, VPM1002, and MTBVAC might present a safety risk for PLHIV. This risk needs to be evaluated in the context of ART, viral suppression, CD4 recovery, and completion of TPT. Inactivated mycobacterial, viral-vectored and protein-subunit candidate vaccines, including M72/AS01E, might be safer for vaccination of individuals with HIV and other immune-suppressive conditions
TB Paed prevention gap
In 2020 2/3 of 1.1mil eligible contacts <5y did not access TB preventive treatment (TPT) and less than 5% of eligible HIV-uninfected older child/adolescent contacts accessed TPT
TB RF for paed TB
Infectiousness of the index case, age of child, proximity to and duration of contact with index case, immune status of child, children of families living with HIV, other illnesses (HIV, pertussis, malnutrition, post-measles
TB Paed TB clinical features
Persistent unremitting cough >2-3 weeks, intermittent fever, weight loss/failure to gain weight - other common sx loss of appetite, cough, night sweats, reduced energy/playfulness, recent measles, pertussis and not returning to normal health
TB Tuberculin Skin Testing (TST)
Based on delayed-type hypersensitivity reaction to PPD, positive result suggests infection or sensitisation, do not indicate or rule out TB disease, false positive with previous BCG vaccine, NTM and HIV - positive >=10mm regardless of BCG, >=5mm in children with HIV/malnutrition
TB Interferon gamma release assay (IGRA)
Rely on measurement of IFNg released by memory CD4 T cells stimulated with TB antigens ESAT-6 CFP-10 Pro: one visit Con: expensive, sophisticated lab technology, not available in most resource-poor settings, suboptimal sens in children
TB TST/IGRA limitation
Most people will be sensitised from a very early age, so both TST and IGRA have a low positive predictive value – limits use, as knowledge of epidemiology is just as useful. IGRA NNT (no needed to test) ~80 to make one additional diagnosis
TB Xpert MTB/Rif
SEN ~66% (Ultra ~72%); SPE >98%, does not differentiate between viable and non-viable MTB, SEN lower in routine testing compared to research findings
TB Paed TB diagnosis
Confirmed Mycobacterial confirmation (smear, Xpert or culture) with or without CXR changes, positive TST/IGRA, improvement on antiTB Rx and no confirmed alternative diagnosis - unconfirmed is same minus micro
TB Paed TB diagnostic challenges
Smear sens <10% Xpert sens lower than adults, Culture pos <30%, CXR changes non-specific, TST/IGRA of limited value in TB-endemic settings
TB Paed TB treatment pulmonary, lymphadenitis
2HRZE4HR - daily in intensive phase, intermittent 3x/wk in continuation phase - shorter treatment for children and adolescents with non-severe/smear neg TB are an option
TB Paed TB treatment meningitis, miliary, bone
2HRZE10HR
TB Paed TB treatment
Fixed dose combinations widely available - ensures accurate dosing, simplifies treatment, improves compliance
TB BCG culture process
M bovis in media with ox bile, gradually lost virulence over 18y
TB BCG first administered
1921 infant of mother who died of TB
TB BCG Lubeck disaster
1929 MTB administered to 250 infants instead of BCG, 72 died
TB BCG explanation for variable efficacy
Differences in methods, genetics, geography (works better away from equator), epidemiology (differences in annual risk of infection), nutrition, BCG strains over time, environmental mycobacterial exposure - cellular immunity may be formed due to NTM exposure which blocks/masks BCG effect
TB BCG NTM exposure
BCG more effective in those who are immunologically naïve than in those with prior mycobacterial sensitivity
TB BCG effects
BCG has very good protection against TB meningitis, whereas it is a mess for pulmonary - BCG is a better vaccine against leprosy than it is against TB – major factor behind the worldwide decline in leprosy
TB BCG WHO policy
Single dose at birth, to protect (primarily ?) against childhood TB disease eg: one case of TB meningitis prevented for each 3,500 doses (c.$200 per year of life saved). This policy has relatively little impact on adult pulmonary tuberculosis, or on transmission of M tuberculosis nb: WHO does not advocate repeat vaccination
TB TB vaccine future
Much interest, several candidates, world is ‘saturated’ with BCG - cannot get BCG-free individuals in high endemic TB regions, major problem is no ‘correlate’ of protection - no Ab level etc - very difficult to design immunologic and/or epidemiologic study
