The role of the Childhood TB Subgroup in vaccine research

Gunnar BjuneTB in the 21st Century

Consortium

Not to loose what we have (BCG)

Reduces child mortalityPrime the immune response for strong Th1 reactivity

Protects against allergyModulates the immune response to ags towards Th1 pattern, not Th2

The gateway to EPIQuality of MC servicesAdministered at birth (institutional

delivery, registration, vaccination card)

BCG coverage

Institutional delivery Quality, referral

services/transport Side effects and other SEFIs Control, management,

registration/reporting Evaluation

BCG and immune deficiencies

HIVMothers’ HIV status MeaslesLack of maternal antibodies Malnutrition/immaturity Low birth weigth babies

Watch introduction of ”emerging successful Mtb strains”

Relative strain prevalence in <15 yrs versus >40 yrs TB pats

TB diagnosis in children, gastric lavage

Efficacy of BCG vaccination Case-control studies with strain typing TB meningitis and BCG status

New anti-TB vaccines

”BCG boosting vaccines” Mtb specific antigens + new

adjuvance Live vectors with rec. Mtb antigens Vaccines to prevent reactivation of

latent TB (therapeutic/post-exposure) ”2nd generation” anti-TB vaccines

(resistance/escape)

Diverse TB epidemiology and diverse vaccine needs

A: Stable, mainly reactivation of latent TB, low HIV prevalence (small overlap)

B: Increase, recent infections, low HIV (more overlap)

C: Increase, recent infections, high HIV (full overlap)

Overlap.. (age/socioec./gender…)

Norway

Russia

Tanzania

HIV TB

A: Stable, mainly reactivation of latent TB, low HIV prevalence (small overlap)

High cost-effectiveness of coordinated preventive programs

Childhood cases few and mainly among household contacts

Full coverage of newborns with BCG Post-exposure vaccine preferably as

a BCG boostering strategy (previous BCG coverage?)

Overlap.. (stage of the epidemics)

Early Late

% sp+ TBCosts HS Cost

Transmission

Cost/effective

The cost of human immunodeficiency virus co-infection to health services in Sudan. Asma Elsony et al. 2004

4% of TB pts HIV+ Total cost of management of HIV+ pts

was 6% of all costs for TB management. Marginal cost attributable to HIV-

positivity was 0.9% of the total cost. Still total cost significantly higher for

HIV+/ HIV- TB ptss ($ 105.1 vs $ 73.9, p=0.003).

Cost… continued

No sign. difference in costs between HIV+ / HIV- TB pats for: diagnostic tests, drugs and management of adverse reactions

Slightly more side effects of treatment among HIV+ / HIV – TB pats (14% vs 9.6%).

Cost difference due to more hospitalization (mortality and morbidity) of HIV+ / HIV- TB pts ($190.8 vs $141)

B: Increase, recent infections, low HIV (more overlap)

High cost-effectiveness of coordinated preventive programs

More childhood cases, but HIV neg. (TBmeningitis in < 5yrs old)

Full coverage of newborn BCG ”2nd generation” anti-TB vaccines

(prevalence of emerging successful strains?)

C: Increase, recent infections, high HIV (full overlap)

Cost-effectiveness of coordinated preventive programs low

Childhood cases many, community contacts (more HIV pos.)

BCG to newborns with caution ”2nd generation” anti-TB vaccines,

no live vector

TB meningitis (BCG failure?)

Efficiently prevented by BCG No effect of environmental

mycobacteria < 1 y of age Diagnostic performance, recording,

reporting? Strain epidemiology?

Emerging successful strains

Rate in TB pats < 15yrs / <40 yrs RFLP + spoligotyping + ? Culture (gastric lavage)? BCG coverage registration / reporting Other selective factors?

(drugs, BCG, HIV, urbanization, MOT..)

What to do??? Meet EPI Support full coverage of BCG to newborns (quality of

services, evaluation, documentation) Meet NTP TB meningitis, strains from pts < 15 yrs (quality of

services, evaluation, documentation) BCG status of TB pts (by scar) recording Meet NHAP HIV+ among TB pts; TB among HIV+s (overlap) Meet the vaccine carpenters and funders and tell them

what you need (post-exposure and second generation ignored)

The End???? or the beginning?