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The role of the Childhood TB Subgroup in vaccine research. Gunnar Bjune TB in the 21st Century Consortium. Not to loose what we have (BCG). Reduces child mortality Prime the immune response for strong Th1 reactivity Protects against allergy Modulates the immune response

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The role of the childhood tb subgroup in vaccine research l.jpg

The role of the Childhood TB Subgroup in vaccine research

Gunnar Bjune

TB in the 21st Century Consortium


Not to loose what we have bcg l.jpg
Not to loose what we have (BCG)

Reduces child mortality

Prime the immune response for

strong Th1 reactivity

Protects against allergy

Modulates the immune response

to ags towards Th1 pattern, not Th2

The gateway to EPI

Quality of MC services

Administered at birth (institutional delivery, registration, vaccination card)


Bcg coverage l.jpg
BCG coverage

  • Institutional delivery

    Quality, referral services/transport

  • Side effects and other SEFIs

    Control, management, registration/reporting

  • Evaluation


Bcg and immune deficiencies l.jpg
BCG and immune deficiencies

  • HIV

    Mothers’ HIV status

  • Measles

    Lack of maternal antibodies

  • Malnutrition/immaturity

    Low birth weigth babies


Watch introduction of emerging successful mtb strains l.jpg
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 l.jpg
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 l.jpg
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 l.jpg
Overlap.. (age/socioec./gender…)

TB

  • Norway

  • Russia

  • Tanzania

HIV


A stable mainly reactivation of latent tb low hiv prevalence small overlap l.jpg
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 l.jpg
Overlap.. prevalence (small overlap)(stage of the epidemics)

% sp+ TB

Costs HS

Cost

Cost/

effective

Transmission

Early

Late


Slide11 l.jpg
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 l.jpg
Cost… continued health services in Sudan.

  • 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 l.jpg
B: Increase, recent infections, low HIV (more overlap) health services in Sudan.

  • 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 l.jpg
C: Increase, recent infections, high HIV (full overlap) health services in Sudan.

  • 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 l.jpg
TB meningitis (BCG failure?) health services in Sudan.

  • Efficiently prevented by BCG

  • No effect of environmental mycobacteria < 1 y of age

  • Diagnostic performance, recording, reporting?

  • Strain epidemiology?


Emerging successful strains l.jpg
Emerging successful strains health services in Sudan.

  • 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 l.jpg
What to do??? health services in Sudan.

  • 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)


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The End???? health services in Sudan. or the beginning?