*4.5.9. BCG vaccination and HIV infection*

Approaches for prevention of TB include prevention of infection (through immunization) or of progression from latent infection to disease (chemoprophylaxis). Bacille Calmette-Guérin (BCG) vaccine, a live attenuated vaccine derived from Mycobacterium bovis that was developed in the 1920s, is administered to children at birth in many countries. WHO guidelines recommend administration of BCG soon after birth to all infants in countries with a high TB prevalence. Current WHO guidelines advise that all children below 5 years of age, who are in close contact with a sputum smear-positive index patient, should be actively traced, screened for TB, and provided preventive chemotherapy after active TB has been excluded (Marais et al., 2004).

Although this is good policy, implementation is fraught with challenges, including difficulty in diagnosing latent TB in a highly BCG-vaccinated population, ruling out incipient active disease, and the lack of procedures for documentation and follow-up of contact screening and chemoprophylaxis in national programs. Because the majority of transmission in children below 3 years of age occurs in the household and they are also the group at highest risk of progression to disease after primary infection, this activity should be given higher priority in national infection-control programs. Moreover, active tracing and screening of household contacts at high risk would allow children with disease to receive a diagnosis earlier, thus reducing complications.

Furthermore, additional protection by revaccination with BCG has not been demonstrated (Rodrigues et al., 2005). To date, the efficacy of the BCG vaccination has not been determined in HIV infected individuals in whom the immune responses to BCG may be reduced, (Hesseli et al., 2007) although this is the subject of ongoing trials. Due to the risk of disseminated BCG disease which may rarely complicate use of this live vaccine in immunocompromised indi‐ viduals, BCG vaccination is no longer recommended in children known to be HIV-infected (Hesseling et al., 2007). In practice, this has had little impact in HIV-endemic countries, where the HIV-status of the baby is rarely established at birth, the usual time of BCG vaccination.

A large trial in southern India that included over 350,000 participants aged above 1 year concluded that BCG vaccine did not offer protection against the development of adult pulmonary TB (WHO, 2006). However, BCG vaccine has been shown to be protective against disseminated forms of TB in young children, with a protective estimate ranging from 67%– 79% against TB meningitis and 58%–87% against miliary disease. A theoretical model esti‐ mated that a universal BCG vaccine program would have a beneficial impact in settings with prevalence rates of greater than 30 sputum smear-positive cases/100,000 population (WHO, 2007). However, there is no evidence of any BCG-induced protective effect in HIV-infected children. On the contrary, studies have documented BCG-induced disseminated disease and adverse reactions. Therefore, the WHO recommendations have been revised, making HIV infection a contraindication for BCG vaccination, even in settings where TB is highly endemic. Strategies required for effective implementation of this policy change include high uptake of maternal HIV testing coupled with implementation of proven strategies to prevent mother-tochild HIV transmission, including maternal treatment with HAART and early virological diagnosis of HIV infection in infants, followed by treatment.

The revised recommendations present a dilemma for national programs. Although the benefits of BCG vaccine far outweigh the risk among HIV-uninfected children living in high areas with a high prevalence of TB, the risk is higher among HIV-infected infants with or without symptoms at the time of vaccination. National recommendations will need to consider a variety of factors, including the prevalence of TB in the population, the prevalence of HIV infection, the availability of HIV testing and facilities for prevention of mother-to-child transmission during pregnancy, the capacity to conduct follow-up of vaccinated children, and the availa‐ bility of early infant diagnosis of HIV infection. Abandoning the use of BCG vaccine before newer vaccines become available may put millions of young children at risk of TB. There is an urgent need for operational research in TB endemic countries to determine the best way to manage this issue programmatically.
