The level and longevity of protective antibodies elicited by a measles vaccine is significantly shortened by HIV infection in Zambian children, according to the findings of a prospective study published in the August 1st issue of the Journal of Infectious Diseases. Measles immunisation programs may have to consider repeated vaccinations in areas of high HIV-1 prevalence.
Measles still remains a significant cause of childhood mortality in sub-Saharan Africa despite the availability of a vaccine. Barriers to successful measles control by vaccination include poor logistics and insufficient resources, lack of political will, and HIV/AIDS.
HIV infection alters the clinical course of measles in infants: they may not develop the characteristic measles rash and often have a prolonged period of viral shedding. Children born to HIV-infected mothers are more susceptible to measles because of lower levels of maternally acquired antibodies.
HIV-infected children may also respond poorly to measles vaccines and may not maintain protective antibody levels after measles vaccination. Successful measles control in southern Africa with a high HIV prevalence suggests that the HIV epidemic is not a bottleneck to control. The determinants of this success must be identified so that it is replicated in other regions. Specifically, how can a high population immunity be achieved in regions with high HIV prevalence so that measles can be eliminated?
Previous studies of the ability of measles vaccines to stimulate antibodies have taken place in developed countries with no escalating HIV problem. There is a shortage of such immunogenicity studies in Africa with co-endemic HIV. An international team of Zambian, American, and British investigators have addressed this issue in a study of Zambian children.
The study took place at the Chawama Clinic in an urban township of Lusaka. Study participants were children aged 2-8 months who were enrolled from May 2000 to November 2002 as they visited the clinic for childhood immunisation. The Edmonton-Zagreb measles vaccine was administered at about nine months of age to both HIV-positive and HIV-negative children.
Blood samples were collected at 1, 3, 15, and 27 months after vaccination. Total white blood cell counts, haemoglobin levels, and CD4 and CD8 counts were determined. HIV status was re-confirmed using two independent tests. A viral neutralisation assay was used to measure titres of measles antibodies.
Within six months of vaccination, 88% of 50 HIV-positive children developed antibody levels of 120 mIU/ml, compared with 94% of the 98 HIV-seronegative children and 94% of 211 HIV-seropositive but uninfected children (P= 0.3). Three to six months after vaccination, there was no significant difference between seroconversion in HIV-infected, HIV-seropositive but uninfected, and HIV-negative children. During the first six months after vaccination, geometric mean measles antibody concentrations did not differ by HIV status.
After adjusting for HIV status, stunting and wasting were the only significant risk factors associated with lower antibody levels (P = 0.04) and measles seronegative status (P = 0.05). Higher levels of maternal measles antibodies at vaccination were associated with lower levels of measles antibodies 1-3 months but not 3-6 months after vaccination.
Persistence of measles neutralising antibodies at follow-up were analysed by HIV-1 status in 194 and 89 children 15 and 27 months, respectively, after vaccination. The proportion of children who were measles seropositive 15 months after vaccination was significantly lower in children who were HIV-infected at the time of vaccination than the proportion in those who were not HIV-infected (P
By 27 months after vaccination, only half of the 18 HIV-infected children who survived and returned for follow-up maintained measles antibody levels of 120 mIU/ml, compared with 89% of the 71 uninfected children (P =.001). The mean measles antibody concentration at 27 months after vaccination were significantly lower in children infected with HIV at the time of vaccination (P = 0.03) or after vaccination (P = 0.01).
Stunted children had significantly lower antibody levels when data at 15 and 27 months were pooled and adjusted for HIV infection. Severely immunosuppressed children (CD4 cell counts less than 15 %) and those with wasting were more likely to be measles seronegative during follow-up.
After a revaccination program, 11/12 (92 %) HIV-infected children were seropositive but the antibody levels still remained significantly lower by comparison with those in HIV-uninfected children. Generally HIV-infected children with a CD4 cell counts less than 15 % had a 75 % lower antibody levels than those with CD4 cell counts of 25 %.
The findings of Moss et al. show that despite robust primary measles antibody responses by HIV-infected children, the antibody levels and longevity are severely curtailed by the immunosuppression during follow-up.
The policy implication is that measles vaccination campaigns must be repeated more frequently in regions of high HIV-1 prevalence. However, given that effective coverage by the measles vaccine has hitherto been hampered by various reasons, the logistics of repeated vaccinations will be an added constraint.
References
Moss WJ et al. Immunogenicity of standard-titer measles vaccine in HIV-1-infected and uninfected Zambian children: an observational study. J. Infect Dis 196: 347-355, 2007.