Hilton Whittle

Effect of subclinical infection on maintaining immunity against measles in vaccinated children in West Africa

BACKGROUND Despite a high coverage with measles vaccines in parts of west Africa, epidemics of measles occur with reduced severity in an increasing proportion of older children who have been vaccinated. We examined the effect of exposure to natural measles on immunity in vaccinated children. METHODS Our study was carried out in 1992 during an epidemic of measles in Niakhar, a rural area of Senegal with about 27,000 inhabitants who mostly live in compounds that include several households; within each household people live in different huts. Vaccine coverage in Niakhar was 81% at the time of our study. We measured haemagglutinin-inhibiting antibody at exposure and twice thereafter (after 4-5 weeks and at 6 months) in 36 vaccinated and 87 unvaccinated children. The frequency of measles and subclinical measles--defined as a four-fold or greater rise in antibody titre without clinical signs or symptoms--was related to intensity of exposure according to whether the index case was in the same hut, household, or compound. FINDINGS Clinical measles occurred in 20 (56%) of 36 unvaccinated children and in one (1%) of 87 vaccinated children. Subclinical measles occurred in 39 (45%) of 86 vaccinated children who were exposed to measles and in four (25%) of 16 unvaccinated children. The frequency was inversely related to pre-exposure antibody concentration (p<0.001 for trend) and directly related to intensity of exposure (p=0.002 for trend). Antibody concentrations in subclinical cases increased on average by 45-fold and remained raised for at least 6 months. INTERPRETATION Increased antibody titre after subclinical measles may be common in vaccinated children in West Africa where the intensity of exposure is high. As measles vaccination coverage increases, the circulation of wild measles will decrease, and vaccine-induced antibody is less likely to be boosted. Thus, new epidemics, albeit milder in form, may occur in vaccinated areas which should be recognised in campaigns to eradicate measles.

TRIAL OF HIGH-DOSE EDMONSTON-ZAGREB MEASLES VACCINE IN GUINEA-BISSAU: PROTECTIVE EFFICACY

In a randomised study of 558 children in an urban African community, the protective effect of the Edmonston-Zagreb (EZ) measles vaccine given in a dose of 40,000 plaque forming units from the age of 4 months was compared with the effects of a standard dose (6000 tissue culture infectious units) of Schwarz measles vaccine given from the age of 9 months. During two years of follow-up, all 14 clinical cases of measles occurred in the Schwarz group; 10 of the children contracted measles before vaccination and 4 after measles vaccination. Thus the EZ vaccine provided significant protection against measles both before and after the usual age of vaccination. Among the children who were exposed to measles at home, those given EZ vaccine were better protected than either unvaccinated children or those given the Schwarz vaccine.

CD4 intragenic SNPs associate with HIV-2 plasma viral load and CD4 count in a community-based study from Guinea-Bissau, West Africa.

Objectives:The human genetics of HIV-2 infection and disease progression is understudied. Therefore, we studied the effect of variation in 2 genes that encode products critical to HIV pathogenesis and disease progression: CD4 and CD209. Design:This cross-sectional study consisted of 143 HIV-2, 30 HIV-1 + HIV-2 and 29 HIV-1-infected subjects and 194 uninfected controls recruited from rural Guinea-Bissau. Methods:We genotyped 14 CD4 and 4 CD209 single nucleotide polymorphisms (SNPs) that were tested for association with HIV infection, HIV-2 plasma viral load (high vs. low), and CD4+ T-cell count (high vs. low). Results:The most significant association was between a CD4 haplotype rs11575097-rs10849523 and high viral load [odds ratio (OR): = 2.37, 95% confidence interval (CI): 1.35 to 4.19, P = 0.001, corrected for multiple testing], suggesting increased genetic susceptibility to HIV-2 disease progression for individuals carrying the high-risk haplotype. Significant associations were also observed at a CD4 SNP (rs2255301) with HIV-2 infection (OR: = 2.36, 95% CI: 1.19 to 4.65, P = 0.01) and any HIV infection (OR: = 2.50, 95% CI: 1.34 to 4.69, P = 0.004). Conclusions:Our results support a role of CD4 polymorphisms in HIV-2 infection, in agreement with recent data showing that CD4 gene variants increase risk to HIV-1 in Kenyan female sex workers. These findings indicate at least some commonality in HIV-1 and HIV-2 susceptibility.