Predominant human herpesvirus 6 variant A infant infections in an HIV-1 endemic region of Sub-Saharan Africa.

Human herpesvirus 6, HHV-6, commonly infects children, causing febrile illness and can cause more severe pathology, especially in an immune compromised setting. There are virulence distinctions between variants HHV-6A and B, with evidence for increased severity and neurotropism for HHV-6A. While HHV-6B is the predominant infant infection in USA, Europe and Japan, HHV-6A appears rare. Here HHV-6 prevalence, loads and variant genotypes, in asymptomatic compared to symptomatic infants were investigated from an African region with endemic HIV-1/AIDS. DNA was extracted from blood or sera from asymptomatic infants at 6 and 18 months age in a population-based micronutrient study, and from symptomatic infants hospitalised for febrile disease. DNA was screened by qualitative and quantitative real-time PCR, then genotyped by sequencing at variable loci, U46 (gN) and U47 (gO). HIV-1 serostatus of infants and mothers were also determined. HHV-6 DNA prevalence rose from 15% to 22% (80/371) by 18 months. At 6 months, infants born to HIV-1 positive mothers had lower HHV-6 prevalence (11%, 6/53), but higher HCMV prevalence (25%, 17/67). HHV-6 positive febrile hospitalized infants had higher HIV-1, 57% (4/7), compared to asymptomatic infants, 3% (2/74). HHV-6A was detected exclusively in 86% (48/56) of asymptomatic HHV-6 positive samples genotyped. Co-infections with both strain variants were linked with higher viral loads and found in 13% (7/56) asymptomatic infants and 43% (3/7) HIV-1 positive febrile infants. Overall, the results show HHV-6A as the predominant variant significantly associated with viremic infant-infections in this African population, distinct from other global cohorts, suggesting emergent infections elsewhere.

Reduced Poliovirus vaccine neutralising-antibody titres in infants with maternal HIV-exposure.

BACKGROUND: Maternally HIV-exposed (mHIV-EU) infants have poor health even without HIV-1 infection. The responses to vaccination are less well defined. Immunity to oral Poliovirus vaccine (OPV) was studied in Zambian infants participating in a randomised controlled trial of micronutrient fortification to improve child health. METHOD: Maternally HIV-unexposed and mHIV-EU infants were recruited at 6 months age and randomised to basal or enriched micronutrient-fortified diets for 12 months. HIV-exposed mother-infant pairs had received perinatal nevirapine to prevent mother-to-child-transmission. In the cohort of 597 infants, neutralising-antibody titres to OPV were analysed at 18 months with respect to micronutrient fortification, maternal or infant HIV-1 infection, and human cytomegalovirus (HCMV) infection detected by antibodies and viraemia (serum DNA). Vaccine protection was defined as log2 titre>3. RESULTS: Compared to uninfected children, HIV-1-infected children had reduced neutralising antibody titres to OPV, irrespective of diet: log2 titre difference (95% confidence interval) -3.44 (-2.41; -4.46), P<0.01. OPV antibody titres were lower in HIV-infected children with HCMV viraemia compared to those without viraemia at 18 months, but did not reach significance: difference -2.55 (-6.10; 1.01), P=0.14. Breast-feeding duration was independently associated with increasing OPV titre (P-value<0.01). In mHIV-EU children there were reduced neutralising antibody titres to Poliovirus compared with maternally HIV-unexposed, irrespective of diet, maternal education and socioeconomic status: log2 titre difference (95% confidence interval) -0.56 (-0.98; -0.15), P<0.01. This difference was noticeably decreased after adjusting for breast-feeding duration, suggesting that in our study population less breast-feeding by HIV-positive mothers could explain the reduced OPV titres in mHIV-EU infants. CONCLUSION: The mHIV-EU infants had reduced polio vaccine antibody titres which were associated with reduced breast-feeding duration. This has important implications for polio eradication and control of vaccine-preventable diseases, in countries where childhood HIV-1 infection and maternal exposure are public health threats.