Human immunodeficiency virus (HIV) type 1 load in breast milk and mastitis were examined as risk factors for vertical transmission of HIV-1. Six weeks after delivery, HIV-1 load and sodium (an indicator of mastitis) were measured in breast milk from 334 HIV-1-infected women in Malawi. Median breast milk HIV-1 load was 700 copies/mL among women with HIV-1-infected infants versus undetectable (<200 copies/mL) among those with uninfected infants, respectively (P<. 0001). Elevated breast milk sodium levels consistent with mastitis occurred in 16.4% of HIV-1-infected women and were associated with increased vertical transmission of HIV-1 (P<.0001). Median breast milk HIV-1 load was 920 copies/mL among women with versus undetectable among those without elevated breast milk sodium levels, respectively (P<.0001). Mastitis and breast milk HIV-1 load may increase the risk of vertical transmission of HIV-1 through breast-feeding.

Aim-To determine the influence of placental malaria, maternal HIV infection, and maternal hypergammaglobulinaemia on transplacental IgG antibody transfer. Methods-One hundred and eighty materno-neonatal pairs from a Malawian population were assessed. Cord and maternal serum samples were tested for total serum IgG antibody titres using nephelometry, and for specific IgG antibody titres to Streptococcus pneumoniae, measles, and tetanus toxoid antibodies using an enzyme linked immunsorbent assay (ELISA). Results-Multiple regression analyses showed that placental malaria was associated with a decrease in placental IgG antibody transfer to S pneumoniae and measles to 82% and 81%, respectively. Maternal HIV infection was associated with a reduction in IgG antibody transfer to S pneumoniae to 79%; raised maternal total serum IgG titres were correlated with S pneumoniae and measles IgG antibody transfer reduction to 86% and 87%, respectively. No eVect was seen with tetanus toxoid antibody transfer. Conclusion-The combined influence of placental malaria, maternal HIV infection, and maternal hypergammaglobulinaemia seems to be linked to the low transplacental antibody transfer observed in the Malawian population.

In a 2-year study of viral gastroenteritis in children in Blantyre, Malawi, the diversity of rotavirus strains was investigated by using electropherotyping, reverse transcription-PCR amplification of the VP7 and VP4 genes (G and P genotyping), and nucleotide sequencing. Of 414 rotavirus strains characterized, the following strain types were identified: P[8], G1 (n ‫؍‬ 111; 26.8%); P[6], G8 (n ‫؍‬ 110; 26.6%); P[8], G3 (n ‫؍‬ 93; 22.5%); P[4], G8 (n ‫؍‬ 31; 7.5%); P[8], G4 (n ‫؍‬ 21; 5.1%); P[6], G3 (n ‫؍‬ 12; 2.9%); P[6], G1 (n ‫؍‬ 7; 1.7%); P[6], G9 (n ‫؍‬ 3; 0.7%); P[6], G4 (n ‫؍‬ 3; 0.7%); P[4], G3 (n ‫؍‬ 1; 0.2%); and mixed (n ‫؍‬ 15; 3.6%). While all strains could be assigned a G type, seven strains (1.7%) remained P nontypeable. The majority of serotype G8 strains and all serotype G9 strains had short electropherotype profiles. All remaining typeable strains had long electropherotypes. Divergent serotype G1 rotaviruses, which contained multiple base substitutions in the 9T-1 primer binding site, were commonly identified in the second year of surveillance. Serotype G2 was not identified. Overall, G8 was the most frequently identified VP7 serotype (n ‫؍‬ 144; 34.8%) and P[8] was the most frequently detected VP4 genotype (n ‫؍‬ 227; 54.8%). Partial sequence analysis of the VP4 gene of genotype P[8] rotaviruses identified three distinct clusters, which predominantly (but not exclusively) comprised strains belonging to a distinct VP7 serotype (G1, G3, or G4). As a result of mutations in the 1T-1 primer binding site, strains belonging to each cluster required a separate primer for efficient typing. One cluster, represented by P[8], G4 strain OP354, was highly divergent from the established Wa and F45 VP4 P[8] lineages. As is the case for some other countries, the diversity of rotaviruses in Malawi implies that rotavirus vaccines in development will need to protect against a wider panel of serotypes than originally envisioned.In developing countries severe, dehydrating diarrhea caused by human rotavirus (HRV) results in an estimated 500,000 to 870,000 childhood deaths annually (13, 43). The routine implementation of safe and effective rotavirus vaccine programs in developing countries is expected to reduce dramatically the high level of mortality attributed to HRV, but the differing epidemiology of rotavirus in such settings may pose special challenges to successful vaccine use (6). In particular, the greater diversity of HRV strains encountered in some developing countries has implications for the formulation of rotavirus vaccines, since the original targets of these vaccines were the four most globally common HRV serotypes, G1 to G4, and some candidate vaccines were designed to provide serotypespecific (homotypic) protection (42). Thus, the first licensed vaccine, the tetravalent rhesus-human reassortant rotavirus (RRV-TV) vaccine, incorporated strains with these four mostcommon G-serotypes. The RRV-TV vaccine proved highly effective in preventing severe rotavirus diarrhea in infants and young children (3,35,49...

Summaryobjectives To examine in pregnant women the relationship between HIV infection and malaria prevalence and to determine, in relation to HIV infection, the effectiveness of sulphadoxine-pyrimethamine in clearing P. falciparum infection.method Descriptive cross-sectional analysis of P. falciparum prevalence in pregnant women at first antenatal visit and of women at delivery who had received two sulphadoxine-pyrimethamine treatments for malaria. HIV status was assessed in 621 women who attended for antenatal care and for delivery at two rural hospitals in southern Malawi in 1993-94. Information was collected on maternal age, parity and gestational age. Prevalence of P. falciparum was measured at first antenatal visit and delivery. Women were given two routine treatment doses of sulphadoxine-pyrimethamine (SP), at first antenatal visit and between 28 and 34 weeks gestation, conforming to Malawi government policy on antimalarial control during pregnancy.results Prevalence of HIV infection was 25.6% and all infections were HIV type-1. In primigravidae malaria prevalence at recruitment was 56.3% in HIV-infected and 36.5% in HIV-uninfected women (P ϭ 0.04). The corresponding figures for multigravidae were 23.8% and 11.0%, respectively (P Ͻ 0.01). HIVinfected primigravidae had increased malaria prevalence at all gestational ages. Peak parasite prevalence occurred earlier in gestation in HIV-infected primigravidae (16-19 weeks if HIV-infected; 20-23 weeks if HIV-uninfected). The relative risk for parasitaemia in HIV-infected compared to HIV-uninfected women was significantly increased in three of five parity groups, including the two highest ones (parity Ͼ3), indicating parity-specific immunity to malaria was impaired. Malaria prevalence at delivery remained high in HIV-infected women despite prior routine treatment with sulphadoxine-pyrimethamine in pregnancy. There was no significant difference in parasite prevalence at delivery between women who did or did not use sulphadoxine-pyrimethamine.conclusions HIV infection is associated with a significant increase in malaria prevalence in pregnant women of all parities with the effect apparent from early in gestation. Two treatment doses of sulphadoxine-pyrimethamine were inadequate to clear parasitaemia in many women by the time of delivery and this occurred independently of HIV status and despite high sensitivity to SP in this area. There is a need to undertake longitudinal studies to determine the incidence of P. falciparum infection in HIV-infected and uninfected pregnant women and to reassess the frequency and timing of sulphadoxine-pyrimethamine treatment doses in these women. Late pregnancy re-infections with P. falciparum probably explain the high parasite prevalence at delivery following sulphadoxinepyrimethamine treatment at 28-34 weeks gestation. keywords pregnancy, malaria, HIV, antimalarial control, sulphadoxine-pyrimethamine correspondence Professor B.J. Brabin,