Acute gastroenteritis caused by rotavirus infection is an important cause of morbidity and mortality among infants and young children in Africa. From 1997 through 2007, we enrolled 3740 children <5 ...years of age with acute gastroenteritis who received hospital care at the Queen Elizabeth Central Hospital in Blantyre, Malawi. Group A rotavirus was detected in fecal specimens by enzyme immunoassay. Rotavirus strains were characterized for VP7 (G) and VP4 (P) types with use of reverse-transcription polymerase chain reaction. Overall, rotavirus was detected in one-third of children. The median age of children with rotavirus gastroenteritis was 7.8 months, compared with 10.9 months for those without rotavirus in stool specimens (P<.001). Rotavirus circulated throughout the year, with the detection proportion greatest during the dry season (from May through October). A total of 15 single rotavirus strain types were detected during the study period, with genotypes P8G1, P6G8, P4G8, P6G1, P8G3, and P6G9 comprising 83% of all strains characterized. Serotype G12 was detected for the first time in Blantyre during the final 2 years of study. Zoonotic transmission and viral reassortment contributed to the rich diversity of strains identified. Current rotavirus vaccines have the potential to greatly reduce the rotavirus disease burden in Malawi, but they will be required to protect against a broad range of rotavirus serotypes in a young population with year-round rotavirus exposure.
Background. The present study was undertaken to determine the risk and timing of late postnatal transmission (LPT) of human immunodeficiency virus type 1 (HIV-1). Methods. Breast-fed infants ...previously enrolled in 2 trials of antiretroviral prophylaxis were monitored in Malawi. Kaplan-Meier and proportional hazard models assessed cumulative incidence and association of factors with LPT. Results. Overall, 98 infants were HIV infected, and 1158 were uninfected. The cumulative risk of LPT at age 24 months was 9.68% (95% confidence interval, 7.80%–11.56%). The interval hazards at 1.5–6, 6–12, 12–18, and 18–24 months were 1.22%, 4.05%, 3.48%, and 1.27%, respectively. Conclusions. The risk of LPT beyond 6 months is substantial. Weaning at 6 months could prevent >85% of LPT.
In sub-Saharan Africa, most women present late for delivery with unknown HIV status, which limits the use of intrapartum nevirapine to prevent mother-to-child transmission of HIV. We aimed to ...determine whether post-exposure prophylaxis of nevirapine plus zidovudine given to babies only reduced transmission of HIV more than did a regimen of nevirapine alone.
We randomly assigned 1119 babies of Malawian women with HIV-1 who presented late (ie, within 2 h of expected delivery) to either nevirapine alone or nevirapine and zidovudine. Both drugs were given immediately after birth: one dose of nevirapine (2 mg/kg weight) was given as a single dose; babies in the nevirapine plus zidovudine group also received zidovudine twice daily for 1 week (4 mg/kg weight). Infant HIV infection was determined at birth and at 6–8 weeks. Primary outcome was HIV infection in babies at 6–8 weeks in those not infected at birth. Analysis was by intention to treat.
The overall rate of mother-to-child transmission at 6–8 weeks was 15·3% in 484 babies who received nevirapine and zidovudine and 20·9% in 468 babies who received nevirapine only (p=0·03). At 6–8 weeks, in babies who were HIV negative at birth, 34 (7·7%) babies who had nevirapine and zidovudine and 51 (12·1%) who received nevirapine only were infected (p=0·03)—a protective efficacy of 36%. This finding remained after controlling for maternal viral load and other factors at baseline. Adverse events were mild and of similar frequency in the two groups.
Postexposure prophylaxis can offer protection against HIV infection to babies of women who missed opportunities to be counselled and tested before or during pregnancy. The nevirapine and zidovudine regimen is safe and easy to implement.
CONTEXT Antenatal counseling and human immunodeficiency virus (HIV) testing
are not universal in Africa; thus, women often present in labor with unknown
HIV status without receiving the HIVNET 012 ...nevirapine (NVP) regimen (a single
oral dose of NVP to the mother at the start of labor and to the infant within
72 hours of birth). OBJECTIVE To determine risk of mother-to-child transmission of HIV when either
standard use of NVP alone or in combination with zidovudine (ZDV) was administered
to infants of women tested at delivery. DESIGN, SETTING, AND PARTICIPANTS A randomized, open-label, phase 3 trial conducted between April 1, 2000,
and March 15, 2003, at 6 clinics in Blantyre, Malawi, Africa. The trial included
all infants born to 894 women who were HIV positive, received NVP intrapartum,
and were previously antiretroviral treatment–naive. Infants were randomly
assigned to NVP (n = 448) and NVP plus ZDV (n = 446). Infants were enrolled
at birth, observed at 6 to 8 weeks, and followed up through 3 to 18 months.
The HIV status of 90% of all infants was established at 6 to 8 weeks. INTERVENTION Mothers received a 200-mg single oral dose of NVP intrapartum and infants
received either 2-mg/kg oral dose of NVP or NVP (same dose) plus 4 mg/kg of
ZDV twice per day for a week. MAIN OUTCOME MEASURES HIV infection of infant at birth and 6 to 8 weeks, and adverse events. RESULTS The mother-to-child transmission of HIV at birth was 8.1% (36/445) in
infants administered NVP only and 10.1% (45/444) in those administered NVP
plus ZDV (P = .30). A life table estimate of transmission
at 6 to 8 weeks was 14.1% (95% confidence interval CI, 10.7%-17.4%) in infants
who received NVP and 16.3% (95% CI, 12.7%-19.8%) in those who received NVP
plus ZDV (P = .36). For infants not infected at birth
and retested at 6 to 8 weeks, transmission was 6.5% (23/353) in those who
received NVP only and 6.9% (25/363) in those who received NVP plus ZDV (P = .88). Almost all infants (99%-100%) were breastfed
at 1 week and 6 to 8 weeks. Grades 3 and 4 adverse events were comparable;
4.9% (22/448) and 5.4% (24/446) in infants receiving NVP only and NVP plus
ZDV, respectively (P = .76). CONCLUSIONS The frequency of mother-to-child HIV transmission at 6 to 8 weeks in
our 2 study groups was comparable with that observed for other perinatal HIV
intervention studies among breastfeeding women in Africa. The safety of the
regimen containing neonatal ZDV was similar to that of a standard NVP regimen.
We assessed the impact of breastfeeding by women infected with human immunodeficiency virus (HIV)-1 on their morbidity and risk of mortality and on the mortality of their children.
We analysed ...longitudinal data from two previous randomized clinical trials of mother-to-child transmission of HIV conducted between April 2000 and March 2003 in the Republic of Malawi, Africa. Mothers infected with HIV, and their newborns, were enrolled at the time of their child's birth; they then returned for follow-up visits when the child was aged 1 week, 6-8 weeks and then 3, 6, 9, 15, 18, 21 and 24 months. Patterns of breastfeeding (classified as exclusive, mixed or no breastfeeding), maternal morbidity and mortality, and mortality among their children were assessed at each visit. Descriptive and multivariate analyses were performed to determine the association between breastfeeding and maternal and infant outcomes.
A total of 2000 women infected with HIV were enrolled in the original studies. During the 2 years after birth, 44 (2.2%) mothers and 310 (15.5%) children died. (Multiple births were excluded.) The median duration of breastfeeding was 18 months (interquartile range (IQR)=9.0-22.5), exclusive breastfeeding 2 months (IQR=2-3) and mixed feeding 12 months (IQR=6-18). Breastfeeding patterns were not significantly associated with maternal mortality or morbidity after adjusting for maternal viral load and other covariates. Breastfeeding was associated with reduced mortality among infants and children: the adjusted hazard ratio for overall breastfeeding was 0.44 (95% confidence interval (CI)=0.28-0.70), for mixed feeding 0.45 (95% CI=0.28-0.71) and for exclusive breastfeeding 0.40 (95% CI=0.22-0.72). These protective effects were seen both in infants who were infected with HIV and those who were not.
Breastfeeding by women infected with HIV was not associated with mortality or morbidity; it was associated with highly significant reductions in mortality among their children.
We investigated gender-specific risks of mother-to-child transmission (MTCT) at birth and at 6 to 8 weeks among infants born to HIV-infected African women.
Follow-up study of infants enrolled in 2 ...randomized, phase III, clinical trials to prevent MTCT, conducted in Blantyre, Malawi, in southeast Africa.
Infants were enrolled at birth and monitored postnatally, and their HIV status was assessed at birth and at 6 to 8 weeks (assessment beyond 6-8 weeks is ongoing). Statistical analyses were stratified according to gender, and comparisons were made with descriptive, univariate, and multivariate statistical tests. MTCT was estimated at birth and at 6 to 8 weeks among infants who were not infected at birth.
Overall, 966 boys and 998 girls were enrolled. The rate of HIV transmission at birth was 9.5% (187 of 1964 infants). However, at birth significantly more girls (12.6%) than boys (6.3%) were infected with HIV. This association remained significant after controlling for maternal viral load and other factors. Among infants who were uninfected at birth, 8.7% (135 of 1554 infants) acquired HIV by 6 to 8 weeks; of these infants, more girls acquired HIV (10.0%), compared with boys (7.4%).
Female infants may be more susceptible to HIV infection before birth and continuing after birth. Alternatively, in utero mortality rates of HIV-infected male infants may be disproportionately higher and thus more HIV-infected female infants are born. In areas of sub-Saharan Africa, where HIV infection rates are high among women of reproductive age, the magnitude of the gender transmission differences observed in this study could have clinical, preventive, and demographic implications.
To assess patterns of morbidity and associated factors in late infancy and early childhood among human immunodeficiency virus (HIV)-infected and -uninfected African children.
Prospective study.
The ...Queen Elizabeth Central Hospital, Blantyre, Malawi.
Children with known HIV status from an earlier perinatal intervention trial were enrolled during the first year of life and followed to approximately 36 months of age.
Morbidity and mortality information was collected every 3 months by a questionnaire. A physical examination was conducted every 6 months. Blood to determine CD4(+) values was also collected. Age-adjusted and Kaplan-Meier analyses were performed to compare rates of morbidity and mortality among infected and uninfected children.
Overall, 808 children (190 HIV-infected, 499 HIV-uninfected but born to infected mothers, and 119 born to HIV-uninfected mothers) were included in this study. Of these, 109 died during a median follow-up of 18 months. Rates of childhood immunizations were high among all children (eg, lowest was measles vaccination 87% among HIV-infected children). Age-adjusted morbidity rates were significantly higher among HIV-infected than among HIV-uninfected children. HIV-infected children were more immunosuppressed than were uninfected children. By 3 years of age, 89% of the infected children died, 10% were in HIV disease category B or C, and only approximately 1% were without HIV symptoms. Among HIV-infected children, median survival after the first occurrence of acquired immunodeficiency syndrome-related conditions, such as splenomegaly, oral thrush, and developmental delay, was <10 months. These same conditions, in addition to frequent bouts of fever, were the main morbidity predictors of mortality.
The frequency of diseases was high, and progression from asymptomatic or symptomatic HIV disease to death was rapid. Management strategies that effectively reduce morbidity for HIV-infected children are needed.
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