Cytomegalovirus IgG Level and Avidity in Breastfeeding Infants of HIV-Infected Mothers in Malawi

Cytomegalovirus (CMV) infection is common among infants of HIV-infected mothers in resource-limited settings. We examined the prevalence and timing of infant CMV infection during the first year of life using IgG antibody and avidity among HIV-exposed infants in Malawi and correlated the results with the presence of detectable CMV DNA in the blood. The Breastfeeding, Antiretrovirals and Nutrition (BAN) study randomized 2,369 mothers and their infants to maternal antiretrovirals, infant nevirapine, or neither for 28 weeks of breastfeeding, followed by weaning. Stored plasma specimens were tested for CMV IgG and antibody avidity from a random subset of infants who had been previously tested with blood CMV PCR and had available specimens at birth and at 24 and 48 weeks of age. Ninety-four of 127 infants (74.0%) tested at 24 weeks of age had CMV IgG of low or intermediate avidity, signifying primary CMV infections. An additional 22 infants (17.3%) had IgG of high avidity; 19 of them had CMV DNA detected in their blood, indicating infant infections. Taken together, these results show that the estimated prevalence of CMV infection at 24 weeks was 88.9%. By 48 weeks of age, 81.3% of infants had anti-CMV IgG; most of them (70.9%) had IgG of high avidity. The CMV serology and avidity testing, combined with the PCR results, confirmed a high rate of primary CMV infection by 6 months of life among breastfeeding infants of HIV-infected mothers. The CMV PCR in blood detected most, but not all, infant CMV infections.     

Use of lipid-based nutrient supplements by HIV-infected Malawian women during lactation has no effect on infant growth from 0 to 24 weeks

The Breastfeeding, Antiretrovirals, and Nutrition Study evaluated the effect of daily consumption of lipid-based nutrient supplements (LNS) by 2121 lactating, HIV-infected mothers on the growth of their exclusively breast-fed, HIV-uninfected infants from 0 to 24 wk. The study had a 2 × 3 factorial design. Malawian mothers with CD4(+) ≥250 cells/mm(3), hemoglobin ≥70 g/L, and BMI ≥17 kg/m(2) were randomized within 36 h of delivery to receive either no LNS or 140 g/d of LNS to meet lactation energy and protein needs, and mother-infant pairs were assigned to maternal antiretroviral drugs (ARV), infant ARV, or no ARV. Sex-stratified, longitudinal, random effects models were used to estimate the effect of the 6 study arms on infant weight, length, and BMI. Logistic regression models were used to calculate the odds of growth faltering [decline in weight-for-age Z-score (WAZ) or length-for-age Z-score (LAZ) >0.67] using the control arm as the reference. Although some differences between study arms emerged with increasing infant age in boys, there were no consistent effects of the maternal supplement across the 3 growth outcomes in longitudinal models. At the ages where differences were observed, the effects on weight and BMI were quite small (≤200 g and ≤0.4 kg/m(2)) and unlikely to be of clinical importance. Overall, 21 and 34% of infants faltered in WAZ and LAZ, respectively. Maternal supplementation did not reduce the odds of infant weight or length faltering from 0 to 24 wk in any arm. These results indicate that blanket supplementation of HIV-infected lactating women may have little impact on infant growth.     

Maternal mid-upper arm circumference is associated with birth weight among HIV-infected Malawians

The authors examined the relationship of maternal anthropometry to fetal growth and birth weight among 1005 human immunodeficiency virus (HIV)-infected women in Lilongwe, Malawi, who consented to enrollment in the Breastfeeding, Antiretrovirals, and Nutrition Study (www.thebanstudy.org). Anthropometric assessments of mid-upper arm circumference (MUAC), arm muscle area (AMA), and arm fat area (AFA) were collected at the baseline visit between 12 and 30 weeks' gestation and in up to 4 follow-up prenatal visits. In longitudinal analysis, fundal height increased monotonically at an estimated rate of 0.92 cm/wk and was positively and negatively associated with AMA and AFA, respectively. These latter relationships varied over weeks of follow-up. Baseline MUAC, AMA, and AFA were positively associated with birth weight (MUAC: 31.84 g/cm(2), 95% confidence interval [CI], 22.18-41.49 [P < .01]; AMA: 6.88 g/cm(2), 95% CI, 2.51-11.26 [P < .01]; AFA: 6.97 g/cm(2), 95% CI, 3.53-10.41 [P < .01]). In addition, MUAC and AMA were both associated with decreased odds for low birth weight (LBW; <2500 g) (MUAC: odds ratio [OR] = 0.85, 95% CI, 0.77-0.94 [P < .01]; AMA: OR = 0.95, 95% CI, 0.91-0.99 [P < .05]). These findings support the use of MUAC as an efficient, cost-effective screening tool for LBW in HIV-infected women, as in HIV-uninfected women.     

Genetic analysis of circulating and sequestered populations of Plasmodium falciparum in fatal pediatric malaria

Falciparum malaria is characterized by cytoadherence of host erythrocytes containing mature asexual-stage parasites and the consequent sequestration of these forms in tissue microvasculature. A postmortem study of pediatric malaria provided us with the opportunity to compare the genetic complexity of circulating and sequestered Plasmodium falciparum populations, in patients with fatal cerebral malaria (CM) versus control subjects with incidental P. falciparum parasitemia who died of causes other than malaria. Parasite genotypes identified in peripheral blood collected at the time of admission to the hospital constituted a subset of those detected in the tissues at death. Despite a higher tissue burden of parasitized erythrocytes in patients with CM than in parasitemic control subjects, parasite populations in tissues from patients with CM were less genetically complex, and the genotypes were more homogeneously distributed throughout the body, than in patients with incidental infection. Our findings support the notion that CM is associated with the emergence of a small number of dominant genotypes in an infected individual.     

Preterm birth in rural Malawi: high incidence in ultrasound-dated population

BACKGROUND: Preterm birth is the major cause of neonatal death, and has an incidence in industrialized countries of 7%. We have found a high incidence (25-30%) previously in a population of anaemic, pregnant women in southern Malawi, studied with ultrasound dating. METHODS: Cohort study of 512 unselected pregnant women in rural communities in Malawi. All had ultrasound fetal measurements before 24 weeks. RESULTS: 20.3% of women delivered before 37 completed weeks of pregnancy. Babies born before 37 completed weeks but after 32 weeks (16%) were twice as likely to die as babies born at term (6.9 versus 3.4%) but this difference did not achieve statistical significance. For those born between 24 and 33 weeks gestation (4.4%) there was a highly significant increase in perinatal mortality (75%) (p <0 .000001). CONCLUSIONS: This population has a very high rate of preterm birth, which is probably infection-related. It may be representative of many rural populations in sub-Saharan Africa. Tackling the problem of neonatal mortality in low income countries will require effective methods to prevent preterm birth.     

The effect of HIV infection on paediatric bacterial meningitis in Blantyre, Malawi

Aim: To compare presentation, progress, and outcome of acute bacterial meningitis in HIV seropositive and seronegative children. Methods: A double blind randomised placebo controlled study of the use of dexamethasone as adjuvant therapy in acute bacterial meningitis, in children aged 2 months to 13 years, was carried out from July 1997 to March 2001. A total of 598 children were enrolled, of whom 459 were tested for HIV serostatus. Results: Of the 459 children, 34% were HIV seropositive. Their presentation was similar to HIV seronegative children but more were shocked on arrival at hospital (33/157 v 12/302), and more had a focus of infection (85/157 v 57/302). HIV positive children had a higher incidence of Streptococcus pneumoniae infections (52% v 32%). Sixty four cases relapsed; 67% were in HIV positive patients. The mortality in HIV positive children was 65% compared with 36% in HIV negative children. The number of survivors in each group was similar. Hearing loss was more common in HIV negative than HIV positive children (66.3% v 47.2%). Steroid therapy had no influence on meningitis in HIV positive children, but the mortality in HIV negative children was 61% in children given steroids, and 39% in those who did not receive steroids. Conclusion: HIV seropositive children who develop bacterial meningitis have a high mortality and are prone to recurrent disease. There is an urgent need to prevent both primary and recurrent infections.