Associations between maternal helminth and malaria infections in pregnancy and clinical malaria in the offspring: a birth cohort in entebbe, Uganda.

BACKGROUND: Helminth and malaria coinfections are common in the tropics. We investigated the hypothesis that prenatal exposure to these parasites might influence susceptibility to malaria in childhood. METHODS: In a birth cohort of 2345 mother-child pairs in Uganda, maternal helminth and malaria infection status was determined during pregnancy, and childhood malaria episodes were recorded from birth to age 5 years. We examined associations between maternal infections and malaria in the offspring. RESULTS: Common maternal infections were hookworm (45%), Mansonella perstans (21%), Schistosoma mansoni (18%), and Plasmodium falciparum (11%). At age 5 years, 69% of the children were still under follow-up. The incidence of malaria was 34 episodes per 100 child-years, and the mean prevalence of asymptomatic malaria at annual visits was 5.4%. Maternal hookworm and M. perstans infections were associated with an increased rate of childhood clinical malaria (adjusted hazard ratio [aHR], 1.24, 95% confidence interval [CI], 1.10-1.41; aHR, 1.20, 95% CI, 1.05-1.38, respectively). S. mansoni infection had no consistent association with childhood malaria. CONCLUSIONS: This is the first report of an association between helminth infections in pregnancy and malaria in the offspring and indicates that helminth infections in pregnancy may increase the burden of childhood malaria morbidity.

A description of congenital anomalies among infants in Entebbe, Uganda.

BACKGROUND: Data on congenital anomalies from developing countries of the sub-Saharan region are scarce. However, it is important to have comprehensive and reliable data on the description and prevalence of congenital anomalies to allow surveillance and the implementation of appropriate public health strategies for prevention and management. In this study, we describe the profile of congenital anomalies seen in a birth cohort in Entebbe, Uganda. METHODS: Congenital anomalies were defined as any structural defect present at birth. Pregnant women were recruited to the cohort between 2003 and 2005. Defects present at birth were recorded by the midwife at delivery and by physicians at the routine six-week postnatal visit and at illness-related visits until 1 year of life. The anomalies were classified by organ system according to the 10th version of the World Health Organization International Classification of Diseases (ICD-10). RESULTS: There were 180 infants with a congenital anomaly among 2365 births. The most commonly affected systems were the musculoskeletal (42.7 per 1000 births) and skin (16.1 per 1000 births). The prevalence of major anomalies was 20.3 per 1000 births; 1.7 per 1000 births for cardiac anomalies and 1.3 per 1000 births for neural system anomalies. Forty (22%) of the congenital anomalies were identified at birth, 131 (73%) at the 6-week postnatal visit, and nine (5%) at illness-related visits. CONCLUSION: Congenital anomalies are common in developing countries. Establishment of comprehensive databases for surveillance would be helpful for surveillance of effects of new exposures, for prevention, management, and health care planning.

Effect of single-dose anthelmintic treatment during pregnancy on an infant's response to immunisation and on susceptibility to infectious diseases in infancy: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Helminth infections affect the human immune response. We investigated whether prenatal exposure to and treatment of maternal helminth infections affects development of an infant's immune response to immunisations and unrelated infections. METHODS: In this randomised, double-blind, placebo-controlled trial, we enrolled 2507 women in the second or third trimester of pregnancy who were planning to deliver in Entebbe General Hospital, Entebbe, Uganda. With a computer-generated random number sequence in blocks of 100, we assigned patients to 440 mg albendazole and 40 mg/kg praziquantel (n=628), 440 mg albendazole and a praziquantel-matching placebo (n=625), 40 mg/kg praziquantel and an albendazole-matching placebo (n=626), or an albendazole-matching placebo and praziquantel-matching placebo (n=628). All participants and hospital staff were masked to allocation. Primary outcomes were immune response at age 1 year to BCG, tetanus, and measles immunisation; incidence of infectious diseases during infancy; and vertical HIV transmission. Analysis was by intention-to-treat. This trial is registered, number ISRCTN32849447. FINDINGS: Data were available at delivery for 2356 women, with 2345 livebirths; 2115 (90%) of liveborn infants remained in follow-up at 1 year of age. Neither albendazole nor praziquantel treatments affected infant response to BCG, tetanus, or measles immunisation. However, in infants of mothers with hookworm infection, albendazole treatment reduced interleukin-5 (geometric mean ratio 0·50, 95% CI 0·30-0·81, interaction p=0·02) and interleukin-13 (0·52, 0·34-0·82, 0·0005) response to tetanus toxoid. The rate per 100 person-years of malaria was 40·9 (95% CI 38·3-43·7), of diarrhoea was 134·1 (129·2-139·2), and of pneumonia was 22·3 (20·4-24·4). We noted no effect on infectious disease incidence for albendazole treatment (malaria [hazard ratio 0·95, 95% CI 0·79-1.14], diarrhoea [1·06, 0·96-1·16], pneumonia [1·11, 0·90-1·38]) or praziquantel treatment (malaria [1·00, 0·84-1·20], diarrhoea [1·07, 0·98-1·18], pneumonia [1·00, 0·80-1·24]). In HIV-exposed infants, 39 (18%) were infected at 6 weeks; vertical transmission was not associated with albendazole (odds ratio 0·70, 95% CI 0·35-1·42) or praziquantel (0·60, 0·29-1·23) treatment. INTERPRETATION: These results do not accord with the recently advocated policy of routine antenatal anthelmintic treatment, and the value of such a policy may need to be reviewed. FUNDING: Wellcome Trust.