Timing of malaria in pregnancy and impact on infant growth and morbidity: a cohort study in Uganda.

BACKGROUND: Malaria in pregnancy (MiP) is a major cause of fetal growth restriction and low birth weight in endemic areas of sub-Saharan Africa. Understanding of the impact of MiP on infant growth and infant risk of malaria or morbidity is poorly characterized. The objective of this study was to describe the impact of MIP on subsequent infant growth, malaria and morbidity. METHODS: Between 2006 and 2009, 82 % (832/1018) of pregnant women with live-born singletons and ultrasound determined gestational age were enrolled in a prospective cohort with active weekly screening and treatment for malaria. Infants were followed monthly for growth and morbidity and received active monthly screening and treatment for malaria during their first year of life. Multivariate analyses were performed to analyse the association between malaria exposure during pregnancy and infants' growth, malaria infections, diarrhoea episodes and acute respiratory infections. RESULTS: Median time of infant follow-up was 12 months and infants born to a mother who had MiP were at increased risk of impaired height and weight gain (-2.71 cm, 95 % CI -4.17 to -1.25 and -0.42 kg, 95 % CI -0.76 to -0.08 at 12 months for >1 MiP compared to no MiP) and of malaria infection (relative risk 10.42, 95 % CI 2.64-41.10 for infants born to mothers with placental malaria). The risks of infant growth restriction and infant malaria infection were maximal when maternal malaria occurred in the 12 weeks prior to delivery. Recurrent MiP was also associated with acute respiratory infection (RR 1.96, 95 % CI 1.25-3.06) and diarrhoea during infancy (RR 1.93, 95 % CI 1.02-3.66). CONCLUSION: This study shows that despite frequent active screening and prompt treatment of MiP, impaired growth and an increased risk of malaria and non-malaria infections can be observed in the infants. Effective preventive measures in pregnancy remain a research priority. This study was registered with ClinicalTrials.gov, number NCT00495508.

Impact of malaria during pregnancy on pregnancy outcomes in a Ugandan prospective cohort with intensive malaria screening and prompt treatment.

BACKGROUND: Malaria in pregnancy (MiP) is a major public health problem in endemic areas of sub-Saharan Africa and has important consequences on birth outcome. Because MiP is a complex phenomenon and malaria epidemiology is rapidly changing, additional evidence is still required to understand how best to control malaria. This study followed a prospective cohort of pregnant women who had access to intensive malaria screening and prompt treatment to identify factors associated with increased risk of MiP and to analyse how various characteristics of MiP affect delivery outcomes. METHODS: Between October 2006 and May 2009, 1,218 pregnant women were enrolled in a prospective cohort. After an initial assessment, they were screened weekly for malaria. At delivery, blood smears were obtained from the mother, placenta, cord and newborn. Multivariate analyses were performed to analyse the association between mothers' characteristics and malaria risk, as well as between MiP and birth outcome, length and weight at birth. This study is a secondary analysis of a trial registered with ClinicalTrials.gov, number NCT00495508. RESULTS: Overall, 288/1,069 (27%) mothers had 345 peripheral malaria infections. The risk of peripheral malaria was higher in mothers who were younger, infected with HIV, had less education, lived in rural areas or reported no bed net use, whereas the risk of placental infection was associated with more frequent malaria infections and with infection during late pregnancy. The risk of pre-term delivery and of miscarriage was increased in mothers infected with HIV, living in rural areas and with MiP occurring within two weeks of delivery.In adjusted analysis, birth weight but not length was reduced in babies of mothers exposed to MiP (-60 g, 95%CI: -120 to 0 for at least one infection and -150 g, 95%CI: -280 to -20 for >1 infections). CONCLUSIONS: In this study, the timing, parasitaemia level and number of peripherally-detected malaria infections, but not the presence of fever, were associated with adverse birth outcomes. Hence, prompt malaria detection and treatment should be offered to pregnant women regardless of symptoms or other preventive measures used during pregnancy, and with increased focus on mothers living in remote areas.

Artemether-lumefantrine to treat malaria in pregnancy is associated with reduced placental haemozoin deposition compared to quinine in a randomized controlled trial.

BACKGROUND: Data on efficacy of artemisinin-based combination therapy (ACT) to treat Plasmodium falciparum during pregnancy in sub-Saharan Africa is scarce. A recent open label, randomized controlled trial in Mbarara, Uganda demonstrated that artemether-lumefantrine (AL) is not inferior to quinine to treat uncomplicated malaria in pregnancy. Haemozoin can persist in the placenta following clearance of parasites, however there is no data whether ACT can influence the amount of haemozoin or the dynamics of haemozoin clearance. METHODS: Women attending antenatal clinics with weekly screening and positive blood smears by microscopy were eligible to participate in the trial and were followed to delivery. Placental haemozoin deposition and inflammation were assessed by histology. To determine whether AL was associated with increased haemozoin clearance, population haemozoin clearance curves were calculated based on the longitudinal data. RESULTS: Of 152 women enrolled in each arm, there were 97 and 98 placental biopsies obtained in the AL and quinine arms, respectively. AL was associated with decreased rates of moderate to high grade haemozoin deposition (13.3% versus 25.8%), which remained significant after correcting for gravidity, time of infection, re-infection, and parasitaemia. The amount of haemozoin proportionately decreased with the duration of time between treatment and delivery and this decline was greater in the AL arm. Haemozoin was not detected in one third of biopsies and the prevalence of inflammation was low, reflecting the efficacy of antenatal care with early detection and prompt treatment of malaria. CONCLUSIONS: Placental haemozoin deposition was decreased in the AL arm demonstrating a relationship between pharmacological properties of drug to treat antenatal malaria and placental pathology at delivery. Histology may be considered an informative outcome for clinical trials to evaluate malaria control in pregnancy. REGISTRY: http://clinicaltrials.gov/ct2/show/NCT00495508.

Performance of a histidine-rich protein 2 rapid diagnostic test, Paracheck Pf®, for detection of malaria infections in Ugandan pregnant women.

Improved laboratory diagnosis is critical to reduce the burden of malaria in pregnancy. Peripheral blood smears appear less sensitive than Plasmodium falciparum histidine-rich protein 2-based rapid diagnostic tests (RDTs) for placental malaria infections in studies conducted at delivery. In this study, 81 women in Uganda in the second or third trimester of pregnancy were followed-up until delivery. At each visit, peripheral blood was tested by blood smear, RDT, and nested species-specific polymerase chain reaction (PCR). Sensitivity and specificity of the tests was calculated with PCR, which detected 22 infections of P. falciparum, as the gold standard. The sensitivity and specificity of blood smears were 36.4% (95% confidence interval [CI] = 18.0-59.2%) and 99.6% (95% CI = 97.7-100%), respectively. The corresponding values for RDT were 31.8% (95% CI = 14.7-54.9%) and 100% (95% CI = 98.3-100%). The RDTs could replace blood smears for diagnosis of malaria in pregnancy by virtue of their relative ease of use. Field-based sensitive tests for malaria in pregnancy are urgently needed.

Standardized patients for HIV/AIDS training in resource-poor settings: the expert patient-trainer.

This article presents a unique approach to HIV/AIDS training in resource-poor settings that incorporates the use of standardized patients (SPs). Integrated Management of Adolescent and Adult Illness (IMAI) is a World Health Organization health systems strengthening initiative with a strong emphasis on training health workers in the management of common diseases and conditions. In IMAI, SPs are called Expert Patient-Trainers (EPTs) to emphasize their role in the training of health workers. EPTs were first used in IMAI training in Uganda in 2004. Since then, the method has been adopted by a number of other countries in Africa, Latin America, and Asia. EPTs are usually recruited from groups of people living with HIV/AIDS. In the classroom, EPTs discuss living with HIV and help participants understand HIV as it affects patients. Course participants spend approximately two hours per day in "skill stations," multiple-station assessments consisting of one-on-one encounters with EPTs. In each encounter, the health worker interacts with an EPT portraying a standardized case. Instructions on how to portray each case provide only broad outlines of the major clinical and counseling points; the EPT is expected to use his or her own life experiences to fill in emotional details. Course facilitators noted that health workers were often initially skeptical about EPTs, but this generally turned to enthusiasm after participating in the skill stations. EPTs benefited from the sense of being part of the training team, the satisfaction of improving the skills of health workers, and learning more about their illness.