Abstract
BackgroundHIV-exposed, uninfected (HEU) infants suffer high morbidity and mortality in the first year of life compared to HIV-unexposed, uninfected (HUU) infants, but accurate data on the contribution of malaria are limited.MethodsThe incidence of febrile illnesses and malaria were evaluated in a birth cohort of HEU infants. Infants were prescribed daily trimethoprim–sulfamethoxazole (TS) prophylaxis from 6 weeks of age until exclusion of HIV-infection after cessation of breastfeeding. Infants were followed for all illnesses using passive surveillance and routine blood smears were done monthly. Malaria was diagnosed as a positive blood smear plus fever. Placental malaria was determined by histopathology, placental blood smear and PCR. Risk factors for time to first episode of malaria were assessed using a Cox proportional hazards model. Malaria incidence among HEU infants aged 6–12 months was compared to that in other cohorts of HEU and HUU infants from the same region.ResultsAmong 361 HEU infants enrolled, 248 completed 12 months of follow-up resulting in 1562 episodes of febrile illness and 253 episodes of malaria after 305 person-years of follow-up. The incidence of febrile illness was 5.12 episodes per person-year (PPY), ranging from 4.13 episodes PPY in the first 4 months of life to 5.71 episodes PPY between 5 and 12 months of age. The overall malaria incidence was 0.83 episodes per person-year (PPY), increasing from 0.03 episodes PPY in the first 2 months of life to 2.00 episodes PPY between 11 and 12 months of age. There were no episodes of complicated malaria. The prevalence of asymptomatic parasitaemia was 1.2 % (19 of 1568 routine smears positive). Infants born to mothers with parasites detected from placental blood smears were at higher risk of malaria (hazard ratio = 4.51, P < 0.001). HEU infants in this study had a 2.4- to 3.5-fold lower incidence of malaria compared to HUU infants in other cohort studies from the same area.ConclusionThe burden of malaria in this birth cohort of HEU infants living in a high-transmission setting and taking daily TS prophylaxis was relatively low. Alternative etiologies of fever should be considered in HEU-infants taking daily TS prophylaxis who present with fever. Trial Registration NCT00993031, registered 8 October, 2009
Highlights
HIV-exposed, uninfected (HEU) infants suffer high morbidity and mortality in the first year of life compared to HIV-unexposed, uninfected (HUU) infants, but accurate data on the contribution of malaria are limited
Study design, setting and population This was a planned secondary data analysis in a birth cohort of HEU infants born to HIV-infected mothers who were part of a randomized controlled trial of lopinavir/ritonavir versus efavirenz-based antiretroviral therapy (ART) living in Tororo district, Uganda [Protease Inhibitors to Reduce Malaria Morbidity in HIV-Infected Pregnant Women (PROMOTE-PIs), NCT00993031)] [13]
Infants born with low birth weight had a lower risk of developing malaria in the first year of life but this did not reach statistical significance. In this birth cohort of HEU infants living in an area of high transmission intensity, the burden of malaria was relatively low in the first year of life compared to HUU infants from the same area
Summary
HIV-exposed, uninfected (HEU) infants suffer high morbidity and mortality in the first year of life compared to HIV-unexposed, uninfected (HUU) infants, but accurate data on the contribution of malaria are limited. Accurate data on the incidence of malaria among infants of HIV-infected mothers receiving ART and who, themselves receive TS, are needed to guide clinical management. The objective of this study was to describe the natural history of malaria in a birth cohort of Ugandan HEU infants who were born to mothers who received ART as part of a clinical trial during pregnancy and who themselves received TS prophylaxis starting at ~6 weeks of life, as per current WHO guidelines. Risk factors for malaria in the first year of life were assessed at the time of birth
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