AbstractBackground: 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.Methods: The incidence of febrile illnesses and malaria were evaluated in a birth cohort of HEU infants. Infantswere prescribed daily trimethoprimâsulfamethoxazole (TS) prophylaxis from 6 weeks of age until exclusion of HIVinfection after cessation of breastfeeding. Infants were followed for all illnesses using passive surveillance and routineblood smears were done monthly. Malaria was diagnosed as a positive blood smear plus fever. Placental malaria wasdetermined by histopathology, placental blood smear and PCR. Risk factors for time to first episode of malaria wereassessed using a Cox proportional hazards model. Malaria incidence among HEU infants aged 6â12 months was compared to that in other cohorts of HEU and HUU infants from the same region.Results: Among 361 HEU infants enrolled, 248 completed 12 months of follow-up resulting in 1562 episodes offebrile illness and 253 episodes of malaria after 305 person-years of follow-up. The incidence of febrile illness was5.12 episodes per person-year (PPY), ranging from 4.13 episodes PPY in the first 4 months of life to 5.71 episodes PPYbetween 5 and 12 months of age. The overall malaria incidence was 0.83 episodes per person-year (PPY), increasingfrom 0.03 episodes PPY in the first 2 months of life to 2.00 episodes PPY between 11 and 12 months of age. Therewere no episodes of complicated malaria. The prevalence of asymptomatic parasitaemia was 1.2 % (19 of 1568 routinesmears positive). Infants born to mothers with parasites detected from placental blood smears were at higher riskof malaria (hazard ratio = 4.51, P < 0.001). HEU infants in this study had a 2.4- to 3.5-fold lower incidence of malariacompared to HUU infants in other cohort studies from the same area.Conclusion: The burden of malaria in this birth cohort of HEU infants living in a high-transmission setting and takingdaily TS prophylaxis was relatively low. Alternative etiologies of fever should be considered in HEU-infants taking dailyTS prophylaxis who present with fever.
