The Effect of Cotrimoxazole Prophylaxis and Insecticide-treated Bednets on the Risk of Malaria among HIV-infected Ugandan Children
Anne Gasasira*1, M Kamya1, J Achan1, T Mebrahtu2, T Ruel2, A Kekitiinwa3, E Charlebois2, P Rosenthal2, D Havlir2, and G Dorsey2
1Makerere Univ Med Sch, Kampala, Uganda; 2Univ of California, San Francisco, US; and 3Mulago Hosp, Kampala, Uganda
infection is associated with an increased risk of malaria among adults, which
can be reduced with cotrimoxazole (CTX) prophylaxis. However, data are limited
on the protective effect of CTX prophylaxis on malaria risk in children, the
group that suffers the greatest burden of this disease. We evaluated the
efficacy of CTX for prevention of malaria among HIV-infected children in Kampala, Uganda,
where antifolate resistance to malaria is common.
Methods: Between October 2005 and September 2006 we
enrolled a cohort of 300 HIV-infected children aged 1 to 10 years in the
Children with HIV and Malaria Project (CHAMP) in Kampala, Uganda.
All children were prescribed CTX prophylaxis, and 88% reported using
insecticide-treated bed-nets. Parasite
prevalence was measured at enrollment and every 3 months. Thick blood smears
were done for all children who presented with a new episode of fever. A
concurrent cohort of 561 healthy children aged 1 to 10 years was followed simultaneously, using identical
assessment schedules for malaria; these children were not prescribed CTX
prophylaxis, and only 12% used insecticide-treated bed-nets.
of the 300 HIV-infected children and 20% of children recruited from the
community (p <0.0001) had a
positive malaria blood smear at enrollment. Between October 2005 and September
2006, only 9 episodes of malaria were diagnosed among HIV-infected children
(incidence = 0.07/person-year) compared to 440 episodes among children
recruited from the community (incidence = 0.90/person-year, p <0.0001) for an incidence rate
ratio of 0.08 (0.04 to 0.15). The prevalence of the dhfr/dhps quintuple mutation, which has been associated with
antifolate resistance, was common in samples both from patients taking CTX
(100%) and those not taking CTX (75%). Compared with no intervention, the risk
of malaria among HIV-infected children receiving CTX alone was decreased by 35%
(IRR 0.65, 0.27 to 1.57) and the risk in those receiving CTX and using insecticide-treated
bed-nets was decreased by 97% (IRR
0.03, 0.01 to 0.11). Malaria accounted for only 4% of all fever episodes in the
HIV-infected cohort compared to 33% in the community-based cohort (p <0.0001).
In a malaria-endemic area with high-level antifolate resistance, CTX prophylaxis and insecticide-treated bed-nets were
associated with dramatic reductions in malaria among HIV-infected children compared
to healthy controls. Fevers among HIV-infected children receiving CTX and
insecticide-treated bed-nets are unlikely due to malaria, and other etiologies
should be sought.