Browsing by Author "Bigira, Victor"

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    Efficacy and Safety of Three Regimens for the Prevention of Malaria in Young HIV-Exposed Ugandan Children: A Randomized Controlled Trial
    (AIDS, 2014) Kamya, Moses R.; Kapisi, James; Bigira, Victor; Tamara, D. Clark; Kinara, Stephen; Mwangwa, Florence; Muhindo, Mary K.; Kakuru, Abel; Aweeka, Francesca T.; Achan, Jane; Havlir, Diane V.; Rosenthal, Philip J.; Dorsey, Grant
    Trimethoprim-sulfamethoxazole (TS) prophylaxis is recommended for HIV-exposed infants until breastfeeding ends and HIV infection has been excluded. Extending prophylaxis with a focus on preventing malaria may be beneficial in high transmission areas. We investigated three regimens for the prevention of malaria in young HIV-exposed children. Tororo, Uganda, a rural area with intense, year-round, malaria transmission. 200 infants aged 4-5 months enrolled and 186 randomized after cessation of breastfeeding and confirmed to be HIV uninfected (median 10 months of age). No chemoprevention, monthly sulfadoxine-pyrimethamine (SP), daily TS, or monthly dihydroartemisinin-piperaquine (DP) given from randomization to 24 months of age. The primary outcome was the incidence of malaria during the intervention period. Secondary outcomes included the incidence of hospitalization, diarrheal illness, or respiratory tract infection; prevalence of anemia and asymptomatic parasitemia; measures of safety; and incidence of malaria over 1 year after the intervention was stopped. During the intervention, the incidence of malaria in the no chemoprevention group was 6.28 episodes per person-year at risk. Protective efficacy was 69% (95% CI, 53-80%, p<0.001) for DP, 49% (95% CI, 23-66%, p=0.001) for TS, and 9% for SP (95% CI, −35 to 38%, p=0.65). There were no significant differences in any secondary outcomes, with the exception of a lower prevalence of asymptomatic parasitemia in the DP arm. Monthly chemoprevention with DP was safe and associated with a significant reduction in malaria in young HIV-exposed children.
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    Factors Associated with Malaria Parasitaemia, Malnutrition, and Anaemia among HIV-Exposed and Unexposed Ugandan Infants: A Cross-Sectional Survey
    (Malaria journal, 2012) Osterbauer, Beth; Kapisi, James; Bigira, Victor; Mwangwa, Florence; Kinara, Stephen; Kamya, Moses R.; Dorsey, Grant
    Malaria, malnutrition and anaemia are major causes of morbidity and mortality in African children. The interplay between these conditions is complex and limited data exist on factors associated with these conditions among infants born to HIV-uninfected and infected women. Two hundred HIV-exposed (HIV-uninfected infants born to HIV-infected mothers) and 400 HIV-unexposed infants were recruited from an area of high malaria transmission in rural Uganda. A cross-sectional survey was performed at enrolment to measure the prevalence of malaria parasitaemia, measures of malnutrition (z-scores <2 standard deviations below mean) and anaemia (haemoglobin <8 gm/dL). Multivariate logistic regression was used to measure associations between these conditions and risk factors of interest including household demographics, malaria prevention practices, breastfeeding practices, household structure and wealth index. The prevalence of malaria parasitaemia was 20%. Factors protective against parasitaemia included female gender (OR = 0.66, p = 0.047), mother’s age (OR = 0.81 per five-year increase, p = 0.01), reported bed net use (OR = 0.63, p = 0.03) and living in a well-constructed house (OR = 0.25, p = 0.01). Although HIV-unexposed infants had a higher risk of parasitaemia compared to HIV-exposed infants (24% vs 14%, p = 0.004), there was no significant association between HIV-exposure status and parasitaemia after controlling for the use of malaria preventative measures including bed net use and trimethoprim-sulphamethoxazole prophylaxis. The prevalence of stunting, underweight, and wasting were 10%, 7%, and 3%, respectively. HIV-exposed infants had a higher odds of stunting (OR = 2.23, p = 0.005), underweight (OR = 1.73, p = 0.09) and wasting (OR = 3.29, p = 0.02). The prevalence of anaemia was 12%. Risk factors for anaemia included older infant age (OR = 2.05 per one month increase, p = 0.003) and having malaria parasitaemia (OR = 5.74, p < 0.001). Compared to HIV-unexposed infants, HIV-exposed infants had a higher use of malaria preventative measures and lower odds of malaria parasitaemia. Having a better constructed house was also protective against malaria parasitaemia. HIV-exposure was the primary risk factor for measures of malnutrition. The primary risk factor for anaemia was malaria parasitaemia. These findings suggest the need to better target existing interventions for malaria, malnutrition and anaemia as well as the need to explore further the mechanisms behind the observed associations.
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    Impact of Antimalarial Treatment and Chemoprevention on the Drug Sensitivity of Malaria Parasites Isolated from Ugandan Children
    (Antimicrobial agents and chemotherapy, 2015) Tumwebaze, Patrick; Conrad, Melissa D.; Walakira, Andrew; LeClair, Norbert; Byaruhanga, Oswald; Nakazibwe, Christine; Okiring, Jaffer; Kakuru, Abel; Bigira, Victor; Kapisi, James; Kamya, Moses R.; Greenhouse, Bryan; Nsobya, Samuel L.; Rosenthal, Philip J.
    Changing treatment practices may be selecting for changes in the drug sensitivity of malaria parasites. We characterized ex vivo drug sensitivity and parasite polymorphisms associated with sensitivity in 459 Plasmodium falciparum samples obtained from subjects enrolled in two clinical trials in Tororo, Uganda, from 2010 to 2013. Sensitivities to chloroquine and monodesethylamodiaquine varied widely; sensitivities to quinine, dihydroartemisinin, lumefantrine, and piperaquine were generally good. Associations between ex vivo drug sensitivity and parasite polymorphisms included decreased chloroquine and monodesethylamodiaquine sensitivity and increased lumefantrine and piperaquine sensitivity with pfcrt 76T, as well as increased lumefantrine sensitivity with pfmdr1 86Y, Y184, and 1246Y. Over time, ex vivo sensitivity decreased for lumefantrine and piperaquine and increased for chloroquine, the prevalences of pfcrt K76 and pfmdr1 N86 and D1246 increased, and the prevalences of pfdhfr and pfdhps polymorphisms associated with antifolate resistance were unchanged. In recurrent infections, recent prior treatment with artemether-lumefantrine was associated with decreased ex vivo lumefantrine sensitivity and increased prevalence of pfcrt K76 and pfmdr1 N86, 184F, and D1246. In children assigned chemoprevention with monthly dihydroartemisinin-piperaquine with documented circulating piperaquine, breakthrough infections had increased the prevalence of pfmdr1 86Y and 1246Y compared to untreated controls. The noted impacts of therapy and chemoprevention on parasite polymorphisms remained significant in multivariate analysis correcting for calendar time. Overall, changes in parasite sensitivity were consistent with altered selective pressures due to changing treatment practices in Uganda. These changes may threaten the antimalarial treatment and preventive efficacies of artemether-lumefantrine and dihydroartemisinin-piperaquine, respectively.
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    Poor Housing Construction Associated with Increased Malaria Incidence in a Cohort of Young Ugandan Children
    (The American journal of tropical medicine and hygiene, 2015) Snyman, Katherine; Mwangwa, Florence; Bigira, Victor; Kapisi, James; Tamara, D. Clark; Sturrock, Hugh; Gosling, Roly; Dorsey, Grant
    Despite the use of accepted interventions to combat malaria, such as insecticide-treated bed nets and artemisinin-based combination therapy, malaria remains a leading cause of morbidity and mortality in Uganda. We investigated associations between household factors and malaria incidence in a cohort of children living in a highly endemic region of Uganda. Living in a modern house, defined as the use of non-earth floors, non-thatched roofs, and non-mud walls, was associated with approximately half malaria incidence compared with living in a traditional home (incidence rate ratio [IRR] = 0.54, P = 0.001). Other factors found to be associated with a lower incidence of malaria included living in town versus rural setting; sleeping in a room with openings to the outside (windows, eaves, and airbricks); and having an older and more educated primary caregiver. This study adds to the growing body of evidence that improved house construction may be associated with a lower risk of malaria.
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    Protective Efficacy and Safety of Three Antimalarial Regimens for the Prevention of Malaria in Young Ugandan Children: A Randomized Controlled Trial doi:10.1371/journal.pmed.1001689
    (PLoS medicine, 2014) Bigira, Victor; Kapisi, James; Clark, Tamara D.; Kinara, Stephen; Mwangwa, Stephen; Muhindo, Mary K.; Osterbauer, Beth; Aweeka, Francesca T.; Huang, Liusheng; Achan, Jane; Havlir, Diane V.; Rosenthal, Philip J.; Kamya, Moses R.; Dorsey, Grant
    Chemoprevention offers a promising strategy for prevention of malaria in African children. However, the optimal chemoprevention drug and dosing strategy is unclear in areas of year-round transmission and resistance to many antimalarial drugs. To compare three available regimens, we conducted an open-label randomized controlled trial of chemoprevention in Ugandan children. Methods and Findings: This study was conducted between June 28, 2010, and September 25, 2013. 400 infants were enrolled and 393 randomized at 6 mo of age to no chemoprevention, monthly sulfadoxine-pyrimethamine (SP), daily trimethoprim-sulfamethoxazole (TS), or monthly dihydroartemisinin-piperaquine (DP). Study drugs were administered at home without supervision. Piperaquine (PQ) levels were used as a measure of compliance in the DP arm. Participants were given insecticide-treated bednets, and caregivers were encouraged to bring their child to a study clinic whenever they were Chemoprevention was stopped at 24 mo of age, and participants followed-up an additional year. Primary outcome was the incidence of malaria during the intervention period. During the intervention, the incidence of malaria in the no chemoprevention arm was 6.95 episodes per person-year at risk. Protective efficacy was 58% (95% CI, 45%–67%, p,0.001) for DP, 28% (95% CI, 7%–44%, p = 0.01) for TS, and 7% for SP (95% CI, 219% to 28%, p = 0.57). PQ levels were below the detection limit 52% of the time when malaria was diagnosed in the DP arm, suggesting non-adherence. There were no differences between the study arms in the incidence of serious adverse events during the intervention and the incidence of malaria during the 1-y period after the intervention was stopped.Conclusions: For preventing malaria in children living in an area of high transmission intensity, monthly DP was the mostefficacious and safe, although adherence may pose a problem.Monthly SP and daily TS may not be appropriate in areas with high transmission intensity and frequent resistance to antifolates.