Single dose primaquine for clearance of Plasmodium falciparum gametocytes in children with uncomplicated malaria in Uganda: a randomised, controlled, double-blind, dose-ranging trial.

Background: Primaquine is the only available drug that clears mature Plasmodium falciparum gametocytes in infected human hosts, thereby preventing transmission of malaria to mosquitoes. However, concerns about dose-dependent haemolysis in people with glucose-6-phosphate dehydrogenase (G6PD) deficiencies have limited its use. We assessed the dose-response association of single-dose primaquine for gametocyte clearance and for safety in P falciparum malaria.

Changes in population HIV RNA levels in Mbarara, Uganda, during scale-up of HIV antiretroviral therapy access.

Objective: In a rural Ugandan community scaling up antiretroviral therapy (ART), we sought to determine if population-based HIV RNA levels [population viral load (VL)] decreased from 2011 to 2012.

Design: Serial cross-sectional analyses (May 2011 and May 2012) of a defined study community of 6300 persons in a district with HIV prevalence of 8%.

Methods: We measured HIV-1 RNA (VL) levels on all individuals testing positive for HIV during a 5-day high-throughput multidisease community health campaign in May 2012 that recruited two-thirds of the population.

Hair and plasma data show that lopinavir, ritonavir, and efavirenz all transfer from mother to infant in utero, but only efavirenz transfers via breastfeeding.

Background: As efforts intensify to eliminate perinatal HIV transmission, understanding kinetics of maternal-to-child transfer of antiretrovirals during pregnancy and breastfeeding is critical. Antiretroviral levels in plasma, cord blood, and breastmilk reflect exposure over short intervals. Hair concentrations reflect cumulative exposure and can uniquely quantify in utero transfer of maternal medications to infants.

The PROCESS study: a protocol to evaluate the implementation, mechanisms of effect and context of an intervention to enhance public health centres in Tororo, Uganda.

Background: Despite significant investments into health improvement programmes in Uganda, health indicators and access to healthcare remain poor across the country. The PRIME trial aims to evaluate the impact of a complex intervention delivered in public health centres on health outcomes of children and management of malaria in rural Uganda. The intervention consists of four components: Health Centre Management; Fever Case Management; Patient- Centered Services; and support for supplies of malaria diagnostics and antimalarial drugs.

The PRIME trial protocol: evaluating the impact of an intervention implemented in public health centres on management of malaria and health outcomes of children using a cluster-randomised design in Tororo, Uganda.

Background: In Africa, inadequate health services contribute to the lack of progress on malaria control. Evidence of the impact of interventions to improve health services on population-level malaria indicators is needed. We are conducting a cluster-randomised trial to assess whether a complex intervention delivered at public health centres in Uganda improves health outcomes of children and treatment of malaria, as compared to the current standard of care.

Changes in the timing of antiretroviral therapy initiation in HIV-infected patients with tuberculosis in Uganda: a study of the diffusion of evidence into practice in the global response to HIV/AIDS.

Background: We aimed to determine the extent to which emerging evidence and changing guidelines regarding timing of antiretroviral therapy (ART) among human immunodeficiency virus (HIV)-infected patients with tuberculosis influenced "real-world" clinical practice in Uganda.

Methods: We evaluated ART-naive, HIV-infected adults starting tuberculosis therapy at 2 HIV clinics in Uganda between 26 August 2006 and 29 September 2012. We used multivariate regression to calculate associations between 4 calendar periods reflecting publication of seminal clinical studies or changes in guidelines and timing of ART after tuberculosis therapy initiation.

A qualitative study of barriers to enrollment into free HIV care: perspectives of never-in-care HIV-positive patients and providers in Rakai, Uganda.

Background: Early entry into HIV care is low in Sub-Saharan Africa. In Rakai, about a third (31.5%) of HIV-positive clients who knew their serostatus did not enroll into free care services.

Pharmacokinetics of lopinavir/ritonavir and efavirenz in food insecure HIV-infected pregnant and breastfeeding women in Tororo, Uganda.

Pregnancy and food insecurity may impact antiretroviral (ART) pharmacokinetics (PK), adherence and response. We sought to quantify and characterize the PK of lopinavir/ritonavir (LPV/r) and efavirenz (EFV) by pregnancy and nutritional status among HIV-infected women in Tororo, Uganda. In 2011, 62/225 ante-partum/post-partum single dried blood spot samples DBS and 43 post-partum hair samples for LPV/r were derived from 116 women, 51/194 ante-/post-partum DBS and 53 post-partum hair samples for EFV from 105 women.

Intermittent preventive therapy with sulfadoxine-pyrimethamine for malaria in pregnancy: a cross-sectional study from Tororo, Uganda.

Background: Intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is widely recommended in sub-Saharan Africa to reduce the risk of malaria and improve birth outcomes. However, there are reports that the efficacy of IPTp with SP is waning, especially in parts of Africa where antimalarial resistance to this drug has become widespread.

Methodology/principal Findings: We conducted a cross-sectional study of 565 HIV-uninfected women giving birth at Tororo District Hospital in southeastern Uganda.

Among patients with sustained viral suppression in a resource-limited setting, CD4 gains are continuous although gender-based differences occur.

Introduction: There is conflicting data on long-term CD4 immune recovery after combination antiretroviral therapy (ART) in resource-limited settings. Virologic suppression is rarely documented in cohorts from sub-Saharan Africa so objective evidence of adherence is biologically unsubstantiated. We sought to investigate long-term patterns of immune recovery in Ugandan patients on ART with sustained viral suppression.

Acceptability and feasibility of serial HIV antibody testing during pregnancy/postpartum and male partner testing in Tororo, Uganda.

Our objective was to determine whether serial HIV testing during pregnancy and the postpartum period as well as male partner testing are acceptable and feasible in Tororo, Uganda. This was a prospective study of pregnant women at the Tororo District Hospital (TDH) Antenatal Clinic. Patients presenting for routine antenatal care were asked to participate in a serial HIV testing integrated into standard antenatal and postpartum/child immunization visits, and to invite their male partners for HIV testing.

High retention in care among HIV-infected patients entering care with CD4 levels >350 cells/μL under routine program conditions in Uganda.

Background: In Africa, human immunodeficiency virus (HIV)-infected patients who present to care with CD4 levels >350 cells/µL (ie, current antiretroviral treatment thresholds) are often thought to be poorly retained in care, but most estimates do not account for outcomes among patients lost to follow-up.

Methods: We evaluated HIV-infected adults who had made a visit in the last 2.5 years in a program in Uganda.

Anti-malarial prescription practices among outpatients with laboratory-confirmed malaria in the setting of a health facility-based sentinel site surveillance system in Uganda.

Background: Most African countries have adopted artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria. The World Health Organization now recommends limiting anti-malarial treatment to those with a positive malaria test result. Limited data exist on how these policies have affected ACT prescription practices.

Impaired T-cell proliferation among HAART-treated adults with suboptimal CD4 recovery in an African cohort.

Background: Most HIV-infected subjects exhibit a progressive rise in CD4 T-cell counts after initiation of highly active antiretroviral therapy (HAART). However, a subset of individuals exhibit very poor CD4 T-cell recovery despite effective control of HIV-RNA viraemia. We evaluated CD4 T-cell proliferation among suboptimal responders and its correlation with CD4 T-cell activation.

Neonatal mortality in HIV-exposed infants born to women receiving combination antiretroviral therapy in Rural Uganda.

As human immunodeficiency virus (HIV)-infected women gain access to combination antiretroviral therapy throughout sub-Saharan Africa, a growing number of infants are being born HIV-exposed but uninfected. Data about neonatal mortality and the impact of premature delivery, in this population are limited. We describe the 28-day mortality outcomes in a cohort of HIV-exposed infants who had ultrasound-confirmed gestational age in rural Uganda.

Asymptomatic Plasmodium infection and cognition among primary schoolchildren in a high malaria transmission setting in Uganda.

Asymptomatic parasitemia is common among schoolchildren living in areas of high malaria transmission, yet little is known about its effect on cognitive function in these settings. To investigate associations between asymptomatic parasitemia, anemia, and cognition among primary schoolchildren living in a high malaria transmission setting, we studied 740 children enrolled in a clinical trial in Tororo, Uganda. Parasitemia, measured by thick blood smears, was present in 30% of the children.

Study protocol for a randomised controlled double-blinded trial of the dose-dependent efficacy and safety of primaquine for clearance of gametocytes in children with uncomplicated falciparum malaria in Uganda.

Objectives: For the purpose of blocking transmission of Plasmodium falciparum malaria from humans to mosquitoes, a single dose of primaquine is recommended by the WHO as an addition to artemisinin combination therapy. Primaquine clears gametocytes but causes dose-dependent haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Evidence is needed to inform the optimal dosing of primaquine for malaria elimination programmes and for the purpose of interrupting the spread of artemisinin-resistant malaria.

The effect of indoor residual spraying on malaria and anemia in a high-transmission area of northern Uganda.

Indoor residual spraying (IRS) with insecticide is now recommended for malaria control in high-transmission settings. However, concerns about insecticide resistance have increased. We conducted a cross-sectional household survey in high-transmission northern Uganda in two districts previously sprayed with pyrethroids before documentation of pyrethroid resistance and at least one round of carbamates and in one contiguous district that was not sprayed.

The effects of ACT treatment and TS prophylaxis on Plasmodium falciparum gametocytemia in a cohort of young Ugandan children.

Artemisinin-based combination therapies (ACTs) and trimethoprim-sulfamethoxazole (TS) prophylaxis are important tools for malaria control, but there are concerns about their effect on gametocytes, the stage of the parasite responsible for transmission. We conducted a longitudinal clinical trial in a cohort of HIV-infected and uninfected children living in an area of high malaria transmission intensity in Uganda. Study participants were randomized to artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) for all treatments of uncomplicated malaria (N = 4,380) as well as TS prophylaxis for different durations.

Fertility and contraceptive decision-making and support for HIV infected individuals: client and provider experiences and perceptions at two HIV clinics in Uganda.

Background: Some people living with HIV/AIDS (PLHIV) want to have children while others want to prevent pregnancies; this calls for comprehensive services to address both needs. This study explored decisions to have or not to have children and contraceptive preferences among PLHIV at two clinics in Uganda.

Methods: This was a qualitative cross-sectional study.

Prevalence of asymptomatic parasitemia and gametocytemia among HIV-infected Ugandan children randomized to receive different antiretroviral therapies.

In a recent randomized controlled trial, the use of protease inhibitor (PI)-based antiretroviral therapy (ART) was associated with a significantly lower incidence of malaria compared with non-nucleoside reverse transcriptase inhibitor-based ART in a cohort of human immunodeficiency virus-infected Ugandan children living in an area of high malaria transmission intensity. In this report, we compared the prevalence of asymptomatic parasitemia and gametocytemia using data from the same cohort. The prevalence of asymptomatic parasitemia did not differ between the two ART treatment arms.

The effect of HIV on malaria in the context of the current standard of care for HIV-infected populations in Africa.

HIV infection affects the clinical pattern of malaria. There is emerging evidence to suggest that previously documented interactions may be modified by recently scaled-up HIV and malaria interventions. Prophylaxis with trimethoprim-sulfamethoxazole (TS) in combination with use of insecticide-treated nets can markedly decrease the incidence of malaria in HIV-infected pregnant and nonpregnant adults and children even in the setting of antifolate resistance-conferring mutations that are currently common in Africa.

Increasing incidence of malaria in children despite insecticide-treated bed nets and prompt anti-malarial therapy in Tororo, Uganda.

Background: The burden of malaria has decreased in parts of Africa following the scaling up of control interventions. However, similar data are limited from high transmission settings.

Methods: A cohort of 100 children, aged six weeks to 10 months of age, were enrolled in an area of high malaria transmission intensity and followed through 48 months of age.

Factors associated with malaria parasitaemia, malnutrition, and anaemia among HIV-exposed and unexposed Ugandan infants: a cross-sectional survey.

Background: 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.

Methods: 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.