Evidence favoring earlier HIV ART initiation at high CD4+ T-cell counts (CD4>350/uL) has grown, and guidelines now recommend earlier HIV treatment. However, the cost of providing ART to individuals with CD4>350 in Sub-Saharan Africa has not been well estimated. This remains a major barrier to optimal global cost projections for accelerating the scale-up of ART. Our objective was to compute costs of ART delivery to high CD4+count individuals in a typical rural Ugandan health center-based HIV clinic, and use these data to construct scenarios of efficient ART scale-up.

Optimizing quality of care for malaria and other febrile illnesses is a complex challenge of major public health importance. To evaluate the impact of an intervention aiming to improve malaria case management on the health of community children, a cluster-randomized trial was conducted from 2010-2013 in Tororo, Uganda, where malaria transmission is high. Twenty public health centers were included; 10 were randomized in a 1:1 ratio to intervention or control. Households within 2 km of health centers provided the sampling frame for the evaluation. The PRIME intervention included training in fever case management using malaria rapid diagnostic tests (mRDTs), patient-centered services, and health center management; plus provision of mRDTs and artemether-lumefantrine. Cross-sectional community surveys were conducted at baseline and endline (N = 8,766), and a cohort of children was followed for approximately 18 months (N = 992). The primary outcome was prevalence of anemia (hemoglobin < 11.0 g/dL) in children under 5 years of age in the final community survey. The intervention was delivered successfully; however, no differences in prevalence of anemia or parasitemia were observed between the study arms in the final community survey or the cohort. In the final survey, prevalence of anemia in children under 5 years of age was 62.5% in the intervention versus 63.1% in control (adjusted risk ratio = 1.01; 95% confidence interval = 0.91-1.13; P = 0.82). The PRIME intervention, focusing on training and commodities, did not produce the expected health benefits in community children in Tororo. This challenges common assumptions that improving quality of care and access to malaria diagnostics will yield health gains.

The high burden of undiagnosed HIV in sub-Saharan Africa limits treatment and prevention efforts. Community-based HIV testing campaigns can address this challenge and provide an untapped opportunity to identify non-communicable diseases (NCDs). We tested the feasibility and diagnostic yield of integrating NCD and communicable diseases into a rapid HIV testing and referral campaign for all residents of a rural Ugandan parish.

Artemisinin-based combination therapy (ACT) is widely recommended as first-line therapy for uncomplicated Plasmodium falciparum malaria worldwide. Artemisinin resistance has now been reported in Southeast Asia with a clinical phenotype manifested by slow parasite clearance. Although there are no reliable reports of artemisinin resistance in Africa, there is a need to better understand the dynamics of parasite clearance in African children treated with ACT in order to better detect the emergence of artemisinin resistance.

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.

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.

Angiogenic processes in the placenta are critical regulators of fetal growth and impact birth outcomes, but there are limited data documenting these processes in HIV-infected women or women from low-resource settings.

To compare the efficacy and safety of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) for treating uncomplicated falciparum malaria in Uganda.

Intermittent preventive treatment (IPT) is a well established malaria control intervention. Evidence that delivering IPT to schoolchildren could provide community-level benefits is limited. We did a cluster-randomised controlled trial to assess the effect of IPT of primary schoolchildren with dihydroartemisinin-piperaquine (DP) on indicators of malaria transmission in the community, in Jinja, Uganda.

Long-lasting insecticidal nets (LLINs) are a key malaria control intervention. To investigate factors associated with ownership and use of LLINs in Uganda, a cross-sectional community survey was conducted in March-June 2017, approximately 3 years after a national Universal Coverage Campaign (UCC).

Malaria control using long-lasting insecticidal nets (LLINs) and indoor residual spraying of insecticide (IRS) has been associated with reduced transmission throughout Africa. However, the impact of transmission reduction on the age distribution of malaria cases remains unclear.

Multiple red blood cell (RBC) variants appear to offer protection against the most severe forms of Plasmodium falciparum malaria. Associations between these variants and uncomplicated malaria are less clear.

There is limited evidence on whether malaria elimination is feasible in high-transmission areas of Africa. Between 2007 and 2018, we measured the impact of malaria control interventions in young children enrolled in three clinical trials and two observational studies in Tororo, Uganda, a historically high-transmission area. Data were pooled from children aged 0.5-2 years. Interventions included individually assigned chemoprevention and repeated rounds of indoor residual spraying (IRS) of insecticide. All children received long-lasting insecticidal nets (LLINs) and treatment for symptomatic malaria with artemisinin-based combination therapy. Malaria incidence was measured using passive surveillance and parasite prevalence by microscopy and molecular methods at regular intervals. Poisson's generalized linear mixed-effects models were used to estimate the impact of various control interventions. In total, 939 children were followed over 1,221.7 person years. In the absence of chemoprevention and IRS (reference group), malaria incidence was 4.94 episodes per person year and parasite prevalence 47.3%. Compared with the reference group, implementation of IRS was associated with a 97.6% decrease (95% CI: 93.3-99.1%, P = 0.001) in the incidence of malaria and a 96.0% decrease (95% CI: 91.3-98.2%, P < 0.001) in parasite prevalence (both measured after the fifth and sixth rounds of IRS). The addition of chemoprevention with monthly dihydroartemisinin-piperaquine to IRS was associated with a 99.5% decrease (95% CI: 98.6-99.9%, P < 0.001) in the incidence of malaria. In a historically high-malaria burden area of Uganda, a combination of LLINs, effective case management, IRS, and chemoprevention was associated with almost complete elimination of malaria in young children.

In Uganda, artemether-lumefantrine (AL) is first-line therapy and dihydroartemisinin-piperaquine (DP) second-line therapy for the treatment of uncomplicated malaria. This study evaluated the efficacy and safety of AL and DP in the management of uncomplicated falciparum malaria and measured the prevalence of molecular markers of resistance in three sentinel sites in Uganda from 2018 to 2019.

Malaria is the leading cause of disease burden in sub-Saharan Africa. In 2010, the East Africa International Center of Excellence for Malaria Research, also known as the Program for Resistance, Immunology, Surveillance, and Modeling of Malaria (PRISM), was established to provide a comprehensive approach to malaria surveillance in Uganda. We instituted cohort studies and a robust malaria and entomological surveillance network at selected public health facilities that have provided a platform for monitoring trends in malaria morbidity and mortality, tracking the impact of malaria control interventions (indoor residual spraying of insecticide [IRS], use of long-lasting insecticidal nets [LLINs], and case management with artemisinin-based combination therapies [ACTs]), as well as monitoring of antimalarial drug and insecticide resistance. PRISM studies have informed Uganda's malaria treatment policies, guided selection of LLINs for national distribution campaigns, and revealed widespread pyrethroid resistance, which led to changes in insecticides delivered through IRS. Our continuous engagement and interaction with policy makers at the Ugandan Ministry of Health have enabled PRISM to share evidence, best practices, and lessons learned with key malaria stakeholders, participate in malaria control program reviews, and contribute to malaria policy and national guidelines. Here, we present an overview of interactions between PRISM team members and Ugandan policy makers to demonstrate how PRISM's research has influenced malaria policy and control in Uganda.

Malaria transmission-blocking vaccines (TBVs) aim to induce antibodies that interrupt malaria parasite development in the mosquito, thereby blocking onward transmission, and provide a much-needed tool for malaria control and elimination. The parasite surface protein Pfs48/45 is a leading TBV candidate. Here, we isolated and characterized a panel of 81 human Pfs48/45-specific monoclonal antibodies (mAbs) from donors naturally exposed to Plasmodium parasites. Genetically diverse mAbs against each of the three domains (D1-D3) of Pfs48/45 were identified. The most potent mAbs targeted D1 and D3 and achieved >80% transmission-reducing activity in standard membrane-feeding assays, at 10 and 2 μg/mL, respectively. Co-crystal structures of D3 in complex with four different mAbs delineated two conserved protective epitopes. Altogether, these Pfs48/45-specific human mAbs provide important insight into protective and non-protective epitopes that can further our understanding of transmission and inform the design of refined malaria transmission-blocking vaccine candidates.

Frequent retesting for HIV among persons at increased risk of HIV infection is critical to early HIV diagnosis of persons and delivery of combination HIV prevention services. There are few evidence-based interventions for promoting frequent retesting for HIV. We sought to determine the effectiveness of financial incentives and deposit contracts in promoting quarterly HIV retesting among adults at increased risk of HIV.

Prevention of malaria infection during pregnancy in HIV-negative women currently relies on the use of long-lasting insecticidal nets together with intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP). Increasing sulfadoxine-pyrimethamine resistance in Africa threatens current prevention of malaria during pregnancy. Thus, a replacement for IPTp-SP is urgently needed, especially for locations with high sulfadoxine-pyrimethamine resistance. Dihydroartemisinin-piperaquine is a promising candidate. We aimed to estimate the cost-effectiveness of intermittent preventive treatment in pregnancy with dihydroartemisinin-piperaquine (IPTp-DP) versus IPTp-SP to prevent clinical malaria infection (and its sequelae) during pregnancy.

In Uganda, Artemether-Lumefantrine and Artesunate are recommended for uncomplicated and severe malaria respectively, but are currently threatened by parasite resistance. Genetic and epigenetic factors play a role in predisposing Plasmodium falciparum parasites to acquiring Pfkelch13 (K13) mutations associated with delayed artemisinin parasite clearance as reported in Southeast Asia. In this study, we report on the prevalence of mutations in the K13, pfmdr-2 (P. falciparum multidrug resistance protein 2), fd (ferredoxin), pfcrt (P. falciparum chloroquine resistance transporter), and arps10 (apicoplast ribosomal protein S10) genes in Plasmodium falciparum parasites prior to (2005) and after (2013) introduction of artemisinin combination therapies for malaria treatment in Uganda. A total of 200 P. falciparum parasite DNA samples were screened. Parasite DNA was extracted using QIAamp DNA mini kit (Qiagen, GmbH, Germany) procedure. The PCR products were sequenced using Sanger dideoxy sequencing method. Of the 200 P. falciparum DNA samples screened, sequencing for mutations in K13, pfmdr-2, fd, pfcrt, arps10 genes was successful in 142, 186, 141, 128 and 74 samples respectively. Overall, we detected six (4.2%, 6/142; 95%CI: 1.4-7.0) K13 single nucleotide polymorphisms (SNPs), of which 3.9% (2/51), 4.4% (4/91) occurred in 2005 and 2013 samples respectively. All four K13 SNPs in 2013 samples were non-synonymous (A578S, E596V, S600C and E643K) while of the two SNPs in 2005 samples, one (Y588N) is non-synonymous and the other (I587I) is synonymous. There was no statistically significant difference in the prevalence of K13 (p = 0.112) SNPs in the samples collected in 2005 and 2013. The overall prevalence of SNPs in pfmdr-2 gene was 39.8% (74/186, 95%CI: 25.1-50.4). Of this, 4.2% (4/95), 76.9% (70/91) occurred in 2005 and 2013 samples respectively. In 2005 samples only one SNP, Y423F (4.2%, 4/95) was found while in 2013, Y423F (38.5%, 35/91) and I492V (38.5%, 35/91) SNPs in the pfmdr-2 gene were found. There was a statistically significant difference in the prevalence of pfmdr-2 SNPs in the samples collected in 2005 and 2013 (p<0.001). The overall prevalence of arps10 mutations was 2.7% (2/72, 95%CI: 0.3-4.2). Two mutations, V127M (4.5%: 1/22) and D128H (4.5%: 1/22) in the arps10 gene were each found in P. falciparum parasite samples collected in 2013. There was no statistically significant difference in the prevalence of arps10 SNPs in the samples collected in 2005 and 2013 (p = 0.238). There were more pfmdr-2 SNPs in P. falciparum parasites collected after introduction of Artemisinin combination therapies in malaria treatment. This is an indicator of the need for continuous surveillance to monitor emergence of molecular markers of artemisinin resistance and its potential drivers in malaria affected regions globally.

Human mobility is a critical aspect of existence and survival, but may compromise care engagement among people living with HIV (PLHIV). We examined the association between various forms of human mobility with retention in HIV care and antiretroviral treatment (ART) interruptions.