Increased physiologic dead space fraction is associated with mortality after comprehensive stage 2 operation.

Objective: Our objective was to assess the predictive value of physiologic dead space fraction for mortality in patients undergoing the comprehensive stage 2 operation.

Methods: This was a single-centre retrospective observational study conducted at a quaternary free-standing children's hospital specialising in hybrid palliation of single ventricle cardiac disease. 180 patients underwent the comprehensive stage 2 operation.

Targeted newborn metabolomics: prediction of gestational age from cord blood.

Objective: Our study sought to determine whether metabolites from a retrospective collection of banked cord blood specimens could accurately estimate gestational age and to validate these findings in cord blood samples from Busia, Uganda.

Study Design: Forty-seven metabolites were measured by tandem mass spectrometry or enzymatic assays from 942 banked cord blood samples. Multiple linear regression was performed, and the best model was used to predict gestational age, in weeks, for 150 newborns from Busia, Uganda.

Effect of universal HIV testing and treatment on socioeconomic wellbeing in rural Kenya and Uganda: a cluster-randomised controlled trial.

Background: Universal testing and treatment for HIV has shown promise as an approach to reduce mortality and lower HIV incidence. Evidence on the economic effects of this approach on individuals and households in low-resource settings is scarce. We aimed to examine the effect of universal HIV testing and treatment on a range of economic outcomes.

Piperaquine-Induced QTc Prolongation Decreases With Repeated Monthly Dihydroartemisinin-Piperaquine Dosing in Pregnant Ugandan Women.

Background: Intermittent preventive treatment with monthly dihydroartemisinin-piperaquine (DHA-PQ) is highly effective at preventing both malaria during pregnancy and placental malaria. Piperaquine prolongs the corrected QT interval (QTc), and it is possible that repeated monthly dosing could lead to progressive QTc prolongation. Intensive characterization of the relationship between piperaquine concentration and QTc interval throughout pregnancy can inform effective, safe prevention guidelines.

Provider and Patient Perspectives of Rapid ART Initiation and Streamlined HIV Care: Qualitative Insights From Eastern African Communities.

The Sustainable East Africa Research in Community Health (SEARCH), a universal test and treat (UTT) trial, implemented 'Streamlined Care'-a multicomponent strategy including rapid linkage to care and antiretroviral therapy (ART) start, 3-monthly refills, viral load counseling, and accessible, patient-centered care provision. To understand patient and provider experiences of Streamlined Care to inform future care innovations, we conducted in-depth interviews with patients ( = 18) and providers ( = 28) at baseline (2014) and follow-up (2015) ( = 17 patients;  = 21 providers). Audio recordings were transcribed, translated, and deductively and inductively coded.

Dimensions of HIV-related stigma in rural communities in Kenya and Uganda at the start of a large HIV 'test and treat' trial.

HIV-related stigma is a frequently cited barrier to HIV testing and care engagement. A nuanced understanding of HIV-related stigma is critical for developing stigma-reduction interventions to optimize HIV-related outcomes. This qualitative study documented HIV-related stigma across eight communities in east Africa during the baseline year of a large HIV test-and-treat trial (SEARCH, NCT: 01864603), prior to implementation of widespread community HIV testing campaigns and efforts to link individuals with HIV to care and treatment.

Costs of integrating hypertension care into HIV care in rural East African clinics.

Objective: Sub-Saharan Africa faces twin epidemics of HIV and noncommunicable diseases including hypertension. Integrating hypertension care into chronic HIV care is a global priority, but cost estimates are lacking. In the SEARCH Study, we performed population-level HIV/hypertension testing, and offered integrated streamlined chronic care.

SEARCH Human Immunodeficiency Virus (HIV) Streamlined Treatment Intervention Reduces Mortality at a Population Level in Men With Low CD4 Counts.

Background: We tested the hypothesis that patient-centered, streamlined human immunodeficiency virus (HIV) care would achieve lower mortality than the standard treatment model for persons with HIV and CD4 ≤ 350/uL in the setting of population-wide HIV testing.

Methods: In the SEARCH (Sustainable East Africa Research in Community Health) Study (NCT01864603), 32 communities in rural Uganda and Kenya were randomized to country-guided antiretroviral therapy (ART) versus streamlined ART care that included rapid ART start, visit spacing, flexible clinic hours, and welcoming environment. We assessed persons with HIV and CD4 ≤ 350/uL, ART eligible in both arms, and estimated the effect of streamlined care on ART initiation and mortality at 3 years.

Predicting HIV Incidence in the SEARCH Trial: A Mathematical Modeling Study.

Background: The SEARCH study provided community-based HIV and multidisease testing and antiretroviral therapy (ART) to 32 communities in East Africa and reported no statistically significant difference in 3-year HIV incidence. We used mathematical modeling to estimate the effect of control arm viral suppression and community mixing on SEARCH trial outcomes.

Setting: Uganda and Kenya.

Social Networks and HIV Care Outcomes in Rural Kenya and Uganda.

Background: Social isolation among HIV-positive persons might be an important barrier to care. Using data from the SEARCH Study in rural Kenya and Uganda, we constructed 32 community-wide, sociocentric networks and evaluated whether less socially connected HIV-positive persons were less likely to know their status, have initiated treatment, and be virally suppressed.

Methods: Between 2013 and 2014, 168,720 adult residents in the SEARCH Study were census-enumerated, offered HIV testing, and asked to name social contacts.

Age-Related Changes in Malaria Clinical Phenotypes During Infancy Are Modified by Sickle Cell Trait.

Background: Infants are protected against Plasmodium falciparum malaria. Mechanisms that drive this protection remain unclear due to a poor understanding of malaria clinical phenotypes during infancy.

Methods: We enrolled a birth cohort of 678 infants in Busia, Uganda, an area of high malaria transmission.

HIV incidence after pre-exposure prophylaxis initiation among women and men at elevated HIV risk: A population-based study in rural Kenya and Uganda.

Background: Oral pre-exposure prophylaxis (PrEP) is highly effective for HIV prevention, but data are limited on HIV incidence among PrEP users in generalized epidemic settings, particularly outside of selected risk groups. We performed a population-based PrEP study in rural Kenya and Uganda and sought to evaluate both changes in HIV incidence and clinical and virologic outcomes following seroconversion on PrEP.

Methods And Findings: During population-level HIV testing of individuals ≥15 years in 16 communities in the Sustainable East Africa Research in Community Health (SEARCH) study (NCT01864603), we offered universal access to PrEP with enhanced counseling for persons at elevated HIV risk (based on serodifferent partnership, machine learning-based risk score, or self-identified HIV risk).

Characteristics of HIV seroconverters in the setting of universal test and treat: Results from the SEARCH trial in rural Uganda and Kenya.

Background: Additional progress towards HIV epidemic control requires understanding who remains at risk of HIV infection in the context of high uptake of universal testing and treatment (UTT). We sought to characterize seroconverters and risk factors in the SEARCH UTT trial (NCT01864603), which achieved high uptake of universal HIV testing and ART coverage in 32 communities of adults (≥15 years) in rural Uganda and Kenya.

Methods: In a pooled cohort of 117,114 individuals with baseline HIV negative test results, we described those who seroconverted within 3 years, calculated gender-specific HIV incidence rates, evaluated adjusted risk ratios (aRR) for seroconversion using multivariable targeted maximum likelihood estimation, and assessed potential infection sources based on self-report.

Pathways for reduction of HIV-related stigma: a model derived from longitudinal qualitative research in Kenya and Uganda.

Introduction: The rollout of antiretroviral therapy (ART) has been associated with reductions in HIV-related stigma, but pathways through which this reduction occurs are poorly understood. In the newer context of universal test and treat (UTT) interventions, where rapid diffusion of ART uptake takes place, there is an opportunity to understand the processes through which HIV-related stigma can decline, and how UTT strategies may precipitate more rapid and widespread changes in stigma. This qualitative study sought to evaluate how a UTT intervention influenced changes in beliefs, attitudes and behaviours related to HIV.

Infant sex modifies associations between placental malaria and risk of malaria in infancy.

Background: Placental malaria (PM) has been associated with a higher risk of malaria during infancy. However, it is unclear whether this association is causal, and is modified by infant sex, and whether intermittent preventive treatment in pregnancy (IPTp) can reduce infant malaria by preventing PM.

Methods: Data from a birth cohort of 656 infants born to HIV-uninfected mothers randomised to IPTp with dihydroartemisinin-piperaquine (DP) or Sulfadoxine-pyrimethamine (SP) was analysed.

Piperaquine Exposure Is Altered by Pregnancy, HIV, and Nutritional Status in Ugandan Women.

Dihydroartemisinin-piperaquine (DHA-PQ) provides highly effective therapy and chemoprevention for malaria in pregnant African women. PQ concentrations of >10.3 ng/ml have been associated with reduced maternal parasitemia, placental malaria, and improved birth outcomes.

Impact of intermittent preventive treatment of malaria in pregnancy with dihydroartemisinin-piperaquine versus sulfadoxine-pyrimethamine on the incidence of malaria in infancy: a randomized controlled trial.

Background: Intermittent preventive treatment of malaria during pregnancy (IPTp) with dihydroartemisinin-piperaquine (DP) significantly reduces the burden of malaria during pregnancy compared to sulfadoxine-pyrimethamine (SP), the current standard of care, but its impact on the incidence of malaria during infancy is unknown.

Methods: We conducted a double-blind randomized trial to compare the incidence of malaria during infancy among infants born to HIV-uninfected pregnant women who were randomized to monthly IPTp with either DP or SP. Infants were followed for all their medical care in a dedicated study clinic, and routine assessments were conducted every 4 weeks.

Population-level viral suppression among pregnant and postpartum women in a universal test and treat trial.

Objective(s): We sought to determine whether universal 'test and treat' (UTT) can achieve gains in viral suppression beyond universal antiretroviral treatment (ART) eligibility during pregnancy and postpartum, among women living with HIV.

Design: A community cluster randomized trial.

Methods: The SEARCH UTT trial compared an intervention of annual population testing and universal ART with a control of baseline population testing with ART by country standard, including ART eligibility for all pregnant/postpartum women, in 32 communities in Kenya and Uganda.

Anemia and Micronutrient Status during Pregnancy, and Their Associations with Obstetric and Infant Outcomes among HIV-Infected Ugandan Women Receiving Antiretroviral Therapy.

Background: Women living with HIV (WLHIV) are at higher risk of micronutrient deficiencies and adverse health outcomes. There are limited data on the burden or sequelae of micronutrient deficiencies among pregnant WLHIV receiving antiretroviral therapy (ART).

Objectives: We aimed to examine anemia and vitamin B-12, folate, and vitamin D deficiencies, and their associations with obstetric and infant outcomes, among pregnant WLHIV initiating combination antiretroviral therapy (cART) in rural Uganda.

Uptake, engagement, and adherence to pre-exposure prophylaxis offered after population HIV testing in rural Kenya and Uganda: 72-week interim analysis of observational data from the SEARCH study.

Background: Optimal strategies for pre-exposure prophylaxis (PrEP) engagement in generalised HIV epidemics are unknown. We aimed to assess PrEP uptake and engagement after population-level HIV testing and universal PrEP access to characterise gaps in the PrEP cascade in rural Kenya and Uganda.

Methods: We did a 72-week interim analysis of observational data from the ongoing SEARCH (Sustainable East Africa Research in Community Health) study.

The age-specific burden and household and school-based predictors of child and adolescent tuberculosis infection in rural Uganda.

Background: The age-specific epidemiology of child and adolescent tuberculosis (TB) is poorly understood, especially in rural areas of East Africa. We sought to characterize the age-specific prevalence and predictors of TB infection among children and adolescents living in rural Uganda, and to explore the contribution of household TB exposure on TB infection.

Methods: From 2015-2016 we placed and read 3,121 tuberculin skin tests (TST) in children (5-11 years old) and adolescents (12-19 years old) participating in a nested household survey in 9 rural Eastern Ugandan communities.

Hypertension testing and treatment in Uganda and Kenya through the SEARCH study: An implementation fidelity and outcome evaluation.

Background: Hypertension (HTN) is the single leading risk factor for human mortality worldwide, and more prevalent in sub-Saharan Africa than any other region [1]-although resources for HTN screening, treatment, and control are few. Most regional pilot studies to leverage HIV programs for HTN control have achieved blood pressure control in half of participants or fewer [2,3,4]. But this control gap may be due to inconsistent delivery of services, rather than ineffective underlying interventions.

Associations between alcohol use and HIV care cascade outcomes among adults undergoing population-based HIV testing in East Africa.

Objective: To assess the impact of alcohol use on HIV care cascade outcomes.

Design: Cross-sectional analyses.

Methods: We evaluated HIV care cascade outcomes and alcohol use in adults (≥15 years) during baseline (2013--2014) population-based HIV testing in 28 Kenyan and Ugandan communities.

Machine Learning to Identify Persons at High-Risk of Human Immunodeficiency Virus Acquisition in Rural Kenya and Uganda.

Background: In generalized epidemic settings, strategies are needed to prioritize individuals at higher risk of human immunodeficiency virus (HIV) acquisition for prevention services. We used population-level HIV testing data from rural Kenya and Uganda to construct HIV risk scores and assessed their ability to identify seroconversions.

Methods: During 2013-2017, >75% of residents in 16 communities in the SEARCH study were tested annually for HIV.