Sex-disaggregated analysis of acute kidney injury in hospitalized children with sickle cell anemia in Uganda.

A growing body of research is categorizing sex differences in both sickle cell anemia (SCA) and acute kidney injury (AKI); however, most of this work is being conducted in high-resource settings. Here, we evaluated risk factors and clinical parameters associated with AKI and AKI severity, stratified by sex, in a cohort of children hospitalized with SCA and vaso-occlusive pain crisis (VOC). The purpose of this study was to explore sex disparities in a high-risk, vulnerable population.

Intestinal barrier disruption with Plasmodium falciparum infection in pregnancy and risk of preterm birth: a cohort study.

Background: Malaria in early pregnancy is a risk factor for preterm birth and is associated with sustained inflammation and dysregulated angiogenesis across gestation. This study investigated whether malaria is associated with increased gut leak and whether this contributes to systemic inflammation, altered angiogenesis, and preterm birth.

Methods: We quantified plasma concentrations of gut leak markers, soluble CD14 (sCD14) and lipopolysaccharide binding protein (LBP) from 1339 HIV-negative pregnant Malawians at <24 weeks gestational age.

Inflammatory profiles in febrile children with moderate and severe malnutrition presenting at-hospital in Uganda are associated with increased mortality.

Background: Children in Africa carry a disproportionate burden of malnutrition and infectious disease. Together, malnutrition and infection are major contributors to global child mortality; however, their collective impact on immune activation are not well described.

Methods: This was a secondary analysis of a prospective cohort study of children hospitalized with acute febrile illness at a single centre in Uganda.

Sequential disruptions to inflammatory and angiogenic pathways and risk of spontaneous preterm birth in Malawian women.

Preterm birth is a leading cause of death in children under five years of age. We hypothesized that sequential disruptions to inflammatory and angiogenic pathways during pregnancy increase the risk of placental insufficiency and spontaneous preterm labor and delivery. We conducted a secondary analysis of inflammatory and angiogenic analytes measured in plasma samples collected across pregnancy from 1462 Malawian women.

Prognostic accuracy of biomarkers of immune and endothelial activation in Mozambican children hospitalized with pneumonia.

Pneumonia is a leading cause of child mortality. However, currently we lack simple, objective, and accurate risk-stratification tools for pediatric pneumonia. Here we test the hypothesis that measuring biomarkers of immune and endothelial activation in children with pneumonia may facilitate the identification of those at risk of death.

A Comprehensive Approach to Medical Oxygen Ecosystem Building: An Implementation Case Study in Kenya, Rwanda, and Ethiopia.

Medical oxygen is an essential treatment for life-threatening hypoxemic conditions and is commonly indicated for the clinical management of most leading causes of mortality in children aged younger than 5 years, obstetric complications at delivery, and surgical procedures. In resource-constrained settings, access to medical oxygen is unreliable due to cost, distance from production centers, undermaintained infrastructure, and a fragmented supply chain. To increase availability of medical oxygen in underserved communities, Assist International, the GE Foundation, Grand Challenges Canada, the Center for Public Health and Development (Kenya), Health Builders (Rwanda), and the National Ministries of Health and Regional Health Bureaus in Kenya, Rwanda, and Ethiopia partnered to implement a social enterprise model for the production and distribution of medical oxygen to hospitals at reduced cost.

Developmental origins of disease highlight the immediate need for expanded access to comprehensive prenatal care.

The prenatal environment plays a critical role in shaping fetal development and ultimately the long-term health of the child. Here, we present data linking prenatal health, maternal nutrition, comorbidities in pregnancy (e.g.

Allometric scaling relationships in mouse placenta.

Fetal growth and maturation are highly intertwined with placental development during pregnancy. Here we used placental vascular morphology measurements (depth and span) as well as the umbilical artery (UA) diameter of previously published studies on three different mouse strains (C57BL6/J, CD-1 and BALB/c), which were exposed to different conditions (combination antiretroviral therapy, chronic maternal hypoxia and malaria infection) at different embryonic days, to test the hypothesis that placental vascularization and specifically the UA size affect conceptus weight. Interaction of each study parameter with embryonic day, strain and exposure to treatments are studied to investigate the stability of the scaling relationships across and/or within strains and conditions.

Sex as a determinant of disease severity and clinical outcome in febrile children under five presenting to a regional referral hospital in Uganda.

Sex and gender are well-established determinants of health in adult and adolescent populations in low resource settings. There are limited data on sex as a determinant of host response to disease and clinical outcome in febrile children in sub-Saharan Africa, where the risk of infection-related mortality is greatest. We examined sex differences and gender biases in health-seeking behavior, clinical care, biological response to infection, or outcome in a prospective observational cohort of febrile children under 5 years of age presenting to a regional referral hospital in Jinja, Uganda.

Genome Sequences of Microbacterium foliorum Phages Anseraureola, Pondwater, and Yasuo.

Anseraureola, Pondwater, and Yasuo are bacteriophages with siphovirus morphology that infect Microbacterium foliorum NRRL B-24224. They were isolated from soil collected in Amherst, Massachusetts, and have genome lengths between 17,362 bp and 17,453 bp. These phages each contain 25 predicted protein-coding genes and are assigned to phage cluster EE.

Immune and endothelial activation markers and risk stratification of childhood pneumonia in Uganda: A secondary analysis of a prospective cohort study.

Background: Despite the global burden of pneumonia, reliable triage tools to identify children in low-resource settings at risk of severe and fatal respiratory tract infection are lacking. This study assessed the ability of circulating host markers of immune and endothelial activation quantified at presentation, relative to currently used clinical measures of disease severity, to identify children with pneumonia who are at risk of death.

Methods And Findings: We conducted a secondary analysis of a prospective cohort study of children aged 2 to 59 months presenting to the Jinja Regional Hospital in Jinja, Uganda between February 2012 and August 2013, who met the Integrated Management of Childhood Illness (IMCI) diagnostic criteria for pneumonia.

Soluble Urokinase-Type Plasminogen Activator Receptor as a Prognostic Marker of Ugandan Children at Risk of Severe and Fatal Malaria.

Background: Current malaria diagnostic tests do not reliably identify children at risk of severe and fatal infection. Host immune and endothelial activation contribute to malaria pathogenesis. Soluble urokinase-type plasminogen activator receptor (suPAR) is a marker of these pathways.

Plasma concentrations of leptin at mid-pregnancy are associated with gestational weight gain among pregnant women in Tanzania: a prospective cohort study.

Background: Gestational weight gain (GWG) has critical implications for maternal and child health. Inflammation and angiogenesis are implicated in various aspects of maternal metabolism that may play a role in gestational weight gain. The associations of inflammatory, angiogenic, and metabolic pathways with GWG are yet to be elucidated.

Neurocognitive outcomes in Malawian children exposed to malaria during pregnancy: An observational birth cohort study.

Background: Annually 125 million pregnancies are at risk of malaria infection. However, the impact of exposure to malaria in pregnancy on neurodevelopment in children is not well understood. We hypothesized that malaria in pregnancy and associated maternal immune activation result in neurodevelopmental delay in exposed offspring.

Malaria in Pregnancy and Adverse Birth Outcomes: New Mechanisms and Therapeutic Opportunities.

Malaria infection during pregnancy is associated with adverse birth outcomes but underlying mechanisms are poorly understood. Here, we discuss the impact of malaria in pregnancy on three pathways that are important regulators of healthy pregnancy outcomes: L-arginine-nitric oxide biogenesis, complement activation, and the heme axis. These pathways are not mutually exclusive, and they collectively create a proinflammatory, antiangiogenic milieu at the maternal-fetal interface that interferes with placental function and development.

Vitamin D Concentration during Early Pregnancy and Adverse Outcomes among HIV-Negative Women in Dar-es-Salaam, Tanzania: A Case-Control Study.

We examined the associations of plasma vitamin D concentration and adverse pregnancy outcomes among HIV-negative women in Dar-es-Salaam, Tanzania. We used an unmatched case-control study design, with 25-hydroxyvitamin D [25(OH)D] concentration assessed in the first trimester. Cases were individuals with adverse pregnancy outcomes, including stillbirth, premature birth, or small for gestational age births (SGA).

Early malaria infection, dysregulation of angiogenesis, metabolism and inflammation across pregnancy, and risk of preterm birth in Malawi: A cohort study.

Background: Malaria in pregnancy is associated with adverse birth outcomes. However, the underlying mechanisms remain poorly understood. Tight regulation of angiogenic, metabolic, and inflammatory pathways are essential for healthy pregnancies.

The Impact of Infection in Pregnancy on Placental Vascular Development and Adverse Birth Outcomes.

Healthy fetal development is dependent on nutrient and oxygen transfer the placenta. Optimal growth and function of placental vasculature is therefore essential to support development. Vasculogenesis, the formation of blood vessels, and angiogenesis, the branching and remodeling of existing vasculature, mediate the development and maturation of placental villi, which form the materno-fetal interface.

Perspective: L-arginine and L-citrulline Supplementation in Pregnancy: A Potential Strategy to Improve Birth Outcomes in Low-Resource Settings.

The available data support the hypothesis that L-arginine or L-citrulline supplementation would be suitable for implementation in resource-constrained settings and will enhance placental vascular development and improve birth outcomes. In resource-constrained settings, the rates of adverse birth outcomes, including fetal growth restriction, preterm birth, and low birth weight, are disproportionately high. Complications resulting from preterm birth are now the leading cause of mortality in children <5 y of age worldwide.

Systemic inflammation is associated with malaria and preterm birth in women living with HIV on antiretrovirals and co-trimoxazole.

Women living with HIV (WLHIV) have an increased risk of malaria in pregnancy (MiP). It is unclear if MiP in WLHIV causes a systemic inflammatory response and increases the risk of adverse birth outcomes, especially for women receiving antiretroviral therapy (ART) and daily trimethoprim-sulfamethoxazole (TMP/SXT). We analyzed repeated plasma samples in a cohort of malaria-exposed Ugandan WLHIV receiving ART and daily TMP/SXT to examine changes in inflammatory markers across pregnancy and their association with birth outcomes.

Integrated fever management: disease severity markers to triage children with malaria and non-malarial febrile illness.

Febrile symptoms in children are a leading cause of health-care seeking behaviour worldwide. The majority of febrile illnesses are uncomplicated and self-limited, without the need for referral or hospital admission. However, current diagnostic tools are unable to identify which febrile children have self-limited infection and which children are at risk of progressing to life-threatening infections, such as severe malaria.

Malaria in pregnancy alters l-arginine bioavailability and placental vascular development.

Reducing adverse birth outcomes due to malaria in pregnancy (MIP) is a global health priority. However, there are few safe and effective interventions. l-Arginine is an essential amino acid in pregnancy and an immediate precursor in the biosynthesis of nitric oxide (NO), but there are limited data on the impact of MIP on NO biogenesis.

Estradiol Levels Are Altered in Human Immunodeficiency Virus-Infected Pregnant Women Randomized to Efavirenz-Versus Lopinavir/Ritonavir-Based Antiretroviral Therapy.

Background: Combination antiretroviral therapy (cART) use in pregnancy has been associated with hormonal dysregulation. We performed a secondary retrospective analysis of longitudinal progesterone and estradiol levels in pregnancy using specimens from the Protease Inhibitors to Reduce Malaria Morbidity in HIV-infected Pregnant Women study, which randomized Ugandan human immunodeficiency virus (HIV)-infected ART-naive women to initiate either lopinavir/ritonavir (LPV/r)-based or efavirenz (EFV)-based cART.

Methods: Three hundred twenty-six women (160 randomized to the EFV arm and 166 women to the LPV/r arm) with at least 1 plasma sample collected during pregnancy were included.

Altered angiogenesis as a common mechanism underlying preterm birth, small for gestational age, and stillbirth in women living with HIV.

Background: 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.

Objective: We sought to determine whether angiogenic factors are associated with adverse birth outcomes in HIV-infected pregnant women started on antiretroviral therapy.

Study Design: This is a secondary analysis of samples collected as part of a clinical trial randomizing pregnant women and adolescents infected with HIV to lopinavir/ritonavir-based (n = 166) or efavirenz-based (n = 160) antiretroviral therapy in Tororo, Uganda.