Endothelial transcriptomic analysis identifies biomarkers of severe and cerebral malaria.

Malaria can quickly progress from an uncomplicated infection into a life-threatening severe disease. However, the unspecificity of early symptoms often makes it difficult to identify patients at high risk of developing severe disease. Additionally, one of the most feared malaria complications - cerebral malaria - is challenging to diagnose, often resulting in treatment delays that can lead to adverse outcomes.

The epidemiology of severe malaria at Manhiça District Hospital, Mozambique: a retrospective analysis of 20 years of malaria admissions surveillance data.

Background: Most malaria burden estimates rely on modelling infection prevalence to case incidence data, with insufficient attention having been paid to the changing clinical presentation of severe disease and its relationship with changing transmission intensity. We present 20 years of longitudinal surveillance data to contribute to the understanding of the relationship between malaria transmission and the burden and clinical presentation of severe malaria and to inform policy.

Methods: This retrospective analysis of clinical surveillance hospital data included all children younger than 15 years admitted with malaria to Manhiça District Hospital (MDH), Mozambique, from July 1, 1997, to June 30, 2017.

Host age and expression of genes involved in red blood cell invasion in Plasmodium falciparum field isolates.

Plasmodium falciparum proteins involved in erythrocyte invasion are main targets of acquired immunity and important vaccine candidates. We hypothesized that anti-parasite immunity acquired upon exposure would limit invasion-related gene (IRG) expression and affect the clinical impact of the infection. 11 IRG transcript levels were measured in P.

Cytoadhesion to gC1qR through Plasmodium falciparum Erythrocyte Membrane Protein 1 in Severe Malaria.

Cytoadhesion of Plasmodium falciparum infected erythrocytes to gC1qR has been associated with severe malaria, but the parasite ligand involved is currently unknown. To assess if binding to gC1qR is mediated through the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family, we analyzed by static binding assays and qPCR the cytoadhesion and var gene transcriptional profile of 86 P.

Hypoxaemia in Mozambican children <5 years of age admitted to hospital with clinical severe pneumonia: clinical features and performance of predictor models.

Objective: To determine the prevalence of hypoxaemia among under-five children admitted to hospital with clinical severe pneumonia and to assess the performance to diagnose hypoxaemia of models based on clinical signs.

Methods: We conducted a hospital-based survey in a district hospital from Southern Mozambique.

Results: A total of 825 children were recruited after obtaining an informed consent.

Changing Trends in P. falciparum Burden, Immunity, and Disease in Pregnancy.

Background: Prevention of reinfection and resurgence is an integral component of the goal to eradicate malaria. However, the adverse effects of malaria resurgences are not known.

Methods: We assessed the prevalence of Plasmodium falciparum infection among 1819 Mozambican women who delivered infants between 2003 and 2012.

Diarrheal Disease in Rural Mozambique: Burden, Risk Factors and Etiology of Diarrheal Disease among Children Aged 0-59 Months Seeking Care at Health Facilities.

Background: Diarrheal disease remains a leading cause of illness and death, particularly in low-income countries. Its burden, microbiological causes and risk factors were examined in children aged 0-59 months living in Manhiça, rural southern Mozambique.

Methods: Trends of diarrhea-related burden of disease were estimated during the period 2001-2012.

Perceptions of malaria in pregnancy and acceptability of preventive interventions among Mozambican pregnant women: implications for effectiveness of malaria control in pregnancy.

Background: Intermittent Preventive Treatment (IPTp) and insecticide treated nets (ITNs) are recommended malaria in pregnancy preventive interventions in sub-Saharan Africa. Despite their cost-effectiveness and seemingly straight-forward delivery mechanism, their uptake remains low. We aimed at describing perceptions of pregnant women regarding malaria and the recommended prevention interventions to understand barriers to uptake and help to improve their effectiveness.

Lower respiratory tract infections associated with rhinovirus during infancy and increased risk of wheezing during childhood. A cohort study.

Background And Objectives: Although association between respiratory syncytial virus infection and later asthma development has been established, little is known about the role of other respiratory viruses. Rhinovirus was considered a mild pathogen of the upper respiratory tract but current evidence suggests that rhinovirus is highly prevalent among children with lower respiratory tract infections (LRTI). The aim of the study was to evaluate whether LRTI hospitalization associated with rhinovirus during infancy was associated with an increased risk of wheezing - a proxy measure of asthma - during childhood.

Severe malnutrition among children under the age of 5 years admitted to a rural district hospital in southern Mozambique.

Objective: To describe the burden, clinical characteristics and prognostic factors of severe malnutrition in children under the age of 5 years.

Design: Retrospective study of hospital-based data systematically collected from January 2001 to December 2010.

Setting: Rural Mozambican district hospital.

A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants.

Background: The candidate malaria vaccine RTS,S/AS01 reduced episodes of both clinical and severe malaria in children 5 to 17 months of age by approximately 50% in an ongoing phase 3 trial. We studied infants 6 to 12 weeks of age recruited for the same trial.

Methods: We administered RTS,S/AS01 or a comparator vaccine to 6537 infants who were 6 to 12 weeks of age at the time of the first vaccination in conjunction with Expanded Program on Immunization (EPI) vaccines in a three-dose monthly schedule.

Comparison of placental blood microscopy and the ICT HRP2 rapid diagnostic test to detect placental malaria.

Monitoring interventions to prevent malaria in pregnancy requires sensitive detection of placental infection. Rapid diagnostic tests (RDTs) are good candidates, but little information is available on their sensitivity on placental blood. We have evaluated the agreement (kappa coefficient) between microscopy and a Plasmodium falciparum histidine-rich protein 2 (HRP2)-based immuno-chromatographic test (ICT) on placental blood from 1151 women at delivery.

Low antibodies against Plasmodium falciparum and imbalanced pro-inflammatory cytokines are associated with severe malaria in Mozambican children: a case-control study.

Background: The factors involved in the progression from Plasmodium falciparum infection to severe malaria (SM) are still incompletely understood. Altered antibody and cellular immunity against P. falciparum might contribute to increase the risk of developing SM.

Glucose-6-phosphate dehydrogenase deficiency, chlorproguanil-dapsone with artesunate and post-treatment haemolysis in African children treated for uncomplicated malaria.

Background: Malaria is a leading cause of mortality, particularly in sub-Saharan African children. Prompt and efficacious treatment is important as patients may progress within a few hours to severe and possibly fatal disease. Chlorproguanil-dapsone-artesunate (CDA) was a promising artemisinin-based combination therapy (ACT), but its development was prematurely stopped because of safety concerns secondary to its associated risk of haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals.

Inadequate efficacy of a new formulation of fosmidomycin-clindamycin combination in Mozambican children less than three years old with uncomplicated Plasmodium falciparum malaria.

The combination of fosmidomycin and clindamycin (F/C) is effective in adults and older children for the treatment of malaria and could be an important alternative to existing artemisinin-based combinations (ACTs) if proven to work in younger children. We conducted an open-label clinical trial to assess the efficacy, safety, and tolerability of F/C for the treatment of uncomplicated P. falciparum malaria in Mozambican children <3 years of age.

Similar efficacy and safety of artemether-lumefantrine (Coartem®) in African infants and children with uncomplicated falciparum malaria across different body weight ranges.

Background: Artemisinin-based combination therapy, including artemether-lumefantrine (AL), is currently recommended for the treatment of uncomplicated Plasmodium falciparum malaria. The objectives of the current analysis were to compare the efficacy and safety of AL across different body weight ranges in African children, and to examine the age and body weight relationship in this population.

Methods: Efficacy, safety and pharmacokinetic data from a randomized, investigator-blinded, multicentre trial of AL for treatment of acute uncomplicated P.

Drug exposure and pregnancy outcome in Mozambique.

Background: The intake of medicines during pregnancy can have negative or toxic effects on the fetus, possibly leading to adverse pregnancy outcomes.

Objective: The aim of this study was to describe the level of drug exposure during pregnancy in a rural area of Mozambique and its relation to pregnancy outcome.

Methods: A total of 3105 pregnant women were interviewed in a cohort study.

Distinguishing malaria from severe pneumonia among hospitalized children who fulfilled integrated management of childhood illness criteria for both diseases: a hospital-based study in Mozambique.

Malaria and severe pneumonia in hospitalized young children may show striking clinical similarities, making differential diagnosis challenging. We investigated ways to increase diagnostic accuracy in patients hospitalized with clinical symptoms compatible with malaria and severe pneumonia, in an area with high a prevalence of infection with human immunodeficiency virus. A total of 646 children admitted at the Manhiça District Hospital in Manhiça, Mozambique who met the World Health Organization clinical criteria for severe pneumonia and malaria were recruited for 12 months and thoroughly investigated to ascertain an accurate diagnosis.

Erythropoietin levels are not independently associated with malaria-attributable severe disease in Mozambican children.

Background: Severe malaria is difficult to differentiate from other forms of malaria or other infections with similar symptoms. Any parameter associated to malaria-attributable severe disease could help to improve severe malaria diagnosis.

Methodology: This study assessed the relation between erythropoietin (EPO) and malaria-attributable severe disease in an area of Mozambique with moderate malaria transmission.

Inherent illnesses and attacks: an ethnographic study of interpretations of childhood Acute Respiratory Infections (ARIs) in Manhiça, southern Mozambique.

Background: Pneumonia is a leading cause of childhood hospitalisation and child mortality in Africa. This study explores local interpretations of Acute Respiratory Infections (ARIs), focusing on caretakers of children under five in the context of hospital care seeking.

Methods: The study took place in Manhiça, southern Mozambique and used Focused Ethnographic Study tools (FES) including field exercises and interviews.

Association of severe malaria outcomes with platelet-mediated clumping and adhesion to a novel host receptor.

Introduction: Severe malaria has been attributed partly to the sequestration of Plasmodium falciparum-infected erythrocytes (IEs) in the microvasculature of vital host organs. Identification of P. falciparum cytoadherence phenotypes that are associated with severe malaria may lead to the development of novel strategies against life-threatening malaria.

Parity and placental infection affect antibody responses against Plasmodium falciparum during pregnancy.

Women are at higher risk of Plasmodium falciparum infection when pregnant. The decreasing risk of malaria with subsequent pregnancies is attributed to parity-dependent acquisition of antibodies against placental parasites expressing variant surface antigens, VAR2CSA, that mediate placental sequestration through adhesion to chondroitin sulfate A (CSA). However, modulation of immunity during pregnancy may also contribute to increase the risk of malaria.

Procalcitonin and C-reactive protein for invasive bacterial pneumonia diagnosis among children in Mozambique, a malaria-endemic area.

Background: Pneumonia is the major cause of mortality and morbidity in children worldwide. Procalcitonin (PCT) and C-reactive protein (CRP) are used in developed countries to differentiate between viral and bacterial causes of pneumonia. Validity of these markers needs to be further explored in Africa.

Etiology and epidemiology of viral pneumonia among hospitalized children in rural Mozambique: a malaria endemic area with high prevalence of human immunodeficiency virus.

Background: The role of viruses in pediatric pneumonia remains poorly studied in sub-Saharan Africa, where pneumonia-associated mortality is high.

Methods: During a 1-year hospital-based surveillance, a nasopharyngeal aspirate (NPA) was collected from children aged <5 years admitted to hospital in rural Mozambique with clinically severe pneumonia. Identification of 12 respiratory viruses was performed by polymerase chain reactions (PCR).

Antimicrobial drug resistance trends of bacteremia isolates in a rural hospital in southern Mozambique.

Antibiotic resistance in Africa is increasing but insufficiently recognized as a public health problem. However, there are scarce data for antimicrobial resistance trends among bloodstream isolates in sub-Saharan Africa. Antimicrobial drug resistance trends among bacteria isolated from blood of children < 15 years of age admitted to the Manhiça District Hospital in Mozambique during May 2001-April 2006 were monitored by disk diffusion.