Kathryn Maitland

KEMRI-Wellcome Trust Research Programme · Clinical Trials Facility

Background: Accurate estimation of dietary intake is challenging. However, whilst some progress has been made in high-income countries, low- and middle-income countries (LMICs) remain behind, contributing to critical nutritional data gaps. This study aimed to validate an objective, passive image-based dietary intake assessment method against weighe...

Blood group O is associated with protection against severe malaria and reduced size and stability of P . falciparum- host red blood cell (RBC) rosettes compared to non-O blood groups. Whether the non-O blood groups encoded by the specific ABO genotypes AO , BO , AA , BB and AB differ in their associations with severe malaria and rosetting is unknow...

Background: Accurate estimation of dietary intake is challenging. But whilst some progress has been made in high-income countries, low- and middle-income countries (LMICs) remain behind, contributing to critical nutritional data gaps. This study aimed to validate an objective, passive image-based dietary intake assessment method against weighed foo...

Background Children hospitalised with severe malnutrition (SM) have high mortality and relapse/readmission rates. Current milk-based formulations targets restoring ponderal growth but not modification of gut barrier integrety or microbiome which increase risk of gram-negative sepsis and poor outcomes. Objectives We propose that legume-based feeds r...

Introduction Shock-induced endotheliopathy (SHINE), defined as a profound sympathoadrenal hyperactivation in shock states leading to endothelial activation, glycocalyx damage, and eventual compromise of end-organ perfusion, was first described in 2017. The aggressive resuscitation therapies utilised in treating shock states could potentially lead t...

Objective: To describe chest radiograph findings among children hospitalized with clinically diagnosed severe pneumonia and hypoxaemia at three tertiary facilities in Uganda. Methods: The study involved clinical and radiograph data on a random sample of 375 children aged 28 days to 12 years enrolled in the Children's Oxygen Administration Strate...

Background: Outcomes in children hospitalised with severe acute malnutrition (SAM) remain poor. The current milk-based formulations focus on restoring weight-gain but fail to address modification of the integrity of the gut barrier and may exacerbate malabsorption owing to functional lactase, maltase and sucrase deficiency. We hypothesise that nutr...

Background: African children with severe malaria are susceptible to Gram-negative bacterial co-infection, largely non-typhoidal Salmonellae, leading to a substantially higher rates of in-hospital and post-discharge mortality than those without bacteraemia. Current evidence for treating co-infection is lacking, and there is no consensus on the dosag...

Shock-induced endotheliopathy (SHINE), defined as a profound sympathoadrenal hyperactivation in shock states leading to endothelial activation, glycocalyx damage, and eventual compromise of end-organ perfusion, was first described in 2017. The aggressive resuscitation therapies utilised in treating shock states could potentially lead to further wor...

Background WHO recommends gametocytocidal, single low-dose primaquine for blocking the transmission of Plasmodium falciparum; however, safety concerns have hampered the implementation of this strategy in sub-Saharan Africa. We aimed to investigate the safety of age-dosed, single low-dose primaquine in children from Uganda and the Democratic Republi...

Background and objectives: Adequate supplies of donor blood remain a major challenge in sub-Saharan Africa. This is exacerbated by a lack of confirmatory testing for transfusion-transmitted infections by blood transfusion services (BTS), leading to significant blood disposal owing to putatively high seroprevalence rates amongst Ugandan blood donor...

Blood group O is associated with protection against severe malaria and reduced size and stability of P. falciparum-host red blood cell (RBC) rosettes compared to non-O blood groups. Whether the non-O blood groups encoded by the specific ABO genotypes AO, BO, AA, BB and AB differ in their associations with severe malaria and rosetting is unknown. Th...

Invasive bacterial disease is a major cause of morbidity and mortality in African children. Despite being caused by diverse pathogens, children with sepsis are clinically indistinguishable from one another. In spite of this, most genetic susceptibility loci for invasive infection that have been discovered to date are pathogen specific and are not t...

Severe malaria caused by Plasmodium falciparum is difficult to diagnose accurately in children in high-transmission settings. Using data from 2649 pediatric and adult patients enrolled in four studies of severe illness in three countries (Bangladesh, Kenya, and Uganda), we fitted Bayesian latent class models using two diagnostic markers: the platel...

Background: Sickle cell anaemia (SCA) has historically been associated with high levels of childhood mortality in Africa. Although malaria has a major contribution to this mortality, to date, the clinical pathology of malaria among children with SCA has been poorly described. We aimed to explore the relationship between SCA and Plasmodium falcipar...

Objectives: Fluid bolus resuscitation in African children is harmful. Little research has evaluated physiologic effects of maintenance-only fluid strategy. Design: We describe the efficacy of fluid-conservative resuscitation of septic shock using case-fatality, hemodynamic, and myocardial function endpoints. Setting: Pediatric wards of Mbale R...

Background The TRACT trial established the timing of transfusion in children with uncomplicated anaemia (haemoglobin 4–6 g/dL) and the optimal volume (20 vs 30 mL/kg whole blood or 10 vs 15 mL/kg red cell concentrates) for transfusion in children admitted to hospital with severe anaemia (haemoglobin <6 g/dL) on day 28 mortality (primary endpoint)....

Invasive bacterial disease is a major cause of morbidity and mortality in African children. Despite being caused by diverse pathogens, children with sepsis are clinically indistinguishable from one another. In spite of this, most genetic susceptibility loci for invasive infection that have been discovered to date are pathogen specific and are not t...

Severe falciparum malaria is a major cause of preventable child mortality in sub-Saharan Africa. The sequestration of parasitized erythrocytes in the microvasculature of vital organs is a central pathophysiological feature. The plasma concentration of the parasite protein P. falciparum Histidine-Rich Protein 2 (PfHRP2) has diagnostic and prognostic...

Sickle cell anemia (SCA) is common in sub‐Saharan Africa where approximately 1% of births are affected. Severe anemia is a common cause for hospital admission within the region yet few studies have investigated the contribution made by SCA. The TRACT trial (ISRCTN84086586) investigated various treatment strategies in 3,983 children admitted with se...

Background Severe anaemia (haemoglobin < 6 g/dL) is a leading cause of recurrent hospitalisation in African children. We investigated predictors of readmission in children hospitalised with severe anaemia in the TRACT trial (ISRCTN84086586) in order to identify potential future interventions. Methods Secondary analyses of the trial examined 3894 c...

Background Severe falciparum malaria is difficult to diagnose accurately in children in high transmission settings. Platelet counts and plasma concentrations of P. falciparum histidine-rich protein-2 (PfHRP2) are potential biomarkers to increase diagnostic accuracy. Methods We fitted Bayesian latent class models to platelet counts and PfHRP2 concen...

Background: To prevent poor long-term outcomes (deaths and readmissions) the integrated global action plan for pneumonia and diarrhoea recommends under the ‘Treat’ element of Protect, Prevent and Treat interventions the importance of continued feeding but gives no specific recommendations for nutritional support. Early nutritional support has been...

Background: To prevent poor long-term outcomes (deaths and readmissions) the integrated global action plan for pneumonia and diarrhoea recommends under the ‘Treat’ element of Protect, Prevent and Treat interventions the importance of continued feeding but gives no specific recommendations for nutritional support. Early nutritional support has been...

Background: Outcomes in children hospitalised with severe acute malnutrition (SAM) remain poor. The current milk-based formulations focus on restoring weight-gain but fail to address modification of the integrity of the gut barrier and may exacerbate malabsorption owing to functional lactase, maltase and sucrase deficiency. We hypothesise that nutr...

BACKGROUND: Severe anaemia (haemoglobin < 6 g/dL) is a leading cause of recurrent hospitalisation in African children. We investigated predictors of readmission in children hospitalised with severe anaemia in the TRACT trial (ISRCTN84086586) in order to identify potential future interventions. METHODS: Secondary analyses of the trial examined 3894...

Severe falciparum malaria has substantially affected human evolution. Genetic association studies of patients with clinically defined severe malaria and matched population controls have helped characterise human genetic susceptibility to severe malaria, but phenotypic imprecision compromises discovered associations. In areas of high malaria transmi...

Background: Children hospitalised with severe acute malnutrition (SAM) are frequently complicated (>50%) by diarrhoea ( ≥ 3 watery stools/day) which is accompanied by poor outcomes. Rehydration guidelines for SAM are exceptionally conservative and controversial, based upon expert opinion. The guidelines only permit use of intravenous fluids for cas...

Background: African children with severe malaria are susceptible to Gram-negative bacterial co-infection, largely non-typhoidal Salmonellae, leading to a substantially higher rates of in-hospital and post-discharge mortality than those without bacteraemia. Current evidence for treating co-infection is lacking, and there is no consensus on the dosag...

Background: Children hospitalised with severe acute malnutrition (SAM) are frequently complicated (>50%) by diarrhoea (≥3 watery stools/day) which is accompanied by poor outcomes. Rehydration guidelines for SAM are exceptionally conservative and controversial, based upon expert opinion. The guidelines only permit use of intravenous fluids for cases...

Background: African children with severe malaria are susceptible to Gram-negative bacterial co-infection, largely non-typhoidal Salmonellae, leading to a substantially higher rates of in-hospital and post-discharge mortality than those without bacteraemia. Current evidence for treating co-infection is lacking, and there is no consensus on the dosag...

Owing to the rapid turnaround time in the assessment of haemoglobin level by point‐of‐care tests (POC Hb), these have grown in popularity and scope in large parts of the world. However, whilst POC testing for malaria and HIV remains has been integrated into patient management in Africa, the use of POC haemoglobin testing remains neglected by health...

Purpose: The life-saving role of oxygen therapy in African children with severe pneumonia is not yet established. Methods: The open-label fractional-factorial COAST trial randomised eligible Ugandan and Kenyan children aged > 28 days with severe pneumonia and severe hypoxaemia stratum (SpO2 < 80%) to high-flow nasal therapy (HFNT) or low-flow ox...

The phase III Transfusion and Treatment of severe anaemia in African Children Trial (TRACT) found that conservative management of uncomplicated severe anaemia [haemoglobin (Hb) 40–60 g/l] was safe, and that transfusion volume (20 vs. 30 ml/kg whole blood equivalent) for children with severe anaemia (Hb <60 g/l) had strong but opposing effects on mo...

Case fatality among African children with severe acute malnutrition remains high. We report a 3-arm pilot trial in 58 Ugandan children, comparing feeds targeting disordered gastrointestinal function containing cowpea (CpF, n = 20) or inulin (InF, n = 20) with conventional feeds (ConF, n = 18). Baseline measurements of gut permeability (lactulose:ma...

Severe falciparum malaria has substantially affected human evolution. Genetic association studies of patients with clinically defined severe malaria and matched population controls have helped characterise human genetic susceptibility to severe malaria, but phenotypic imprecision compromises discovered associations. In areas of high malaria transmi...

Few previous studies have reported the effects of glucose-6-phosphate dehydrogenase (G6PD)–deficiency on child health in Africa. We conducted a case-control study in which cases (n = 6829) were children admitted, for any reason, to Kilifi County Hospital, Kenya, while controls (n = 10 179) were recruited from the surrounding community. Cases were s...

Abstract Background Few recent descriptions of severe childhood malaria have been published from high-transmission regions. In the current study, the clinical epidemiology of severe malaria in Mbale, Eastern Uganda, is described, where the entomological inoculation rate exceeds 100 infective bites per year. Methods A prospective descriptive study w...

Background: Most previous studies support a direct link between total parasite load and the clinical severity of Plasmodium falciparum malaria infections. Methods: We estimated P. falciparum parasite loads in three groups of children with malaria infections of differing severity: (1) children with WHO-defined severe malaria (n=1,544); (2) childr...

Background: In Uganda to date, there are neither established registries nor descriptions of facility-based sickle cell disease (SCD) patient characteristics beyond the central region. Here, we summarize data on the baseline clinical characteristics and routine care available to patients at four clinics in Eastern Uganda as a prelude to a clinical t...

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency state in humans. The clinical phenotype is variable and includes asymptomatic individuals, episodic hemolysis induced by oxidative stress, and chronic hemolysis. G6PD deficiency is common in malaria-endemic regions, an observation hypothesized to b...

Background : In Uganda to date, there are neither established registries nor descriptions of facility-based sickle cell disease (SCD) patient characteristics beyond the central region. Here, we summarize data on the baseline clinical characteristics and routine care available to patients at four clinics in Eastern Uganda as a prelude to a clinical...

Background The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. Methods We formed a panel of 36 experts from 12 countri...

Introduction Many HIV‐positive individuals in Africa have advanced disease when initiating antiretroviral therapy (ART) so have high risks of opportunistic infections and death. The REALITY trial found that an enhanced‐prophylaxis package including fluconazole reduced mortality by 27% in individuals starting ART with CD4 <100 cells/mm³. We investig...

Background: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. Methods: We formed a panel of 36 experts from 12 co...

Malnutrition is a major concern in low- and middle-income countries (LMIC), but the full extent of nutritional deficiencies remains unknown largely due to lack of accurate assessment methods. This study seeks to develop and validate an objective, passive method of estimating food and nutrient intake in households in Ghana and Uganda. Household memb...

Introduction: Many HIV-positive individuals in Africa have advanced disease when initiating antiretroviral therapy (ART) so have high risks of opportunistic infections and death. The REALITY trial found that an enhanced-prophylaxis package including fluconazole reduced mortality by 27% in individuals starting ART with CD4<100 cells/mm3. We investig...

Background: African children hospitalised with severe febrile illness have a high risk of mortality. The Fluid Expansion As Supportive Therapy (FEAST) trial (ISCRTN 69856593) demonstrated increased mortality risk associated with fluid boluses, but the temporal relationship to bolus therapy and underlying mechanism remains unclear. Methods: In a...

Background: Severe anaemia is a leading cause of paediatric admission to hospital in Africa; post-discharge outcomes remain poor, with high 6-month mortality (8%) and re-admission (17%). We aimed to investigate post-discharge interventions that might improve outcomes. Methods: Within the two-stratum, open-label, multicentre, factorial randomised...

Background : Owing to inadequate supplies of donor blood for transfusion in sub-Saharan Africa (sSA) World Health Organization paediatric guidelines recommend restrictive transfusion practices, based on expert opinion. We examined whether survival amongst hospitalised children by admission haemoglobin and whether this was influenced by malaria infe...

In many countries in sub‐Saharan Africa (sSA) whole blood is more commonly available from blood transfusion services than red cell concentrates. Although in recent years, many countries have made significant progress in the implementing component preparation, this has largely been facilitated by external funding support. The large majority of rathe...

Background: The World Health Organization recommends not performing transfusions in African children hospitalized for uncomplicated severe anemia (hemoglobin level of 4 to 6 g per deciliter and no signs of clinical severity). However, high mortality and readmission rates suggest that less restrictive transfusion strategies might improve outcomes....

Background: Severe anemia (hemoglobin level, <6 g per deciliter) is a leading cause of hospital admission and death in children in sub-Saharan Africa. The World Health Organization recommends transfusion of 20 ml of whole-blood equivalent per kilogram of body weight for anemia, regardless of hemoglobin level. Methods: In this factorial, open-lab...

Background: Sickle cell disease is the most common severe monogenic disorder in humans. In Africa, 50-90% of children born with sickle cell disease die before they reach their fifth birthday. In this study, we aimed to describe the comparative incidence of specific clinical outcomes among children aged between birth and 5 years with and without si...

Background: The World Health Organization recommends a haemoglobin transfusion threshold of <4g/dl for children with uncomplicated anaemia. High rates of mortality and re-admission in African children with severe anaemia suggest a less restrictive transfusion threshold might improve outcomes. Methods: The TRACT factorial open-label trial randomized...

Background: Severe anaemia (haemoglobin<6g/dl) is a leading cause of hospital admission and mortality in children in sub-Saharan Africa. World Health Organization recommends 20mls/kg whole blood equivalent regardless of haemoglobin, which standard calculations suggest is insufficient for deficit-correction. Methods: The TRACT factorial open-label t...

Background: Many parts of Africa have witnessed reductions in Plasmodium falciparum transmission over the last 15 years. Since immunity to malaria is acquired more rapidly at higher transmission, the slower acquisition of immunity at lower transmission may partially offset the benefits of reductions in transmission. We examined the clinical spectr...

Background: World Health Organization rehydration management guidelines (plan C) for severe dehydration are widely practiced in resource-poor settings, but never formally evaluated in a trial. The Fluid Expansion as a Supportive Therapy trial raised concerns regarding the safety of bolus therapy for septic shock, warranting a formal evaluation of...

Background: Sickle cell disease (SCD) is the commonest severe monogenic disorder of humans. In Africa, 50-90% of children born with SCD die before they reach their fifth birthday. Methods: We conducted a prospective study among a cohort of children on the coast of Kenya. Members were typed for SCD and followed for survival status and disease-specif...

Objectives: Herein we describe a new system we have developed for assessment of dietary intake, meal timing, and food-related activities, adapted for use in low- and middle-income countries. Methods: System components include one or more wearable cameras (the Automatic Ingestion Monitor-2 (AIM), an eyeglasses-mounted wearable chewing sensor and...