Imperial College London

ProfessorKathMaitland

Faculty of MedicineDepartment of Surgery & Cancer

Professor of Tropical Paediatric Infectious Disease
 
 
 
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k.maitland CV

 
 
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Based full-time at KEMRI/Wellcome Programme, KenyaNorfolk PlaceSt Mary's Campus

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Summary

 

Publications

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234 results found

Kiguli S, Olopot-Olupot P, Alaroker F, Engoru C, Opoka R, Tagoola A, Hamaluba M, Mnjalla H, Mpoya A, Mogaka C, Nalwanga D, Nabawanuka E, Nokes J, Nyaigoti C, Briend A, van Woensel J, Grieve R, Sadique Z, Williams T, Thomas K, Harrison D, Rowan K, Maitland Ket al., 2021, Children’s Oxygen Administration Strategies And Nutrition Trial (COAST-Nutrition): a protocol for a phase II randomised controlled trial, Wellcome Open Research, ISSN: 2398-502X

<ns3:p> <h4>Background: </h4> 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 practiced in a wide variety of critically ill patients to provide vital cell substrates, antioxidants, vitamins, and minerals essential for normal cell function and decreasing hypermetabolism. We hypothesise that the excess post-discharge mortality associated with pneumonia may relate to the catabolic response and muscle wasting induced by severe infection and inadequacy of the diet to aid recovery. We suggest that providing additional energy-rich, protein, fat and micronutrient ready-to-use therapeutic feeds (RUTF) to help meet additional nutritional requirements may improve outcome.</ns3:p><ns3:p> <h4>Methods: </h4>:</ns3:bold><ns3:bold> </ns3:bold>COAST-Nutrition is an open, multicentre, Phase II randomised controlled trial in children aged 6 months to 12 years hospitalised with suspected severe pneumonia (and hypoxaemia, SpO<ns3:sub>2</ns3:sub> <92%) to establish whether supplementary feeds with RUTF given in addition to usual diet for 56-days (experimental) improves outcomes at 90-days compared to usual diet alone (control). Primary endpoint is change in mid-upper arm circumference (MUAC) at 90 days and/or as a composite with 90-day mortality. Secondary outcomes include anthropometric status, mortality, readmission at days 28 and 180. The trial will be conducted in four sites in two countries (Uganda and Kenya) enrolling 840 children followed up to 180 days. Ancillary studies include cost-economic analysis, molecular characterisation of bacterial and viral pathogens, evaluation of putative biomarkers of pneumonia

Journal article

Walsh K, Delamare de la Villenaise de Chenevarin G, McGurk J, Maitland K, Frost Get al., 2021, Development of a legume-enriched feed for treatment of severe acute malnutrition [version 1; peer review: 1 approved with reservations], Wellcome Open Research, Vol: 6, ISSN: 2398-502X

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 nutritional feeds should be designed to promote bacterial diversity and restore gastrointestinal (GI) barrier function.</ns3:p><ns3:p> <ns3:bold>Methods:</ns3:bold> Our major objective was to develop a lactose-free, fermentable carbohydrate-containing alternative to traditional F75 and F100 formulae for the inpatient treatment of SAM. New target nutritional characteristics were developed and relevant food and infant food specific legislation were reviewed. Suitable certified suppliers of ingredients were identified. Processing and manufacture steps were evaluated and optimised for safety (nutritional, chemical and microbiological), and efficacy at meeting target characteristics (lactose-free, containing resistant starch 0.4-0.5% final product weight).</ns3:p><ns3:p> <ns3:bold>Results:</ns3:bold> A final validated production process was developed and implemented to produce a novel food product for the inpatient treatment of SAM in children in Africa designed to reduce risk of osmotic diarrhoea and support symbiotic gut microbial populations. The final product matched the macronutrient profile of double-concentrated F100, adhered to all relevant legislation regulating infant foods, was lactose free, and contained 0.6% resistant starch. Chickpeas were selected as the source of resistant starch, since they are widely grown and eaten throughout Africa. Micronutrient content could not be matched in this ready-to-use product, so this was replaced at the point of feeding, as was fluid lost through concentration.</ns3:p><ns3:p> <ns3:bold>Conclusions:</ns3:bold> The processes a

Journal article

Connon R, George EC, Olupot-Olupot P, Kiguli S, Chagaluka G, Alaroker F, Opoka RO, Mpoya A, Walsh K, Engoru C, Nteziyaremye J, Mallewa M, Kennedy N, Nakuya M, Namayanja C, Nabawanuka E, Sennyondo T, Amorut D, Williams Musika C, Bates I, Boele van Hensbroek M, Evans JA, Uyoga S, Williams TN, Frost G, Gibb DM, Maitland K, Walker AS, TRACT trial groupet al., 2021, Incidence and predictors of hospital readmission in children presenting with severe anaemia in Uganda and Malawi: a secondary analysis of TRACT trial data, BMC Public Health, Vol: 21, ISSN: 1471-2458

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 children from Uganda and Malawi surviving a hospital episode of severe anaemia. Predictors of all-cause readmission within 180 days of discharge were identified using multivariable regression with death as a competing risk. Groups of children with similar characteristics were identified using hierarchical clustering. RESULTS: Of the 3894 survivors 682 (18%) were readmitted; 403 (10%) had ≥2 re-admissions over 180 days. Three main causes of readmission were identified: severe anaemia (n = 456), malaria (n = 252) and haemoglobinuria/dark urine syndrome (n = 165). Overall, factors increasing risk of readmission included HIV-infection (hazard ratio 2.48 (95% CI 1.63-3.78), p < 0.001); ≥2 hospital admissions in the preceding 12 months (1.44(1.19-1.74), p < 0.001); history of transfusion (1.48(1.13-1.93), p = 0.005); and missing ≥1 trial medication dose (proxy for care quality) (1.43 (1.21-1.69), p < 0.001). Children with uncomplicated severe anaemia (Hb 4-6 g/dL and no severity features), who never received a transfusion (per trial protocol) during the initial admission had a substantially lower risk of readmission (0.67(0.47-0.96), p = 0.04). Malaria (among children with no prior history of transfusion) (0.60(0.47-0.76), p < 0.001); younger-age (1.07 (1.03-1.10) per 1 year younger, p < 0.001) and known sickle cell disease (0.62(0.46-0.82), p = 0.001) also decreased risk of readmission. For anaemia re-admissions, gross

Journal article

Watson JA, Ndila CM, Uyoga S, Macharia A, Nyutu G, Mohammed S, Ngetsa C, Mturi N, Peshu N, Tsofa B, Rockett K, Leopold S, Kingston H, George EC, Maitland K, Day NP, Dondorp AM, Bejon P, Williams T, Holmes CC, White NJet al., 2021, Improving statistical power in severe malaria genetic association studies by augmenting phenotypic precision., eLife, Vol: 10, Pages: 1-39, ISSN: 2050-084X

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 transmission the diagnosis of severe malaria in young children and, in particular, the distinction from bacterial sepsis, is imprecise. We developed a probabilistic diagnostic model of severe malaria using platelet and white count data. Under this model we re-analysed clinical and genetic data from 2,220 Kenyan children with clinically defined severe malaria and 3,940 population controls, adjusting for phenotype mis-labelling. Our model, validated by the distribution of sickle trait, estimated that approximately one third of cases did not have severe malaria. We propose a data-tilting approach for case-control studies with phenotype mis-labelling and show that this reduces false discovery rates and improves statistical power in genome-wide association studies.

Journal article

Olupot-Olupot P, Aloroker F, Mpoya A, Mnjalla H, Passi G, Nakuya M, Houston K, Obonyo N, Hamaluba M, Evans J, Connon R, George E, Gibb D, Maitland Ket al., 2021, Gastroenteritis rehydration of children with severe acute malnutrition (GASTROSAM): a phase II randomised controlled trial: trial protocol, Wellcome Open Research, Vol: 6, Pages: 1-16, ISSN: 2398-502X

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 with advanced shock and exclusive use of low sodium intravenous and oral rehydration solutions (ORS) for fear of fluid and/or sodium overload. Children managed in accordance to these guidelines have a very high mortality. The proposed GASTROSAM trial is the first step in reappraising current recommendations. We hypothesize that liberal rehydration strategies for both intravenous and oral rehydration in SAM children with diarrhoea may reduce adverse outcomes. Methods An open Phase II trial, with a partial factorial design, enrolling Ugandan and Kenyan children aged 6 months to 12 years with SAM hospitalised with gastroenteritis (>3 loose stools/day) and signs of moderate and severe dehydration. In Stratum A (severe dehydration) children will be randomised (1:1:2) to WHO plan C (100mls/kg Ringers Lactate (RL) with intravenous rehydration given over 3-6 hours according to age including boluses for shock), slow rehydration (100 mls/kg RL over 8 hours (no boluses)) or WHO SAM rehydration regime (ORS only (boluses for shock (standard of care)). Stratum B incorporates all children with moderate dehydration and severe dehydration post-intravenous rehydration and compares (1:1 ratio) standard WHO ORS given for non-SAM (experimental) versus WHO SAM-recommended low-sodium ReSoMal. The primary outcome for intravenous rehydration is urine output (mls/kg/hour at 8 hours post-randomisation), and for oral rehydration a change in sodium levels at 24 hours post-randomisation. This trial will also generate feasibility, safety and preliminary data on survival to 28 days. Discussion. If current rehydration strategies for non-maln

Journal article

Olupot-Olupot P, Okiror W, Mnjalla H, Muhindo R, Uyoga S, Mpoya A, Williams T, terHeine R, Burger D, Urban B, Connon R, George E, Gibb D, Walker S, Maitland Ket al., 2021, Pharmacokinetics and pharmacodynamics of azithromycin in severe malaria bacterial co-infection in African children (TABS-PKPD): a protocol for a Phase II randomised controlled trial, Wellcome Open Research, Vol: 6, ISSN: 2398-502X

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 dosage or length of treatment required. We therefore aimed to establish the appropriate dose of oral dispersible azithromycin as an antimicrobial treatment for children with severe malaria and to investigate whether antibiotics can be targeted to those at greatest risk of bacterial co-infection using clinical criteria alone or in combination with rapid diagnostic biomarker tests. Methods: A Phase I/II open-label trial comparing three doses of azithromycin: 10, 15 and 20 mg/kg spanning the lowest to highest mg/kg doses previously demonstrated to be equally effective as parenteral treatment for other salmonellae infection. Children with the highest risk of bacterial infection will receive five days of azithromycin and followed for 90 days. We will generate relevant pharmacokinetic data by sparse sampling during dosing intervals. We will use population pharmacokinetic modelling to determine the optimal azithromycin dose in severe malaria and investigate azithromycin exposure to change in C-reactive protein, a putative marker of sepsis at 72 hours, and microbiological cure (seven-day), alone and as a composite with seven-day survival. We will also evaluate whether a combination of clinical, point-of-care diagnostic tests, and/or biomarkers can accurately identify the sub-group of severe malaria with culture-proven bacteraemia by comparison with a control cohort of children hospitalized with severe malaria at low risk of bacterial co-infection. Discussion : We plan to study azithromycin because of its favourable microbiological spectrum, its inherent antimalarial and immunomodulatory properties and dosing and safety profile. This st

Journal article

Uyoga S, George EC, Bates I, Olupot-Olupot P, Chimalizeni Y, Molyneux EM, Maitland Ket al., 2021, Point-of-Care Haemoglobin testing in African hospitals: a neglected essential diagnostic test, British Journal of Haematology, Vol: 193, Pages: 894-901, ISSN: 0007-1048

Owing to the rapid turnaround time in the assessment of haemoglobin level by point-of-care (POC) tests, it has 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 has remains neglected by health services. The main users of transfusions (paediatric, maternity and trauma services) present largely as emergencies. Ward-based POCHb could result in more rapid and accurate diagnosis of anaemia, contributing to saving of lives and at the same time reduce unnecessary transfusions which deplete the limited supplies of donated blood in Africa. Severe anaemia requiring transfusion is a major cause of paediatric admission in Africa. A dissemination meeting to discuss the results of a large phase III paediatric transfusion trial and steps to implementation of the findings members strongly recommended that one of the most pressing actions required was to prioritise the use of POC haemoglobin testing. This would facilitate implementation of the new transfusion algorithm, developed at the meeting which refine patient management including blood transfusions. We present the rationale for strongly recommended prioritization of POCHb, using paediatric transfusion as an examplar.

Journal article

Maitland K, Kiguli S, Olupot-Olupot P, Opoka RO, Chimalizeni Y, Alaroker F, Uyoga S, Kyeyune Byabazaire D, Mbaya B, Bates I, Williams TN, Mbanya D, Munube D, Molyneux EM, South A, Walker AS, Gibb DM, George EMet al., 2021, Transfusion management of severe anaemia in African children: a consensus algorithm, British Journal of Haematology, Vol: 193, Pages: 1247-1259, ISSN: 0007-1048

The phase III Transfusion and Treatment of severe anaemia in African Children Trial(TRACT) found that conservative management of uncomplicated severe anaemia (haemoglobin(Hb)4-6g/dl) was safe and that transfusion volume(20 versus30 mls/kg whole blood equivalent)for children with severe anaemia (Hb<6g/dl) had strong but opposing effects on mortality, depending on fever status (>37.5oC). In 2020 a stakeholder meeting of paediatric and blood transfusion groups from Africa reviewed the results and additional analyses. Among all children (3196) receiving an initial transfusion, there was no evidence that nutritional status, presence of shock, malaria parasite burden, or sickle cell disease status influenced outcomes, or modified the interaction with fever status on volume required. Fever status at the time of ordering blood was a reliable determinant of volume required for optimal outcome. Elevated heart and respiratory rates normalised irrespective of transfusion volume and without diuretics. By consensus, a transfusion management algorithm was developed, incorporating 3 additional measurements of Hb post-admission, alongside clinical monitoring. The proposed algorithm should help clinicians safely implement findings from TRACT. Further research should assess its implementation in routine clinical practice

Journal article

Maitland K, Kiguli S, Olupot-Olupot P, Hamaluba M, Thomas K, Alaroker F, Opoka RO, Tagoola A, Bandika V, Mpoya A, Mnjalla H, Nabawanuka E, Okiror W, Nakuya M, Aromut D, Engoru C, Oguda E, Williams TN, Fraser JF, Harrison D, Rowan K, on behalf of the COAST trial groupet al., 2021, Randomised controlled trial of oxygen therapy and high flow nasal therapy in African children with pneumonia, Intensive Care Medicine, Vol: 47, Pages: 566-576, ISSN: 0342-4642

PurposeThe life-saving role of oxygen therapy in African children with severe pneumonia is not yet established.MethodsThe 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 oxygen (LFO: standard care) and hypoxaemia stratum (SpO2 80–91%) to HFNT or LFO (liberal strategies) or permissive hypoxaemia (ratio 1:1:2). Children with cyanotic heart disease, chronic lung disease or > 3 h receipt of oxygen were excluded. The primary endpoint was 48 h mortality; secondary endpoints included mortality or neurocognitive sequelae at 28 days.ResultsThe trial was stopped early after enrolling 1852/4200 children, including 388 in the severe hypoxaemia stratum (median 7 months; median SpO2 75%) randomised to HFNT (n = 194) or LFO (n = 194) and 1454 in the hypoxaemia stratum (median 9 months; median SpO2 88%) randomised to HFNT (n = 363) vs LFO (n = 364) vs permissive hypoxaemia (n = 727). Per-protocol 15% of patients in the permissive hypoxaemia group received oxygen (when SpO2 < 80%). In the severe hypoxaemia stratum, 48-h mortality was 9.3% for HFNT vs. 13.4% for LFO groups. In the hypoxaemia stratum, 48-h mortality was 1.1% for HFNT vs. 2.5% LFO and 1.4% for permissive hypoxaemia. In the hypoxaemia stratum, adjusted odds ratio for 48-h mortality in liberal vs permissive comparison was 1.16 (0.49–2.74; p = 0.73); HFNT vs LFO comparison was 0.60 (0.33–1.06; p = 0.08). Strata-specific 28 day mortality rates were, respectively: 18.6, 23.4 and 3.3, 4.1, 3.9%. Neurocognitive sequelae were rare.ConclusionsRespiratory support with HFNT showing potential benefit should prompt further trials.

Journal article

Calder N, Walsh K, Olupot-Olupot P, Ssenyondo T, Muhindo R, Mpoya A, Brignardello J, Wang X, McKay E, Morrison D, Holmes E, Frost G, Maitland Ket al., 2021, Modifying gut integrity and microbiome in children with severe acute malnutrition using legume-based feeds (MIMBLE): A pilot trial, Cell Reports Medicine, Vol: 2, Pages: 100280-100280, ISSN: 2666-3791

Journal article

Kiguli S, Olopot-Olupot P, Alaroker F, Engoru C, Opoka RO, Tagoola A, Hamaluba M, Mnjalla H, Mpoya A, Mogaka C, Nalwanga D, Nabawanuka E, Nokes J, Nyaigoti C, Briend A, van Woensel JBM, Grieve R, Sadique Z, Williams TN, Thomas K, Harrison DA, Rowan K, Maitland Ket al., 2021, Children's Oxygen Administration Strategies And Nutrition Trial (COAST-Nutrition): a protocol for a phase II randomised controlled trial., Wellcome Open Res, Vol: 6, ISSN: 2398-502X

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 practiced in a wide variety of critically ill patients to provide vital cell substrates, antioxidants, vitamins, and minerals essential for normal cell function and decreasing hypermetabolism. We hypothesise that the excess post-discharge mortality associated with pneumonia may relate to the catabolic response and muscle wasting induced by severe infection and inadequacy of the diet to aid recovery. We suggest that providing additional energy-rich, protein, fat and micronutrient ready-to-use therapeutic feeds (RUTF) to help meet additional nutritional requirements may improve outcome. Methods: COAST-Nutrition is an open, multicentre, Phase II randomised controlled trial in children aged 6 months to 12 years hospitalised with suspected severe pneumonia (and hypoxaemia, SpO 2 <92%) to establish whether supplementary feeds with RUTF given in addition to usual diet for 56-days (experimental) improves outcomes at 90-days compared to usual diet alone (control). Primary endpoint is change in mid-upper arm circumference (MUAC) at 90 days and/or as a composite with 90-day mortality. Secondary outcomes include anthropometric status, mortality, readmission at days 28 and 180. The trial will be conducted in four sites in two countries (Uganda and Kenya) enrolling 840 children followed up to 180 days. Ancillary studies include cost-economic analysis, molecular characterisation of bacterial and viral pathogens, evaluation of putative biomarkers of pneumonia, assessment of muscle and fat mass and host genetic studies.   Discussion: This study is the first step in providing an option for nutritional support following severe p

Journal article

Uyoga S, Alex W M, Ndila CM, Nyutu G, Shebe M, Awuondo KO, Mturi N, Peshu N, Tsofa B, Scott JAG, Maitland K, Williams Tet al., 2020, Glucose-6-phosphate dehydrogenase deficiency and susceptibility to childhood diseases in Kilifi, Kenya, Blood Advances, Vol: 4, Pages: 5942-5950, ISSN: 2473-9529

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 subclassified based on their clinical and laboratory findings at admission. We calculated the prevalence of specific diseases by G6PD c.202 genotype, the only significant cause of G6PD-deficiency in this area, then estimated the association between genotype and admission with specific conditions using logistic regression. Among neonates, the prevalence of jaundice was higher in both G6PD c.202T heterozygotes (40/88; 45.5%; P = .004) and homo/hemizygotes (81/134; 60.5%; P < .0001) than in wild-type homozygotes (157/526; 29.9%). Median bilirubin levels also increased across the groups, being highest (239 mmol/L; interquartile range 96-390 mmol/L) in G6PD c.202T homo/hemizygotes. No differences were seen in admission hemoglobin concentrations or the prevalence of anemia or severe anemia by G6PD c.202 genotype. On case control analysis, G6PD heterozygosity was negatively associated with all-cause hospital admission (odds ratio 0.81; 95% confidence interval 0.73-0.90; P < .0001) and, specifically, admission with either pneumonia or Plasmodium falciparum parasitemia; while, conversely, it was positively associated with Gram-positive bacteremia. G6PD c.202T homo/heterozygosity was positively associated with neonatal jaundice, severe pneumonia, the receipt of a transfusion, and in-patient death. Our study supports the conclusion that G6PD c.202T is a balanced polymorphism in which a selective advantage afforded to heterozygous females against malaria is counterbalanced by increased risks of neonatal jaundice, invasive bacterial infections, and anemia.

Journal article

Olupot-Olupot P, Engoru C, Nteziyaremye J, Chebet M, Ssenyondo T, Muhindo R, Nyutu G, Macharia A, Uyoga S, Ndila CM, Karamagi C, Maitland K, Williams Tet al., 2020, The clinical spectrum of severe childhood malaria in Eastern Uganda, Malaria Journal, Vol: 19, ISSN: 1475-2875

BackgroundFew 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.MethodsA prospective descriptive study was conducted to determine the prevalence, clinical spectrum and outcome of severe Plasmodium falciparum malaria at Mbale Regional Referral Hospital in Eastern Uganda. All children aged 2 months–12 years who presented on Mondays to Fridays between 8.00 am and 5.00 pm from 5th May 2011 until 30th April 2012 were screened for parasitaemia. Clinical and laboratory data were then collected from all P. falciparum positive children with features of WHO-defined severe malaria by use of a standardized proforma.ResultsA total of 10 208 children were screened of which 6582 (64%) had a positive blood film. Of these children, 662 (10%) had clinical features of severe malaria and were consented for the current study. Respiratory distress was the most common severity feature (554; 83.7%), while 365/585 (62.4%) had hyperparasitaemia, 177/662 (26.7%) had clinical jaundice, 169 (25.5%) had severe anaemia, 134/660 (20.2%) had hyperlactataemia (lactate ≥ 5 mmol/L), 93 (14.0%) had passed dark red or black urine, 52 (7.9%) had impaired consciousness and 49/662 (7.4%) had hypoxaemia (oxygen saturations < 90%). In-hospital mortality was 63/662 (9.5%) overall but was higher in children with either cerebral malaria (33.3%) or severe anaemia (19.5%). Factors that were independently associated with mortality on multivariate analysis included severe anaemia [odds ratio (OR) 5.36; 2.16–1.32; P = 0.0002], hyperlactataemia (OR 3.66; 1.72–7.80; P = 0.001), hypoxaemia (OR) 3.64 (95% CI 1.39–9.52; P = 0.008), and hepatomegaly (OR 2.29; 1.29–4.06; P = 

Journal article

Uyoga S, Wanjiku P, Rop J, Makale J, Macharia A, Nyutu G, Shebbe M, Awuondo K, Mturi N, Woodrow C, Dondorp A, Maitland K, Williams T, Williams TNet al., 2020, Plasma Plasmodium falciparum Histidine-Rich Protein-2 concentrations in children with malaria infections of differing severity in Kilifi, Kenya, Clinical Infectious Diseases, Vol: 73, Pages: e2415-e2423, ISSN: 1058-4838

BackgroundMost previous studies support a direct link between total parasite load and the clinical severity of Plasmodium falciparum malaria infections.MethodsWe 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) children admitted with malaria but without features of severity (n=200) and; (3) children in the community with asymptomatic parasitemia (n=33).ResultsPeripheral parasitemias were highest in those with uncomplicated malaria (geometric mean 111,064; 95%CI 86,798-141,819 parasites/μl), being almost three times higher than those with severe malaria (39,588; 34,990-44,791 parasites/μl) and >100 times higher than in those with asymptomatic malaria (1,092; 523-2,280 parasites/μl). However, geometric mean PfHRP2 values (95% CI) increased with severity, being 7 (4-12) ng/ml in asymptomatic malaria, 843 (655-1,084) ng/ml in uncomplicated malaria and 1,369 (1,244-1,506) ng/ml in severe malaria. PfHRP2 concentrations were markedly lower in the sub-group of severe malaria patients with concomitant invasive bacterial infections (IBIs) of blood or CSF (GM 312 ng/ml; 95%CI 175-557; p<0.0001) than in those without IBIs (GM 1,439 ng/ml; 1,307-1,584; P<0.001).ConclusionsThe clinical severity of malaria infections related strongly to the total burden of P. falciparum parasites. A quantitative test for plasma concentrations of PfHRP2 could be useful in identifying children at the greatest clinical risk and to identify critically ill children in whom malaria is not the primary cause.

Journal article

Olupot-Olupot P, Wabwire H, Ndila C, Adong R, Ochen L, Amorut D, Abongo G, Okalebo C, Akello SR, Oketcho J, Okiror W, Asio S, Odiit A, Alaroker F, Nyutu G, Maitland K, Williams Tet al., 2020, Characterising demographics, knowledge, practices and clinical care among patients attending sickle cell disease clinics in Eastern Uganda

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 trial. Methods : Between February and August 2018, we conducted a cross-sectional survey of patients attending four SCD clinics in Mbale, Soroti, Atutur and Ngora, all in Eastern Uganda, the planned sites for an upcoming clinical trial (H-PRIME:  ISRCTN15724013 ). Data on socio-demographic characteristics, diagnostic methods, clinic schedules, the use of prophylactic and therapeutic drugs, clinical complications and patient understanding of SCD were collected using a structured questionnaire. Results : Data were collected on 1829 patients. Their ages ranged from 0 to 64 years with a median (IQR) of 6 (3-11) years. 49.1% of participants were male. The majority (1151; 62.9%) reported a positive family history for SCD. Approximately half knew that SCD is inherited from both parents but a substantial proportion did not know how SCD is transmitted and small numbers believed that it is acquired by either transfusion or from other people. Only 118/1819 (6.5%) participants had heard about or were using hydroxyurea while 356/1794 (19.8%) reported stigmatization. Participants reported a median of three (IQR 1-4) hospital admissions during the preceding 12 months; 80.8% had been admitted at least once, while 14.2% had been admitted more than five times. Pain was the most common symptom, while 83.9% of those admitted had received at least one blood transfusion. Conclusion:  The majority of patients attending SCD clinics in Eastern Uganda are children and few are currently being treated with hydroxyurea. The data collected through this facility-based survey will provide background data that will be useful in planning for the

Working paper

Olupot-Olupot P, Wabwire H, Ndila C, Adong R, Ochen L, Amorut D, Abongo G, Okalebo CB, Akello SR, Oketcho JB, Okiror W, Asio S, Odiit A, Alaroker F, Nyutu G, Maitland K, Williams TNet al., 2020, Characterising demographics, knowledge, practices and clinical care among patients attending sickle cell disease clinics in Eastern Uganda [version 2; peer review: 2 approved], Wellcome Open Research, Vol: 5, Pages: 87-87, ISSN: 2398-502X

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 trial.Methods: Between February and August 2018, we conducted a cross-sectional survey of patients attending four SCD clinics in Mbale, Soroti, Atutur and Ngora, all in Eastern Uganda, the planned sites for an upcoming clinical trial (H-PRIME: ISRCTN15724013). Data on socio-demographic characteristics, diagnostic methods, clinic schedules, the use of prophylactic and therapeutic drugs, clinical complications and patient understanding of SCD were collected using a structured questionnaire.Results: Data were collected on 1829 patients. Their ages ranged from 0 to 64 years with a median (IQR) of 6 (3-11) years. 49.1% of participants were male. The majority (1151; 62.9%) reported a positive family history for SCD. Approximately half knew that SCD is inherited from both parents but a substantial proportion did not know how SCD is transmitted and small numbers believed that it is acquired by either transfusion or from other people. Only 118/1819 (6.5%) participants had heard about or were using hydroxyurea while 356/1794 (19.8%) reported stigmatization. Participants reported a median of three (IQR 1-4) hospital admissions during the preceding 12 months; 80.8% had been admitted at least once, while 14.2% had been admitted more than five times. Pain was the most common symptom, while 83.9% of those admitted had received at least one blood transfusion.Conclusion: The majority of patients attending SCD clinics in Eastern Uganda are children and few are currently being treated with hydroxyurea. The data collected through this facility-based survey will provide background data that will be useful in planning for the H-PRIME trial.

Journal article

Uyoga S, Mpoya A, Olupot-Olupot P, Kiguli S, Opoka RO, Engoru C, Mallewa M, Kennedy N, M'baya B, Kyeyune D, Wabwire B, Bates I, Gibb DM, Walker AS, George EC, Williams TN, Maitland Ket al., 2020, Corrigendum: Haematological quality and age of donor blood issued for paediatric transfusion to four hospitals in sub-Saharan Africa, Vox Sanguinis: international journal of transfusion medicine, Vol: 115, Pages: 478-478, ISSN: 0042-9007

Journal article

Gilchrist JJ, Uyoga S, Pirinen M, Rautanen A, Mwarumba S, Njuguna P, Mturi N, Hill AVS, Scott JAG, Williams Tet al., 2020, Risk of pneumococcal bacteremia in Kenyan children with glucose-6-phosphate dehydrogenase deficiency, BMC Medicine, Vol: 18, Pages: 1-10, ISSN: 1741-7015

BackgroundGlucose-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 be due to balancing selection at the G6PD locus driven by malaria. G6PD deficiency increases risk of severe malarial anemia, a key determinant of invasive bacterial disease in malaria-endemic settings. The pneumococcus is a leading cause of invasive bacterial infection and death in African children. The effect of G6PD deficiency on risk of pneumococcal disease is undefined. We hypothesized that G6PD deficiency increases pneumococcal disease risk and that this effect is dependent upon malaria.MethodsWe performed a genetic case-control study of pneumococcal bacteremia in Kenyan children stratified across a period of falling malaria transmission between 1998 and 2010.ResultsFour hundred twenty-nine Kenyan children with pneumococcal bacteremia and 2677 control children were included in the study. Among control children, G6PD deficiency, secondary to the rs1050828 G>A mutation, was common, with 11.2% (n = 301 of 2677) being hemi- or homozygotes and 33.3% (n = 442 of 1329) of girls being heterozygotes. We found that G6PD deficiency increased the risk of pneumococcal bacteremia, but only during a period of high malaria transmission (P = 0.014; OR 2.33, 95% CI 1.19–4.57). We estimate that the population attributable fraction of G6PD deficiency on risk of pneumococcal bacteremia in areas under high malaria transmission is 0.129.ConclusionsOur data demonstrate that G6PD deficiency increases risk of pneumococcal bacteremia in a manner dependent on malaria. At the population level, the impact of G6PD deficiency on invasive pneumococcal disease risk in malaria-endemic regions is substantia

Journal article

Alhazzani W, Møller MH, Arabi YM, Loeb M, Gong MN, Fan E, Oczkowski S, Levy MM, Derde L, Dzierba A, Du B, Aboodi M, Wunsch H, Cecconi M, Koh Y, Chertow DS, Maitland K, Alshamsi F, Belley-Cote E, Greco M, Laundy M, Morgan JS, Kesecioglu J, McGeer A, Mermel L, Mammen MJ, Alexander PE, Arrington A, Centofanti JE, Citerio G, Baw B, Memish ZA, Hammond N, Hayden FG, Evans L, Rhodes Aet al., 2020, Surviving sepsis campaign: guidelines on the management of critically Ill adults with coronavirus disease 2019 (COVID-19), Critical Care Medicine, Vol: 48, Pages: e440-e469, ISSN: 0090-3493

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 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations.Results: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which four are best practice statements, nine are strong recommendations, and 35 are weak recommendations. No recommendation was provided for six questions. The topics were: 1) infection control, 2) laboratory diagnosis and specimens, 3) hemodynamic support, 4) ventilatory support, and 5) COVID-19 therapy.Conclusion: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new evidence in further releases of these guidelines.

Journal article

Olupot-Olupot P, Wabwire H, Ndila C, Adong R, Ochen L, Amorut D, Abongo G, Okalebo CB, Akello SR, Okecho JB, Okiror W, Asio S, Odiit A, Alaroker F, Nyutu G, Maitland K, Williams Tet al., 2020, Characterising demographics, knowledge, practices and clinical care among patients attending sickle cell disease clinics in Eastern Uganda [version 1; peer review: 1 approved, 1 approved with reservations], Wellcome Open Research, Vol: 5, Pages: 1-13, ISSN: 2398-502X

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 trial.Methods: Between February and August 2018, we conducted a cross-sectional survey of patients attending four SCD clinics in Mbale, Soroti, Atutur and Ngora, all in Eastern Uganda, the planned sites for an upcoming clinical trial (H-PRIME: ISRCTN15724013). Data on socio-demographic characteristics, diagnostic methods, clinic schedules, the use of prophylactic and therapeutic drugs, clinical complications and patient understanding of SCD were collected using a structured questionnaire.Results: Data were collected on 1829 patients. Their ages ranged from 0 to 64 years with a median (IQR) of 6 (3-11) years. 50.9% of participants were male. The majority (1151; 62.9%) reported a positive family history for SCD. Approximately half knew that SCD is inherited from both parents but a substantial proportion did not know how SCD is transmitted and small numbers believed that it is acquired by either transfusion or from other people. Only 118/1819 (6.5%) participants had heard about or were using hydroxyurea while 356/1794 (19.8%) reported stigmatization. Participants reported a median of three (IQR 1-4) hospital admissions during the preceding 12 months; 80.8% had been admitted at least once, while 14.2% had been admitted more than five times. Pain was the most common symptom, while 83.9% of those admitted had received at least one blood transfusion.Conclusion: The majority of patients attending SCD clinics in Eastern Uganda are children and few are currently being treated with hydroxyurea. The data collected through this facility-based survey will provide background data that will be useful in planning for the H-PRIME trial.

Journal article

Alhazzani W, Møller MH, Arabi YM, Loeb M, Gong MN, Fan E, Oczkowski S, Levy MM, Derde L, Dzierba A, Du B, Aboodi M, Wunsch H, Cecconi M, Koh Y, Chertow DS, Maitland K, Alshamsi F, Belley-Cote E, Greco M, Laundy M, Morgan JS, Kesecioglu J, McGeer A, Mermel L, Mammen MJ, Alexander PE, Arrington A, Centofanti JE, Citerio G, Baw B, Memish ZA, Hammond N, Hayden FG, Evans L, Rhodes Aet al., 2020, Surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19), Intensive Care Medicine, Vol: 46, Pages: 854-887, ISSN: 0342-4642

BackgroundThe 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.MethodsWe formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations.ResultsThe Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which 4 are best practice statements, 9 are strong recommendations, and 35 are weak recommendations. No recommendation was provided for 6 questions. The topics were: (1) infection control, (2) laboratory diagnosis and specimens, (3) hemodynamic support, (4) ventilatory support, and (5) COVID-19 therapy.ConclusionThe Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new recommendations in further releases of these guidelines.

Journal article

Walker SM, Cox E, Revill P, Musiime V, BwakuraDangarembizi M, Mallewa J, Cheruiyot P, Maitland K, Ford N, Gibb DM, Walker AS, Soares M, Mugyenyi P, Kityo C, Musiime V, Wavamunno P, Nambi E, Ocitti P, Ndigendawani M, Kabahenda S, Kemigisa M, Acen J, Olebo D, Mpamize G, Amone A, Okweny D, Mbonye A, Nambaziira F, Rweyora A, Kangah M, Kabaswahili V, Abach J, Abongomera G, Omongin J, Aciro I, Philliam A, Arach B, Ocung E, Amone G, Miles P, Adong C, Tumsuiime C, Kidega P, Otto B, Apio F, Baleeta K, Mukuye A, Abwola M, Ssennono F, Baliruno D, Tuhirwe S, Namisi R, Kigongo F, Kikyonkyo D, Mushahara F, Okweny D, Tusiime J, Musiime A, Nankya A, Atwongyeire D, Sirikye S, Mula S, Noowe N, Lugemwa A, Kasozi M, Mwebe S, Atwine L, Senkindu T, Natuhurira T, Katemba C, Ninsiima E, Acaku M, Kyomuhangi J, Ankunda R, Tukwasibwe D, Ayesiga L, Hakim J, Nathoo K, BwakuraDangarembizi M, Reid A, Chidziva E, Mhute T, Tinago GC, Bhiri J, Mudzingwa S, Phiri M, Steamer J, Nhema R, Warambwa C, Musoro G, Mutsai S, Nemasango B, Moyo C, Chitongo S, Rashirai K, Vhembo S, Mlambo B, Nkomani S, Ndemera B, Willard M, Berejena C, Musodza Y, Matiza P, Mudenge B, Guti V, Etyang A, Agutu C, Berkley J, Maitland K, Njuguna P, Mwaringa S, Etyang T, Awuondo K, Wale S, Shangala J, Kithunga J, Mwarumba S, Said Maitha S, Mutai R, Lozi Lewa M, Mwambingu G, Mwanzu A, Kalama C, Latham H, Shikuku J, Fondo A, Njogu A, Khadenge C, Mwakisha B, Siika A, WoolsKaloustian K, Nyandiko W, Cheruiyot P, Sudoi A, Wachira S, Meli B, Karoney M, Nzioka A, Tanui M, Mokaya M, Ekiru W, Mboya C, Mwimali D, Mengich C, Choge J, Injera W, Njenga K, Cherutich S, Anyango Orido M, Omondi Lwande G, Rutto P, Mudogo A, Kutto I, Shali A, Jaika L, Jerotich H, Pierre M, Mallewa J, Kaunda S, Van Oosterhout J, O'Hare B, Heydermann R, Gonzalez C, Dzabala N, Kelly C, Denis B, Selemani G, Nyondo Mipando L, Chirwa E, Banda P, Mvula L, Msuku H, Ziwoya M, Manda Y, Nicholas S, Masesa C, Mwalukomo T, Makhaza L, Sheha I, Bwanali J, Limbuni M, Gibb D, Thomaset al., 2020, The cost‐effectiveness of prophylaxis strategies for individuals with advanced HIV starting treatment in Africa, Journal of the International AIDS Society, Vol: 23, Pages: 1-11, ISSN: 1758-2652

IntroductionMany 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 investigated the cost‐effectiveness of this enhanced‐prophylaxis package versus other strategies, including using cryptococcal antigen (CrAg) testing, in individuals with CD4 <200 cells/mm3 or <100 cells/mm3 at ART initiation and all individuals regardless of CD4 count.MethodsThe REALITY trial enrolled from June 2013 to April 2015. A decision‐analytic model was developed to estimate the cost‐effectiveness of six management strategies in individuals initiating ART in the REALITY trial countries. Strategies included standard‐prophylaxis, enhanced‐prophylaxis, standard‐prophylaxis with fluconazole; and three CrAg testing strategies, the first stratifying individuals to enhanced‐prophylaxis (CrAg‐positive) or standard‐prophylaxis (CrAg‐negative), the second to enhanced‐prophylaxis (CrAg‐positive) or enhanced‐prophylaxis without fluconazole (CrAg‐negative) and the third to standard‐prophylaxis with fluconazole (CrAg‐positive) or without fluconazole (CrAg‐negative). The model estimated costs, life‐years and quality‐adjusted life‐years (QALY) over 48 weeks using three competing mortality risks: cryptococcal meningitis; tuberculosis, serious bacterial infection or other known cause; and unknown cause.ResultsEnhanced‐prophylaxis was cost‐effective at cost‐effectiveness thresholds of US$300 and US$500 per QALY with an incremental cost‐effectiveness ratio (ICER) of US$157 per QALY in the CD4 <200 cells/mm3 population providing enhanced‐prophylaxis components are sourced at lowest available prices. The ICER reduced in more severely immunosuppressed individuals (US$113 per QALY in the CD4 <100 cells/mm3 population) and increased

Journal article

Jobarteh ML, McCrory MA, Lo B, Sun M, Sazonov E, Anderson AK, Jia W, Maitland K, Qiu J, Steiner-Asiedu M, Higgins JA, Baranowski T, Olupot-Olupot P, Frost Get al., 2020, Development and validation of objective, passive dietary assessment Method for estimating food and nutrient intake in households in Low and Middle-Income Countries (LMICs): a study protocol, Current Developments in Nutrition, Vol: 4, Pages: 1-11, ISSN: 2475-2991

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 members (including under-5s and adolescents) are assigned a wearable camera device to capture images of their food intake during waking hours. Using custom software, images captured are then used to estimate an individual's food and nutrient (i.e., protein, fat, carbohydrate, energy, and micronutrients) intake. Passive food image capture and assessment provides an objective measure of food and nutrient intake in real time, minimizing some of the limitations associated with self-reported dietary intake methods. Its use in LMIC could potentially increase the understanding of a population's nutritional status, and the contribution of household food intake to the malnutrition burden. This project is registered at clinicaltrials.gov (NCT03723460).

Journal article

George EC, Kiguli S, Olupot PO, Opoka RO, Engoru C, Akech SO, Nyeko R, Mtove G, Mpoya A, Thomason MJ, Crawley J, Evans JA, Gibb DM, Babiker AG, Maitland K, Walker ASet al., 2019, Mortality risk over time after early fluid resuscitation in African children, Critical Care (UK), Vol: 23, Pages: 1-9, ISSN: 1364-8535

BackgroundAfrican 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.MethodsIn a post hoc retrospective analysis, flexible parametric models were used to compare change in mortality risk post-randomisation in children allocated to bolus therapy with 20–40 ml/kg 5% albumin or 0.9% saline over 1–2 h or no bolus (control, 4 ml/kg/hour maintenance), overall and for different terminal clinical events (cardiogenic, neurological, respiratory, or unknown/other).ResultsTwo thousand ninety-seven and 1041 children were randomised to bolus vs no bolus, of whom 254 (12%) and 91 (9%) respectively died within 28 days. Median (IQR) bolus fluid in the bolus groups received by 4 h was 20 (20, 40) ml/kg and was the same at 8 h; total fluids received in bolus groups at 4 h and 8 h were 38 (28, 43) ml/kg and 40 (30, 50) ml/kg, respectively. Total fluid volumes received in the control group by 4 h and 8 h were median (IQR) 10 (6, 15) ml/kg and 10 (10, 26) ml/kg, respectively. Mortality risk was greatest 30 min post-randomisation in both groups, declining sharply to 4 h and then more slowly to 28 days. Maximum mortality risk was similar in bolus and no bolus groups; however, the risk declined more slowly in the bolus group, with significantly higher mortality risk compared to the no bolus group from 1.6 to 101 h (4 days) post-randomisation. The delay in decline in mortality risk in the bolus groups was most pronounced for cardiogenic modes of death.ConclusionsThe increased risk from bolus therapy was not due to a mechanism occurring immediately after bolus administration. Excess mortality risk in the bolus group resul

Journal article

Maitland K, Gibb DM, Babiker A, 2019, Secondary re-analysis of the FEAST trial, The Lancet Respiratory Medicine, Vol: 7, Pages: E29-E29, ISSN: 2213-2600

Journal article

Uyoga S, Macharia AW, Mochamah G, Ndila CM, Nyutu G, Makale J, Tendwa M, Nyatichi E, Ojal J, Otiende M, Shebe M, Awuondo KO, Mturi N, Peshu N, Tsofa B, Maitland K, Scott JAG, Williams TNet al., 2019, The epidemiology of sickle cell disease in children recruited in infancy in Kilifi, Kenya: a prospective cohort study., The Lancet Global Health, Vol: 7, Pages: e1458-e1466, ISSN: 2214-109X

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 sickle cell disease, who were resident within the Kilifi area of Kenya. METHODS: This prospective cohort study was done on members of the Kilifi Genetic Birth Cohort Study (KGBCS) on the Indian Ocean coast of Kenya. Recruitment to the study was facilitated through the Kilifi Health and Demographic Surveillance System (KHDSS), which covers a resident population of 260 000 people, and was undertaken between Jan 1, 2006, and April 30, 2011. All children who were born within the KHDSS area and who were aged 3-12 months during the recruitment period were eligible for inclusion. Participants were tested for sickle cell disease and followed up for survival status and disease-specific admission to Kilifi County Hospital by passive surveillance until their fifth birthday. Children with sickle cell disease were offered confirmatory testing and care at a dedicated outpatient clinic. FINDINGS: 15 737 infants were recruited successfully to the KGBCS, and 128 (0·8%) of these infants had sickle cell disease, of whom 70 (54·7%) enrolled at the outpatient clinic within 12 months of recruitment. Mortality was higher in children with sickle cell disease (58 per 1000 person-years of observation, 95% CI 40-86) than in those without sickle cell disease (2·4 per 1000 person-years of observation, 2·0-2·8; adjusted incidence rate ratio [IRR] 23·1, 95% CI 15·1-35·3). Among children with sickle cell disease, mortality was lower in those who enrolled at the clinic (adjusted IRR 0·26, 95% CI 0·11-0·62) and in those with higher levels of haemoglobin F (HbF; adjusted IRR 0·

Journal article

Maitland K, Olupot-Olupot P, Kiguli S, Chagaluka G, Alaroker F, Opoka RO, Mpoya A, Walsh K, Engoru C, Nteziyaremye J, Mallewa M, Kennedy N, Nakuya M, Namayanja C, Kayaga J, Nabawanuka E, Sennyondo T, Aromut D, Kumwenda F, Musika CW, Thomason MJ, Bates I, von Hensbroek MB, Evans JA, Uyoga S, Williams TN, Frost G, George EC, Gibb DM, Walker ASet al., 2019, Co-trimoxazole or multivitamin multimineral supplement for post-discharge outcomes after severe anaemia in African children: a randomised controlled trial, The Lancet Global Health, Vol: 7, Pages: e1435-e1447, ISSN: 2214-109X

BackgroundSevere 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.MethodsWithin the two-stratum, open-label, multicentre, factorial randomised TRACT trial, children aged 2 months to 12 years with severe anaemia, defined as haemoglobin of less than 6 g/dL, at admission to hospital (three in Uganda, one in Malawi) were randomly assigned, using sequentially numbered envelopes linked to a second non-sequentially numbered set of allocations stratified by centre and severity, to enhanced nutritional supplementation with iron and folate-containing multivitamin multimineral supplements versus iron and folate alone at treatment doses (usual care), and to co-trimoxazole versus no co-trimoxazole. All interventions were administered orally and were given for 3 months after discharge from hospital. Separately reported randomisations investigated transfusion management. The primary outcome was 180-day mortality. All analyses were done in the intention-to-treat population; follow-up was 180 days. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN84086586, and follow-up is complete.FindingsFrom Sept 17, 2014, to May 15, 2017, 3983 eligible children were randomly assigned to treatment, and followed up for 180 days. 164 (4%) were lost to follow-up. 1901 (95%) of 1997 assigned multivitamin multimineral supplement, 1911 (96%) of 1986 assigned iron and folate, and 1922 (96%) of 1994 assigned co-trimoxazole started treatment. By day 180, 166 (8%) children in the multivitamin multimineral supplement group versus 169 (9%) children in the iron and folate group had died (hazard ratio [HR] 0·97, 95% CI 0·79–1·21; p=0·81) and 172 (9%) who received co-trimoxazole versus 163 (8%) who did not receive co-trimoxazole h

Journal article

Maitland K, Ohuma EO, Mpoya A, Uyoga S, Hassall O, Williams TNet al., 2019, Informing thresholds for paediatric transfusion in Africa: the need for a trial [version 2; peer review: 2 approved], Wellcome open research, Vol: 4, Pages: 1-25, ISSN: 2398-502X

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 infection and/or transfusion. Methods: A retrospective analysis of standardised clinical digital records in an unselected population of children admitted to a rural hospital in Kenya over an 8-year period. We describe baseline parameters with respect to categories of anaemia and outcome (in-hospital death) by haemoglobin (Hb), malaria and transfusion status. Results: Among 29,226 children, 1,143 (3.9%) had profound anaemia (Hb <4g/dl) and 3,469 (11.9%) had severe anaemia (Hb 4-6g/d). In-hospital mortality rate was 97/1,143 (8.5%) if Hb<4g/dl or 164/2,326 (7.1%) in those with severe anaemia (Hb ≥4.0-<6g/dl). Admission Hb <3g/dl was associated with higher risk of death versus those with higher Hbs (OR=2.41 (95%CI: 1.8 - 3.24; P<0.001), increasing to OR=6.36, (95%CI: 4.21-9.62; P<0.001) in malaria positive children. Conversely, mortality in non-malaria admissions was unrelated to Hb level. Transfusion was associated with a non-significant improvement in outcome if Hb<3g/dl (malaria-only) OR 0.72 (95%CI 0.29 - 1.78), albeit the number of cases were too few to show a statistical difference. For those with Hb levels above 4g/dl, mortality was significantly higher in those receiving a transfusion compared to the non-transfused group. For non-malarial cases, transfusion did not affect survival-status, irrespective of baseline Hb level compared to children who were not transfused at higher Hb levels. Conclusion: Although severe anaemia is common among children admitted to hospital in sSA (~16%), our data do not indicate that outcome is improved by transfusion irrespective of malaria status. Given the limitations

Journal article

Maitland K, Ohuma E, Mpoya A, Uyoga S, Hassall O, Williams Tet al., 2019, Informing thresholds for paediatric transfusion in Africa: the need for a trial [version 2: peer review: 2 approved], Wellcome Open Research, Vol: 4, ISSN: 2398-502X

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 infection and/or transfusion. Methods : A retrospective analysis of standardised clinical digital records in an unselected population of children admitted to a rural hospital in Kenya over an 8-year period. We describe baseline parameters with respect to categories of anaemia and outcome (in-hospital death) by haemoglobin (Hb), malaria and transfusion status. Results : Among 29,226 children, 1,143 (3.9%) had profound anaemia (Hb <4g/dl) and 3,469 (11.9%) had severe anaemia (Hb 4-6g/d). In-hospital mortality rate was 97/1,143 (8.5%) if Hb<4g/dl or 164/2,326 (7.1%) in those with severe anaemia (Hb ≥4.0-<6g/dl). Admission Hb <3g/dl was associated with higher risk of death versus those with higher Hbs (OR=2.41 (95%CI: 1.8 - 3.24; P<0.001), increasing to OR=6.36, (95%CI: 4.21–9.62; P<0.001) in malaria positive children. Conversely, mortality in non-malaria admissions was unrelated to Hb level. Transfusion was associated with a non-significant improvement in outcome if Hb<3g/dl (malaria-only) OR 0.72 (95%CI 0.29 - 1.78), albeit the number of cases were too few to show a statistical difference. For those with Hb levels above 4g/dl, mortality was significantly higher in those receiving a transfusion compared to the non-transfused group. For non-malarial cases, transfusion did not affect survival-status, irrespective of baseline Hb level compared to children who were not transfused at higher Hb levels. Conclusion : Although severe anaemia is common among children admitted to hospital in sSA (~16%), our data do not indicate that outcome is improved by transfusion irrespective of malaria status. Given the li

Journal article

Maitland K, Olupot-Olupot P, Kiguli S, Chagaluka G, Alaroker F, Opoka RO, Mpoya A, Engoru C, Nteziyaremye J, Mallewa M, Kennedy N, Nakuya M, Namayanja C, Kayaga J, Uyoga S, Byabazaire DK, M'baya B, Wabwire B, Frost G, Bates I, Evans JA, Williams TN, Goncalves PS, George EC, Gibb DM, Walker ASet al., 2019, Transfusion Volume for Children with Severe Anemia in Africa, New England Journal of Medicine, Vol: 381, Pages: 420-431, ISSN: 0028-4793

BackgroundSevere 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.MethodsIn this factorial, open-label trial, we randomly assigned Ugandan and Malawian children 2 months to 12 years of age with a hemoglobin level of less than 6 g per deciliter and severity features (e.g., respiratory distress or reduced consciousness) to receive immediate blood transfusion with 20 ml per kilogram or 30 ml per kilogram. Three other randomized analyses investigated immediate as compared with no immediate transfusion, the administration of postdischarge micronutrients, and postdischarge prophylaxis with trimethoprim–sulfamethoxazole. The primary outcome was 28-day mortality.ResultsA total of 3196 eligible children (median age, 37 months; 2050 [64.1%] with malaria) were assigned to receive a transfusion of 30 ml per kilogram (1598 children) or 20 ml per kilogram (1598 children) and were followed for 180 days. A total of 1592 children (99.6%) in the higher-volume group and 1596 (99.9%) in the lower-volume group started transfusion (median, 1.2 hours after randomization). The mean (±SD) volume of total blood transfused per child was 475±385 ml and 353±348 ml, respectively; 197 children (12.3%) and 300 children (18.8%) in the respective groups received additional transfusions. Overall, 55 children (3.4%) in the higher-volume group and 72 (4.5%) in the lower-volume group died before 28 days (hazard ratio, 0.76; 95% confidence interval [CI], 0.54 to 1.08; P=0.12 by log-rank test). This finding masked significant heterogeneity in 28-day mortality according to the presence or absence of fever (>37.5°C) at screening (P=0.001 after Sidak correction). Among the 1943 children (60.8%) without fever, mortality was lower with

Journal article

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