38 results found
Heys M, Kesler E, Sassoon Y, et al., 2023, Development and implementation experience of a learning healthcare system for facility based newborn care in low resource settings: The Neotree, Learning Health Systems, Vol: 7, ISSN: 2379-6146
Introduction:Improving peri- and postnatal facility-based care in low-resource settings (LRS) could save over 6000 babies' lives per day. Most of the annual 2.4 million neonatal deaths and 2 million stillbirths occur in healthcare facilities in LRS and are preventable through the implementation of cost-effective, simple, evidence-based interventions. However, their implementation is challenging in healthcare systems where one in four babies admitted to neonatal units die. In high-resource settings healthcare systems strengthening is increasingly delivered via learning healthcare systems to optimise care quality, but this approach is rare in LRS.Methods:Since 2014 we have worked in Bangladesh, Malawi, Zimbabwe, and the UK to co-develop and pilot the Neotree system: an android application with accompanying data visualisation, linkage, and export. Its low-cost hardware and state-of-the-art software are used to support healthcare professionals to improve postnatal care at the bedside and to provide insights into population health trends. Here we summarise the formative conceptualisation, development, and preliminary implementation experience of the Neotree.Results:Data thus far from ~18 000 babies, 400 healthcare professionals in four hospitals (two in Zimbabwe, two in Malawi) show high acceptability, feasibility, usability, and improvements in healthcare professionals' ability to deliver newborn care. The data also highlight gaps in knowledge in newborn care and quality improvement. Implementation has been resilient and informative during external crises, for example, coronavirus disease 2019 (COVID-19) pandemic. We have demonstrated evidence of improvements in clinical care and use of data for Quality Improvement (QI) projects.Conclusion:Human-centred digital development of a QI system for newborn care has demonstrated the potential of a sustainable learning healthcare system to improve newborn care and outcomes in LRS. Pilot implementation evaluation is ongoin
Jullien S, Fitzgerald F, Keddie S, et al., 2022, Diagnostic accuracy of multiplex respiratory pathogen panels for influenza or respiratory syncytial virus infections: systematic review and meta-analysis, BMC Infectious Diseases, Vol: 22, ISSN: 1471-2334
Respiratory syncytial virus (RSV) and influenza viruses are important global causes of morbidity and mortality. We evaluated the diagnostic accuracy of the Luminex NxTAG respiratory pathogen panels (RPPs)™ (index) against other RPPs (comparator) for detection of RSV and influenza viruses. Studies comparing human clinical respiratory samples tested with the index and at least one comparator test were included. A random-effect latent class meta-analysis was performed to assess the specificity and sensitivity of the index test for RSV and influenza. Risk of bias was assessed using the QUADAS-2 tool and certainty of evidence using GRADE. Ten studies were included. For RSV, predicted sensitivity was 99% (95% credible interval [CrI] 96–100%) and specificity 100% (95% CrI 98–100%). For influenza A and B, predicted sensitivity was 97% (95% CrI 89–100) and 98% (95% CrI 88–100) respectively; specificity 100% (95% CrI 99–100) and 100% (95% CrI 99–100), respectively. Evidence was low certainty. Although index sensitivity and specificity were excellent, comparators’ performance varied. Further research with clear patient recruitment strategies could ascertain performance across different populations.
Chimhini G, Magwenzi M, Fitzgerald FC, 2022, Infection Prevention and Control in low-resource settings: the need for the local, the contextual and the pragmatic, Infection Prevention in Practice, Vol: 4, Pages: 1-2, ISSN: 2590-0889
Dramowski A, Aucamp M, Beales E, et al., 2022, Healthcare-associated infection prevention interventions for neonates in resource-limited settings, Frontiers in Pediatrics, Vol: 10, ISSN: 2296-2360
Healthcare-associated infections (HAIs) and antimicrobial-resistant (AMR) infections are leading causes of neonatal morbidity and mortality, contributing to an extended hospital stay and increased healthcare costs. Although the burden and impact of HAI/AMR in resource-limited neonatal units are substantial, there are few HAI/AMR prevention studies in these settings. We reviewed the mechanism of action and evidence supporting HAI/AMR prevention interventions, including care bundles, for hospitalized neonates in low- and middle-income countries (LMIC).
Wilson E, Gannon H, Chimhini G, et al., 2022, Protocol for an intervention development and pilot implementation evaluation study of an e-health solution to improve newborn care quality and survival in two low-resource settings, Malawi and Zimbabwe: Neotree., BMJ Open, Vol: 12, Pages: 1-8, ISSN: 2044-6055
INTRODUCTION: Every year 2.4 million deaths occur worldwide in babies younger than 28 days. Approximately 70% of these deaths occur in low-resource settings because of failure to implement evidence-based interventions. Digital health technologies may offer an implementation solution. Since 2014, we have worked in Bangladesh, Malawi, Zimbabwe and the UK to develop and pilot Neotree: an android app with accompanying data visualisation, linkage and export. Its low-cost hardware and state-of-the-art software are used to improve bedside postnatal care and to provide insights into population health trends, to impact wider policy and practice. METHODS AND ANALYSIS: This is a mixed methods (1) intervention codevelopment and optimisation and (2) pilot implementation evaluation (including economic evaluation) study. Neotree will be implemented in two hospitals in Zimbabwe, and one in Malawi. Over the 2-year study period clinical and demographic newborn data will be collected via Neotree, in addition to behavioural science informed qualitative and quantitative implementation evaluation and measures of cost, newborn care quality and usability. Neotree clinical decision support algorithms will be optimised according to best available evidence and clinical validation studies. ETHICS AND DISSEMINATION: This is a Wellcome Trust funded project (215742_Z_19_Z). Research ethics approvals have been obtained: Malawi College of Medicine Research and Ethics Committee (P.01/20/2909; P.02/19/2613); UCL (17123/001, 6681/001, 5019/004); Medical Research Council Zimbabwe (MRCZ/A/2570), BRTI and JREC institutional review boards (AP155/2020; JREC/327/19), Sally Mugabe Hospital Ethics Committee (071119/64; 250418/48). Results will be disseminated via academic publications and public and policy engagement activities. In this study, the care for an estimated 15 000 babies across three sites will be impacted. TRIAL REGISTRATION NUMBER: NCT0512707; Pre-results.
Chimhuya S, Neal SR, Chimhini G, et al., 2022, Indirect impacts of the COVID-19 pandemic at two tertiary neonatal units in Zimbabwe and Malawi: an interrupted time series analysis., BMJ Open, Vol: 12, Pages: 1-8, ISSN: 2044-6055
OBJECTIVES: To examine indirect impacts of the COVID-19 pandemic on neonatal care in low-income and middle-income countries. DESIGN: Interrupted time series analysis. SETTING: Two tertiary neonatal units in Harare, Zimbabwe and Lilongwe, Malawi. PARTICIPANTS: We included a total of 6800 neonates who were admitted to either neonatal unit from 1 June 2019 to 25 September 2020 (Zimbabwe: 3450; Malawi: 3350). We applied no specific exclusion criteria. INTERVENTIONS: The first cases of COVID-19 in each country (Zimbabwe: 20 March 2020; Malawi: 3 April 2020). PRIMARY OUTCOME MEASURES: Changes in the number of admissions, gestational age and birth weight, source of admission referrals, prevalence of neonatal encephalopathy, and overall mortality before and after the first cases of COVID-19. RESULTS: Admission numbers in Zimbabwe did not initially change after the first case of COVID-19 but fell by 48% during a nurses' strike (relative risk (RR) 0.52, 95% CI 0.41 to 0.66, p<0.001). In Malawi, admissions dropped by 42% soon after the first case of COVID-19 (RR 0.58, 95% CI 0.48 to 0.70, p<0.001). In Malawi, gestational age and birth weight decreased slightly by around 1 week (beta -1.4, 95% CI -1.62 to -0.65, p<0.001) and 300 g (beta -299.9, 95% CI -412.3 to -187.5, p<0.001) and outside referrals dropped by 28% (RR 0.72, 95% CI 0.61 to 0.85, p<0.001). No changes in these outcomes were found in Zimbabwe and no significant changes in the prevalence of neonatal encephalopathy or mortality were found at either site (p>0.05). CONCLUSIONS: The indirect impacts of COVID-19 are context-specific. While our study provides vital evidence to inform health providers and policy-makers, national data are required to ascertain the true impacts of the pandemic on newborn health.
Fitzgerald FC, Zingg W, Chimhini G, et al., 2022, The impact of interventions to prevent neonatal healthcare-associated infections in low- and middle-income countries: a systematic review., The Pediatric Infectious Disease Journal, Vol: 41, Pages: S26-S35, ISSN: 0891-3668
BACKGROUND: Clinically suspected and laboratory-confirmed bloodstream infections are frequent causes of morbidity and mortality during neonatal care. The most effective infection prevention and control interventions for neonates in low- and middle-income countries (LMIC) are unknown. AIM: To identify effective interventions in the prevention of hospital-acquired bloodstream infections in LMIC neonatal units. METHODS: Medline, PUBMED, the Cochrane Database of Systematic Reviews, EMBASE and PsychInfo (January 2003 to October 2020) were searched to identify studies reporting single or bundled interventions for prevention of bloodstream infections in LMIC neonatal units. RESULTS: Our initial search identified 5206 articles; following application of filters, 27 publications met the inclusion and Integrated Quality Criteria for the Review of Multiple Study Designs assessment criteria and were summarized in the final analysis. No studies were carried out in low-income countries, only 1 in Sub-Saharan Africa and just 2 in multiple countries. Of the 18 single-intervention studies, most targeted skin (n = 4) and gastrointestinal mucosal integrity (n = 5). Whereas emollient therapy and lactoferrin achieved significant reductions in proven neonatal infection, glutamine and mixed probiotics showed no benefit. Chlorhexidine gluconate for cord care and kangaroo mother care reduced infection in individual single-center studies. Of the 9 studies evaluating bundles, most focused on prevention of device-associated infections and achieved significant reductions in catheter- and ventilator-associated infections. CONCLUSIONS: There is a limited evidence base for the effectiveness of infection prevention and control interventions in LMIC neonatal units; bundled interventions targeting device-associated infections were most effective. More multisite studies with robust study designs are needed to inform infection prevention and control intervention strategies in low-resource neonatal units
George EC, Uyoga S, M'baya B, et al., 2022, Whole blood versus red cell concentrates for children with severe anaemia: a secondary analysis of the Transfusion and Treatment of African Children (TRACT) trial, The Lancet Global Health, Vol: 10, Pages: e360-e368, ISSN: 2214-109X
Background:The multicentre Transfusion and Treatment of African Children (TRACT) trial established best evidence on the timing of transfusion in children with uncomplicated anaemia (haemoglobin 4-6g/dl) and optimal volume (20 versus 30ml/kg whole blood (or 10 vs 15ml/kg red cell concentrates) for transfusion in children hospitalised with severe anaemia (Hb <6g/dl) on Day 28 mortality (primary endpoint) and secondary endpoints including safety. As evidence on the safety of blood components is limited we undertook a secondary analysis comparing children receiving whole blood versus red cell concentrates as their initial transfusion on clinical outcomes. Methods :This analysis includes 3188 children with severe anaemia (Hb <6g/dl) who received either whole blood or red cell concentrates. Whole blood or cell concentrates were issued routinely by the blood transfusion services, but not prespecified on the request form. The impact of blood pack type on haematological correction, re-transfusion, and other clinical endpoints was explored using multivariate regression models. Findings:1632/3992 (41%) transfusions in 3188 children were whole blood. Compared with whole blood, children receiving cell concentrates in their first transfusion had less haemoglobin recovery at 8 hours (packed cells mean(95%CI): -1.3(-1.5,-1.0) 20ml/kg arm,-1.4(-1.6,-1.1) 30ml/kg; settled cells mean(95%CI) -1.1g/dl(-1.2,-0.9) 20ml/kg arm, -1.5g/dl(-1.7,-1.3) 30ml/kg arm; p<0.001 for pack type comparisons, p=0.003 heterogeneity by arm), higher odds of receiving a second transfusion [ORs 2.32 (95%CI 1.30,4.12) and 2.97 (2.18,4.05) respectively; p<0.001], and had a longer time to discharge [sub-Hazard Ratios 0.94 (95%CI 0.81,1.10) and 0.86 (95% CI 0.79,0.94) respectively; p=0.002]. No child developed features of cardio-pulmonary overload. Interpretation: Whole blood is safe to use in children, resulting in superior aematologic
Chimhini G, Olaru ID, Fitzgerald F, et al., 2021, Evaluation of a Novel Culture System for Rapid Pathogen Identification and Detection of Cephalosporin Resistance in Neonatal Gram-negative Sepsis at a Tertiary Referral Unit in Harare, Zimbabwe, PEDIATRIC INFECTIOUS DISEASE JOURNAL, Vol: 40, Pages: 785-791, ISSN: 0891-3668
Evans M, Corden MH, Crehan C, et al., 2021, Refining clinical algorithms for a neonatal digital platform for low-income countries: a modified Delphi technique., BMJ Open, Vol: 11, Pages: e042124-e042124, ISSN: 2044-6055
OBJECTIVES: To determine whether a panel of neonatal experts could address evidence gaps in local and international neonatal guidelines by reaching a consensus on four clinical decision algorithms for a neonatal digital platform (NeoTree). DESIGN: Two-round, modified Delphi technique. SETTING AND PARTICIPANTS: Participants were neonatal experts from high-income and low-income countries (LICs). METHODS: This was a consensus-generating study. In round 1, experts rated items for four clinical algorithms (neonatal sepsis, hypoxic ischaemic encephalopathy, respiratory distress of the newborn, hypothermia) and justified their responses. Items meeting consensus for inclusion (≥80% agreement) were incorporated into the algorithms. Items not meeting consensus were either excluded, included following revisions or included if they contained core elements of evidence-based guidelines. In round 2, experts rated items from round 1 that did not reach consensus. RESULTS: Fourteen experts participated in round 1, 10 in round 2. Nine were from high-income countries, five from LICs. Experts included physicians and nurse practitioners with an average neonatal experience of 20 years, 12 in LICs. After two rounds, a consensus was reached on 43 of 84 items (52%). Per experts' recommendations, items in line with local and WHO guidelines yet not meeting consensus were still included to encourage consistency for front-line healthcare workers. As a result, the final algorithms included 53 items (62%). CONCLUSION: Four algorithms in a neonatal digital platform were reviewed and refined by consensus expert opinion. Revisions to NeoTree will be made in response to these findings. Next steps include clinical validation of the algorithms.
Gannon H, Chimhuya S, Chimhini G, et al., 2021, Electronic application to improve management of infections in low-income neonatal units: pilot implementation of the NeoTree beta app in a public sector hospital in Zimbabwe, BMJ Open Quality, Vol: 10, ISSN: 2399-6641
There are 2. 4 million annual neonatal deaths worldwide. Simple, evidence-based interventions such as temperature control could prevent approximately two-thirds of these deaths. However, key problems in implementing these interventions are a lack of newborn-trained healthcare workers and a lack of data collection systems. NeoTree is a digital platform aiming to improve newborn care in low-resource settings through real-time data capture and feedback alongside education and data linkage. This project demonstrates proof of concept of the NeoTree as a real-time data capture tool replacing handwritten clinical paper notes over a 9-month period in a tertiary neonatal unit at Harare Central Hospital, Zimbabwe. We aimed to deliver robust data for monthly mortality and morbidity meetings and to improve turnaround time for blood culture results among other quality improvement indicators. There were 3222 admissions and discharges entered using the NeoTree software with 41 junior doctors and 9 laboratory staff trained over the 9-month period. The NeoTree app was fully integrated into the department for all admission and discharge documentation and the monthly presentations became routine, informing local practice. An essential factor for this success was local buy-in and ownership at each stage of the project development, as was monthly data analysis and presentations allowing us to rapidly troubleshoot emerging issues. However, the laboratory arm of the project was negatively affected by nationwide economic upheaval. Our successes and challenges piloting this digital tool have provided key insights for effective future roll-out in Zimbabwe and other low-income healthcare settings.
Herbec A, Chimhini G, Rosenberg-Pacareu J, et al., 2020, Barriers and facilitators to infection prevention and control in a neonatal unit in Zimbabwe - a theory-driven qualitative study to inform design of a behaviour change intervention, JOURNAL OF HOSPITAL INFECTION, Vol: 106, Pages: 804-811, ISSN: 0195-6701
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Olaru ID, Meierkord A, Godman B, et al., 2020, Assessment of antimicrobial use and prescribing practices among pediatric inpatients in Zimbabwe., Journal of Chemotherapy, Vol: 32, Pages: 456-459, ISSN: 1973-9478
This study aims to assess antimicrobial consumption in the pediatric department of a tertiary care public hospital in Zimbabwe. Clinical records of pediatric inpatients admitted to Harare Central Hospital over a 3-week period were reviewed prospectively. Antimicrobial consumption was described as days of therapy per 100 inpatient days (DOT/100 PD). Adherence of antimicrobial drug prescriptions to the National Guidelines was also evaluated. A total of 121 (93.1%) children were prescribed at least one antimicrobial out of 130 children admitted. The median age was 14 months (IQR: 3 - 48 months). Overall antimicrobial consumption was 155.4 DOT/100 PD (95% CI 146-165.2). The most frequently prescribed antimicrobials were benzylpenicillin, gentamicin and ceftriaxone. Prescriptions were adherent to national guidelines in 57.7% of children. This study shows that there is high antimicrobial drug usage in hospitalized children in Zimbabwe and a considerable proportion of prescriptions are non-adherent with national guidelines.
Neal SR, Musorowegomo D, Gannon H, et al., 2020, Clinical prediction models to diagnose neonatal sepsis: a scoping review protocol., BMJ Open, Vol: 10, Pages: 1-5, ISSN: 2044-6055
INTRODUCTION: Neonatal sepsis is responsible for significant morbidity and mortality worldwide. Diagnosis is often difficult due to non-specific clinical features and the unavailability of laboratory tests in many low-income and middle-income countries (LMICs). Clinical prediction models have the potential to improve diagnostic accuracy and rationalise antibiotic usage in neonatal units, which may result in reduced antimicrobial resistance and improved neonatal outcomes. In this paper, we outline our scoping review protocol to map the literature concerning clinical prediction models to diagnose neonatal sepsis. We aim to provide an overview of existing models and evidence underlying their use and compare prediction models between high-income countries and LMICs. METHODS AND ANALYSIS: The protocol was developed with reference to recommendations by the Joanna Briggs Institute. Searches will include six electronic databases (Ovid MEDLINE, Ovid Embase, Scopus, Web of Science, Global Index Medicus and the Cochrane Library) supplemented by hand searching of reference lists and citation analysis on included studies. No time period restrictions will be applied but only studies published in English or Spanish will be included. Screening and data extraction will be performed independently by two reviewers, with a third reviewer used to resolve conflicts. The results will be reported by narrative synthesis in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines. ETHICS AND DISSEMINATION: The nature of the scoping review methodology means that this study does not require ethical approval. Results will be disseminated through peer-reviewed publications and conference presentations, as well as through engagement with peers and relevant stakeholders.
Chimhini G, Chimhuya S, Madzudzo L, et al., 2020, Auditing use of antibiotics in Zimbabwean neonates, Infection Prevention in Practice, Vol: 2, ISSN: 2590-0889
BACKGROUND: Neonatal sepsis is a major cause of morbidity and mortality in low-income settings. As signs of sepsis are non-specific and deterioration precipitous, antibiotics are often used profusely in these settings where diagnostics may not be readily available. Harare Central Hospital, Zimbabwe, delivers 12000 babies per annum admitting ∼4800 to the neonatal unit. Overcrowding, understaffing and rapid staff turnover are consistent problems. Suspected sepsis is highly prevalent, and antibiotics widely used. We audited the impact of training and benchmarking intervention on rationalizing antibiotic prescription using local, World Health Organization-derived, guidelines as the standard. METHODS: An initial audit of admission diagnosis and antibiotic use was performed between 8th May - 6th June 2018 as per the audit cycle. An intern training programme, focusing on antimicrobial stewardship and differentiating between babies 'at risk of' versus 'with' clinically-suspected sepsis was instituted post-primary audit. Re-audit was conducted after 5 months. RESULTS: Sepsis was the most common admitting diagnosis by interns at both time points but reduced at repeat audit (81% versus 59%, P<0.0001). Re-audit after 5 months demonstrated a decrease in antibiotic prescribing at admission and discharge. Babies prescribed antibiotics at admission decreased from 449 (98%) to 96 (51%), P<0.0001. Inpatient days of therapy (DOT) reduced from 1243 to 1110/1000 patient-days. Oral amoxicillin prescription at discharge reduced from 349/354 (99%) to 1% 1/161 (P<0.0001). CONCLUSION: A substantial decrease in antibiotic use was achieved by performance feedback, training and leadership, although ongoing performance review will be key to ensuring safety and sustainability.
Evans C, Fitzgerald F, Cunnington A, 2019, Review of UK malaria treatment guidelines 2016 (Public Health England Advisory Committee on Malaria Prevention), Archives of Disease in Childhood: Education and Practice Edition, Vol: 104, Pages: 218-220, ISSN: 1743-0585
Fitzgerald FC, Lhomme E, Harris K, et al., 2019, Microbial translocation does not drive immune activation in Ugandan children infected with HIV, Journal of Infectious Diseases, Vol: 219, Pages: 89-100, ISSN: 0022-1899
Objective: Immune activation is associated with morbidity and mortality during human immunodeficiency virus (HIV) infection, despite receipt of antiretroviral therapy (ART). We investigated whether microbial translocation drives immune activation in HIV-infected Ugandan children. Methods: Nineteen markers of immune activation and inflammation were measured over 96 weeks in HIV-infected Ugandan children in the CHAPAS-3 Trial and HIV-uninfected age-matched controls. Microbial translocation was assessed using molecular techniques, including next-generation sequencing. Results: Of 249 children included, 142 were infected with HIV; of these, 120 were ART naive, with a median age of 2.8 years (interquartile range [IQR], 1.7-4.0 years) and a median baseline CD4+ T-cell percentage of 20% (IQR, 14%-24%), and 22 were ART experienced, with a median age of 6.5 years (IQR, 5.9-9.2 years) and a median baseline CD4+ T-cell percentage of 35% (IQR, 31%-39%). The control group comprised 107 children without HIV infection. The median increase in the CD4+ T-cell percentage was 17 percentage points (IQR, 12-22 percentage points) at week 96 among ART-naive children, and the viral load was <100 copies/mL in 76% of ART-naive children and 91% of ART-experienced children. Immune activation decreased with ART use. Children could be divided on the basis of immune activation markers into the following 3 clusters: in cluster 1, the majority of children were HIV uninfected; cluster 2 comprised a mix of HIV-uninfected children and HIV-infected ART-naive or ART-experienced children; and in cluster 3, the majority were ART naive. Immune activation was low in cluster 1, decreased in cluster 3, and persisted in cluster 2. Blood microbial DNA levels were negative or very low across groups, with no difference between clusters except for Enterobacteriaceae organisms (the level was higher in cluster 1; P < .0001). Conclusion: Immune activation decreased with ART use, with marker clustering indicatin
Howlett PJ, Walder AR, Lisk DR, et al., 2018, Case series of severe neurologic sequelae of Ebola Virus Disease during epidemic, Sierra Leone., Emerging Infectious Diseases, Vol: 24, Pages: 1412-1421, ISSN: 1080-6040
We describe a case series of 35 Ebola virus disease (EVD) survivors during the epidemic in West Africa who had neurologic and accompanying psychiatric sequelae. Survivors meeting neurologic criteria were invited from a cohort of 361 EVD survivors to attend a preliminary clinic. Those whose severe neurologic features were documented in the preliminary clinic were referred for specialist neurologic evaluation, ophthalmologic examination, and psychiatric assessment. Of 35 survivors with neurologic sequelae, 13 had migraine headache, 2 stroke, 2 peripheral sensory neuropathy, and 2 peripheral nerve lesions. Of brain computed tomography scans of 17 patients, 3 showed cerebral and/or cerebellar atrophy and 2 confirmed strokes. Sixteen patients required mental health followup; psychiatric disorders were diagnosed in 5. The 10 patients who experienced greatest disability had co-existing physical and mental health conditions. EVD survivors may have ongoing central and peripheral nervous system disorders, including previously unrecognized migraine headaches and stroke.
Post FA, Szubert AJ, Prendergast AJ, et al., 2018, Causes and timing of mortality and morbidity smong late presenters dtarting antiretroviral therapy in the REALITY trial, Clinical Infectious Diseases, Vol: 66, Pages: S132-S139, ISSN: 1058-4838
BackgroundIn sub-Saharan Africa, 20%–25% of people starting antiretroviral therapy (ART) have severe immunosuppression; approximately 10% die within 3 months. In the Reduction of EArly mortaLITY (REALITY) randomized trial, a broad enhanced anti-infection prophylaxis bundle reduced mortality vs cotrimoxazole. We investigate the contribution and timing of different causes of mortality/morbidity.MethodsParticipants started ART with a CD4 count <100 cells/µL; enhanced prophylaxis comprised cotrimoxazole plus 12 weeks of isoniazid + fluconazole, single-dose albendazole, and 5 days of azithromycin. A blinded committee adjudicated events and causes of death as (non–mutually exclusively) tuberculosis, cryptococcosis, severe bacterial infection (SBI), other potentially azithromycin-responsive infections, other events, and unknown.ResultsMedian pre-ART CD4 count was 37 cells/µL. Among 1805 participants, 225 (12.7%) died by week 48. Fatal/nonfatal events occurred early (median 4 weeks); rates then declined exponentially. One hundred fifty-four deaths had single and 71 had multiple causes, including tuberculosis in 4.5% participants, cryptococcosis in 1.1%, SBI in 1.9%, other potentially azithromycin-responsive infections in 1.3%, other events in 3.6%, and unknown in 5.0%. Enhanced prophylaxis reduced deaths from cryptococcosis and unknown causes (P < .05) but not tuberculosis, SBI, potentially azithromycin-responsive infections, or other causes (P > .3); and reduced nonfatal/fatal tuberculosis and cryptococcosis (P < .05), but not SBI, other potentially azithromycin-responsive infections, or other events (P > .2).ConclusionsEnhanced prophylaxis reduced mortality from cryptococcosis and unknown causes and nonfatal tuberculosis and cryptococcosis. High early incidence of fatal/nonfatal events highlights the need for starting enhanced-prophylaxis with ART in advanced disease.
Siika A, McCabe L, Bwakura-Dangarembizi M, et al., 2018, Late presentation with HIV in Africa: phenotypes, risk, and risk stratification in the REALITY trial, Clinical Infectious Diseases, Vol: 66, Pages: S140-S146, ISSN: 1058-4838
© 2018 World Health Organization. Background. Severely immunocompromised human immunodefciency virus (HIV)-infected individuals have high mortality shortly afer starting antiretroviral therapy (ART). We investigated predictors of early mortality and "late presenter" phenotypes. Methods. Te Reduction of EArly MortaLITY (REALITY) trial enrolled ART-naive adults and children =5 years of age with CD4 counts < 100 cells/μL initiating ART in Uganda, Zimbabwe, Malawi, and Kenya. Baseline predictors of mortality through 48 weeks were identifed using Cox regression with backwards elimination (exit P > .1). Results. Among 1711 included participants, 203 (12%) died. Mortality was independently higher with older age; lower CD4 count, albumin, hemoglobin, and grip strength; presence of World Health Organization stage 3/4 weight loss, fever, or vomiting; and problems with mobility or self-care at baseline (all P < .04). Receiving enhanced antimicrobial prophylaxis independently reduced mortality (P =.02). Of fve late-presenter phenotypes, Group 1 (n = 355) had highest mortality (25%; median CD4 count, 28 cells/μL), with high symptom burden, weight loss, poor mobility, and low albumin and hemoglobin. Group 2 (n = 394; 11% mortality; 43 cells/μL) also had weight loss, with high white cell, platelet, and neutrophil counts suggesting underlying inflammation/infection. Group 3 (n = 218; 10% mortality) had low CD4 counts (27 cells/μL), but low symptom burden and maintained fat mass. Te remaining groups had 4%-6% mortality. Conclusions. Clinical and laboratory features identifed groups with highest mortality following ART initiation. A screening tool could identify patients with low CD4 counts for prioritizing same-day ART initiation, enhanced prophylaxis, and intensive follow-up.
Fitzgerald F, Wing K, Naveed A, et al., 2018, Development of a pediatric Ebola predictive score, Sierra Leone, Emerging Infectious Diseases, Vol: 24, Pages: 311-319, ISSN: 1080-6040
We compared children who were positive for Ebola virus disease (EVD) with those who were negative to derive a pediatric EVD predictor (PEP) score. We collected data on all children <13 years of age admitted to 11 Ebola holding units in Sierra Leone during August 2014-March 2015 and performed multivariable logistic regression. Among 1,054 children, 309 (29%) were EVD positive and 697 (66%) EVD negative, with 48 (5%) missing. Contact history, conjunctivitis, and age were the strongest positive predictors for EVD. The PEP score had an area under receiver operating characteristics curve of 0.80. A PEP score of 7/10 was 92% specific and 44% sensitive; 3/10 was 30% specific, 94% sensitive. The PEP score could correctly classify 79%-90% of children and could be used to facilitate triage into risk categories, depending on the sensitivity or specificity required.
, 2018, Ebola Virus Disease, Publisher: Springer International Publishing, ISBN: 9783319948539
Patel A, Harris KA, Fitzgerald F, 2017, What is broad-range 16S rDNA PCR?, Archives of Disease in Childhood: Education and Practice Edition, Vol: 102, Pages: 261-264, ISSN: 1743-0585
Hakim J, Musiime V, Szubert AJ, et al., 2017, Enhanced prophylaxis plus antiretroviral therapy for advanced HIV infection in Africa, New England Journal of Medicine, Vol: 377, Pages: 233-245, ISSN: 0028-4793
BACKGROUNDIn sub-Saharan Africa, among patients with advanced human immunodeficiency virus (HIV)infection, the rate of death from infection (including tuberculosis and cryptococcus) shortlyafter the initiation of antiretroviral therapy (ART) is approximately 10%.METHODSIn this factorial open-label trial conducted in Uganda, Zimbabwe, Malawi, and Kenya, weenrolled HIV-infected adults and children 5 years of age or older who had not received previousART and were starting ART with a CD4+ count of fewer than 100 cells per cubic millimeter.They underwent simultaneous randomization to receive enhanced antimicrobialprophylaxis or standard prophylaxis, adjunctive raltegravir or no raltegravir, and supplementaryfood or no supplementary food. Here, we report on the effects of enhanced antimicrobialprophylaxis, which consisted of continuous trimethoprim–sulfamethoxazole plus atleast 12 weeks of isoniazid–pyridoxine (coformulated with trimethoprim–sulfamethoxazolein a single fixed-dose combination tablet), 12 weeks of fluconazole, 5 days of azithromycin,and a single dose of albendazole, as compared with standard prophylaxis (trimethoprim–sulfamethoxazole alone). The primary end point was 24-week mortality.RESULTSA total of 1805 patients (1733 adults and 72 children or adolescents) underwent randomizationto receive either enhanced prophylaxis (906 patients) or standard prophylaxis (899 patients)and were followed for 48 weeks (loss to follow-up, 3.1%). The median baseline CD4+count was 37 cells per cubic millimeter, but 854 patients (47.3%) were asymptomatic ormildly symptomatic. In the Kaplan–Meier analysis at 24 weeks, the rate of death with enhancedprophylaxis was lower than that with standard prophylaxis (80 patients [8.9% vs. 108[12.2%]; hazard ratio, 0.73; 95% confidence interval [CI], 0.55 to 0.98; P=0.03); 98 patients(11.0%) and 127 (14.4%), respectively, had died by 48 weeks (hazard ratio, 0.76; 95% CI, 0.58to 0.99; P=0.04). Patients in the
Fitzgerald F, Wing K, Naveed A, et al., 2017, Risk in the "Red Zone": outcomes for children admitted to Ebola holding units in Sierra Leone without Ebola virus disease, Clinical Infectious Diseases, Vol: 65, Pages: 162-165, ISSN: 1058-4838
We collected data on 1054 children admitted to Ebola Holding Units in Sierra Leone and describe outcomes of 697/1054 children testing negative for Ebola virus disease (EVD) and accompanying caregivers. Case-fatality was 9%; 3/630 (0.5%) children discharged testing negative were readmitted EVD-positive. Nosocomial EVD transmission risk may be lower than feared.
Fitzgerald F, Baion DE, Wing K, et al., 2017, The predicament of patients with suspected Ebola, The Lancet Global Health, Vol: 5, Pages: e659-e659, ISSN: 2214-109X
Nambiar B, Hargreaves DS, Morroni C, et al., 2017, Improving health-care quality in resource-poor settings, Bulletin of the World Health Organization, Vol: 95, Pages: 76-78, ISSN: 0042-9686
Improvements in health-care quality can contribute to healthier populations. However, many global and national health strategies are not sufficiently considering the issues of measuring and improving health-care quality in low-resource settings.1 The barriers to delivering high-quality care are often similar across different health systems. However, the extent and mechanisms through which these barriers affect quality improvement interventions may be different in resource-poor settings.2 Investments in health systems strengthening without continuous quality improvement is thought to be a useless effort.3 Conversely, only focusing on quality improvement in a resource-poor context without engaging the broader health system for support is of limited value. Hence, both areas must be improved simultaneously.
Fitzgerald F, Naveed A, Wing K, et al., 2016, Ebola virus disease in children, Sierra Leone, 2014-2015., Emerging Infectious Diseases, Vol: 22, Pages: 1769-1777, ISSN: 1080-6040
Little is known about potentially modifiable factors in Ebola virus disease in children. We undertook a retrospective cohort study of children <13 years old admitted to 11 Ebola holding units in the Western Area, Sierra Leone, during 2014-2015 to identify factors affecting outcome. Primary outcome was death or discharge after transfer to Ebola treatment centers. All 309 Ebola virus-positive children 2 days-12 years old were included; outcomes were available for 282 (91%). Case-fatality was 57%, and 55% of deaths occurred in Ebola holding units. Blood test results showed hypoglycemia and hepatic/renal dysfunction. Death occurred swiftly (median 3 days after admission) and was associated with younger age and diarrhea. Despite triangulation of information from multiple sources, data availability was limited, and we identified no modifiable factors substantially affecting death. In future Ebola virus disease epidemics, robust, rapid data collection is vital to determine effectiveness of interventions for children.
Fitzgerald F, Awonuga W, Shah T, et al., 2016, Ebola response in Sierra Leone: The impact on children, 13th Hot Topics in Infection and Immunity in Children Meeting, Publisher: W B SAUNDERS CO LTD, Pages: S6-S12, ISSN: 0163-4453
Fitzgerald F, Yeung S, Gibb DM, et al., 2015, Ebola vaccination, LANCET, Vol: 386, Pages: 2478-2478, ISSN: 0140-6736
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