Browsing by Author "Queen Elizabeth Central Hospital Malawi"

Filter results by typing the first few letters
Now showing 1 - 7 of 7
  • No Thumbnail Available
    PublicationMetadata only
    ChloS-HRM, a novel assay to identify chloramphenicol-susceptible Escherichia coli and Klebsiella pneumoniae in Malawi
    (2019-01-01) Christopher T. Williams; Patrick Musicha; Nicholas A. Feasey; Emily R. Adams; Thomas Edwards; Queen Elizabeth Central Hospital Malawi; Liverpool School of Tropical Medicine; Mahidol University; Nuffield Department of Clinical Medicine
    © 2019 The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. Objectives: Chloramphenicol is a broad-spectrum antimicrobial widely available in sub-Saharan Africa. With susceptibility re-emerging among Enterobacteriaceae in Blantyre, Malawi, we designed and evaluated a new high-resolution melt (HRM) RT-PCR assay, ChloS-HRM, to identify chloramphenicol-susceptible infections in a hospital setting. Methods: Seventy-two previously whole-genome sequenced isolates of Escherichia coli and Klebsiella pneumoniae from the Queen Elizabeth Central Hospital, Malawi, were subjected to determination of chloramphenicol MICs. Primers were designed to detect 18 chloramphenicol resistance genes that produce seven distinct peaks correlating with different gene groups (catA1, catA2, catA3, catB2, catB group 3, cmlA and floR) following HRM analysis. ChloS-HRM results were compared with MIC and WGS results. Results: ChloS-HRM correctly identified 15 of 17 phenotypically susceptible isolates and 54 of 55 resistant isolates, giving an accuracy of 88% in identifying susceptibility and 98% in identifying resistance. WGS identified 16 of 17 susceptible and 54 of 55 resistant isolates, giving an accuracy of 94% in identifying susceptibility and 98% in identifying resistance. The single false-susceptible result had no detectable gene by ChloS-HRM or WGS. Compared with WGS, ChloS-HRM had 100% sensitivity and specificity for catA (catA1-3), cmlA and floR, and 96% specificity for catB; sensitivity could not be estimated due to the lack of catB in the clinical sample collection. The overall agreement between MIC and HRM was 96% and between MIC and WGS it was 97%. Conclusions: ChloS-HRM could support antimicrobial stewardship in enabling de-escalation from third-generation cephalosporins by identifying chloramphenicol-susceptible infections. This would be valuable in areas with chloramphenicol-susceptible MDR and XDR Enterobacteriaceae.
  • No Thumbnail Available
    PublicationMetadata only
    Goal directed therapy for suspected acute bacterial meningitis in adults and adolescents in sub-Saharan Africa
    (2017-10-01) Emma C. Wall; Mavuto Mukaka; Brigitte Denis; Veronica S. Mlozowa; Malango Msukwa; Khumbo Kasambala; Mulinda Nyrienda; Theresa J. Allain; Brian Faragher; Robert S. Heyderman; David G. Lalloo; Malawi-Liverpool-Wellcome Trust Clinical Research Programme; Liverpool School of Tropical Medicine; UCL; Mahidol University; Nuffield Department of Clinical Medicine; Queen Elizabeth Central Hospital Malawi; University of Malawi College of Medicine
    © 2017 Wall et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background: Mortality from acute bacterial meningitis (ABM) in sub-Saharan African adults and adolescents exceeds 50%. We tested if Goal Directed Therapy (GDT) was feasible for adults and adolescents with clinically suspected ABM in Malawi. Materials and methods: Sequential patient cohorts of adults and adolescents with clinically suspected ABM were recruited in the emergency department of a teaching hospital in Malawi using a before/after design. Routine care was monitored in year one (P1). In year two (P2), nurses delivered protocolised GDT (rapid antibiotics, airway support, oxygenation, seizure control and fluid resuscitation) to a second cohort. The primary endpoint was composite mean number of clinical goals attained. Secondary endpoints were individual goals attained and death or disability from proven or probable ABM at day 40. Results: 563 patients with suspected ABM were enrolled in the study; 273 were monitored in P1; 290 patients with suspected ABM received GDT in P2. 61% were male, median age 33 years and 90% were HIV co-infected. ABM was proven or probable in 132 (23%) patients. GDT attained more clinical goals compared to routine care: composite mean number of goals in P1 was 055 vs. 157 in P2 GDT (p<0001); Death or disability by day 40 from proven or probable ABM occurred in 29/57 (51%) in P1 and 38/60 (63%) in P2 (p = 019). Conclusion: Nurse-led GDT in a resource-constrained setting was associated with improved delivery of protocolised care. Outcome was unaffected. Trial registration: www.isrctn.com ISRCTN96218197.
  • No Thumbnail Available
    PublicationMetadata only
    Initiating a network to support engagement between health researchers and schools: Recommendations from an international meeting of schools engagement practitioners held in Kilifi, Kenya
    (2020-01-01) Alun Davies; Grace Mwango; Bernard Appiah; James J. Callery; Vu Duy Thanh; Nozibusiso Gumede; Robert Inglis; Shane McCracken; Kestern Mkoola; Kagisho Montjane; Alice Ochanda; Charity Shonai; Kathryn Woods-Townsend; Faculty of Social Sciences; Oxford University Clinical Research Unit; Queen Elizabeth Central Hospital Malawi; Kenya Medical Research Institute; Texas A&M University; Mahidol University; Nuffield Department of Medicine; University Hospital Southampton NHS Foundation Trust; University of Cape Town; Science CEO Academy; Science Spaza an initiative of Jive Media Africa; Zimbabwe Early Intervention in Psychosis; Centre for Science and Health Communication; Gallomanor Communications Ltd; Africa Regional Office
    © 2020 Davies A et al. Engagement between health researchers and local schools, or School Engagement, has become incorporated into the engagement strategies of many research institutions worldwide. Innovative initiatives have emerged within Wellcome Trust-funded African and Asian Programmes (APPs) and elsewhere, and continued funding from the Wellcome Trust and other funders is likely to catalyse further innovation. Engagement between scientists and schools is well-described in the scientific literature (1-4), however, engagement between health researchers and schools is much newer, particularly in sub-Saharan Africa, and rarely documented. In November 2018 the KEMRI-Wellcome Trust Research Programme (KWTRP) hosted an international workshop in Kilifi, Kenya, drawing on an emerging community of School Engagement practitioners towards exploring the broad range of goals for School Engagement, learning about the breadth of evaluation approaches and exploring the potential usefulness of establishing a practitioner network. The workshop was attended by 29 engagement researchers/practitioners representing 21 institutions from 10 countries in sub-Saharan Africa and South East Asia and the UK. Workshop sessions combining small group discussions with plenary presentations, enabled a range of goals, activities and evaluation approaches to be shared. This report summarises these discussions, and shares participant views on the possible functions of a network of School Engagement practitioners. A breadth of 'deep' and 'wide' engagement activities were described addressing four broad goals: contributing to science education; capacity strengthening for health research; contributing to goals of community engagement; and health promotion. While wide approaches have greater outreach for raising student awareness, deeper approaches are more likely enable informed student views to be incorporated into research. All activities ultimately aimed at improving health, but also at supporting development in low- and middle-income countries through promoting science-career uptake. Participants identified a range of potential benefits which could emerge from a practitioner network: sharing experiences and resources; facilitating capacity strengthening; and fostering collaboration
  • No Thumbnail Available
    PublicationMetadata only
    Kaposi sarcoma risk in HIV-infected children and adolescents on combination antiretroviral therapy from sub-Saharan Africa, Europe, and Asia
    (2016-11-01) Eliane Rohner; Kurt Schmidlin; Marcel Zwahlen; Rana Chakraborty; Gary Clifford; Niels Obel; Sophie Grabar; Annelies Verbon; Antoni Noguera-Julian; Ali Judd; Intira Jeannie Collins; Pablo Rojo; Norbert Brockmeyer; Maria Campbell; Geneviève Chene; Hans Prozesky; Brian Eley; D'Cristina Stefan; Alan Davidson; Cleophas Chimbetete; Shobna Sawry; Mary Ann Davies; Azar Kariminia; Ung Vibol; Annette Sohn; Matthias Egger; Julia Bohlius; Frank Tanser; Michael Vinikoor; Eusebio Macete; Robin Wood; Kathryn Stinson; Daniela Garone; Geoffrey Fatti; Sam Phiri; Janet Giddy; Kennedy Malisita; Christiane Fritz; Michael Hobbins; Kamelia Kamenova; Matthew Fox; Karl Technau; Robert Zangerle; Giota Touloumi; Josiane Warszawski; Laurence Meyer; François Dabis; Murielle Mary Krause; Jade Ghosn; Catherine Leport; Linda Wittkop; Peter Reiss; Ferdinand Wit; Maria Prins; Heiner Bucher; Caroline Sabin; Diana Gibb; Gerd Fätkenheuer; Julia Del Amo; Claire Thorne; Amanda Mocroft; Ole Kirk; Christoph Stephan; Santiago Pérez-Hoyos; Osamah Hamouda; Barbara Bartmeyer; Nikoloz Chkhartishvili; Andrea Antinori; Antonella D.Arminio Monforte; Luis Prieto; Antoni Soriano-Arandes; Manuel Battegay; Roger Kouyos; Cristina Mussini; Pat Tookey; Jordi Casabona; Jose M. Miró; Antonella Castagna; Deborah Konopnick; Tessa Goetghebuer; Anders Sönnerborg; Carlo Torti; Ramon Teira; Myriam Garrido; David Haerry; Stéphane De Wit; Dominique Costagliola; Dorthe Raben; Diana Barger; Christine Schwimmer; Monique Termote; Casper Frederiksen; Nina Friis-Møller; Juan Berenguer; Vincent Bouteloup; Alessandro Cozzi-Lepri; Maria Dorrucci; University of KwaZulu-Natal; Centre for Infectious Disease Research in Zambia; Centro de Investigação em Saúde de Manhiça; Desmond Tutu HIV Centre (Gugulethu and Masiphumelele clinics); Médecins Sans Frontières Khayelitsha; Kheth'Impilo Programme; Lighthouse Trust; McCord Hospital; Newlands Clinic; Queen Elizabeth Central Hospital Malawi; University of Cape Town; SolidarMed SMART Programme; SolidarMed SMART Programme; SolidarMed SMART Programme; Themba Lethu Clinic; Tygerberg Hospital; Rahima Moosa Mother and Child Hospital; Baragwanath Hospital; AHIVCOS; AMACS; ANRS CO1 EPF/ANRS CO11 OBSERVATOIRE EPF; ANRS CO2 SEROCO; ANRS CO3 AQUITAINE; ANRS CO4 FHDH; ANRS CO6 PRIMO; ANRS CO8 COPILOTE; ANRS CO13 HEPAVIH; ATHENA; Cascade; UK CHIC; CHIPS; Cologne-Bonn; CoRIS; Danish HIV Cohort; ECS; EuroSIDA; GEMES-Haemo; German ClinSurv; Georgian National HIV/AIDS; CORISPE-cat; ICC; ICONA; KOMPNET; Madrid PMTCT Cohort; CORISPES-Madrid; NENEXP; SHCS; Modena Cohort; NSHPC; PISCIS; St. Pierre Cohort; St Pierre Paediatric Cohort; Swedish InfCare; The Italian Master Cohort; VACH; European AIDS Treatment Group; Centre Hospitalier Universitaire Saint Pierre, Brussels; FHDH; Copenhagen Regional Coordinating Centre; Bordeaux Regional Coordinating Centre; Paediatric Cohort Representatives; Bordeaux RCC; Copenhagen RCC; National Hospital of Pediatrics Hanoi
    © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. Background. The burden of Kaposi sarcoma (KS) in human immunodeficiency virus (HIV)-infected children and adolescents on combination antiretroviral therapy (cART) has not been compared globally. Methods. We analyzed cohort data from the International Epidemiologic Databases to Evaluate AIDS and the Collaboration of Observational HIV Epidemiological Research in Europe.We included HIV-infected children aged <16 years at cART initiation from 1996 onward. We used Cox models to calculate hazard ratios (HRs), adjusted for region and origin, sex, cART start year, age, and HIV/AIDS stage at cART initiation. Results. We included 24 991 children from eastern Africa, southern Africa, Europe and Asia; 26 developed KS after starting cART. Incidence rates per 100 000 person-years (PYs) were 86 in eastern Africa (95% confidence interval [CI], 55-133), 11 in southern Africa (95% CI, 4-35), and 81 (95% CI, 26-252) in children of sub-Saharan African (SSA) origin in Europe. The KS incidence rates were 0/100 000 PYs in children of non-SSA origin in Europe (95% CI, 0-50) and in Asia (95% CI, 0-27). KS risk was lower in girls than in boys (adjusted HR [aHR], 0.3; 95% CI, .1-.9) and increased with age (10-15 vs 0-4 years; aHR, 3.4; 95% CI, 1.2-10.1) and advanced HIV/AIDS stage (CDC stage C vs A/B; aHR, 2.4; 95% CI, .8-7.3) at cART initiation. Conclusions. HIV-infected children from SSA but not those from other regions, have a high risk of developing KS after cART initiation. Early cART initiation in these children might reduce KS risk.
  • No Thumbnail Available
    PublicationMetadata only
    The laboratory diagnosis of melioidosis
    (1996-12-01) Amanda L. Walsh; Vanaporn Wuthiekanun; Mahidol University; Nuffield Department of Clinical Medicine; Queen Elizabeth Central Hospital Malawi
    The recognition of unusual, but important, pathogens such as Burkholderia pseudomallei is essential for the rapid implementation of appropriate antimicrobial therapy - delays can be fatal. Melioidosis should be considered as a potential diagnosis for any patient with exposure to areas of endemicity, and thus laboratories should be aware of the differential features of the disease and the causative organism. Isolation of B. pseudomallei is readily achieved using standard culture media such as blood, MacConkey or cystine-lactose- electrolyte-deficient (CLED) agars, and routine blood culture broths. Selective media, Ashdown's agar and selective broth, are required for respiratory tract specimens to ensure reliable isolation from amongst the normal or contaminating flora. These media are easily prepared from common media constituents. Colonial morphology and simple biochemical tests will suggest the identity of the organism, which can then be confirmed by additional tests for 'non-fermenters' such as the API20NE.
  • No Thumbnail Available
    PublicationMetadata only
    Magnetic resonance imaging of cerebral malaria patients reveals distinct pathogenetic processes in different parts of the brain
    (2017-05-01) Sanjib Mohanty; Laura A. Benjamin; Megharay Majhi; Premanand Panda; Sam Kampondeni; Praveen K. Sahu; Akshaya Mohanty; Kishore C. Mahanta; Rajyabardhan Pattnaik; Rashmi R. Mohanty; Sonia Joshi; Anita Mohanty; Ian W. Turnbull; Arjen M. Dondorp; Terrie E. Taylor; Samuel C. Wassmer; Ispat General Hospital; University of Liverpool; Queen Elizabeth Central Hospital Malawi; Institute of Life Sciences India; North Manchester General Hospital; Mahidol University; Nuffield Department of Clinical Medicine; Michigan State University; University of Malawi College of Medicine; London School of Hygiene & Tropical Medicine
    © 2017 Mohanty et al. The mechanisms underlying the rapidly reversible brain swelling described in patients with cerebral malaria (CM) are unknown. Using a 1.5-Tesla (T) magnetic resonance imaging (MRI) scanner, we undertook an observational study in Rourkela, India, of 11 Indian patients hospitalized with CM and increased brain volume. Among the 11 cases, there were 5 adults and 6 children. All patients had reduced consciousness and various degrees of cortical swelling at baseline. The latter was predominately posterior in distribution. The findings on diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps were consistent with vasogenic edema in all cases. Reversibility after 48 to 72 h was observed in > 90% of cases. DWI/ADC mismatch suggested the additional presence of cytotoxic edema in the basal nuclei of 5 patients; all of these had perfusion parameters consistent with vascular engorgement and not with ischemic infarcts. Our results suggest that an impairment of the blood-brain barrier is responsible for the brain swelling in CM. In 5 cases, vasogenic edema occurred in conjunction with changes in the basal nuclei consistent with venous congestion, likely to be caused by the sequestration of Plasmodium falciparum-infected erythrocytes. While both mechanisms have been individually postulated to play an important role in the development of CM, this is the first demonstration of their concurrent involvement in different parts of the brain. The clinical and radiological characteristics observed in the majority of our patients are consistent with posterior reversible encephalopathy syndrome (PRES), and we show for the first time a high frequency of PRES in the context of CM.
  • No Thumbnail Available
    PublicationMetadata only
    Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa
    (2018-01-18) W. Robert Taylor; Htee Khu Naw; Kathryn Maitland; Thomas N. Williams; Melissa Kapulu; Umberto D'Alessandro; James A. Berkley; Philip Bejon; Joseph Okebe; Jane Achan; Alfred Ngwa Amambua; Muna Affara; Davis Nwakanma; Jean Pierre van Geertruyden; Muhindo Mavoko; Pascal Lutumba; Junior Matangila; Philipe Brasseur; Patrice Piola; Rindra Randremanana; Estrella Lasry; Caterina Fanello; Marie Onyamboko; Birgit Schramm; Zolia Yah; Joel Jones; Rick M. Fairhurst; Mahamadou Diakite; Grace Malenga; Malcolm Molyneux; Claude Rwagacondo; Charles Obonyo; Endalamaw Gadisa; Abraham Aseffa; Mores Loolpapit; Marie Claire Henry; Grant Dorsey; Chandy John; Sodiomon B. Sirima; Karen I. Barnes; Peter Kremsner; Nicholas P. Day; Nicholas J. White; Mavuto Mukaka; Unité de Recherche sur les Maladies Infectieuses et Tropicales émergentes; Universite de Kinshasa; Queen Elizabeth Central Hospital Malawi; Malawi-Liverpool-Wellcome Trust Clinical Research Programme; Institut Pasteur de Madagascar; Centre de Recherche Entomologique de Cotonou; Medical Research Council Laboratories Gambia; Armauer Hansen Research Institute; Kenya Medical Research Institute; Wellcome Trust Research Laboratories Nairobi; African Medical Research Foundation Nairobi; London School of Hygiene & Tropical Medicine; Indiana University-Purdue University Indianapolis; University of California, San Francisco; Wellcome Trust; National Institute of Allergy and Infectious Diseases; Universität Tübingen; Universiteit Antwerpen; Epicentre; Mahidol University; Hôpitaux universitaires de Genève; Nuffield Department of Clinical Medicine; Medecins Sans Frontieres; University of Cape Town; Kinshasa Mahidol Oxford Research Unit; USTTB; National Malaria Control Programme; Groupe de Recherche Action en Santé (GRAS); National Malaria Control Program; Kinshasa School of Public Health; Centre National de Recherche et de Formation sur le Paludisme
    © 2018 The Author(s). Background: In 2012, the World Health Organization recommended blocking the transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ, target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be suitable for sub-Saharan Africa. Methods: Using data on the anti-infectivity efficacy and tolerability of primaquine (PQ), the epidemiology of anaemia, and the risks of PQ-induced acute haemolytic anaemia (AHA) and clinically significant anaemia (CSA), we prospectively defined therapeutic-dose ranges of 0.15-0.4 mg PQ base/kg for children aged 1-5 years and 0.15-0.5 mg PQ base/kg for individuals aged ≥6 years (therapeutic indices 2.7 and 3.3, respectively). We chose 1.25 mg PQ base for infants aged 6-11 months because they have the highest rate of baseline anaemia and the highest risks of AHA and CSA. We modelled an anthropometric database of 661,979 African individuals aged ≥6 months (549,127 healthy individuals, 28,466 malaria patients and 84,386 individuals with other infections/illnesses) by the Box-Cox transformation power exponential and tested PQ doses of 1-15 mg base, selecting dosing groups based on calculated mg/kg PQ doses. Results: From the Box-Cox transformation power exponential model, five age categories were selected: (i) 6-11 months (n = 39,886, 6.03%), (ii) 1-5 years (n = 261,036, 45.46%), (iii) 6-9 years (n = 20,770, 3.14%), (iv) 10-14 years (n = 12,155, 1.84%) and (v) ≥15 years (n = 328,132, 49.57%) to receive 1.25, 2.5, 5, 7.5 and 15 mg PQ base for corresponding median (1st and 99th centiles) mg/kg PQ base of: (i) 0.16 (0.12-0.25), (ii) 0.21 (0.13-0.37), (iii) 0.25 (0.16-0.38), (iv) 0.26 (0.15-0.38) and (v) 0.27 (0.17-0.40). The proportions of individuals predicted to receive optimal therapeutic PQ doses were: 73.2 (29,180/39,886), 93.7 (244,537/261,036), 99.6 (20,690/20,770), 99.4 (12,086/12,155) and 99.8% (327,620/328,132), respectively. Conclusions: We plan to test the safety of this age-based dosing regimen in a large randomised placebo-controlled trial (ISRCTN11594437) of uncomplicated falciparum malaria in G6PDd African children aged 0.5 - 11 years. If the regimen is safe and demonstrates adequate pharmacokinetics, it should be used to support malaria elimination.