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Browsing by Author "Ojok D"

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    Characterization of Rotavirus Strains Responsible for Breakthrough Diarrheal Diseases among Zambian Children Using Whole Genome Sequencing.
    (2023-Nov-26) Mwape I; Laban NM; Chibesa K; Moono A; Silwamba S; Malisheni MM; Chisenga C; Chauwa A; Simusika P; Phiri M; Simuyandi M; Chilengi R; De Beer C; Ojok D; Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.; Institute of Basic and Biomedical Sciences, Levy Mwanawasa Medical University, Lusaka 10101, Zambia.; Division of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 241, Cape Town 8000, South Africa.; Influenza Research Institute, University of Wisconsin-Madison, Madison, WI 53706-13380, USA.; University Teaching Hospitals, Lusaka 10101, Zambia.; Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia.; Division of Medical Virology, School of Pathology, Faculty of Health Sciences, University of the Free State, Bloemfontein P.O. Box 339, South Africa.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    The occurrence of rotavirus (RV) infection among vaccinated children in high-burden settings poses a threat to further disease burden reduction. Genetically altered viruses have the potential to evade both natural infection and vaccine-induced immune responses, leading to diarrheal diseases among vaccinated children. Studies characterizing RV strains responsible for breakthrough infections in resource-limited countries where RV-associated diarrheal diseases are endemic are limited. We aimed to characterize RV strains detected in fully vaccinated children residing in Zambia using next-generation sequencing. We conducted whole genome sequencing on Illumina MiSeq. Whole genome assembly was performed using Geneious Prime 2023.1.2. A total of 76 diarrheal stool specimens were screened for RV, and 4/76 (5.2%) were RV-positive. Whole genome analysis revealed RVA/Human-wt/ZMB/CIDRZ-RV2088/2020/
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    Circumstances for treatment and control of invasive Enterobacterales infections in eight hospitals across sub-Saharan Africa: a cross-sectional study.
    (2023) Aiken AM; Nyamwaya B; Madrid L; Edessa D; Labi AK; Obeng-Nkrumah N; Mwabaya W; Chimenya M; Cocker D; Iregbu KC; Princewill-Nwajiobi PIP; Dramowski A; Sonda T; Mmbaga BT; Ojok D; Fwoloshi S; Scott JAG; Whitelaw A; School of Pharmacy, Haramaya University, Harar, Ethiopia.; Department of Medicine, University Teaching Hospital, Ministry of Health, Lusaka, Zambia.; Kilimanjaro Clinical Research Institute-Kilimanjaro Christian Medical Centre, Moshi, Tanzania.; Malawi-Liverpool Wellcome Programme, Kamuzu University of Health Sciences, Blantyre, Malawi.; Department of Medical Microbiology, University of Ghana Medical School, Accra, Ghana.; KEMRI Centre for Geographic Medicine Research, Kilifi, Kenya.; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.; Department of Paediatric and Child Health, Kilimanjaro Christian Medical University College, Moshi, Tanzania.; Division of Medical Microbiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.; Infectious Disease Epidemiology Department, London School of Hygiene and Tropical Medicine, London, UK.; Department of Medical Laboratory Sciences, University of Ghana, Accra, Ghana.; Department of Medical Microbiology, National Hospital Abuja, Abuja, Nigeria.; National Health Laboratory Service, Tygerberg Hospital, Cape Town, South Africa.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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    Field performance of the Determine HBsAg point-of-care test for diagnosis of hepatitis B virus co-infection among HIV patients in Zambia.
    (2018-Jan) Chisenga CC; Musukuma K; Chilengi R; Zürcher S; Munamunungu V; Siyunda A; Ojok D; Bauer S; Wandeler G; Vinikoor M; Institute for Infectious Diseases, University of Bern, Bern, Switzerland.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. Electronic address: caroline.chisenga@cidrz.org.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; School of Medicine, University of Zambia, Lusaka, Zambia.; Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; School of Medicine, University of Zambia, Lusaka, Zambia; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    BACKGROUND: We evaluated the field performance of a rapid point-of-care (POC) test for hepatitis B surface antigen (HBsAg) that could support decentralization and scale-up of hepatitis B virus (HBV) diagnosis in Africa. OBJECTIVE: To determine the field performance of the Determine HBsAg POC test for diagnosis of HBV co-infection among HIV patients in Zambia. STUDY DESIGN: Between 2013-2014, we screened HIV-infected adults for HBsAg at two urban clinics in Zambia. A subset were tested with the POC Determine HBsAg (Alere, USA) by finger prick in the clinic and HBsAg serology (Access2Analyzer, Beckman Coulter) at a reference laboratory. If either test was reactive, we determined HBV viral load (VL) and genotype. We described patient demographic and clinical characteristics (including liver fibrosis) and assessed the sensitivity, specificity, positive and negative predictive values (PPV and NPV) of the Determine test. In secondary analyses, we assessed sensitivity among patients with replicating HBV (i.e., VL>20 IU/ml) and with high HBV VL (i.e.,>20,000IU/ml). RESULTS: Among 412 participants with both HBsAg tests, median age was 34 years, 51% were women, and median CD4 was 208 cells/mm CONCLUSIONS: Determine HBsAg is a cheaper alternative HBV testing option compared to the gold standard ELISA and has high specificity and good sensitivity in the field among HIV-infected individuals.
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    Mortality associated with third-generation cephalosporin resistance in Enterobacterales bloodstream infections at eight sub-Saharan African hospitals (MBIRA): a prospective cohort study.
    (2023-Nov) Aiken AM; Rehman AM; de Kraker MEA; Madrid L; Kebede M; Labi AK; Obeng-Nkrumah N; Nyamwaya B; Kagucia E; Cocker D; Kawaza K; Lester R; Iregbu KC; Medugu N; Nwajiobi-Princewill PI; Dramowski A; Sonda T; Hemed A; Fwoloshi S; Ojok D; Scott JAG; Whitelaw A; Department of Medicine, University Teaching Hospital, Ministry of Health, Lusaka, Zambia.; Department of Medical Microbiology, University of Ghana Medical School, University of Ghana, Accra, Ghana.; Infection Control Program and WHO Collaborating Center on Patient Safety and Antimicrobial Resistance, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland.; Infectious Disease Epidemiology Department, London School of Hygiene & Tropical Medicine, London, UK; College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia.; Department of Paediatrics and Child Health, Malawi-Liverpool Wellcome Programme, Kamuzu University of Health Sciences, Blantyre, Malawi.; College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia.; Kilimanjaro Clinical Research Institute, Kilimanjaro Christian Medical Centre, Moshi, Tanzania.; Infectious Disease Epidemiology Department, London School of Hygiene & Tropical Medicine, London, UK.; Department of Medicine, Malawi-Liverpool Wellcome Programme, Kamuzu University of Health Sciences, Blantyre, Malawi; Liverpool School of Tropical Medicine, Liverpool, UK.; Department of Medical Laboratory Sciences, School of Biomedical and Allied Health Sciences, University of Ghana, Accra, Ghana.; Department of Medical Microbiology, National Hospital Abuja, Abuja, Nigeria.; Department of Medical Microbiology, National Hospital Abuja, Abuja, Nigeria; Nile University of Nigeria, Abuja, Nigeria.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.; Infectious Disease Epidemiology Department, London School of Hygiene & Tropical Medicine, London, UK. Electronic address: alexander.aiken@lshtm.ac.uk.; Department of Medical Microbiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; National Health Laboratory Service, Tygerberg Hospital, Cape Town, South Africa.; Department of Medicine, Malawi-Liverpool Wellcome Programme, Kamuzu University of Health Sciences, Blantyre, Malawi; David Price Evans Infectious Diseases & Global Health Group, University of Liverpool, Liverpool, UK; Liverpool School of Tropical Medicine, Liverpool, UK.; KEMRI Centre for Geographic Medical Research, Kilifi, Kenya.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    BACKGROUND: Bacteria of the order Enterobacterales are common pathogens causing bloodstream infections in sub-Saharan Africa and are frequently resistant to third-generation cephalosporin antibiotics. Although third-generation cephalosporin resistance is believed to lead to adverse outcomes, this relationship is difficult to quantify and has rarely been studied in this region. We aimed to measure the effects associated with resistance to third-generation cephalosporins in hospitalised patients with Enterobacterales bloodstream infection in Africa. METHODS: We conducted a prospective, matched, parallel cohort study at eight hospitals across sub-Saharan Africa. We recruited consecutive patients of all age groups with laboratory-confirmed Enterobacterales bloodstream infection and matched them to at least one patient without bloodstream infection on the basis of age group, hospital ward, and admission date. Date of infection onset (and enrolment) was defined as the day of blood sample collection for culturing. Patients infected with bacteria with a cefotaxime minimum inhibitory concentration of 1 mg/L or lower were included in the third-generation cephalosporin-susceptible (3GC-S) cohort, and the remainder were included in the third-generation cephalosporin-resistant (3GC-R) cohort. The primary outcomes were in-hospital death and death within 30 days of enrolment. We used adjusted multivariable regression models to first compare patients with bloodstream infection against matched patients within the 3GC-S and 3GC-R cohorts, then compared estimates between cohorts. FINDINGS: Between Nov 1, 2020, and Jan 31, 2022, we recruited 878 patients with Enterobacterales bloodstream infection (221 [25·2%] to the 3GC-S cohort and 657 [74·8%] to the 3GC-R cohort) and 1634 matched patients (420 [25·7%] and 1214 [74·3%], respectively). 502 (57·2%) bloodstream infections occurred in neonates and infants (age 0-364 days). Klebsiella pneumoniae (393 [44·8%] infections) and Escherichia coli (224 [25·5%] infections) were the most common Enterobacterales species identified. The proportion of patients who died in hospital was higher in patients with bloodstream infection than in matched controls in the 3GC-S cohort (62 [28·1%] of 221 vs 22 [5·2%] of 420; cause-specific hazard ratio 6·79 [95% CI 4·06-11·37] from Cox model) and the 3GC-R cohort (244 [37·1%] of 657 vs 115 [9·5%] of 1214; 5·01 [3·96-6·32]). The ratio of these cause-specific hazard ratios showed no significant difference in risk of in-hospital death in the 3GC-R cohort versus the 3GC-S cohort (0·74 [0·42-1·30]). The ratio of relative risk of death within 30 days (0·82 [95% CI 0·53-1·27]) also indicated no difference between the cohorts. INTERPRETATION: Patients with bloodstream infections with Enterobacterales bacteria either resistant or susceptible to third-generation cephalosporins had increased mortality compared with uninfected matched patients, with no differential effect related to third-generation cephalosporin-resistance status. However, this finding does not account for time to appropriate antibiotic treatment, which remains clinically important to optimise. Measures to prevent transmission of Enterobacterales could reduce bloodstream infection-associated mortality from both drug-resistant and drug-susceptible bacterial strains in Africa. FUNDING: Bill & Melinda Gates Foundation.

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