Browsing by Author "Mwape I"

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Characterization of human respiratory syncytial virus in children with severe acute respiratory infection before and during the COVID-19 pandemic.
(2024-Jun) Simusika P; Okamoto M; Dapat C; Muleya W; Malisheni M; Azam S; Imamura T; Saito M; Mwape I; Mpabalwani E; Monze M; Oshitani H; Tohoku University Graduate School of Medicine, Department of Virology, Sendai, Japan.; Center for Infectious Disease Research in Zambia, Lusaka, Zambia.; University Teaching Hospitals, Pathology and Microbiology Department, Virology Laboratory, Lusaka, Zambia.; University of Zambia, School of Veterinary Medicine, Department of Biomedical Sciences, Lusaka, Zambia.; University of Zambia, School of Medicine, Department of Pediatrics and Child Health, Lusaka, Zambia.; Levy Mwanawasa Medical University, Institute of Basic and Biomedical Sciences ,Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVES: Annual outbreaks of human respiratory syncytial virus (HRSV) are caused by newly introduced and locally persistent strains. During the COVID-19 pandemic, global and local circulation of HRSV significantly decreased. This study was conducted to characterize HRSV in 2018-2022 and to analyze the impact of COVID-19 on the evolution of HRSV. DESIGN/METHODS: Combined oropharyngeal and nasopharyngeal swabs were collected from children hospitalized with severe acute respiratory infection at two hospitals in Zambia. The second hypervariable region of the attachment gene G was targeted for phylogenetic analysis. RESULTS: Of 3113 specimens, 504 (16.2%) were positive for HRSV, of which 131 (26.0%) and 66 (13.1%) were identified as HRSVA and HRSVB, respectively. In early 2021, an increase in HRSV was detected, caused by multiple distinct clades of HRSVA and HRSVB. Some were newly introduced, whereas others resulted from local persistence. CONCLUSIONS: This study provides insights into the evolution of HRSV, driven by global and local circulation. The COVID-19 pandemic had a temporal impact on the evolution pattern of HRSV. Understanding the evolution of HRSV is vital for developing strategies for its control.
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/
Evaluation of ROTARIX
(2023-Feb-03) Laban NM; Bosomprah S; Simuyandi M; Chibuye M; Chauwa A; Chirwa-Chobe M; Sukwa N; Chipeta C; Velu R; Njekwa K; Mubanga C; Mwape I; Goodier MR; Chilengi R; Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.; Department of Global Health, Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam University Medical Centers, University of Amsterdam, Paasheuvelweg 25, 1105 BP Amsterdam, The Netherlands.; Division of Medical Microbiology, Department of Pathology, Stellenbosch University & National Health Laboratory Service, Tygerberg Hospital Francie van Zijl Drive, Tygerberg, P.O. Box 241, Cape Town 8000, South Africa.; Department of Biostatistics, School of Public Health, University of Ghana, Accra P.O. Box LG13, Ghana.; Flow Cytometry and Immunology Facility, Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine, Fajara, Banjul P.O. Box 273, The Gambia.; Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka P.O. Box 50110, Zambia.; Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Oral rotavirus vaccines show diminished immunogenicity in low-resource settings where rotavirus burden is highest. This study assessed the safety and immune boosting effect of a third dose of oral ROTARIX
Immunogenicity of rotavirus vaccine (RotarixTM) in infants with environmental enteric dysfunction.
(2017) Mwape I; Bosomprah S; Mwaba J; Mwila-Kazimbaya K; Laban NM; Chisenga CC; Sijumbila G; Simuyandi M; Chilengi R; Department of Physiological sciences,University of Zambia, Lusaka, Zambia.; Center for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Biostatistics, School of Public Health, University of Ghana, Legon, Accra, Ghana.; University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
INTRODUCTION: Deployment of rotavirus vaccines has contributed to significant declines in diarrheal morbidity and mortality globally. Unfortunately, vaccine performance in low-middle income countries (LMICs) is generally lower than in developed countries. The cause for this has been associated with several host and maternal factors including poor water sanitation and hygiene (WASH) status, which are predominant in LMICs. More recently, environmental enteric dysfunction (EED) has specifically been hypothesized to contribute to poor vaccine uptake and response. The aim of this study was to examine the association between serological biomarkers of EED and seroconversion to rotavirus vaccine in Zambian infants. METHODS: This was a retrospective cohort study of 142 infants who had been fully immunized with Rotarix™, and had known seroconversion status. Seroconversion was defined as 4-fold or more increase in rotavirus-specific IgA titres between pre-vaccination and one month post-dose two vaccination. We performed ELISA assays to assess soluble CD14 (sCD14), Endotoxin Core IgG Antibodies (EndoCAb), intestinal fatty acid binding protein (i-FABP) and Zonulin according to the manufacturers protocols. Generalised linear model with family-poisson, link-log and robust standard error was used to estimate the independent effects of biomarkers on seroconversion adjusting for important cofounders. RESULTS: The median concentration of Zonulin, Soluble CD14, EndoCaB, and IFABP were 209.3 (IQR = 39.7, 395.1), 21.5 (IQR = 21.5, 21.5), 0.3 (IQR = 0.3, 0.3), and 107.7 (IQR = 6.4, 1141.4) respectively. In multivariable analyses adjusting for the independent effect of other biomarkers and confounders (i.e. age of child at vaccination, breast-milk anti-rotavirus IgA, infant serum anti-rotavirus IgG, and IgA seropositivity at baseline), there was strong evidence of about 24% increase in seroconversion due to doubling Zonulin concentration (Adjusted risk ratio (aRR) = 1.24; 95% CI = 1.12 to1.37; p<0.0001). Similarly, we found about 7% increase in seroconversion due to doubling IFABP concentration (aRR = 1.07; 95% CI = 1.02 to 1.13; p = 0.006). CONCLUSION: We found that high levels of zonulin and IFABP played a role in seroconversion. It is plausible that increased gut permeability in EED allows greater uptake of the live virus within the vaccine, but later consequences result in deleterious local structural distortions and malabsorption syndromes.
Maternal and Infant Histo-Blood Group Antigen (HBGA) Profiles and Their Influence on Oral Rotavirus Vaccine (Rotarix
(2023-Jul-31) Chauwa A; Bosomprah S; Laban NM; Phiri B; Chibuye M; Chilyabanyama ON; Munsaka S; Simuyandi M; Mwape I; Mubanga C; Chobe MC; Chisenga C; Chilengi R; Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.; Department of Global Health, Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam University Medical Centers, University of Amsterdam, 1012 WP Amsterdam, The Netherlands.; Department of Biostatistics, School of Public Health, University of Ghana, Accra P.O. Box LG13, Ghana.; Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka P.O. Box 50110, Zambia.; Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Live-attenuated, oral rotavirus vaccines have significantly reduced rotavirus-associated diarrhoea morbidity and infant mortality. However, vaccine immunogenicity is diminished in low-income countries. We investigated whether maternal and infant intrinsic susceptibility to rotavirus infection via histo-blood group antigen (HBGA) profiles influenced rotavirus (ROTARIX
Norovirus infections in young children in Lusaka Province, Zambia: clinical characteristics and molecular epidemiology.
(2017-Jan-23) Howard LM; Mwape I; Siwingwa M; Simuyandi M; Guffey MB; Stringer JS; Chi BH; Edwards KM; Chilengi R; Department of Pediatrics, Division of Pediatric Infectious Diseases, Vanderbilt University Medical Center, D-7228 MCN; 1161 21st Ave S, Nashville, TN, 37232, USA. leigh.howard@vanderbilt.edu.; Centre for Infectious Disease Research in Zambia (CIDRZ), P.O. Box 34681, Lusaka, 10101, Zambia.; Division of Global Women's Health, University of North Carolina (UNC) - Chapel Hill, 130 Mason Farm Rd., 2nd Floor, Campus Box #7030, 27599-7030, Chapel Hill, NC, USA. Roma.Chilengi@cidrz.org.; Division of Global Women's Health, University of North Carolina (UNC) - Chapel Hill, 130 Mason Farm Rd., 2nd Floor, Campus Box #7030, 27599-7030, Chapel Hill, NC, USA.; Centre for Infectious Disease Research in Zambia (CIDRZ), P.O. Box 34681, Lusaka, 10101, Zambia. Roma.Chilengi@cidrz.org.; Department of Pediatrics, Division of Pediatric Infectious Diseases, Vanderbilt University Medical Center, D-7228 MCN; 1161 21st Ave S, Nashville, TN, 37232, USA.
BACKGROUND: The burden, clinical features, and molecular epidemiology of norovirus infection in young children in southern Africa are not well defined. METHODS: Using data from a health facility-based surveillance study of children <5 years in Lusaka Province, Zambia presenting with diarrhea, we assessed the burden of norovirus infection. A convenience sample of 454 stool specimens was tested for norovirus using reverse-transcriptase polymerase chain reaction (RT-PCR). RT-PCR positive samples underwent additional nucleotide sequencing for genogroup and genotype identification. Clinical features and severity of diarrheal illnesses were compared between norovirus-positive and -negative subjects using Chi-squared and t-tests. RESULTS: Norovirus was detected in 52/454 (11.5%) specimens tested. Abdominal pain, fever, and vomiting were the most common presenting features in norovirus-associated illnesses. However, there were no significant differences in the clinical features of norovirus-positive compared to norovirus-negative illnesses. Of 43 isolates that were available for sequencing, 31 (72.1%) were genogroup II (GII) and 12 (27.9%) were genogroup I (GI). The distribution of genotypes was diverse. CONCLUSIONS: Noroviruses were detected in approximately 10% of young children with diarrhea in the Lusaka Province of Zambia, with GII representing the majority of infections. These findings support the role of norovirus in symptomatic diarrhea disease in Africa. Further studies are needed to confirm these observations and to evaluate prevention strategies.
Single genome amplification of proviral HIV-1 DNA from dried blood spot specimens collected during early infant screening programs in Lusaka, Zambia.
(2014-Jul) Seu L; Mwape I; Guffey MB; University of Alabama at Birmingham, Division of Infectious Diseases, 1900 University Boulevard, THT 215E, Birmingham, AL 35294, United States. Electronic address: Innocent.Mwape@cidrz.org.; Centre for Infectious Disease Research Zambia, 5032 Great North Road, P.O. Box 34681, Lusaka, Zambia; University of Alabama at Birmingham, Division of Infectious Diseases, 1900 University Boulevard, THT 215E, Birmingham, AL 35294, United States. Electronic address: ls2026@uab.edu.; Centre for Infectious Disease Research Zambia, 5032 Great North Road, P.O. Box 34681, Lusaka, Zambia; University of Alabama at Birmingham, Division of Infectious Diseases, 1900 University Boulevard, THT 215E, Birmingham, AL 35294, United States. Electronic address: guffey@uab.edu.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
The ability to evaluate individual HIV-1 virions from the quasispecies of vertically infected infants was evaluated in a field setting at the Centre for Infectious Disease Research in Zambia. Infant heel-prick blood specimens were spotted onto dried blood spot (DBS) filter paper cards at government health clinics. Nucleic acid was extracted and used as a template for HIV-1 proviral DNA detection by a commercial Amplicor HIV-1 PCR test (Roche, version 1.5). On samples that tested positive by commercial diagnostic assay, amplification of DNA was performed using an in-house assay of the 5' and 3' region of the HIV-1 genome. Additionally, fragments covering 1200 nucleotides within pol (full length protease and partial reverse transcriptase) and 1400 nucleotides within env (variable 1-variable 5 region) were further analyzed by single genome amplification (SGA). In summary, we have demonstrated an in-house assay for amplifying the 5' and 3' proviral HIV-1 DNA as well as pol and env proviral DNA fragments from DBS cards collected and analyzed entirely in Zambia. In conclusion, this study shows the feasibility of utilizing DBS cards to amplify the whole proviral HIV-1 genome as well as perform SGA on key HIV-1 genes.