Browsing by Author "Chisenga C"

Now showing 1 - 11 of 11

A pilot study on use of live attenuated rotavirus vaccine (Rotarix™) as an infection challenge model.
(2020-Oct-27) Chilengi R; Simuyandi M; Chibuye M; Chirwa M; Sukwa N; Laban N; Chisenga C; Silwamba S; Grassly N; Bosomprah S; Research Division, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana.; MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College, London, United Kingdom.; Research Division, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. Electronic address: Roma.Chilengi@cidrz.org.; Research Division, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Rotavirus remains the commonest cause of dehydrating diarrhoea, particularly in developing countries. Human infection challenge studies in children in these countries offers an opportunity to rapidly evaluate new vaccine candidates that may have improved efficacy. We evaluated use of Rotarix™ as a live-attenuated challenge agent. METHODS: We undertook an open label, exploratory study in infants receiving two standard doses of Rotarix™ at 6 and 10 weeks of age in a cohort of 22 Zambian infants. The first vaccine dose was considered as primary vaccination, and the second at day 28 as a live-attenuated virus challenge. Saliva, stool and serum samples were collected on days 0, 3, 5, 7, 14, and 28 following each dose. The primary outcome was stool shedding of rotavirus, determined by NSP2 qPCR. We calculated mean shedding index as average of natural logarithm of viral copies per gram of stool. FINDINGS: After the first dose, viral shedding was high at day 3, peaked by day 5. After the second dose, viral shedding at day 3 was low and reduced gradually in most infants until day 14. Mean shedding index was significantly lower post dose 2 across all infants and timepoints (5.0 virus copies/g of stool [95%CI: 0.3-9.7] vs 10.4 virus copies/g of stool [95%CI: 6.2-14.6]; p-value < 0.0001; rho = 0.20, SD = 4.97. Seroconversion at day 28 was associated with a mean reduction of -1.03 (95%CI = -8.07, 6.01) in viral shedding after challenge dose but this was not statistically significant (p = 0.774). A borderline positive correlation between fold-change in IgA titre at day 28 from day 0 in saliva and serum was observed; Spearman's correlation coefficient, r = 0.69; p = 0.086. INTERPRETATION: Shedding after the 'challenge' dose was reduced compared with the first dose, consistent with the induction of mucosal immunity by the first dose. This supports the use of Rotarix vaccine as a live-attenuated infection challenge. FUNDING: Medical Research Council (UK) through the HIC-Vac Network.
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/
Characterizing Epstein-Barr virus infection of the central nervous system in Zambian adults living with HIV.
(2023-Dec) Musukuma-Chifulo K; Ghebremichael M; Chilyabanyama ON; Bates M; Munsaka S; Simuyandi M; Chisenga C; Tembo J; Sinkala E; Koralnik IJ; Dang X; Chilengi R; Siddiqi OK; Harvard Medical School and Ragon Institute of Mass General, MIT and Harvard, Boston, MA, USA.; Department of Biomedical Sciences, School of Health Sciences, The University of Zambia, Lusaka, Zambia. kalomusukuma@gmail.com.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia. kalomusukuma@gmail.com.; Center for Vaccines and Virology Research, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.; HerpeZ, University Teaching Hospital, Lusaka, Zambia.; Global Neurology Program, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA.; Department of Internal Medicine, University of Zambia School of Medicine, Lusaka, Zambia.; School of Life & Environmental Sciences, University of Lincoln, Lincoln, UK.; Department of Biomedical Sciences, School of Health Sciences, The University of Zambia, Lusaka, Zambia.; Zambia National Public Health Institute, Ministry of Health, 10101, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
The significance of Epstein-Barr virus (EBV) detection in the cerebrospinal spinal fluid (CSF) in people living with HIV (PLWH) is not entirely understood. The detection of EBV DNA may represent active central nervous system (CNS) infection, reactivation in the setting of another CNS pathogen or due to impaired immunity, or detection of quiescent virus. We screened 470 adult PLWH in Zambia with neurological symptoms for the presence of EBV DNA in the CSF. We performed quantitative EBV PCR on the CSF and blood. We then performed quantitative EBV DNA PCR on the blood of controls with documented HIV viral suppression without CNS symptoms. The prevalence of EBV DNA in the CSF of patients with CNS symptoms was 28.9% (136/470). EBV DNA positivity was associated with younger age, shorter duration of HIV diagnosis, lower CSF glucose levels, higher CSF protein and white blood cell levels, and a positive CSF Mycobacterium tuberculosis result. The median EBV DNA load was 8000 cps/mL in both the CSF and blood with a range of 2000-2,753,000 cps/mL in the CSF and 1000 to 1,871,000 cps/mL in the blood. Molecular screening of CSF for other possible causes of infection identified Mycobacterium tuberculosis in 30.1% and cytomegalovirus (CMV) in 10.5% of samples. EBV DNA load in the blood and CSF was not associated with mortality. Our results suggest that even though EBV DNA was commonly detected in the CSF of our population, it appears to have limited clinical significance regardless of EBV DNA load.
Drivers of informal sector and non-prescription medication use in pediatric populations in a low- and middle-income setting: A prospective cohort study in Zambia.
(2023) Wildbret S; Stuck L; Luchen CC; Simuyandi M; Chisenga C; Schultsz C; Harris VC; Department of Global Health, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands.; Department of Medical Microbiology, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands.; Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands.; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, The Netherlands.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Division of Infectious Diseases, Department of Internal Medicine, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Obtaining medication from the informal sector is common in low- and middle- income countries. Informal sector use increases the risk for inappropriate medication use, including inappropriate antibiotic usage. Infants are at the highest risk of complications from inappropriate medication use, yet there is insufficient knowledge about the risk factors driving caregivers to obtain medication from the informal sector for young children. We aimed to define infant and illness characteristics associated with use of medication purchased in the informal sector for infants up to fifteen months of age in Zambia. We used data from, a prospective cohort study (ROTA-biotic) conducted among 6 weeks to 15 months old children in Zambia, which is nested within an ongoing phase III rotavirus vaccine trial (Clinicaltrial.gov NCT04010448). Weekly in-person surveys collected information about illness episodes and medication usage for the trial population and for a community control cohort. The primary outcome for this study was whether medication was purchased in the formal sector (hospital or clinic) or informal sector (pharmacy, street vendor, friend/relative/neighbor, or chemical shop) per illness episode. Descriptive analyses were used to describe the study population, and the independent and medication use variables stratified by the outcome. A mixed-effects logistic regression model with a participant-level random intercept was used to identify independent variables associated with the outcome. The analysis included 439 participants accounting for 1927 illness episodes over fourteen months in time. Medication was purchased in the informal sector for 386 (20.0%) illness episodes, and in the formal sector for 1541 (80.0%) illness episodes. Antibiotic usage was less common in the informal sector than in the formal sector (29.3% vs 56.2%, p < 0.001, chi-square). Most medications purchased in the informal sector were orally administered (93.4%), and non-prescribed (78.8%). Increased distance from the closest study site (OR: 1.09; 95% CI: 1.01, 1.17), being included in the community cohort site (OR: 3.18; 95% CI: 1.86, 5.46), illnesses with general malaise fever, or headache (OR: 2.62; 95% CI: 1.75, 3.93), and wound/skin disease (OR: 0.36; 95% CI: 0.18, 0.73) were associated with use of medication from the informal sector. Sex, socioeconomic status, and gastrointestinal disease were not associated with use of medication from the informal sector. Informal sector medication use is common and, in this study, risk factors for obtaining medications in the informal sector included a long distance to a formal clinic, type of illness, and not being enrolled in a clinical trial. Continued research on medication use from the informal sector is crucial and should include generalizable study populations, information on severity of disease, emphasis on qualitative research, and a move towards testing interventions that aim to improve access to formal health care settings. Our findings suggest that improved access to formal health care services may decrease reliance on medication from the informal sector for infants.
Human cytomegalovirus seropositivity and its influence on oral rotavirus vaccine immunogenicity: a specific concern for HIV-exposed-uninfected infants.
(2024-Jun-20) Laban N; Bosomprah S; Chilengi R; Simuyandi M; Chisenga C; Ng'ombe H; Musukuma-Chifulo K; Goodier M; Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.; Flow Cytometry and Immunology Facility, Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine, Fajara, Banjul, The Gambia.; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana.; Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Oral rotavirus vaccines demonstrate diminished immunogenicity in low-income settings where human cytomegalovirus infection is acquired early in childhood and modulates immunity. We hypothesized that human cytomegalovirus infection around the time of vaccination may influence immunogenicity. We measured plasma human cytomegalovirus-specific immunoglobulin M antibodies in rotavirus vaccinated infants from 6 weeks to 12 months old and compared rotavirus immunoglobulin A antibody titers between human cytomegalovirus seropositive and seronegative infants. There was no evidence of an association between human cytomegalovirus serostatus at 9 months and rotavirus-specific antibody titers at 12 months (geometric mean ratio 1.01, 95% CI: 0.70, 1.45; P = 0.976) or fold-increase in RV-IgA titer between 9 and 12 months (risk ratio 0.999, 95%CI: 0.66, 1.52; P = 0.995) overall. However, HIV-exposed-uninfected infants who were seropositive for human cytomegalovirus at 9 months old had a 63% reduction in rotavirus antibody geometric mean titers at 12 months compared to HIV-exposed-uninfected infants who were seronegative for human cytomegalovirus (geometric mean ratio 0.37, 95% CI: 0.17, 0.77; P = 0.008). While the broader implications of human cytomegalovirus infections on oral rotavirus vaccine response might be limited in the general infant population, the potential impact in the HIV-exposed-uninfected infants cannot be overlooked. This study highlights the complexity of immunological responses and the need for targeted interventions to ensure oral rotavirus vaccine efficacy, especially in vulnerable subpopulations.
Identification of cholera hotspots in Zambia: A spatiotemporal analysis of cholera data from 2008 to 2017.
(2020-Apr) Mwaba J; Debes AK; Shea P; Mukonka V; Chewe O; Chisenga C; Simuyandi M; Kwenda G; Sack D; Chilengi R; Ali M; Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Zambia National Public Health Institute, Lusaka, Zambia.; University of Zambia, School of Health Sciences, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
The global burden of cholera is increasing, with the majority (60%) of the cases occurring in sub-Saharan Africa. In Zambia, widespread cholera outbreaks have occurred since 1977, predominantly in the capital city of Lusaka. During both the 2016 and 2018 outbreaks, the Ministry of Health implemented cholera vaccination in addition to other preventative and control measures, to stop the spread and control the outbreak. Given the limitations in vaccine availability and the logistical support required for vaccination, oral cholera vaccine (OCV) is now recommended for use in the high risk areas ("hotspots") for cholera. Hence, the aim of this study was to identify areas with an increased risk of cholera in Zambia. Retrospective cholera case data from 2008 to 2017 was obtained from the Ministry of Health, Department of Public Health and Disease Surveillance. The Zambian Central Statistical Office provided district-level population data, socioeconomic and water, sanitation and hygiene (WaSH) indicators. To identify districts at high risk, we performed a discrete Poisson-based space-time scan statistic to account for variations in cholera risk across both space and time over a 10-year study period. A zero-inflated negative binomial regression model was employed to identify the district level risk factors for cholera. The risk map was generated by classifying the relative risk of cholera in each district, as obtained from the space-scan test statistic. In total, 34,950 cases of cholera were reported in Zambia between 2008 and 2017. Cholera cases varied spatially by year. During the study period, Lusaka District had the highest burden of cholera, with 29,080 reported cases. The space-time scan statistic identified 16 districts to be at a significantly higher risk of having cholera. The relative risk of having cholera in these districts was significantly higher and ranged from 1.25 to 78.87 times higher when compared to elsewhere in the country. Proximity to waterbodies was the only factor associated with the increased risk for cholera (P<0.05). This study provides a basis for the cholera elimination program in Zambia. Outside Lusaka, the majority of high risk districts identified were near the border with the DRC, Tanzania, Mozambique, and Zimbabwe. This suggests that cholera in Zambia may be linked to movement of people from neighboring areas of cholera endemicity. A collaborative intervention program implemented in concert with neighboring countries could be an effective strategy for elimination of cholera in Zambia, while also reducing rates at a regional level.
Impact of antibiotics on gut microbiome composition and resistome in the first years of life in low- to middle-income countries: A systematic review.
(2023-Jun) Luchen CC; Chibuye M; Spijker R; Simuyandi M; Chisenga C; Bosomprah S; Chilengi R; Schultsz C; Mende DR; Harris VC; Amsterdam UMC, location University of Amsterdam, Department of Global Health, Amsterdam Institute for Global Health and Development, Amsterdam, the Netherlands.; Zambia National Public Health Institute, Ministry of Health, Lusaka, Zambia.; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana.; Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology, Amsterdam, the Netherlands.; Republic of Zambia State House, Lusaka, Zambia.; Research Division, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Amsterdam UMC, location University of Amsterdam, Department of Internal Medicine, Division of Infectious Diseases, Amsterdam, the Netherlands.; Amsterdam Institute of Infection and Immunity, Infectious Diseases, Amsterdam University Medical Center, Amsterdam, the Netherlands.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Inappropriate antimicrobial usage is a key driver of antimicrobial resistance (AMR). Low- and middle-income countries (LMICs) are disproportionately burdened by AMR and young children are especially vulnerable to infections with AMR-bearing pathogens. The impact of antibiotics on the microbiome, selection, persistence, and horizontal spread of AMR genes is insufficiently characterized and understood in children in LMICs. This systematic review aims to collate and evaluate the available literature describing the impact of antibiotics on the infant gut microbiome and resistome in LMICs. METHODS AND FINDINGS: In this systematic review, we searched the online databases MEDLINE (1946 to 28 January 2023), EMBASE (1947 to 28 January 2023), SCOPUS (1945 to 29 January 2023), WHO Global Index Medicus (searched up to 29 January 2023), and SciELO (searched up to 29 January 2023). A total of 4,369 articles were retrieved across the databases. Duplicates were removed resulting in 2,748 unique articles. Screening by title and abstract excluded 2,666 articles, 92 articles were assessed based on the full text, and 10 studies met the eligibility criteria that included human studies conducted in LMICs among children below the age of 2 that reported gut microbiome composition and/or resistome composition (AMR genes) following antibiotic usage. The included studies were all randomized control trials (RCTs) and were assessed for risk of bias using the Cochrane risk-of-bias for randomized studies tool. Overall, antibiotics reduced gut microbiome diversity and increased antibiotic-specific resistance gene abundance in antibiotic treatment groups as compared to the placebo. The most widely tested antibiotic was azithromycin that decreased the diversity of the gut microbiome and significantly increased macrolide resistance as early as 5 days posttreatment. A major limitation of this study was paucity of available studies that cover this subject area. Specifically, the range of antibiotics assessed did not include the most commonly used antibiotics in LMIC populations. CONCLUSION: In this study, we observed that antibiotics significantly reduce the diversity and alter the composition of the infant gut microbiome in LMICs, while concomitantly selecting for resistance genes whose persistence can last for months following treatment. Considerable heterogeneity in study methodology, timing and duration of sampling, and sequencing methodology in currently available research limit insights into antibiotic impacts on the microbiome and resistome in children in LMICs. More research is urgently needed to fill this gap in order to better understand whether antibiotic-driven reductions in microbiome diversity and selection of AMR genes place LMIC children at risk for adverse health outcomes, including infections with AMR-bearing pathogens.
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
T-Cell Responses after Rotavirus Infection or Vaccination in Children: A Systematic Review.
(2022-Feb-23) Laban NM; Goodier MR; Bosomprah S; Simuyandi M; Chisenga C; Chilyabanyama ON; Chilengi R; Department of Biostatistics, School of Public Health, University of Ghana, Accra P.O. Box LG13, Ghana.; Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia.; Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.; 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.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Cellular immunity against rotavirus in children is incompletely understood. This review describes the current understanding of T-cell immunity to rotavirus in children. A systematic literature search was conducted in Embase, MEDLINE, Web of Science, and Global Health databases using a combination of "t-cell", "rotavirus" and "child" keywords to extract data from relevant articles published from January 1973 to March 2020. Only seventeen articles were identified. Rotavirus-specific T-cell immunity in children develops and broadens reactivity with increasing age. Whilst occurring in close association with antibody responses, T-cell responses are more transient but can occur in absence of detectable antibody responses. Rotavirus-induced T-cell immunity is largely of the gut homing phenotype and predominantly involves Th1 and cytotoxic subsets that may be influenced by IL-10 Tregs. However, rotavirus-specific T-cell responses in children are generally of low frequencies in peripheral blood and are limited in comparison to other infecting pathogens and in adults. The available research reviewed here characterizes the T-cell immune response in children. There is a need for further research investigating the protective associations of rotavirus-specific T-cell responses against infection or vaccination and the standardization of rotavirus-specific T-cells assays in children.
Three transmission events of Vibrio cholerae O1 into Lusaka, Zambia.
(2021-Jun-14) Mwaba J; Debes AK; Murt KN; Shea P; Simuyandi M; Laban N; Kazimbaya K; Chisenga C; Li S; Almeida M; Meisel JS; Shibemba A; Kantenga T; Mukonka V; Kwenda G; Sack DA; Chilengi R; Stine OC; Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, USA.; Zambia National Public Health Institute, Lusaka, Zambia.; Department of Biomedical Sciences, University of Zambia School of Health Sciences, Lusaka, Zambia.; Department of Pathology and Microbiology, University Teaching Hospitals, Lusaka, Zambia.; University of Maryland School of Medicine, Baltimore, MD, USA.; University of Maryland, College Park, College Park, MD, USA.; University of Maryland School of Medicine, Baltimore, MD, USA. cstine@som.umaryland.edu.; Université Paris-Saclay, INRAE, MGP, 78350, Jouy-en-Josas, France.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Cholera has been present and recurring in Zambia since 1977. However, there is a paucity of data on genetic relatedness and diversity of the Vibrio cholerae isolates responsible for these outbreaks. Understanding whether the outbreaks are seeded from existing local isolates or if the outbreaks represent separate transmission events can inform public health decisions. RESULTS: Seventy-two V. cholerae isolates from outbreaks in 2009/2010, 2016, and 2017/2018 in Zambia were characterized using multilocus variable number tandem repeat analysis (MLVA) and whole genome sequencing (WGS). The isolates had eight distinct MLVA genotypes that clustered into three MLVA clonal complexes (CCs). Each CC contained isolates from only one outbreak. The results from WGS revealed both clustered and dispersed single nucleotide variants. The genetic relatedness of isolates based on WGS was consistent with the MLVA, each CC was a distinct genetic lineage and had nearest neighbors from other East African countries. In Lusaka, isolates from the same outbreak were more closely related to themselves and isolates from other countries than to isolates from other outbreaks in other years. CONCLUSIONS: Our observations are consistent with i) the presence of random mutation and alternative mechanisms of nucleotide variation, and ii) three separate transmission events of V. cholerae into Lusaka, Zambia. We suggest that locally, case-area targeted invention strategies and regionally, well-coordinated plans be in place to effectively control future cholera outbreaks.
Use of an ETEC Proteome Microarray to Evaluate Cross-Reactivity of ETVAX
(2023-May-04) Mubanga C; Simuyandi M; Mwape K; Chibesa K; Chisenga C; Chilyabanyama ON; Randall A; Liang X; Glashoff RH; Chilengi R; Division of Medical Microbiology, Department of Pathology, Stellenbosch University & National Health Laboratory Service, Tygerberg Hospital Francie van Zijl Drive, P.O. Box 241, Cape Town 8000, South Africa.; Division of Virology, School of Pathology, Faculty of Health Sciences, University of the Free State, 205 Nelson Mandela, P.O. Box 339, Bloemfontein 9300, South Africa.; Antigen Discovery Inc., 1 Technology Dr., Suite E309, Irvine, CA 92618, USA.; Water and Health Research Center, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein 2028, South Africa.; 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)
Developing a broadly protective vaccine covering most ETEC variants has been elusive. The most clinically advanced candidate yet is an oral inactivated ETEC vaccine (ETVAX