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Browsing by Author "Kwenda G"

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    Antimicrobial resistance and heterogeneity of Neisseria gonorrhoeae isolated from patients attending sexually transmitted infection clinics in Lusaka, Zambia.
    (2024-Mar-18) Sarenje KL; van Zwetselaar M; Kumburu H; Sonda T; Mmbaga B; Ngalamika O; Maimbolwa MC; Siame A; Munsaka S; Kwenda G; Kilimanjaro Christian Medical University College, Moshi, Tanzania.; Department of Midwifery Child, and Women's Health, School of Nursing Sciences, University of Zambia, Lusaka, Zambia.; Department of Dermato-venereology, University Teaching Hospital, Lusaka, Zambia.; Kilimanjaro Christian Medical Centre, Moshi, Tanzania.; Kilimanjaro Clinical Research Institute, Moshi, Kilimanjaro, Tanzania.; Department of Dermato-venereology, University Teaching Hospital, Lusaka, Zambia. kelvinsarenje@gmail.com.; Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka, P.O. Box 50110, Zambia.; Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka, P.O. Box 50110, Zambia. kelvinsarenje@gmail.com.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    BACKGROUND: Antimicrobial resistance (AMR) of Neisseria gonorrhoeae is a threat to public health as strains have developed resistance to antimicrobials available for the treatment of gonorrhea. Whole genome sequencing (WGS) can detect and predict antimicrobial resistance to enhance the control and prevention of gonorrhea. Data on the molecular epidemiology of N. gonorrhoeae is sparse in Zambia. This study aimed to determine the genetic diversity of N. gonorrhoeae isolated from patients attending sexually transmitted infection (STI) clinics in Lusaka, Zambia. METHODS: A cross-sectional study that sequenced 38 N. gonorrhoeae isolated from 122 patients with gonorrhea from 2019 to 2020 was conducted. The AMR profiles were determined by the E-test, and the DNA was extracted using the NucliSens easyMaG magnetic device. Whole genome sequencing was performed on the Illumina NextSeq550 platform. The Bacterial analysis pipeline (BAP) that is readily available at: https://cge.cbs.dtu.dk/services/CGEpipeline-1.1 was used for the identification of the species, assembling the genome, multi-locus sequence typing (MLST), detection of plasmids and AMR genes. Phylogeny by single nucleotide polymorphisms (SNPs) was determined with the CCphylo dataset. RESULTS: The most frequent STs with 18.4% of isolates each were ST CONCLUSION: This study revealed remarkable heterogeneity of N. gonorrhoeae with bla
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    Ecological Niche Modeling of
    (2023-Sep-08) Velu RM; Kwenda G; Bosomprah S; Chisola MN; Simunyandi M; Chisenga CC; Bumbangi FN; Sande NC; Simubali L; Mburu MM; Tembo J; Bates M; Simuunza MC; Chilengi R; Orba Y; Sawa H; Simulundu E; Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia.; Macha Research Trust, Choma P.O. Box 630166, Zambia.; Division of Molecular Pathobiology, International Institute for Zoonosis Control, Hokkaido University, N 20 W10, Kita-Ku, Sapporo 001-0020, Japan.; Department of Disease Control, School of Veterinary Medicine, University of Zambia, Lusaka P.O. Box 32379, Zambia.; International Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University, Hokkaido 060-0808, Japan.; Zambia National Public Health Institute, Ministry of Health, Lusaka P.O. Box 51925, Zambia.; One Health Research Center, Hokkaido University, Sapporo 001-0020, Japan.; Department of Geography and Environmental Studies, School of Natural Sciences, University of Zambia, Lusaka P.O. Box 32379, Zambia.; Department of Biostatistics, School of Public Health, University of Ghana, Accra P.O. Box LG13, Ghana.; National Malaria Elimination Centre, Chainama Hills Hospital Grounds, Lusaka P.O. Box 32509, Zambia.; Joseph Banks Laboratories, School of Life and Environmental Sciences, University of Lincoln, Lincolnshire LN6 7TS, UK.; Institute for Vaccine Research and Development, Hokkaido University, Sapporo 001-0021, Japan.; Africa Centre of Excellence for Infectious Diseases of Humans and Animals, University of Zambia, Lusaka P.O. Box 32379, Zambia.; Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka P.O. Box 50110, Zambia.; International Collaboration Unit, Global Virus Network, Baltimore, MD 21201, USA.; Department of Medicine and Clinical Sciences, School of Medicine, Eden University, Lusaka P.O. Box 37727, Zambia.; HerpeZ, University Teaching Hospital, Lusaka 10101, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    The circulation of both West Nile Virus (WNV) and Chikungunya Virus (CHIKV) in humans and animals, coupled with a favorable tropical climate for mosquito proliferation in Zambia, call for the need for a better understanding of the ecological and epidemiological factors that govern their transmission dynamics in this region. This study aimed to examine the contribution of climatic variables to the distribution of
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    Field evaluation of a novel, rapid diagnostic assay, and molecular epidemiology of enterotoxigenic E. coli among Zambian children presenting with diarrhea.
    (2022-Aug) Silwamba S; Chilyabanyama ON; Liswaniso F; Chisenga CC; Chilengi R; Dougan G; Kwenda G; Chakraborty S; Simuyandi M; Department of International Health, Johns Hopkins University, Baltimore, Maryland, United States of America.; Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka, Zambia.; Enteric Diseases and Vaccines Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Cambridge Institute for Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, United Kingdom.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) is one of the top aetiologic agents of diarrhea in children under the age of 5 in low-middle income countries (LMICs). The lack of point of care diagnostic tools for routine ETEC diagnosis results in limited data regarding the actual burden and epidemiology in the endemic areas. We evaluated performance of the novel Rapid LAMP based Diagnostic Test (RLDT) for detection of ETEC in stool as a point of care diagnostic assay in a resource-limited setting. METHODS: We conducted a cross-sectional study of 324 randomly selected stool samples from children under 5 presenting with moderate to severe diarrhea (MSD). The samples were collected between November 2012 to September 2013 at selected health facilities in Zambia. The RLDT was evaluated by targeting three ETEC toxin genes [heat labile toxin (LT) and heat stable toxins (STh and STp)]. Quantitative PCR was used as the "gold standard" to evaluate the diagnostic sensitivity and specificity of RLDT for detection of ETEC. We additionally described the prevalence and seasonality of ETEC. RESULTS: The study included 324 participants, 50.6% of which were female. The overall prevalence of ETEC was 19.8% by qPCR and 19.4% by RLDT. The children between 12 to 59 months had the highest prevalence of 22%. The study determined ETEC toxin distribution was LT 28/321(9%), ST 18/321(6%) and LT/ST 16/321(5%). The sensitivity and specificity of the RLDT compared to qPCR using a Ct 35 as the cut-off, were 90.7% and 97.5% for LT, 85.2% and 99.3% for STh and 100% and 99.7% for STp, respectively. CONCLUSION: The results of this study suggest that RLDT is sufficiently sensitive and specific and easy to implement in the endemic countries. Being rapid and simple, the RLDT also presents as an attractive tool for point-of-care testing at the health facilities and laboratories in the resource-limited settings.
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    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.
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    Identification of viral and bacterial pathogens from hospitalized children with severe acute respiratory illness in Lusaka, Zambia, 2011-2012: a cross-sectional study.
    (2015-Feb-12) Simusika P; Bateman AC; Theo A; Kwenda G; Mfula C; Chentulo E; Monze M; Centre for Infectious Disease Research in Zambia, 34681, Lusaka, Zambia. bateman.allen@gmail.com.; Virology Laboratory, University Teaching Hospital, RW1X, Lusaka, Zambia. psimusika@yahoo.co.uk.; Virology Laboratory, University Teaching Hospital, RW1X, Lusaka, Zambia. mmonze@uthlabs.org.zm.; Virology Laboratory, University Teaching Hospital, RW1X, Lusaka, Zambia. masoziuk@gmail.com.; Virology Laboratory, University Teaching Hospital, RW1X, Lusaka, Zambia. edwardchents@yahoo.com.; Department of Biomedical Sciences, School of Medicine, University of Zambia, P.O. Box 50110, Lusaka, Zambia. jaffekwenda@gmail.com.; Department of Biomedical Sciences, School of Medicine, University of Zambia, P.O. Box 50110, Lusaka, Zambia. christine.mfula@gmail.com.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    BACKGROUND: Morbidity and mortality from respiratory infections are higher in resource-limited countries than developed countries, but limited studies have been conducted in resource-limited settings to examine pathogens from patients with acute respiratory infections. Influenza surveillance has been conducted in Zambia since 2008; however, only 4.3% of patients enrolled in 2011-2012 were positive for influenza. Therefore, we examined non-influenza respiratory pathogens in children with severe acute respiratory illness (SARI) in Zambia, to estimate the scope of disease burden and determine commonly-identified respiratory pathogens. METHODS: Two reverse transcriptase polymerase chain reaction (rRT-PCR) methods (single and multiplex) were used to analyze nasopharyngeal and throat swabs collected from SARI cases under five years of age from January 2011 through December 2012. All specimens were negative for influenza by rRT-PCR. The panel of singleplex reactions targeted seven viruses, while the multiplex assay targeted thirty-three bacteria, fungi, and viruses. RESULTS: A set of 297 specimens were tested by singleplex rRT-PCR, and a different set of 199 were tested by multiplex rRT-PCR. Using the singleplex assay, 184/297 (61.9%) specimens were positive for one or more viruses. The most prevalent viruses were human rhinovirus (57/297; 19.2%), human adenovirus (50/297; 16.8%), and respiratory syncytial virus (RSV) (45/297; 15.2%). Using multiplex PCR, at least one virus was detected from 167/199 (83.9%) specimens, and at least one bacteria was detected from 197/199 (99.0%) specimens. Cytomegalovirus (415/199; 208.5%) and RSV (67/199; 33.7%) were the most commonly detected viruses, while Streptococcus pneumonie (109/199; 54.8%) and Moraxella catarrhalis (92/199; 46.2%) were the most commonly detected bacteria. CONCLUSIONS: Single infections and co-infections of many viruses and bacteria were identified in children with SARI. These results provide an estimate of the prevalence of infection and show which respiratory pathogens are commonly identified in patients. Further studies should investigate causal associations between individual pathogens and SARI.
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    Immunogenicity and waning immunity from the oral cholera vaccine (Shanchol™) in adults residing in Lukanga Swamps of Zambia.
    (2022) Ng Ombe H; Simuyandi M; Mwaba J; Luchen CC; Alabi P; Chilyabanyama ON; Mubanga C; Hatyoka LM; Muchimba M; Bosomprah S; Chilengi R; Kwenda G; Chisenga CC; Center for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana.; Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    INTRODUCTION: In cholera endemic areas, the periodicity of cholera outbreaks remains unpredictable, making it difficult to organize preventive efforts. Lack of data on duration of protection conferred by oral cholera vaccines further makes it difficult to determine when to deploy preemptive vaccination. We report on the immunogenicity and waning of immunity to Shanchol™ in Lukanga Swamps. METHODS: We enrolled a cohort of 223 participants aged between 18 and 65 years old from whom serum samples were collected at baseline, day 28 before administration of the second dose, and consecutively at 6, 12, 24, 30, 36, and 48 months. Vibriocidal antibody titres were measured and expressed as geometric mean titres. Box plots and 95% CI were computed at each visit for both Inaba and Ogawa. Seroconversion was defined as a four fold or greater increase in antibody titres compared to baseline titres. RESULTS: Overall, seroconversion against V. cholerae Inaba and Ogawa after 1st dose was 35/134 (26%) and 34/134 (25%) respectively. We observed a statistical difference in seroconversion between the two subgroups of baseline titres (low <80 and high ≥80) for both Inaba (p = 0.02) and Ogawa (p<0.0001). From a baseline of 13.58, anti-Ogawa GMT increased to 21.95 after the first dose, but rapidly waned to 14.52, 13.13, and 12.78 at months 6, 12 and 24 respectively, and then increased to 13.21, 18.67 and 23.65 at months 30, 36 and 48 respectively. A similar trend was observed for anti-Inaba GMT across the same time points. CONCLUSION: We found that Shanchol™ was immunogenic in our study population and that vibriocidal antibodies may not be a good marker for long-term immunity. The observed rise in titres after 36 months suggests natural exposure, and this may be a critical time window opening for natural transmission in an endemic areas. We recommend re-vaccination at this time point in high risk areas.
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    Microbiologic and virulence characteristics of Moraxella catarrhalis isolates from Zambian children presenting with acute pneumonia.
    (2022-Dec) Nawa M; Mwansa J; Mwaba J; Kaonga P; Mukubesa AN; Simuyandi M; Chisenga CC; Alabi P; Mwananyanda L; Thea DM; Chilengi R; Kwenda G; Department of Postgraduate Studies and Research, School of Medicine, Lusaka Apex Medical University, Lusaka, Zambia.; Department of Global Health, Boston University School of Public Health, Boston, Massachusetts, USA.; Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka, Zambia.; Department of Disease Control, School of Veterinary Medicine, University of Zambia, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Internal Medicine, School of Medicine, University of Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    BACKGROUND: Moraxella catarrhalis is one of the bacterial pathogens associated with childhood pneumonia, but its clinical importance is not clearly defined. OBJECTIVE: This study aimed to investigate the microbiologic and virulence characteristics of M. catarrhalis isolates obtained from children with pneumonia in Lusaka, Zambia. METHODS: This retrospective, cross-sectional study analyzed 91 M. catarrhalis isolates from induced sputum samples of children less than 5 years of age with pneumonia enrolled in the Pneumonia Etiology Research for Child Health study in Lusaka, Zambia between 2011 and 2014. Bacteria identification and virulence genes detection were performed by PCR and DNA sequencing, while antimicrobial susceptibility testing was determined by the Kirby-Bauer method. RESULTS: All the M. catarrhalis isolates were obtained from good-quality sputum samples and were the predominant bacteria. These isolates harbored virulence genes copB (100%), ompE (69.2%), ompCD (71.4%), uspA1 (92.3%), and uspA2 (69.2%) and were all β-lactamase producers. They showed resistance to ampicillin (100%), amoxicillin (100%), trimethoprim-sulfamethoxazole (92.3%), ciprofloxacin (46.2%), chloramphenicol (45.1%), erythromycin (36.3%), tetracycline (25.3%), cefuroxime (11.0%), and amoxicillin-clavulanate (2.2%), with 71.4% displaying multi-drug resistant phenotype but all susceptible to imipenem (100%). CONCLUSION: This study showed that M. catarrhalis isolates were the predominant or only bacterial isolates from the sputum samples analyzed. The findings provide supportive evidence for the pathogenic potential role of this bacterium in pediatric pneumonia. High multidrug resistance was also observed amongst the isolates, which can result in affected patients not responding to standard treatment, leading to prolonged illness, increased healthcare costs, and risk of death.
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    Mosquito-Borne Viral Pathogens Detected in Zambia: A Systematic Review.
    (2021-Aug-10) Velu RM; Kwenda G; Libonda L; Chisenga CC; Flavien BN; Chilyabanyama ON; Simunyandi M; Bosomprah S; Sande NC; Changula K; Muleya W; Mburu MM; Mubemba B; Chitanga S; Tembo J; Bates M; Kapata N; Orba Y; Kajihara M; Takada A; Sawa H; Chilengi R; Simulundu E; HerpeZ Infection Research and Training, University Teaching Hospital, Lusaka Private Bag RW1X Ridgeway, Lusaka P.O. Box 10101, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia.; School of Life Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.; School of Life Sciences, University of Lincoln, Brayford Pool, Lincoln LN6 7TS, UK.; Department of Paraclinical Studies, School of Veterinary Medicine, University of Zambia, Lusaka P.O. Box 32379, Zambia.; Macha Research Trust, Choma P.O. Box 630166, Zambia.; Division of Molecular Pathobiology, International Institute for Zoonosis Control, Hokkaido University, N 20 W10, Kita-ku, Sapporo 001-0020, Japan.; Department of Biomedical Sciences, School of Veterinary Medicine, University of Zambia, Lusaka P.O. Box 32379, Zambia.; Department of Disease Control, School of Veterinary Medicine, University of Zambia, Lusaka P.O. Box 32379, Zambia.; Division of Global Epidemiology, International Institute for Zoonosis Control, Hokkaido University, N 20 W10, Kita-ku, Sapporo 001-0020, Japan.; School of Veterinary Medicine, University of Namibia, Windhoek Private Bag 13301, Namibia.; Department of Biostatistics, School of Public Health, University of Ghana, Accra P.O. Box LG13, Ghana.; Africa Center of Excellence for Infectious Diseases of Humans and Animals, University of Zambia, Lusaka P.O. Box 32379, Zambia.; Department of Zoology and Aquatic Sciences, School of Natural Resources, Copperbelt University, Kitwe P.O. Box 21692, Zambia.; Global Virus Network, 725 W Lombard St., Baltimore, MD 21201, USA.; Zambia National Public Health Institute, Ministry of Health, Lusaka P.O. Box 30205, Zambia.; Department of Disease Control and Prevention, School of Medicine and Health Sciences, Eden University, Lusaka P.O. Box 37727, Zambia.; Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka P.O. Box 50110, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    Emerging and re-emerging mosquito-borne viral diseases are a threat to global health. This systematic review aimed to investigate the available evidence of mosquito-borne viral pathogens reported in Zambia. A search of literature was conducted in PubMed and Google Scholar for articles published from 1 January 1930 to 30 June 2020 using a combination of keywords. Eight mosquito-borne viruses belonging to three families,
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    Serum vibriocidal responses when second doses of oral cholera vaccine are delayed 6 months in Zambia.
    (2021-Jul-22) Mwaba J; Chisenga CC; Xiao S; Ng'ombe H; Banda E; Shea P; Mabula-Bwalya C; Mwila-Kazimbaya K; Laban NM; Alabi P; Chirwa-Chobe M; Simuyandi M; Harris J; Iyer AS; Bosomprah S; Scalzo P; Murt KN; Ram M; Kwenda G; Ali M; Sack DA; Chilengi R; Debes AK; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Electronic address: adebes1@jhu.edu.; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.; Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka, Zambia.; Research Department, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Research Department, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka, Zambia.; Research Department, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; London School of Hygiene and Tropical Medicine, United Kingdom.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    Two-dose killed oral cholera vaccines (OCV) are currently being used widely to control cholera. The standard dose-interval for OCV is 2 weeks; however, during emergency use of the vaccine, it may be more appropriate to use the available doses to quickly give a single dose to more people and give a delayed second dose when more vaccine becomes available. This study is an open label, randomized, phase 2 clinical trial of the vibriocidal response induced by OCV, comparing the responses when the second dose was given either 2 weeks (standard dose interval) or 6 months (extended dose interval) after the first dose. Vaccine was administered to healthy participants > 1 year of age living in the Lukanga Swamps area of Zambia. Three age cohorts (<5 years, 5-14 years, and ≥ 15 years) were randomized to the either dose-interval. The primary outcome was the vibriocidal GMT 14 days after the second dose. 156 of 172 subjects enrolled in the study were included in this analysis. The Inaba vibriocidal titers were not significantly different 14 days post dose two for a standard dose-interval GMT: 45.6 (32-64.9), as compared to the GMT 47.6 (32.6-69.3), for the extended dose-interval, (p = 0.87). However, the Ogawa vibriocidal GMTs were significantly higher 14 days post dose two for the extended-dose interval at 87.6 (58.9-130.4) compared to the standard dose-interval group at 49.7 (34.1-72.3), p = 0.04. Vibriocidal seroconversion rates (a > 4-fold rise in vibriocidal titer) were not significantly different between dose-interval groups. This study demonstrated that vibriocidal titers 14 days after a second dose when given at an extended\ dose interval were similar to the standard dose-interval. The findings suggest that a flexible dosing schedule may be considered when epidemiologically appropriate. The trial was registered at Clinical Trials.gov (NCT03373669).
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    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.

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