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The CIDRZ Research Repository serves as an open-access archive for peer-reviewed publications, conference papers, and other scholarly outputs from CIDRZ researchers. Our goal is to promote the dissemination of knowledge and support evidence-based public health initiatives.
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Item 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; Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana.; Flow Cytometry and Immunology Facility, Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine, Fajara, Banjul, The Gambia.; 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.Item Application of a Novel Proteomic Microarray Reveals High Exposure to Diarrhoeagenic(2024-Feb-20) Mwape K; Mubanga C; Chilyabanyama ON; Chibesa K; Chisenga CC; Silwamba S; Randall A; Liang X; Barnard TG; Simuyandi M; Chilengi R; Antigen Discovery Inc., 1 Technology Dr., STE E309, Irvine, CA 92618, USA.; Department of Basic Medical Sciences, Michael Chilufya Sata School of Medicine, Copperbelt University, Ndola P.O. Box 71191, Zambia.; Enteric Disease and Vaccines Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia.; 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.; Next Generation Sequencing Unit and Division of Virology, School of Pathology, Faculty of Health Sciences, University of the Free State, P.O. Box 339, Bloemfontein 9300, South Africa.; Water and Health Research Center, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein, Johannesburg 2028, South Africa.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)DiarrhoeagenicItem The Incidence and Risk Factors for Enterotoxigenic(2024-Mar-29) Sukwa N; Bosomprah S; Somwe P; Muyoyeta M; Mwape K; Chibesa K; Luchen CC; Silwamba S; Mulenga B; Munyinda M; Muzazu S; Chirwa M; Chibuye M; Simuyandi M; Chilengi R; Svennerholm AM; Department of Microbiology and Immunology, University of Gothenburg, 40530 Gothenburg, Sweden.; Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka P.O. Box 34681, Zambia.; Department of Biostatistics, School of Public Health, University of Ghana, Accra P.O. Box LG13, Ghana.This study aimed to estimate the incidence and risk factors for EnterotoxigenicItem Seroconversion and Kinetics of Vibriocidal Antibodies during the First 90 Days of Re-Vaccination with Oral Cholera Vaccine in an Endemic Population.(2024-Apr-08) Chisenga CC; Phiri B; Ng'ombe H; Muchimba M; Musukuma-Chifulo K; Silwamba S; Laban NM; Luchen C; Liswaniso F; Chibesa K; Mubanga C; Mwape K; Simuyandi M; Cunningham AF; Sack D; Bosomprah S; Institute of Immunology and Immunotherapy, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.; 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.; Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)Despite the successful introduction of oral cholera vaccines, Zambia continues to experience multiple, sporadic, and protracted cholera outbreaks in various parts of the country. While vaccines have been useful in staying the cholera outbreaks, the ideal window for re-vaccinating individuals resident in cholera hotspot areas remains unclear. Using a prospective cohort study design, 225 individuals were enrolled and re-vaccinated with two doses of Shanchol™, regardless of previous vaccination, and followed-up for 90 days. Bloods were collected at baseline before re-vaccination, at day 14 prior to second dosing, and subsequently on days 28, 60, and 90. Vibriocidal assay was performed on samples collected at all five time points. Our results showed that anti-LPS and vibriocidal antibody titers increased at day 14 after re-vaccination and decreased gradually at 28, 60, and 90 days across all the groups. Seroconversion rates were generally comparable in all treatment arms. We therefore conclude that vibriocidal antibody titers generated in response to re-vaccination still wane quickly, irrespective of previous vaccination status. However, despite the observed decline, the levels of vibriocidal antibodies remained elevated over baseline values across all groups, an important aspect for Zambia where there is no empirical evidence as to the ideal time for re-vaccination.Item Comparative analysis of cholera serum vibriocidal antibodies from Convalescent and vaccinated adults in Zambia.(2024-Aug-13) Ng'ombe H; Bosomprah S; Phiri B; Muchimba M; Liswaniso F; Chibuye M; Luchen CC; Chibesa K; Musukuma-Chifulo K; Mwape K; Tigere S; Silwamba S; Sinkala A; Simuyandi M; Mbewe N; Kapaya F; Cunningham AF; Chilengi R; Sack D; Chisenga CC; Centre for Infectious Disease Research in Zambia, Corner of Lukasu and Danny Pule Roads, Mass Media, Lusaka, Zambia.; Ministry of Health, Levy Mwanawasa University Teaching Hospital, Chainama, Off Great East, P.0 Box 310084, Lusaka, Zambia.; Institute of Immunology and Immunotherapy, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom.; Zambia National Public Health Institute, Stand 1186, Corner of Chaholi & Addis Ababa Roads Rhodes Park, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Corner of Lukasu and Danny Pule Roads, Mass Media, Lusaka, Zambia; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana. Electronic address: Samuel.Bosomprah@cidrz.org.; John Hopkins University, 615 N Wolfe St, Baltimore, United States of America.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)Cholera is responsible for 1.3 to 4.0 million cholera cases globally and poses a significant threat, with Zambia reporting 17,169 cases as of 4th February 2024. Recognizing the crucial link between natural cholera infections and vaccine protection, this study aimed to assess immune responses post cholera infection and vaccination. This was a comparative study consisting of 50 participants enrolled during a cholera outbreak in Zambia's Eastern Province and an additional 56 participants who received oral cholera vaccinations in Zambia's Central Province. Vibriocidal antibodies were plotted as geometric mean titres in the naturally infected and vaccinated individuals. A significant difference (p < 0.047) emerged when comparing naturally infected to fully vaccinated individuals (2 doses) on day 28 against V. cholerae Ogawa. Those who received two doses of the oral cholera vaccine had higher antibody titres than those who were naturally infected. Notably, the lowest titres occurred between 0-9 days post onset, contrasting with peak responses at 10-19 days. This study addresses a critical knowledge gap in understanding cholera immunity dynamics, emphasizing the potential superiority of vaccination-induced immune responses. We recommend post infection vaccination after 40 days for sustained immunity and prolonged protection, especially in cholera hotspots.Item Association of Maternal Immunity with Rotavirus Vaccine Immunogenicity in Zambian Infants.(2016) Chilengi R; Simuyandi M; Beach L; Mwila K; Becker-Dreps S; Emperador DM; Velasquez DE; Bosomprah S; Jiang B; Centres for Disease Control and Prevention, Atlanta, Georgia, United States of America.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; 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: Live attenuated oral vaccines against rotavirus (RV) have been shown to be less efficacious in children from developing countries. Reasons for this disparity are not fully understood. We assessed the role of maternal factors including breast milk RV-specific IgA, transplacentally acquired infant serum RV-specific IgG and maternal HIV status in seroconversion among Zambian infants routinely immunized with Rotarix™ (RV1). METHODS: 420 mother-child pairs were recruited at infant age 6-12 weeks in Lusaka. Clinical information and samples were collected at baseline and at one month following the second dose of RV1. Determination of breast milk RV-specific IgA and serum RV-specific IgA and IgG was done using standardized ELISA. Seroconversion was defined as a ≥ 4 fold rise in serum IgA titre from baseline to one-month post RV1 dose 2, while seropositivity of IgA was defined as serum titre ≥ 40 and antibody variables were modelled on log-base 2. Logistic regression was used to identify predictors of the odds of seroconversion. RESULTS: Baseline infant seropositivity was 25.5% (91/357). The seroconversion frequency was 60.2% (130/216). Infants who were IgA seropositive at baseline were less likely to seroconvert compared to their seronegative counterparts (P = 0.04). There was no evidence of an association between maternal HIV status and seroconversion (P = 0.25). Higher titres of breast milk rotavirus-specific IgA were associated with a lower frequency of seroconverson (Nonparametric test for trend Z = -2.84; P<0.01): a two-fold increase in breast milk RV-specific IgA titres was associated with a 22% lower odds of seroconversion (OR = 0.80; 95% CI = 0.68-0.94; P = 0.01). There was seasonal variation in baseline breast milk rotavirus-specific IgA titres, with significantly higher GMTs during the cold dry months (P = 0.01). CONCLUSION: Low immunogenicity of RV1 vaccine could be explained in part by exposure to high antibody titres in breast milk and early exposure to wild-type rotavirus infections. Potential interference of anti-RV specific IgA in breast milk and pre-vaccination serum RV specific-IgA and IgG titres with RV1 seroconversion and effectiveness requires further research.Item Anti-microbial peptide gene expression during oral vaccination: analysis of a randomized controlled trial.(2016-Nov) Simuyandi M; Kapulu M; Kelly P; Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia. m.p.kelly@qmul.ac.uk.; Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia.; Programme for the Awareness and Elimination of Diarrhoea (PAED), Centre for Infectious Disease Research in Zambia.; Barts and the London School of Medicine, London, UK. m.p.kelly@qmul.ac.uk.; Biological Sciences Department, School of Natural Sciences, University of Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)We have observed previously that micronutrient supplementation ameliorated suppression of α-defensin expression during diarrhoea. However, how interactions between anti-microbial peptide (AMP) expression and diarrhoeal disease are altered by micronutrient supplementation remain unclear. Using oral vaccination as a model of intestinal infection, we measured changes in AMP expression during multiple micronutrient supplementation. In the first part, volunteers underwent duodenal jejunal biopsy before and at 1, 2, 4 or 7 days after administration of one of three live, attenuated oral vaccines against rotavirus, typhoid and enterotoxigenic Escherichia coli. In the second part, participants were randomized to receive a multiple micronutrient supplement or placebo for 6 weeks before undergoing intestinal biopsy, vaccination against typhoid and rebiopsy after 14 days. Expression of human alpha-defensin (HD)5, HD6, hBD1, hBD2 and LL-37 was measured by quantitative reverse transcription-polymerase chain reaction. Taken together, the bacterial vaccines, but not rotavirus vaccine, reduced HD5 expression (P = 0·02, signed-rank test) and reduced LL-37 expression in seven of the eight individuals whose biopsies had expression prevaccination (P = 0·03). hBD2 was not detected. In the controlled trial, HD5 and HD6 expression after vaccination was lower [median ratio 0·5, interquartile range (IQR) = 0·07-2·2 and 0·58, IQR = 0·13-2·3, respectively] than before vaccination. There was no significant effect detected of micronutrient supplementation on expression of HD5, HD6, hBD1 or LL-37. We conclude that live attenuated bacterial vaccines, but not rotavirus vaccine, can reduce intestinal α-defensins, and typhoid vaccine reduced LL-37 expression. We found no evidence that micronutrient supplementation in the short term had any impact on anti-microbial peptide expression.Item Contribution of Maternal Immunity to Decreased Rotavirus Vaccine Performance in Low- and Middle-Income Countries.(2017-Jan) Mwila K; Chilengi R; Simuyandi M; Permar SR; Becker-Dreps S; Department of Family Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia Roma.Chilengi@cidrz.org sbd@unc.edu.; Department of Family Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA Roma.Chilengi@cidrz.org sbd@unc.edu.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Pediatrics, Human Vaccine Institute, Duke University, Durham, North Carolina, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)The role of maternal immunity, received by infants either transplacentally or orally from breast milk, in rotavirus vaccine (RV) performance is evaluated here. Breastfeeding withholding has no effect on vaccine responses, but higher levels of transplacental rotavirus-specific IgG antibody contribute to reduced vaccine seroconversion. The gaps in knowledge on the factors associated with low RV efficacy in low- and middle-income countries (LMIC) remain, and further research is needed to shed more light on these issues.Item Effect of innate antiviral glycoproteins in breast milk on seroconversion to rotavirus vaccine (Rotarix) in children in Lusaka, Zambia.(2017) Mwila-Kazimbaya K; Garcia MP; Bosomprah S; Laban NM; Chisenga CC; Permar SR; Simuyandi M; Munsaka S; Chilengi R; University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, North Carolina, United States of America.; Department of Paediatrics, Human Vaccine Institute, Duke University, Durham, North Carolina.; Department of biomedical sciences, School of Health sciences, University of Zambia, Lusaka, Zambia.; Department of Biostatistics, School of Public Health, University of Ghana, Legon, Accra, Ghana.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)INTRODUCTION: Rotavirus vaccines have been introduced into national immunization programmes to mitigate morbidity and mortality associated rotavirus diarrhoea. Lower vaccine effectiveness has however been noted in low-middle income countries, but little is known about the role of maternal components found in breast milk. This study assessed the effect of lactoferrin, lactadherin, and tenascin-c on rotavirus vaccine seroconversion. METHODS: This was a retrospective cohort study of 128 infants who had been fully immunized with Rotarix™. Serum samples were collected from the infant at baseline and one month after second rotavirus vaccine dose. Breast milk samples were collected from mothers at baseline. Standard ELISA was used to determine titres of rotavirus-specific immunologlobulin G and A in breast milk and serum as well as concentrations of lactoferrin, lactadherin, and tenascin-c. Poisson regression model with robust standard error was used to estimate the effect of breast milk components on seroconversion. The components were modelled on log base 2 so that the effect would be interpreted as a doubling of the concentration. RESULTS: In a multivariable analysis adjusting for maternal age, maternal HIV status, seropositivity at baseline, sex, age of child at vaccination as well as breast milk IgA and IgG, we found evidence of independent effect of LA (Adjusted IRR = 0.95; 95% CI = 0.91-0.99; P = 0.019) on seroconversion while there was no evidence for TNC (Adjusted IRR = 1.00; 95% CI = 0.85-1.17; P = 0.967) and LF (Adjusted RR = 1.01; 95% CI = 0.96-1.05); P = 0.802). We explored the joint effects of the three components but we found no evidence (Adjusted RR = 0.95; 95% CI = 0.81; P = 0.535). CONCLUSION: High breast milk concentrations of lactadherin might play a role in infant's failure to seroconvert to rotavirus vaccines. Further research to understand this observed association is an important consideration.Item Evaluating the costs of cholera illness and cost-effectiveness of a single dose oral vaccination campaign in Lusaka, Zambia.(2019) Tembo T; Simuyandi M; Chiyenu K; Sharma A; Chilyabanyama ON; Mbwili-Muleya C; Mazaba ML; Chilengi R; Lusaka District Health Office/ Ministry of Health, Lusaka, Zambia.; Zambia National Public Health Institute, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)INTRODUCTION: In 2016, for the very first time, the Ministry of Health in Zambia implemented a reactive outbreak response to control the spread of cholera and vaccinated at-risk populations with a single dose of Shancol-an oral cholera vaccine (OCV). This study aimed to assess the costs of cholera illness and determine the cost-effectiveness of the 2016 vaccination campaign. METHODOLOGY: From April to June 2017, we conducted a retrospective cost and cost-effectiveness analysis in three peri-urban areas of Lusaka. To estimate costs of illness from a household perspective, a systematic random sample of 189 in-patients confirmed with V. cholera were identified from Cholera Treatment Centre registers and interviewed for out-of-pocket costs. Vaccine delivery and health systems costs were extracted from financial records at the District Health Office and health facilities. The cost of cholera treatment was derived by multiplying the subsidized cost of drugs by the quantity administered to patients during hospitalisation. The cost-effectiveness analysis measured incremental cost-effectiveness ratio-cost per case averted, cost per life saved and cost per DALY averted-for a single dose OCV. RESULTS: The mean cost per administered vaccine was US$1.72. Treatment costs per hospitalized episode were US$14.49-US$18.03 for patients ≤15 years old and US$17.66-US$35.16 for older patients. Whereas households incurred costs on non-medical items such as communication, beverages, food and transport during illness, a large proportion of medical costs were borne by the health system. Assuming vaccine effectiveness of 88.9% and 63%, a life expectancy of 62 years and Gross Domestic Product (GDP) per capita of US$1,500, the costs per case averted were estimated US$369-US$532. Costs per life year saved ranged from US$18,515-US$27,976. The total cost per DALY averted was estimated between US$698-US$1,006 for patients ≤15 years old and US$666-US$1,000 for older patients. CONCLUSION: Our study determined that reactive vaccination campaign with a single dose of Shancol for cholera control in densely populated areas of Lusaka was cost-effective.