Browsing by Author "Chisenga CC"

Now showing 1 - 20 of 25

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; 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.; Department of Basic Medical Sciences, Michael Chilufya Sata School of Medicine, Copperbelt University, Ndola P.O. Box 71191, Zambia.; Water and Health Research Center, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein, Johannesburg 2028, South Africa.; Enteric Disease and Vaccines Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia.; Antigen Discovery Inc., 1 Technology Dr., STE E309, Irvine, CA 92618, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Diarrhoeagenic
Assessment of the influence of ABO blood groups on oral cholera vaccine immunogenicity in a cholera endemic area in Zambia.
(2023-Jan-23) Chisenga CC; Bosomprah S; Chilyabanyama ON; Alabi P; Simuyandi M; Mwaba J; Ng'ombe H; Laban NM; Luchen CC; Chilengi R; Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka, Zambia.; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. Caroline.Chisenga@cidrz.org.; School of Medicine, University of Lusaka, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Histo-blood group antigens (HBGAs) which include the ABO and Lewis antigen systems have been known for determining predisposition to infections. For instance, blood group O individuals have a higher risk of severe illness due to V. cholerae compared to those with non-blood group O antigens. We set out to determine the influence that these HBGAs have on oral cholera vaccine immunogenicity and seroconversion in individuals residing within a cholera endemic area in Zambia. METHODOLOGY: We conducted a longitudinal study nested under a clinical trial in which samples from a cohort of 223 adults who were vaccinated with two doses of Shanchol™ and followed up over 4 years were used. We measured serum vibriocidal geometric mean titers (GMTs) at Baseline, Day 28, Months 6, 12, 24, 30, 36 and 48 in response to the vaccine. Saliva obtained at 1 year post vaccination was tested for HBGA phenotypes and secretor status using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Of the 133/223 participants included in the final analysis, the majority were above 34 years old (58%) and of these, 90% were males. Seroconversion rates to V. cholerae O1 Inaba with non-O (23%) and O (30%) blood types were comparable. The same pattern was observed against O1 Ogawa serotype between non-O (25%) and O (35%). This trend continued over the four-year follow-up period. Similarly, no significant differences were observed in seroconversion rates between the non-secretors (26%) and secretors (36%) against V. cholerae O1 Inaba. The same was observed for O1 Ogawa in non-secretors (22%) and the secretors (36%). CONCLUSION: Our results do not support the idea that ABO blood grouping influence vaccine uptake and responses against cholera.
Association of biomarkers of enteric dysfunction, systemic inflammation, and growth hormone resistance with seroconversion to oral rotavirus vaccine: A lasso for inference approach.
(2023) Mwila-Kazimbaya K; Bosomprah S; Chilyabanyama ON; Chisenga CC; Chibuye M; Laban NM; Simuyandi M; Huffer B; Iturriza-Gomara M; Choy RKM; Chilengi R; Department of Global Health, Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana.; PATH, Seattle, Washington, United States of America.; Research Division, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Cincinnati Childrens Hospital Medical Center, Cincinnati, Ohio, United States of America.; Centre for Vaccine Innovation and Access, PATH, Geneve, Switzerland.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Rotavirus gastroenteritis remains a leading cause of morbidity and mortality despite the introduction of vaccines. Research shows there are several factors contributing to the reduced efficacy of rotavirus vaccines in low- and middle-income settings. Proposed factors include environmental enteric dysfunction (EED), malnutrition, and immune dysfunction. This study aimed to assess the effect of these factors on vaccine responses using a machine learning lasso approach. METHODS: Serum samples from two rotavirus clinical trials (CVIA 066 n = 99 and CVIA 061 n = 124) were assessed for 11 analytes using the novel Micronutrient and EED Assessment Tool (MEEDAT) multiplex ELISA. Immune responses to oral rotavirus vaccines (Rotarix, Rotavac, and Rotavac 5D) as well as a parenteral rotavirus vaccine (trivalent P2-VP8) were also measured and machine learning using the lasso approach was then applied to investigate any associations between immune responses and environmental enteric dysfunction, systemic inflammation, and growth hormone resistance biomarkers. RESULTS: Both oral and parenteral rotavirus vaccine responses were negatively associated with retinol binding protein 4 (RBP4), albeit only weakly for oral vaccines. The parenteral vaccine responses were positively associated with thyroglobulin (Tg) and histidine-rich protein 2 (HRP2) for all three serotypes (P8, P6 and P4), whilst intestinal fatty acid binding protein (I-FABP) was negatively associated with P6 and P4, but not P8, and soluble transferrin receptor (sTfR) was positively associated with P6 only. CONCLUSION: MEEDAT successfully measured biomarkers of growth, systemic inflammation, and EED in infants undergoing vaccination, with RBP4 being the only analyte associated with both oral and parenteral rotavirus vaccine responses. Tg and HRP2 were associated with responses to all three serotypes in the parenteral vaccine, while I-FABP and sTfR results indicated possible strain specific immune responses to parenteral immunization.
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; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana. Electronic address: Samuel.Bosomprah@cidrz.org.; 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.; 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.; 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.
Diagnostic accuracy of saliva-based testing as a Vibrio cholerae surveillance tool among naturally infected patients.
(2025-Jan-21) Chisenga CC; Phiri B; Ng'ombe H; Muchimba M; Liswaniso F; Bernshtein B; Cunningham AF; Sack D; Bosomprah S; 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.; Institute of Immunology and Immunotherapy, University of Birmingham, Edgbaston, Birmingham, UK.; Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.; Alter Lab, Ragon Institute of MGH, MIT and Harvard, Boston, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Saliva, as a diagnostic medium, offers a promising alternative to blood by virtue of its non-invasive collection, which enhances patient compliance, especially in paediatric and geriatric populations. In this study, we assessed the utility of saliva as a non-invasive medium for measuring Vibrio cholerae-specific serum antibodies in naturally infected individuals. We tested paired serum and saliva samples obtained from a total of 63 patients with cholera enrolled in a cohort study. Vibriocidal antibodies assay (IgM/IgG) as markers for accurate determination was used to determine cholera-specific antibody levels. Using receiver operating characteristics (ROC) curve, we found that the best cut-off that maximizes (sensitivity + specificity) is 10 titres. At this saliva titre, the sensitivity is 76.9% (95%CI: 60.9%, 87.7%) and specificity is 80.0% (95%CI: 56.6%, 92.5%). Using Spearman's correlation coefficient, we also found evidence of a positive correlation between V. cholerae saliva and serum antibodies (rho = 0.66, P < 0.001). In conclusion, saliva-based diagnostic cholera tests have high diagnostic accuracy and would be advantageous, cheaper, and quicker for early diagnosis of severe cholera outcomes.
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
Effect of HIV status and retinol on immunogenicity to oral cholera vaccine in adult population living in an endemic area of Lukanga Swamps, Zambia.
(2021) Luchen CC; Mwaba J; Ng'ombe H; Alabi PIO; Simuyandi M; Chilyabanyama ON; Hatyoka LM; Mubanga C; Bosomprah S; Chilengi R; Chisenga CC; Amsterdam UMC, University of Amsterdam, Institute for Infection and Immunity, Amsterdam, the Netherlands.; Enteric Diseases and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana.; University of Zambia, School of Health Sciences, Lusaka, Zambia.
BACKGROUND: We set out to assess the impact of human immunodeficiency virus (HIV) and micronutrient deficiency as indicated by serum retinol levels on the immune responses to Oral Cholera Vaccine (Shanchol™) in a cohort of participants in Lukanga Swamps, Zambia. Cholera remains endemic in Zambia with vaccines being the only effective preventive measures. However, the effect of these vaccines on populations living with HIV has not been widely documented. METHODS: HIV testing and confirmation was done using the Alere Determine™ HIV-1/2 and Uni-Gold™ kits while vibriocidal antibody assay was applied for vaccine immunogenicity. Serum retinol analysis was assessed by Shimadzu Prominence HCT-2010 High Performance Liquid Chromatography (HPLC). The primary outcome was log transformed geometric mean titre. RESULTS: From 47 participants screened for HIV, 51% (24) tested positive. There was a statistically significant reduction in Ogawa geometric mean ratio (GMR) by 67% (GMR = 0.33; 95% CI: -0.15, 0.76; p-value = 0.009) attributable to HIV positivity with a non-significant reduction in Inaba GMR by about 50% due to HIV positivity. When doubling of retinol levels modelled, GMR reduction against Ogawa were non-significant but that against Inaba resulted in a significant reduction in geometric mean titer (GMT) (GMT-0.33, C.I 0.16-0.66, p-value 0.002). At 1000copies/ml viral load cut off and 350 cells/μl CD4 counts, Ogawa GMT was two times higher 11.16 (95%CI: 8.20-15.19) versus 6.06 (95%CI: 4.04-9.10) in low viremia participants, and three times higher in above threshold CD4 count participants; 24.81 (95%CI: 18.94-32.50) versus 7.07 (95%CI: 5.22-9.58). CONCLUSION: Our results show that while Shanchol™ is immunogenic in both HIV+/- individuals, HIV + participants responded poorly. Viral load and CD4 count affected vaccine immunogenicity. More research is required for detailed understanding of this in order to appropriately inform policy and practice.
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; Department of Paediatrics, Human Vaccine Institute, Duke University, Durham, North Carolina.; University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, North Carolina, United States of America.; 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.
Epstein-Barr Virus Detection in the Central Nervous System of HIV-Infected Patients.
(2022-Sep-22) Musukuma-Chifulo K; Siddiqi OK; Chilyabanyama ON; Bates M; Chisenga CC; Simuyandi M; Sinkala E; Dang X; Koralnik IJ; Chilengi R; Munsaka S; HerpeZ Infection Research and Training, University Teaching Hospital, Lusaka Private Bag RW1X Ridgeway, Lusaka P.O. Box 10101, Zambia.; Department of Biomedical Science, School of Health Sciences, University of Zambia, Lusaka P.O. Box 50110, Zambia.; Department of Research, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia.; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.; School of Life & Environmental Sciences, University of Lincoln, Lincoln LN6 7TS, UK.; Department of Internal Medicine, School of Medicine, University of Zambia, Lusaka P.O. Box 50110, Zambia.; Department of Internal Medicine, Center for Virology and Vaccines Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.; Global Neurology Program, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Simply detecting Epstein-Barr virus deoxyribonucleic acid (EBV-DNA) is insufficient to diagnose EBV-associated diseases. The current literature around EBV-DNA detection from cerebrospinal fluid (CSF) in human immunodeficiency virus (HIV)-positive non-lymphoma patients was systematically reviewed and a meta-analysis reporting the estimated pooled prevalence in this population when PCR methods are employed, targeting different sequence segments within the EBV genome, was conducted. Using a combination of three key concepts-Epstein-Barr virus detection, central nervous system disease, and human cerebrospinal fluid-and their MeSH terms, the PubMed database was searched. A total of 273 papers reporting the detection of EBV in CNS were screened, of which 13 met the inclusion criteria. The meta-analysis revealed a pooled prevalence of EBV-DNA in CSF of 20% (CI: 12-31%). The highest pooled prevalence was from studies conducted on the African population at 39% (CI: 27-51%). The investigation of the presence of EBV-DNA in the CSF was also very varied, with several gene targets used. While most patients from the articles included in this review and meta-analysis were symptomatic of CNS disorders, the pathogenicity of EBV in non-lymphoma HIV patients when detected in CSF has still not been determined. The presence of EBV-DNA in the CNS remains a concern, and further research is warranted to understand its significance in causing CNS disorders.
Experiences of capacity strengthening in sanitation and hygiene research in Africa and Asia: the SHARE Research Consortium.
(2019-Aug-05) Torondel B; Balls E; Chisenga CC; Kumwenda S; Okello E; Simiyu S; Morse T; Smith K; Mumma J; Banzi J; Harvey E; Chidziwisano K; Chipungu J; Grosskurth H; Beda A; Kapiga S; EstevesMills J; Cumming O; Cairncross S; Chilengi R; Centre for Water, Sanitation, Hygiene and Appropriate Technology Development, University of Malawi - The Polytechnic, Blantyre, Malawi.; Center for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Disease Control, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, United Kingdom.; WaterAid Tanzania, Dar es Salaam, Tanzania.; Mwanza Intervention Trials Unit, Mwanza, Tanzania.; Department of Disease Control, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, United Kingdom. belen.torondel@lshtm.ac.uk.; WaterAid, London, United Kingdom.; Great Lakes University of Kisumu, Kisumu, Kenya.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
The Sanitation and Hygiene Applied Research for Equity (SHARE) Research Programme consortium is a programme funded by the United Kingdom Department for International Development (DFID) that aims to contribute to achieving universal access to effective, sustainable, and equitable sanitation and hygiene worldwide. The capacity development component is an important pillar for this programme and different strategies were designed and implemented during the various phases of SHARE. This paper describes and reflects on the capacity-building strategies of this large multi-country research consortium, identifying lessons learnt and proposing recommendations for future global health research programmes. In the first phase, the strategy focused on increasing the capacity of individuals and institutions from low- and middle-income countries in conducting their own research. SHARE supported six PhD students and 25 MSc students, and organised a wide range of training events for different stakeholders. SHARE peer-reviewed all proposals that researchers submitted through several rounds of funding and offered external peer-review for all the reports produced under the partner's research platforms. In the second phase, the aim was to support capacity development of a smaller number of African research institutions to move towards their independent sustainability, with a stronger focus on early and mid-career scientists within these institutions. In each institution, a Research Fellow was supported and a specific capacity development plan was jointly developed.Strategies that yielded success were learning by doing (supporting institutions and postgraduate students on sanitation and hygiene research), providing fellowships to appoint mid-career scientists to support personal and institutional development, and supporting tailored capacity-building plans. The key lessons learnt were that research capacity-building programmes need to be driven by local initiatives tailored with support from partners. We recommend that future programmes seeking to strengthen research capacity should consider targeted strategies for individuals at early, middle and later career stages and should be sensitive to other institutional operations to support both the research and management capacities.
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.
Field performance of the Determine HBsAg point-of-care test for diagnosis of hepatitis B virus co-infection among HIV patients in Zambia.
(2018-Jan) Chisenga CC; Musukuma K; Chilengi R; Zürcher S; Munamunungu V; Siyunda A; Ojok D; Bauer S; Wandeler G; Vinikoor M; Institute for Infectious Diseases, University of Bern, Bern, Switzerland.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. Electronic address: caroline.chisenga@cidrz.org.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; School of Medicine, University of Zambia, Lusaka, Zambia.; Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; School of Medicine, University of Zambia, Lusaka, Zambia; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: We evaluated the field performance of a rapid point-of-care (POC) test for hepatitis B surface antigen (HBsAg) that could support decentralization and scale-up of hepatitis B virus (HBV) diagnosis in Africa. OBJECTIVE: To determine the field performance of the Determine HBsAg POC test for diagnosis of HBV co-infection among HIV patients in Zambia. STUDY DESIGN: Between 2013-2014, we screened HIV-infected adults for HBsAg at two urban clinics in Zambia. A subset were tested with the POC Determine HBsAg (Alere, USA) by finger prick in the clinic and HBsAg serology (Access2Analyzer, Beckman Coulter) at a reference laboratory. If either test was reactive, we determined HBV viral load (VL) and genotype. We described patient demographic and clinical characteristics (including liver fibrosis) and assessed the sensitivity, specificity, positive and negative predictive values (PPV and NPV) of the Determine test. In secondary analyses, we assessed sensitivity among patients with replicating HBV (i.e., VL>20 IU/ml) and with high HBV VL (i.e.,>20,000IU/ml). RESULTS: Among 412 participants with both HBsAg tests, median age was 34 years, 51% were women, and median CD4 was 208 cells/mm CONCLUSIONS: Determine HBsAg is a cheaper alternative HBV testing option compared to the gold standard ELISA and has high specificity and good sensitivity in the field among HIV-infected individuals.
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.
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.
In-vitro inhibitory effect of maternal breastmilk components on rotavirus vaccine replication and association with infant seroconversion to live oral rotavirus vaccine.
(2020) Kazimbaya KM; Chisenga CC; Simuyandi M; Phiri CM; Laban NM; Bosomprah S; Permar SR; Munsaka S; Chilengi R; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Pediatrics, Human Vaccine Institute, Duke University, Durham, North Carolina, United States of America.; 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.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Despite contributing to a significant reduction in rotavirus associated diarrhoea in highly burdened low- and middle-income countries, live attenuated, oral rotavirus vaccines have lower immunogenicity and efficacy in these settings in comparison to more developed countries. Breastmilk has been implicated among factors contributing to this lowered oral vaccine efficacy. We conducted in-vitro experiments to investigate the inhibitory effects of maternal antibody and other non-antibody components in breastmilk on rotavirus vaccine strain (Rotarix) multiplication in MA104 cell culture system and assessed associations with in-vivo vaccine seroconversion in vaccinated infants. METHODS: Breastmilk samples were collected from mothers before routine rotavirus vaccination of their infant at 6 weeks of age. For each sample, whole breastmilk, purified IgA, purified IgG and IgG and IgA depleted breastmilk samples were prepared as exposure preparations. A 96 well microtitre plate was set up for each sample including a control in which only MA104 cells were grown as well as a virus control with MA104 cells and virus only. The outcome of interest was 50% inhibition dilution of each of the exposure preparations calculated as the titer at which 50% of virus dilution was achieved. Samples from 30 women were tested and correlated to vaccine seroconversion status of the infant. HIV status was also correlated to antiviral breastmilk proteins. RESULTS: The mean 50% inhibitory dilution titer when whole breastmilk was added to virus infected MA104 cells was 14.3 (95% CI: 7.1, 22.7). Incubation with purified IgG resulted in a mean 50% inhibitory dilution of 5 (95%CI -1.6, 11.6). Incubating with purified IgA resulted in a mean 50% inhibitory dilution of 6.5 (95% CI -0.7, 13.7) and IgG and IgA depleted breastmilk did not yield any inhibition with a titer of 1.06 (95%CI 0.9, 1.2). Higher milk IgA levels contributed to a failure of infants to seroconvert. HIV was also not associated with any antiviral breastmilk proteins. DISCUSSION AND CONCLUSION: Whole breastmilk and breastmilk purified IgG and IgA fractions showed inhibitory activity against the rotavirus vaccine Rotarix™ whilst IgA and IgG depleted breastmilk with non-antibody breastmilk fraction failed to show any inhibition activity in-vitro. These findings suggest that IgA and IgG may have functional inhibitory properties and indicates a possible mechanism of how mothers in rotavirus endemic areas with high titres of IgA and IgG may inhibit viral multiplication in the infant gut and would potentially contribute to the failure of their infants to serocovert. There was not association of HIV with either lactoferrin, lactadherin or tenascin-C concentrations.
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.
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,
Performance of Machine Learning Classifiers in Classifying Stunting among Under-Five Children in Zambia.
(2022-Jul-20) Chilyabanyama ON; Chilengi R; Simuyandi M; Chisenga CC; Chirwa M; Hamusonde K; Saroj RK; Iqbal NT; Ngaruye I; Bosomprah S; African Centre of Excellence in Data Science, College of Business Studies Kigali, University of Rwanda, Gikondo-Street, KK 737, Kigali P.O. Box 4285, Rwanda.; Department of Biostatistics, School of Public Health, University of Ghana, Accra P.O. Box LG13, Ghana.; College of Science of Technology, University of Rwanda, KN 7 Ave, Kigali P.O. Box 4285, Rwanda.; Enteric Disease and Vaccines Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia.; Department of Community Medicine, Sikkim Manipal Institute of Medical Sciences (SIMMS) Sikkim Manipal University, Gangtok 03592, India.; Department of Paediatrics and Child Health, Biological and Biomedical Sciences, Aga Khan University Hospital, Karachi 74800, Pakistan.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Stunting is a global public health issue. We sought to train and evaluate machine learning (ML) classification algorithms on the Zambia Demographic Health Survey (ZDHS) dataset to predict stunting among children under the age of five in Zambia. We applied Logistic regression (LR), Random Forest (RF), SV classification (SVC), XG Boost (XgB) and Naïve Bayes (NB) algorithms to predict the probability of stunting among children under five years of age, on the 2018 ZDHS dataset. We calibrated predicted probabilities and plotted the calibration curves to compare model performance. We computed accuracy, recall, precision and F1 for each machine learning algorithm. About 2327 (34.2%) children were stunted. Thirteen of fifty-eight features were selected for inclusion in the model using random forest. Calibrating the predicted probabilities improved the performance of machine learning algorithms when evaluated using calibration curves. RF was the most accurate algorithm, with an accuracy score of 79% in the testing and 61.6% in the training data while Naïve Bayesian was the worst performing algorithm for predicting stunting among children under five in Zambia using the 2018 ZDHS dataset. ML models aids quick diagnosis of stunting and the timely development of interventions aimed at preventing stunting.
Prevalence of Diarrhoeagenic
(2023-Nov-17) Mwape K; Bosomprah S; Chibesa K; Silwamba S; Luchen CC; Sukwa N; Mubanga C; Phiri B; Chibuye M; Liswaniso F; Somwe P; Chilyabanyama O; Chisenga CC; Muyoyeta M; Simuyandi M; Barnard TG; 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.; Department of Global Health, Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.; Amsterdam Institute of Infection and Immunity, Amsterdam University Medical Centers, 1105 AZ Amsterdam, The Netherlands.; Department of Basic Medical Sciences, Michael Chilufya Sata School of Medicine, Copperbelt University, Ndola P.O. Box 71191, Zambia.; Department of Biostatistics, School of Public Health, University of Ghana, Accra P.O. Box LG13, Ghana.; Next Generation Sequencing Unit and Division of Virology, Faculty of Health Sciences, University of the Free State, P.O. Box 339, Bloemfontein 9300, South Africa.; Enteric Disease and Vaccine Research Unit, Center for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia.; Water and Health Research Center, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein 2028, South Africa.; 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)
Diarrhoea is a major contributor to childhood morbidity and mortality in developing countries, with diarrhoeagenic
Sensitivity and predictive value of dysentery in diagnosing shigellosis among under five children in Zambia.
(2023) Miti S; Chilyabanyama ON; Chisenga CC; Chibuye M; Bosomprah S; Mumba C; Chitondo S; Siziya S; Cohen D; Chilengi R; Simuyandi M; Center for Infectious Disease Research in Zambia, Lusaka, Zambia.; Arthur Davison Children's Hospital, Ndola, Zambia.; School of Public Health, Tel Aviv University, Tel Aviv, Israel.; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana.; Tropical Diseases Research Center, Ndola, Zambia.; School of Medicine, Copperbelt University, Ndola, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Shigella is a leading cause of bacterial diarrhea morbidity and mortality affecting mainly children under five in the developing world. In Zambia, Shigella has a high prevalence of 34.7% in children with diarrhea and an attributable fraction of 6.7% in Zambian children with moderate to severe diarrhea. Zambian diarrhea management guidelines and the health ministry reporting tool Health Management Information System (HMIS) heavily rely on the WHO clinical classification of dysentery to potentially identify and estimate the burden of Shigella in children. This reliance on clinical dysentery as a proxy to shigellosis in under five children may be resulting in gross under-estimation of shigella disease burden in Zambia. METHODS: We used existing laboratory and clinical data to examine the sensitivity and predictive value of dysentery to correctly identify Shigella infection in under five children with PCR confirmed Shigella infection in Lusaka and Ndola districts, Zambia. RESULTS: Clinical dysentery had a sensitivity of 8.5% (34/401) in identifying under five children with Shigella by stool PCR. Dysentery was able to correctly classify Shigella in 34 of 68 bloody stool samples giving a corresponding positive predictive value of 50%. Of the 1087 with non-bloody diarrhea, 720 did not have Shigella giving a negative predictive value of 66.2%. CONCLUSIONS: Use of clinical dysentery as a screening symptom for Shigella infection in children under five presenting with moderate to severe diarrhea has low sensitivity and low positive predictive value respectively. Clinical dysentery as a screening symptom for Shigella contributes to gross under diagnosis and reporting of Shigella infection among under five children in Zambia. Further research is required to better inform practice on more accurate methods or tools to use in support of routine diagnosis, particularly in low middle-income settings where laboratory diagnosis remains a challenge.