Browsing by Author "Chilyabanyama ON"

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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.
Characterizing Epstein-Barr virus infection of the central nervous system in Zambian adults living with HIV.
(2023-Dec) Musukuma-Chifulo K; Ghebremichael M; Chilyabanyama ON; Bates M; Munsaka S; Simuyandi M; Chisenga C; Tembo J; Sinkala E; Koralnik IJ; Dang X; Chilengi R; Siddiqi OK; Harvard Medical School and Ragon Institute of Mass General, MIT and Harvard, Boston, MA, USA.; Department of Biomedical Sciences, School of Health Sciences, The University of Zambia, Lusaka, Zambia. kalomusukuma@gmail.com.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia. kalomusukuma@gmail.com.; Center for Vaccines and Virology Research, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.; HerpeZ, University Teaching Hospital, Lusaka, Zambia.; Global Neurology Program, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA.; Department of Internal Medicine, University of Zambia School of Medicine, Lusaka, Zambia.; School of Life & Environmental Sciences, University of Lincoln, Lincoln, UK.; Department of Biomedical Sciences, School of Health Sciences, The University of Zambia, Lusaka, Zambia.; Zambia National Public Health Institute, Ministry of Health, 10101, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
The significance of Epstein-Barr virus (EBV) detection in the cerebrospinal spinal fluid (CSF) in people living with HIV (PLWH) is not entirely understood. The detection of EBV DNA may represent active central nervous system (CNS) infection, reactivation in the setting of another CNS pathogen or due to impaired immunity, or detection of quiescent virus. We screened 470 adult PLWH in Zambia with neurological symptoms for the presence of EBV DNA in the CSF. We performed quantitative EBV PCR on the CSF and blood. We then performed quantitative EBV DNA PCR on the blood of controls with documented HIV viral suppression without CNS symptoms. The prevalence of EBV DNA in the CSF of patients with CNS symptoms was 28.9% (136/470). EBV DNA positivity was associated with younger age, shorter duration of HIV diagnosis, lower CSF glucose levels, higher CSF protein and white blood cell levels, and a positive CSF Mycobacterium tuberculosis result. The median EBV DNA load was 8000 cps/mL in both the CSF and blood with a range of 2000-2,753,000 cps/mL in the CSF and 1000 to 1,871,000 cps/mL in the blood. Molecular screening of CSF for other possible causes of infection identified Mycobacterium tuberculosis in 30.1% and cytomegalovirus (CMV) in 10.5% of samples. EBV DNA load in the blood and CSF was not associated with mortality. Our results suggest that even though EBV DNA was commonly detected in the CSF of our population, it appears to have limited clinical significance regardless of EBV DNA load.
Clinical presentation of congenital syphilis in a rotavirus vaccine cohort study in Lusaka: a case series.
(2021-Apr-01) Sukwa N; Simuyandi M; Chirwa M; Kumwimba YM; Chilyabanyama ON; Laban N; Koyuncu A; Chilengi R; Enteric Disease and Vaccines Research Unit (EDVRU), Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. Michelo.Simuyandi@cidrz.org.; Enteric Disease and Vaccines Research Unit (EDVRU), Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Despite an otherwise robust national antenatal clinic program, maternal and congenital syphilis remains an important public health issue in Zambia. This case series reports the clinical presentation of seven infants diagnosed with congenital syphilis in Lusaka, Zambia. CASE PRESENTATIONS: The cases in this series were incidental findings from a cohort of infants enrolled in a rotavirus vaccine immunogenicity study recruiting infants at 6 weeks of age. As part of clinical care for enrolled participants, we screened mothers of children who presented with adverse events of (i) repeated upper respiratory tract infections/coryza, (ii) skin lesions, and (iii) poor weight gain, for syphilis using rapid plasma reagin test. From a cohort of 214 mother-infant pairs enrolled between September and December 2018, a total of 115 (44.4%) of the mothers reported to have not been screened during antenatal care. Of these, four (3.5%) reported to have tested positive; and only two received treatment. Seven out of 57 (26.6%) children meeting the screening criteria had a positive rapid plasma reagin test result. The mean age at diagnosis was 4.5 months (1.3 months standard deviation), and the common presenting features included coryza (6/7), skin lesions (4/7), conjunctivitis (3/7), pallor/anemia (5/7), wasting (2/7), and underweight (5/7). Three of the seven infants were exposed to human immunodeficiency virus. Following diagnosis, all seven cases received standard treatment according to national treatment guidelines. That is, 6/7 cases received inpatient care with benzylpenicillin for 10 days, while 1/7 was treated as an outpatient and received daily procaine penicillin for 10 days. CONCLUSION: These findings suggest that, though screening for syphilis is part of the standard antenatal care in Zambia, it is not offered optimally. There is urgent need to address programmatic shortcomings in syphilis screening and treatment to avoid long-term sequelae. Additionally, clinicians need to raise their index of suspicion and rule out syphilis when confronted with these clinical symptoms, regardless of the mother's human immunodeficiency virus status.
Comparing growth velocity of HIV exposed and non-exposed infants: An observational study of infants enrolled in a randomized control trial in Zambia.
(2021) Chilyabanyama ON; Chilengi R; Laban NM; Chirwa M; Simunyandi M; Hatyoka LM; Ngaruye I; Iqbal NT; Bosomprah S; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana.; College of Science and Technology, University of Rwanda, Kigali, Rwanda.; Research Division, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Aga Khan University Hospital, Karachi, Pakistan.; African Centre of Excellence in Data Science (ACEDS), University of Rwanda, Kigali, Rwanda.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Impaired growth among infants remains one of the leading nutrition problems globally. In this study, we aimed to compare the growth trajectory rate and evaluate growth trajectory characteristics among children, who are HIV exposed uninfected (HEU) and HIV unexposed uninfected (HUU), under two years in Zambia. METHOD: Our study used data from the ROVAS II study (PACTR201804003096919), an open-label randomized control trial of two verses three doses of live, attenuated, oral RotarixTM administered 6 &10 weeks or at 6 &10 weeks plus an additional dose at 9 months of age, conducted at George clinic in Lusaka, Zambia. Anthropometric measurements (height and weight) were collected on all scheduled and unscheduled visits. We defined linear growth velocity as the rate of change in height and estimated linear growth velocity as the first derivative of the mixed effect model with fractional polynomial transformations and, thereafter, used the second derivative test to determine the peak height and age at peak heigh. RESULTS: We included 212 infants in this study with median age 6 (IQR: 6-6) weeks of age. Of these 97 (45.3%) were female, 35 (16.4%) were stunted, and 59 (27.6%) were exposed to HIV at baseline. Growth velocity was consistently below the 3rd percentile of the WHO linear growth standard for HEU and HUU children. The peak height and age at peak height among HEU children were 74.7 cm (95% CI = 73.9-75.5) and 15.5 months (95% CI = 14.7-16.3) respectively and those for HUU were 73 cm (95% CI = 72.1-74.0) and 15.6 months (95% CI = 14.5-16.6) respectively. CONCLUSION: We found no difference in growth trajectories between infants who are HEU and HUU. However, the data suggests that poor linear growth is universal and profound in this cohort and may have already occurred in utero.
Development of a diarrhoea severity scoring scale in a passive health facility-based surveillance system.
(2022) St Jean DT; Chilyabanyama ON; Bosomprah S; Asombang M; Velu RM; Chibuye M; Mureithi F; Sukwa N; Chirwa M; Mokha P; Chilengi R; Simuyandi M; Department of Biostatistics, School of Public Health, University of Ghana, Ghana, Accra.; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Diarrhoeal disease remains a leading cause of death among children mostly in low and middle-income countries. Factors contributing to disease severity are complex and there is currently no consensus on a scoring tool for use in community-based studies. METHODS: Data were collected during a passive surveillance system in an outpatient health facility in Lusaka, Zambia from March 2019 to July 2019. Diarrhea episodes were assessed for severity using an in-house severity scoring tool (CIDRZ) and previously published scores (Vesikari, Clark, CODA, and DHAKA). The CIDRZ score was constructed using fieldworker-reported clinical signs and exploratory factor analysis. We used precision-recall curves measuring severe diarrhoea (i.e., requiring intravenous rehydration or referred for hospital admission) to determine the best performing scores. Then, we used Cronbach's alpha to assess the scale's internal consistency. Finally, we used Cohen's kappa to assess agreement between the scores. RESULTS: Of 110 diarrhea episodes, 3 (3%) required intravenous rehydration or were referred for hospital admission. The precision-recall area under the curve of each score as a predictor of severe diarrhoea requiring intravenous rehydration or hospital admission was 0.26 for Vesikari, 0.18 for CODA, 0.24 for Clark, 0.59 for DHAKA, and 0.59 for CIDRZ. The CIDRZ scale had substantial reliability and performed similarly to the DHAKA score. CONCLUSIONS: Diarrhoea severity scores focused on characteristics specific to dehydration status may better predict severe diarrhea among children in Lusaka. Aetiology-specific scoring tools may not be appropriate for use in community healthcare settings. Validation studies for the CIDRZ score in diverse settings and with larger sample sizes are warranted.
Early linear growth retardation: results of a prospective study of Zambian infants.
(2019-Jan-14) Chilengi R; Asombang M; Kadota JL; Chilyabanyama ON; Mwila-Kazimbaya K; Ng'ombe H; Simuyandi M; Bosomprah S; Research Division, Centre for Infectious Disease Research in Zambia, Plot # 34620, Off Alick Nkhata Road, PO Box 34681, Lusaka, Zambia. sbosomprah@gmail.com.; Department of Biostatistics, School of Public Health, University of Ghana, Legon, Accra, Ghana. sbosomprah@gmail.com.; Research Division, Centre for Infectious Disease Research in Zambia, Plot # 34620, Off Alick Nkhata Road, PO Box 34681, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Linear growth retardation is the most dominant nutritional problem globally. We aimed to describe linear growth trajectory among infants under 2 years of age using the WHO growth velocity standards. METHOD: This was a prospective cohort study of infants enrolled at 6 weeks of age and followed up for up to 24 months in Kamwala Urban Health Centre, Lusaka, Zambia. The study was conducted between April 2013 and March 2015. Infants were enrolled if they were 6-12 weeks of age and the mother was willing to participate voluntarily and provided informed consent. Anthropometric data were collected at scheduled clinic visits at 1 month, 2 months, 3 months, then quarterly until the infant was 24 months old. We defined linear growth velocity as the rate of change in height. We estimated linear growth velocity as the first derivative of the penalized cubic spline mixed effects model. RESULTS: A total of 338 children were included in the analysis. Of these, 185 (54.7%) were female, 115 (34.1%) were born to HIV positive mothers and thus classified as HIV Exposed (HE). The mean age of children at enrollment was 1.6 months (SD = 0.15). On average, the growth velocity for 3-month length increments conditional on age were 0-3 months = 2.97 cm/3mo (95%CI = 2.69, 3.25); 3-6 months = 2.62 cm/3mo (95%CI = 2.38, 2.87); 6-9 months = 1.57 cm/3mo (95%CI = 1.43, 1.71); 9-12 months = 1.18 cm/3mo (95%CI = 1.08, 1.28); 12-15 month = 1.14 cm/3mo (95%CI = 1.02, 1.27); 15-18 months = 0.87 cm/3mo (95%CI = 0.79, 0.96); 18-21 months = 0.80 cm/3mo (95%CI = 0.72, 0.89); and 21-24 months = 0.86 cm/3mo (95%CI = 0.77, 0.96). For both boys and girls, the growth velocity in our cohort were consistently below the 3rd percentile of the WHO linear growth velocity standard. The estimated mean height and the age at which growth begins to falter were 68.6 cm (95%CI = 68.0, 69.2) and 13.6 months (95%CI = 13.2, 14.1) respectively. CONCLUSION: We found slower rate of growth among otherwise healthy Zambian infants. The data suggests that growth retardation is universal and profound in this cohort and may have already been occurring in utero.
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.
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.
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.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Zambia National Public Health Institute, 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.
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.
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.
Machine Learning Algorithms for understanding the determinants of under-five Mortality.
(2022-Sep-24) Saroj RK; Yadav PK; Singh R; Chilyabanyama ON; Department of Biostatistics and Epidemiology, International Institute for Population Sciences, Mumbai, 400088, India.; Department of Mathematics and Statistics, Banasthali Vidyapith, Vanasthali Rd, Aliyabad, Tonk, Rajasthan, 304022, India.; Department of Community Medicine, Sikkim Manipal Institute of Medical Sciences-Sikkim Manipal University, Gangtok, Sikkim, 737102, India. rakesh.saroj@bhu.ac.in.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; African Centre of Excellency in Data Science (ACEDS), University of Rwanda, KK 737 Street, Gikondo, Kigali, Rwanda.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Under-five mortality is a matter of serious concern for child health as well as the social development of any country. The paper aimed to find the accuracy of machine learning models in predicting under-five mortality and identify the most significant factors associated with under-five mortality. METHOD: The data was taken from the National Family Health Survey (NFHS-IV) of Uttar Pradesh. First, we used multivariate logistic regression due to its capability for predicting the important factors, then we used machine learning techniques such as decision tree, random forest, Naïve Bayes, K- nearest neighbor (KNN), logistic regression, support vector machine (SVM), neural network, and ridge classifier. Each model's accuracy was checked by a confusion matrix, accuracy, precision, recall, F1 score, Cohen's Kappa, and area under the receiver operating characteristics curve (AUROC). Information gain rank was used to find the important factors for under-five mortality. Data analysis was performed using, STATA-16.0, Python 3.3, and IBM SPSS Statistics for Windows, Version 27.0 software. RESULT: By applying the machine learning models, results showed that the neural network model was the best predictive model for under-five mortality when compared with other predictive models, with model accuracy of (95.29% to 95.96%), recall (71.51% to 81.03%), precision (36.64% to 51.83%), F1 score (50.46% to 62.68%), Cohen's Kappa value (0.48 to 0.60), AUROC range (93.51% to 96.22%) and precision-recall curve range (99.52% to 99.73%). The neural network was the most efficient model, but logistic regression also shows well for predicting under-five mortality with accuracy (94% to 95%)., AUROC range (93.4% to 94.8%), and precision-recall curve (99.5% to 99.6%). The number of living children, survival time, wealth index, child size at birth, birth in the last five years, the total number of children ever born, mother's education level, and birth order were identified as important factors influencing under-five mortality. CONCLUSION: The neural network model was a better predictive model compared to other machine learning models in predicting under-five mortality, but logistic regression analysis also shows good results. These models may be helpful for the analysis of high-dimensional data for health research.
Maternal and Infant Histo-Blood Group Antigen (HBGA) Profiles and Their Influence on Oral Rotavirus Vaccine (Rotarix
(2023-Jul-31) Chauwa A; Bosomprah S; Laban NM; Phiri B; Chibuye M; Chilyabanyama ON; Munsaka S; Simuyandi M; Mwape I; Mubanga C; Chobe MC; Chisenga C; Chilengi R; Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.; Department of Global Health, Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam University Medical Centers, University of Amsterdam, 1012 WP Amsterdam, The Netherlands.; Department of Biostatistics, School of Public Health, University of Ghana, Accra P.O. Box LG13, Ghana.; Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka P.O. Box 50110, Zambia.; Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Live-attenuated, oral rotavirus vaccines have significantly reduced rotavirus-associated diarrhoea morbidity and infant mortality. However, vaccine immunogenicity is diminished in low-income countries. We investigated whether maternal and infant intrinsic susceptibility to rotavirus infection via histo-blood group antigen (HBGA) profiles influenced rotavirus (ROTARIX
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,
Patients' Satisfaction with HIV Care Providers in Public Health Facilities in Lusaka: A Study of Patients who were Lost-to-Follow-Up from HIV Care and Treatment.
(2020-Apr) Mukamba N; Chilyabanyama ON; Beres LK; Simbeza S; Sikombe K; Padian N; Holmes C; Sikazwe I; Geng E; Schwartz SR; Division of HIV, ID and Global Medicine, University of California, San Francisco, Zuckerberg San Francisco General Hospital, San Francisco, CA, USA.; Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD, USA. sschwartz@jhu.edu.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. njekwa.mukamba@gmail.com.; Centre for Global Health and Quality, Georgetown University Medical Center, Washington, DC, USA.; Department of International Health, Johns Hopkins School of Public Health, Baltimore, MD, USA.; Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Division of Epidemiology, University of California, Berkeley, Berkeley, CA, USA.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Prognosis among those who are HIV infected has improved but long-term retention is challenging. Health systems may benefit from routinely measuring patient satisfaction which is a potential driver of engagement in HIV care, but it is not often measured in Africa, and Zambia in particular. This study aims to internally validate a patient satisfaction tool, assess satisfaction among patients previously lost-to-follow up (LTFU) from HIV care in Lusaka province and to measure association between patient satisfaction with their original clinic and re-engagement in HIV care. A cross-sectional assessment of satisfaction was conducted by tracing sampled patients drawn from public health facilities. Our findings suggest that satisfaction tool, previously validated in USA, exhibits high internal consistency for measuring patient satisfaction in the Zambian health system. Patient satisfaction with healthcare providers is associated with re-engagement in HIV care. Future interventions on patient-centred care are likely to optimize and support retention in care.
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.
Performance of Xpert
(2020-Dec-21) Kasaro MP; Chilyabanyama ON; Shah NS; Muluka B; Kapata N; Krüüner A; Mwaba I; Kaunda K; Coggin WL; Wen XJ; Henostroza G; Reid S; Centers for Disease Control and Prevention, Atlanta, GA, USA.; Ministry of Health Zambia National TB Programme, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; University of Alabama at Birmingham, Birmingham, AL, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
SETTING: Peri-urban health facilities providing HIV and TB care in Zambia. OBJECTIVE: To evaluate 1) the impact of Xpert DESIGN: Quasi-experimental study design with the first cohort evaluated per standard-of-care (SOC; first sputum tested using smear microscopy) and the second cohort per an algorithm using Xpert as initial test (intervention phase; IP). Xpert testing was provided onsite in Chongwe District, while samples were transported 5-10 km in Kafue District. TB was confirmed using mycobacterial culture. RESULTS: Among 1350 PLHIV enrolled, 156 (15.4%) had confirmed TB. Time from TB evaluation to diagnosis ( CONCLUSION: Xpert improved time to diagnosis and treatment initiation, but there was no difference in all-cause mortality. High sensitivity of Determine TB-LAM Ag at lower CD4 count supports increased use in settings providing care to PLHIV, particularly with advanced HIV disease.
Safety, tolerability, and immunogenicity of an oral inactivated ETEC vaccine (ETVAX®) with dmLT adjuvant in healthy adults and children in Zambia: An age descending randomised, placebo-controlled trial.
(2023-Nov-02) Sukwa N; Mubanga C; Hatyoka LM; Chilyabanyama ON; Chibuye M; Mundia S; Munyinda M; Kamuti E; Siyambango M; Badiozzaman S; Bosomprah S; Carlin N; Kaim J; Sjöstrand B; Simuyandi M; Chilengi R; Svennerholm AM; Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. Electronic address: nsofwa.sukwa@cidrz.org.; Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Division of Medical Microbiology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa.; Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana.; Scandinavian Biopharma, Sweden.; Department of Microbiology and Immunology, University of Gothenburg, Sweden.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) is an important cause of moderate to severe diarrhoea in children for which there is no licensed vaccine. We evaluated ETVAX®, an oral, inactivated ETEC vaccine containing four E. coli strains over-expressing the major colonization factors CFA/I, CS3, CS5, and CS6, a toxoid (LCTBA) and double mutant heat-labile enterotoxin (dmLT) adjuvant for safety, tolerability, and immunogenicity. METHODS: A double-blind, placebo-controlled, age-descending, dose-finding trial was undertaken in 40 adults, 60 children aged 10-23 months, and 146 aged 6-9 months. Adults received one full dose of ETVAX® and children received 3 doses of either 1/4 or 1/8 dose. Safety was evaluated as solicited and unsolicited events for 7 days following vaccination. Immunogenicity was assessed by evaluation of plasma IgA antibody responses to CFA/I, CS3, CS5, CS6, and LTB, and IgG responses to LTB. RESULTS: Solicited adverse events were mostly mild or moderate with only 2 severe fever reports which were unrelated to the vaccine. The most common events were abdominal pain in adults (26.7 % in vaccinees vs 20 % in placebos), and fever in children aged 6-9 months (44 % vs 54 %). Dosage, number of vaccinations and decreasing age had no influence on severity or frequency of adverse events. The vaccine induced plasma IgA and IgG responses against LTB in 100 % of the adults and 80-90 % of the children. In the 6-23 months cohort, IgA responses to more than 3 vaccine antigens after 3 doses determined as ≥2-fold rise was significantly higher for 1/4 dose compared to placebo (56.7 % vs 27.2 %, p = 0.01). In the 6-9 months cohort, responses to the 1/4 dose were significantly higher than 1/8 dose after 3 rather than 2 doses. CONCLUSION: ETVAX® was safe, tolerable, and immunogenic in Zambian adults and children. The 1/4 dose induced significantly stronger IgA responses and is recommended for evaluation of protection in children. CLINICAL TRIALS REGISTRATION: The trial is registered with the Pan African Clinical Trials Registry (PACTR Ref. 201905764389804) and a description of this clinical trial is available on: https://pactr.samrc.ac.za/Trial Design.