Browsing by Author "Chirwa M"

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A pilot study on use of live attenuated rotavirus vaccine (Rotarix™) as an infection challenge model.
(2020-Oct-27) Chilengi R; Simuyandi M; Chibuye M; Chirwa M; Sukwa N; Laban N; Chisenga C; Silwamba S; Grassly N; Bosomprah S; Research Division, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana.; MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College, London, United Kingdom.; Research Division, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. Electronic address: Roma.Chilengi@cidrz.org.; Research Division, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Rotavirus remains the commonest cause of dehydrating diarrhoea, particularly in developing countries. Human infection challenge studies in children in these countries offers an opportunity to rapidly evaluate new vaccine candidates that may have improved efficacy. We evaluated use of Rotarix™ as a live-attenuated challenge agent. METHODS: We undertook an open label, exploratory study in infants receiving two standard doses of Rotarix™ at 6 and 10 weeks of age in a cohort of 22 Zambian infants. The first vaccine dose was considered as primary vaccination, and the second at day 28 as a live-attenuated virus challenge. Saliva, stool and serum samples were collected on days 0, 3, 5, 7, 14, and 28 following each dose. The primary outcome was stool shedding of rotavirus, determined by NSP2 qPCR. We calculated mean shedding index as average of natural logarithm of viral copies per gram of stool. FINDINGS: After the first dose, viral shedding was high at day 3, peaked by day 5. After the second dose, viral shedding at day 3 was low and reduced gradually in most infants until day 14. Mean shedding index was significantly lower post dose 2 across all infants and timepoints (5.0 virus copies/g of stool [95%CI: 0.3-9.7] vs 10.4 virus copies/g of stool [95%CI: 6.2-14.6]; p-value < 0.0001; rho = 0.20, SD = 4.97. Seroconversion at day 28 was associated with a mean reduction of -1.03 (95%CI = -8.07, 6.01) in viral shedding after challenge dose but this was not statistically significant (p = 0.774). A borderline positive correlation between fold-change in IgA titre at day 28 from day 0 in saliva and serum was observed; Spearman's correlation coefficient, r = 0.69; p = 0.086. INTERPRETATION: Shedding after the 'challenge' dose was reduced compared with the first dose, consistent with the induction of mucosal immunity by the first dose. This supports the use of Rotarix vaccine as a live-attenuated infection challenge. FUNDING: Medical Research Council (UK) through the HIC-Vac Network.
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.
Immunogenicity and safety of two monovalent rotavirus vaccines, ROTAVAC® and ROTAVAC 5D® in Zambian infants.
(2021-Jun-16) Chilengi R; Mwila-Kazimbaya K; Chirwa M; Sukwa N; Chipeta C; Velu RM; Katanekwa N; Babji S; Kang G; McNeal MM; Meyer N; Gompana G; Hazra S; Tang Y; Flores J; Bhat N; Rathi N; PATH, India. Electronic address: nrathi@path.org.; Centre for Infectious Disease Research in Zambia, Zambia.; Department of Pediatrics, University of Cincinnati College of Medicine, Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; The Wellcome Trust Research Laboratory, Vellore, India.; PATH, India.; PATH, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND AND AIMS: ROTAVAC® (frozen formulation stored at -20 °C) and ROTAVAC 5D® (liquid formulation stable at 2-8 °C) are rotavirus vaccines derived from the 116E human neonatal rotavirus strain, developed and licensed in India. This study evaluated and compared the safety and immunogenicity of these vaccines in an infant population in Zambia. METHODS: We conducted a phase 2b, open-label, randomized, controlled trial wherein 450 infants 6 to 8 weeks of age were randomized equally to receive three doses of ROTAVAC or ROTAVAC 5D, or two doses of ROTARIX®. Study vaccines were administered concomitantly with routine immunizations. Blood samples were collected pre-vaccination and 28 days after the last dose. Serum anti-rotavirus IgA antibodies were measured by ELISA, with WC3 and 89-12 rotavirus strains as viral lysates in the assays. The primary analysis was to assess non-inferiority of ROTAVAC 5D to ROTAVAC in terms of the geometric mean concentration (GMC) of serum IgA (WC3) antibodies. Seroresponse and seropositivity were also determined. Safety was evaluated as occurrence of immediate, solicited, unsolicited, and serious adverse events after each dose. RESULTS: The study evaluated 388 infants in the per-protocol population. All three vaccines were well tolerated and immunogenic. The post-vaccination GMCs were 14.0 U/mL (95% CI: 10.4, 18.8) and 18.1 U/mL (95% CI: 13.7, 24.0) for the ROTAVAC and ROTAVAC 5D groups, respectively, yielding a ratio of 1.3 (95% CI: 0.9, 1.9), thus meeting the pre-set non-inferiority criteria. Solicited and unsolicited adverse events were similar across all study arms. No death or intussusception case was reported during study period. CONCLUSIONS: Among Zambian infants, both ROTAVAC and ROTAVAC 5D were well tolerated and the immunogenicity of ROTAVAC 5D was non-inferior to that of ROTAVAC. These results are consistent with those observed in licensure trials in India and support use of these vaccines across wider geographical areas.
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.
Sickle Cell Disease in Early Infancy: A Case Report.
(2022) Muzazu SGY; Chirwa M; Khatanga-Chihana S; Munyinda M; Simuyandi M; Enteric Disease and Vaccines Research Unit, Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.
Sickle cell disease (SCD) refers to a group of hereditary disorders that result in faulty hemoglobin carriage by the red blood cells. This paper discusses an atypical presentation of SCD in early infancy. Despite current literature suggesting protection by fetal hemoglobin in the first few months of life, we report a diagnosis of SCD at 2 months of age with severe symptoms requiring hospitalization. It is therefore important for clinicians to raise their clinical index of suspicion of SCD in children presenting with severe anemia even though they are less than 6 months old and do not present with classic dactylitis or pain syndromes. Expansion and sustained newborn screening programs for SCD in developing countries could help clinicians and parents plan for early treatment, appropriate prophylaxis, and improved management of SCD complications.
The Incidence and Risk Factors for Enterotoxigenic
(2024-Mar-29) Sukwa N; Bosomprah S; Somwe P; Muyoyeta M; Mwape K; Chibesa K; Luchen CC; Silwamba S; Mulenga B; Munyinda M; Muzazu S; Chirwa M; Chibuye M; Simuyandi M; Chilengi R; Svennerholm AM; Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka P.O. Box 34681, Zambia.; Department of Microbiology and Immunology, University of Gothenburg, 40530 Gothenburg, Sweden.; Department of Biostatistics, School of Public Health, University of Ghana, Accra P.O. Box LG13, Ghana.
This study aimed to estimate the incidence and risk factors for Enterotoxigenic