Browsing by Author "Laban N"

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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.
Human cytomegalovirus seropositivity and its influence on oral rotavirus vaccine immunogenicity: a specific concern for HIV-exposed-uninfected infants.
(2024-Jun-20) Laban N; Bosomprah S; Chilengi R; Simuyandi M; Chisenga C; Ng'ombe H; Musukuma-Chifulo K; Goodier M; Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.; Flow Cytometry and Immunology Facility, Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine, Fajara, Banjul, The Gambia.; 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.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Oral rotavirus vaccines demonstrate diminished immunogenicity in low-income settings where human cytomegalovirus infection is acquired early in childhood and modulates immunity. We hypothesized that human cytomegalovirus infection around the time of vaccination may influence immunogenicity. We measured plasma human cytomegalovirus-specific immunoglobulin M antibodies in rotavirus vaccinated infants from 6 weeks to 12 months old and compared rotavirus immunoglobulin A antibody titers between human cytomegalovirus seropositive and seronegative infants. There was no evidence of an association between human cytomegalovirus serostatus at 9 months and rotavirus-specific antibody titers at 12 months (geometric mean ratio 1.01, 95% CI: 0.70, 1.45; P = 0.976) or fold-increase in RV-IgA titer between 9 and 12 months (risk ratio 0.999, 95%CI: 0.66, 1.52; P = 0.995) overall. However, HIV-exposed-uninfected infants who were seropositive for human cytomegalovirus at 9 months old had a 63% reduction in rotavirus antibody geometric mean titers at 12 months compared to HIV-exposed-uninfected infants who were seronegative for human cytomegalovirus (geometric mean ratio 0.37, 95% CI: 0.17, 0.77; P = 0.008). While the broader implications of human cytomegalovirus infections on oral rotavirus vaccine response might be limited in the general infant population, the potential impact in the HIV-exposed-uninfected infants cannot be overlooked. This study highlights the complexity of immunological responses and the need for targeted interventions to ensure oral rotavirus vaccine efficacy, especially in vulnerable subpopulations.
Three transmission events of Vibrio cholerae O1 into Lusaka, Zambia.
(2021-Jun-14) Mwaba J; Debes AK; Murt KN; Shea P; Simuyandi M; Laban N; Kazimbaya K; Chisenga C; Li S; Almeida M; Meisel JS; Shibemba A; Kantenga T; Mukonka V; Kwenda G; Sack DA; Chilengi R; Stine OC; Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, USA.; Zambia National Public Health Institute, Lusaka, Zambia.; Department of Biomedical Sciences, University of Zambia School of Health Sciences, Lusaka, Zambia.; Department of Pathology and Microbiology, University Teaching Hospitals, Lusaka, Zambia.; University of Maryland School of Medicine, Baltimore, MD, USA.; University of Maryland, College Park, College Park, MD, USA.; University of Maryland School of Medicine, Baltimore, MD, USA. cstine@som.umaryland.edu.; Université Paris-Saclay, INRAE, MGP, 78350, Jouy-en-Josas, France.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Cholera has been present and recurring in Zambia since 1977. However, there is a paucity of data on genetic relatedness and diversity of the Vibrio cholerae isolates responsible for these outbreaks. Understanding whether the outbreaks are seeded from existing local isolates or if the outbreaks represent separate transmission events can inform public health decisions. RESULTS: Seventy-two V. cholerae isolates from outbreaks in 2009/2010, 2016, and 2017/2018 in Zambia were characterized using multilocus variable number tandem repeat analysis (MLVA) and whole genome sequencing (WGS). The isolates had eight distinct MLVA genotypes that clustered into three MLVA clonal complexes (CCs). Each CC contained isolates from only one outbreak. The results from WGS revealed both clustered and dispersed single nucleotide variants. The genetic relatedness of isolates based on WGS was consistent with the MLVA, each CC was a distinct genetic lineage and had nearest neighbors from other East African countries. In Lusaka, isolates from the same outbreak were more closely related to themselves and isolates from other countries than to isolates from other outbreaks in other years. CONCLUSIONS: Our observations are consistent with i) the presence of random mutation and alternative mechanisms of nucleotide variation, and ii) three separate transmission events of V. cholerae into Lusaka, Zambia. We suggest that locally, case-area targeted invention strategies and regionally, well-coordinated plans be in place to effectively control future cholera outbreaks.