Browsing by Author "Phiri M"

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Characterization of Rotavirus Strains Responsible for Breakthrough Diarrheal Diseases among Zambian Children Using Whole Genome Sequencing.
(2023-Nov-26) Mwape I; Laban NM; Chibesa K; Moono A; Silwamba S; Malisheni MM; Chisenga C; Chauwa A; Simusika P; Phiri M; Simuyandi M; Chilengi R; De Beer C; Ojok D
The occurrence of rotavirus (RV) infection among vaccinated children in high-burden settings poses a threat to further disease burden reduction. Genetically altered viruses have the potential to evade both natural infection and vaccine-induced immune responses, leading to diarrheal diseases among vaccinated children. Studies characterizing RV strains responsible for breakthrough infections in resource-limited countries where RV-associated diarrheal diseases are endemic are limited. We aimed to characterize RV strains detected in fully vaccinated children residing in Zambia using next-generation sequencing. We conducted whole genome sequencing on Illumina MiSeq. Whole genome assembly was performed using Geneious Prime 2023.1.2. A total of 76 diarrheal stool specimens were screened for RV, and 4/76 (5.2%) were RV-positive. Whole genome analysis revealed RVA/Human-wt/ZMB/CIDRZ-RV2088/2020/
Evaluation of plasma anti-CS3 and anti-LTB IgG avidity among Zambian children vaccinated with ETVAX.
(2026) Mubanga C; Mubanga M; Chilyabanyama ON; Phiri M; Chisenga CC; Glashoff RH; Chilengi R
BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) remains a major cause of diarrheal disease in low- and middle-income countries (LMICs). To curb ETEC related diarrhoea, several candidate vaccines are in development, with ETVAX® being the most advanced. Although immunogenicity studies have primarily focused on measuring antibody titres, assessing antibody avidity offers additional valuable insight into antibody quality and immune maturity. This study assessed anti-CS3 and anti-LTB IgG avidity in Zambian children to better understand vaccine-induced antibody responses in an endemic setting. METHODS: Children aged 6-23 months (n = 60) received three quarter-doses of ETVAX® with dmLT adjuvant on days 1, 14, and 90. Plasma samples collected at baseline prior to the first vaccination (Day 1; V1), seven days after the second dose (Day 22; V5), and seven days after the third dose (Day 97; V7) were analysed by limiting antigen dilution ELISA to calculate avidity indices (AI). Naïve classification was performed using titre-based thresholds (20th percentile of baseline titres) and avidity-defined naivety (AI < 0.5). Receiver operating characteristic (ROC) analysis was used to evaluate the discriminatory performance of avidity indices against titre-defined naïve status. RESULTS: Baseline avidity was detectable for both CS3 and LTB, consistent with prior natural exposure. Mean CS3 IgG avidity decreased from 0.7 at baseline to 0.6 after the third dose (p < 0.001), while LTB IgG avidity showed transient decreases but no net gain. Naïve classification at baseline revealed that 9/60 children had titres but low avidity (functional naivety), and 6/60 had waned titres but high avidity. Only one child was naïve by both criteria for CS3, and none for LTB. ROC analysis demonstrated moderate discrimination for CS3 (AUC = 0.65; optimal cut-off AI = 0.36) but poor discrimination for LTB (AUC = 0.30). CONCLUSION: In this endemic population, ETVAX® induced strong antibody titres but minimal changes in avidity over time, with notable inter-individual variability. ROC analysis highlighted context-specific limitations in using avidity to discriminate immune maturity. Together, these findings suggest that while antibody avidity may provide complementary information on antibody quality, its interpretation should be cautious and considered alongside antibody titres in endemic settings.
Measuring Oral Pre-exposure Prophylaxis (PrEP) Continuation Through Electronic Health Records During Program Scale-Up Among the General Population in Zambia.
(2023-Jul) Heilmann E; Okuku J; Itoh M; Hines JZ; Prieto JT; Phiri M; Watala K; Nsofu C; Luhana-Phiri M; Vlahakis N; Kabongo M; Kaliki B; Minchella PA; Musonda B
HIV pre-exposure prophylaxis (PrEP) is being scaled-up in Zambia, but PrEP continuation data are limited by paper-based registers and aggregate reports. Utilization of Zambia's electronic health record (EHR) system, SmartCare, may address this gap. We analyzed individuals aged ≥ 15 years who initiated PrEP between October 2020 and September 2021 in four provinces in Zambia in SmartCare versus aggregate reports. We measured PrEP continuation using Kaplan-Meier survival analysis and Cox proportional hazards models. SmartCare captured 29% (16,791/58,010) of new PrEP clients; 49% of clients continued at one month, and 89% discontinued PrEP by February 2022. Women were less likely than men to discontinue PrEP (adjusted hazard ratio [aHR]: 0.89, 95% CI 0.86-0.92, z = - 6.99, p < 0.001), and PrEP clients aged ≥ 50 years were less likely to discontinue PrEP compared to clients 15-19 years (aHR: 0.53, 95% CI 0.48-0.58, z = - 13.04, p < 0.001). Zambia's EHR is a valuable resource for measuring individual-level PrEP continuation over time and can be used to inform HIV prevention programs.