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Item Statistical Modelling of Waning Immunity After Shanchol Vaccination: A Prospective Cohort Study(Vaccines, 2026-01-30) Bosomprah, Samuel; Liswaniso, Fraser; Phiri, Bernard; Chibuye, Mwelwa; Luchen, Charlie C.; Ng’ombe, Harriet; Chibesa, Kennedy; Ngosa, Dennis; Muchimba, Mutinta; Debes, Amanda K.; Chilengi, Roma; Sack, David A.; Chisenga, Caroline C.Abstract Introduction: Cholera remains a major public health threat in endemic settings, and oral cholera vaccine (Shanchol™) campaigns are increasingly used amid constrained global supply. However, practical decisions on revaccination require clearer, setting-specific estimates of how rapidly vaccine-induced vibriocidal antibodies peak and wane. Methods: We conducted a prospective cohort kinetics analysis in Lukanga Swamps (Central Province, Zambia), enrolling adults (18–65 years) stratified by prior Shanchol™ exposure (0, 1, or 2 previous doses). All participants received two Shanchol™ doses 14 days apart, with serum collected at baseline and days 14, 28, 60, and 90 (end of follow-up). Ogawa and Inaba vibriocidal titres were measured using a complement-based assay and analysed on the log10 scale. Serotype-specific mixed-effects models with natural cubic splines for time (knots: 14, 28, 60 days) assessed trajectories by prior-dose strata, adjusting for age, sex, and HIV status. Peak timing and post-peak half-life were derived from model-based predictions with participant-level bootstrap CIs (1000 replications). Results: The analysis included 225 participants: 68 (30.2%) with zero prior doses, 89 (39.6%) with one, and 68 (30.2%) with two; median age was 33 years (IQR 25–49), 56.4% were female, and 19.2% were HIV-positive. Modelled titres for both serotypes rose steeply after vaccination, peaking around day 36–37 across prior-dose strata. Ogawa titres reached half of peak by about day 73–78, corresponding to post-peak half-lives of 37–41 days; Inaba declined more slowly with half-lives of 42–46 days. Confidence intervals overlapped across prior-dose strata, indicating minimal differences by vaccination history. Conclusions: In this cholera-endemic adult population, Shanchol™ induced vibriocidal responses that peaked at ~5 weeks and waned over the following 5–7 weeks, with broadly similar kinetics regardless of prior vaccination and slightly slower decay for Inaba than Ogawa. These parameters can inform booster timing in hotspot settings.Item Rotavirus Prevalence, Genetic Diversity, and Co-Infections during the 2023- 2024 Cholera Outbreak in Zambia: Insights from Multi-Pathogen Diagnostics(2026-02-28) Chauwa, Adriace; Bosomprah, Samuel; Phiri, Bernard; Laban, Natasha M.; Kuntawala, Dhvani H.; Ngosa, Dennis; Ng'ombe, Harriet; Liswaniso, Fraser; Luchen, Chaluma C.; Muchimba, Mutinta; Mwape, Innocent; Nzangwa, Bertha T.; Tigere, Sekayi F.; Chibesa, Kennedy; Silwamba, Suwilanji; Simuyandi, Michelo; Mbewe, Nyuma; Chilengi, Roma; Chisenga, Caroline C.Abstract During cholera outbreaks in Zambia, diagnostic strategies that rely on single-plex or targeted assays risk overlooking concomitant infections with other clinically important enteric pathogens. We estimated the prevalence of rotavirus and described co-detected enteropathogens and rotavirus genotypes among patients admitted with clinically suspected cholera during Zambia’s 2023–2024 cholera outbreak. We conducted a sub-analysis of diarrhoeal specimens collected from patients admitted to five cholera treatment centres who met the syndromic suspected cholera case definition. Stool samples were tested using the Bosphore® Gastroenteritis Panel v2, a multiplex PCR enteric panel, to detect rotavirus and other gastrointestinal pathogens. Rotavirus-positive specimen with sufficient viral load were further characterised by RT-PCR genotyping and Sanger sequencing targeting VP7 and VP4 genes. Among 319 suspected cholera admissions, rotavirus was detected in 18 patients, yielding a prevalence of 5.6% (95% CI 3.4%, 8.8%). Rotavirus detections occurred predominantly in children aged <5 years (87.5%) and 6-15 years (80.0%). Co-infection was common - 93.7%, (15/16) of rotavirus-positive samples showed co-infection with at least one additional enteric pathogen, primarily Campylobacter. Genotyping was successful in five samples and showed heterogenous circulating strains, including G1P[8], G2P[4], G3P[6], G12P[6], and a rare G1P[6] reassortant. During a large 2023–2024 cholera outbreak in Zambia, rotavirus accounted for a modest but clinically important fraction of the suspected cholera admissions and was typically identified within mixed enteric infections. These findings highlight the limitations of syndromic diagnosis in outbreak settings and support integrating multi-pathogen diagnostics and sustained molecular surveillance to improve case management, antimicrobial stewardship, and vaccine-era monitoring.Item Faecal Coliforms and Escherichia coli Contamination in Drinking Water Sources in Cholera Hotspot Areas of Lusaka District, Zambia: A Cross-Sectional Study(Microorganisms, 2026-02-11) Ng’ombe, Harriet; Luchen, Charlie C.; Phiri, Bernard; Ngosa, Dennis; Kapikila, Robby; Sakanya, Sydney; Sakala, Chikondi; Mbewe, Nyuma; Liswaniso, Fraser; Chilengi, Roma; Wilkinson, Eduan; Liebenberg, Lenine; Khan, Wesaal; Thomson, Nicholas R; Sack, David; Bosomprah, Samuel; Chisenga, Caroline C.Abstract The October 2023 to 2024 cholera outbreak demonstrates significant challenges related to water quality and sanitation, especially in peri-urban areas with limited access to clean water. This study assesses the presence of faecal coliforms and Escherichia coli (E. coli) in drinking water sources across five townships, identified as cholera transmission hotspots, two months post the cholera outbreak in the Lusaka District. A total of 169 water samples were collected from protected sources, treated piped water, and unprotected sources, including dams and shallow wells. Faecal coliforms and E. coli were detected across all source types. Among unprotected sources, 92.3% (12/13) of samples contained ≥100 CFU/100 mL of both faecal coliforms and E. coli. Protected sources showed variable contamination, with 18.3% exceeding ≥100 CFU/100 mL for faecal coliforms and 15.4% for E. coli. Treated water sources showed the lowest contamination, with 88.5% of samples having no detectable faecal coliforms and 90.4% having no detectable E. coli. Zero-inflated negative binomial regression showed that treated water sources were associated with substantially lower faecal coliform counts compared with protected sources (PR = 0.11, 95% CI: 0.03–0.35), while unprotected sources exhibited higher contamination intensity (PR = 1.77, 95% CI: 0.94–3.31). Treated sources were significantly more likely to be structurally free of contamination, whereas unprotected sources had an extremely low probability of yielding zero counts. These findings indicate that current water safety conditions in Lusaka’s cholera hotspot areas remain inadequate for preventing faecal-oral transmission.Item Genomic Analysis and Antimicrobial Resistance of Vibrio Cholerae Isolated During Zambia’s 2023 Cholera Epidemic(2025-12-02) Ng'ombe, Harriet; Luchen, Charlie C.; Bote, Lia; Kasonde, Mpanga; Musonda, Kunda; Mwape, Kapambwe K.; Kuntawala, Dhvani H.; Silwamba, Suwilanji; Chibuye, Mwelwa; Chibesa, Kennedy; Mbewe, Nyuma; Bosomprah, Samuel; Khan, Wesaal; Liebenberg, Lenine; Oliveira, Tulio de; Wilkinson, Eduan; Dorman, Matthew J.; Coghlan, Avril; Simuyandi, Michelo; Chilengi, Roma; Chisenga, Caroline C.; Thomson, Nicholas R.Introduction. Cholera, caused by Vibrio cholerae, remains a priority public health concern, particularly in developing countries. The first cholera outbreak in Zambia was documented in the 1970s, with recurring epidemics reported since then. In 2023, a cholera outbreak affected Zambia, particularly in districts bordering Malawi, Mozambique and the Democratic Republic of Congo, with significant cases reported in these neighbouring countries. This study aims to analyse cholera cases and isolates obtained during the 2023 epidemic, focusing on geographical distribution, genetic relatedness of isolates and their antibiotic resistance profiles. Methods. Stool samples were collected from patients presenting with cholera-like symptoms across three provinces of Zambia. A total of 98 samples were cultured on thiosulphate citrate bile salts sucrose agar, resulting in 32 sequenced V. cholerae isolates. Whole-genome sequencing was performed using Oxford Nanopore Technology, and phylogenetic inference was also achieved by the analysis of SNPs. Phenotypic antimicrobial resistance testing was conducted following Clinical and Laboratory Standards Institute guidelines. The genomic data were analysed for virulence factors and antimicrobial resistance profiles. Results. Of the 98 stool samples tested, 38 confirmed cholera cases were identified. A subset of 32 confirmed V. cholerae isolates, predominantly from the Eastern Province of Zambia (n=21), was selected for whole-genome sequencing. Genomic analysis revealed that all isolates belonged to the seventh pandemic El Tor lineage and the O1 serogroup, with two distinct clades identified corresponding to the 10th (T10) and 15th (T15) transmission events. Geographical analysis indicated a predominance of Ogawa serotypes in Eastern Province and Inaba in Northern Province. The virulence gene analysis confirmed the presence of key cholera toxin genes (ctxA and ctxB) and intestinal colonization factors. All isolates carried genes or mutations predicted to confer resistance to multiple antibiotics, including decreased susceptibility to ciprofloxacin, recommended for the treatment of cholera by the World Health Organization. Conclusion. The findings highlight the critical need for enhanced surveillance and targeted interventions to mitigate cholera outbreaks in Zambia. The emergence of resistant V. cholerae strains necessitates innovative strategies, including improved water sanitation, vaccination efforts and novel therapeutic approaches to combat this enduring public health threat.Item Prevalence and Patterns of Enteric Co-Infections Among Individuals Presenting with Cholera-like Diarrheal Disease During Seasonal Cholera Outbreaks(Pathogens, 2025-11-30) Kuntawala, Dhvani H.; Bosomprah, Samuel; Phiri, Bernard; Ng’ombe, Harriet; Liswaniso, Fraser; Muchimba, Mutinta; Silwamba, Suwilanji; Chibesa, Kennedy; Nzangwa, Bertha T.; Luchen, Charlie C.; Mwape, Innocent; Tigere, Sekayi F.; Simuyandi, Michelo; Mbewe, Nyuma; Chilengi, Roma; Debes, Amanda K.; Thomson, Nicholas R.; Sack, David A.; Chisenga, Caroline C.Abstract Cholera remains a major public health challenge, and co-infections can complicate clinical outcomes. In a cross-sectional study, we investigated the prevalence and patterns of enteric co-infections during Zambia’s 2023–2024 cholera outbreak and evaluated their implications for disease severity. 240 suspected cholera patients were enrolled from five healthcare facilities in Lusaka. Stools were tested for 11 enteric pathogens using the Bosphore® Gastroenteritis Panel Kit v2 on the QuantStudio 5 qPCR, with Vibrio cholerae confirmed by real-time PCR (quantitative PCR). Co-infections were highly prevalent, affecting 79.2% of participants. Campylobacter was the most frequently detected pathogen (70.0%), followed by Norovirus GI/GII (20.0%). Persons living with HIV were significantly more likely to present with co-infections than their counterparts (adjusted PR 1.27, 95% CI: 1.07–1.51; p = 0.008). Participants with confirmed V. cholerae + coinfections (N = 62) were less likely to developed moderate to severe disease compared to those with mono-infections (adjusted PR 0.59, 95% CI: 0.38–0.90; p = 0.014). These findings highlight the high prevalence and complexity of co-infections during cholera outbreaks, potentially contributing to antimicrobial resistance. They also highlight the need for targeted clinical management, particularly among persons living with HIV.Item Risk of hospitalization or death does not differ in children exposed to HIV, yet uninfected compared to nonexposed peers in Lusaka, Zambia.(2025-Jul-01) Herlihy, Julie M.; Zulu, Ethan; Mwananyanda, Lawrence; Forman, Leah; Heeren, Tim; Gill, Christopher J.; Chilengi, Roma; Namuziya, Natasha; Payne-Lohman, Barbara; Chavuma, Roy; Duffy, Cassandra R.; Thea, Donald M.OBJECTIVE: Increased mortality and morbidity has been observed among children who are HIV-exposed, uninfected (CHEU). It is unknown if health disparities remain despite promotion of exclusive breastfeeding and adoption of universal combination antiretroviral therapy (cART) for pregnant women. DESIGN: We conducted a longitudinal cohort study among pregnant women with and without HIV [Zambia Infant Cohort (ZICS)] with the primary goal to measure the morbidity/mortality experienced by CHEU in first 6 months of life, and secondarily whether such disparities could be explained by timing of cART initiation or elevated maternal immune activation. METHODS: Pregnant women with/without HIV (1 : 1) were enrolled prior to 26 weeks gestation by ultrasound and assessed twice antenatally. Infants were seen at birth, 6 days, 6, 10, 14, 20, and 24 weeks of age and assessed for illnesses, sick visits/hospitalizations, infant feeding, immunizations, and co-trimoxazole compliance. RESULTS: From 1276 livebirths, there were 36 deaths and 89 hospitalizations over 6 months. Preconception cART uptake was 73%, and majority of pregnant women with HIV had suppressed viral loads at enrollment. There was no difference in hospitalization or death rates for CHEU as compared to HIV-unexposed children [incidence rate ratio (IRR) 1.27, 95% CI 0.79-2.04, P = 0.33]. This did not shift after adjusting for maternal immune activation prematurity or small for gestational age (SGA). Exclusive breastfeeding reduced risk of hospitalization by 43%. CONCLUSION: In this setting of moderate cART uptake, we found no evidence of increased hospitalizations or deaths among CHEU. We conclude that the observed increased morbidity among CHEU can be effectively mitigated through early initiation of cART and exclusive breastfeeding.Item How can Africa sustain its HIV response amid US aid cuts?(2025-Jul) Mutale, Wilbroad; Semeere, Aggrey; Bukusi, Elizabeth A.; Ojji, Dike; Venter, Francois; Odeny, Thomas; Chilengi, Roma; Mosepele, Mosepele; Geng, Elvin; Sikazwe, Izukanji; Bosomprah, Samuel; Mulenga, Llyod; Simitala, FredItem Present or Absent: Risks and protective factors of sudden infant death syndrome (SIDS) in the Zambian context.(2025-May-13) Zulu, Ethan M.; Mwananyanda, Lawrence; Pieciak, Rachel C.; Forman, Leah S.; Shah, Janaki ; Heeren, Tim; Gill, Christopher J.; Chilengi, Roma; Payne-Lohman, Barbara; Duffy, Cassandra R.; Osei-Poku, Godwin; Thea, Donald M.; Wa Somwe, Somwe; Herlihy, Julie M.BACKGROUND: Despite a reduction in Sudden Unexplained Infant Death (SUID) in high-income countries, the incidence of SUID and the prevalence of its risk and protective factors remain poorly understood in Zambia due to limited research. The aim of our study was to describe the infant sleep positions and sleep environments in an urban Zambian population to gain a better understanding of the modifiable risk factors for SUID. METHODS: Data from the Zambian Infant Cohort Study (ZICS), a prospective birth cohort, were collected to describe infant sleep practices in Chawama, a densely populated peri-urban community in Lusaka, Zambia. During the 20-week study visit a structured questionnaire was administered to obtain data about the sleeping and environmental risks associated with SUID. RESULTS: Data were collected from 596 caregivers and 605 infants. Only 6.4% of caregivers did attain an education beyond secondary school, and a significant proportion of infants (20.2%) had low birth weights, with 10.7% of infants confirmed by ultrasound as preterm. Furthermore, 96.5% of infants were placed to sleep on their side or in a prone position, and 98.2% of infants shared a sleep surface with their caregiver. Breastfeeding, a protective factor, was highly prevalent, with 90.2% of infants receiving some form of breastfeeding at the 24-week visit. CONCLUSION: The results of this study show that both modifiable (bed-sharing and prone sleep position) and non-modifiable risk factors (low birthweight and prematurity) of SUID are prevalent in this low socioeconomic setting in Zambia. Public health strategies to prevent SUID will need to be innovative and culturally congruent in addressing modifiable risks, such as bedsharing, in settings where there is a lack of space. TRIAL REGISTRATION: Trial number: 1R01HD094650.Item Community Engagement Strategy for Building Trust in Human Challenge Studies Using Participatory and Creative Methods: An Ethical Imperative.(2025-Sep-12) Kunda-Ng'andu, Evelyn M.; Chirwa, Masuzyo; Muzazu, Seke; Laban, Natasha; Chisenga, Caroline C.; Simuyandi, Michelo; Mwale, Stanley; Chilengi, Roma; Sharma, AnjaliHuman Infection Challenge studies (HICs) are crucial for advancing global understanding of disease pathogenesis, immune responses, and accelerating vaccine and drug development. Explorations on willingness to participate among medical students revealed the need to ensure full understanding of HIC requirements, for example, for residency, by the broader community. This raised the question of 'How could we ensure informed and understood consent for the ethical conduct of HIC?' We employed iterative participatory discovery and creative design methods, including three Zoom meetings and discussions with university students and community leaders. Neighbourhood Health Committee leaders further refined suggested creatives of a future mass-media campaign for building trust in HICs. Deliberative focus group discussions and workshops were conducted on communication strategies on HICs' requirements, risks, requirements, and benefits. The final creative brief suggested (1) using a pyramid approach utilizing existing community structures, to introduce HIC concepts progressively to larger groups, (2) engaging communities through theatre for development, community dialogue, and engagement meetings, and wide society through social and mass media advertisements, and (3) preference for the term 'Human Challenge Studies' over 'Human Infection Challenge Studies'. We learned that community engagement, if properly conducted, can create systems of ownership of research and build communication strategies to achieve an accurate understanding of HICs and use informed participation that results in trustworthy data. We need further research, including in rural areas, pilot testing of evaluation strategies, and continued engagement with diverse stakeholders to create products that can be adapted by future HIC studies in settings such as Zambia.