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The CIDRZ Research Repository serves as an open-access archive for peer-reviewed publications, conference papers, and other scholarly outputs from CIDRZ researchers. Our goal is to promote the dissemination of knowledge and support evidence-based public health initiatives.
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Item "(2020-Jun) Topp SM; Carbone NB; Tseka J; Kamtsendero L; Banda G; Herce MEBACKGROUND: In the era of Option B+ and 'treat all' policies for HIV, challenges to retention in care are well documented. In Malawi, several large community-facility linkage (CFL) models have emerged to address these challenges, training lay health workers (LHW) to support the national prevention of mother-to-child transmission (PMTCT) programme. This qualitative study sought to examine how PMTCT LHW deployed by Malawi's three most prevalent CFL models respond to known barriers to access and retention to antiretroviral therapy (ART) and PMTCT. METHODS: We conducted a qualitative study, including 43 semi-structured interviews with PMTCT clients; 30 focus group discussions with Ministry of Health (MOH)-employed lay and professional providers and PMTCT LHWs; a facility CFL survey and 2-4 hours of onsite observation at each of 8 sites and in-depth interviews with 13 programme coordinators and MOH officials. Thematic analysis was used, combining inductive and deductive approaches. RESULTS: Across all three models, PMTCT LHWs carried out a number of 'targeted' activities that respond directly to a range of known barriers to ART uptake and retention. These include: (i) fulfilling counselling and educational functions that responded to women's fears and uncertainties; (ii) enhancing women's social connectedness and participation in their own care and (iii) strengthening service function by helping clinic-based providers carry out duties more efficiently and effectively. Beyond absorbing workload or improving efficiency, however, PMTCT LHWs supported uptake and retention through foundational but often intangible work to strengthen CFL, including via efforts to strengthen facility-side responsiveness, and build community members' recognition of and trust in services. CONCLUSION: PMTCT LHWs in each of the CFL models examined, addressed social, cultural and health system factors influencing client access to, and engagement with, HIV care and treatment. Findings underscore the importance of person-centred design in the 'treat-all' era and the contribution LHWs can make to this, but foreground the challenges of achieving person-centredness in the context of an under-resourced health system. Further work to understand the governance and sustainability of these project-funded CFL models and LHW cadres is now urgently required.Item A Bayesian modelling framework with model comparison for epidemics with super-spreading(2025-12) Craddock Hannah; Spencer Simon E.F.; Didelot XavierItem A challenging case of refractory infection following fish fin injury: Successful treatment through combined therapy(2025-11) Chen Yanqing; Mo Shifu; Li Jianjian; Zhong Huiting; Chao Chikit; Liu Ting; Ma HanItem A cluster randomized trial of routine HIV-1 viral load monitoring in Zambia: study design, implementation, and baseline cohort characteristics.(2010-Mar-12) Koethe JR; Westfall AO; Luhanga DK; Clark GM; Goldman JD; Mulenga PL; Cantrell RA; Chi BH; Zulu I; Saag MS; Stringer JSBACKGROUND: The benefit of routine HIV-1 viral load (VL) monitoring of patients on antiretroviral therapy (ART) in resource-constrained settings is uncertain because of the high costs associated with the test and the limited treatment options. We designed a cluster randomized controlled trial to compare the use of routine VL testing at ART-initiation and at 3, 6, 12, and 18 months, versus our local standard of care (which uses immunological and clinical criteria to diagnose treatment failure, with discretionary VL testing when the two do not agree). METHODOLOGY: Dedicated study personnel were integrated into public-sector ART clinics. We collected participant information in a dedicated research database. Twelve ART clinics in Lusaka, Zambia constituted the units of randomization. Study clinics were stratified into pairs according to matching criteria (historical mortality rate, size, and duration of operation) to limit the effect of clustering, and independently randomized to the intervention and control arms. The study was powered to detect a 36% reduction in mortality at 18 months. PRINCIPAL FINDINGS: From December 2006 to May 2008, we completed enrollment of 1973 participants. Measured baseline characteristics did not differ significantly between the study arms. Enrollment was staggered by clinic pair and truncated at two matched sites. CONCLUSIONS: A large clinical trial of routing VL monitoring was successfully implemented in a dynamic and rapidly growing national ART program. Close collaboration with local health authorities and adequate reserve staff were critical to success. Randomized controlled trials such as this will likely prove valuable in determining long-term outcomes in resource-constrained settings. TRIAL REGISTRATION: Clinicaltrials.gov NCT00929604.Item A color-coded tape for uterine height measurement: a tool to identify preterm pregnancies in low resource settings.(2015) Althabe F; Berrueta M; Hemingway-Foday J; Mazzoni A; Bonorino CA; Gowdak A; Gibbons L; Bellad MB; Metgud MC; Goudar S; Kodkany BS; Derman RJ; Saleem S; Iqbal S; Ala SH; Goldenberg RL; Chomba E; Manasyan A; Chiwila M; Imenda E; Mbewe F; Tshefu A; Lokomba V; Bose CL; Moore J; Meleth S; McClure EM; Koso-Thomas M; Buekens P; Belizán JMINTRODUCTION: Neonatal mortality associated with preterm birth can be reduced with antenatal corticosteroids (ACS), yet <10% of eligible pregnant women in low-middle income countries. The inability to accurately determine gestational age (GA) leads to under-identification of high-risk women who could receive ACS or other interventions. To facilitate better identification in low-resource settings, we developed a color-coded tape for uterine height (UH) measurement and estimated its accuracy identifying preterm pregnancies. METHODS: We designed a series of colored-coded tapes with segments corresponding to UH measurements for 20-23.6 weeks, 24.0-35.6 weeks, and >36.0 weeks GA. In phase 1, UH measurements were collected prospectively in the Democratic Republic of Congo, India and Pakistan, using distinct tapes to address variation across regions and ethnicities. In phase 2, we tested accuracy in 250 pregnant women with known GA from early ultrasound enrolled at prenatal clinics in Argentina, India, Pakistan and Zambia. Providers masked to the ultrasound GA measured UH. Receiver operating characteristics (ROC) analysis was conducted. RESULTS: 1,029 pregnant women were enrolled. In all countries the tapes were most effective identifying pregnancies between 20.0-35.6 weeks, compared to the other GAs. The ROC areas under the curves and 95% confidence intervals were: Argentina 0.69 (0.63, 0.74); Zambia 0.72 (0.66, 0.78), India 0.84 (0.80, 0.89), and Pakistan 0.83 (0.78, 0.87). The sensitivity and specificity (and 95% confidence intervals) for identifying pregnancies between 20.0-35.6 weeks, respectively, were: Argentina 87% (82%-92%) and 51% (42%-61%); Zambia 91% (86%-95%) and 50% (40%-60%); India 78% (71%-85%) and 89% (83%-94%); Pakistan 63% (55%-70%) and 94% (89%-99%). CONCLUSIONS: We observed moderate-good accuracy identifying pregnancies ≤ 35.6 weeks gestation, with potential usefulness at the community level in low-middle income countries to facilitate the preterm identification and interventions to reduce preterm neonatal mortality. Further research is needed to validate these findings on a population basis.Item A controlled study to assess the effects of a Fast Track (FT) service delivery model among stable HIV patients in Lusaka Zambia.(2022) Bolton Moore C; Pry JM; Mukumbwa-Mwenechanya M; Eshun-Wilson I; Topp S; Mwamba C; Roy M; Sohn H; Dowdy DW; Padian N; Holmes CB; Geng EH; Sikazwe IFast Track models-in which patients coming to facility to pick up medications minimize waiting times through foregoing clinical review and collecting pre-packaged medications-present a potential strategy to reduce the burden of treatment. We examine effects of a Fast Track model (FT) in a real-world clinical HIV treatment program on retention to care comparing two clinics initiating FT care to five similar (in size and health care level), standard of care clinics in Zambia. Within each clinic, we selected a systematic sample of patients meeting FT eligibility to follow prospectively for retention using both electronic medical records as well as targeted chart review. We used a variety of methods including Kaplan Meier (KM) stratified by FT, to compare time to first late pick up, exploring late thresholds at >7, >14 and >28 days, Cox proportional hazards to describe associations between FT and late pick up, and linear mixed effects regression to assess the association of FT with medication possession ratio. A total of 905 participants were enrolled with a median age of 40 years (interquartile range [IQR]: 34-46 years), 67.1% were female, median CD4 count was 499 cells/mm3 (IQR: 354-691), and median time on ART was 5 years (IQR: 3-7). During the one-year follow-up period FT participants had a significantly reduced cumulative incidence of being >7 days late for ART pick-up (0.36, 95% confidence interval [CI]: 0.31-0.41) compared to control participants (0.66; 95% CI: 0.57-0.65). This trend held for >28 days late for ART pick-up appointments, at 23% (95% CI: 18%-28%) among intervention participants and 54% (95% CI: 47%-61%) among control participants. FT models significantly improved timely ART pick up among study participants. The apparent synergistic relationship between refill time and other elements of the FT suggest that FT may enhance the effects of extending visit spacing/multi-month scripting alone. ClinicalTrials.gov Identifier: NCT02776254 https://clinicaltrials.gov/ct2/show/NCT02776254.Item A Cross-Sectional Study on Socio-Ecological and Socio-Anthropological Determinants of COVID-19 in Lusaka Province of Zambia(2022-9-28) Fonchin Alyce Fri; Mumba Chisoni; Basikolo Linda; Kallu Simegnew Adugna; Kainga Henson; Mwiinde Jezreel; Benhard Vistorina; Muma John Bwalya; Munyeme MussoThe COVID-19 disease constitutes a pandemic that has created an international public health emergency. Besides the significant health challenges, the impact of the COVID-19 disease has been the restriction of movements that have heavily affected the global economy. The first case of COVID-19 in Zambia was identified on March 18th, 2020. By the end of November 2020, the number of districts reporting COVID-19 infections had increased from 68 to 96, with reports of the highest transmission in the capital city, Lusaka, the Copperbelt, and Ndola districts. As COVID-19 spread across the nation of Zambia, several factors are responsible for the spread of the virus. Despite the extensive collection of research done on determinants of COVID-19 disease, the spatial distribution of the disease along socio-demographical and socio-ecological domains remains speculative and infectious diseases have been less looked into in the areas of anthropological dynamics. This study used a cross-sectional design to investigate the ecological and anthropological determinants of COVID-19 disease in four compounds in the Lusaka district of Zambia. A guided questionnaire was used to collect data from 301 participants. A descriptive analysis of all independent variables was done. Analysis for associations of dependent and independent variables and multivariate analysis of the independent variables significant at the bi-variate level was conducted to investigate the association between the dependent variable (Knowledge of anyone infected with COVID-19 virus) and the independent variables. The bi-variate analysis results showed that 14 independent variables with odds ratios greater than one were significantly associated with the spread of COVID-19. Two variables were found to be highly significant in the multivariable logistic regression analysis model. These included beliefs about COVID-19 (odds = 3.0; p = 0.003; CI 1.2-3.3), and participants area of residence (odds = 2.6; p = 0.003; CI = 1.2-5.5). Other significant multivariate variables were ecological variable; climate and anthropological variables; hand hygienic practices. The current research provides further insight into the potential role ecology and anthropology contribute to the spread of communicable diseases. The study recommends awareness of the population to enhance preparedness and response to reduce the spread of COVID-19.Item A Deterministic Risk Assessment of the Human Exposure to Cadmium, Lead and Chromium Through the Consumption of Well and Bottled Water in Lusaka District, Zambia(2023-2-28) Banda Mkuzi; Muma John Bwalya; Bumbangi Flavien N.; M'kandawire Ethel; Mukuma Mercy; Munyeme Musso; Musawa Grace; Ndaki Enock M; Benhard Vistorina; Mumba ChisoniThe United Nations Sustainable Development Goal number six is to ‘Ensure availability and sustainable management of water and sanitation for all, which is an essential component for human survival. Access to safe drinking water is essential for health, a basic human right and a component of effective policy for health protection. Safe drinking water implies that the water does not represent any significant risk to health over a lifetime of consumption, including different sensitivities that may occur between life stages. However, water is prone to contamination with heavy metals through natural and anthropogenic sources, making it unsuitable for human consumption due to the cumulative potential risks associated with the presence of heavy metals. This study was conducted to assess the non-carcinogenic and carcinogenic risk of human exposure to cadmium, lead and chromium through the consumption of well and bottled water in Lusaka district of Zambia. Secondary data was used to determine the mean concentrations of heavy metals in well and bottled water in Lusaka district as well as to calculate the hazard index (non-carcinogenic risk) and cancer risk for the metals under study. The results revealed that a hazard index for cadmium, lead and chromium in both well and bottled water was higher than 1, indicating adverse effects on human health over a lifetime of consumption. Similarly, the total cancer risk through exposure to cadmium and chromium in well and bottled water was 1.2 x 10-1 and 2.25 x 10-1, respectively, higher than the safe threshold limit set by the United States Environmental Protection Agency (USEPA) of 1 × 10−4. The study concludes that there is a possible non-carcinogenic risk of exposure to cadmium, lead and chromium through the consumption of well and bottled water in Lusaka district. Further, the study concludes that there is a possible carcinogenic risk of exposure to cadmium and chromium through the consumption of both well and bottled water. Owing to the proportion of both well and bottled water samples that exceeded the Zambia Bureau of Standards threshold limit, cadmium poses the greatest concern and requires intervention to reduce exposure. Therefore, it is recommended that heavy metal concentrations in drinking water should be periodically monitored to minimize health risks to consumers.Item A discrete SIR epidemic model incorporating media impact, resource limitaions and threshold switching strategies(2025-12) Qin Wenjie; Zhang Shan; Yang Yi; Zhang JiaminItem A fatal incidence of Yersinia enterocolitica meningitis. Case report(2025-11) Dutschke Alexander; Hønge Bo Langhoff; Nielsen Tine Birkelund; Schjørring Susanne; Hansen Kristoffer SkaalumItem A Hybrid Epidemiological Model Approach to Improvement of Predictive Accuracy in Zambian Infectious Diseases Modelling(2025-4-16) Chibawe Grey; Nyirenda MayumboRecurrent infectious disease outbreaks, including cholera and influenza, as well as recent global pandemics like COVID-19, pose persistent public health challenges in Zambia. Traditional compartmental models based on Ordinary Differential Equations (ODEs), particularly Susceptible-Exposed-Infectious-Recovered (SEIR) frameworks, have long been used to predict disease spread. While these models are relatively simple and require fewer data, they often lack the flexibility to capture non-linear and stochastic factors—such as environmental variables and abrupt policy shifts—that can critically influence epidemic trajectories in resource-limited settings. In contrast, Artificial Neural Network (ANN) approaches excel at learning complex, non-linear relationships directly from data. By incorporating diverse inputs (e.g., climatic variables, demographic distributions), ANNs can adapt to evolving outbreak patterns more effectively than traditional ODE-based methods. However, their reliance on large, high-quality datasets and considerable computational resources can hinder adoption in places with fragmented surveillance systems. To address these complementary strengths and weaknesses, this study explores a hybrid modelling strategy that integrates a parameter-optimised SEIR model with a Transformer-based ANN. Historical COVID-19 data from 2020 to 2024 and environmental data (temperature, rainfall, humidity) were used to develop and validate three models: (1) an SEIR model whose parameters were estimated via curve fitting, (2) a standalone Transformer ANN, and (3) a combined SEIR-ANN ensemble. Model performance was assessed using metrics such as Root Mean Squared Error (RMSE), Mean Absolute Error (MAE), and R-squared (R²). Results indicate that the hybrid model consistently outperformed the individual SEIR and ANN models, exhibiting the lowest RMSE and MAE. Furthermore, integrating environmental factors into the ANN substantially improved predictive accuracy. These findings highlight the promise of hybrid frameworks in capturing the multifaceted dynamics of infectious diseases in Zambia. By leveraging SEIR’s mechanistic insights alongside the ANN’s capacity to learn from diverse datasets, public health practitioners can improve outbreak predictions and resource allocation. Nevertheless, barriers—such as limited data availability, computational infrastructure, and model interpretability—must be addressed to foster broader implementation. Strengthened data collection systems, increased investment in computational tools, and targeted capacity-building programs are recommended to fully realise the benefits of hybrid epidemiological modelling in Zambia.Item A mixed methods study on men's and women's tuberculosis care journeys in Lusaka, Zambia-Implications for gender-tailored tuberculosis health promotion and case finding strategies.(2023) Kerkhoff AD; Mwamba C; Pry JM; Kagujje M; Nyangu S; Mateyo K; Sanjase N; Chilukutu L; Christopoulos KA; Muyoyeta M; Sharma AMen and women with undiagnosed tuberculosis (TB) in high burden countries may have differential factors influencing their healthcare seeking behaviors and access to TB services, which can result in delayed diagnoses and increase TB-related morbidity and mortality. A convergent, parallel, mixed-methods study design was used to explore and evaluate TB care engagement among adults (≥18 years) with newly diagnosed, microbiologically-confirmed TB attending three public health facilities in Lusaka, Zambia. Quantitative structured surveys characterized the TB care pathway (time to initial care-seeking, diagnosis, and treatment initiation) and collected information on factors influencing care engagement. Multinomial multivariable logistic regression was used to determine predicted probabilities of TB health-seeking behaviors and determinants of care engagement. Qualitative in-depth interviews (IDIs; n = 20) were conducted and analyzed using a hybrid approach to identify barriers and facilitators to TB care engagement by gender. Overall, 400 TB patients completed a structured survey, of which 275 (68.8%) and 125 (31.3%) were men and women, respectively. Men were more likely to be unmarried (39.3% and 27.2%), have a higher median daily income (50 and 30 Zambian Kwacha [ZMW]), alcohol use disorder (70.9% [AUDIT-C score ≥4] and 31.2% [AUDIT-C score ≥3]), and a history of smoking (63.3% and 8.8%), while women were more likely to be religious (96.8% and 70.8%) and living with HIV (70.4% and 36.0%). After adjusting for potential confounders, the probability of delayed health-seeking ≥4 weeks after symptom onset did not differ significantly by gender (44.0% and 36.2%, p = 0.14). While the top reasons for delayed healthcare-seeking were largely similar by gender, men were more likely to report initially perceiving their symptoms as not being serious (94.8% and 78.7%, p = 0.032), while women were more likely to report not knowing the symptoms of TB before their diagnosis (89.5% and 74.4%; p = 0.007) and having a prior bad healthcare experience (26.4% and 9.9%; p = 0.036). Notably, women had a higher probability of receiving TB diagnosis ≥2 weeks after initial healthcare seeking (56.5% and 41.0%, p = 0.007). While men and women reported similar acceptability of health-information sources, they emphasized different trusted messengers. Also, men had a higher adjusted probability of stating that no one influenced their health-related decision making (37.9% and 28.3%, p = 0.001). In IDIs, men recommended TB testing sites at convenient community locations, while women endorsed an incentivized, peer-based, case-finding approach. Sensitization and TB testing strategies at bars and churches were highlighted as promising approaches to reach men and women, respectively. This mixed-methods study found important differences between men and women with TB in Zambia. These differences suggest the need for gender-tailored TB health promotion, including addressing harmful alcohol use and smoking among men, and sensitizing HCWs to prolonged delays in TB diagnosis among women, and also using gender-specific approaches as part of community-based, active case-finding strategies to improve TB diagnosis in high burden settings.Item A mobile phone-based, community health worker program for referral, follow-up, and service outreach in rural Zambia: outcomes and overview.(2014-Aug) Schuttner L; Sindano N; Theis M; Zue C; Joseph J; Chilengi R; Chi BH; Stringer JS; Chintu NBACKGROUND: Mobile health (m-health) utilizes widespread access to mobile phone technologies to expand health services. Community health workers (CHWs) provide first-level contact with health facilities; combining CHW efforts with m-health may be an avenue for improving primary care services. As part of a primary care improvement project, a pilot CHW program was developed using a mobile phone-based application for outreach, referral, and follow-up between the clinic and community in rural Zambia. MATERIALS AND METHODS: The program was implemented at six primary care sites. Computers were installed at clinics for data entry, and data were transmitted to central servers. In the field, using a mobile phone to send data and receive follow-up requests, CHWs conducted household health surveillance visits, referred individuals to clinic, and followed up clinic patients. RESULTS: From January to April 2011, 24 CHWs surveyed 6,197 households with 33,304 inhabitants. Of 15,539 clinic visits, 1,173 (8%) had a follow-up visit indicated and transmitted via a mobile phone to designated CHWs. CHWs performed one or more follow-ups on 74% (n=871) of active requests and obtained outcomes on 63% (n=741). From all community visits combined, CHWs referred 840 individuals to a clinic. CONCLUSIONS: CHWs completed all planned aspects of surveillance and outreach, demonstrating feasibility. Components of this pilot project may aid clinical care in rural settings and have potential for epidemiologic and health system applications. Thus, m-health has the potential to improve service outreach, guide activities, and facilitate data collection in Zambia.Item A model of tuberculosis screening for pregnant women in resource-limited settings using Xpert MTB/RIF.(2012) Turnbull ER; Kancheya NG; Harris JB; Topp SM; Henostroza G; Reid SETimely diagnosis and treatment of maternal tuberculosis (TB) is important to reduce morbidity and mortality for both the mother and child, particularly in women who are coinfected with HIV. The World Health Organization (WHO) recommends the integration of TB/HIV screening into antenatal services but available diagnostic tools are slow and insensitive, resulting in delays in treatment initiation. Recently the WHO endorsed Xpert MTB/RIF, a highly sensitive, real-time PCR assay for Mycobacterium tuberculosis that simultaneously detects rifampicin resistance directly from sputum and provides results within 100 minutes. We propose a model for same-day TB screening and diagnosis of all pregnant women at antenatal care using Xpert MTB/RIF. Pilot studies are urgently required to evaluate strategies for the integration of TB screening into antenatal clinics using new diagnostic technologies.Item A new approach to prevent, diagnose, and treat hepatitis B in Africa.(2023) Spearman CW; Andersson MI; Bright B; Davwar PM; Desalegn H; Guingane AN; Johannessen A; Kabagambe K; Lemoine M; Matthews PC; Ndow G; Riches N; Shimakawa Y; Sombié R; Stockdale AJ; Taljaard JJ; Vinikoor MJ; Wandeler G; Okeke E; Sonderup MThere are 82 million people living with hepatitis B (PLWHB) in the World Health Organization Africa region, where it is the main cause of liver disease. Effective vaccines have been available for over 40 years, yet there are 990,000 new infections annually, due to limited implementation of hepatitis B birth dose vaccination and antenatal tenofovir prophylaxis for highly viraemic women, which could eliminate mother-to-child transmission. Despite effective and cheap antiviral treatment which can suppress hepatitis B virus replication and reduce the risk of hepatocellular carcinoma (HCC), < 2% of PLWHB are diagnosed, and only 0.1% are treated. As a result, PLWHB are frequently diagnosed only when they have already developed decompensated cirrhosis and late-stage HCC, and consequently 80,000 hepatitis B-associated deaths occur each year. Major barriers include complex treatment guidelines which were derived from high-income settings, lack of affordable diagnostics, lack or insufficient domestic funding for hepatitis care, and limited healthcare infrastructure. Current treatment criteria may overlook patients at risk of cirrhosis and HCC. Therefore, expanded and simplified treatment criteria are needed. We advocate for decentralized community treatment programmes, adapted for low-resource and rural settings with limited laboratory infrastructure. We propose a strategy of treat-all except patients fulfilling criteria that suggest low risk of disease progression. Expanded treatment represents a financial challenge requiring concerted action from policy makers, industry, and international donor agencies. It is crucial to accelerate hepatitis B elimination plans, integrate hepatitis B care into existing healthcare programmes, and prioritize longitudinal and implementation research to improve care for PLWHB.Item A phase 2b randomized, controlled trial of the efficacy of the GMZ2 malaria vaccine in African children.(2016-Aug-31) Sirima SB; Mordmüller B; Milligan P; Ngoa UA; Kironde F; Atuguba F; Tiono AB; Issifou S; Kaddumukasa M; Bangre O; Flach C; Christiansen M; Bang P; Chilengi R; Jepsen S; Kremsner PG; Theisen MBACKGROUND: GMZ2 is a recombinant protein malaria vaccine, comprising two blood-stage antigens of Plasmodium falciparum, glutamate-rich protein and merozoite surface protein 3. We assessed efficacy of GMZ2 in children in Burkina Faso, Gabon, Ghana and Uganda. METHODS: Children 12-60months old were randomized to receive three injections of either 100μg GMZ2 adjuvanted with aluminum hydroxide or a control vaccine (rabies) four weeks apart and were followed up for six months to measure the incidence of malaria defined as fever or history of fever and a parasite density ⩾5000/μL. RESULTS: A cohort of 1849 children were randomized, 1735 received three doses of vaccine (868 GMZ2, 867 control-vaccine). There were 641 malaria episodes in the GMZ2/Alum group and 720 in the control group. In the ATP analysis, vaccine efficacy (VE), adjusted for age and site was 14% (95% confidence interval [CI]: 3.6%, 23%, p-value=0.009). In the ITT analysis, age-adjusted VE was 11.3% (95% CI 2.5%, 19%, p-value=0.013). VE was higher in older children. In GMZ2-vaccinated children, the incidence of malaria decreased with increasing vaccine-induced anti-GMZ2 IgG concentration. There were 32 cases of severe malaria (18 in the rabies vaccine group and 14 in the GMZ2 group), VE 27% (95% CI -44%, 63%). CONCLUSIONS: GMZ2 is the first blood-stage malaria vaccine to be evaluated in a large multicenter trial. GMZ2 was well tolerated and immunogenic, and reduced the incidence of malaria, but efficacy would need to be substantially improved, using a more immunogenic formulation, for the vaccine to have a public health role.Item A pilot case-control study using a one health approach to evaluate behavioral, environmental, and occupational risk factors for chronic kidney disease of unknown etiology in Sri Lanka.(2021) M Pry J; Jackson W; Rupasinghe R; Lishanthe G; Badurdeen Z; Abeysekara T; Chandrajith R; Smith W; Wickramasinghe SBACKGROUND: Chronic kidney disease of unknown etiology (CKDu) was first recognized in Sri Lanka in the early 1990s, and since then it has reached epidemic levels in the North Central Province of the country. The prevalence of CKDu is reportedly highest among communities that engage in chena and paddy farming, which is most often practiced in the dry zone including the North Central and East Central Provinces of Sri Lanka. Previous studies have suggested varied hypotheses for the etiology of CKDu; however, there is not yet a consensus on the primary risk factors, possibly due to disparate study designs, sample populations, and methodologies. METHODS: The goal of this pilot case-control study was to evaluate the relationships between key demographic, cultural, and occupational variables as risk factors for CKDu, with a primary interest in pesticide exposure both occupationally and through its potential use as an ingredient in brewed kasippu alcohol. An extensive one health focused survey was developed with in cooperation with the Centre for Research, Education, and Training on Kidney Diseases of Sri Lanka. RESULTS: A total of 56 CKDu cases and 54 control individuals were surveyed using a proctored, self-reported questionnaire. Occupational pesticide exposure and alcohol consumption were not found to be significant risk factors for CKDu. However, a statistically significant association with CKDu was observed with chewing betel (adjusted odds ratio [aOR]: 6.11, 95% confidence interval [CI]: 1.93, 19.35), age (aOR: 1.07, 95% CI: 1.02, 1.13), owning a pet dog (aOR: 3.74, 95% CI: 1.38, 10.11), water treatment (aOR: 3.68, 95% CI: 1.09, 12.43) and pests in the house (aOR: 5.81, 95% CI: 1.56, 21.60). CONCLUSIONS: The findings of this study suggest future research should focus on practices associated with chewing betel, potential animal interactions including pests in the home and pets, and risk factors associated with water. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s42522-020-00034-3.Item A pilot study of food supplementation to improve adherence to antiretroviral therapy among food-insecure adults in Lusaka, Zambia.(2008-Oct-01) Cantrell RA; Sinkala M; Megazinni K; Lawson-Marriott S; Washington S; Chi BH; Tambatamba-Chapula B; Levy J; Stringer EM; Mulenga L; Stringer JSBACKGROUND: The provision of food supplementation to food-insecure patients initiating antiretroviral therapy (ART) may improve adherence to medications. METHODS: A home-based adherence support program at 8 government clinics assessed patients for food insecurity. Four clinics provided food supplementation, and 4 acted as controls. The analysis compared adherence (assessed by medication possession ratio), CD4, and weight gain outcomes among food-insecure patients enrolled at the food clinics with those enrolled at the control clinics. RESULTS: Between May 1, 2004, and March 31, 2005, 636 food- insecure adults were enrolled. Food supplementation was associated with better adherence to therapy. Two hundred fifty-eight of 366 (70%) patients in the food group achieved a medication possession ratio of 95% or greater versus 79 of 166 (48%) among controls (relative risk = 1.5; 95% confidence interval: 1.2 to 1.8). This finding was unchanged after adjustment for sex, age, baseline CD4 count, baseline World Health Organization stage, and baseline hemoglobin. We did not observe a significant effect of food supplementation on weight gain or CD4 cell response. CONCLUSIONS: This analysis suggests that providing food to food-insecure patients initiating ART is feasible and may improve adherence to medication. A large randomized study of the clinical benefits of food supplementation to ART patients is urgently needed to inform international policy.Item 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 SBACKGROUND: 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.Item A population-based cohort study of stillbirth among twins in Lusaka, Zambia.(2015-Jul) Stringer EM; Chibwesha C; Stoner M; Vwalika B; Joseph J; Chi BH; Kaunda E; Goodnight W; Stringer JSOBJECTIVE: To determine rates of stillbirth and the associated risk factors for stillbirth among twins delivered in Lusaka, Zambia. METHODS: A retrospective cohort analysis was conducted of singletons and twins delivered at 26 public sector facilities between February 1, 2006, and May 31, 2013. Data were obtained from the Zambian Electronic Perinatal Record System. Risk of stillbirth was estimated using logistic regression. RESULTS: Overall, 260 657 singletons and 4021 twin pairs were included. There were 5105 stillbirths; 317 twins were stillborn. The crude stillbirth rate for twins was 39.4 per 1000 births (95% confidence interval [CI] 35.2-43.7) whereas the rate for singletons was 18.4 per 1000 births (95% CI 17.9-18.9; P<0.001). Factors associated with stillbirth among twins were increased interval between delivery (>60 minutes), low birth weight (<2500 g), birth order (being the second-born), and difference in birth weights (>30% discordance). CONCLUSION: Twins were at an increased risk of stillbirth. Improved understanding of factors associated with stillbirth in this population could help to improve perinatal outcomes globally.
