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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 Mixed methods approach to examining the implementation experience of a phone-based survey for a SARS-CoV-2 test-negative case-control study in California.(2024) Fukui N; Li SS; DeGuzman J; Myers JF; Openshaw J; Sharma A; Watt J; Lewnard JA; Jain S; Andrejko KL; Pry JMOBJECTIVE: To describe the implementation of a test-negative design case-control study in California during the Coronavirus Disease 2019 (COVID-19) pandemic. STUDY DESIGN: Test-negative case-control study. METHODS: Between February 24, 2021 - February 24, 2022, a team of 34 interviewers called 38,470 Californians, enrolling 1,885 that tested positive for SARS-CoV-2 (cases) and 1,871 testing negative for SARS-CoV-2 (controls) for 20-minute telephone survey. We estimated adjusted odds ratios for answering the phone and consenting to participate using mixed effects logistic regression. We used a web-based anonymous survey to compile interviewer experiences. RESULTS: Cases had 1.29-fold (95% CI: 1.24-1.35) higher adjusted odds of answering the phone and 1.69-fold (1.56-1.83) higher adjusted odds of consenting to participate compared to controls. Calls placed from 4pm to 6pm had the highest adjusted odds of being answered. Some interviewers experienced mental wellness challenges interacting with participants with physical (e.g., food, shelter, etc.) and emotional (e.g., grief counseling) needs, and enduring verbal harassment from individuals called. CONCLUSIONS: Calls placed during afternoon hours may optimize response rate when enrolling controls to a case-control study during a public health emergency response. Proactive check-ins and continual collection of interviewer experience(s) and may help maintain mental wellbeing of investigation workforce. Remaining adaptive to the dynamic needs of the investigation team is critical to a successful study, especially in emergent public health crises, like that represented by the COVID-19 pandemic.Item An exploration of multi-level factors affecting routine linkage to HIV care in Zambia's PEPFAR-supported treatment program in the treat all era.(2024) Chipungu J; Smith H; Mwamba C; Haambokoma M; Sharma A; Savory T; Musheke M; Pry J; Bolton C; Sikazwe I; Herce MEMultiple steps from HIV diagnosis to treatment initiation and confirmed engagement with the health system are required for people living with HIV to establish full linkage to care in the modern treat all era. We undertook a qualitative study to gain an in-depth understanding of the impeding and enabling factors at each step of this linkage pathway. In-depth interviews were conducted with fifty-eight people living with HIV recruited from ten routine HIV care settings supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) in Lusaka, Zambia. Using a semi-structured interview guide informed by an established conceptual framework for linkage to care, questions explored the reasons behind late, missed, and early linkage into HIV treatment, as well as factors influencing the decision to silently transfer to a different clinic after an HIV diagnosis. We identified previously established and intersecting barriers of internal and external HIV-related stigma, concerns about ART side effects, substance use, uncertainties for the future, and a perceived lack of partner and social support that impeded linkage to care at every step of the linkage pathway. However, we also uncovered newer themes specific to the current test and treat era related to the rapidity of ART initiation and insufficient patient-centered post-test counseling that appeared to exacerbate these well-known barriers, including callous health workers and limited time to process a new HIV diagnosis before treatment. Long travel distance to the clinic where they were diagnosed was the most common reason for silently transferring to another clinic for treatment. On the other hand, individual resilience, quality counseling, patient-centered health workers, and a supportive and empathetic social network mitigated these barriers. These findings highlight potential areas for strengthening linkage to care and addressing early treatment interruption and silent transfer in the test and treat era in Zambia.Item Systematic review of associations between gut microbiome composition and stunting in under-five children.(2024-May-23) Chibuye M; Mende DR; Spijker R; Simuyandi M; Luchen CC; Bosomprah S; Chilengi R; Schultsz C; Harris VCChildhood stunting is associated with impaired cognitive development and increased risk of infections, morbidity, and mortality. The composition of the enteric microbiota may contribute to the pathogenesis of stunting. We systematically reviewed and synthesized data from studies using high-throughput genomic sequencing methods to characterize the gut microbiome in stunted versus non-stunted children under 5 years in LMICs. We included 14 studies from Asia, Africa, and South America. Most studies did not report any significant differences in the alpha diversity, while a significantly higher beta diversity was observed in stunted children in four out of seven studies that reported beta diversity. At the phylum level, inconsistent associations with stunting were observed for Bacillota, Pseudomonadota, and Bacteroidota phyla. No single genus was associated with stunted children across all 14 studies, and some associations were incongruent by specific genera. Nonetheless, stunting was associated with an abundance of pathobionts that could drive inflammation, such as Escherichia/Shigella and Campylobacter, and a reduction of butyrate producers, including Faecalibacterium, Megasphera, Blautia, and increased Ruminoccoccus. An abundance of taxa thought to originate in the oropharynx was also reported in duodenal and fecal samples of stunted children, while metabolic pathways, including purine and pyrimidine biosynthesis, vitamin B biosynthesis, and carbohydrate and amino acid degradation pathways, predicted linear growth. Current studies show that stunted children can have distinct microbial patterns compared to non-stunted children, which could contribute to the pathogenesis of stunting.Item Prospective multicentre accuracy evaluation of the FUJIFILM SILVAMP TB LAM test for the diagnosis of tuberculosis in people living with HIV demonstrates lot-to-lot variability.(2024) Székely R; Sossen B; Mukoka M; Muyoyeta M; Nakabugo E; Hella J; Nguyen HV; Ubolyam S; Chikamatsu K; Macé A; Vermeulen M; Centner CM; Nyangu S; Sanjase N; Sasamalo M; Dinh HT; Ngo TA; Manosuthi W; Jirajariyavej S; Mitarai S; Nguyen NV; Avihingsanon A; Reither K; Nakiyingi L; Kerkhoff AD; MacPherson P; Meintjes G; Denkinger CM; Ruhwald MThere is an urgent need for rapid, non-sputum point-of-care diagnostics to detect tuberculosis. This prospective trial in seven high tuberculosis burden countries evaluated the diagnostic accuracy of the point-of-care urine-based lipoarabinomannan assay FUJIFILM SILVAMP TB LAM (FujiLAM) among inpatients and outpatients living with HIV. Diagnostic performance of FujiLAM was assessed against a mycobacterial reference standard (sputum culture, blood culture, and Xpert Ultra from urine and sputum at enrollment, and additional sputum culture ≤7 days from enrollment), an extended mycobacterial reference standard (eMRS), and a composite reference standard including clinical evaluation. Of 1637 participants considered for the analysis, 296 (18%) were tuberculosis positive by eMRS. Median age was 40 years, median CD4 cell count was 369 cells/ul, and 52% were female. Overall FujiLAM sensitivity was 54·4% (95% CI: 48·7-60·0), overall specificity was 85·2% (83·2-87·0) against eMRS. Sensitivity and specificity estimates varied between sites, ranging from 26·5% (95% CI: 17·4%-38·0%) to 73·2% (60·4%-83·0%), and 75·0 (65·0%-82·9%) to 96·5 (92·1%-98·5%), respectively. Post-hoc exploratory analysis identified significant variability in the performance of the six FujiLAM lots used in this study. Lot variability limited interpretation of FujiLAM test performance. Although results with the current version of FujiLAM are too variable for clinical decision-making, the lipoarabinomannan biomarker still holds promise for tuberculosis diagnostics. The trial is registered at clinicaltrials.gov (NCT04089423).Item Benzathine penicillin G stockouts and other barriers to documented syphilis treatment in pregnancy in Zambia.(2024) Jones AV; Manasyan A; Xue Y; Kapesa H; Mwendafilumba K; Nalwamba L; Mzumara M; Mubiana-Mbewe M; Dionne JAOBJECTIVE: The prevalence of syphilis in Zambia remains high and is a critical public health concern. The Zambian Ministry of Health recommends universal screening and same-day treatment for syphilis in pregnancy, yet the syphilis screening rate is low, and treatment is poorly documented. The goal of this study was to document syphilis treatment rates and associated factors among pregnant women in care in Zambia. METHODS: This retrospective cohort study included pregnant women diagnosed with syphilis according to rapid plasma reagin (RPR) screening during routine antenatal care (ANC) in Lusaka, Zambia in 2018-2019. The main outcome of interest was lack of documented BPG treatment during pregnancy. Additional information about pregnancy and neonatal outcomes, partner referral for therapy, and facility level stockout data were included. Patient characteristics were compared by treatment status using Pearson Chi-Square Test and logistic regression models were created to estimate the association between individual level-factors, facility type, and lack of BPG treatment. A Cochran-Mantel-Haenszel test was used to evaluate facility-level data with significance set at p<0.05. RESULTS: Among 1,231 pregnant women who screened positive for syphilis at clinic, 643 (52%) lacked documented antibiotic treatment at the facility. BPG was the only antibiotic used to treat syphilis in the cohort and 8% of sex partners had evidence of referral for therapy. Preterm delivery rates were higher in women without documented BPG (43% vs 32%; p = 0.003). In adjusted models, only calendar year and hospital facility type were associated with lack of treatment. At the facility level, annual syphilis screening rates ranged from 37-65% and most (7/10) clinics reported at least one stockout of BPG. CONCLUSION: Treatment rates for syphilis in pregnancy in Zambia were low and BPG medication stockouts at the facility level were common. A consistent supply of BPG at all ANC facilities is needed to facilitate timely treatment and improve birth outcomes.Item Virologic Failure and Drug Resistance After Programmatic Switching to Dolutegravir-based First-line Antiretroviral Therapy in Malawi and Zambia.(2025-Feb-05) Skrivankova VW; Huwa J; Muula G; Chiwaya GD; Banda E; Buleya S; Chihota B; Chintedza J; Bolton C; Tweya H; Kalua T; Hossmann S; Kouyos R; Wandeler G; Egger M; Lessells RJBACKGROUND: People with human immunodeficiency virus (PWH) on first-line, nonnucleoside reverse-transcriptase inhibitor-based antiretroviral therapy (ART) were routinely switched to tenofovir-lamivudine-dolutegravir. We examined virologic outcomes and drug resistance in ART programs in Malawi, where switching was irrespective of viral load, and Zambia, where switching depended on a viral load <1000 copies/mL in the past year. METHODS: We compared the risk of viremia (≥400 copies/mL) at 1 and 2 years by viral load at switch and between countries using exact methods and logistic regression adjusted for age and sex. We performed HIV-1 pol Sanger sequencing on plasma samples with viral load ≥1000 copies/mL. RESULTS: A total of 2832 PWH were eligible (Malawi 1422, Zambia 1410); the median age was 37 years, and 2578 (91.0%) were women. At switch, 77 (5.4%) were viremic in Malawi and 42 (3.0%) in Zambia (P = .001). Viremia at switch was associated with viremia at 1 year (adjusted odds ratio (OR), 6.15; 95% confidence interval [CI], 3.13-11.4) and 2 years (7.0; 95% CI, 3.73-12.6). Viremia was less likely in Zambia than in Malawi at 1 year (OR, 0.55; 0.32-0.94) and 2 years (OR, 0.33; 0.18-0.57). Integrase sequencing was successful for 79 of 113 eligible samples. Drug resistance mutations were found in 5 PWH (Malawi 4, Zambia 1); 2 had major mutations (G118R, E138K, T66A and G118R, E138K) leading to high-level dolutegravir resistance. CONCLUSIONS: Restricting switching to dolutegravir-based ART to PWH with a viral load <1000 copies/mL may reduce subsequent viremia and, consequently, the emergence of dolutegravir drug resistance mutations. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov (NCT04612452).Item Evaluating a multifaceted implementation strategy and package of evidence-based interventions based on WHO PEN for people living with HIV and cardiometabolic conditions in Lusaka, Zambia: protocol for the TASKPEN hybrid effectiveness-implementation stepped wedge cluster randomized trial.(2024-Jun-06) Herce ME; Bosomprah S; Masiye F; Mweemba O; Edwards JK; Mandyata C; Siame M; Mwila C; Matenga T; Frimpong C; Mugala A; Mbewe P; Shankalala P; Sichone P; Kasenge B; Chunga L; Adams R; Banda B; Mwamba D; Nachalwe N; Agarwal M; Williams MJ; Tonwe V; Pry JM; Musheke M; Vinikoor M; Mutale WBACKGROUND: Despite increasing morbidity and mortality from non-communicable diseases (NCD) globally, health systems in low- and middle-income countries (LMICs) have limited capacity to address these chronic conditions, particularly in sub-Saharan Africa (SSA). There is an urgent need, therefore, to respond to NCDs in SSA, beginning by applying lessons learned from the first global response to any chronic disease-HIV-to tackle the leading cardiometabolic killers of people living with HIV (PLHIV). We have developed a feasible and acceptable package of evidence-based interventions and a multi-faceted implementation strategy, known as "TASKPEN," that has been adapted to the Zambian setting to address hypertension, diabetes, and dyslipidemia. The TASKPEN multifaceted implementation strategy focuses on reorganizing service delivery for integrated HIV-NCD care and features task-shifting, practice facilitation, and leveraging HIV platforms for NCD care. We propose a hybrid type II effectiveness-implementation stepped-wedge cluster randomized trial to evaluate the effects of TASKPEN on clinical and implementation outcomes, including dual control of HIV and cardiometabolic NCDs, as well as quality of life, intervention reach, and cost-effectiveness. METHODS: The trial will be conducted in 12 urban health facilities in Lusaka, Zambia over a 30-month period. Clinical outcomes will be assessed via surveys with PLHIV accessing routine HIV services, and a prospective cohort of PLHIV with cardiometabolic comorbidities nested within the larger trial. We will also collect data using mixed methods, including in-depth interviews, questionnaires, focus group discussions, and structured observations, and estimate cost-effectiveness through time-and-motion studies and other costing methods, to understand implementation outcomes according to Proctor's Outcomes for Implementation Research, the Consolidated Framework for Implementation Research, and selected dimensions of RE-AIM. DISCUSSION: Findings from this study will be used to make discrete, actionable, and context-specific recommendations in Zambia and the region for integrating cardiometabolic NCD care into national HIV treatment programs. While the TASKPEN study focuses on cardiometabolic NCDs in PLHIV, the multifaceted implementation strategy studied will be relevant to other NCDs and to people without HIV. It is expected that the trial will generate new insights that enable delivery of high-quality integrated HIV-NCD care, which may improve cardiovascular morbidity and viral suppression for PLHIV in SSA. This study was registered at ClinicalTrials.gov (NCT05950919).Item Correcting mortality estimates among children and youth on antiretroviral therapy in southern Africa: A comparative analysis between a multi-country tracing study and linkage to a health information exchange.(2024-Aug) Nyakato P; Schomaker M; Boulle A; Euvrard J; Wood R; Eley B; Prozesky H; Christ B; Anderegg N; Ayakaka I; Rafael I; Kunzekwenyika C; Moore CB; van Lettow M; Chimbetete C; Mbewe S; Ballif M; Egger M; Yiannoutsos CT; Cornell M; Davies MAOBJECTIVES: The objective of this study is to assess the outcomes of children, adolescents and young adults with HIV reported as lost to follow-up, correct mortality estimates for children, adolescents and young adults with HIV for unascertained outcomes in those loss to follow-up (LTFU) based on tracing and linkage data separately using data from the International epidemiology Databases to Evaluate AIDS in Southern Africa. METHODS: We included data from two different populations of children, adolescents and young adults with HIV; (1) clinical data from children, adolescents and young adults with HIV aged ≤24 years from Lesotho, Malawi, Mozambique, Zambia and Zimbabwe; (2) clinical data from children, adolescents and young adults with HIV aged ≤14 years from the Western Cape (WC) in South Africa. Outcomes of patients lost to follow-up were available from (1) a tracing study and (2) linkage to a health information exchange. For both populations, we compared six methods for correcting mortality estimates for all children, adolescents and young adults with HIV. RESULTS: We found substantial variations of mortality estimates among children, adolescents and young adults with HIV reported as lost to follow-up versus those retained in care. Ascertained mortality was higher among lost and traceable children, adolescents and young adults with HIV and lower among lost and linkable than those retained in care (mortality: 13.4% [traced] vs. 12.6% [retained-other Southern Africa countries]; 3.4% [linked] vs. 9.4% [retained-WC]). A high proportion of lost to follow-up children, adolescents and young adults with HIV had self-transferred (21.0% and 47.0%) in the traced and linked samples, respectively. The uncorrected method of non-informative censoring yielded the lowest mortality estimates among all methods for both tracing (6.0%) and linkage (4.0%) approaches at 2 years from ART start. Among corrected methods using ascertained data, multiple imputation, incorporating ascertained data (MI(asc.)) and inverse probability weighting with logistic weights were most robust for the tracing approach. In contrast, for the linkage approach, MI(asc.) was the most robust. CONCLUSIONS: Our findings emphasise that lost to follow-up is non-ignorable and both tracing and linkage improved outcome ascertainment: tracing identified substantial mortality in those reported as lost to follow-up, whereas linkage did not identify out-of-facility deaths, but showed that a large proportion of those reported as lost to follow-up were self-transfers.Item Diagnostic yield as an important metric for the evaluation of novel tuberculosis tests: rationale and guidance for future research.(2024-Jul) Broger T; Marx FM; Theron G; Marais BJ; Nicol MP; Kerkhoff AD; Nathavitharana R; Huerga H; Gupta-Wright A; Kohli M; Nichols BE; Muyoyeta M; Meintjes G; Ruhwald M; Peeling RW; Pai NP; Pollock NR; Pai M; Cattamanchi A; Dowdy DW; Dewan P; Denkinger CMBetter access to tuberculosis testing is a key priority for fighting tuberculosis, the leading cause of infectious disease deaths in people. Despite the roll-out of molecular WHO-recommended rapid diagnostics to replace sputum smear microscopy over the past decade, a large diagnostic gap remains. Of the estimated 10·6 million people who developed tuberculosis globally in 2022, more than 3·1 million were not diagnosed. An exclusive focus on improving tuberculosis test accuracy alone will not be sufficient to close the diagnostic gap for tuberculosis. Diagnostic yield, which we define as the proportion of people in whom a diagnostic test identifies tuberculosis among all people we attempt to test for tuberculosis, is an important metric not adequately explored. Diagnostic yield is particularly relevant for subpopulations unable to produce sputum such as young children, people living with HIV, and people with subclinical tuberculosis. As more accessible non-sputum specimens (eg, urine, oral swabs, saliva, capillary blood, and breath) are being explored for point-of-care tuberculosis testing, the concept of yield will be of growing importance. Using the example of urine lipoarabinomannan testing, we illustrate how even tests with limited sensitivity can diagnose more people with tuberculosis if they enable increased diagnostic yield. Using tongue swab-based molecular tuberculosis testing as another example, we provide definitions and guidance for the design and conduct of pragmatic studies that assess diagnostic yield. Lastly, we show how diagnostic yield and other important test characteristics, such as cost and implementation feasibility, are essential for increased effective population coverage, which is required for optimal clinical care and transmission impact. We are calling for diagnostic yield to be incorporated into tuberculosis test evaluation processes, including the WHO Grading of Recommendations, Assessment, Development, and Evaluations process, providing a crucial real-life implementation metric that complements traditional accuracy measures.Item Programme science in action: lessons from an observational study of HIV prevention programming for key populations in Lusaka, Zambia.(2024-Jul) Sikazwe I; Musheke M; Chiyenu K; Ngosa B; Pry JM; Mulubwa C; Zimba M; Sakala M; Sakala M; Somwe P; Nyirenda G; Savory T; Bolton-Moore C; Herce MEINTRODUCTION: Optimizing uptake of pre-exposure prophylaxis (PrEP) for individuals at risk of HIV acquisition has been challenging despite clear scientific evidence and normative guidelines, particularly for key populations (KPs) such as men who have sex with men (MSM), female sex workers (FSWs), transgender (TG) people and persons who inject drugs (PWID). Applying an iterative Programme Science cycle, building on the effective programme coverage framework, we describe the approach used by the Centre for Infectious Disease Research in Zambia (CIDRZ) to scale up PrEP delivery and address inequities in PrEP access for KP in Lusaka, Zambia. METHODS: In 2019, CIDRZ partnered with 10 local KP civil society organizations (CSOs) and the Ministry of Health (MOH) to offer HIV services within KP-designated community safe spaces. KP CSO partners led KP mobilization, managed safe spaces and delivered peer support; MOH organized clinicians and clinical commodities; and CIDRZ provided technical oversight. In December 2021, we introduced a community-based intervention focused on PrEP delivery in venues where KP socialize. We collected routine programme data from September 2019 to June 2023 using programme-specific tools and the national electronic health record. We estimated the before-after effects of our intervention on PrEP uptake, continuation and equity for KP using descriptive statistics and interrupted time series regression, and used mixed-effects regression to estimate marginal probabilities of PrEP continuity. RESULTS: Most (25,658) of the 38,307 (67.0%) Key Population Investment Fund beneficiaries were reached with HIV prevention services at community-based venues. In total, 23,527 (61.4%) received HIV testing services, with 15,508 (65.9%) testing HIV negative and found PrEP eligible, and 15,241 (98.3%) initiating PrEP. Across all programme quarters and KP types, PrEP uptake was >90%. After introducing venue-based PrEP delivery, PrEP uptake (98.7% after vs. 96.5% before, p < 0.001) and the number of initiations (p = 0.014) increased significantly. The proportion of KP with ≥1 PrEP continuation visit within 6 months of initiation was unchanged post-intervention (46.7%, 95% confidence interval [CI]: 45.7%, 47.6%) versus pre-intervention (47.2%, 95% CI: 45.4%, 49.1%). CONCLUSIONS: Applying Programme Science principles, we demonstrate how decentralizing HIV prevention services to KP venues and safe spaces in partnership with KP CSOs enabled successful community-based PrEP delivery beyond the reach of traditional facility-based services.