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Welcome to the CIDRZ Published Research Collection. This collection serves as a central repository of peer-reviewed publications authored, co-authored, or supported by the Centre for Infectious Disease Research in Zambia (CIDRZ). It provides open access to scientific knowledge that contributes to public health, clinical research, and evidence-based policy in Zambia and beyond.
Browse the collection to explore research covering HIV, TB, maternal and child health, health systems strengthening, and other key public health topics. Articles are frequently harvested from PubMed and other trusted databases.
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Item The Tuberculosis Sentinel Research Network (TB-SRN) of the International epidemiology Databases to Evaluate AIDS (IeDEA): protocol for a prospective cohort study in Africa, Southeast Asia and Latin America.(2024-Jan-09) Enane LA; Duda SN; Chanyachukul T; Bolton-Moore C; Navuluri N; Messou E; Mbonze N; McDade LR; Figueiredo MC; Ross J; Evans D; Diero L; Akpata R; Zotova N; Freeman A; Pierre MF; Rupasinghe D; Ballif M; Byakwaga H; de Castro N; Tabala M; Sterling TR; Sohn AH; Fenner L; Wools-Kaloustian K; Poda A; Yotebieng M; Huebner R; Marcy O; Vanderbilt Institute of Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.; Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.; Division of General Internal Medicine, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Duke Global Health Institute, Duke University, Durham, North Carolina, USA.; Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.; Indiana University Center for Global Health Equity, Indianapolis, Indiana, USA.; Mbarara University of Science and Technology Faculty of Medicine, Mbarara, Uganda.; Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland.; Center for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.; The Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic Infections (GHESKIO), Port-au-Prince, Haiti.; The Kirby Institute, UNSW, Sydney, New South Wales, Australia.; Health Economics and Epidemiology Research Office, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; Centre Hospitalier Universitaire Sourô Sanou, Bobo Dioulasso, Burkina Faso.; TREAT Asia/amfAR - The Foundation for AIDS Research, Bangkok, Thailand.; Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.; Kinshasa School of Public Health, University of Kinshasa, Kinshasa, Democratic Republic of the Congo.; The Ryan White Center for Pediatric Infectious Diseases and Global Health, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA lenane@iu.edu.; Vanderbilt Tuberculosis Center, Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.; Centre de Prise en Charge de Recherche et de Formation (Aconda-CePReF), Abidjan, Côte d'Ivoire.; Université de Bordeaux, Bordeaux, France.; Department of Medicine, Moi University College of Health Sciences, Eldoret, Kenya.INTRODUCTION: Tuberculosis (TB) is a leading infectious cause of death globally. It is the most common opportunistic infection in people living with HIV, and the most common cause of their morbidity and mortality. Following TB treatment, surviving individuals may be at risk for post-TB lung disease. The TB Sentinel Research Network (TB-SRN) provides a platform for coordinated observational TB research within the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. METHODS AND ANALYSIS: This prospective, observational cohort study will assess treatment and post-treatment outcomes of pulmonary TB (microbiologically confirmed or clinically diagnosed) among 2600 people aged ≥15 years, with and without HIV coinfection, consecutively enrolled at 16 sites in 11 countries, across 6 of IeDEA's global regions. Data regarding clinical and sociodemographic factors, mental health, health-related quality of life, pulmonary function, and laboratory and radiographic findings will be collected using standardised questionnaires and data collection tools, beginning from the initiation of TB treatment and through 12 months after the end of treatment. Data will be aggregated for proposed analyses. ETHICS AND DISSEMINATION: Ethics approval was obtained at all implementing study sites, including the Vanderbilt University Medical Center Human Research Protections Programme. Participants will provide informed consent; for minors, this includes both adolescent assent and the consent of their parent or primary caregiver. Protections for vulnerable groups are included, in alignment with local standards and considerations at sites. Procedures for requesting use and analysis of TB-SRN data are publicly available. Findings from TB-SRN analyses will be shared with national TB programmes to inform TB programming and policy, and disseminated at regional and global conferences and other venues.Item 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; Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.; Institute of Basic and Biomedical Sciences, Levy Mwanawasa Medical University, Lusaka 10101, Zambia.; Division of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 241, Cape Town 8000, South Africa.; Influenza Research Institute, University of Wisconsin-Madison, Madison, WI 53706-13380, USA.; University Teaching Hospitals, Lusaka 10101, Zambia.; Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia.; Division of Medical Virology, School of Pathology, Faculty of Health Sciences, University of the Free State, Bloemfontein P.O. Box 339, South Africa.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)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/Item HIV programme sustainability in Southern and Eastern Africa and the changing role of external assistance for health.(2024-Jan-23) Neel AH; Rodríguez DC; Sikazwe I; Pillay Y; Barron P; Pereira SK; Makakole-Nene S; Bennett SC; Department of Global Health, Stellenbosch University, Stellenbosch, South Africa.; Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA.; School of Public Health, University of the Witwatersrand, Johannesburg 2193, South Africa.; Centre for Infectious Disease Research in Zambia (CIDRZ), 34620 Lukasu Road, Mass Media, Lusaka 10101, Zambia.; SCMN Global Health Consulting, 261 Middel Street, Pretoria 0181, South Africa.High human immunodeficiency virus (HIV)-prevalence countries in Southern and Eastern Africa continue to receive substantial external assistance (EA) for HIV programming, yet countries are at risk of transitioning out of HIV aid without achieving epidemic control. We sought to address two questions: (1) to what extent has HIV EA in the region been programmed and delivered in a way that supports long-term sustainability and (2) how should development agencies change operational approaches to support long-term, sustainable HIV control? We conducted 20 semi-structured key informant interviews with global and country-level respondents coupled with an analysis of Global Fund budget data for Malawi, Uganda, and Zambia (from 2017 until the present). We assessed EA practice along six dimensions of sustainability, namely financial, epidemiological, programmatic, rights-based, structural and political sustainability. Our respondents described HIV systems' vulnerability to donor departure, as well as how development partner priorities and practices have created challenges to promoting long-term HIV control. The challenges exacerbated by EA patterns include an emphasis on treatment over prevention, limiting effects on new infection rates; resistance to service integration driven in part by 'winners' under current EA patterns and challenges in ensuring coverage for marginalized populations; persistent structural barriers to effectively serving key populations and limited capacity among organizations best positioned to respond to community needs; and the need for advocacy given the erosion of political commitment by the long-term and substantive nature of HIV EA. Our recommendations include developing a robust investment case for primary prevention, providing operational support for integration processes, investing in local organizations and addressing issues of political will. While strategies must be locally crafted, our paper provides initial suggestions for how EA partners could change operational approaches to support long-term HIV control and the achievement of universal health coverage.Item Neonatal mortality risk of vulnerable newborns by fine stratum of gestational age and birthweight for 230 679 live births in nine low- and middle-income countries, 2000-2017.(2024-Jan-16) Hazel EA; Erchick DJ; Katz J; Lee ACC; Diaz M; Wu LSF; West KP; Shamim AA; Christian P; Ali H; Baqui AH; Saha SK; Ahmed S; Roy AD; Silveira MF; Buffarini R; Shapiro R; Zash R; Kolsteren P; Lachat C; Huybregts L; Roberfroid D; Zhu Z; Zeng L; Gebreyesus SH; Tesfamariam K; Adu-Afarwuah S; Dewey KG; Gyaase S; Poku-Asante K; Boamah Kaali E; Jack D; Ravilla T; Tielsch J; Taneja S; Chowdhury R; Ashorn P; Maleta K; Ashorn U; Mangani C; Mullany LC; Khatry SK; Ramokolo V; Zembe-Mkabile W; Fawzi WW; Wang D; Schmiegelow C; Minja D; Msemo OA; Lusingu JPA; Smith ER; Masanja H; Mongkolchati A; Keentupthai P; Kakuru A; Kajubi R; Semrau K; Hamer DH; Manasyan A; Pry JM; Chasekwa B; Humphrey J; Black RE; Pediatric Newborn Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.; Child Health Research Foundation, Dhaka, Bangladesh.; Department of Global and Community Health, College of Public Health, George Mason University, Fairfax, Virginia, USA.; Infectious Diseases Research Collaboration, Kampala, Uganda.; Columbia University's Mailman School of Public Health, New York, New York, USA.; Post-Graduate Program in Epidemiology-Federal University of Pelotas, Pelotas, Brazil.; BRAC JP Grant School of Public Health, Dhaka, Bangladesh.; Health Systems Research Unit, South African Medical Research Council, Cape Town, South Africa.; Department of Immunology and Microbiology, Centre for Medical Parasitology, University of Copenhagen, Copenhagen, Denmark.; Section of Infectious Diseases, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.; Division of Global Health Equity, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.; JiVitA Maternal and Child Health Research Project, Rangpur, Bangladesh.; Department of Food Technology, Safety, and Health, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium.; International Health Department, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.; Poverty, Health and Nutrition Division, International Food Policy Research Institute, Washington, District of Columbia, USA.; Research and Development Division, Ghana Health Service, Accra, Ghana.; Department of International Health, Center for Human Nutrition, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.; Ariadne Labs, Brigham and Women's Hospital and Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.; Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland.; College of Medicine and Public Health, Ubon Ratchathani University, Ubon Ratchathani, Thailand.; Department of Nutrition, Institute for Global Nutrition, University of California, Davis, California, USA.; Gertrude H Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York, USA.; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.; Namur University, Namur, Belgium.; Ifakara Health Institute, Dar es Salaam, Tanzania.; Kintampo Health Research Centre, Kintampo, Ghana.; National Institute of Medical Research, Tanga, Tanzania.; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; Department of Nutrition and Food Science, University of Ghana, Accra, Ghana.; Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.; Aravind Eye Hospital, Madurai, India.; Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong University Health Science Centre, Xi'an, China.; University of Alabama at Birmingham, Birmingham, Alabama, USA.; Department of Food Technology, Safety and Health, Ghent University, Ghent, Belgium.; School of Global and Public Health, Kamuzu University of Health Sciences, Blantyre, Malawi.; George Washington University Milken Institute School of Public Health, Washington, District of Columbia, USA.; HIV and Other Infectious Diseases Research Unit, South African Medical Research Council, Cape Town, South Africa.; ASEAN Institute for Health Development, Mahidol University, Salaya, Thailand.; Belgian Health Care Knowledge Centre, Brussels, Belgium.; Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.; Department of Global Health, Boston University School of Public Health, Boston, Massachusetts, USA.; Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.; College Graduate of Studies, University of South Africa, Pretoria, South Africa.; Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark.; Projahnmo Research Foundation, Dhaka, Bangladesh.; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Nutrition and Dietetics, School of Public Health, Addis Ababa University, Addis Ababa, Ethiopia.; Department of Global Health, Milken Institute School of Public Health, Washington, District of Columbia, USA.; NNIPS, Kathmandu, Nepal.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)OBJECTIVE: To describe the mortality risks by fine strata of gestational age and birthweight among 230 679 live births in nine low- and middle-income countries (LMICs) from 2000 to 2017. DESIGN: Descriptive multi-country secondary data analysis. SETTING: Nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America. POPULATION: Liveborn infants from 15 population-based cohorts. METHODS: Subnational, population-based studies with high-quality birth outcome data were invited to join the Vulnerable Newborn Measurement Collaboration. All studies included birthweight, gestational age measured by ultrasound or last menstrual period, infant sex and neonatal survival. We defined adequate birthweight as 2500-3999 g (reference category), macrosomia as ≥4000 g, moderate low as 1500-2499 g and very low birthweight as <1500 g. We analysed fine strata classifications of preterm, term and post-term: ≥42 MAIN OUTCOME MEASURES: Median and interquartile ranges by study for neonatal mortality rates (NMR) and relative risks (RR). We also performed meta-analysis for the relative mortality risks with 95% confidence intervals (CIs) by the fine categories, stratified by regional study setting (sub-Saharan Africa and Southern Asia) and study-level NMR (≤25 versus >25 neonatal deaths per 1000 live births). RESULTS: We found a dose-response relationship between lower gestational ages and birthweights with increasing neonatal mortality risks. The highest NMR and RR were among preterm babies born at <28 weeks (median NMR 359.2 per 1000 live births; RR 18.0, 95% CI 8.6-37.6) and very low birthweight (462.8 per 1000 live births; RR 43.4, 95% CI 29.5-63.9). We found no statistically significant neonatal mortality risk for macrosomia (RR 1.1, 95% CI 0.6-3.0) but a statistically significant risk for all preterm babies, post-term babies (RR 1.3, 95% CI 1.1-1.5) and babies born at 37 CONCLUSIONS: In addition to tracking vulnerable newborn types, monitoring finer categories of birthweight and gestational age will allow for better understanding of the predictors, interventions and health outcomes for vulnerable newborns. It is imperative that all newborns from live births and stillbirths have an accurate recorded weight and gestational age to track maternal and neonatal health and optimise prevention and care of vulnerable newborns.Item Protocol for an evaluation of the initiation of an integrated longitudinal outpatient care model for severe chronic non-communicable diseases (PEN-Plus) at secondary care facilities (district hospitals) in 10 lower-income countries.(2024-Jan-30) Adler AJ; Wroe EB; Atzori A; Bay N; Bekele W; Bhambhani VM; Nkwiro RB; Boudreaux C; Calixte D; Chiwanda Banda J; Coates MM; Dagnaw WW; Domingues K; Drown L; Dusabeyezu S; Fenelon D; Gupta N; Ssinabulya I; Jain Y; Kalkonde Y; Kamali I; Karekezi C; Karmacharya BM; Koirala B; Makani J; Manenti F; Mangwiro A; Manuel B; Masiye JK; Goma FM; Mayige MT; McLaughlin A; Mensah E; Salipa NM; Mutagaywa R; Mutengerere A; Ngoga G; Patiño M; Putoto G; Ruderman T; Salvi D; Sesay S; Taero F; Tostão E; Toussaint S; Bukhman G; Mocumbi AO; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; Kathmandu Institute of Child Health, Kathmandu, Nepal.; Partners In Health, Maryland County, Liberia.; Doctors with Africa CUAMM, Padova, Italy.; Chhattisgarh NCD Plus Initiative, Ambikapur, Chhattisgarh, India.; Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.; Partners In Health/Inshuti Mu Buzima, Rwinkwavu, Rwanda.; School of Medical Sciences, Kathmandu University, Kathmandu, Nepal.; Partners In Health Sierra Leone, Kono, Sierra Leone.; Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA.; Mozambique Institute for Health Education and Research, Maputo, Mozambique.; Instituto Nacional de Saúde, Maputo, Mozambique.; Clinton Health Access Initiative, Harare, Zimbabwe.; Center for Integration Science, Brigham and Women's Hospital, Boston, Massachusetts, USA aadler2@bwh.harvard.edu.; NCDI Poverty Network, Surguja, Chhattisgarh, India.; Jakaya Kikwete Cardiac Institute, Dar es Salaam, Tanzania.; Department of Agricultural Economics and Development, Universidade Eduardo Mondlane, Maputo, Mozambique.; Center for Integration Science, Brigham and Women's Hospital, Boston, Massachusetts, USA.; Noncommunicable Diseases and Mental Health, Sierra Leone Ministry of Health and Sanitation, Freetown, Sierra Leone.; SolidarMed, Harare, Zimbabwe.; Universidade Eduardo Mondlane, Maputo, Mozambique.; NCD Division, Ministry of Health, Lilongwe, Malawi.; Partners In Health, Boston, Massachusetts, USA.; National Institute for Medical Research, Dar es Salaam, Tanzania.; NCDI Poverty Network, Addis Ababa, Ethiopia.; Non-Communicable Diseases Alliance Kenya, Nairobi, Kenya.; Noncommunicable Diseases and Mental Health Clinical Services, Malawi Ministry of Health, Lilongwe, Malawi.; Partners In Health, Neno, Malawi.; Department of Community Health, Universidade Eduardo Mondlane, Maputo, Mozambique.; Uganda Initiative for Integrated Management of Non-Communicable Diseases, Kampala, Uganda.; Zamni Lasante, Croix-des-Bouquets, Haiti.; Mathiwos Wondu-Ye Ethiopia Cancer Society, Addis Ababa, Ethiopia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)INTRODUCTION: The Package of Essential Noncommunicable Disease Interventions-Plus (PEN-Plus) is a strategy decentralising care for severe non-communicable diseases (NCDs) including type 1 diabetes, rheumatic heart disease and sickle cell disease, to increase access to care. In the PEN-Plus model, mid-level clinicians in intermediary facilities in low and lower middle income countries are trained to provide integrated care for conditions where services traditionally were only available at tertiary referral facilities. For the upcoming phase of activities, 18 first-level hospitals in 9 countries and 1 state in India were selected for PEN-Plus expansion and will treat a variety of severe NCDs. Over 3 years, the countries and state are expected to: (1) establish PEN-Plus clinics in one or two district hospitals, (2) support these clinics to mature into training sites in preparation for national or state-level scale-up, and (3) work with the national or state-level stakeholders to describe, measure and advocate for PEN-Plus to support development of a national operational plan for scale-up. METHODS AND ANALYSIS: Guided by Proctor outcomes for implementation research, we are conducting a mixed-method evaluation consisting of 10 components to understand outcomes in clinical implementation, training and policy development. Data will be collected through a mix of quantitative surveys, routine reporting, routine clinical data and qualitative interviews. ETHICS AND DISSEMINATION: This protocol has been considered exempt or covered by central and local institutional review boards. Findings will be disseminated throughout the project's course, including through quarterly M&E discussions, semiannual formative assessments, dashboard mapping of progress, quarterly newsletters, regular feedback loops with national stakeholders and publication in peer-reviewed journals.Item New Window Into Hepatitis B in Africa: Liver Sampling Combined With Single-Cell Omics Enables Deep and Longitudinal Assessment of Intrahepatic Immunity in Zambia.(2024-Nov-15) Musonda T; Wallace MS; Patel H; Martin OP; Oetheimer C; Mwakamui S; Sinkala E; Nsokolo B; Kanunga A; Lauer G; Chung RT; Wandeler G; Bhattacharya D; Kelly P; Alatrakchi N; Vinikoor MJ; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Division of Infectious Diseases, University of California Los Angeles, Los Angeles, California, USA.; Blizard Institute, Queen Mary University of London, London, United Kingdom.; Tropical Gastroenterology and Nutrition Group, University of Zambia, Lusaka, Zambia.; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.; Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA.; Department of Medicine, Levy Mwanawasa University Teaching Hospital, Lusaka, Zambia.; Division of Infectious Diseases, University of Alabama Birmingham, Birmingham, Alabama, USA.; Department of Research, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Medicine, University Teaching Hospital, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)In Lusaka, Zambia, we introduced liver fine-needle aspiration biopsy (FNAB) into a research cohort of adults with treatment-naive chronic hepatitis B virus (HBV) infection, with and without human immunodeficiency virus (HIV) coinfection, as well as with acute HBV infection. From 117 enrollment and 47 longitudinal FNABs (at 1-year follow-up), we established participant acceptability and safety. We also demonstrated the quality of the material through single-cell RNA sequencing of selected enrollment FNAs, which revealed a range of immune cells. This approach can drive new insights into HBV immunology, informing cure strategies, and can improve our understanding of HBV natural history in Africa.Item Preferences for services in a patient's first six months on antiretroviral therapy for HIV in South Africa and Zambia (PREFER): research protocol for a prospective observational cohort study.(2023) Maskew M; Ntjikelane V; Juntunen A; Scott N; Benade M; Sande L; Hasweeka P; Haimbe P; Lumano-Mulenga P; Shakewelele H; Mukumbwa-Mwenechanya M; Rosen S; Center for Infectious Disease Research in Zambia, Lusaka, Lusaka Province, Zambia.; Department of Medical Microbiology, Amsterdam University Medical Center, Amstersdam, The Netherlands.; Global Health, Boston University, Boston, MA, 02118, USA.; CHAI-Zambia, Clinton Health Access Initiative, Lusaka, Zambia.; Health Economics and Epidemiology Research Office, Faculty of Health Sciences, University of the Witwatersrand Johannesburg, Johannesburg, Gauteng, South Africa.; MOH Zambia, Ministry of Health, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)BACKGROUND: For patients on HIV treatment in sub-Saharan Africa, the highest risk for loss from care remains the first six months after antiretroviral (ART) initiation, when patients are not yet eligible for differentiated service delivery (DSD) models that offer lower-burden, patient-centred care and thus improve treatment outcomes. To reduce early disengagement from care, the PREFER study will use a sequential mixed-methods approach to describe the characteristics, needs, concerns, and preferences of patients in South Africa and Zambia 0-6 months after ART initiation or re-initiation. PROTOCOL: PREFER is an observational, prospective cohort study of adults on ART for ≤6 months at 12 public healthcare facilities in Zambia and 18 in South Africa. Its objective is to describe and understand the needs and preferences of initiating and re-initiating ART clients to inform the design of DSD models for the early HIV treatment period, improve early treatment outcomes, and distinguish the barriers encountered by naïve patients from those facing re-initiators. It has four components: 1) survey of clients 0-6 months after ART initiation (identify characteristics and preferences of clients starting ART); 2) follow up through routinely collected medical records for <24 months after enrollment (describe resource utilization and patterns and predictors of engagement in care); 3) focus group discussions and discrete choice experiment (explore reported barriers to and facilitators of retention); and 4) in South Africa only, collection of blood samples (assess the prevalence of ARV metabolites indicating prior ART use). CONCLUSIONS: PREFER aims to understand why the early treatment period is so challenging and how service delivery can be amended to address the obstacles that lead to early disengagement from care. It will generate information about client characteristics and preferences to help respond to patients' needs and design better strategies for service delivery and improve resource allocation going forward.Item Fourth Controlled Human Infection Model (CHIM) meeting, CHIM regulatory issues, May 24, 2023.(2024-Feb) Cavaleri M; Kaslow D; Boateng E; Chen WH; Chiu C; Choy RKM; Correa-Oliveira R; Durbin A; Egesa M; Gibani M; Kapulu M; Katindi M; Olotu A; Pongsuwan P; Simuyandi M; Speder B; Talaat KR; Weller C; Wills B; Baay M; Balasingam S; Olesen OF; Neels P; Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand.; PATH Center for Vaccine Innovation and Access, Seattle, WA, USA. Electronic address: rchoy@path.org.; European Vaccine Initiative, Heidelberg, Germany. Electronic address: ole.olesen@euvaccine.eu.; Imperial College London, UK. Electronic address: c.chiu@imperial.ac.uk.; Centre for Infectious Disease Research, Zambia. Electronic address: Michelo.Simuyandi@cidrz.org.; Center for Vaccine Development, University of Maryland School of Medicine, USA. Electronic address: wilbur.chen@som.umaryland.edu.; IABS-EU, Lyon, France. Electronic address: pieter.neels@vaccine-advice.be.; Imperial College London, UK. Electronic address: m.gibani@imperial.ac.uk.; Johns Hopkins Bloomberg School of Public Health, Baltimore, USA. Electronic address: ktalaat@jhu.edu.; KEMRI-Wellcome Trust Research Programme, Kenya. Electronic address: mkapulu@kemri-wellcome.org.; HVIVO plc, UK. Electronic address: b.speder@hvivo.com.; Wellcome Trust, London, UK. Electronic address: shobana.balasingam@wellcome.org.; Johns Hopkins Bloomberg School of Public Health, Baltimore, USA. Electronic address: adurbin1@jhu.edu.; US Food & Drugs Administration, USA. Electronic address: david.kaslow@fda.hhs.gov.; P95 Epidemiology & Pharmacovigilance, Leuven, Belgium. Electronic address: marc.baay@p-95.com.; Food and Drugs Authority, Ghana. Electronic address: gus4tee@gmail.com.; European Medicines Agency, Netherlands. Electronic address: marco.cavaleri@ema.europa.eu.; Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam. Electronic address: bwills@oucru.org.; Wellcome Trust, London, UK. Electronic address: C.Weller@wellcome.org.; Ifakara Health Institute, Tanzania. Electronic address: aolotu@ihi.or.tz.; Fundação Oswaldo Cruz (Fiocruz), Brazil.; Katindi & Company, Kenya. Electronic address: mkatindi@katindilawyers.co.ke.; MRC/UVRI and LSHTM Uganda Research Unit, Uganda; London School of Hygiene and Tropical Medicine, UK. Electronic address: Moses.Egesa@mrcuganda.org.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)Many aspects of Controlled Human Infection Models (CHIMs, also known as human challenge studies and human infection studies) have been discussed extensively, including Good Manufacturing Practice (GMP) production of the challenge agent, CHIM ethics, environmental safety in CHIM, recruitment, community engagement, advertising and incentives, pre-existing immunity, and clinical, immunological, and microbiological endpoints. The fourth CHIM meeting focused on regulation of CHIM studies, bringing together scientists and regulators from high-, middle-, and low-income countries, to discuss barriers and hurdles in CHIM regulation. Valuable initiatives for regulation of CHIMs have already been undertaken but further capacity building remains essential. The Wellcome Considerations document is a good starting point for further discussions.Item Effects of preterm birth, maternal ART and breastfeeding on 24-month infant HIV-free survival in a randomized trial.(2024-Jul-15) Dadabhai S; Chou VB; Pinilla M; Chinula L; Owor M; Violari A; Moodley D; Stranix-Chibanda L; Matubu TA; Chareka GT; Theron G; Kinikar AA; Mubiana-Mbewe M; Fairlie L; Bobat R; Mmbaga BT; Flynn PM; Taha TE; McCarthy KS; Browning R; Mofenson LM; Brummel SS; Fowler MG; Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Soweto.; Department of Paediatrics and Child Health, University of KwaZulu-Natal, Durban, South Africa.; National Institute of Allergy and Infectious Diseases/NIH, Rockville, MD.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD.; Division of Global Women's Health, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; St. Jude Children's Research Hospital, Memphis, TN.; B.J. Government Medical College, Department of Paediatrics, Pune, India.; Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.; Elizabeth Glaser Pediatric AIDS Foundation, Washington DC, USA.; MU-JHU Research Collaboration; Upper Mulago Hill Road, Kampala, Uganda.; Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA.; Wits RHI, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg.; University of North Carolina Project Malawi, Tidziwe Centre, Lilongwe, Malawi.; Centre for Infectious Disease Research in Zambia, George CRS, Lusaka, Zambia.; Centre for the AIDS Programme of Research in South Africa and School of Clinical Medicine, University of KwaZulu Natal, Congella, South Africa.; Kamuzu University of Health Sciences-Johns Hopkins Research Project, Blantyre, Malawi.; Child, Adolescent and Women's Health Department, Faculty of Medicine and Health Sciences, University of Zimbabwe, Avondale.; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health.; Kilimanjaro Christian Medical Centre, Kilimanjaro Clinical Research Institute and Kilimanjaro Christian Medical University College/Kilimanjaro CRS, Moshi, Tanzania.; University of Zimbabwe Clinical Trials Research Centre, Belgravia, Harare, Zimbabwe.; FHI 360, Durham, NC.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)BACKGROUND: IMPAACT 1077BF/FF (PROMISE) compared the safety/efficacy of two HIV antiretroviral therapy (ART) regimens to zidovudine (ZDV) alone during pregnancy for HIV prevention. PROMISE found an increased risk of preterm delivery (<37 weeks) with antepartum triple ART (TDF/FTC/LPV+r or ZDV/3TC/LPV+r) compared with ZDV alone. We assessed the impact of preterm birth, breastfeeding, and antepartum ART regimen on 24-month infant survival. METHODS: We compared HIV-free and overall survival at 24 months for liveborn infants by gestational age, time-varying breastfeeding status, and antepartum ART arm at 14 sites in Africa and India. Kaplan-Meier survival probabilities and Cox proportional hazards ratios were estimated. RESULTS: Three thousand four hundred and eighty-two live-born infants [568 (16.3%) preterm and 2914 (83.7%) term] were included. Preterm birth was significantly associated with lower HIV-free survival [0.85; 95% confidence interval (CI) 0.82-0.88] and lower overall survival (0.89; 95% CI 0.86-0.91) versus term birth (0.96; 95% CI 0.95-0.96). Very preterm birth (<34 weeks) was associated with low HIV-free survival (0.65; 95% CI 0.54-0.73) and low overall survival (0.66; 95% CI 0.56-0.74). Risk of HIV infection or death at 24 months was higher with TDF-ART than ZDV-ART (adjusted hazard ratio 2.37; 95% CI 1.21-4.64). Breastfeeding initiated near birth decreased risk of infection or death at 24 months (adjusted hazard ratio 0.05; 95% CI 0.03-0.08) compared with not breastfeeding. CONCLUSION: Preterm birth and antepartum TDF-ART were associated with lower 24-month HIV-free survival compared with term birth and ZDV-ART. Any breastfeeding strongly promoted HIV-free survival, especially if initiated close to birth. Reducing preterm birth and promoting infant feeding with breastmilk among HIV/antiretroviral drug-exposed infants remain global health priorities.Item Long-term outcomes after new onset seizure in children living with HIV: A cohort study.(2024-Apr) Birbeck GL; Mwenechanya M; Ume-Ezeoke I; Mathews M; Bositis CM; Kalungwana L; Bearden D; Elafros M; Gelbard HA; Theodore WH; Koralnik IJ; Okulicz JF; Johnson BA; Musonda N; Siddiqi OK; Potchen MJ; Sikazwe I; Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.; University Teaching Hospitals Neurology Research Office, Lusaka, Zambia.; Department of Biostatistics, University of Rochester, Rochester, New York, USA.; Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.; Department of Neurology, University of Rochester, Rochester, New York, USA.; Department of Medicine, San Antonio Military Medical Center, San Antonio, Texas, USA.; Department of Psychology, University of Zambia, Lusaka, Zambia.; Zambian College of Medicine and Surgery, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Clinical Epilepsy Section, US National Institute of Health, Bethesda, Maryland, USA.; Department of Imaging Sciences, University of Rochester, Rochester, New York, USA.; University Teaching Hospitals Children's Hospital, Lusaka, Zambia.; Chikankata Epilepsy Care Team, Mazabuka, Zambia.; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Department of Family and Community Medicine, University of California San Francisco, San Francisco, California, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)OBJECTIVE: To determine the long-term outcomes, including mortality and recurrent seizures, among children living with HIV (CLWH) who present with new onset seizure. METHODS: Zambian CLWH and new onset seizure were enrolled prospectively to determine the risk of and risk factors for recurrent seizures. Demographic data, clinical profiles, index seizure etiology, and 30-day mortality outcomes were previously reported. After discharge, children were followed quarterly to identify recurrent seizures and death. Given the high risk of early death, risk factors for recurrent seizure were evaluated using a model that adjusted for mortality. RESULTS: Among 73 children enrolled, 28 died (38%), 22 within 30-days of the index seizure. Median follow-up was 533 days (IQR 18-957) with 5% (4/73) lost to follow-up. Seizure recurrence was 19% among the entire cohort. Among children surviving at least 30-days after the index seizure, 27% had a recurrent seizure. Median time from index seizure to recurrent seizure was 161 days (IQR 86-269). Central nervous system opportunistic infection (CNS OI), as the cause for the index seizure was protective against recurrent seizures and higher functional status was a risk factor for seizure recurrence. SIGNIFICANCE: Among CLWH presenting with new onset seizure, mortality risks remain elevated beyond the acute illness period. Recurrent seizures are common and are more likely in children with higher level of functioning even after adjusting for the outcome of death. Newer antiseizure medications appropriate for co-usage with antiretroviral therapies are needed for the care of these children. CNS OI may represent a potentially reversible provocation for the index seizure, while seizures in high functioning CLWH without a CNS OI may be the result of a prior brain injury or susceptibility to seizures unrelated to HIV and thus represent an ongoing predisposition to seizures. PLAIN LANGUAGE SUMMARY: This study followed CLWH who experienced a new onset seizure to find out how many go on to have more seizures and identify any patient characteristics associated with having more seizures. The study found that mortality rates continue to be high beyond the acute clinical presentation with new onset seizure. Children with a CNS OI causing the new onset seizure had a lower risk of later seizures, possibly because the trigger for the seizure can be treated. In contrast, high functioning children without a CNS OI were at higher risk of future seizures.