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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 Closing the gap in paediatric HIV infections: how available tools and technology can accelerate progress towards ending AIDS by 2030.(2024-Apr-06) Mutale W; Herce ME; Department of Health Policy and Management, University of Zambia School of Public Health, Lusaka, Zambia; Southern Africa Institute for Collaborative Research and Innovation Organisation, Lusaka, Zambia. Electronic address: wmutale@gmail.com.; Implementation Science Unit, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)Item Antimicrobial resistance and heterogeneity of Neisseria gonorrhoeae isolated from patients attending sexually transmitted infection clinics in Lusaka, Zambia.(2024-Mar-18) Sarenje KL; van Zwetselaar M; Kumburu H; Sonda T; Mmbaga B; Ngalamika O; Maimbolwa MC; Siame A; Munsaka S; Kwenda G; Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka, P.O. Box 50110, Zambia. kelvinsarenje@gmail.com.; Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka, P.O. Box 50110, Zambia.; Department of Dermato-venereology, University Teaching Hospital, Lusaka, Zambia. kelvinsarenje@gmail.com.; Department of Dermato-venereology, University Teaching Hospital, Lusaka, Zambia.; Kilimanjaro Christian Medical Centre, Moshi, Tanzania.; Department of Midwifery Child, and Women's Health, School of Nursing Sciences, University of Zambia, Lusaka, Zambia.; Kilimanjaro Clinical Research Institute, Moshi, Kilimanjaro, Tanzania.; Kilimanjaro Christian Medical University College, Moshi, Tanzania.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)BACKGROUND: Antimicrobial resistance (AMR) of Neisseria gonorrhoeae is a threat to public health as strains have developed resistance to antimicrobials available for the treatment of gonorrhea. Whole genome sequencing (WGS) can detect and predict antimicrobial resistance to enhance the control and prevention of gonorrhea. Data on the molecular epidemiology of N. gonorrhoeae is sparse in Zambia. This study aimed to determine the genetic diversity of N. gonorrhoeae isolated from patients attending sexually transmitted infection (STI) clinics in Lusaka, Zambia. METHODS: A cross-sectional study that sequenced 38 N. gonorrhoeae isolated from 122 patients with gonorrhea from 2019 to 2020 was conducted. The AMR profiles were determined by the E-test, and the DNA was extracted using the NucliSens easyMaG magnetic device. Whole genome sequencing was performed on the Illumina NextSeq550 platform. The Bacterial analysis pipeline (BAP) that is readily available at: https://cge.cbs.dtu.dk/services/CGEpipeline-1.1 was used for the identification of the species, assembling the genome, multi-locus sequence typing (MLST), detection of plasmids and AMR genes. Phylogeny by single nucleotide polymorphisms (SNPs) was determined with the CCphylo dataset. RESULTS: The most frequent STs with 18.4% of isolates each were ST CONCLUSION: This study revealed remarkable heterogeneity of N. gonorrhoeae with blaItem Engagement of private health care facilities in TB management in Lusaka district of Zambia: lessons learned and achievements.(2024-Mar-14) Hambwalula R; Kagujje M; Mwaba I; Musonda D; Singini D; Mutti L; Sanjase N; Kaumba PC; Ziko LM; Zimba KM; Kasese-Chanda P; Muyoyeta M; TB department, Centre of Infectious Disease Research in Zambia, Plot # 34620 Off Alick Nkhata Road, Mass Media, P.O. Box 34681, Lusaka, 10101, Zambia. Mary.Kagujje@cidrz.org.; Lusaka District Health Office, Ministry of Health, Great East Road, Lusaka, Zambia.; TB department, Centre of Infectious Disease Research in Zambia, Plot # 34620 Off Alick Nkhata Road, Mass Media, P.O. Box 34681, Lusaka, 10101, Zambia.; Division of Health, United States Agency for International Development, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)BACKGROUND: Globally, at least 3 million TB patients are missed every year. In Zambia, the TB treatment coverage increased from 66% in 2020 to 92% in 2022. Involvement of all levels of health care service delivery is critical to finding all the missing TB patients. METHODS: A survey was undertaken in 15 private facilities in Lusaka district of Zambia using a structured tool administered by project team and a district health team member. Data collected during the survey was analysed and results were used to determine the type of TB services that were offered as well as barriers and enablers to TB service provision. This was followed by a set of interventions that included; training and mentorship on active case finding and systematic TB screening, increased diagnostic capacity, provision of national recording and reporting tools and provision of TB medication through linkage with the National TB program (NTP). We report findings from the baseline survey and changes in presumptive TB identification and notification following interventions. RESULTS: Major barriers to TB service delivery were the high cost of TB diagnostic testing and treatment in facilities where services were not supported by the National TB program; the mean cost was 33 (SD 33) and 93 (SD 148) for GeneXpert testing and a full course of treatment respectively. Pre-intervention, presumptive TB identification appeared to increase monthly by 4 (P = 0.000, CI=[3.00-5.00]). The monthly trends of presumptive TB identification during the intervention period increased by 5.32 (P = 0.000, [CI 4.31-6.33. Pre-intervention, the notification of TB appeared to decrease every month by -4.0 (P = 0.114, CI=[-9.00-0.10]) followed by an immediate increase in notifications of 13.94 TB patients (P = 0.001, CI [6.51, 21.36] in the first month on intervention. The monthly trends of notification during the intervention period changed by 0.34 (P = 0.000 [CI 0.19-0.48]). Private facility contribution to TB notification increased from 3 to 7%. CONCLUSION: Engagement and inclusion of private health facilities in TB service provision through a systems strengthening approach can increase contribution to TB notification by private health facilities.Item Acceptability and tolerability of long-acting injectable cabotegravir or rilpivirine in the first cohort of virologically suppressed adolescents living with HIV (IMPAACT 2017/MOCHA): a secondary analysis of a phase 1/2, multicentre, open-label, non-comparative dose-finding study.(2024-Apr) Lowenthal ED; Chapman J; Ohrenschall R; Calabrese K; Baltrusaitis K; Heckman B; Yin DE; Agwu AL; Harrington C; Van Solingen-Ristea RM; McCoig CC; Adeyeye A; Kneebone J; Chounta V; Smith-Anderson C; Camacho-Gonzalez A; D'Angelo J; Bearden A; Crauwels H; Huang J; Buisson S; Milligan R; Ward S; Bolton-Moore C; Gaur AH; Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA, USA.; National Institute of Allergy and Infectious Diseases (NIAID) Division of AIDS, National Institutes of Health (NIH), Rockville, MD, USA.; Janssen Research and Development, Beerse, Belgium.; ViiV Healthcare, Madrid, Spain.; The Children's Hospital of Philadelphia, Division of General Pediatrics and Global Health Center, Philadelphia, PA, USA.; Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Emory University School of Medicine, Atlanta, GA, USA.; Northwestern University and Lurie Children's Hospital of Chicago, Chicago, IL, USA.; Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.; St Jude Children's Research Hospital, Memphis, TN, USA.; ViiV Healthcare, Research Triangle Park, NC, USA.; Centre for Infectious Disease Research in Zambia/University of Alabama Birmingham, Lusaka, Zambia.; FHI 360 IMPAACT Operations Center, Durham, NC, USA.; Frontier Science Foundation, Amherst, NY, USA.; University of Colorado School of Medicine, Aurora, CO, USA.; The Children's Hospital of Philadelphia, Division of General Pediatrics and Global Health Center, Philadelphia, PA, USA; University of Pennsylvania Perelman School of Medicine, Departments of Pediatrics and Biostatistics, Epidemiology and Informatics, Philadelphia, PA, USA. Electronic address: lowenthale@chop.edu.; University of Pennsylvania School of Nursing, Philadelphia, PA, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)BACKGROUND: Long-acting injectable cabotegravir and rilpivirine have demonstrated safety, acceptability, and efficacy in adults living with HIV-1. The IMPAACT 2017 study (MOCHA study) was the first to use these injectable formulations in adolescents (aged 12-17 years) living with HIV-1. Herein, we report acceptability and tolerability outcomes in cohort 1 of the study. METHODS: In this a secondary analysis of a phase 1/2, multicentre, open-label, non-comparative dose-finding study, with continuation of pre-study oral combination antiretroviral treatment (ART), 55 adolescents living with HIV-1 were enrolled to receive sequential doses of either long-acting cabotegravir or rilpivirine and 52 received at least two injections. Participants had a body weight greater than 35 kg and BMI less than 31·5 kg/m FINDINGS: Between March 19, 2019, and Nov 25, 2021, 55 participants were enrolled into cohort 1. Using the six-point face scale, 43 (83%) of participants at week 4 and 38 (73%) at week 8 reported that the injection caused "no hurt" or "hurts little bit", while only a single (2%) participant for each week rated the pain as one of the two highest pain levels. Quality of life was not diminished by the addition of one injectable antiretroviral. In-depth interviews revealed that parents and caregivers in the USA frequently had more hesitancy than adolescents about use of long-acting formulations, but parental acceptance was higher after their children received injections. INTERPRETATION: High acceptability and tolerability of long-acting cabotegravir or rilpivirine injections suggests that these are likely to be favoured treatment options for some adolescents living with HIV. FUNDING: National Institutes of Health and ViiV Healthcare.Item Safety and pharmacokinetics of oral and long-acting injectable cabotegravir or long-acting injectable rilpivirine in virologically suppressed adolescents with HIV (IMPAACT 2017/MOCHA): a phase 1/2, multicentre, open-label, non-comparative, dose-finding study.(2024-Apr) Gaur AH; Capparelli EV; Calabrese K; Baltrusaitis K; Marzinke MA; McCoig C; Van Solingen-Ristea RM; Mathiba SR; Adeyeye A; Moye JH; Heckman B; Lowenthal ED; Ward S; Milligan R; Samson P; Best BM; Harrington CM; Ford SL; Huang J; Crauwels H; Vandermeulen K; Agwu AL; Smith-Anderson C; Camacho-Gonzalez A; Ounchanum P; Kneebone JL; Townley E; Bolton Moore C; Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA, USA.; Janssen Research and Development, Beerse, Belgium.; University of California San Diego, La Jolla, CA, USA.; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD, USA.; Emory University School of Medicine-Children's Healthcare of Atlanta, Atlanta, GA, USA.; Frontier Science Foundation, Boston, MA, USA.; ViiV Healthcare, Madrid, Spain.; ViiV Healthcare, ResearchTriangle Park, NC, USA.; Baragwanath Academic Hospital, Johannesburg, South Africa.; FHI 360, Durham, NC, USA.; Frontier Science Foundation, Amherst, NY, USA.; St Jude Children's Research Hospital, Memphis, TN, USA. Electronic address: aditya.gaur@stjude.org.; Johns Hopkins University School of Medicine, Baltimore, MD, USA.; University of Colorado School of Medicine, Aurora, CO, USA.; Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand.; University of Pennsylvania Perelman School of Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; GlaxoSmithKline, Mississauga, ON, Canada.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; University of Alabama, Birmingham, AL, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)BACKGROUND: Combined intramuscular long-acting cabotegravir and long-acting rilpivirine constitute the first long-acting combination antiretroviral therapy (ART) regimen approved for adults with HIV. The goal of the IMPAACT 2017 study (MOCHA [More Options for Children and Adolescents]) was to assess the safety and pharmacokinetics of these drugs in adolescents. METHODS: In this phase 1/2, multicentre, open-label, non-comparative, dose-finding study, virologically suppressed adolescents (aged 12-17 years; weight ≥35 kg; BMI ≤31·5 kg/m FINDINGS: Between March 19, 2019, and Nov 25, 2021, 55 participants were enrolled: 30 in cohort 1C and 25 in cohort 1R. At week 16, 28 (97%, 95% CI 82-100) of the 29 dose-evaluable participants in cohort 1C and 21 (91%; 72-99) of the 23 dose-evaluable participants in cohort 1R had reported at least one adverse event, with the most common being injection-site pain (nine [31%] in cohort 1C; nine [39%] in cohort 1R; none were severe). One (4%, 95% CI 0-22) participant in cohort 1R had an adverse event of grade 3 or higher, leading to treatment discontinuation, which was defined as acute rilpivirine-related allergic reaction (self-limiting generalised urticaria) after the first oral dose. No deaths or life-threatening events occurred. In cohort 1C, the week 2 median cabotegravir AUC INTERPRETATION: Study data support using long-acting cabotegravir or long-acting rilpivirine, given every 4 weeks or 8 weeks, per the adult dosing regimens, in virologically suppressed adolescents aged 12 years and older and weighing at least 35 kg. FUNDING: The National Institutes of Health and ViiV Healthcare.Item Human cytomegalovirus seropositivity and its influence on oral rotavirus vaccine immunogenicity: a specific concern for HIV-exposed-uninfected infants.(2024-Jun-20) Laban N; Bosomprah S; Chilengi R; Simuyandi M; Chisenga C; Ng'ombe H; Musukuma-Chifulo K; Goodier M; Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana.; Flow Cytometry and Immunology Facility, Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine, Fajara, Banjul, The Gambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)Oral rotavirus vaccines demonstrate diminished immunogenicity in low-income settings where human cytomegalovirus infection is acquired early in childhood and modulates immunity. We hypothesized that human cytomegalovirus infection around the time of vaccination may influence immunogenicity. We measured plasma human cytomegalovirus-specific immunoglobulin M antibodies in rotavirus vaccinated infants from 6 weeks to 12 months old and compared rotavirus immunoglobulin A antibody titers between human cytomegalovirus seropositive and seronegative infants. There was no evidence of an association between human cytomegalovirus serostatus at 9 months and rotavirus-specific antibody titers at 12 months (geometric mean ratio 1.01, 95% CI: 0.70, 1.45; P = 0.976) or fold-increase in RV-IgA titer between 9 and 12 months (risk ratio 0.999, 95%CI: 0.66, 1.52; P = 0.995) overall. However, HIV-exposed-uninfected infants who were seropositive for human cytomegalovirus at 9 months old had a 63% reduction in rotavirus antibody geometric mean titers at 12 months compared to HIV-exposed-uninfected infants who were seronegative for human cytomegalovirus (geometric mean ratio 0.37, 95% CI: 0.17, 0.77; P = 0.008). While the broader implications of human cytomegalovirus infections on oral rotavirus vaccine response might be limited in the general infant population, the potential impact in the HIV-exposed-uninfected infants cannot be overlooked. This study highlights the complexity of immunological responses and the need for targeted interventions to ensure oral rotavirus vaccine efficacy, especially in vulnerable subpopulations.Item Application of a Novel Proteomic Microarray Reveals High Exposure to Diarrhoeagenic(2024-Feb-20) Mwape K; Mubanga C; Chilyabanyama ON; Chibesa K; Chisenga CC; Silwamba S; Randall A; Liang X; Barnard TG; Simuyandi M; Chilengi R; Antigen Discovery Inc., 1 Technology Dr., STE E309, Irvine, CA 92618, USA.; Department of Basic Medical Sciences, Michael Chilufya Sata School of Medicine, Copperbelt University, Ndola P.O. Box 71191, Zambia.; Enteric Disease and Vaccines Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia.; Division of Medical Microbiology, Department of Pathology, Stellenbosch University & National Health Laboratory Service, Tygerberg Hospital Francie van Zijl Drive, P.O. Box 241, Cape Town 8000, South Africa.; Next Generation Sequencing Unit and Division of Virology, School of Pathology, Faculty of Health Sciences, University of the Free State, P.O. Box 339, Bloemfontein 9300, South Africa.; Water and Health Research Center, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein, Johannesburg 2028, South Africa.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)DiarrhoeagenicItem Trends in SARS-CoV-2 seroprevalence among pregnant women attending first antenatal care visits in Zambia: A repeated cross-sectional survey, 2021-2022.(2024) Heilmann E; Tembo T; Fwoloshi S; Kabamba B; Chilambe F; Kalenga K; Siwingwa M; Mulube C; Seffren V; Bolton-Moore C; Simwanza J; Yingst S; Yadav R; Rogier E; Auld AF; Agolory S; Kapina M; Gutman JR; Savory T; Kangale C; Mulenga LB; Sikazwe I; Hines JZ; Surveillance and Disease Intelligence, Zambia National Public Health Institute, Lusaka, Zambia.; Public Health Institute, Oakland, California, United States of America.; Adult Centre of Excellence, University Teaching Hospital, Lusaka, Zambia.; Division of Parasitic Diseases and Malaria, U.S. Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.; PATH, Lusaka, Zambia.; Division of Infectious Diseases, Ministry of Health, Lusaka, Zambia.; Division of Global HIV and Tuberculosis, U.S. Centers for Disease Control and Prevention, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)SARS-CoV-2 serosurveys help estimate the extent of transmission and guide the allocation of COVID-19 vaccines. We measured SARS-CoV-2 seroprevalence among women attending ANC clinics to assess exposure trends over time in Zambia. We conducted repeated cross-sectional SARS-CoV-2 seroprevalence surveys among pregnant women aged 15-49 years attending their first ANC visits in four districts of Zambia (two urban and two rural) during September 2021-September 2022. Serologic testing was done using a multiplex bead assay which detects IgG antibodies to the nucleocapsid protein and the spike protein receptor-binding domain (RBD). We calculated monthly SARS-CoV-2 seroprevalence by district. We also categorized seropositive results as infection alone, infection and vaccination, or vaccination alone based on anti-RBD and anti-nucleocapsid test results and self-reported COVID-19 vaccination status (vaccinated was having received ≥1 dose). Among 8,304 participants, 5,296 (63.8%) were cumulatively seropositive for SARS-CoV-2 antibodies from September 2021 through September 2022. SARS-CoV-2 seroprevalence primarily increased from September 2021 to September 2022 in three districts (Lusaka: 61.8-100.0%, Chongwe: 39.6-94.7%, Chipata: 56.5-95.0%), but in Chadiza, seroprevalence increased from 27.8% in September 2021 to 77.2% in April 2022 before gradually dropping to 56.6% in July 2022. Among 5,906 participants with a valid COVID-19 vaccination status, infection alone accounted for antibody responses in 77.7% (4,590) of participants. Most women attending ANC had evidence of prior SARS-CoV-2 infection and most SARS-CoV-2 seropositivity was infection-induced. Capturing COVID-19 vaccination status and using a multiplex bead assay with anti-nucleocapsid and anti-RBD targets facilitated distinguishing infection-induced versus vaccine-induced antibody responses during a period of increasing COVID-19 vaccine coverage in Zambia. Declining seroprevalence in Chadiza may indicate waning antibodies and a need for booster vaccines. ANC clinics have a potential role in ongoing SARS-CoV-2 serosurveillance and can continue to provide insights into SARS-CoV-2 antibody dynamics to inform near real-time public health responses.Item Characterization of human respiratory syncytial virus in children with severe acute respiratory infection before and during the COVID-19 pandemic.(2024-Jun) Simusika P; Okamoto M; Dapat C; Muleya W; Malisheni M; Azam S; Imamura T; Saito M; Mwape I; Mpabalwani E; Monze M; Oshitani H; University Teaching Hospitals, Pathology and Microbiology Department, Virology Laboratory, Lusaka, Zambia.; Levy Mwanawasa Medical University, Institute of Basic and Biomedical Sciences ,Lusaka, Zambia.; Tohoku University Graduate School of Medicine, Department of Virology, Sendai, Japan.; University of Zambia, School of Medicine, Department of Pediatrics and Child Health, Lusaka, Zambia.; University of Zambia, School of Veterinary Medicine, Department of Biomedical Sciences, Lusaka, Zambia.; Center for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)OBJECTIVES: Annual outbreaks of human respiratory syncytial virus (HRSV) are caused by newly introduced and locally persistent strains. During the COVID-19 pandemic, global and local circulation of HRSV significantly decreased. This study was conducted to characterize HRSV in 2018-2022 and to analyze the impact of COVID-19 on the evolution of HRSV. DESIGN/METHODS: Combined oropharyngeal and nasopharyngeal swabs were collected from children hospitalized with severe acute respiratory infection at two hospitals in Zambia. The second hypervariable region of the attachment gene G was targeted for phylogenetic analysis. RESULTS: Of 3113 specimens, 504 (16.2%) were positive for HRSV, of which 131 (26.0%) and 66 (13.1%) were identified as HRSVA and HRSVB, respectively. In early 2021, an increase in HRSV was detected, caused by multiple distinct clades of HRSVA and HRSVB. Some were newly introduced, whereas others resulted from local persistence. CONCLUSIONS: This study provides insights into the evolution of HRSV, driven by global and local circulation. The COVID-19 pandemic had a temporal impact on the evolution pattern of HRSV. Understanding the evolution of HRSV is vital for developing strategies for its control.Item The Incidence and Risk Factors for Enterotoxigenic(2024-Mar-29) Sukwa N; Bosomprah S; Somwe P; Muyoyeta M; Mwape K; Chibesa K; Luchen CC; Silwamba S; Mulenga B; Munyinda M; Muzazu S; Chirwa M; Chibuye M; Simuyandi M; Chilengi R; Svennerholm AM; Department of Microbiology and Immunology, University of Gothenburg, 40530 Gothenburg, Sweden.; Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka P.O. Box 34681, Zambia.; Department of Biostatistics, School of Public Health, University of Ghana, Accra P.O. Box LG13, Ghana.This study aimed to estimate the incidence and risk factors for Enterotoxigenic