Centre for Infectious Disease Research in Zambia
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Recent Submissions
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)
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 bla
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.
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.
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.