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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 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 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 EnterotoxigenicItem Seroconversion and Kinetics of Vibriocidal Antibodies during the First 90 Days of Re-Vaccination with Oral Cholera Vaccine in an Endemic Population.(2024-Apr-08) Chisenga CC; Phiri B; Ng'ombe H; Muchimba M; Musukuma-Chifulo K; Silwamba S; Laban NM; Luchen C; Liswaniso F; Chibesa K; Mubanga C; Mwape K; Simuyandi M; Cunningham AF; Sack D; Bosomprah S; Institute of Immunology and Immunotherapy, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.; Department of Biostatistics, School of Public Health, University of Ghana, Accra P.O. Box LG13, Ghana.; Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia.; Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)Despite the successful introduction of oral cholera vaccines, Zambia continues to experience multiple, sporadic, and protracted cholera outbreaks in various parts of the country. While vaccines have been useful in staying the cholera outbreaks, the ideal window for re-vaccinating individuals resident in cholera hotspot areas remains unclear. Using a prospective cohort study design, 225 individuals were enrolled and re-vaccinated with two doses of Shanchol™, regardless of previous vaccination, and followed-up for 90 days. Bloods were collected at baseline before re-vaccination, at day 14 prior to second dosing, and subsequently on days 28, 60, and 90. Vibriocidal assay was performed on samples collected at all five time points. Our results showed that anti-LPS and vibriocidal antibody titers increased at day 14 after re-vaccination and decreased gradually at 28, 60, and 90 days across all the groups. Seroconversion rates were generally comparable in all treatment arms. We therefore conclude that vibriocidal antibody titers generated in response to re-vaccination still wane quickly, irrespective of previous vaccination status. However, despite the observed decline, the levels of vibriocidal antibodies remained elevated over baseline values across all groups, an important aspect for Zambia where there is no empirical evidence as to the ideal time for re-vaccination.Item Junk food use and neurodevelopmental and growth outcomes in infants in low-resource settings.(2024) Chiwila MK; Krebs NF; Manasyan A; Chomba E; Mwenechanya M; Mazariegos M; Sami N; Pasha O; Tshefu A; Lokangaka A; Goldenberg RL; Bose CL; Koso-Thomas M; Goco N; Do BT; McClure EM; Hambidge KM; Westcott JE; Carlo WA; School of Public Health, University of Kinshasa, Kinshasa, Democratic Republic of Congo.; Research Triangle Institute International, Durham, NC, United States.; Department of Community Health Sciences, Aga Khan University, Karachi, Pakistan.; Department of Obstetrics and Gynecology, Columbia University, New York, NY, United States.; Eunice Kennedy Shiver National Institute of Child Health and Human Development, Bethesda, MD, United States.; Department of Pediatrics, University of North Carolina, Chapel Hill, NC, United States.; Global Network, University Teaching Hospital, Lusaka, Zambia.; University of Colorado School of Medicine, Aurora, CO, United States.; Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, United States.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Instituto de Nutrición de Centro América y Panamá, Guatemala City, Guatemala.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)INTRODUCTION: Feeding infants a sub-optimal diet deprives them of critical nutrients for their physical and cognitive development. The objective of this study is to describe the intake of foods of low nutritional value (junk foods) and identify the association with growth and developmental outcomes in infants up to 18 months in low-resource settings. METHODS: This is a secondary analysis of data from an iron-rich complementary foods (meat versus fortified cereal) randomized clinical trial on nutrition conducted in low-resource settings in four low- and middle-income countries (Democratic Republic of the Congo, Guatemala, Pakistan, and Zambia). Mothers in both study arms received nutritional messages on the importance of exclusive breastfeeding up to 6 months with continued breastfeeding up to at least 12 months. This study was designed to identify the socio-demographic predictors of feeding infants' complementary foods of low nutritional value (junk foods) and to assess the associations between prevalence of junk food use with neurodevelopment (assessed with the Bayley Scales of Infant Development II) and growth at 18 months. RESULTS: 1,231 infants were enrolled, and 1,062 (86%) completed the study. Junk food feeding was more common in Guatemala, Pakistan, and Zambia than in the Democratic Republic of Congo. 7% of the infants were fed junk foods at 6 months which increased to 70% at 12 months. Non-exclusive breastfeeding at 6 months, higher maternal body mass index, more years of maternal and paternal education, and higher socioeconomic status were associated with feeding junk food. Prevalence of junk foods use was not associated with adverse neurodevelopmental or growth outcomes. CONCLUSION: The frequency of consumption of junk food was high in these low-resource settings but was not associated with adverse neurodevelopment or growth over the study period.Item The Social Construction of Aging Among a Clinic-Based Population and Their Healthcare Workers in Zambia.(2024) Sharma A; Mwamba C; St Clair-Sullivan N; Chihota BV; Pry JM; Bolton-Moore C; Vinikoor MJ; Muula GK; Daultrey H; Gittelsohn J; Mulenga LB; Siyumbwa N; Wandeler G; Vera JH; Department of Medicine, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States.; Ministry of Health, Lusaka Zambia, Lusaka, Zambia.; Department of Preclinical Medicine, Faculty of Medicine, Institute for Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Medical Faculty, Institute for Infectious Diseases, University of Bern, Bern, Switzerland.; Brighton and Sussex Medical School, Brighton, United Kingdom.; Center for Human Nutrition, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; School of Medicine, University of California, Davis, Sacramento, CA, United States.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)OBJECTIVES: We sought to understand the social construction of aging in a clinic-based population, with and without HIV, to address gaps in care for older individuals living with HIV in Zambia. METHODS: Our exploratory qualitative study included 36 in-depth interviews with clinic clients and four focus group discussions with 36 professional and lay healthcare workers providing services to the clients. We identified themes based on social construction theory. RESULTS: At the individual level, aging was multidimensional, perceived both as an achievement in the HIV era and as a period of cognitive, physical, and economic decline. In social interactions, older individuals were often stereotyped and treated as helpless, poor, and "witches." Those living with HIV faced the additional stigma of being labeled as promiscuous. Some of the participants living without HIV refused to take daily medication for non-communicable diseases to avoid being mistaken for taking antiretroviral therapy for HIV. Older individuals wanted quality healthcare and family support to address the intersectional stigma of aging, poverty, and chronic illness. CONCLUSION: Multifaceted interventions are required to combat age-related prejudice, intersectional stigma, and discriminatory practices, particularly for people living with HIV.