Impact of major disease outbreaks in the third millennium on adolescent and youth sexual and reproductive health and rights in low and/or middle-income countries: a systematic scoping review protocol

Introduction Sexual and Reproductive Health and Rights (SRHR) of young people continue to present a high burden and remain underinvested. This is more so in low and middle-income countries (LMICs), where empirical evidence reveals disruption of SRHR maintenance, need for enhancement of programmes, resources and services during pandemics. Despite the importance of the subject, there is no published review yet combining recent disease outbreaks such as (H1N1/09, Zika, Ebola and SARS-COV-2) to assess their impact on adolescents and youth SRHR in LMICs. Methods and analysis We will adopt a four-step search to reach the maximum possible number of studies. In the first step, we will carry out a limitedpreliminary search in databases for getting relevant keywords (appendix 1). Second, we will search in four databases: Pubmed, Cochrane Library, Embase and PsycINFO. The search would begin from the inception of the first major outbreak in 2009 (H1N1/09) up to the date of publication of the protocol in early 2022. We will search databases using related keywords, screen title & abstract and review full texts of the selected titles to arrive at the list of eligible studies. In the third stage, we will check their eligibility to the included article’s reference list. In the fourth stage, we will check the citations of included papers in phase 2 to complete our study selection. We will include all types of original studies and without any language restriction in our final synthesis. Our review results will be charted for each pandemic separately and include details pertaining to authors, year, country, region of the study, study design, participants (disaggregated by age and gender), purpose and report associated SRHR outcomes. The review will adhere to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guideline (PRISMA-ScR). Patient and public involvement Patients or public were not involved in this study. Ethics and dissemination Ethical assessment is not required for this study. The results of the study will be presented in peer-reviewed publications and conferences on adolescent SRHR

Age, Spatial, and Temporal Variations in Hospital Admissions with Malaria in Kilifi County, Kenya: A 25-Year Longitudinal Observational Study

Background Encouraging progress has been seen with reductions in Plasmodium falciparum malaria transmission in some parts of Africa. Reduced transmission might lead to increasing susceptibility to malaria among older children, which has implications for ongoing control strategies. Methods and findings We conducted a longitudinal observational study of children admitted to Kilifi County Hospital in Kenya and linked to data on residence and Insecticide Treated Net (ITN) ownership. This included data from 69,104 children admitted to Kilifi County Hospital aged from 3 months to 13 years between 1st January 1990 and 31st December 2014. The variation in malaria slide positivity among admissions was examined in logistic regression models using the predictors; location of residence, calendar time, child’s age, ITN use and Enhanced Vegetation Index (a proxy for soil moisture). The proportion of malaria slide positive admissions declined from 0.56 with 95% confidence interval (95%CI) 0.54 to 0.58 in 1998 to 0.07 95%CI 0.06 to 0.08 in 2009, but then increased again through to 0.24 95%CI 0.22 to 0.25 in 2014. Older children accounted for most of the increase after 2009 (0.035 95%CI (0.030 to 0.040) among young children compared to 0.22 95%CI 0.21 to 0.23 in older children). There was a non-linear relationship between malaria risk and prevalence of ITN use within a 2km radius of an admitted child’s residence such that the predicted malaria positive fraction varied from ~0.4 to <0.1 as the prevalence of ITN use varied from 20% to 80%. In this observational analysis we were unable to determine the cause of the decline in malaria between 1998 and 2009, which pre-dated the dramatic scale-up in ITN distribution and use. Conclusion Following a period of reduced transmission a cohort of older children emerged who have increased susceptibility to malaria. Further reductions in malaria transmission are needed to mitigate against the increasing burden among older children and universal ITN coverage is a promising strategy to achieve this

Development of a Clinical Prediction Score Including Monocyte-to-Lymphocyte Ratio to Inform Tuberculosis Treatment Among Children With HIV: A Multicountry Study

BACKGROUND: Clinical pediatric tuberculosis (TB) diagnosis may lead to overdiagnosis particularly among children with human immunodeficiency virus (CHIV). We assessed the performance of monocyte-lymphocyte ratio (MLR) as a diagnostic biomarker and constructed a clinical prediction score to improve specificity of TB diagnosis in CHIV with limited access to microbiologic testing. METHODS: We pooled data from cohorts of children aged ≤13 years from Vietnam, Cameroon, and South Africa to validate the use of MLR ≥0.378, previously found as a TB diagnostic marker among CHIV. Using multivariable logistic regression, we created an internally validated prediction score for diagnosis of TB disease in CHIV. RESULTS: The combined cohort had 601 children (median age, 1.9 [interquartile range, 0.9-5.3] years); 300 (50%) children were male, and 283 (47%) had HIV. Elevated MLR ≥0.378 had sensitivity of 36% (95% confidence interval [CI], 23%-51%) and specificity of 79% (95% CI, 71%-86%) among CHIV in the validation cohort. A model using MLR ≥0.28, age ≥4 years, tuberculin skin testing ≥5 mm, TB contact history, fever >2 weeks, and chest radiograph suggestive of TB predicted active TB disease in CHIV with an area under the receiver operating characteristic curve of 0.85. A prediction score of ≥5 points had a sensitivity of 94% and specificity of 48% to identify confirmed TB, and a sensitivity of 82% and specificity of 48% to identify confirmed and unconfirmed TB groups combined. CONCLUSIONS: Our score has comparable sensitivity and specificity to algorithms including microbiological testing and should enable clinicians to rapidly initiate TB treatment among CHIV when microbiological testing is unavailable

Brief Report: Diagnostic Accuracy of Oral Mucosal Transudate Tests Compared with Blood-Based Rapid Tests for HIV Among Children Aged 18 Months to 18 Years in Kenya and Zimbabwe.

BACKGROUND: Gaps persist in HIV testing for children who were not tested in prevention of mother-to-child HIV transmission programs. Oral mucosal transudate (OMT) rapid HIV tests have been shown to be highly sensitive in adults, but their performance has not been established in children. METHODS: Antiretroviral therapy-naive children aged 18 months to 18 years in Kenya and Zimbabwe were tested for HIV using rapid OraQuick ADVANCE Rapid HIV-1/2 Antibody test on oral fluids (OMT) and blood-based rapid diagnostic testing (BBT). BBT followed Kenyan and Zimbabwean national algorithms. Sensitivity and specificity were calculated using the national algorithms as the reference standard. RESULTS: A total of 1776 children were enrolled; median age was 7.3 years (interquartile range: 4.7-11.6). Among 71 children positive by BBT, all 71 were positive by OMT (sensitivity: 100% [97.5% confidence interval (CI): 94.9% to 100%]). Among the 1705 children negative by BBT, 1703 were negative by OMT (specificity: 99.9% [95% CI: 99.6% to 100.0%]). Due to discrepant BBT and OMT results, 2 children who initially tested BBT-negative and OMT-positive were subsequently confirmed positive within 1 week by further tests. Excluding these 2 children, the sensitivity and specificity of OMT compared with those of BBT were each 100% (97.5% CI: 94.9% to 100% and 99.8% to 100%, respectively). CONCLUSIONS: Compared to national algorithms, OMT did not miss any HIV-positive children. These data suggest that OMTs are valid in this age range. Future research should explore the acceptability and uptake of OMT by caregivers and health workers to increase pediatric HIV testing coverage

Impact of major disease outbreaks in the third millennium on adolescent and youth sexual and reproductive health and rights in low and/or middle-income countries: a systematic scoping review protocol

INTRODUCTION: Sexual and Reproductive Health and Rights (SRHR) of young people continue to present a high burden and remain underinvested. This is more so in low and middle-income countries (LMICs), where empirical evidence reveals disruption of SRHR maintenance, need for enhancement of programmes, resources and services during pandemics. Despite the importance of the subject, there is no published review yet combining recent disease outbreaks such as (H1N1/09, Zika, Ebola and SARS-COV-2) to assess their impact on adolescents and youth SRHR in LMICs. METHODS AND ANALYSIS: We will adopt a four-step search to reach the maximum possible number of studies. In the first step, we will carry out a limitedpreliminary search in databases for getting relevant keywords (appendix 1). Second, we will search in four databases: Pubmed, Cochrane Library, Embase and PsycINFO. The search would begin from the inception of the first major outbreak in 2009 (H1N1/09) up to the date of publication of the protocol in early 2022. We will search databases using related keywords, screen title & abstract and review full texts of the selected titles to arrive at the list of eligible studies. In the third stage, we will check their eligibility to the included article's reference list. In the fourth stage, we will check the citations of included papers in phase 2 to complete our study selection. We will include all types of original studies and without any language restriction in our final synthesis. Our review results will be charted for each pandemic separately and include details pertaining to authors, year, country, region of the study, study design, participants (disaggregated by age and gender), purpose and report associated SRHR outcomes. The review will adhere to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guideline (PRISMA-ScR). PATIENT AND PUBLIC INVOLVEMENT: Patients or public were not involved in this study. ETHICS AND DISSEMINATION: Ethical assessment is not required for this study. The results of the study will be presented in peer-reviewed publications and conferences on adolescent SRHR

PedVacc 002: a phase I/II randomized clinical trial of MVA. HIVA vaccine administered to infants born to human immunodeficiency virus type 1-positive mothers in Nairobi

Background A safe, effective vaccine for breastfeeding infants born to HIV-1-positive mothers could complement antiretroviral therapy (ART) for prevention of mother-to-child transmission of HIV-1. To date, only a few HIV-1 vaccine candidates have been tested in infants. Trial design A phase I/II randomized controlled trial PedVacc 002 was conducted to determine the safety and immunogenicity of a single, low dose of MVA.HIVA vaccine delivered intramuscularly to healthy 20-week-old infants born to HIV-1-positive mothers in Nairobi, Kenya. Methods Pregnant HIV-1-positive women in the 2nd/3rd trimester of gestation were enrolled, provided with ART and self-selected their infant-feeding modality. Infants received nevirapine and cotrimoxazole prophylaxis. At 20 weeks of age, eligible HIV-1-negative infants were randomized to vaccine versus no-treatment arms and followed to 48 weeks of age for assessments of vaccine safety, HIV-1-specific T-cell responses and antibodies to routine childhood vaccines. Results Between February and November 2010, 182 mothers were screened, 104 were eligible and followed on ART during pregnancy/postpartum, of whom 73 had eligible infants at 20 weeks postpartum. Thirty-six infants were randomized to vaccine and 37 to no treatment. Eighty-four percent of infants breastfed, and retention at 48 weeks was 99%. Adverse events were rare and similar between the two arms. HIV-1-specific T-cell frequencies in interferon-γ ELISPOT assay were transiently higher in the MVA.HIVA arm (p = 0.002), but not above the threshold for a positive assay. Protective antibody levels were adequate and similar between arms for all routine childhood vaccines except HBV, where 71% of MVA.HIVA subjects compared to 92% of control subjects were protected (p = 0.05). Conclusions This trial tested for the first time an MVA-vectored candidate HIV-1 vaccine in HIV-1-exposed infants in Africa, demonstrating trial feasibility and vaccine safety, low immunogenicity, and compatibility with routine childhood vaccinations. These results are reassuring for use of the MVA vector in more potent prime-boost regimens

Cohort profile: longitudinal and population comparison of children who are HIV-exposed uninfected and children who are HIV unexposed in Kenya (HOPE study)

Purpose Globally, the number of children/adolescents exposed to HIV but uninfected (HIV-exposed uninfected, HEU) is growing. The HEU outcomes: population-evaluation and screening strategies study was designed to provide population-level evidence of the impact of HIV and recent antiretroviral therapy regimen exposure on neurodevelopmental, hearing and mental health outcomes from infancy to adolescence.Participants The study includes a prospective mother–infant cohort and cross-sectional child/youth–caregiver cohorts conducted in Kenya.Between 2021 and 2022, the study enrolled 2000 mother–infant pairs (1000 HEU and 1000 HIV-unexposed uninfected (HUU)) for longitudinal follow-up. Infants were eligible if they were aged 4–10 weeks and healthy. Mothers were eligible if their HIV status was known and were ≥18 years. Study visits are 6 monthly until the child reaches age 3 years.Cross-sectional cohorts spanning ages 3–18 years started enrolment in 2022. Target enrolment is 4400 children/youth (4000 HEU and 400 HUU). Children and youth are eligible if they are HIV negative, maternal HIV status and timing of diagnosis is known, and caregivers are ≥18 years.Data on infant/child/youth growth, neurodevelopment, mental health, morbidity and hearing are collected at enrolment using standardised tools. Dry blood spots samples are collected for telomere length assessment at baseline and yearly for the longitudinal cohort. Growth z-scores, neurodevelopmental scores, telomere length and prevalence of developmental and hearing problems will be compared between HEU/HUU populations.Findings to date Full cohort enrolment for the longitudinal cohort is complete and participants are in follow-up. At 1 year of age, comparing HEU to HUU neurodevelopment using the Malawi developmental assessment tool, we found that HEU infants had higher language scores and comparable scores in fine motor, gross motor and social scores. The cross-sectional cohort has enrolled over 2000 participants and recruitment is ongoing.Future plans Longitudinal cohort follow-up and enrolment to the cross-sectional study will be completed in June 2024

Phagocytosis of Plasmodium falciparum ring-stage parasites predicts protection against malaria

Ring-infected erythrocytes are the predominant asexual stage in the peripheral circulation but are rarely investigated in the context of acquired immunity against Plasmodium falciparum malaria. Here we compare antibody-dependent phagocytosis of ring-infected parasite cultures in samples from a controlled human malaria infection (CHMI) study (NCT02739763). Protected volunteers did not develop clinical symptoms, maintained parasitaemia below a predefined threshold of 500 parasites/μl and were not treated until the end of the study. Antibody-dependent phagocytosis of both ring-infected and uninfected erythrocytes from parasite cultures was strongly correlated with protection. A surface proteomic analysis revealed the presence of merozoite proteins including erythrocyte binding antigen-175 and −140 on ring-infected and uninfected erythrocytes, providing an additional antibody-mediated protective mechanism for their activity beyond invasion-inhibition. Competition phagocytosis assays support the hypothesis that merozoite antigens are the key mediators of this functional activity. Targeting ring-stage parasites may contribute to the control of parasitaemia and prevention of clinical malaria