Editorial: Improving the delivery of pre-exposure prophylaxis (PrEP) to eliminate vertical HIV transmission

HIV pre-exposure prophylaxis (PrEP) significantly reduces new HIV infections. Among pregnant and lactating cisgender women in high HIV prevalence settings PrEP offers dual benefits for maternal and infant HIV prevention and is increasingly integral to vertical transmission prevention programs. Many countries in East and Southern Africa with high HIV burden have integrated oral PrEP into HIV prevention programs, in the form of daily oral tenofovir disoproxil fumarate (TDF) containing regimens. While daily oral TDF-based PrEP use in pregnancy and lactation is considered safe and effective, only recently are data on PrEP implementation and extended safety emerging. As additional PrEP options become available, there is a need for more evidence on how to ensure effective antenatal and postnatal use

Prevalence of bovine mastitis and antimicrobial sensitivities of the bacterial causes in smallholder farms of Kisumu County, Kenya

Prevalence of bovine mastitis in Kisumu County, risk factors and antibiotic sensitivities of the causative bacteria were determined in this cross-sectional study. Sub-clinical mastitis (SCM) was diagnosed using California Mastitis Test (CMT). Risk factors were identified through the administration of 64 questionnaires and assessment of 134 lactating cows. Bacteria were identified by culturing 72 CMT-positive udder quarter milk samples and their sensitivities to antibiotics investigated using Kirby-Bauer disc diffusion test. Only SCM was detected and had cow level prevalence of 33% (44/134). Prevalence of SCM was significantly (p0.05) higher in cows under complete and semi-zero grazing systems, at mid lactation, those pregnant and with parity of 1-3.  Staphylococcus species was the most common (63.8%, n=58) isolate. Other isolates were E. coli (13.8%), Streptococcus species (12.1%) and Pseudomonas (5.2%). Staphylococcus and Streptococcus isolates were 100% sensitive to streptomycin, kanamycin, gentamycin and chloramphenicol. Additionally, Streptococcus species were 100% sensitive to ampicillin, tetracycline and cotrimoxazole. Staphylococcus species had developed varying levels of resistance against sulphamethoxazole, cotrimoxazole, ampicillin and tetracycline. Streptococcus species was 100% resistant to sulfamethoxazole. A significantly high SCM prevalence was reported in this study thus an appropriate control strategy is needed that consists of awareness creation, good milking hygiene practices, teat disinfection, regular screening for SCM and preventing spread of mastitis in the herd by milking infected cow(s) last.   

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

From pediatric to adolescent HIV: mortality, viral suppression and transition to adult care

Thesis (Ph.D.)--University of Washington, 2019University of Washington Abstract From pediatric to adolescent HIV: mortality, viral suppression and transition to adult care Irene Nyambura Njuguna Chair of the Supervisory Committee: Professor Grace John-Stewart Departments of Global Health and Epidemiology Introduction: Global scale-up of prevention of mother to child transmission (PMTCT) programs and expansion of pediatric HIV testing and treatment have dramatically changed the course of pediatric HIV. Fewer infants are born with HIV, and early treatment significantly improves survival, growth, neurodevelopment and prevents morbidity. However, challenges with early diagnosis and achieving treatment goals during adolescence exist. A majority of HIV infected children present for care while severely ill, and experience high morbidity and mortality despite initiation of treatment. For children surviving to adolescence, maintaining viral suppression remains challenging, and mortality during adolescence is high. As children grow into adulthood, how to support them transition to adult care and gain independence in their own care remain unanswered questions. Methods: The aims of the dissertation address the following questions: Chapter 1) what are the common diagnoses at death and what are the correlates of viral suppression among severely ill, hospitalized, antiretroviral therapy (ART) naïve HIV-positive children aged 0-12 years in Kenya? Using data from a randomized controlled trial (RCT) on urgent versus post–stabilization antiretroviral treatment (ART) (PUSH trial), we use survival analysis methods examined sociodemographic and clinical correlates of mortality. Chapter 2) What is the prevalence of viral suppression and what clinic and individual level factors are associated with viral suppression among HIV-positive adolescents and young adults (AYA) age 10-24 years, on ART for more than 6 months and enrolled in HIV care programs in Kenya? We used multilevel logistic regression methods to estimate association of viral suppression with hypothesized individual and clinic level factors. Chapter 3) What are the current adolescent transition practices in Kenya, and how can we define transition and its success in programmatic settings in Kenya. We used descriptive statistics to describe adolescent HIV care practice, disclosure and transition services in Kenya and a user-centered design workshop to develop transition definitions and key elements for programmatic use in Kenya. Results: Chapter 1: Overall 39/181 (22%) of hospitalized HIV-positive children enrolled in the PUSH RCT died. Pneumonia or suspected tuberculosis, and gastroenteritis were the most common diagnoses at the time of death. Young age (<2 years) and being an orphaned or vulnerable child (OVC) were independently associated with mortality. Chapter 2: Among 9921 AYA enrolled in 99 facilities, 2664 (27%) had unsuppressed viral load. Adjusting for clinic and individual factors, young age (10-24 and 15-19), perinatal HIV infection, male sex and increasing duration on ART were associated with poor viral suppression. Adolescents in clinics with separate adolescent spaces, lower-level clinic, and faster viral load turnaround time were more likely to have viral suppression. Chapter 3: The majority of HIV clinics in Kenya had included models of care to meet specific adolescent needs. Adolescent days, most on weekend days were common. Transition definitions were heterogeneous, and tracking systems had limited ability to monitor individual progress or assess outcomes. Conclusions: The findings of this dissertation emphasize on the need to develop strategies to identify HIV infected children early and link them to care, and to optimize hospital management for severely ill children. As children grow into adolescence, strategies to aggressively identify and manage virologic failure are needed particularly for perinatal infected AYA. At program level, consistent transition definitions and defining measures of success are first steps in studying transitional care. Tools to support HIV disclosure services and support adolescents gain skills and knowledge they need to independently manage their care are needed

Financial incentives to increase pediatric HIV testing in Kenya: A pilot randomized trial

Thesis (Master's)--University of Washington, 2017-06Background Initiating antiretroviral therapy (ART) prior to the onset of symptomatic disease improves survival in HIV-infected children. However, HIV diagnosis in children is often delayed due to caregiver reluctance to test and financial barriers. A pilot study was conducted to assess acceptability of financial incentives to motivate pediatric testing, and to determine incentive amount and format for a larger efficacy trial. Materials and Methods HIV-infected female caregivers at Kisumu County Hospital, Kenya, who had children of unknown HIV status aged 0-12 years, were randomized to receive KSH 500 (~$5), KSH 1000 (~$10) or, KSH 1500 (~$15) payment conditional on child testing within 2 months. At the child HIV testing visit, data on socio-demographics, incentive preference, and impact of testing on health seeking behavior was collected. Results Of 1,991 female caregivers screened, 71 (4$0, $1.25,$2.50, $5, and$10 arms began in January 2017