"Something Like That": Awareness and Acceptability of HIV PrEP and PEP Among Kenyan Adolescents.

BACKGROUND: Adolescents account for 15% of new HIV cases in Kenya. HIV pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) are highly effective prevention tools, but uptake is low among adolescents, particularly in resource-limited settings. We assessed awareness and acceptability of PrEP and PEP among Kenyan adolescents. METHOD: Focus group discussions were conducted with 120 adolescent boys and girls ages 15 to 19 in Kisumu. Data were analyzed using the Framework Approach. RESULTS: Adolescent participants often had not heard of or could not differentiate between PrEP and PEP. They also confused these HIV prevention tools with emergency contraceptives. Taking a daily pill to prevent HIV was perceived as analogous to taking a pill to treat HIV. Boys were aware of and willing to consider using PrEP and PEP due to their dislike for using condoms. Adolescents identified insufficient information, cost, and uncomfortableness speaking with healthcare workers about their HIV prevention needs due to sexuality stigma as barriers to using PrEP and PEP. CONCLUSION: Low awareness and poor understanding of PrEP and PEP among adolescents reveal the need for increased education and sensitization about these HIV prevention options. Expanding access to sexual and reproductive health services that are tailored to the needs of adolescents and staffed with non-judgmental providers could help reduce sexuality stigma as a barrier to accessing care. New HIV prevention approaches such as long-acting injectables or implants, on-demand regimens, and multipurpose prevention technologies may encourage increased uptake of PrEP and PEP by adolescents.

Adapting the preterm birth phenotyping framework to a low-resource, rural setting and applying it to births from Migori County in western Kenya.

BACKGROUND: Preterm birth is the leading cause of neonatal and under-five mortality worldwide. It is a complex syndrome characterized by numerous etiologic pathways shaped by both maternal and fetal factors. To better understand preterm birth trends, the Global Alliance to Prevent Prematurity and Stillbirth published the preterm birth phenotyping framework in 2012 followed by an application of the model to a global dataset in 2015 by Barros, et al. Our objective was to adapt the preterm birth phenotyping framework to retrospective data from a low-resource, rural setting and then apply the adapted framework to a cohort of women from Migori, Kenya. METHODS: This was a single centre, observational, retrospective chart review of eligible births from November 2015 - March 2017 at Migori County Referral Hospital. Adaptations were made to accommodate limited diagnostic capabilities and data accuracy concerns. Prevalence of the phenotyping conditions were calculated as well as odds of adverse outcomes. RESULTS: Three hundred eighty-seven eligible births were included in our study. The largest phenotype group was none (no phenotype could be identified; 41.1%), followed by extrauterine infection (25.1%), and antepartum stillbirth (16.7%). Extrauterine infections included HIV (75.3%), urinary tract infections (24.7%), malaria (4.1%), syphilis (3.1%), and general infection (3.1%). Severe maternal condition was ranked fourth (15.6%) and included anaemia (69.5%), chronic respiratory distress (22.0%), chronic hypertension prior to pregnancy (5.1%), diabetes (3.4%), epilepsy (3.4%), and sickle cell disease (1.7%). Fetal anaemia cases were the most likely to transfer to the newborn unit (OR 5.1, 95% CI 0.8, 30.9) and fetal anomaly cases were the most likely to result in a pre-discharge mortality (OR 3.9, 95% CI 0.8, 19.2). CONCLUSIONS: Using routine data sources allowed for a retrospective analysis of an existing dataset, requiring less time and fewer resources than a prospective study and demonstrating a feasible approach to preterm phenotyping for use in low-resource settings to inform local prevention strategies.

Preterm birth is a complex syndrome, yet it is the leading cause of death in children worldwide. To help unravel the clinical complexities, preterm birth phenotyping is a framework that considers multiple diagnoses in the mother, helping to evaluate trends in causes of preterm birth in a given region. In our study, we adapted this international phenotyping framework to accommodate a rural, low-resource setting where obstetrical and neonatal technologies were limited, but preterm birth rates were high. We evaluated data from the patient records of a large hospital in Migori, Kenya, in the southwestern region of the country. By lowering the threshold of diagnostic criteria, we were able to apply this framework to our dataset and see that maternal infection and maternal chronic illness appear to be a significant driving forces of preterm birth. Given high rates of HIV and malaria in the region, this is not a surprising finding, but one that can inform antenatal care practices, mainly the need to test and treat for common infections (HIV, malaria, as well as urinary and reproductive tract infections), and to increase the frequency of antenatal care interactions per the World Health Organization recommendations.

Community Conversations About COVID-19.

"Community Conversations About COVID-19" was a multi-group program designed to address the need for culturally sensitive health information about COVID-19 for Latinx and Native American communities. Three medical librarians worked closely with Latinx and/or Spanish-speaking promotores, also known as community health workers (CHWs), and native patient navigators (NPNs) from Native American communities in Tucson, Arizona. In addition, the librarians collaborated with second-year medical students from the University of Arizona College of Medicine - Phoenix. The focus was to train the CHWs, NPNs, and students on how to access health information resources from the National Library of Medicine, National Institutes of Health, Centers for Disease Control and Prevention, and other reliable agencies. The second segment of the program provided the opportunity for the groups to learn from each other's experiences working with health information through this pandemic, which is especially important given the fact the CHWs and NPNs live in, care for, and were brought up in these communities.

"We Don't Fear HIV. We Just Fear Walking around Pregnant.": A Qualitative Analysis of Adolescent Sexuality and Pregnancy Stigma in Informal Settlements in Kisumu, Kenya.

In Kenya, adolescent pregnancy rates are high, contraception utilization is low, and adolescent sexuality is stigmatized. We describe how perceptions of sexuality and pregnancy stigma influence decision-making among adolescents in the informal settlements of Kisumu. We used purposive sampling to recruit 120 adolescent boys and girls aged 15-19 for focus group discussions. A semistructured interview guide was used to elicit social norms and community attitudes about sexual and reproductive health. We analyzed the data using the Framework Approach. The social stigma of adolescent sexuality and the related fear of pregnancy as an unambiguous marker of sexual activity emerged as main themes. This stigma led adolescents to fear social retribution but did not lead to more frequent contraception use due to additional stigma. The intensity of this fear was most acutely expressed by girls, leading some to seek unsafe, sometimes fatal, abortions, and to contemplate suicide. Fear of pregnancy outweighed fear of contracting HIV that was viewed as both treatable and less stigmatized. Our findings illustrate how fear of pregnancy among these adolescents is driven primarily by fears that their community will discover that they are sexually active. Interventions are urgently needed to address adolescent sexual stigma and to prevent negative outcomes.

Brief Report: HIV Pre-Exposure Prophylaxis Awareness and Use Among Adolescents in Kenya.

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) is an effective prevention tool; however, use among adolescents is thought to be low. To determine the unmet need and opportunity to expand use, we assessed awareness, prior use, and willingness to take PrEP among Kenyan adolescents. METHODS: The Maneno Yetu study recruited a community-based sample of adolescents aged 15-19 years (N = 3061) in Kisumu for a survey using respondent-driven sampling. RESULTS: Overall, 50% of adolescents had heard of PrEP and 2% had used PrEP. Girls were more likely than boys to have heard of PrEP (53.4% vs. 45.1%; P < 0.001) and used PrEP (3.6% vs. 0.3%; P < 0.001). Among participants, 14% engaged in transactional sex and 21% experienced forced sexual contact. PrEP use was higher among adolescents who engaged in transactional sex (4.8% vs. 0.6%; P < 0.001) and experienced forced sexual contact (2.7% vs. 0.7%; P < 0.001) compared with those who did not. Among adolescents with no prior use, 53% were willing to consider using PrEP, although girls were less willing than boys (49.7% vs. 55.9%; P = 0.001). CONCLUSIONS: PrEP is an important prevention tool, especially for adolescents whose circumstances potentially expose them to HIV-positive or unknown status sexual partners, yet remains underused, particularly in resource-limited settings. Although many expressed willingness to use PrEP, low awareness and use highlight the need to expand HIV prevention education and services tailored for adolescents. Our finding that boys were more willing to use PrEP suggests campaigns should also be designed to reach male youth to narrow the gender gap and expand uptake in the adolescent population.

Simulation and team training to improve preterm birth knowledge, evidence-based practices, and communication skills in midwives in Kenya and Uganda: Findings from a pre- and post-intervention analysis.

Simulation training in basic and emergency obstetric and neonatal care has previously shown success in reducing maternal and neonatal mortality in low-resource settings. Though preterm birth is the leading cause of neonatal deaths, application of this training methodology geared specifically towards reducing preterm birth mortality and morbidity has not yet been implemented and evaluated. The East Africa Preterm Birth Initiative (PTBi-EA) was a multi-country cluster randomized controlled (CRCT) trial that successfully improved outcomes of preterm neonates in Migori County, Kenya and the Busoga region of Uganda through an intrapartum package of interventions. PRONTO simulation and team training (STT) was one component of this package and was introduced to maternity unit providers in 13 facilities. This analysis was nested within the larger CRCT and specifically looked at the impact of the STT portion of the intervention package. The PRONTO STT curriculum was modified to emphasize prematurity-related intrapartum and immediate postnatal care practices, such as assessment of gestational age, identification of preterm labour, and administration of antenatal corticosteroids. Knowledge and communication techniques were assessed at the beginning and end of the intervention through a multiple-choice knowledge test. Clinical skills and communication techniques used in context were assessed through the use of evidence-based practiced (EBPs) as documented in video-recorded simulations through StudioCodeTM video analysis. Pre-and-post scores were compared in both categories using Chi-squared tests. Knowledge assessment scores improved from 51% to 73% with maternal-related questions improving from 61% to 74%, neonatal questions from 55% to 73%, and communication technique questions from 31% to 71%. The portion of indicated preterm birth EBPs performed in simulation increased from 55% to 80% with maternal-related EBPs improving from 48% to 73%, neonatal-related EBPs from 63% to 93%, and communication techniques from 52% to 69%. STT substantially increased preterm birth-specific knowledge and EBPs performed in simulation.

Quality improvement collaboratives as part of a quality improvement intervention package for preterm births at sub-national level in East Africa: a multi-method analysis.

BACKGROUND: Quality improvement collaboratives (QIC) are an approach to accelerate the spread and impact of evidence-based interventions across health facilities, which are found to be particularly successful when combined with other interventions such as clinical skills training. We implemented a QIC as part of a quality improvement intervention package designed to improve newborn survival in Kenya and Uganda. We use a multi-method approach to describe how a QIC was used as part of an overall improvement effort and describe specific changes measured and participant perceptions of the QIC. METHODS: We examined QIC-aggregated run charts on three shared indicators related to uptake of evidence-based practices over time and conducted key informant interviews to understand participants' perceptions of quality improvement practice. Run charts were evaluated for change from baseline medians. Interviews were analysed using framework analysis. RESULTS: Run charts for all indicators reflected an increase in evidence-based practices across both countries. In Uganda, pre-QIC median gestational age (GA) recording of 44% improved to 86%, while Kangaroo Mother Care (KMC) initiation went from 51% to 96% and appropriate antenatal corticosteroid (ACS) use increased from 17% to 74%. In Kenya, these indicators went from 82% to 96%, 4% to 74% and 4% to 57%, respectively. Qualitative results indicate that participants appreciated the experience of working with data, and the friendly competition of the QIC was motivating. The participants reported integration of the QIC with other interventions of the package as a benefit. CONCLUSIONS: In a QIC that demonstrated increased evidence-based practices, QIC participants point to data use, friendly competition and package integration as the drivers of success, despite challenges common to these settings such as health worker and resource shortages. TRIAL REGISTRATION NUMBER: NCT03112018.

HIV Infection Among Adolescents Residing in Urban Informal Settlements of Kenya.

Adolescents comprise approximately 15% of new HIV infections in Kenya. Impoverished living conditions in informal settlements place residents at high risk for HIV infection. We assessed factors associated with HIV infection among adolescents residing in urban informal settlements in Kisumu. We recruited 3,061 adolescent boys and girls aged 15-19. HIV prevalence was 2.5% overall, all newly identified cases were among girls and infection was positively associated with not completing a secondary education (p < .001). Girls who had ever been pregnant (p < .001) or out-of-school without completing a secondary education (p < .001) were more likely to be HIV-positive. Our findings of higher HIV prevalence among adolescent girls who had been pregnant or did not complete secondary school highlight the need to facilitate access to HIV testing, HIV pre-exposure prophylaxis, and sexual and reproductive health services as components of a comprehensive prevention strategy to decrease HIV infections in this priority population.

Deciphering the Path of S-nitrosation of Human Thioredoxin: Evidence of an Internal NO Transfer and Implication for the Cellular Responses to NO.

Nitric oxide (NO) is a free radical with a signaling capacity. Its cellular functions are achieved mainly through S-nitrosation where thioredoxin (hTrx) is pivotal in the S-transnitrosation to specific cellular targets. In this study, we use NMR spectroscopy and mass spectrometry to follow the mechanism of S-(trans)nitrosation of hTrx. We describe a site-specific path for S-nitrosation by measuring the reactivity of each of the 5 cysteines of hTrx using cysteine mutants. We showed the interdependence of the three cysteines in the nitrosative site. C73 is the most reactive and is responsible for all S-transnitrosation to other cellular targets. We observed NO internal transfers leading to C62 S-nitrosation, which serves as a storage site for NO. C69-SNO only forms under nitrosative stress, leading to hTrx nuclear translocation.

Seeking a "Sponyo": Insights Into Motivations and Risks Around Intergenerational Transactional Sex Among Adolescent Boys and Girls in Kenya.

PURPOSE: Intergenerational transactional sex (ITS) occurs in Sub-Saharan Africa within the context of widespread poverty and limited employment opportunities. We examined how adolescents describe these relationships, why their peers engage in ITS, and what repercussions adolescents shoulder as a result. METHODS: We conducted 14 focus group discussions with boys and girls (N = 120) aged 15-19 years in informal settlement communities in Kisumu, Kenya. We used a framework approach to guide data analysis. RESULTS: Adolescents referred to a relatively well-off older partner in ITS relationships as a "sponsor." Poverty proved the main driver of ITS. Boys and girls noted family and peer pressure to have a "better life" via sponsors who provided for three levels of need: urgent (e.g., food), critical (e.g., school fees), and material (e.g., clothes). Adolescents described multiple risks, including "no power" to negotiate condom use. Repercussions included dropping out of school because of community stigma, "abandonment" in the event of pregnancy, and unsafe abortions. CONCLUSIONS: Adolescents face the difficult choice between the need for money to contribute to their families' income and the discomfort and health risks of a sponsor relationship. The pressure to have a sponsor was higher among out-of-school adolescents and adolescent mothers because of heightened poverty and vulnerability. Structural interventions, such as eliminating school fees, could help reduce adolescents' perceived need to acquire sponsors. Our findings suggest a need to update guidelines for sexual and reproductive health counseling in schools and community settings to openly discuss why ITS is so commonplace and engage in risk reduction conversations with adolescents.

Working with what you have: How the East Africa Preterm Birth Initiative used gestational age data from facility maternity registers.

OBJECTIVE: Preterm birth is the primary driver of neonatal mortality worldwide, but it is defined by gestational age (GA) which is challenging to accurately assess in low-resource settings. In a commitment to reducing preterm birth while reinforcing and strengthening facility data sources, the East Africa Preterm Birth Initiative (PTBi-EA) chose eligibility criteria that combined GA and birth weight. This analysis evaluated the quality of the GA data as recorded in maternity registers in PTBi-EA study facilities and the strength of the PTBi-EA eligibility criteria. METHODS: We conducted a retrospective analysis of maternity register data from March-September 2016. GA data from 23 study facilities in Migori, Kenya and the Busoga Region of Uganda were evaluated for completeness (variable present), consistency (recorded versus calculated GA), and plausibility (falling within the 3rd and 97th birth weight percentiles for GA of the INTERGROWTH-21st Newborn Birth Weight Standards). Preterm birth rates were calculated using: 1) recorded GA <37 weeks, 2) recorded GA <37 weeks, excluding implausible GAs, 3) birth weight <2500g, and 4) PTBi-EA eligibility criteria of <2500g and between 2500g and 3000g if the recorded GA is <37 weeks. RESULTS: In both countries, GA was the least recorded variable in the maternity register (77.6%). Recorded and calculated GA (Kenya only) were consistent in 29.5% of births. Implausible GAs accounted for 11.7% of births. The four preterm birth rates were 1) 14.5%, 2) 10.6%, 3) 9.6%, 4) 13.4%. CONCLUSIONS: Maternity register GA data presented quality concerns in PTBi-EA study sites. The PTBi-EA eligibility criteria of <2500g and between 2500g and 3000g if the recorded GA is <37 weeks accommodated these concerns by using both birth weight and GA, balancing issues of accuracy and completeness with practical applicability.

Effect of a quality improvement package for intrapartum and immediate newborn care on fresh stillbirth and neonatal mortality among preterm and low-birthweight babies in Kenya and Uganda: a cluster-randomised facility-based trial.

BACKGROUND: Although gains in newborn survival have been achieved in many low-income and middle-income countries, reductions in stillbirth and neonatal mortality have been slow. Prematurity complications are a major driver of stillbirth and neonatal mortality. We aimed to assess the effect of a quality improvement package for intrapartum and immediate newborn care on stillbirth and preterm neonatal survival in Kenya and Uganda, where evidence-based practices are often underutilised. METHODS: This unblinded cluster-randomised controlled trial was done in western Kenya and eastern Uganda at facilities that provide 24-h maternity care with at least 200 births per year. The study assessed outcomes of low-birthweight and preterm babies. Eligible facilities were pair-matched and randomly assigned (1:1) into either the intervention group or the control group. All facilities received maternity register data strengthening and a modified WHO Safe Childbirth Checklist; facilities in the intervention group additionally received provider mentoring using PRONTO simulation and team training as well as quality improvement collaboratives. Liveborn or fresh stillborn babies who weighed between 1000 g and 2500 g, or less than 3000 g with a recorded gestational age of less than 37 weeks, were included in the analysis. We abstracted data from maternity registers for maternal and birth outcomes. Follow-up was done by phone or in person to identify the status of the infant at 28 days. The primary outcome was fresh stillbirth and 28-day neonatal mortality. This trial is registered with ClinicalTrials.gov, NCT03112018. FINDINGS: Between Oct 1, 2016, and April 30, 2019, 20 facilities were randomly assigned to either the intervention group (n=10) or the control group (n=10). Among 5343 eligible babies in these facilities, we assessed outcomes of 2938 newborn and fresh stillborn babies (1447 in the intervention and 1491 in the control group). 347 (23%) of 1491 infants in the control group were stillborn or died in the neonatal period compared with 221 (15%) of 1447 infants in the intervention group at 28 days (odds ratio 0·66, 95% CI 0·54-0·81). No harm or adverse effects were found. INTERPRETATION: Fresh stillbirth and neonatal mortality among low-birthweight and preterm babies can be decreased using a package of interventions that reinforces evidence-based practices and invests in health system strengthening. FUNDING: Bill & Melinda Gates Foundation.

Animal models for radiation injury, protection and therapy.

Current events throughout the world underscore the growing threat of different forms of terrorism, including radiological or nuclear attack. Pharmaceutical products and other approaches are needed to protect the civilian population from radiation and to treat those with radiation-induced injuries. In the event of an attack, radiation exposures will be heterogeneous in terms of both dose and quality, depending on the type of device used and each victim's location relative to the radiation source. Therefore, methods are needed to protect against and treat a wide range of early and slowly developing radiation-induced injuries. Equally important is the development of rapid and accurate biodosimetry methods for estimating radiation doses to individuals and guiding clinical treatment decisions. Acute effects of high-dose radiation include hematopoietic cell loss, immune suppression, mucosal damage (gastrointestinal and oral), and potential injury to other sites such as the lung, kidney and central nervous system (CNS). Long-term effects, as a result of both high- and low-dose radiation, include dysfunction or fibrosis in a wide range of organs and tissues and cancer. The availability of appropriate types of animal models, as well as adequate numbers of animals, is likely to be a major bottleneck in the development of new or improved radioprotectors, mitigators and therapeutic agents to prevent or treat radiation injuries and of biodosimetry methods to measure radiation doses to individuals.

Lymphatic function and the immune response to microbial or viral infection.

The National Institute of Allergy and Infectious Diseases (NIAID) is the primary institute within the National Institutes of Health (NIH) that conducts and supports basic and applied research to better understand, treat, and ultimately prevent infectious, immunologic, and allergic diseases. For more than 60 years, NIAID research has led to new therapies, vaccines, diagnostic tests, and other technologies that have improved the health of millions of people in the United States and around the world.