The Role of Maternal Secretor Status and Human Milk Oligosaccharides on Early Childhood Development: A Systematic Review and Meta-Analysis.

Background: Breast milk is the gold standard of infant nutrition, delivering nutrients and bioactive molecules as needed to support optimal infant growth and cognitive development. Increasing evidence links human milk oligosaccharides (HMOs) to these early childhood development milestones. Aims: To summarize and synthesize the evidence relating to HMOs and infant brain development, physical growth, and cognitive development. In addition, HMO concentrations in secretor and nonsecretor mothers were compared via a meta-analysis. Study Design: A systematic review and meta-analysis were carried out in accordance with the PRISMA statement. This review used three databases (PubMed, Scopus, and Web of Science) and was limited to English-language articles published between 2000 and June 30, 2023. Results: The initial searches yielded 245 articles, 27 of which were included in the systematic review and 12 in the meta-analysis. The meta-analysis revealed a substantial between-study heterogeneity, I2 = 97.3%. The pooled effect was 0.21 (95% CI: -0.41 to 0.83; p = 0.484), indicating that secretors had higher HMO concentrations, although this difference was not statistically significant. At one month of age, 2'FL, 3FL, and 3'SL play an important role in brain maturation and thus play a critical role in cognitive development. Secretors produce higher concentrations of 2'FL and 3'SL, explaining the benefits to infants of secretor mothers. Growth velocity was correlated to fucosylated and sialylated HMO concentrations, with lower concentrations linked to stunting. Conclusions: According to evidence from the systematically reviewed articles, HMOs are essential for a child's early development, but the extent to which they have an impact depends on maternal secretor status.

Risk factors of adverse birth outcomes among a cohort of pregnant women in Coastal Kenya, 2017-2019.

INTRODUCTION: Adverse birth outcomes particularly preterm births and congenital anomalies, are the leading causes of infant mortality globally, and the burden is highest in developing countries. We set out to determine the frequency of adverse birth outcomes and the risk factors associated with such outcomes in a cohort of pregnant women in Kenya. METHODS: From October 2017 to July 2019, pregnant women < 28 weeks gestation were enrolled and followed up until delivery in three hospitals in coastal Kenya. Newborns were examined at delivery. Among women with birth outcome data, we assessed the frequency of congenital anomalies defined as gastroschisis, umbilical hernia, limb abnormalities and Trisomy 21, and adverse birth outcomes, defined as either stillbirth, miscarriage, preterm birth, small for gestational age, or microcephaly. We used log-binomial regression to identify maternal characteristics associated with the presence of at least one adverse outcome. RESULTS: Among the 2312 women enrolled, 1916 (82.9%) had birth outcome data. Overall, 402/1916 (20.9%; 95% confidence interval (CI): 19.1-22.8) pregnancies had adverse birth outcomes. Specifically, 66/1916 (3.4%; 95% CI: 2.7-4.4) were stillbirths, 34/1916 (1.8%; 95% CI: 1.2-2.4) were miscarriages and 23/1816 (1.2%; 95% CI: 0.8-1.9) had congenital anomalies. Among the participants with anthropometric measurements data, 142/1200 (11.8%; 95% CI: 10.1 - 13.8) were small for gestational age and among the participants with ultrasound records, 143/1711 (8.4%; 95% CI: 7.1-9.8) were preterm. Febrile illnesses in current pregnancy (adjusted risk ratio (aRR): 1.7; 95% CI: 1.1-2.8), a history of poor birth outcomes in prior pregnancy (aRR: 1.8; 95% CI: 1.3-2.4) and high blood pressure in pregnancy (aRR: 3.9, 95% CI: (1.7-9.2) were independently associated with adverse birth outcomes in a model that included age, education, human immunodeficiency virus status and high blood pressure at enrolment. CONCLUSION: We found similar rates of overall adverse birth outcomes, congenital anomalies, and small for gestational age but higher rates of stillbirths and lower rates of prematurity compared to the rates that have been reported in the sub-Saharan Africa region. However, the rates of adverse birth outcomes in this study were comparable to other studies conducted in Kenya. Febrile illnesses during the current pregnancy, previous history of poor birth outcomes and high blood pressure in pregnancy are predictive of an increased risk of adverse birth outcomes.

Factors associated with viral load non-suppression among treatment-experienced pre-teenage children living with HIV in Kenya: a nationwide population-based cohort study, 2015-2021.

Background: Viral load non-suppression (VLNS) in children is a major public health concern because of attendant HIV disease progression and risk of morbidity and mortality. Based on a nationally representative database we present estimates of the prevalence, trends and factors associated with VLNS in Kenyan pre-teenage children between 2015 and 2021. Methods: Kenya National AIDS & STI Control Program's (NASCOP) maintains an early infant diagnosis and viral load (EID/VL) database for all persons living with HIV who are enrolled in the country's primary care clinics for purposes of monitoring progress towards achievement of the 95% viral suppression goals. Participants were eligible if they were children living with HIV (CLHIV), on combination ART (cART) treatment, and ≤12 years old. The modified Mann-Kendall trend test for serially correlated data was used to identify VLNS trends. Generalized estimating equations (GEE) with a logit link was used to assess the effects of covariates on the odds of VLNS (VL ≥1,000 copies/mL) over repeated points in time, allowing for the correlation among the repeated measures. Findings: Between January 2015 and December 2021, 508,743 viral load tests were performed on samples collected from 109,682 pre-teenage children. The prevalence of VLNS decreased from 22.9% (95% CI 22.4-23.3) to 12.5% (95% CI 12.1-12.9), p < 0.0001, and mean age increased from 3.1 (4.2) to 8.0 (3.2) years in 2015 and 2021 respectively. A modified Mann-Kendall trend test for serially correlated data denotes a statistically significant decreasing trend (τ = -0.300, p < 0.0001) over the study period. In the multivariable GEE analysis adjusted for covariates, the odds of VLNS decreased by 11% per year during the study period, (GEE-aOR 0.89, 95% CI 0.88-0.90; p < 0.0001). Factors positively associated with VLNS were EFV/NVP-based first-line cART regimen (GEE-aOR 1.74, 95% CI 1.65-1.84, p < 0.0001), PI-based cART regimen (GEE-aOR 1.82, 95% CI 1.72-1.92, p < 0.0001), and children aged 1-3 years (toddlers) (GEE-aOR: 1.84, 95% CI 1.79-1.90, p < 0.0001). On the contrary, DTG-based cART regimen, were negatively associated with VLNS (GEE-aOR 0.70, 95% CI 0.65-0.75, p < 0.0001). Interpretation: There is a strong evidence of decreasing viremia between 2015 and 2021. To sustain the decreasing trend, accelerating the switch from the suboptimal EVP/NVP first-line regimen to optimised DTG regimen is warranted. Funding: U.S. President's Emergency Plan for AIDS Relief (PEPFAR) and Clinton Health Access Initiative (CHAI).

Mothers' Willingness to Use Workplace Lactation Supports: Evidence from Formally Employed Mothers in Central Kenya.

Background: Formally employed mothers are vulnerable to early cessation of exclusive breastfeeding. Kenyan national policy requires employer-provided maternity benefits and workplace lactation supports. Objective: The objective of this study was to evaluate willingness to use nationally mandated workplace lactation supports among formally employed women in Kenya. Methods: We conducted a cross-sectional survey among 304 mothers of children ages ≤12 mo in Naivasha, Kenya, who were currently formally employed and employed before delivery of the most recent child to assess availability of and willingness to use current and potential future workplace lactation supports. Results: The most available reported workplace lactation supports were schedule flexibility to arrive late or leave early (87.8%) or visit a child to nurse during lunch (24.7%), followed by company-funded community-based daycare (7.6%). Few (<4.0%) reported the availability of lactation rooms, on-site daycares, transportation to breastfeed during lunch, refrigerators for expressed milk, or manual or electric breastmilk pumps. If made available, >80% of mothers reported moderate or strong willingness to use flexible schedules to arrive late or leave early, break during lunch, and transportation to visit a child to nurse. A moderate proportion reported strong willingness to use on-site daycares (63.8%), company-funded community-based daycare (56.9%), on-site lactation rooms (60.5%), refrigeration for expressed milk (49.3%), manual (40.5%), and electric pumps (27.6%). Mothers expressed fear of missing production targets and reported more willingness to use on-site compared with off-site daycare to save transportation time but noted concerns about chemical exposures and early arrival times with young infants. Hesitations regarding the use of on-site lactation rooms included concerns about privacy, milk identification and storage, and use and sharing of pumps. Conclusions: Flexible schedules were the workplace lactation supports in highest demand among formally employed mothers. Maternal willingness to use lactation rooms, refrigeration, and pumping equipment was moderate to low, suggesting sensitization may help to increase demand as the implementation of Kenyan policies moves forward.

Understanding sexual behaviors of youth from the lens of caregivers, teachers, local leaders and youth in Homabay County, Kenya.

In Kenya similar to other countries in Eastern and Southern Africa There is a disproportionately high burden of the global HIV incidence among youth ages 15-24 years, and where adolescent girls and young women account for up to a third of all incident HIV infections and more than double the burden of HIV compared to their male peers. Previous work has shown early sexual debut as entry point into risks to sexual and reproductive health among young people including STI/HIV acquisition. This was a formative assessment of the local context of three sexual risk behaviors among youth ages of 15-24 years: early sexual debut, multiple sexual partnerships, and age-mixing /intergenerational sex for purposes of informing comprehensive combination HIV intervention program design. We conducted a cross-sectional formative qualitative study in four sub-counties within Homabay county a high HIV prevalence region of Kenya. Participants were recruited through youth groups, schools, government offices and, community gatekeepers using approved fliers, referred to a designated venue for focus group discussion (FGD). After oral informed consent, twelve FGDs of 8-10 participants were carried out. Transcripts and field notes were uploaded to Atlas.ti qualitative data analysis and research software (version 8.0, 2017, ATLAS.ti GmbH). Open coding followed by grouping, categorization of code groups, and thematic abstraction was used to draw meaning for the data. A total of 111 youth participated in the FGD, 65 males and 46 females. The main findings were that youth engaged in early sex for fear of being labeled 'odd' by their peers, belief (among both male and female) that 'practice makes perfect', curiosity about sex, media influence, need to prove if one can father a child (among male), the notion that sex equals love with some of the youth using this excuse to coerce their partners into premature sex, and the belief that sex is a human right and parents/guardians should not intervene. Male youth experienced more peer-pressure to have sex earlier. Female youths cited many reasons to delay coitarche that included fear of pregnancy, burden of taking care of a baby, and religious doctrines. Having multiple sexual partners and intergenerational sexual relationships were common among the youth driven by perceived financial gain and increased sexual prowess. HIV prevention strategies need to address gender vulnerabilities, as well as promoting a protective environment, hence application of combination prevention methods is a viable solution to the HIV pandemic.Trial registration number: The study was approved by the KNH/UoN Ethics review committee (KNH/UoN ERC-P73/03/2011) and New York University (NYU Reg no.-00000310).

Passively Acquired Constant Region 5-Specific Antibodies Associated With Improved Survival in Infants Who Acquire Human Immunodeficiency Virus.

Studying vertical human immunodeficiency virus (HIV) transmission enables the impact of passively transferred antibodies on HIV transmission and pathogenesis to be examined. Using phage display of HIV envelope peptides and peptide enzyme-linked immunosorbent assay (ELISA), we found that, in infants who acquired HIV, passive antibody responses to constant region 5 (C5) were associated with improved survival in 2 cohorts. In a combined analysis, C5 peptide ELISA activity was correlated directly with survival and estimated infection time and inversely with set point viral load. These results suggest that preexisting C5-specific antibodies may be correlated with the survival of infants living with HIV, motivating additional research into their protective potential.

Age and CD4+ T cell counts are inversely associated with HIV drug resistance mutations in treatment naive female sex workers.

The increasing prevalence of human immunodeficiency virus (HIV) drug resistance mutations (HIVDRM) in untreated seropositive persons has consequences for future treatment options. This is extremely important in key populations such as female sex workers (FSWs), where the prevalence of pretreatment drug resistance (PDR) and associated risk factors are unknown. In this study, we analyzed PDR and associated risk factors in recently diagnosed and treatment-naive FSWs in Nairobi, Kenya. In this cross-sectional study, we used 64 HIV-seropositive plasma samples collected from FSWs between November 2020 and April 2021. To identify HIVDRM, the pol gene was amplified and genotyped using sanger sequencing. The effects of age, tropism, CD4+ T cell count, subtype, and location on HIVDRM counts were examined using Poisson regression. Overall, the prevalence of PDR was 35.9% (95% CI: 24.3-48.9), which was strongly influenced by K103N and M184V mutations, which confer resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTI), respectively. Subtype A1 was predominant followed by subtype D with a notable increase in inter-subtype recombinants. We found statistically significant evidence that age was inversely related to HIVDRM. A FSW who is 1 year older had 12% less HIVDRM (incidence rate ratios [IRR]: 0.88; 95% CI: 0.82-0.95; P < .001), after adjusting for CD4+ T cell count, subtype, location, and tropism. Similarly, an increase in CD4+ T cell count by 1 unit, was associated with 0.4% fewer HIVDRM (IRR: 0.996; 95% CI: 0.994-0.998; P = .001), while controlling for the other variables. HIV-1 tropism was not associated with HIVDRM counts. In conclusion, our findings show a high prevalence of NNRTIs. Lower CD4+ T cell counts and younger age were significant risk factors that influenced HIVDRM loads. This finding underscores the relevance of targeted interventions and the importance of continuing to focus on FSWs as a way of addressing the HIV epidemic.

Reconstruction of a polyclonal ADCC antibody repertoire from an HIV-1 non-transmitting mother.

Human natural history and vaccine studies support a protective role of antibody dependent cellular cytotoxicity (ADCC) activity against many infectious diseases. One setting where this has consistently been observed is in HIV-1 vertical transmission, where passively acquired ADCC activity in HIV-exposed infants has correlated with reduced acquisition risk and reduced pathogenesis in HIV+ infants. However, the characteristics of HIV-specific antibodies comprising a maternal plasma ADCC response are not well understood. Here, we reconstructed monoclonal antibodies (mAbs) from memory B cells from late pregnancy in mother MG540, who did not transmit HIV to her infant despite several high-risk factors. Twenty mAbs representing 14 clonal families were reconstructed, which mediated ADCC and recognized multiple HIV Envelope epitopes. In experiments using Fc-defective variants, only combinations of several mAbs accounted for the majority of plasma ADCC of MG540 and her infant. We present these mAbs as evidence of a polyclonal repertoire with potent HIV-directed ADCC activity.

Perinatal care and breastfeeding education during the COVID-19 pandemic: Perspectives from Kenyan mothers and healthcare workers.

The impact of the COVID-19 pandemic on breastfeeding (BF) practices in low- and middle-income countries (LMICs) is not well understood. Modifications in BF guidelines and delivery platforms for breastfeeding education during the COVID-19 pandemic are hypothesised to have affected BF practices. We aimed to understand the experiences with perinatal care, BF education and practice among Kenyan mothers who delivered infants during the COVID-19 pandemic. We conducted in-depth key informant interviews with 45 mothers who delivered infants between March 2020 and December 2021, and 26 health care workers (HCW) from four health facilities in Naivasha, Kenya. While mothers noted that HCWs provided quality care and BF counselling, individual BF counselling was cited to be less frequent than before the pandemic due to altered conditions in health facilities and COVID-19 safety protocols. Mothers stated that some HCW messages emphasised the immunologic importance of BF. However, knowledge among mothers about the safety of BF in the context of COVID-19 was limited, with few participants reporting specific counselling or educational materials on topics such as COVID-19 transmission through human milk and the safety of nursing during a COVID-19 infection. Mothers described COVID-19-related income loss and lack of support from family and friends as the major challenge to practising exclusive breastfeeding (EBF) as they wished or planned. COVID-19 restrictions limited or prevented mothers' access to familial support at facilities and at home, causing them stress and fatigue. In some cases, mothers reported job loss, time spent seeking new means of employment and food insecurity as causes for milk insufficiency, which contributed to mixed feeding before 6 months. The COVID-19 pandemic created changes to the perinatal experience for mothers. While messages about the importance of practising EBF were provided, altered HCW education delivery methods, reduced social support and food insecurity limit EBF practices for mothers in this context.

The Systems Analysis and Improvement Approach: specifying core components of an implementation strategy to optimize care cascades in public health.

BACKGROUND: Healthcare systems in low-resource settings need simple, low-cost interventions to improve services and address gaps in care. Though routine data provide opportunities to guide these efforts, frontline providers are rarely engaged in analyzing them for facility-level decision making. The Systems Analysis and Improvement Approach (SAIA) is an evidence-based, multi-component implementation strategy that engages providers in use of facility-level data to promote systems-level thinking and quality improvement (QI) efforts within multi-step care cascades. SAIA was originally developed to address HIV care in resource-limited settings but has since been adapted to a variety of clinical care systems including cervical cancer screening, mental health treatment, and hypertension management, among others; and across a variety of settings in sub-Saharan Africa and the USA. We aimed to extend the growing body of SAIA research by defining the core elements of SAIA using established specification approaches and thus improve reproducibility, guide future adaptations, and lay the groundwork to define its mechanisms of action. METHODS: Specification of the SAIA strategy was undertaken over 12 months by an expert panel of SAIA-researchers, implementing agents and stakeholders using a three-round, modified nominal group technique approach to match core SAIA components to the Expert Recommendations for Implementing Change (ERIC) list of distinct implementation strategies. Core implementation strategies were then specified according to Proctor's recommendations for specifying and reporting, followed by synthesis of data on related implementation outcomes linked to the SAIA strategy across projects. RESULTS: Based on this review and clarification of the operational definitions of the components of the SAIA, the four components of SAIA were mapped to 13 ERIC strategies. SAIA strategy meetings encompassed external facilitation, organization of provider implementation meetings, and provision of ongoing consultation. Cascade analysis mapped to three ERIC strategies: facilitating relay of clinical data to providers, use of audit and feedback of routine data with healthcare teams, and modeling and simulation of change. Process mapping matched to local needs assessment, local consensus discussions and assessment of readiness and identification of barriers and facilitators. Finally, continuous quality improvement encompassed tailoring strategies, developing a formal implementation blueprint, cyclical tests of change, and purposefully re-examining the implementation process. CONCLUSIONS: Specifying the components of SAIA provides improved conceptual clarity to enhance reproducibility for other researchers and practitioners interested in applying the SAIA across novel settings.

Bioequivalence of micronutrient powders to Corn-soy Blend on serum zinc concentration of children (6-36 months) with Moderate Acute Malnutrition in Thika urban slums, Kenya: A cluster-randomized controlled trial.

Zinc deficiency is common among children with Moderate Acute Malnutrition (MAM) and contributes to growth failure, increased morbidity and mortality. Diarrhoea and poor dietary practices are the main causes of zinc deficiency. Corn-soy Blend (CSB), the standard product in management of children with MAM has a limitation of poor micronutrient bioavailability. Micronutrient powders (MNPs) which are added at the point of consumption have a potential in improving micronutrient status however, scientific evidence on efficacy on improving the zinc status is scarce. A cluster-randomized clinical trial was designed to establish bioequivalence of MNPs to CSB on serum zinc status among children (6-36 months) with MAM in Thika informal settlements, Kenya. Sample size was calculated to show bioequivalence within ±20% limit. Twelve villages were randomized to four study groups. Three experimental groups received different formulations of MNPs added to unfortified CSB porridge as; multiple micronutrients containing zinc (CSB-MNP-A n = 84), multiple micronutrients without zinc (CSB-MNP-B n = 88) and zinc only (CSB-MNP-C n = 94). Control group (n = 80) received standard CSB fortified with multiple micronutrients. Standard amount of CSB was consumed in feeding centres for six months. Serum zinc concentration was assessed pre- and post-intervention. Data was analyzed based on treatment assignment regardless of adherence and drop-out status. Mixed effects linear regression was used to model pre-post change in serum zinc concentration, adjusting for clustering effect and baseline differences. Bioequivalence was assessed using two one-sided t-tests. At baseline, 84.4% were zinc deficient (serum zinc <65µg/dL) and zinc intake was sub-optimal (<3 mg/day) for 95.7% of children. Mean change in serum zinc concentration was significantly higher (p = 0.024) in CSB-MNP-A (18.7 ± 2.1) µg/dL compared to control group (11.8 ± 2.6 µg/dL). MNPs are not bioequivalent to CSB within the ±20% bioequivalence limit. MNPs are more effective in improving serum zinc status compared to CSB. Trials with larger sample sizes are recommended to validate the current findings. Trial registration: Pan African Clinical Trials Registry: PACTR201907492232376.

Prevalence of microcephaly and Zika virus infection in a pregnancy cohort in Kenya, 2017-2019.

BACKGROUND: Zika virus (ZIKV), first discovered in Uganda in 1947, re-emerged globally in 2013 and was later associated with microcephaly and other birth defects. We determined the incidence of ZIKV infection and its association with adverse pregnancy and fetal outcomes in a pregnancy cohort in Kenya. METHODS: From October 2017 to July 2019, we recruited and followed up women aged ≥ 15 years and ≤ 28 weeks pregnant in three hospitals in coastal Mombasa. Monthly follow-up included risk factor questions and a blood sample collected for ZIKV serology. We collected anthropometric measures (including head circumference), cord blood, venous blood from newborns, and any evidence of birth defects. Microcephaly was defined as a head circumference (HC) < 2 standard deviations (SD) for sex and gestational age. Severe microcephaly was defined as HC < 3 SD for sex and age. We tested sera for anti-ZIKV IgM antibodies using capture enzyme-linked immunosorbent assay (ELISA) and confirmed positives using the plaque reduction neutralization test (PRNT90) for ZIKV and for dengue (DENV) on the samples that were ZIKV neutralizing antibody positive. We collected blood and urine from participants reporting fever or rash for ZIKV testing. RESULTS: Of 2889 pregnant women screened for eligibility, 2312 (80%) were enrolled. Of 1916 recorded deliveries, 1816 (94.6%) were live births and 100 (5.2%) were either stillbirths or spontaneous abortions (< 22 weeks of gestation). Among 1236 newborns with complete anthropometric measures, 11 (0.9%) had microcephaly and 3 (0.2%) had severe microcephaly. A total of 166 (7.2%) participants were positive for anti-ZIKV IgM, 136 of whom became seropositive during follow-up. Among the 166 anti-ZIKV IgM positive, 3 and 18 participants were further seropositive for ZIKV and DENV neutralizing antibodies, respectively. Of these 3 and 18 pregnant women, one and 13 (72.2%) seroconverted with antibodies to ZIKV and DENV, respectively. All 308 samples (serum and urine samples collected during sick visits and samples that were anti-ZIKV IgM positive) tested by RT-PCR were negative for ZIKV. No adverse pregnancy or neonatal outcomes were reported among the three participants with confirmed ZIKV exposure. Among newborns from pregnant women with DENV exposure, four (22.2%) were small for gestational age and one (5.6%) had microcephaly. CONCLUSIONS: The prevalence of severe microcephaly among newborns in coastal Kenya was high relative to published estimates from facility-based studies in Europe and Latin America, but little evidence of ZIKV transmission. There is a need for improved surveillance for microcephaly and other congenital malformations in Kenya.

Developing an Unstructured Supplementary Service Data-based mobile phone app to provide adolescents with sexual reproductive health information: a human-centered design approach.

BACKGROUND: Adolescent pregnancies and sexually-transmitted infections continue to impact 15 - 19-year-olds across the globe. The lack of sexual reproductive health information (SRH) in resource-limited settings due to cultural and societal attitudes towards adolescent SRH could be contributing to the negative outcomes. Innovative approaches, including mobile phone technologies, are needed to address the need for reliable adolescent SRH information. OBJECTIVE: The study aimed to co-design a Unstructured Supplementary Service Data (USSD) based mobile app prototype to provide confidential adolescent SRH information on-demand and evaluate the mobile app's usability and user experience. METHODS: A human-centered design methodology was applied. This practice framework allowed the perspectives and feedback of adolescent users to be included in the iterative design process. To participate, an adolescent must have been 15 to 19 years old, resided in Kibra and would be able to access a mobile phone. Adolescents were enrolled for the alpha and field testing of the app prototype at different time-points. The Mobile Application Rating Scale (MARS) a multidimensional mobile phone evaluation tool was used to access the functionality, engagement, aesthetics and quality of information in the app. Responses from the MARS were reported as mean scores for each category and a mean of the aggregate scores making the app's quality score. The MARS data was also evaluated as categorical data, A Chi square test of independence was carried out to show significance of any observed differences using cumulative and inverse cumulative distribution functions. RESULTS: During the usability test, 62/109 (54.9%) of the adolescents that were followed-up had used the app at least once, 30/62 (48.4%) of these were male participants and 32/62 (51.6%) female. On engagement, the app had a mean score of 4.3/5 (SD 0.44), 4.6/5 (SD 0.38) on functionality, 4.3/5 (SD 0.57) on aesthetics and 4.4/5 (SD 0.60) on the quality of information. The overall app quality mean score was 4.4/5 (SD 0.31). The app was described as 'very interesting' to use by 44/62 (70.9%) of the participants, 20/44 males and 24/44 females. The content was deemed to be either 'perfectly' or 'well targeted' on sexual reproductive health by 60/62 (96.7%) adolescents, and the app was rated 'best app' by 45/62 (72.6%) adolescents, 27/45 females and 18/45 males, with a p-value = 0.011. CONCLUSIONS: Adolescents need on-demand, accurate and trusted SRH information. A mobile phone app is a feasible and acceptable way to deliver adolescent SRH information in resource-limited settings. The USSD mobile phone technology shows promise in the delivery of much needed adolescent SRH information on-demand..

Providing "a beam of light to see the gaps": determinants of implementation of the Systems Analysis and Improvement Approach applied to the pediatric and adolescent HIV cascade in Kenya.

BACKGROUND: Children and adolescents living with HIV have poorer rates of HIV testing, treatment, and virologic suppression than adults. Strategies that use a systems approach to optimize these multiple, linked steps simultaneously are critical to close these gaps. METHODS: The Systems Analysis and Improvement Approach (SAIA) was adapted and piloted for the pediatric and adolescent HIV care and treatment cascade (SAIA-PEDS) at 6 facilities in Kenya. SAIA-PEDS includes three tools: continuous quality improvement (CQI), flow mapping, and pediatric cascade analysis (PedCAT). A predominately qualitative evaluation utilizing focus group discussions (N = 6) and in-depth interviews (N = 19) was conducted with healthcare workers after implementation to identify determinants of implementation. Data collection and analysis were grounded in the Consolidated Framework for Implementation Research (CFIR). RESULTS: Overall, the adapted SAIA-PEDS strategy was acceptable, and the three tools complemented one another and provided a relative advantage over existing processes. The flow mapping and CQI tools were compatible with existing workflows and resonated with team priorities and goals while providing a structure for group problem solving that transcended a single department's focus. The PedCAT was overly complex, making it difficult to use. Leadership and hierarchy were complex determinants. All teams reported supportive leadership, with some describing in detail how their leadership was engaged and enthusiastic about the SAIA-PEDS process, by providing recognition, time, and resources. Hierarchy was similarly complex: in some facilities, leadership stifled rapid innovation by insisting on approving each change, while at other facilities, leadership had strong and supportive oversight of processes, checking on the progress frequently and empowering teams to test innovative ideas. CONCLUSION: CQI and flow mapping were core components of SAIA-PEDS, with high acceptability and consistent use, but the PedCAT was too complex. Leadership and hierarchy had a nuanced role in implementation. Future SAIA-PEDS testing should address PedCAT complexity and further explore the modifiability of leadership engagement to maximize implementation.

Systems Analysis and Improvement Approach to optimize the pediatric and adolescent HIV Cascade (SAIA-PEDS): a pilot study.

INTRODUCTION: Children and adolescents lag behind adults in achieving UNAIDS 95-95-95 targets for HIV testing, treatment, and viral suppression. The Systems Analysis and Improvement Approach (SAIA) is a multi-component implementation strategy previously shown to improve the HIV care cascade for pregnant women and infants. SAIA merits adaptation and testing to reduce gaps in the pediatric and adolescent HIV cascade. METHODS: We adapted the SAIA strategy components to be applicable to the pediatric and adolescent HIV care cascade (SAIA-PEDS) in Nairobi and western Kenya. We tested whether this SAIA-PEDS strategy improved HIV testing, linkage to care, antiretroviral treatment (ART), viral load (VL) testing, and viral load suppression for children and adolescents ages 0-24 years at 5 facilities. We conducted a pre-post analysis with 6 months pre- and 6 months post-implementation strategy (coupled with an interrupted time series sensitivity analysis) using abstracted routine program data to determine changes attributable to SAIA-PEDS. RESULTS: Baseline levels of HIV testing and care cascade indicators were heterogeneous between facilities. Per facility, the monthly average number of children/adolescents attending outpatient and inpatient services eligible for HIV testing was 842; on average, 253 received HIV testing services, 6 tested positive, 6 were linked to care, and 5 initiated ART. Among those on treatment at the facility, an average of 15 had a VL sample taken and 13 had suppressed VL results returned. Following the SAIA-PEDS training and mentorship, there was no substantial or significant change in the ratio of HIV testing (RR: 0.803 [95% CI: 0.420, 1.532]) and linkage to care (RR: 0.831 [95% CI: 0.546, 1.266]). The ratio of ART initiation increased substantially and trended towards significance (RR: 1.412 [95% CI: 0.999, 1.996]). There were significant and substantial improvements in the ratio of VL tests ordered (RR: 1.939 [95% CI: 1.230, 3.055]) but no substantial or significant change in the ratio of VL results suppressed (RR: 0.851 [95% CI: 0.554, 1.306]). CONCLUSIONS: The piloted SAIA-PEDS implementation strategy was associated with increases in health system performance for indicators later in the HIV care cascade, but not for HIV testing and treatment indicators. This strategy merits further rigorous testing for effectiveness and sustainment.

An Unstructured Supplementary Service Data-Based mHealth App Providing On-Demand Sexual Reproductive Health Information for Adolescents in Kibra, Kenya: Randomized Controlled Trial.

BACKGROUND: Adolescents transitioning from childhood to adulthood need to be equipped with sexual reproductive health (SRH) knowledge, skills, attitudes, and values that empower them. Accessible, reliable, appropriate, and friendly information can be provided through mobile phone-based health interventions. OBJECTIVE: This study aims to investigate the effectiveness and impact of an Unstructured Supplementary Service Data (USSD)-based app in increasing adolescents' knowledge about contraceptives, gender-based stereotypes, sexually transmitted infections (STIs), abstinence, and perceived vulnerability, and helping adolescents make informed decisions about their SRH. METHODS: A randomized controlled trial (RCT) methodology was applied to investigate the potential of a USSD-based app for providing on-demand SRH information. To be eligible, adolescents aged 15 to 19 years residing in Kibra, Kenya, had to have access to a phone and be available for the 3-month follow-up visit. Participants were randomly assigned to the intervention (n=146) and control (n=154) groups using sequentially numbered, opaque, sealed envelopes. The primary outcome was improved SRH knowledge. The secondary outcome was improved decision-making on SRH. The outcomes were measured using validated tools on adolescent SRH and user perceptions during the follow-up visit. A paired sample t test was used to compare the changes in knowledge scores in both groups. The control group did not receive any SRH information. RESULTS: During the RCT, 54.9% (62/109) of adolescents used the USSD-based app at least once. The mean age by randomization group was 17.3 (SD 1.23) years for the control group and 17.3 (SD 1.12) years for the intervention group. There was a statistically significant difference in the total knowledge scores in the intervention group (mean 10.770, SD 2.012) compared with the control group (mean 10.170, SD 2.412) conditions (t179=2.197; P=.03). There was a significant difference in abstinence (P=.01) and contraceptive use (P=.06). Of the individuals who used the app, all participants felt the information received could improve decision-making regarding SRH. Information on STIs was of particular interest, with 27% (20/62) of the adolescents seeking information in this area, of whom 55% (11/20) were female. In relation to improved decision-making, 21.6% (29/134) of responses showed the adolescents were able to identify STIs and were likely to seek treatment; 51.7% (15/29) of these were female. Ease of use was the most important feature of the app for 28.3% (54/191) of the responses. CONCLUSIONS: Adolescents require accurate and up-to-date SRH information to guide their decision-making and improve health outcomes. As adolescents already use mobile phones in their day-to-day lives, apps provide an ideal platform for this information. A USSD-based app could be an appropriate tool for increasing SRH knowledge among adolescents in low-resource settings. Adolescents in the study valued the information provided because it helped them identify SRH topics on which they needed more information. TRIAL REGISTRATION: Pan African Clinical Trial Registry PACTR202204774993198; https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=22623.

Comparable Pregnancy Outcomes for HIV-Uninfected and HIV-Infected Women on Antiretroviral Treatment in Kenya.

BACKGROUND: The impact of human immunodeficiency virus (HIV) on pregnancy outcomes for women on antiretroviral therapy (ART) in sub-Saharan Africa remains unclear. METHODS: Pregnant women in Kenya were enrolled in the second trimester and followed up to delivery. We estimated effects of treated HIV with 3 pregnancy outcomes: loss, premature birth, and low birth weight and factors associated with HIV-positive status. RESULTS: Of 2113 participants, 311 (15%) were HIV infected and on ART. Ninety-one of 1762 (5%) experienced a pregnancy loss, 169/1725 (10%) a premature birth (<37 weeks), and 74/1317 (6%) had a low-birth-weight newborn (<2500 g). There was no evidence of associations between treated HIV infection and pregnancy loss (adjusted relative risk [aRR], 1.19; 95% confidence interval [CI], .65-2.16; P = .57), prematurity (aRR, 1.09; 95% CI, .70-1.70; P = .69), and low birth weight (aRR, 1.36; 95% CI, .77-2.40; P = .27). Factors associated with an HIV-positive status included older age, food insecurity, lower education level, higher parity, lower gestation at first antenatal clinic, anemia, and syphilis. Women who were overweight or underweight were less likely to be HIV infected compared to those with normal weight. CONCLUSIONS: Currently treated HIV was not significantly associated with adverse pregnancy outcomes. HIV-infected women, however, had a higher prevalence of other factors associated with adverse pregnancy outcomes.

Past intimate partner violence (IPV) predicts incident IPV during pregnancy and postpartum in pregnant women in Kisumu, Kenya.

OBJECTIVE: To investigate how identifying factors associated with peripartum and postpartum intimate partner violence (IPV) may facilitate prioritizing women for psychosocial support. METHODS: Pregnant women in Kenya were asked about IPV by their current partner at baseline (screening), during pregnancy and at 6 weeks and 6 months postpartum. IPV was defined as being physically hurt or forced to participate in sexual activities or being threatened or frightened by a partner. RESULTS: A total of 502 women (11.8% HIV-positive) enrolled during pregnancy and were successfully followed for 6 months postpartum, 430 (85.7%) reported never experiencing IPV, 32 (6.4%) reported IPV at least once in their lifetime but not in the past 6 months, and 31 (6.2%) reported IPV in the past 6 months but not in the past month. During pregnancy and postpartum, 61 (12.2%) reported incident IPV. Women who at baseline reported IPV in the past 6 months were at 2.7-fold higher odds of experiencing IPV peripartum and postpartum (odds ratio 2.77; 95% confidence interval 1.17-6.53; P = 0.020) compared with women who had never experienced IPV. This association remained significant in multivariable analysis. CONCLUSION: Screening for recent IPV during antenatal care visits may be an effective means to identify women at highest risk of IPV and offer targeted prevention interventions.

Net charge and position 22 of the V3 loop are associated with HIV-1 tropism in recently infected female sex workers in Nairobi, Kenya.

Human immunodeficiency virus (HIV) infection affects around 37 million people worldwide, and in Kenya, key populations especially female sex workers (FSW), are thought to play a substantial role in the wider, mostly heterosexual HIV-1 transmission structure. Notably, HIV tropism has been found to correlate with HIV-1 transmission and disease progression in HIV-infected patients. In this study, recently infected FSWs from Nairobi, Kenya, were assessed for HIV tropism and the factors related to it. We used a cross-sectional study design to analyze 76 HIV-1 positive plasma samples obtained from FSWs enrolled in sex worker outreach program clinics in Nairobi between November 2020 and April 2021. The effects of clinical, demographic, and viral genetic characteristics were determined using multivariable logistic regression. HIV-1 subtype A1 accounted for 89.5% of all cases, with a prevalence of CXCR4-tropic viruses of 26.3%. WebPSSMR5X4 and Geno2Pheno [G2P:10-15% false positive rate] showed high concordance of 88%. Subjects infected with CXCR4-tropic viruses had statistically significant lower baseline CD4+T-cell counts than those infected with CCR5-tropic viruses (P = .044). Using multivariable logistic regression and adjusting for potential confounders, we found that net charge, the amino acid at position 22 of the V3 loop, and the geographic location of the subject were associated with tropism. A unit increase in V3 loop's net-charge increased the odds of a virus being CXCR4-tropic by 2.4 times (OR = 2.40, 95%CI = 1.35-5.00, P = .007). Second, amino acid threonine at position 22 of V3 loop increased the odds of a strain being X4 by 55.7 times compared to the alanine which occurred in CCR5-tropic strains (OR = 55.7, 95%CI = 4.04-84.1, P < .003). The Kawangware sex worker outreach program clinic was associated with CXCR4-tropic strains (P = .034), but there was there was no evidence of a distinct CXCR4-tropic transmission cluster. In conclusion, this study revealed a high concordance of WebPSSMR5X4 and Geno2Pheno in predicting HIV tropism. The most striking finding was that amino acid position 22 of the V3 loop is linked to tropism in HIV-1 subtype A1. Additional studies with a large dataset are warranted to confirm our findings.