Characteristics of children readmitted with severe pneumonia in Kenyan hospitals.

BACKGROUND: Pneumonia is a leading cause of childhood morbidity and mortality. Hospital re-admission may signify missed opportunities for care or undiagnosed comorbidities. METHODS: We conducted a retrospective cohort study including children aged ≥ 2 months-14 years hospitalised with severe pneumonia between 2013 and 2021 in a network of 20 primary referral hospitals in Kenya. Severe pneumonia was defined using the 2013 World Health Organization criteria, and re-admission was based on clinical documentation from individual patient case notes. We estimated the prevalence of re-admission, described clinical management practices, and modelled risk factors for re-admission and inpatient mortality. RESULTS: Among 20,603 children diagnosed with severe pneumonia, 2,274 (11.0%, 95% CI 10.6-11.5) were readmitted. Re-admission was independently associated with age (12-59 months vs. 2-11 months: adjusted odds ratio (aOR) 1.70, 1.54-1.87; >5 years vs. 2-11 months: aOR 1.85, 1.55-2.22), malnutrition (weight-for-age-z-score (WAZ) <-3SD vs. WAZ> -2SD: aOR 2.05, 1.84-2.29); WAZ - 2 to -3 SD vs. WAZ> -2SD: aOR 1.37, 1.20-1.57), wheeze (aOR 1.17, 1.03-1.33) and presence of a concurrent neurological disorder (aOR 4.42, 1.70-11.48). Chest radiography was ordered more frequently among those readmitted (540/2,274 [23.7%] vs. 3,102/18,329 [16.9%], p < 0.001). Readmitted patients more frequently received second-line antibiotics (808/2,256 [35.8%] vs. 5,538/18,173 [30.5%], p < 0.001), TB medication (69/2,256 [3.1%] vs. 298/18,173 [1.6%], p < 0.001), salbutamol (530/2,256 [23.5%] vs. 3,707/18,173 [20.4%], p = 0.003), and prednisolone (157/2,256 [7.0%] vs. 764/18,173 [4.2%], p < 0.001). Inpatient mortality was 2,354/18,329 (12.8%) among children admitted with a first episode of severe pneumonia and 269/2,274 (11.8%) among those who were readmitted (adjusted hazard ratio (aHR) 0.93, 95% CI 0.82-1.07). Age (12-59 months vs. 2-11 months: aHR 0.62, 0.57-0.67), male sex (aHR 0.81, 0.75-0.88), malnutrition (WAZ <-3SD vs. WAZ >-2SD: aHR 1.87, 1.71-2.05); WAZ - 2 to -3 SD vs. WAZ >-2SD: aHR 1.46, 1.31-1.63), complete vaccination (aHR 0.74, 0.60-0.91), wheeze (aHR 0.87, 0.78-0.98) and anaemia (aHR 2.14, 1.89-2.43) were independently associated with mortality. CONCLUSIONS: Children readmitted with severe pneumonia account for a substantial proportion of pneumonia hospitalisations and deaths. Further research is required to develop evidence-based approaches to screening, case management, and follow-up of children with severe pneumonia, prioritising those with underlying risk factors for readmission and mortality.

Seroprevalence of Antibodies to Severe Acute Respiratory Syndrome Coronavirus 2 Among Healthcare Workers in Kenya.

BACKGROUND: Few studies have assessed the seroprevalence of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among healthcare workers (HCWs) in Africa. We report findings from a survey among HCWs in 3 counties in Kenya. METHODS: We recruited 684 HCWs from Kilifi (rural), Busia (rural), and Nairobi (urban) counties. The serosurvey was conducted between 30 July and 4 December 2020. We tested for immunoglobulin G antibodies to SARS-CoV-2 spike protein, using enzyme-linked immunosorbent assay. Assay sensitivity and specificity were 92.7 (95% CI, 87.9-96.1) and 99.0% (95% CI, 98.1-99.5), respectively. We adjusted prevalence estimates, using bayesian modeling to account for assay performance. RESULTS: The crude overall seroprevalence was 19.7% (135 of 684). After adjustment for assay performance, seroprevalence was 20.8% (95% credible interval, 17.5%-24.4%). Seroprevalence varied significantly (P < .001) by site: 43.8% (95% credible interval, 35.8%-52.2%) in Nairobi, 12.6% (8.8%-17.1%) in Busia and 11.5% (7.2%-17.6%) in Kilifi. In a multivariable model controlling for age, sex, and site, professional cadre was not associated with differences in seroprevalence. CONCLUSION: These initial data demonstrate a high seroprevalence of antibodies to SARS-CoV-2 among HCWs in Kenya. There was significant variation in seroprevalence by region, but not by cadre.

Malaria hospitalisation in East Africa: age, phenotype and transmission intensity.

BACKGROUND: Understanding the age patterns of disease is necessary to target interventions to maximise cost-effective impact. New malaria chemoprevention and vaccine initiatives target young children attending routine immunisation services. Here we explore the relationships between age and severity of malaria hospitalisation versus malaria transmission intensity. METHODS: Clinical data from 21 surveillance hospitals in East Africa were reviewed. Malaria admissions aged 1 month to 14 years from discrete administrative areas since 2006 were identified. Each site-time period was matched to a model estimated community-based age-corrected parasite prevalence to provide predictions of prevalence in childhood (PfPR2-10). Admission with all-cause malaria, severe malaria anaemia (SMA), respiratory distress (RD) and cerebral malaria (CM) were analysed as means and predicted probabilities from Bayesian generalised mixed models. RESULTS: 52,684 malaria admissions aged 1 month to 14 years were described at 21 hospitals from 49 site-time locations where PfPR2-10 varied from < 1 to 48.7%. Twelve site-time periods were described as low transmission (PfPR2-10 < 5%), five low-moderate transmission (PfPR2-10 5-9%), 20 moderate transmission (PfPR2-10 10-29%) and 12 high transmission (PfPR2-10 ≥ 30%). The majority of malaria admissions were below 5 years of age (69-85%) and rare among children aged 10-14 years (0.7-5.4%) across all transmission settings. The mean age of all-cause malaria hospitalisation was 49.5 months (95% CI 45.1, 55.4) under low transmission compared with 34.1 months (95% CI 30.4, 38.3) at high transmission, with similar trends for each severe malaria phenotype. CM presented among older children at a mean of 48.7 months compared with 39.0 months and 33.7 months for SMA and RD, respectively. In moderate and high transmission settings, 34% and 42% of the children were aged between 2 and 23 months and so within the age range targeted by chemoprevention or vaccines. CONCLUSIONS: Targeting chemoprevention or vaccination programmes to areas where community-based parasite prevalence is ≥10% is likely to match the age ranges covered by interventions (e.g. intermittent presumptive treatment in infancy to children aged 2-23 months and current vaccine age eligibility and duration of efficacy) and the age ranges of highest disease burden.

The Clinical Profile of Severe Pediatric Malaria in an Area Targeted for Routine RTS,S/AS01 Malaria Vaccination in Western Kenya.

BACKGROUND: The malaria prevalence has declined in western Kenya, resulting in the risk of neurological phenotypes in older children. This study investigates the clinical profile of pediatric malaria admissions ahead of the introduction of the RTS,S/AS01 vaccine. METHODS: Malaria admissions in children aged 1 month to 15 years were identified from routine, standardized, inpatient clinical surveillance data collected between 2015 and 2018 from 4 hospitals in western Kenya. Malaria phenotypes were defined based on available data. RESULTS: There were 5766 malaria admissions documented. The median age was 36 months (interquartile range, 18-60): 15% were aged between 1-11 months of age, 33% were aged 1-23 months of age, and 70% were aged 1 month to 5 years. At admission, 2340 (40.6%) children had severe malaria: 421/2208 (19.1%) had impaired consciousness, 665/2240 (29.7%) had an inability to drink or breastfeed, 317/2340 (13.6%) had experienced 2 or more convulsions, 1057/2340 (45.2%) had severe anemia, and 441/2239 (19.7%) had severe respiratory distress. Overall, 211 (3.7%) children admitted with malaria died; 163/211 (77% deaths, case fatality rate 7.0%) and 48/211 (23% deaths, case fatality rate 1.4%) met the criteria for severe malaria and nonsevere malaria at admission, respectively. The median age for fatal cases was 33 months (interquartile range, 12-72) and the case fatality rate was highest in those unconscious (44.4%). CONCLUSIONS: Severe malaria in western Kenya is still predominantly seen among the younger pediatric age group and current interventions targeted for those <5 years are appropriate. However, there are increasing numbers of children older than 5 years admitted with malaria, and ongoing hospital surveillance would identify when interventions should target older children.

Correction to: An exploration of mortality risk factors in non-severe pneumonia in children using clinical data from Kenya.

CORRECTION: The original article contains an omission in the Acknowledgements sub-section of the Declarations.

An exploration of mortality risk factors in non-severe pneumonia in children using clinical data from Kenya.

BACKGROUND: Childhood pneumonia is the leading infectious cause of mortality in children younger than 5 years old. Recent updates to World Health Organization pneumonia guidelines recommend outpatient care for a population of children previously classified as high risk. This revision has been challenged by policymakers in Africa, where mortality related to pneumonia is higher than in other regions and often complicated by comorbidities. This study aimed to identify factors that best discriminate inpatient mortality risk in non-severe pneumonia and explore whether these factors offer any added benefit over the current criteria used to identify children with pneumonia requiring inpatient care. METHODS: We undertook a retrospective cohort study of children aged 2-59 months admitted with a clinical diagnosis of pneumonia at 14 public hospitals in Kenya between February 2014 and February 2016. Using machine learning techniques, we analysed whether clinical characteristics and common comorbidities increased the risk of inpatient mortality for non-severe pneumonia. The topmost risk factors were subjected to decision curve analysis to explore if using them as admission criteria had any net benefit above the current criteria. RESULTS: Out of 16,162 children admitted with pneumonia during the study period, 10,687 were eligible for subsequent analysis. Inpatient mortality within this non-severe group was 252/10,687 (2.36%). Models demonstrated moderately good performance; the partial least squares discriminant analysis model had higher sensitivity for predicting mortality in comparison to logistic regression. Elevated respiratory rate (≥70 bpm), age 2-11 months and weight-for-age Z-score (WAZ) < -3SD were highly discriminative of mortality. These factors ranked consistently across the different models. For a risk threshold probability of 7-14%, there is a net benefit to admitting the patient sub-populations with these features as additional criteria alongside those currently used to classify severe pneumonia. Of the population studied, 70.54% met at least one of these criteria. Sensitivity analyses indicated that the overall results were not significantly affected by variations in pneumonia severity classification criteria. CONCLUSIONS: Children with non-severe pneumonia aged 2-11 months or with respiratory rate ≥ 70 bpm or very low WAZ experience risks of inpatient mortality comparable to severe pneumonia. Inpatient care is warranted in these high-risk groups of children.

Building Learning Health Systems to Accelerate Research and Improve Outcomes of Clinical Care in Low- and Middle-Income Countries.

Mike English and colleagues argue that as efforts are made towards achieving universal health coverage it is also important to build capacity to develop regionally relevant evidence to improve healthcare.

Oral amoxicillin versus benzyl penicillin for severe pneumonia among kenyan children: a pragmatic randomized controlled noninferiority trial.

BACKGROUND: There are concerns that the evidence from studies showing noninferiority of oral amoxicillin to benzyl penicillin for severe pneumonia may not be generalizable to high-mortality settings. METHODS: An open-label, multicenter, randomized controlled noninferiority trial was conducted at 6 Kenyan hospitals. Eligible children aged 2-59 months were randomized to receive amoxicillin or benzyl penicillin and followed up for the primary outcome of treatment failure at 48 hours. A noninferiority margin of risk difference between amoxicillin and benzyl penicillin groups was prespecified at 7%. RESULTS: We recruited 527 children, including 302 (57.3%) with comorbidity. Treatment failure was observed in 20 of 260 (7.7%) and 21 of 261 (8.0%) of patients in the amoxicillin and benzyl penicillin arms, respectively (risk difference, -0.3% [95% confidence interval, -5.0% to 4.3%]) in per-protocol analyses. These findings were supported by the results of intention-to-treat analyses. Treatment failure by day 5 postenrollment was 11.4% and 11.0% and rising to 13.5% and 16.8% by day 14 in the amoxicillin vs benzyl penicillin groups, respectively. The most frequent cause of cumulative treatment failure at day 14 was clinical deterioration within 48 hours of enrollment (33/59 [55.9%]). Four patients died (overall mortality 0.8%) during the study, 3 of whom were allocated to the benzyl penicillin group. The presence of wheeze was independently associated with less frequent treatment failure. CONCLUSIONS: Our findings confirm noninferiority of amoxicillin to benzyl penicillin, provide estimates of risk of treatment failure in Kenya, and offer important additional evidence for policy making in sub-Saharan Africa. CLINICAL TRIAL REGISTRATION: NCT01399723.

Prevalence and correlates of treatment failure among Kenyan children hospitalised with severe community-acquired pneumonia: a prospective study of the clinical effectiveness of WHO pneumonia case management guidelines.

OBJECTIVE: To determine the extent and pattern of treatment failure (TF) among children hospitalised with community-acquired pneumonia at a large tertiary hospital in Kenya. METHODS: We followed up children aged 2-59 months with WHO-defined severe pneumonia (SP) and very severe pneumonia (VSP) for up to 5 days for TF using two definitions: (i) documentation of pre-defined clinical signs resulting in change of treatment (ii) primary clinician's decision to change treatment with or without documentation of the same pre-defined clinical signs. RESULTS: We enrolled 385 children. The risk of TF varied between 1.8% (95% CI 0.4-5.1) and 12.4% (95% CI 7.9-18.4) for SP and 21.4% (95% CI 15.9-27) and 39.3% (95% CI 32.5-46.4) for VSP depending on the definition applied. Higher rates were associated with early changes in therapy by clinician in the absence of an obvious clinical rationale. Non-adherence to treatment guidelines was observed for 70/169 (41.4%) and 67/201 (33.3%) of children with SP and VSP, respectively. Among children with SP, adherence to treatment guidelines was associated with the presence of wheeze on initial assessment (P = 0.02), while clinician non-adherence to guideline-recommended treatments for VSP tended to occur in children with altered consciousness (P < 0.001). Using propensity score matching to account for imbalance in the distribution of baseline clinical characteristics among children with VSP revealed no difference in TF between those treated with the guideline-recommended regimen vs. more costly broad-spectrum alternatives [risk difference 0.37 (95% CI -0.84 to 0.51)]. CONCLUSION: Before revising current pneumonia case management guidelines, standardised definitions of TF and appropriate studies of treatment effectiveness of alternative regimens are required.

Implementing adaptive e-learning for newborn care in Tanzania: an observational study of provider engagement and knowledge gains.

INTRODUCTION: To improve healthcare provider knowledge of Tanzanian newborn care guidelines, we developed adaptive Essential and Sick Newborn Care (aESNC), an adaptive e-learning environment. The objectives of this study were to (1) assess implementation success with use of in-person support and nudging strategy and (2) describe baseline provider knowledge and metacognition. METHODS: 6-month observational study at one zonal hospital and three health centres in Mwanza, Tanzania. To assess implementation success, we used the Reach, Efficacy, Adoption, Implementation and Maintenance framework and to describe baseline provider knowledge and metacognition we used Howell's conscious-competence model. Additionally, we explored provider characteristics associated with initial learning completion or persistent activity. RESULTS: aESNC reached 85% (195/231) of providers: 75 medical, 53 nursing and 21 clinical officers; 110 (56%) were at the zonal hospital and 85 (44%) at health centres. Median clinical experience was 4 years (IQR 1-9) and 45 (23%) had previous in-service training for both newborn essential and sick newborn care. Efficacy was 42% (SD ±17%). Providers averaged 78% (SD ±31%) completion of initial learning and 7% (SD ±11%) of refresher assignments. 130 (67%) providers had ≥1 episode of inactivity >30 day, no episodes were due to lack of internet access. Baseline conscious-competence was 53% (IQR: 38%-63%), unconscious-incompetence 32% (IQR: 23%-42%), conscious-incompetence 7% (IQR: 2%-15%), and unconscious-competence 2% (IQR: 0%-3%). Higher baseline conscious-competence (OR 31.6 (95% CI 5.8 to 183.5)) and being a nursing officer (aOR: 5.6 (95% CI 1.8 to 18.1)), compared with medical officer, were associated with initial learning completion or persistent activity. CONCLUSION: aESNC reach was high in a population of frontline providers across diverse levels of care in Tanzania. Use of in-person support and nudging increased reach, initial learning and refresher assignment completion, but refresher assignment completion remains low. Providers were often unaware of knowledge gaps, and lower baseline knowledge may decrease initial learning completion or activity. Further study to identify barriers to adaptive e-learning normalisation is needed.

Evaluating the Implementation of the Pediatric Acute Care Education (PACE) Program in Northwestern Tanzania: A Mixed-Methods Study Guided by Normalization Process Theory.

Background: In low- and -middle-income countries (LMICs) like Tanzania, the competency of healthcare providers critically influences the quality of pediatric care. To address this, we introduced PACE (Pediatric Acute Care Education), an adaptive e-learning program tailored to enhance provider competency in line with Tanzania's national guidelines for managing seriously ill children. Adaptive e-learning presents a promising alternative to traditional in-service education, yet optimal strategies for its implementation in LMIC settings remain to be fully elucidated. Objectives: This study aimed to (1) evaluate the initial implementation of PACE in Mwanza, Tanzania, using the constructs of Normalization Process Theory (NPT), and (2) provide insights into its feasibility, acceptability, and scalability potential. Methods: A mixed-methods approach was employed across three healthcare settings in Mwanza: a zonal hospital and two health centers. NPT was utilized to navigate the complexities of implementing PACE. Data collection involved a customized NoMAD survey, focus groups and in-depth interviews with healthcare providers. Results: The study engaged 82 healthcare providers through the NoMAD survey and 79 in focus groups and interviews. Findings indicated high levels of coherence and cognitive participation, demonstrating that PACE is well-understood and resonates with existing healthcare goals. Providers expressed a willingness to integrate PACE into their practice, distinguishing it from existing educational methods. However, challenges related to resources and infrastructure, particularly affecting collective action, were noted. The short duration of the study limited the assessment of reflexive monitoring, though early indicators point towards the potential for PACE's long-term sustainability. Conclusion: This study offers vital insights into the feasibility and acceptability of implementing PACE in a Tanzanian context. While PACE aligns well with healthcare objectives, addressing resource and infrastructure challenges is crucial for its successful and sustainable implementation. Furthermore, the study underscores the value of NPT as a framework in guiding implementation processes, with broader implications for implementation science and pediatric acute care in LMICs.

Regional and temporal trends in malaria commodity costs: an analysis of Global Fund data for 79 countries.

BACKGROUND: Although procurement consumes nearly 40% of Global Fund's money, no analyses have been published to show how costs vary across regions and time. This paper presents an analysis of malaria-related commodity procurement data from 79 countries, as reported through the Global Fund's price and quality reporting (PQR) system for the 2005-2012 period. METHODS: Data were analysed for the three most widely procured commodities for prevention, diagnosis and treatment of malaria. These were long-lasting insecticide-treated nets (LLINs), malaria rapid diagnostic tests (RDTs) and the artemether/lumefantrine (AL) combination treatment. Costs were compared across time (2005-2012), regions, and between individual procurement reported through the PQR and pooled procurement reported through the Global Fund's voluntary pooled procurement (VPP) system. All costs were adjusted for inflation and reported in US dollars. RESULTS: The data included 1,514 entries reported from 79 countries over seven years. Of these, 492 entries were for LLINs, 330 for RDTs and 692 for AL. Considerable variations were seen by commodity, although none showed an increase in cost. The costs for LLINs, RDTs and AL all dropped significantly over the period of analysis. Regional variations were also seen, with the cost for all three commodities showing significant variations. The median cost for a single LLIN ranged from USD 4.3 in East Asia to USD 5.0 in West and Central Africa. The cost of a single RDT was lowest in West and Central Africa at US$ 0.57, and highest in the Latin American region at US$ 1.1. AL had the narrowest margin of between US$ 0.06 per tablet in sub-Saharan Africa and South Asia, and US$ 0.08 in the Latin American and Eastern Europe regions. CONCLUSION: This paper concludes that global procurement costs do vary by region and have reduced overall over time. This suggests a mature market is operating when viewed from the global level, but regional variation needs further attention. Such analyses should be done more often to identify and correct market insufficiencies.

Prevalence and risk factors for long COVID and post-COVID-19 condition in Africa: a systematic review.

BACKGROUND: An improved estimation of the clinical sequelae of SARS-CoV-2 infection is crucial in African countries, where the subject has received little attention despite more than 12 million reported cases and evidence that many more people were infected. We reviewed the evidence on prevalence, associated risk factors for long COVID, and systemic or sociocultural determinants of reporting long COVID. METHODS: We conducted a systematic review, searching PubMed, the Living OVerview of Evidence platform, and grey literature sources for publications from Dec 1, 2019, to Nov 23, 2022. We included articles published in English, French, Spanish, or Portuguese that reported on any study type in Africa with participants of any age who had symptoms for 4 weeks or more after an acute SARS-CoV-2 infection. We excluded secondary research, comments, and correspondence. Screening and data extraction were performed by two reviewers. Summary estimates were extracted, including sociodemographic factors, medical history, prevalence of persistent symptoms, and symptoms and associated factors. Results were analysed descriptively. The study was registered on the Open Science Framework platform. FINDINGS: Our search yielded 294 articles, of which 24 peer-reviewed manuscripts were included, reporting on 9712 patients from eight African countries. Only one study exclusively recruited children, and one other study included children as part of their study population. Studies indicated moderate to low risk of bias. Prevalence of long COVID varied widely, from 2% in Ghana to 86% in Egypt. Long COVID was positively associated with female sex, older age, non-Black ethnicity, low level of education, and the severity of acute infection and underlying comorbidity. HIV and tuberculosis were not identified as risk factors. Factors influencing reporting included absence of awareness, inadequate clinical data and diagnostics, and little access to health-care services. INTERPRETATION: In Africa, research on long COVID is scarce, particularly among children, who represent the majority of the population. However, existing studies show a substantial prevalence across settings, emphasising the importance of vaccination and other prevention strategies to avert the effects of long COVID on individual wellbeing, the increased strain on health systems, and the potential negative effects on economically vulnerable populations. At a global level, including African countries, tools for research on long COVID need to be harmonised to maximise the usefulness of the data collected. FUNDING: None.

Feasibility of an Adaptive E-Learning Environment to Improve Provider Proficiency in Essential and Sick Newborn Care in Mwanza, Tanzania.

Introduction: To improve healthcare provider knowledge of Tanzanian newborn care guidelines, we developed adaptive Essential and Sick Newborn Care (aESNC), an adaptive e-learning environment (AEE). The objectives of this study were to 1) assess implementation success with use of in-person support and nudging strategy and 2) describe baseline provider knowledge and metacognition. Methods: 6-month observational study at 1 zonal hospital and 3 health centers in Mwanza, Tanzania. To assess implementation success, we used the RE-AIM framework and to describe baseline provider knowledge and metacognition we used Howell's conscious-competence model. Additionally, we explored provider characteristics associated with initial learning completion or persistent activity. Results: aESNC reached 85% (195/231) of providers: 75 medical, 53 nursing, and 21 clinical officers; 110 (56%) were at the zonal hospital and 85 (44%) at health centers. Median clinical experience was 4 years [IQR 1,9] and 45 (23%) had previous in-service training for both newborn essential and sick newborn care. Efficacy was 42% (SD±17%). Providers averaged 78% (SD±31%) completion of initial learning and 7%(SD±11%) of refresher assignments. 130 (67%) providers had ≥1 episode of inactivity >30 day, no episodes were due to lack of internet access. Baseline conscious-competence was 53% [IQR:38-63%], unconscious-incompetence 32% [IQR:23-42%], conscious-incompetence 7% [IQR:2-15%], and unconscious-competence 2% [IQR:0-3%]. Higher baseline conscious-competence (OR 31.6 [95%CI:5.8, 183.5) and being a nursing officer (aOR: 5.6 [95%CI:1.8, 18.1]), compared to medical officer) were associated with initial learning completion or persistent activity. Conclusion: aESNC reach was high in a population of frontline providers across diverse levels of care in Tanzania. Use of in-person support and nudging increased reach, initial learning, and refresher assignment completion, but refresher assignment completion remains low. Providers were often unaware of knowledge gaps, and lower baseline knowledge may decrease initial learning completion or activity. Further study to identify barriers to adaptive e-learning normalization is needed.

Development of pediatric acute care education (PACE): An adaptive electronic learning (e-learning) environment for healthcare providers in Tanzania.

Globally, inadequate healthcare provider (HCP) proficiency with evidence-based guidelines contributes to millions of newborn, infant, and child deaths each year. HCP guideline proficiency would improve patient outcomes. Conventional (in person) HCP in-service education is limited in 4 ways: reach, scalability, adaptability, and the ability to contextualize. Adaptive e-learning environments (AEE), a subdomain of e-learning, incorporate artificial intelligence technology to create a unique cognitive model of each HCP to improve education effectiveness. AEEs that use existing internet access and personal mobile devices may overcome limits of conventional education. This paper provides an overview of the development of our AEE HCP in-service education, Pediatric Acute Care Education (PACE). PACE uses an innovative approach to address HCPs' proficiency in evidence-based guidelines for care of newborns, infants, and children. PACE is novel in 2 ways: 1) its patient-centric approach using clinical audit data or frontline provider input to determine content and 2) its ability to incorporate refresher learning over time to solidify knowledge gains. We describe PACE's integration into the Pediatric Association of Tanzania's (PAT) Clinical Learning Network (CLN), a multifaceted intervention to improve facility-based care along a single referral chain. Using principles of co-design, stakeholder meetings modified PACE's characteristics and optimized integration with CLN. We plan to use three-phase, mixed-methods, implementation process. Phase I will examine the feasibility of PACE and refine its components and protocol. Lessons gained from this initial phase will guide the design of Phase II proof of concept studies which will generate insights into the appropriate empirical framework for (Phase III) implementation at scale to examine effectiveness.

Clinical epidemiology of COVID-19 among hospitalized children in rural western Kenya.

The epidemiology of pediatric COVID-19 in sub-Saharan Africa and the role of fecal-oral transmission in SARS-CoV-2 are poorly understood. Among children and adolescents in Kenya, we identify correlates of COVID-19 infection, document the clinical outcomes of infection, and evaluate the prevalence and viability of SARS-CoV-2 in stool. We recruited a prospective cohort of hospitalized children aged two months to 15 years in western Kenya between March 1 and June 30 2021. Children with SARS-CoV-2 were followed monthly for 180-days after hospital discharge. Bivariable logistic regression analysis was used to identify the clinical and sociodemographics correlates of SARS-CoV-2 infection. We also calculated the prevalence of SARS-CoV-2 detection in stool of confirmed cases. Of 355 systematically tested children, 55 (15.5%) were positive and were included in the cohort. The commonest clinical features among COVID-19 cases were fever (42/55, 76%), cough (19/55, 35%), nausea and vomiting (19/55, 35%), and lethargy (19/55, 35%). There were no statistically significant difference in baseline sociodemographic and clinical characteristics between SARS-CoV-2 positive and negative participants. Among positive participants, 8/55 (14.5%, 95%CI: 5.3%-23.9%) died; seven during the inpatient period. Forty-nine children with COVID-19 had stool samples or rectal swabs available at baseline, 9 (17%) had PCR-positive stool or rectal swabs, but none had SARS-CoV-2 detected by culture. Syndromic identification of COVID-19 is particularly challenging among children as the presenting symptoms and signs mirror other common pediatric diseases. Mortality among children hospitalized with COVID-19 was high in this cohort but was comparable to mortality seen with other common illnesses in this setting. Among this small set of children with COVID-19 we detected SARS-CoV-2 DNA, but were not able to culture viable SARs-CoV-2 virus, in stool. This suggests that fecal transmission may not be a substantial risk in children recently diagnosed and hospitalized with COVID-19 infection.

Symptom prevalence and secondary attack rate of SARS-CoV-2 in rural Kenyan households: A prospective cohort study.

BACKGROUND: We estimated the secondary attack rate of SARS-CoV-2 among household contacts of PCR-confirmed cases of COVID-19 in rural Kenya and analysed risk factors for transmission. METHODS: We enrolled incident PCR-confirmed cases and their household members. At baseline, a questionnaire, a blood sample, and naso-oropharyngeal swabs were collected. Household members were followed 4, 7, 10, 14, 21 and 28 days after the date of the first PCR-positive in the household; naso-oropharyngeal swabs were collected at each visit and used to define secondary cases. Blood samples were collected every 1-2 weeks. Symptoms were collected in a daily symptom diary. We used binomial regression to estimate secondary attack rates and survival analysis to analyse risk factors for transmission. RESULTS: A total of 119 households with at least one positive household member were enrolled between October 2020 and September 2022, comprising 503 household members; 226 remained in follow-up at day 14 (45%). A total of 43 secondary cases arose within 14 days of identification of the primary case, and 81 household members remained negative. The 7-day secondary attack rate was 4% (95% CI 1%-10%), the 14-day secondary attack rate was 28% (95% CI 17%-40%). Of 38 secondary cases with data, eight reported symptoms (21%, 95% CI 8%-34%). Antibody to SARS-CoV-2 spike protein at enrolment was not associated with risk of becoming a secondary case. CONCLUSION: Households in our setting experienced a lower 7-day attack rate than a recent meta-analysis indicated as the global average (23%-43% depending on variant), and infection is mostly asymptomatic in our setting.

Serum immunoglobulin G and mucosal immunoglobulin A antibodies from prepandemic samples collected in Kilifi, Kenya, neutralize SARS-CoV-2 in vitro.

OBJECTIVES: Many regions of Africa have experienced lower COVID-19 morbidity and mortality than Europe. Pre-existing humoral responses to endemic human coronaviruses (HCoV) may cross-protect against SARS-CoV-2. We investigated the neutralizing capacity of SARS-CoV-2 spike reactive and nonreactive immunoglobulin (Ig)G and IgA antibodies in prepandemic samples. METHODS: To investigate the presence of pre-existing immunity, we performed enzyme-linked immunosorbent assay using spike antigens from reference SARS-CoV-2, HCoV HKU1, OC43, NL63, and 229E using prepandemic samples from Kilifi in coastal Kenya. In addition, we performed neutralization assays using pseudotyped reference SARS-CoV-2 to determine the functionality of the identified reactive antibodies. RESULTS: We demonstrate the presence of HCoV serum IgG and mucosal IgA antibodies, which cross-react with the SARS-CoV-2 spike. We show pseudotyped reference SARS-CoV-2 neutralization by prepandemic serum, with a mean infective dose 50 of 1: 251, which is 10-fold less than that of the pooled convalescent sera from patients with COVID-19 but still within predicted protection levels. The prepandemic naso-oropharyngeal fluid neutralized pseudo-SARS-CoV-2 at a mean infective dose 50 of 1: 5.9 in the neutralization assay. CONCLUSION: Our data provide evidence for pre-existing functional humoral responses to SARS-CoV-2 in Kilifi, coastal Kenya and adds to data showing pre-existing immunity for COVID-19 from other regions.