Pregnancy-related mortality up to 1 year postpartum in sub-Saharan Africa: an analysis of verbal autopsy data from six countries.

OBJECTIVE: To compare the causes of death for women who died during pregnancy and within the first 42 days postpartum with those of women who died between >42 days and within 1 year postpartum. DESIGN: Open population cohort (Health and Demographic Surveillance Systems). SETTING: Ten Health and Demographic Surveillance Systems (HDSS) in The Gambia, Kenya, Malawi, Tanzania, Ethiopia and South Africa. POPULATION: 2114 deaths which occurred within 1 year of the end of pregnancy where a verbal autopsy interview was conducted from 2000 to 2019. METHODS: InterVA5 and InSilicoVA verbal autopsy algorithms were used to attribute the most likely underlying cause of death, which were grouped according to adapted International Classification of Diseases-Maternal Mortality categories. Multinomial regression was used to compare differences in causes of deaths within 42 days versus 43-365 days postpartum adjusting for HDSS and time period (2000-2009 and 2010-2019). MAIN OUTCOME MEASURES: Cause of death and the verbal autopsy Circumstances of Mortality Categories (COMCATs). RESULTS: Of 2114 deaths, 1212 deaths occurred within 42 days postpartum and 902 between 43 and 365 days postpartum. Compared with deaths within 42 days, deaths from HIV and TB, other infectious diseases, and non-communicable diseases constituted a significantly larger proportion of late pregnancy-related deaths beyond 42 days postpartum, and health system failures were important in the circumstances of those deaths. The contribution of HIV and TB to deaths beyond 42 days postpartum was greatest in Southern Africa. The causes of pregnancy-related mortality within and beyond 42 days postpartum did not change significantly between 2000-2009 and 2010-2019. CONCLUSIONS: Cause of death data from the extended postpartum period are critical to inform prevention. The dominance of HIV and TB, other infectious and non-communicable diseases to (late) pregnancy-related mortality highlights the need for better integration of non-obstetric care with ante-, intra- and postpartum care in high-burden settings.

The influence of malaria control interventions and climate variability on changes in the geographical distribution of parasite prevalence in Kenya between 2015 and 2020.

BACKGROUND: The burden of malaria in Kenya was showing a declining trend, but appears to have reached a plateau in recent years. This study estimated changes in the geographical distribution of malaria parasite risk in the country between the years 2015 and 2020, and quantified the contribution of malaria control interventions and climatic/ environmental factors to these changes. METHODS: Bayesian geostatistical models were used to analyse the Kenyan 2015 and 2020 Malaria Indicator Survey (MIS) data. Bivariate models were fitted to identify the most important control intervention indicators and climatic/environmental predictors of parasitaemia risk by age groups (6-59 months and 5-14 years). Parasitaemia risk and the number of infected children were predicted over a 1 × 1 km2 grid. The probability of the decline in parasitaemia risk in 2020 compared to 2015 was also evaluated over the gridded surface and factors associated with changes in parasitaemia risk between the two surveys were evaluated. RESULTS: There was a significant decline in the coverage of most malaria indicators related to Insecticide Treated Nets (ITN) and Artemisinin Combination Therapies (ACT) interventions. Overall, there was a 31% and 26% reduction in malaria prevalence among children aged < 5 and 5-14 years, respectively. Among younger children, the highest reduction (50%) and increase (41%) were in the low-risk and semi-arid epi zones, respectively; while among older children there was increased risk in both the low-risk (83%) and semi-arid (100%) epi zones. Increase in nightlights and the proportion of individuals using ITNs in 2020 were associated with reduced parasitaemia risk. CONCLUSION: Increased nightlights and ITN use could have led to the reduction in parasitaemia risk. However, the reduction is heterogeneous and there was increased risk in northern Kenya. Taken together, these results suggest that constant surveillance and re-evaluation of parasite and vector control measures in areas with increased transmission is necessary. The methods used in this analysis can be employed in other settings.

Clinical risk factors of adverse outcomes among women with COVID-19 in the pregnancy and postpartum period: a sequential, prospective meta-analysis.

OBJECTIVE: This sequential, prospective meta-analysis sought to identify risk factors among pregnant and postpartum women with COVID-19 for adverse outcomes related to disease severity, maternal morbidities, neonatal mortality and morbidity, and adverse birth outcomes. DATA SOURCES: We prospectively invited study investigators to join the sequential, prospective meta-analysis via professional research networks beginning in March 2020. STUDY ELIGIBILITY CRITERIA: Eligible studies included those recruiting at least 25 consecutive cases of COVID-19 in pregnancy within a defined catchment area. METHODS: We included individual patient data from 21 participating studies. Data quality was assessed, and harmonized variables for risk factors and outcomes were constructed. Duplicate cases were removed. Pooled estimates for the absolute and relative risk of adverse outcomes comparing those with and without each risk factor were generated using a 2-stage meta-analysis. RESULTS: We collected data from 33 countries and territories, including 21,977 cases of SARS-CoV-2 infection in pregnancy or postpartum. We found that women with comorbidities (preexisting diabetes mellitus, hypertension, cardiovascular disease) vs those without were at higher risk for COVID-19 severity and adverse pregnancy outcomes (fetal death, preterm birth, low birthweight). Participants with COVID-19 and HIV were 1.74 times (95% confidence interval, 1.12-2.71) more likely to be admitted to the intensive care unit. Pregnant women who were underweight before pregnancy were at higher risk of intensive care unit admission (relative risk, 5.53; 95% confidence interval, 2.27-13.44), ventilation (relative risk, 9.36; 95% confidence interval, 3.87-22.63), and pregnancy-related death (relative risk, 14.10; 95% confidence interval, 2.83-70.36). Prepregnancy obesity was also a risk factor for severe COVID-19 outcomes including intensive care unit admission (relative risk, 1.81; 95% confidence interval, 1.26-2.60), ventilation (relative risk, 2.05; 95% confidence interval, 1.20-3.51), any critical care (relative risk, 1.89; 95% confidence interval, 1.28-2.77), and pneumonia (relative risk, 1.66; 95% confidence interval, 1.18-2.33). Anemic pregnant women with COVID-19 also had increased risk of intensive care unit admission (relative risk, 1.63; 95% confidence interval, 1.25-2.11) and death (relative risk, 2.36; 95% confidence interval, 1.15-4.81). CONCLUSION: We found that pregnant women with comorbidities including diabetes mellitus, hypertension, and cardiovascular disease were at increased risk for severe COVID-19-related outcomes, maternal morbidities, and adverse birth outcomes. We also identified several less commonly known risk factors, including HIV infection, prepregnancy underweight, and anemia. Although pregnant women are already considered a high-risk population, special priority for prevention and treatment should be given to pregnant women with these additional risk factors.

The long-term impact of HIV/AIDS on socio-economic status: a comparative analysis of households headed by HIV-positive and HIV-negative individuals in Western Kenya.

HIV/AIDS is known to have adverse effects on individual and family socio-economic status due to the loss of productive time and over-expenditure in treatment. However, empirical data on how HIV/AIDS affects households' socio-economic status are insufficient. We linked socio-economic data from a Health and Demographic Surveillance System (HDSS) that implements an HIV/AIDS Longitudinal bio-behavioural survey (LBBS) to understand the long-term impact of HIV/AIDS on households' socio-economic status between 2010 and 2018. We compared changes in socio-economic status between households headed by HIV-negative and -positive individuals. A logistic regression was used to assess factors that influence socio-economic status. The level of education and household size were not significant predictors of households' socio-economic status. Households headed by HIV-positive individuals could maintain their baseline socio-economic status (unadjusted RRR = 1.17, 95% CI: 1.01, 1.36) but improvement chances were reduced despite a non-significant association (unadjusted RRR = 0.98, 95% CI: 0.80, 1.20). While HIV/AIDS is known to disrupt economic growth, in this setting, being a male household head, old and widowed reduces chances of improved socio-economic status. The elderly people, widows and widowers are disadvantaged. Consequently, there is a need for special programmes, which seek to empower the identified vulnerable groups economically. .

Evaluating the impact of DREAMS on HIV incidence among adolescent girls and young women: A population-based cohort study in Kenya and South Africa.

BACKGROUND: Through a multisectoral approach, the DREAMS Partnership aimed to reduce HIV incidence among adolescent girls and young women (AGYW) by 40% over 2 years in high-burden districts across sub-Saharan Africa. DREAMS promotes a combination package of evidence-based interventions to reduce individual, family, partner, and community-based drivers of young women's heightened HIV risk. We evaluated the impact of DREAMS on HIV incidence among AGYW and young men in 2 settings. METHODS AND FINDINGS: We directly estimated HIV incidence rates among open population-based cohorts participating in demographic and HIV serological surveys from 2006 to 2018 annually in uMkhanyakude (KwaZulu-Natal, South Africa) and over 6 rounds from 2010 to 2019 in Gem (Siaya, Kenya). We compared HIV incidence among AGYW aged 15 to 24 years before DREAMS and up to 3 years after DREAMS implementation began in 2016. We investigated the timing of any change in HIV incidence and whether the rate of any change accelerated during DREAMS implementation. Comparable analyses were also conducted for young men (20 to 29/34 years). In uMkhanyakude, between 5,000 and 6,000 AGYW were eligible for the serological survey each year, an average of 85% were contacted, and consent rates varied from 37% to 67%. During 26,395 person-years (py), HIV incidence was lower during DREAMS implementation (2016 to 2018) than in the previous 5-year period among 15- to 19-year-old females (4.5 new infections per 100 py as compared with 2.8; age-adjusted rate ratio (aRR) = 0.62, 95% confidence interval [CI] 0.48 to 0.82), and lower among 20- to 24-year-olds (7.1/100 py as compared with 5.8; aRR = 0.82, 95% CI 0.65 to 1.04). Declines preceded DREAMS introduction, beginning from 2012 to 2013 among the younger and 2014 for the older women, with no evidence of more rapid decline during DREAMS implementation. In Gem, between 8,515 and 11,428 AGYW were eligible each survey round, an average of 34% were contacted and offered an HIV test, and consent rates ranged from 84% to 99%. During 10,382 py, declines in HIV incidence among 15- to 19-year-olds began before DREAMS and did not change after DREAMS introduction. Among 20- to 24-year-olds in Gem, HIV incidence estimates were lower during DREAMS implementation (0.64/100 py) compared with the pre-DREAMS period (0.94/100 py), with no statistical evidence of a decline (aRR = 0.69, 95% CI 0.53 to 2.18). Among young men, declines in HIV incidence were greater than those observed among AGYW and also began prior to DREAMS investments. Study limitations include low study power in Kenya and the introduction of other interventions such as universal treatment for HIV during the study period. CONCLUSIONS: Substantial declines in HIV incidence among AGYW were observed, but most began before DREAMS introduction and did not accelerate in the first 3 years of DREAMS implementation. Like the declines observed among young men, they are likely driven by earlier and ongoing investments in HIV testing and treatment. Longer-term implementation and evaluation are needed to assess the impact of such a complex HIV prevention intervention and to help accelerate reductions in HIV incidence among young women.

Impact of the Introduction of Rotavirus Vaccine on Hospital Admissions for Diarrhea Among Children in Kenya: A Controlled Interrupted Time-Series Analysis.

BACKGROUND: Monovalent rotavirus vaccine, Rotarix (GlaxoSmithKline), was introduced in Kenya in July 2014 and is recommended to infants as oral doses at ages 6 and 10 weeks. A multisite study was established in 2 population-based surveillance sites to evaluate vaccine impact on the incidence of rotavirus-associated hospitalizations (RVHs). METHODS: Hospital-based surveillance was conducted from January 2010 to June 2017 for acute diarrhea hospitalizations among children aged <5 years in 2 health facilities in Kenya. A controlled interrupted time-series analysis was undertaken to compare RVH pre- and post-vaccine introduction using rotavirus-negative cases as a control series. The change in incidence post-vaccine introduction was estimated from a negative binomial model that adjusted for secular trend, seasonality, and multiple health worker industrial actions (strikes). RESULTS: Between January 2010 and June 2017 there were 1513 and 1652 diarrhea hospitalizations in Kilifi and Siaya; among those tested for rotavirus, 28% (315/1142) and 23% (197/877) were positive, respectively. There was a 57% (95% confidence interval [CI], 8-80%) reduction in RVHs observed in the first year post-vaccine introduction in Kilifi and a 59% (95% CI, 20-79%) reduction in Siaya. In the second year, RVHs decreased further at both sites, 80% (95% CI, 46-93%) reduction in Kilifi and 82% reduction in Siaya (95% CI. 61-92%); this reduction was sustained at both sites into the third year. CONCLUSIONS: A substantial reduction in RVHs and all-cause diarrhea was observed in 2 demographic surveillance sites in Kenya within 3 years of vaccine introduction.

Effectiveness of Monovalent Rotavirus Vaccine Against Hospitalization With Acute Rotavirus Gastroenteritis in Kenyan Children.

BACKGROUND: Rotavirus remains a leading cause of pediatric diarrheal illness and death worldwide. Data on rotavirus vaccine effectiveness in sub-Saharan Africa are limited. Kenya introduced monovalent rotavirus vaccine (RV1) in July 2014. We assessed RV1 effectiveness against rotavirus-associated hospitalization in Kenyan children. METHODS: Between July 2014 and December 2017, we conducted surveillance for acute gastroenteritis (AGE) in 3 Kenyan hospitals. From children age-eligible for ≥1 RV1 dose, with stool tested for rotavirus and confirmed vaccination history we compared RV1 coverage among rotavirus positive (cases) vs rotavirus negative (controls) using multivariable logistic regression and calculated effectiveness based on adjusted odds ratio. RESULTS: Among 677 eligible children, 110 (16%) were rotavirus positive. Vaccination data were available for 91 (83%) cases; 51 (56%) had 2 RV1 doses and 33 (36%) 0 doses. Among 567 controls, 418 (74%) had vaccination data; 308 (74%) had 2 doses and 69 (16%) 0 doses. Overall 2-dose effectiveness was 64% (95% confidence interval [CI], 35%-80%); effectiveness was 67% (95% CI, 30%-84%) for children aged <12 months and 72% (95% CI, 10%-91%) for children aged ≥12 months. Significant effectiveness was seen in children with normal weight for age, length/height for age and weight for length/height; however, no protection was found among underweight, stunted, or wasted children. CONCLUSIONS: RV1 in the Kenyan immunization program provides significant protection against rotavirus-associated hospitalization which persisted beyond infancy. Malnutrition appears to diminish vaccine effectiveness. Efforts to improve rotavirus uptake and nutritional status are important to maximize vaccine benefit.

Is maternal HIV infection a risk factor for delayed or missed infant measles vaccination in western Kenya?

Measles is a highly infectious virus and one of the leading causes of childhood morbidity and mortality in areas with low immunization rates. Despite the introduction of the measles vaccine preventing about 20 million deaths between 2000 and 2016, there still is a low uptake of the vaccine, especially in low-income countries. Maternal HIV positive status is identified as one of the factors inhibiting the uptake of the measles vaccine in some settings. Using data from a Health and Demographic surveillance system (HDSS), and a Longitudinal Bio-behavioural Survey (LBBS), we assessed the effect of a mother's HIV status on a child's overall uptake of measles vaccine and timeliness in western Kenya. The findings did not show association between a mother's HIV status and a child's receipt of measles vaccine (OR = 0.84, 95% CI: 0.65, 1.08). However, higher socio-economic status (SES) was a positive factor for receipt of timely measles vaccine (OR = 1.34, 95% CI: 1.03, 1.75) for middle, (OR = 1.43, 95% CI: 1.10, 1.86) upper middle, and (OR = 1.51, 95% CI: 1.15, 1.98) higher quintiles as compared to the lower. Consequently, it is imperative to incorporate interventions that target low SES children and those that improve economic status.

Rotavirus group A genotype circulation patterns across Kenya before and after nationwide vaccine introduction, 2010-2018.

BACKGROUND: Kenya introduced the monovalent G1P [8] Rotarix® vaccine into the infant immunization schedule in July 2014. We examined trends in rotavirus group A (RVA) genotype distribution pre- (January 2010-June 2014) and post- (July 2014-December 2018) RVA vaccine introduction. METHODS: Stool samples were collected from children aged < 13 years from four surveillance sites across Kenya: Kilifi County Hospital, Tabitha Clinic Nairobi, Lwak Mission Hospital, and Siaya County Referral Hospital (children aged < 5 years only). Samples were screened for RVA using enzyme linked immunosorbent assay (ELISA) and VP7 and VP4 genes sequenced to infer genotypes. RESULTS: We genotyped 614 samples in pre-vaccine and 261 in post-vaccine introduction periods. During the pre-vaccine introduction period, the most frequent RVA genotypes were G1P [8] (45.8%), G8P [4] (15.8%), G9P [8] (13.2%), G2P [4] (7.0%) and G3P [6] (3.1%). In the post-vaccine introduction period, the most frequent genotypes were G1P [8] (52.1%), G2P [4] (20.7%) and G3P [8] (16.1%). Predominant genotypes varied by year and site in both pre and post-vaccine periods. Temporal genotype patterns showed an increase in prevalence of vaccine heterotypic genotypes, such as the commonly DS-1-like G2P [4] (7.0 to 20.7%, P < .001) and G3P [8] (1.3 to 16.1%, P < .001) genotypes in the post-vaccine introduction period. Additionally, we observed a decline in prevalence of genotypes G8P [4] (15.8 to 0.4%, P < .001) and G9P [8] (13.2 to 5.4%, P < .001) in the post-vaccine introduction period. Phylogenetic analysis of genotype G1P [8], revealed circulation of strains of lineages G1-I, G1-II and P [8]-1, P [8]-III and P [8]-IV. Considerable genetic diversity was observed between the pre and post-vaccine strains, evidenced by distinct clusters. CONCLUSION: Genotype prevalence varied from before to after vaccine introduction. Such observations emphasize the need for long-term surveillance to monitor vaccine impact. These changes may represent natural secular variation or possible immuno-epidemiological changes arising from the introduction of the vaccine. Full genome sequencing could provide insights into post-vaccine evolutionary pressures and antigenic diversity.

Modelling the relationship between malaria prevalence as a measure of transmission and mortality across age groups.

BACKGROUND: Parasite prevalence has been used widely as a measure of malaria transmission, especially in malaria endemic areas. However, its contribution and relationship to malaria mortality across different age groups has not been well investigated. Previous studies in a health and demographic surveillance systems (HDSS) platform in western Kenya quantified the contribution of incidence and entomological inoculation rates (EIR) to mortality. The study assessed the relationship between outcomes of malaria parasitaemia surveys and mortality across age groups. METHODS: Parasitological data from annual cross-sectional surveys from the Kisumu HDSS between 2007 and 2015 were used to determine malaria parasite prevalence (PP) and clinical malaria (parasites plus reported fever within 24 h or temperature above 37.5 °C). Household surveys and verbal autopsy (VA) were used to obtain data on all-cause and malaria-specific mortality. Bayesian negative binomial geo-statistical regression models were used to investigate the association of PP/clinical malaria with mortality across different age groups. Estimates based on yearly data were compared with those from aggregated data over 4 to 5-year periods, which is the typical period that mortality data are available from national demographic and health surveys. RESULTS: Using 5-year aggregated data, associations were established between parasite prevalence and malaria-specific mortality in the whole population (RRmalaria = 1.66; 95% Bayesian Credible Intervals: 1.07-2.54) and children 1-4 years (RRmalaria = 2.29; 1.17-4.29). While clinical malaria was associated with both all-cause and malaria-specific mortality in combined ages (RRall-cause = 1.32; 1.01-1.74); (RRmalaria = 2.50; 1.27-4.81), children 1-4 years (RRall-cause = 1.89; 1.00-3.51); (RRmalaria = 3.37; 1.23-8.93) and in older children 5-14 years (RRall-cause = 3.94; 1.34-11.10); (RRmalaria = 7.56; 1.20-39.54), no association was found among neonates, adults (15-59 years) and the elderly (60+ years). Distance to health facilities, socioeconomic status, elevation and survey year were important factors for all-cause and malaria-specific mortality. CONCLUSION: Malaria parasitaemia from cross-sectional surveys was associated with mortality across age groups over 4 to 5 year periods with clinical malaria more strongly associated with mortality than parasite prevalence. This effect was stronger in children 5-14 years compared to other age-groups. Further analyses of data from other HDSS sites or similar platforms would be useful in investigating the relationship between malaria and mortality across different endemicity levels.

Rates of hospitalization and death for all-cause and rotavirus acute gastroenteritis before rotavirus vaccine introduction in Kenya, 2010-2013.

BACKGROUND: Rotavirus vaccine was introduced in Kenya immunization program in July 2014. Pre-vaccine disease burden estimates are important for assessing vaccine impact. METHODS: Children with acute gastroenteritis (AGE) (≥3 loose stools and/or ≥ 1 episode of unexplained vomiting followed by loose stool within a 24-h period), hospitalized in Siaya County Referral Hospital (SCRH) from January 2010 through December 2013 were enrolled. Stool specimens were tested for rotavirus (RV) using an enzyme immunoassay (EIA). Hospitalization rates were calculated using person-years of observation (PYO) from the Health Demographic Surveillance System (HDSS) as a denominator, while adjusting for healthcare utilization at household level and proportion of stool specimen collected from patients who met the case definition at the surveillance hospital. Mortality rates were calculated using PYO as the denominator and number of deaths estimated using total deaths in the HDSS, proportion of deaths attributed to diarrhoea by verbal autopsy (VA) and percent positive for rotavirus AGE (RVAGE) hospitalizations. RESULTS: Of 7760 all-cause hospitalizations among children < 5 years of age, 3793 (49%) were included in the analysis. Of these, 21% (805) had AGE; RV was detected in 143 (26%) of 541 stools tested. Among children < 5 years, the estimated hospitalization rates per 100,000 PYO for AGE and RVAGE were 2413 and 429, respectively. Mortality rate associated with AGE and RVAGE were 176 and 45 per 100,000 PYO, respectively. CONCLUSION: AGE and RVAGE caused substantial health care burden (hospitalizations and deaths) before rotavirus vaccine introduction in Kenya.

"We are called the et cetera": experiences of the poor with health financing reforms that target them in Kenya.

BACKGROUND: Through a number of healthcare reforms, Kenya has demonstrated its intention to extend financial risk protection and service coverage for poor and vulnerable groups. These reforms include the provision of free maternity services, user-fee removal in public primary health facilities and a health insurance subsidy programme (HISP) for the poor. However, the available evidence points to inequity and the likelihood that the poor will still be left behind with regards to financial risk protection and service coverage. This study examined the experiences of the poor with health financing reforms that target them. METHODS: We conducted a qualitative cross-sectional study in two purposively selected counties in Kenya. We collected data through focus group discussions (n = 8) and in-depth interviews (n = 30) with people in the lowest wealth quintile residing in the health and demographic surveillance systems, and HISP beneficiaries. We analyzed the data using a framework approach focusing on four healthcare access dimensions; geographical accessibility, affordability, availability, and acceptability. RESULTS: Health financing reforms reduced financial barriers and improved access to health services for the poor in the study counties. However, various access barriers limited the extent to which they benefited from these reforms. Long distances, lack of public transport, poor condition of the roads and high transport costs especially in rural areas limited access to health facilities. Continued charging of user fees despite their abolition, delayed insurance reimbursements to health facilities that HISP beneficiaries were seeking care from, and informal fees exposed the poor to out of pocket payments. Stock-outs of medicine and other medical supplies, dysfunctional medical equipment, shortage of healthcare workers, and frequent strikes adversely affected the availability of health services. Acceptability of care was further limited by discrimination by healthcare workers and ineffective grievance redress mechanisms which led to a feeling of disempowerment among the poor. CONCLUSIONS: Pro-poor health financing reforms improved access to care for the poor to some extent. However, to enhance the effectiveness of pro-poor reforms and to ensure that the poor in Kenya benefit fully from them, there is a need to address barriers to healthcare seeking across all access dimensions.

Evaluation of case definitions to detect respiratory syncytial virus infection in hospitalized children below 5 years in Rural Western Kenya, 2009-2013.

BACKGROUND: In order to better understand respiratory syncytial virus (RSV) epidemiology and burden in tropical Africa, optimal case definitions for detection of RSV cases need to be identified. METHODS: We used data collected between September 2009 - August 2013 from children aged <5 years hospitalized with acute respiratory Illness at Siaya County Referral Hospital. We evaluated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of individual signs, symptoms and standard respiratory disease case definitions (severe acute respiratory illness [SARI]; hospitalized influenza-like illness [hILI]; integrated management of childhood illness [IMCI] pneumonia) to detect laboratory-confirmed RSV infection. We also evaluated an alternative case definition of cough or difficulty breathing plus hypoxia, in-drawing, or wheeze. RESULTS: Among 4714 children hospitalized with ARI, 3810 (81 %) were tested for RSV; and 470 (12 %) were positive. Among individual signs and symptoms, cough alone had the highest sensitivity to detect laboratory-confirmed RSV [96 %, 95 % CI (95-98)]. Hypoxia, wheezing, stridor, nasal flaring and chest wall in-drawing had sensitivities ranging from 8 to 31 %, but had specificities >75 %. Of the standard respiratory case definitions, SARI had the highest sensitivity [83 %, 95 % CI (79-86)] whereas IMCI severe pneumonia had the highest specificity [91 %, 95 % CI (90-92)]. The alternative case definition (cough or difficulty breathing plus hypoxia, in-drawing, or wheeze) had a sensitivity of [55 %, 95 % CI (50-59)] and a specificity of [60 %, 95 % CI (59-62)]. The PPV for all case definitions and individual signs/symptoms ranged from 11 to 20 % while the negative predictive values were >87 %. When we stratified by age <1 year and 1- < 5 years, difficulty breathing, severe pneumonia and the alternative case definition were more sensitive in children aged <1 year [70 % vs. 54 %, p < 0.01], [19 % vs. 11 %, p = 0.01] and [66 % vs. 43 %, p < 0.01] respectively, while non-severe pneumonia was more sensitive [14 % vs. 26 %, p < 0.01] among children aged 1- < 5 years. CONCLUSION: The sensitivity and specificity of different commonly used case definitions for detecting laboratory-confirmed RSV cases varied widely, while the positive predictive value was consistently low. Optimal choice of case definition will depend upon study context and research objectives.

A sham case-control study of effectiveness of DTP-Hib-hepatitis B vaccine against rotavirus acute gastroenteritis in Kenya.

BACKGROUND: In many GAVI-eligible countries, effectiveness of new vaccines will be evaluated by case-control methodology. To inform the design and assess selection bias of a future case-control study of rotavirus vaccine effectiveness (VE) in western Kenya, we performed a sham case-control study evaluating VE of pentavalent vaccine (DTP-Hib-HepB) against rotavirus acute gastroenteritis (AGE). METHODS: From ongoing rotavirus surveillance, we defined cases as children 12 weeks to 23 months old with EIA-confirmed rotavirus AGE. We enrolled one community-based and two hospital-based control groups. We collected vaccination status from cards at enrollment, or later in homes, and evaluated VE by logistic regression. RESULTS: We enrolled 91 cases (64 inpatient, 27 outpatient), 252 non-rotavirus AGE facility-based controls (unmatched), 203 non-AGE facility-based controls (age-matched) and 271 community controls (age-matched). Documented receipt of 3 pentavalent doses was 77% among cases and ranged from 81-86% among controls. One percent of cases and 0-2% of controls had no pentavalent doses. The adjusted odds ratio of three versus zero doses for being a case was 3.27 (95% CI 0.01-1010) for community controls and 0.69 (95% CI 0.06-7.75) for non-rotavirus hospital-based AGE controls, translating to VE of -227% and 31%, respectively, with wide confidence intervals. (No facility-based non-AGE controls were unvaccinated.) Similar results were found for ≥2 pentavalent doses and for severe rotavirus AGE. CONCLUSIONS: The study showed that it is feasible to carry out a real case control in the study area, but this needs to be done as soon as the vaccine is introduced to capture the real impact. Sham case-control or pilot studies before vaccine introduction can be useful in designing case-control VE studies.

Forecasting malaria dynamics based on causal relations between control interventions, climatic factors, and disease incidence in western Kenya.

Background: Malaria remains one of the deadliest diseases worldwide, especially among young children in sub-Saharan Africa. Predictive models are necessary for effective planning and resource allocation; however, statistical models suffer from association pitfalls. In this study, we used empirical dynamic modelling (EDM) to investigate causal links between climatic factors and intervention coverage with malaria for short-term forecasting. Methods: Based on data spanning the period from 2008 to 2022, we used convergent cross-mapping (CCM) to identify suitable lags for climatic drivers and investigate their effects, interaction strength, and suitability ranges on malaria incidence. Monthly malaria cases were collected at St. Elizabeth Lwak Mission Hospital. Intervention coverage and population movement data were obtained from household surveys in Asembo, western Kenya. Daytime land surface temperature (LSTD), rainfall, relative humidity (RH), wind speed, solar radiation, crop cover, and surface water coverage were extracted from remote sensing sources. Short-term forecasting of malaria incidence was performed using state-space reconstruction. Results: We observed causal links between climatic drivers, bed net use, and malaria incidence. LSTD lagged over the previous month; rainfall and RH lagged over the previous two months; and wind speed in the current month had the highest predictive skills. Increases in LSTD, wind speed, and bed net use negatively affected incidence, while increases in rainfall and humidity had positive effects. Interaction strengths were more pronounced at temperature, rainfall, RH, wind speed, and bed net coverage ranges of 30-35°C, 30-120 mm, 67-80%, 0.5-0.7 m/s, and above 90%, respectively. Temperature and rainfall exceeding 35°C and 180 mm, respectively, had a greater negative effect. We also observed good short-term predictive performance using the multivariable forecasting model (Pearson correlation coefficient = 0.85, root mean square error = 0.15). Conclusions: Our findings demonstrate the utility of CCM in establishing causal linkages between malaria incidence and both climatic and non-climatic drivers. By identifying these causal links and suitability ranges, we provide valuable information for modelling the impact of future climate scenarios.

Prevalence and risk factors of sexually transmitted infections in the setting of a generalized HIV epidemic-a population-based study, western Kenya.

BACKGROUND: Sexually transmitted infections (STIs) cause adverse health outcomes, including increasing HIV acquisition/transmission risk. We analyzed data from an HIV biomarker and behavioral survey to estimate STI prevalence, and explore associated factors in the setting of a generalized HIV epidemic in Siaya County, western Kenya. METHODS: Data were collected in March-September 2022 through face-to-face interviews using structured questionnaires; records from 9643 sexually active participants aged 13+ years were included in the analysis. We calculated weighted self-reported STI prevalence, by sex, age, and HIV status and explored associated factors using multivariable logistic regression. RESULTS: Median age was 37 years and 59.9% were female; HIV prevalence was 18.0%. Overall STI prevalence was 1.8%; 1.5-fold higher among males vs. females, and 2.6-fold higher among participants living with HIV vs. those without. HIV status and multiple sexual partners were independently associated with STI in both sexes. Mind-altering substance use and being circumcised were associated with STI among males. CONCLUSIONS: This study estimates STI prevalence in the setting of high HIV prevalence. Findings underscore the importance of: effective STI screening in HIV clinics and HIV testing and counseling in STI clinics; screening and counseling on substance use, and HIV pre-exposure prophylaxis; and intensive sexual health counseling in male circumcision programmes.

The effects of climatic and non-climatic factors on malaria mortality at different spatial scales in western Kenya, 2008-2019.

BACKGROUND: Malaria mortality is influenced by several factors including climatic and environmental factors, interventions, socioeconomic status (SES) and access to health systems. Here, we investigated the joint effects of climatic and non-climatic factors on under-five malaria mortality at different spatial scales using data from a Health and Demographic Surveillance System (HDSS) in western Kenya. METHODS: We fitted Bayesian spatiotemporal (zero-inflated) negative binomial models to monthly mortality data aggregated at the village scale and over the catchment areas of the health facilities within the HDSS, between 2008 and 2019. First order autoregressive temporal and conditional autoregressive spatial processes were included as random effects to account for temporal and spatial variation. Remotely sensed climatic and environmental variables, bed net use, SES, travel time to health facilities, proximity from water bodies/streams and altitude were included in the models to assess their association with malaria mortality. RESULTS: Increase in rainfall (mortality rate ratio (MRR)=1.12, 95% Bayesian credible interval (BCI): 1.04-1.20), Normalized Difference Vegetation Index (MRR=1.16, 95% BCI: 1.06-1.28), crop cover (MRR=1.17, 95% BCI: 1.11-1.24) and travel time to the hospital (MRR=1.09, 95% BCI: 1.04-1.13) were associated with increased mortality, whereas increase in bed net use (MRR=0.84, 95% BCI: 0.70-1.00), distance to the nearest streams (MRR=0.89, 95% BCI: 0.83-0.96), SES (MRR=0.95, 95% BCI: 0.91-1.00) and altitude (MRR=0.86, 95% BCI: 0.81-0.90) were associated with lower mortality. The effects of travel time and SES were no longer significant when data was aggregated at the health facility catchment level. CONCLUSION: Despite the relatively small size of the HDSS, there was spatial variation in malaria mortality that peaked every May-June. The rapid decline in malaria mortality was associated with bed nets, and finer spatial scale analysis identified additional important variables. Time and spatially targeted control interventions may be helpful, and fine spatial scales should be considered when data are available.

Health care-seeking behavior for childhood illnesses in western Kenya: Qualitative findings from the Child Health and Mortality Prevention Surveillance (CHAMPS) Study.

Background: Child mortality in Kenya is 41 per 1,000 live births, despite extensive investment in maternal, newborn, and child health interventions. Caregivers' health-seeking for childhood illness is an important determinant of child survival, and delayed healthcare is associated with high child mortality. We explore determinants of health-seeking decisions for childhood illnesses among caregivers in western Kenya. Methods: We conducted a qualitative study of 88 community members between April 2017 and February 2018 using purposive sampling in an informal urban settlement in Kisumu County, and in rural Siaya County. Key informant interviews, semi-structured interviews and focus group discussions were performed. We adopted the Partners for Applied Social Sciences model focusing on factors that influence the decision-making process to seek healthcare for sick infants and children. The discussions were audio-recorded and transcribed. Data management was completed on Nvivo® software. Iterative analysis process was utilized and themes were identified and collated. Results: Our findings reveal four thematic areas: Illness interpretation, the role of social relationship on illness recognition and response, medical pluralism and healthcare access. Participants reported some illnesses are caused by supernatural powers and some by biological factors, and that the illness etiology would determine the health-seeking pathway. It was common to seek consensus from respected community members on the diagnosis and therefore presumed cause and necessary treatment for a child's illness. Medical pluralism was commonly practiced and caregivers would alternate between biomedicine and traditional medicine. Accessibility of healthcare may determine the health seeking pathway. Caregivers unable to afford biomedical care may choose traditional medicine as a cheaper alternative. Conclusion: Health seeking behavior was driven by illness interpretation, financial cost associated with healthcare and advice from extended family and community. These findings enrich the perspectives of health education programs to develop health messages that address factors that hinder prompt health care seeking.

Impact of DREAMS interventions on attitudes towards gender norms among adolescent girls and young women: Findings from a prospective cohort in Kenya.

The DREAMS partnership aims to deliver a comprehensive package to reduce HIV incidence among adolescent girls and young women (AGYW), including through shifting gender norms. We evaluate DREAMS' effect on attitudes towards gender norms in two Kenyan settings. AGYW aged 15-22 in Nairobi (n = 852) and Gem (n = 761) were randomly selected for cohort enrolment in 2017-18 and followed-up to 2019. We described the proportion of AGYW and their male peers with equitable attitudes towards gender norms, using an adapted version of the GEM scale. We estimated the association between self-reported invitation to DREAMS (in 2017-18) and AGYW's attitudes towards two dimensions of gender norms, and then applied a causal inference framework to estimate the difference in the proportion of AGYW with equitable attitudes under the counterfactual scenarios that all versus none were DREAMS beneficiaries. We estimated that overall, 90.2% versus 87.1% of AGYW would have equitable norms around sexual and reproductive health decision-making in Nairobi if all versus none were DREAMS beneficiaries (+3.1; 95%CI:-2.5, +9.0). In Gem, we estimated a risk difference of +1.0 (89.6% vs 88.6%, 95%CI: -3.6,+5.6). There was no evidence for an effect of DREAMS on attitudes towards violence-related norms (Nairobi: 82.7% vs 82.2%, +0.5; 95%CI: -5.3,+6.5; Gem: 44.3% vs 48.2%, -3.9; 95%CI: -11.7,+3.0). We found no evidence of an impact of DREAMS invitation on individual attitudes towards gender norms. In some cases, equitable attitudes at enrolment left limited scope for improvement, and additional effort may be required to shift inequitable violence attitudes among both AGYW and their male peers.

Influenza and malaria coinfection among young children in western Kenya, 2009-2011.

BACKGROUND: Although children <5 years old in sub-Saharan Africa are vulnerable to both malaria and influenza, little is known about coinfection. METHODS: This retrospective, cross-sectional study in rural western Kenya examined outpatient visits and hospitalizations associated with febrile acute respiratory illness (ARI) during a 2-year period (July 2009-June 2011) in children <5 years old. RESULTS: Across sites, 45% (149/331) of influenza-positive patients were coinfected with malaria, whereas only 6% (149/2408) of malaria-positive patients were coinfected with influenza. Depending on age, coinfection was present in 4%-8% of outpatient visits and 1%-3% of inpatient admissions for febrile ARI. Children with influenza were less likely than those without to have malaria (risk ratio [RR], 0.57-0.76 across sites and ages), and children with malaria were less likely than those without to have influenza (RR, 0.36-0.63). Among coinfected children aged 24-59 months, hospital length of stay was 2.7 and 2.8 days longer than influenza-only-infected children at the 2 sites, and 1.3 and 3.1 days longer than those with malaria only (all P < .01). CONCLUSIONS: Coinfection with malaria and influenza was uncommon but associated with longer hospitalization than single infections among children 24-59 months of age.