BACKGROUND: We sought to estimate SARS-CoV-2 antibody seroprevalence within representative samples of the Kenyan population during the third year of the COVID-19 pandemic and the second year of COVID-19 vaccine use. METHODS: We conducted cross-sectional serosurveys among randomly selected, age-stratified samples of Health and Demographic Surveillance System (HDSS) residents in Kilifi and Nairobi. Anti-spike (anti-S) immunoglobulin G (IgG) serostatus was measured using a validated in-house ELISA and antibody concentrations estimated with reference to the WHO International Standard for anti-SARS-CoV-2 immunoglobulin. RESULTS: HDSS residents were sampled in February-June 2022 (Kilifi HDSS N = 852; Nairobi Urban HDSS N = 851) and in August-December 2022 (N = 850 for both sites). Population-weighted coverage for ≥1 doses of COVID-19 vaccine were 11.1% (9.1-13.2%) among Kilifi HDSS residents by November 2022 and 34.2% (30.7-37.6%) among Nairobi Urban HDSS residents by December 2022. Population-weighted anti-S IgG seroprevalence among Kilifi HDSS residents increased from 69.1% (65.8-72.3%) by May 2022 to 77.4% (74.4-80.2%) by November 2022. Within the Nairobi Urban HDSS, seroprevalence by June 2022 was 88.5% (86.1-90.6%), comparable with seroprevalence by December 2022 (92.2%; 90.2-93.9%). For both surveys, seroprevalence was significantly lower among Kilifi HDSS residents than among Nairobi Urban HDSS residents, as were antibody concentrations (p < 0.001). CONCLUSION: More than 70% of Kilifi residents and 90% of Nairobi residents were seropositive for anti-S IgG by the end of 2022. There is a potential immunity gap in rural Kenya; implementation of interventions to improve COVID-19 vaccine uptake among sub-groups at increased risk of severe COVID-19 in rural settings is recommended.

Background Up-to-date SARS-CoV-2 antibody seroprevalence estimates are important for informing public health planning, including priorities for Coronavirus disease 2019 (COVID-19) vaccination programs. We sought to estimate infection- and vaccination-induced SARS-CoV-2 antibody seroprevalence within representative samples of the Kenyan population approximately two years into the COVID-19 pandemic and approximately one year after rollout of the national COVID-19 vaccination program. Methods We conducted cross-sectional serosurveys within random, age-stratified samples of Kilifi Health and Demographic Surveillance System (HDSS) and Nairobi Urban HDSS residents. Anti-spike (anti-S) immunoglobulin G (IgG) and anti-nucleoprotein (anti-N) IgG were measured using validated in-house ELISAs. Target-specific Bayesian population-weighted seroprevalence was calculated overall, by sex and by age, with adjustment for test performance as appropriate. Anti-S IgG concentrations were estimated with reference to the WHO International Standard (IS) for anti-SARS-CoV-2 immunoglobulin and their reverse cumulative distributions plotted. Results Between February and June 2022, 852 and 851 individuals within the Kilifi HDSS and the Nairobi Urban HDSS, respectively, were sampled. Only 11.0% (95% confidence interval [CI] 9.0-13.3) of all Kilifi HDSS participants and 33.4% (95%CI 30.2-36.6) of all Nairobi Urban HDSS participants had received any doses of COVID-19 vaccine. Population-weighted antiS IgG seroprevalence was 69.1% (95% credible interval [CrI] 65.8-72.3) within the Kilifi HDSS and 88.5% (95%CrI 86.1-90.6) within the Nairobi Urban HDSS. Among COVID-unvaccinated residents of the Kilifi HDSS and Nairobi Urban HDSS, it was 66.7% (95%CrI 63.3-70.0) and 85.3% (95%CrI 82.1-88.2), respectively. Population-weighted, test-adjusted anti-N IgG seroprevalence within the Kilifi HDSS was 53.5% (95%CrI 46.5-61.1) and 65.5% (95%CrI 56.0-75.6) within the Nairobi Urban HDSS. The prevalence of anti-N antibodies was similar in vaccinated and unvaccinated subgroups in both HDSS populations. Anti-S IgG concentrations were significantly lower among Kilifi HDSS residents than among Nairobi Urban HDSS residents (p< 0.001). Conclusions Approximately, 7 in 10 Kilifi residents and 9 in 10 Nairobi residents were seropositive for anti-S IgG by May 2022 and June 2022, respectively. Given COVID-19 vaccination coverage, anti-S IgG seropositivity among COVID-unvaccinated individuals, and anti-N IgG seroprevalence, population-level anti-S IgG seroprevalence was predominantly derived from infection. Interventions to improve COVID-19 vaccination uptake should be targeted to individuals in rural Kenya who are at high risk of severe COVID-19. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.

Background: Maternal immunisation to boost respiratory syncytial virus (RSV) antibodies in pregnant women, is a strategy being considered to enhance infant protection from severe RSV associated disease. However, little is known about the efficiency of transplacental transfer of RSV-specific antibodies in a setting with a high burden of malaria and HIV, to guide the implementation of such a vaccination program. Methods: Using a plaque reduction neutralization assay, we screened 400 pairs of cord and maternal serum specimens from pregnant women for RSV-specific antibodies. Participants were pregnant women of two surveillance cohorts: 200 participants from a hospital cohort in Kilifi, Coastal Kenya and 200 participants from a surveillance cohort in Siaya, Western Kenya. Transplacental transfer efficiency was determined by the cord to maternal titre ratio (CMTR). Logistic regression was used to determine independent predictors of impaired transplacental transfer of RSV-specific antibodies. Results: A total of 800 samples were screened from the 400 participants. At enrollment the median age was 25 years (Interquartile range (IQR): 21-31). Overall, transplacental transfer was efficient and did not differ between Kilifi and Siaya cohort (1.02 vs. 1.02; p=0.946) but was significantly reduced among HIV-infected mothers compared to HIV-uninfected mothers (mean CMTR: 0.98 vs 1.03; p=0.015). Prematurity <33 weeks gestation (Odds ratio [OR]: 0.23, 95% confidence interval [CI] 0.06-0.85; p=0.028), low birth weight <2.5 kgs (OR: 0.25, 95% CI: 0.07-0.94; p=0.041) and HIV infection (OR: 0.47, 95% CI:0.23-0.98; p=0.045) reduced efficiency of transplacental transfer among these women. Conclusions: Transplacental transfer of RSV-specific antibodies among pregnant women in Kenya is efficient. A consideration to integrate other preventive interventions with maternal RSV vaccination targeting infants born premature (<33 weeks gestation), with low birth weight <2.5 kgs, or HIV-infected mothers is likely to improve vaccine outcomes in this setting.

OBJECTIVE: HIV-associated mortality rates in Africa decreased by 10%-20% annually in 2003-2011, after the introduction of antiretroviral therapy (ART). We sought to document HIV-associated mortality rates in the general population in Kenya after 2011 in an era of expanded access to ART. DESIGN: We obtained data on mortality rates and migration from a health and demographic surveillance system (HDSS) in Gem, western Kenya, and data for HDSS residents aged 15-64 years from home-based HIV-counseling and testing (HBCT) rounds in 2011, 2012, 2013, and 2016. METHODS: Mortality trends were determined among a closed cohort of residents who participated in at least the 2011 round of HBCT. RESULTS: Of 32,467 eligible HDSS residents, 22,688 (70%) participated in the 2011 round and comprised the study cohort. All-cause mortality rates declined from 10.0 (95% confidence interval [CI] 8.4-11.7) per 1000 in 2011 to 7.4 (95% CI 5.7-9.0) in 2016, while the mortality rate was stable among HIV-uninfected residents, at 5.7 per 1000 person-years. Among HIV-infected residents, mortality rates declined from 30.5 per 1000 in 2011 to 15.9 per 1000 in 2016 (average decline, 6% per year). The HIV-infected group receiving ART had higher mortality rates than the HIV-uninfected group (adjusted rate ratio (aRR), 2.8; 95% CI 2.2-3.4), as did the HIV-infected group who did not receive ART (aRR, 5.3; 95% CI 4.5-6.2). CONCLUSIONS: Mortality rates among HIV-infected individuals declined substantially during ART expansion between 2011 and 2016, though less than during early ART introduction. Mortality trends among HIV-infected populations are critical to understanding epidemic dynamics.

BACKGROUND: Examining skilled attendance throughout pregnancy, delivery and immediate postnatal period is proxy indicator on the progress towards reduction of maternal and neonatal mortality in developing countries. METHODS: We conducted a cross-sectional baseline survey of households of mothers with at least 1 child under-5 years in 2012 within the KEMRI/CDC health and demographic surveillance system (HDSS) area in rural western Kenya. RESULTS: Out of 8260 mother-child pairs, data on antenatal care (ANC) in the most recent pregnancy was obtained for 89% (n = 8260); 97% (n = 7387) reported attendance. Data on number of ANC visits was available for 89% (n = 7140); 52% (n = 6335) of mothers reported >/=4 ANC visits. Data on gestation month at first ANC was available for 94% (n = 7140) of mothers; 14% (n = 6690) reported first visit was in1(st)trimester (0-12 weeks), 73% in 2nd trimester (14-28 weeks) and remaining 13% in third trimester. Forty nine percent (n = 8259) of mothers delivered in a Health Facility (HF), 48% at home and 3% en route to HF. Forty percent (n = 7140) and 63% (n = 4028) of mothers reporting ANC attendance and HF delivery respectively also reported receiving postnatal care (PNC). About 36% (n = 8259) of mothers reported newborn assessment (NBA). Sixty eight percent (n = 3966) of mothers that delivered at home reported taking newborn for HF check-up, with only 5% (n = 2693) doing so within 48 h of delivery. Being </=34 years (OR 1.8; 95% CI 1.4-2.4) and at least primary education (OR 5.3; 95% CI 1.8-15.3) were significantly associated with ANC attendance. Being </=34 years (OR 1.7; 95% CI 1.5-2.0), post-secondary vs primary education (OR 10; 95% CI 4.4-23.4), ANC attendance (OR 4.5; 95% CI 3.2-6.1), completing >/=4 ANC visits (OR 2.0; 95% CI 1.8-2.2), were strongly associated with HF delivery. The continuum of care was such that 97% (n = 7387) mothers reported ANC attendance, 49% reported both ANC and HF delivery attendance, 34% reported ANC, HF delivery and PNC attendance and only 18% reported ANC, HF delivery, PNC and NBA attendance. CONCLUSION: Uptake of services drastically declined from antenatal to postnatal period, along the continuum of care. Age and education were key determinants of uptake.

The last decade has seen rapid evolution in guidance from the WHO concerning the provision of HIV services along the diagnosis-to-treatment continuum, but the extent to which these recommendations are adopted as national policies in Kenya, and subsequently implemented in health facilities, is not well understood. Identifying gaps in policy coverage and implementation is important for highlighting areas for improving service delivery, leading to better health outcomes. We compared WHO guidance with national policies for HIV testing and counselling, prevention of mother-to-child transmission, HIV treatment and retention in care. We then investigated implementation of these national policies in health facilities in one rural (Kisumu) and one urban (Nairobi) sites in Kenya. Implementation was documented using structured questionnaires that were administered to in-charge staff at 10 health facilities in Nairobi and 34 in Kisumu. Policies were defined as widely implemented if they were reported to occur in > 70% facilities, partially implemented if reported to occur in 30-70% facilities, and having limited implementation if reported to occur in < 30% facilities. Overall, Kenyan national HIV care and treatment policies were well aligned with WHO guidance. Policies promoting access to treatment and retention in care were widely implemented, but there was partial or limited implementation of several policies promoting access to HIV testing, and the more recent policy of Option B+ for HIV-positive pregnant women. Efforts are needed to improve implementation of policies designed to increase rates of diagnosis, thus facilitating entry into HIV care, if morbidity and mortality burdens are to be further reduced in Kenya, and as the country moves towards universal access to antiretroviral therapy.

BACKGROUND: Influenza and respiratory syncytial virus (RSV) associated mortality has not been well-established in tropical Africa. METHODS: We used the negative binomial regression method and the rate-difference method (i.e. deaths during low and high influenza/RSV activity months), to estimate excess mortality attributable to influenza and RSV using verbal autopsy data collected through a health and demographic surveillance system in Western Kenya, 2007-2013. Excess mortality rates were calculated for a) all-cause mortality, b) respiratory deaths (including pneumonia), c) HIV-related deaths, and d) pulmonary tuberculosis (TB) related deaths. RESULTS: Using the negative binomial regression method, the mean annual all-cause excess mortality rate associated with influenza and RSV was 14.1 (95% confidence interval [CI] 0.0-93.3) and 17.1 (95% CI 0.0-111.5) per 100,000 person-years (PY) respectively; and 10.5 (95% CI 0.0-28.5) and 7.3 (95% CI 0.0-27.3) per 100,000 PY for respiratory deaths, respectively. Highest mortality rates associated with influenza were among ≥50 years, particularly among persons with TB (41.6[95% CI 0.0-122.7]); and with RSV were among <5 years. Using the rate-difference method, the excess mortality rate for influenza and RSV was 44.8 (95% CI 36.8-54.4) and 19.7 (95% CI 14.7-26.5) per 100,000 PY, respectively, for all-cause deaths; and 9.6 (95% CI 6.3-14.7) and 6.6 (95% CI 3.9-11.0) per 100,000 PY, respectively, for respiratory deaths. CONCLUSIONS: Our study shows a substantial excess mortality associated with influenza and RSV in Western Kenya, especially among children <5 years and older persons with TB, supporting recommendations for influenza vaccination and efforts to develop RSV vaccines.

The Network for Analysing Longitudinal Population-based HIV/AIDS data on Africa (ALPHA Network) was established in 2005 and aims to: (i) broaden the evidence base on HIV epidemiology for informing policy; (ii) strengthen analytical capacity for HIV research; and (iii) foster collaboration between study sites. All of the study sites participating in the ALPHA Network are independently managed and have their own scientific agendas and tailored research methodologies, but share a common interest in HIV epidemiology and its interactions with the socio-demographic characteristics of the populations they cover.

Malaria is among the leading causes of mortality in the younger under-five group of children zero to four years of age. This study aims at describing the relationship between rainfall and temperature on under-five malaria or anaemia mortality in Kenya Medical Research Institute and United States Centers for Disease Control (KEMRI/CDC) Health and Demographic Surveillance System (HDSS). This study was conducted through the ongoing KEMRI and CDC collaboration. A general additive model with a Poisson link function was fit to model the weekly association of lagged cumulative rainfall and average temperature on malaria/anemia mortality in KEMRI/CDC HDSS for the period 2003 to 2008. A trend function was included in the model to control for time trends and seasonality not explained by weather fluctuations. 95% confidence intervals was presented with estimates. Malaria or anemia mortality was found to be associated with changes in temperature and rainfall in the KEMRI HDSS, with a delay up to 16 weeks. The empirical estimates of associations describe established biological relationships well. This information, and particularly, the strength of the relationships over longer lead times can highlight the possibility of developing a predictive forecast with lead times up to 16 weeks in order to enhance preparedness to high transmission episodes.

BACKGROUND: Mortality from external causes, of all kinds, is an important component of overall mortality on a global basis. However, these deaths, like others in Africa and Asia, are often not counted or documented on an individual basis. Overviews of the state of external cause mortality in Africa and Asia are therefore based on uncertain information. The INDEPTH Network maintains longitudinal surveillance, including cause of death, at population sites across Africa and Asia, which offers important opportunities to document external cause mortality at the population level across a range of settings. OBJECTIVE: To describe patterns of mortality from external causes at INDEPTH Network sites across Africa and Asia, according to the WHO 2012 verbal autopsy (VA) cause categories. DESIGN: All deaths at INDEPTH sites are routinely registered and followed up with VA interviews. For this study, VA archives were transformed into the WHO 2012 VA standard format and processed using the InterVA-4 model to assign cause of death. Routine surveillance data also provide person-time denominators for mortality rates. RESULTS: A total of 5,884 deaths due to external causes were documented over 11,828,253 person-years. Approximately one-quarter of those deaths were to children younger than 15 years. Causes of death were dominated by childhood drowning in Bangladesh, and by transport-related deaths and intentional injuries elsewhere. Detailed mortality rates are presented by cause of death, age group, and sex. CONCLUSIONS: The patterns of external cause mortality found here generally corresponded with expectations and other sources of information, but they fill some important gaps in population-based mortality data. They provide an important source of information to inform potentially preventive intervention designs.

BACKGROUND: As the HIV/AIDS pandemic has evolved over recent decades, Africa has been the most affected region, even though a large proportion of HIV/AIDS deaths have not been documented at the individual level. Systematic application of verbal autopsy (VA) methods in defined populations provides an opportunity to assess the mortality burden of the pandemic from individual data. OBJECTIVE: To present standardised comparisons of HIV/AIDS-related mortality at sites across Africa and Asia, including closely related causes of death such as pulmonary tuberculosis (PTB) and pneumonia. DESIGN: Deaths related to HIV/AIDS were extracted from individual demographic and VA data from 22 INDEPTH sites across Africa and Asia. VA data were standardised to WHO 2012 standard causes of death assigned using the InterVA-4 model. Between-site comparisons of mortality rates were standardised using the INDEPTH 2013 standard population. RESULTS: The dataset covered a total of 10,773 deaths attributed to HIV/AIDS, observed over 12,204,043 person-years. HIV/AIDS-related mortality fractions and mortality rates varied widely across Africa and Asia, with highest burdens in eastern and southern Africa, and lowest burdens in Asia. There was evidence of rapidly declining rates at the sites with the heaviest burdens. HIV/AIDS mortality was also strongly related to PTB mortality. On a country basis, there were strong similarities between HIV/AIDS mortality rates at INDEPTH sites and those derived from modelled estimates. CONCLUSIONS: Measuring HIV/AIDS-related mortality continues to be a challenging issue, all the more so as anti-retroviral treatment programmes alleviate mortality risks. The congruence between these results and other estimates adds plausibility to both approaches. These data, covering some of the highest mortality observed during the pandemic, will be an important baseline for understanding the future decline of HIV/AIDS.

BACKGROUND: Mortality from non-communicable diseases (NCDs) is a major global issue, as other categories of mortality have diminished and life expectancy has increased. The World Health Organization's Member States have called for a 25% reduction in premature NCD mortality by 2025, which can only be achieved by substantial reductions in risk factors and improvements in the management of chronic conditions. A high burden of NCD mortality among much older people, who have survived other hazards, is inevitable. The INDEPTH Network collects detailed individual data within defined Health and Demographic Surveillance sites. By registering deaths and carrying out verbal autopsies to determine cause of death across many such sites, using standardised methods, the Network seeks to generate population-based mortality statistics that are not otherwise available. OBJECTIVE: To describe patterns of adult NCD mortality from INDEPTH Network sites across Africa and Asia, according to the WHO 2012 verbal autopsy (VA) cause categories, with separate consideration of premature (15-64 years) and older (65+ years) NCD mortality. DESIGN: All adult deaths at INDEPTH sites are routinely registered and followed up with VA interviews. For this study, VA archives were transformed into the WHO 2012 VA standard format and processed using the InterVA-4 model to assign cause of death. Routine surveillance data also provide person-time denominators for mortality rates. RESULTS: A total of 80,726 adult (over 15 years) deaths were documented over 7,423,497 person-years of observation. NCDs were attributed as the cause for 35.6% of these deaths. Slightly less than half of adult NCD deaths occurred in the 15-64 age group. Detailed results are presented by age and sex for leading causes of NCD mortality. Per-site rates of NCD mortality were significantly correlated with rates of HIV/AIDS-related mortality. CONCLUSIONS: These findings present important evidence on the distribution of NCD mortality across a wide range of African and Asian settings. This comes against a background of global concern about the burden of NCD mortality, especially among adults aged under 70, and provides an important baseline for future work.

BACKGROUND: Diarrhea is a leading cause of childhood morbidity and mortality in sub-Saharan Africa. Data on risk factors for mortality are limited. We conducted hospital-based surveillance to characterize the etiology of diarrhea and identify risk factors for death among children hospitalized with diarrhea in rural western Kenya. METHODS AND FINDINGS: We enrolled all children <5 years old, hospitalized with diarrhea (≥3 loose stools in 24 hours) at two district hospitals in Nyanza Province, western Kenya. Clinical and demographic information was collected. Stool specimens were tested for bacterial and viral pathogens. Bivariate and multivariable logistic regression analyses were carried out to identify risk factors for death. From May 23, 2005 to May 22, 2007, 1,146 children <5 years old were enrolled; 107 (9%) children died during hospitalization. Nontyphoidal Salmonella were identified in 10% (118), Campylobacter in 5% (57), and Shigella in 4% (42) of 1,137 stool samples; rotavirus was detected in 19% (196) of 1,021 stool samples. Among stools from children who died, nontyphoidal Salmonella were detected in 22%, Shigella in 11%, rotavirus in 9%, Campylobacter in 5%, and S. Typhi in <1%. In multivariable analysis, infants who died were more likely to have nontyphoidal Salmonella (adjusted odds ratio [aOR] = 6.8; 95% CI 3.1-14.9), and children <5 years to have Shigella (aOR = 5.5; 95% CI 2.2-14.0) identified than children who survived. Children who died were less likely to be infected with rotavirus (OR = 0.4; 95% CI 0.2-0.8). Further risk factors for death included being malnourished (aOR = 4.2; 95% CI 2.1-8.7); having oral thrush on physical exam (aOR = 2.3; 95% CI 1.4-3.8); having previously sought care at a hospital for the illness (aOR = 2.2; 95% CI 1.2-3.8); and being dehydrated as diagnosed at discharge/death (aOR = 2.5; 95% CI 1.5-4.1). A clinical diagnosis of malaria, and malaria parasites seen on blood smear, were not associated with increased risk of death. This study only captured in-hospital childhood deaths, and likely missed a substantial number of additional deaths that occurred at home. CONCLUSION: Nontyphoidal Salmonella and Shigella are associated with mortality among rural Kenyan children with diarrhea who access a hospital. Improved prevention and treatment of diarrheal disease is necessary. Enhanced surveillance and simplified laboratory diagnostics in Africa may assist clinicians in appropriately treating potentially fatal diarrheal illness. Please see later in the article for the Editors' Summary.