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.

SARS-CoV-2 seroprevalence and implications for population immunity: Evidence from two Health and Demographic Surveillance System sites in Kenya, February-December 2022.

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.

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.

A long-term observational study of paediatric snakebite in Kilifi County, south-east Kenya.

INTRODUCTION: Estimates suggest that one-third of snakebite cases in sub-Saharan Africa affect children. Despite children being at a greater risk of disability and death, there are limited published data. This study has determined the: population-incidence and mortality rate of hospital-attended paediatric snakebite; clinical syndromes of snakebite envenoming; and predictors of severe local tissue damage. METHODS: All children presenting to Kilifi County Hospital, Kenya with snakebite were identified through the Kilifi Health and Demographic Surveillance System (KHDSS). Cases were prospectively registered, admitted for at least 24-hours, and managed on a paediatric high dependency unit (HDU). Households within the KHDSS study area have been included in 4-monthly surveillance and verbal autopsy, enabling calculation of population-incidence and mortality. Predictors of severe local tissue damage were identified using a multivariate logistic regression analysis. RESULTS: Between 2003 and 2021, there were 19,606 admissions to the paediatric HDU, of which 584 were due to snakebite. Amongst young children (≤5-years age) the population-incidence of hospital-attended snakebite was 11.3/100,000 person-years; for children aged 6-12 years this was 29.1/100,000 person-years. Incidence remained consistent over the study period despite the population size increasing (98,967 person-years in 2006; and 153,453 person-years in 2021). Most cases had local envenoming alone, but there were five snakebite associated deaths. Low haemoglobin; raised white blood cell count; low serum sodium; high systolic blood pressure; and an upper limb bite-site were independently associated with the development of severe local tissue damage. CONCLUSION: There is a substantial burden of disease due to paediatric snakebite, and the annual number of cases has increased in-line with population growth. The mortality rate was low, which may reflect the species causing snakebite in this region. The identification of independent predictors of severe local tissue damage can help to inform future research to better understand the pathophysiology of this important complication.

Spatial heterogeneity of low-birthweight deliveries on the Kenyan coast.

BACKGROUND: Understanding spatial variations in health outcomes is a fundamental component in the design of effective, efficient public health strategies. Here we analyse the spatial heterogeneity of low birthweight (LBW) hospital deliveries from a demographic surveillance site on the Kenyan coast. METHODS: A secondary data analysis on singleton livebirths that occurred between 2011 and 2021 within the rural areas of the Kilifi Health and demographic surveillance system (KHDSS) was undertaken. Individual-level data was aggregated at enumeration zone (EZ) and sub-location level to estimate the incidence of LBW adjusted for accessibility index using the Gravity model. Finally, spatial variations in LBW were assessed using Martin Kulldorf's spatial scan statistic under Discrete Poisson distribution. RESULTS: Access adjusted LBW incidence was estimated as 87 per 1,000 person years in the under 1 population (95% CI: 80, 97) at the sub-location level similar to EZ. The adjusted incidence ranged from 35 to 159 per 1,000 person years in the under 1 population at sub-location level. There were six significant clusters identified at sub-location level and 17 at EZ level using the spatial scan statistic. CONCLUSIONS: LBW is a significant health risk on the Kenya coast, possibly under-estimated from previous health information systems, and the risk of LBW is not homogenously distributed across areas served by the County hospital.

Trends in inpatient and post-discharge mortality among young infants admitted to Kilifi County Hospital, Kenya: a retrospective cohort study.

OBJECTIVES: To describe admission trends and estimate inpatient and post-discharge mortality and its associated exposures, among young infants (YI) admitted to a county hospital in Kenya. DESIGN: Retrospective cohort study. SETTING: Secondary level hospital. PARTICIPANTS: YI aged less than 60 days admitted to hospital from January 2009 to December 2019: 12 271 admissions in 11 877 individuals. YI who were resident within a Kilifi Health and Demographic Surveillance System (KHDSS): n=3625 with 4421 admissions were followed-up for 1 year after discharge. PRIMARY AND SECONDARY OUTCOME MEASURES: Inpatient and 1-year post-discharge mortality, the latter in KHDSS residents. RESULTS: Of 12 271 YI admissions, 4421 (36%) were KHDSS-resident. Neonatal sepsis, preterm complications and birth asphyxia accounted for 83% of the admissions. The proportion of YI among under-5s admissions increased from 19% in 2009 to 34% in 2019 (Ptrend=0.02). Inpatient case fatality was 16%, with 66% of the deaths occurring within 48 hours of admission. The introduction of free maternity care in 2013 was not associated with a change in admissions or inpatient mortality among YI. During 1-year post-discharge, 208/3625 (5.7%) YI died, 64.3 (95% CI 56.2 to 73.7) per 1000 infant-years. 49% of the post-discharge deaths occurred within 1 month of discharge, and 49% of post-discharge deaths occurred at home. Both inpatient and post-discharge deaths were associated with low admission weight. Inpatient mortality was associated with clinical signs of disease severity, while post-discharge mortality was associated with the length of hospitalisation, leaving against advice and referral to a specialised hospital. CONCLUSIONS: YIs accounted for an increasing proportion of paediatric admissions and their overall mortality remains high. Post-discharge mortality accounts for a lower proportion of deaths but mortality rate is higher than among children aged 2-59 months. Services to address post-discharge mortality are needed and should focus on infants at higher risk.

Impact of Intermittent Presumptive Treatment for Malaria in Pregnancy on Hospital Birth Outcomes on the Kenyan Coast.

BACKGROUND: Intermittent preventive treatment (IPTp) for pregnant women with sulfadoxine-pyrimethamine (SP) is widely implemented for the prevention of malaria in pregnancy and adverse birth outcomes. The efficacy of SP is declining, and there are concerns that IPTp may have reduced impact in areas of high resistance. We sought to determine the protection afforded by SP as part of IPTp against adverse birth outcomes in an area with high levels of SP resistance on the Kenyan coast. METHODS: A secondary analysis of surveillance data on deliveries at the Kilifi County Hospital between 2015 and 2021 was undertaken in an area of low malaria transmission and high parasite mutations associated with SP resistance. A multivariable logistic regression model was developed to estimate the effect of SP doses on the risk of low birthweight (LBW) deliveries and stillbirths. RESULTS: Among 27 786 deliveries, 3 or more doses of IPTp-SP were associated with a 27% reduction in the risk of LBW (adjusted odds ratio [aOR], 0.73; 95% confidence interval [CI], .64-.83; P < .001) compared with no dose. A dose-response association was observed with increasing doses of SP from the second trimester linked to increasing protection against LBW deliveries. Three or more doses of IPTp-SP were also associated with a 21% reduction in stillbirth deliveries (aOR, 0.79; 95% CI, .65-.97; P = .044) compared with women who did not take any dose of IPTp-SP. CONCLUSIONS: The continued significant association of SP on LBW deliveries suggests that the intervention may have a non-malaria impact on pregnancy outcomes.

Safety and immunogenicity of ChAdOx1 nCoV-19 (AZD1222) vaccine in adults in Kenya: a phase 1/2 single-blind, randomised controlled trial.

Background: There are limited data on the immunogenicity of coronavirus disease 2019 (COVID-19) vaccines in African populations. Here we report the immunogenicity and safety of the ChAdOx1 nCoV-19 (AZD1222) vaccine from a phase 1/2 single-blind, randomised, controlled trial among adults in Kenya conducted as part of the early studies assessing vaccine performance in different geographical settings to inform Emergency Use Authorisation. Methods: We recruited and randomly assigned (1:1) 400 healthy adults aged ≥18 years in Kenya to receive ChAdOx1 nCoV-19 or control rabies vaccine, each as a two-dose schedule with a 3-month interval. The co-primary outcomes were safety, and immunogenicity assessed using total IgG enzyme-linked immunosorbent assay (ELISA) against SARS-CoV-2 spike protein 28 days after the second vaccination. Results: Between 28 th October 2020 and 19 th August 2021, 400 participants were enrolled and assigned to receive ChAdOx1 nCoV-19 (n=200) or rabies vaccine (n=200). Local and systemic adverse events were self-limiting and mild or moderate in nature. Three serious adverse events were reported but these were deemed unrelated to vaccination. The geometric mean anti-spike IgG titres 28 days after second dose vaccination were higher in the ChAdOx1 group (2773 ELISA units [EU], 95% CI 2447, 3142) than in the rabies vaccine group (61 EU, 95% CI 45, 81) and persisted over the 12 months follow-up. We did not identify any symptomatic infections or hospital admissions with respiratory illness and so vaccine efficacy against clinically apparent infection could not be measured. Vaccine efficacy against asymptomatic SARS-CoV-2 infection was 38.4% (95% CI -26.8%, 70.1%; p=0.188). Conclusions: The safety, immunogenicity and efficacy against asymptomatic infection of ChAdOx1 nCoV-19 among Kenyan adults was similar to that observed elsewhere in the world, but efficacy against symptomatic infection or severe disease could not be measured in this cohort. Pan-African Clinical Trials Registration: PACTR202005681895696 (11/05/2020).

Sero-surveillance for IgG to SARS-CoV-2 at antenatal care clinics in three Kenyan referral hospitals: Repeated cross-sectional surveys 2020-21.

INTRODUCTION: The high proportion of SARS-CoV-2 infections that have remained undetected presents a challenge to tracking the progress of the pandemic and estimating the extent of population immunity. METHODS: We used residual blood samples from women attending antenatal care services at three hospitals in Kenya between August 2020 and October 2021and a validated IgG ELISA for SARS-Cov-2 spike protein and adjusted the results for assay sensitivity and specificity. We fitted a two-component mixture model as an alternative to the threshold analysis to estimate of the proportion of individuals with past SARS-CoV-2 infection. RESULTS: We estimated seroprevalence in 2,981 women; 706 in Nairobi, 567 in Busia and 1,708 in Kilifi. By October 2021, 13% of participants were vaccinated (at least one dose) in Nairobi, 2% in Busia. Adjusted seroprevalence rose in all sites; from 50% (95%CI 42-58) in August 2020, to 85% (95%CI 78-92) in October 2021 in Nairobi; from 31% (95%CI 25-37) in May 2021 to 71% (95%CI 64-77) in October 2021 in Busia; and from 1% (95% CI 0-3) in September 2020 to 63% (95% CI 56-69) in October 2021 in Kilifi. Mixture modelling, suggests adjusted cross-sectional prevalence estimates are underestimates; seroprevalence in October 2021 could be 74% in Busia and 72% in Kilifi. CONCLUSIONS: There has been substantial, unobserved transmission of SARS-CoV-2 in Nairobi, Busia and Kilifi Counties. Due to the length of time since the beginning of the pandemic, repeated cross-sectional surveys are now difficult to interpret without the use of models to account for antibody waning.

Efficiency of transplacental transfer of respiratory syncytial virus (RSV) specific antibodies among pregnant women in Kenya.

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 transfer 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.