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Abstract 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

Abstract The epidemiology and circulation patterns of various rhinovirus types within populations remains under-explored. We generated 803 VP4/VP2 gene sequences from rhinovirus-positive samples collected from acute respiratory illness (ARI) patients, including both in-patient and outpatient cases, between 1st January and 31st December 2014 from eleven surveillance sites across Kenya and used phylogenetics to characterise virus introductions and spread. RVs were detected throughout the year, with the highest detection rates observed from January to March and June to July. We detected a total of 114 of the 169 currently classified types. Our analysis revealed numerous virus introductions into Kenya characterized by local expansion and extinction, and extensive spatial mixing of types within the country due to the widespread transmission of the virus after an introduction. This work demonstrates that in a single year, the circulation of rhinovirus in Kenya was characterized by substantial genetic diversity, multiple introductions, and extensive geographical spread.

Abstract Background Respiratory syncytial virus (RSV) is one of the main causes of hospitalization for lower respiratory tract infection in children under five years of age globally. Maternal vaccines and monoclonal antibodies for RSV prevention among infants are approved for use in high income countries. However, data are limited on the economic burden of RSV disease from low- and middle-income countries (LMIC) to inform decision making on prioritization and introduction of such interventions. This study aimed to estimate household and health system costs associated with childhood RSV in Kenya. Methods A structured questionnaire was administered to caregivers of children aged

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.

Abstract Objective: Identifying factors that may influence aflatoxin exposure in children under 5 years of age living in farming households in western Kenya. Design: We used a mixed methods design. The quantitative component entailed serial cross-sectional interviews in 250 farming households to examine crop processing and conservation practices, household food storage and consumption and local understandings of aflatoxins. Qualitative data collection included focus group discussions (N 7) and key informant interviews (N 13) to explore explanations of harvesting and post-harvesting techniques and perceptions of crop spoilage. Setting: The study was carried out in Asembo, a rural community where high rates of child stunting exist. Participants: A total of 250 female primary caregivers of children under 5 years of age and thirteen experts in farming and food management participated. Results: Study results showed that from a young age, children routinely ate maize-based dishes. Economic constraints and changing environmental patterns guided the application of sub-optimal crop practices involving early harvest, poor drying, mixing spoiled with good cereals and storing cereals in polypropylene bags in confined quarters occupied by humans and livestock and raising risks of aflatoxin contamination. Most (80 %) smallholder farmers were unaware of aflatoxins and their harmful economic and health consequences. Conclusions: Young children living in subsistence farming households may be at risk of exposure to aflatoxins and consequent ill health and stunting. Sustained efforts to increase awareness of the risks of aflatoxins and control measures among subsistence farmers could help to mitigate practices that raise exposure.

Acute febrile illness (AFI) is a common reason for healthcare seeking and hospitalization in Sub-Saharan Africa and is often presumed to be malaria. However, a broad range of pathogens cause fever, and more comprehensive data on AFI etiology can improve clinical management, prevent unnecessary prescriptions, and guide public health interventions. We conducted surveillance for AFI (temperature ≥38.0°C

Antibiotic exposure is associated with resistant bacterial colonization, but this relationship can be obscured in community settings owing to horizontal bacterial transmission and broad distributions. Locality-level exposure estimates considering inhabitants' length of stay, exposure history, and exposure conditions of areas nearby could clarify these relationships. We used prescription data filled during 2010-2015 for 23 antibiotic types for members of georeferenced households in a population-based infectious disease surveillance platform. For each antibiotic and locality, we generated exposure estimates, expressed in defined daily doses (DDD) per 1000 inhabitant days of observation (IDO). We also estimated relevant environmental parameters, such as the distance of each locality to water, sanitation, and other amenities. We used data on ampicillin, ceftazidime, and trimethoprim-and-sulfamethoxazole resistant Escherichia coli colonization from stool cultures of asymptomatic individuals in randomly selected households. We tested exposure-colonization associations using permutation analysis of variance and logistic generalized linear mixed-effect models. Overall, exposure was highest for trimethoprim-sulfamethoxazole (1.8 DDD per 1000 IDO), followed by amoxicillin (0.7 DDD per 1000 IDO). Of 1,386 unique household samples from 195 locations tested between September 2015 and January 2016, 90%, 85% and 4% were colonized with E. coli resistant to trimethoprim and sulfamethoxazole, ampicillin, and ceftazidime, respectively. Ceftazidime-resistant E. coli colonization was common in areas with increased trimethoprim-sulfamethoxazole, cloxacillin, and erythromycin exposure. No association with any of the physical environmental variables was observed. We did not detect relationships between distribution patterns of ampicillin or trimethoprim-and-sulfamethoxazole resistant E. coli colonization and the risk factors assessed. Appropriate temporal and spatial scaling of raw antibiotic exposure data to account for evolution and ecological contexts of antibiotic resistance could clarify exposure-colonization relationships in community settings and inform community stewardship program.

Background Reliable mortality data are important for evaluating the impact of health interventions. However, data on mortality patterns among populations living in urban informal settlements are limited. Objectives To examine the mortality patterns and trends in an urban informal settlement in Kibera, Nairobi, Kenya, Methods Using data from a population-based surveillance platform we estimated overall and cause-specific mortality rates for all age groups using person-year-observation (pyo) denominators and using Poisson regression tested for trends in mortality rates over time. We compared associated mortality rates across groups using incidence rate ratios (IRR). Assignment of probable cause(s) of death was done using the InterVA-4 model. Results We registered 1134 deaths from 2009 to 2018, yielding a crude mortality rate of 4.4 (95% Confidence Interval [CI]4.2–4.7) per 1,000 pyo. Males had higher overall mortality rates than females (incidence rate ratio [IRR], 1.44; 95% CI, 1.28–1.62). The highest mortality rate was observed among children aged

Abstract Assessment of the relative impact of climate change on malaria dynamics is a complex problem. Climate is a well-known factor that plays a crucial role in driving malaria outbreaks in epidemic transmission areas. However, its influence in endemic environments with intensive malaria control interventions is not fully understood, mainly due to the scarcity of high-quality, long-term malaria data. The demographic surveillance systems in Africa offer unique platforms for quantifying the relative effects of weather variability on the burden of malaria. Here, using a process-based stochastic transmission model, we show that in the lowlands of malaria endemic western Kenya, variations in climatic factors played a key role in driving malaria incidence during 2008–2019, despite high bed net coverage and use among the population. The model captures some of the main mechanisms of human, parasite, and vector dynamics, and opens the possibility to forecast malaria in endemic regions, taking into account the interaction between future climatic conditions and intervention scenarios.

Abstract Background Respiratory syncytial virus (RSV) is among the leading childhood causes of viral pneumonia worldwide. Establishing RSV-associated morbidity and mortality is important in informing the development, delivery strategies, and evaluation of interventions. Methods Using data collected during 2010–2018 from base regions (population-based surveillance studies in western Kenya and the Kilifi Health and Demographic Surveillance Study), we estimated age-specific rates of acute respiratory illness (ARI), severe acute respiratory illness (SARI—defined as hospitalization with cough or difficulty breathing with onset within the past 10 days), and SARI-associated deaths. We extrapolated the rates from the base regions to other regions of Kenya, while adjusting for risk factors of ARI and healthcare seeking behavior, and finally applied the proportions of RSV-positive cases identified from various sentinel and study facilities to the rates to obtain regional age-specific rates of RSV-associated outpatient and non-medically attended ARI and hospitalized SARI and severe ARI that was not hospitalized (non-hospitalized SARI). We applied age-specific RSV case fatality ratios to SARI to obtain estimates of RSV-associated in- and out-of-hospital deaths. Results Among Kenyan children aged

Background: SARS-CoV-2 has extensively spread in cities and rural communities, and studies are needed to quantify exposure in the population. We report seroprevalence of SARS-CoV-2 in two well-characterized populations in Kenya at two time points. These data inform the design and delivery of public health mitigation measures. Methods: Leveraging on existing population based infectious disease surveillance (PBIDS) in two demographically diverse settings, a rural site in western Kenya in Asembo, Siaya County, and an urban informal settlement in Kibera, Nairobi County, we set up a longitudinal cohort of randomly selected households with serial sampling of all consenting household members in March and June 2021. Both sites included 1,794 and 1,638 participants in March and June 2021, respectively. Individual seroprevalence of SARS-CoV-2 antibodies was expressed as a percentage of the seropositive among the individuals tested, accounting for household clustering and weighted by the PBIDS age and sex distribution. Results: Overall weighted individual seroprevalence increased from 56.2% (95%CI: 52.1, 60.2%) in March 2021 to 63.9% (95%CI: 59.5, 68.0%) in June 2021 in Kibera. For Asembo, the seroprevalence almost doubled from 26.0% (95%CI: 22.4, 30.0%) in March 2021 to 48.7% (95%CI: 44.3, 53.2%) in July 2021. Seroprevalence was highly heterogeneous by age and geography in these populations—higher seroprevalence was observed in the urban informal settlement (compared to the rural setting), and children aged

BackgroundDespite the importance of non-Typhoidal Salmonella (NTS) disease in Africa, epidemiologic data on carriage and transmission are few. These data are important to understand the transmission of NTS in Africa and to design control strategies.MethodTo estimate the prevalence of stool carriage of NTS in Kenya, we conducted a cross-sectional study in Kilifi, Nairobi, and Siaya, sites with a low, moderate and high incidence of invasive NTS disease, respectively. At each site, we randomly selected 100 participants in each age-group of 0-11 months, 12-59 months, 5-14 years, 15-54 years and ≥55 years. We collected stool, venous blood (for hemoglobin and malaria rapid tests), anthropometric measurements, and administered a questionnaire on Water Access Sanitation and Hygiene (WASH) practices. Stool samples were cultured on selective agar for Salmonella; suspect isolates underwent serotyping and antimicrobial susceptibility testing.ResultOverall, 53 (3.5%) isolates of NTS were cultured from 1497 samples. Age-adjusted prevalence was 13.1% (95%CI 8.8-17.4) in Kilifi, 0.4% (95%CI 0-1.3) in Nairobi, and 0.9% (95%CI 0-2.0) in Siaya. Prevalence was highest among those aged 15-54 years (6.2%). Of 53 isolates; 5 were S. Enteritidis, 1 was S. Typhimurium. No S. Typhi was isolated. None of the risk factors were associated with carriage of NTS. All isolates were susceptible to all antibiotics tested, including ampicillin, chloramphenicol, ciprofloxacin and co-trimoxazole.ConclusionPrevalence of fecal carriage was high in Kilifi, an area of low incidence of invasive NTS disease and was low in areas of higher incidence in Nairobi and Siaya. The age-prevalence, risk factors, geographical and serotype distribution of NTS in carriage differs from invasive disease.

Abstract Background Understanding healthcare-seeking patterns for respiratory illness can help improve estimation of disease burden and target public health interventions to control acute respiratory disease in Kenya. Methods We conducted a cross-sectional survey to determine healthcare utilization patterns for acute respiratory illness (ARI) and severe pneumonia in four diverse counties representing urban, peri-urban, rural mixed farmers, and rural pastoralist communities in Kenya using a two-stage (sub-locations then households) cluster sampling procedure. Healthcare seeking behavior for ARI episodes in the last 14 days, and severe pneumonia in the last 12 months was evaluated. Severe pneumonia was defined as reported cough and difficulty breathing for > 2 days and report of hospitalization or recommendation for hospitalization, or a danger sign (unable to breastfeed/drink, vomiting everything, convulsions, unconscious) for children

Abstract We estimated the prevalence of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE), carbapenem-resistant Enterobacterales (CRE), and methicillin-resistant Staphylococcus aureus (MRSA) in communities and hospitals in Kenya to identify human colonization with multidrug-resistant bacteria. Nasal and fecal specimen were collected from inpatients and community residents in Nairobi (urban) and Siaya (rural) counties. Swabs were plated on chromogenic agar to presumptively identify ESCrE, CRE and MRSA isolates. Confirmatory identification and antibiotic susceptibility testing were done using the VITEK®2 instrument. A total of 1999 community residents and 1023 inpatients were enrolled between January 2019 and March 2020. ESCrE colonization was higher in urban than rural communities (52 vs. 45%; P = 0.013) and in urban than rural hospitals (70 vs. 63%; P = 0.032). Overall, ESCrE colonization was ~ 18% higher in hospitals than in corresponding communities. CRE colonization was higher in hospital than community settings (rural: 7 vs. 1%; urban: 17 vs. 1%; with non-overlapping 95% confidence intervals), while MRSA was rarely detected (≤ 3% overall). Human colonization with ESCrE and CRE was common, particularly in hospitals and urban settings. MRSA colonization was uncommon. Evaluation of risk factors and genetic mechanisms of resistance can guide prevention and control efforts tailored to different environments.

Existing acute febrile illness (AFI) surveillance systems can be leveraged to identify and characterize emerging pathogens, such as SARS-CoV-2, which causes COVID-19. The US Centers for Disease Control and Prevention collaborated with ministries of health and implementing partners in Belize, Ethiopia, Kenya, Liberia, and Peru to adapt AFI surveillance systems to generate COVID-19 response information. Staff at sentinel sites collected epidemiologic data from persons meeting AFI criteria and specimens for SARS-CoV-2 testing. A total of 5,501 patients with AFI were enrolled during March 2020–October 2021; >69% underwent SARS-CoV-2 testing. Percentage positivity for SARS-CoV-2 ranged from 4% (87/2,151, Kenya) to 19% (22/115, Ethiopia). We show SARS-CoV-2 testing was successfully integrated into AFI surveillance in 5 low- to middle-income countries to detect COVID-19 within AFI care-seeking populations. AFI surveillance systems can be used to build capacity to detect and respond to both emerging and endemic infectious disease threats.

Background: Despite considerable progress made over the past 20 years in reducing the global burden of malaria, the disease remains a major public health problem and there is concern that climate change might expand suitable areas for transmission. This study investigated the relative effect of climate variability on malaria incidence after scale-up of interventions in western Kenya. Methods: Bayesian negative binomial models were fitted to monthly malaria incidence data, extracted from records of patients with febrile illnesses visiting the Lwak Mission Hospital between 2008 and 2019. Data pertaining to bed net use and socio-economic status (SES) were obtained from household surveys. Climatic proxy variables obtained from remote sensing were included as covariates in the models. Bayesian variable selection was used to determine the elapsing time between climate suitability and malaria incidence. Results: Malaria incidence increased by 50% from 2008 to 2010, then declined by 73% until 2015. There was a resurgence of cases after 2016, despite high bed net use. Increase in daytime land surface temperature was associated with a decline in malaria incidence (incidence rate ratio [IRR] = 0.70, 95% Bayesian credible interval [BCI]: 0.59–0.82), while rainfall was associated with increased incidence (IRR = 1.27, 95% BCI: 1.10–1.44). Bed net use was associated with a decline in malaria incidence in children aged 6–59 months (IRR = 0.78, 95% BCI: 0.70–0.87) but not in older age groups, whereas SES was not associated with malaria incidence in this population. Conclusions: Variability in climatic factors showed a stronger effect on malaria incidence than bed net use. Bed net use was, however, associated with a reduction in malaria incidence, especially among children aged 6–59 months after adjusting for climate effects. To sustain the downward trend in malaria incidence, this study recommends continued distribution and use of bed nets and consideration of climate-based malaria early warning systems when planning for future control interventions.

Background: Maternal respiratory syncytial virus (RSV) vaccines that are likely to be implementable in low- and middle-income countries (LMICs) are in final stages of clinical trials. Data on the number of women presenting for antenatal care (ANC) per day and proportion attending within the proposed gestational window for vaccine delivery, is a prerequisite to guide development of vaccine vial size and inform vaccine uptake in this setting. Methods: We undertook administrative review and abstraction of ANC attendance records from 2019 registers of 24 selected health facilities, stratified by the level of care, from Kilifi, Siaya and Nairobi counties in Kenya. Additional data were obtained from Mother and Child Health (MCH) booklets of women in each of the Health and Demographic Surveillance System (HDSS) areas of Kilifi, Nairobi and Siaya. Data analysis involved descriptive summaries of the number (mean, median) and proportion of women attending ANC within the gestational window period of 28-32 weeks and 24-36 weeks. Results: A total of 62,153 ANC records were abstracted, 33,872 from Kilifi, 19,438 from Siaya and 8,943 from Nairobi Counties. The median (Interquartile range, IQR) number of women attending ANC per day at a gestational age window of 28-32 and 24-36 weeks, respectively, were: 4 (2-6) and 7 (4-12) in dispensaries, 5 (2-9) and 10 (4-19) in health centres and 6 (4-11) and 16 (10-26) in county referral hospitals. In the HDSS areas of Kilifi, Siaya and Nairobi, pregnant women attending at least one ANC visit, within a window of 28-32 weeks, were: 77% (360/470), 75% (590/791) and 67% (547/821), respectively. Conclusions: About 70% of pregnant women across three distinct geographical regions in Kenya, attend ANC within 28-32 weeks of gestation. A multidose vial size with about five doses per vial, approximates daily ANC attendance and would not incur possible wastage in similar settings.

Abstract 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

BackgroundAccurate and timely diagnosis is essential in limiting the spread of SARS-CoV-2 infection. The reference standard, rRT-PCR, requires specialized laboratories, costly reagents, and a long turnaround time. Antigen RDTs provide a feasible alternative to rRT-PCR since they are quick, relatively inexpensive, and do not require a laboratory. The WHO requires that Ag RDTs have a sensitivity ≥80% and specificity ≥97%.MethodsThis evaluation was conducted at 11 health facilities in Kenya between March and July 2021. We enrolled persons of any age with respiratory symptoms and asymptomatic contacts of confirmed COVID-19 cases. We collected demographic and clinical information and two nasopharyngeal specimens from each participant for Ag RDT testing and rRT-PCR. We calculated the diagnostic performance of the Panbio™ Ag RDT against the US Centers for Disease Control and Prevention's (CDC) rRT-PCR test.ResultsWe evaluated the Ag RDT in 2,245 individuals where 551 (24.5%, 95% CI: 22.8-26.3%) tested positive by rRT-PCR. Overall sensitivity of the Ag RDT was 46.6% (95% CI: 42.4-50.9%), specificity 98.5% (95% CI: 97.8-99.0%), PPV 90.8% (95% CI: 86.8-93.9%) and NPV 85.0% (95% CI: 83.4-86.6%). Among symptomatic individuals, sensitivity was 60.6% (95% CI: 54.3-66.7%) and specificity was 98.1% (95% CI: 96.7-99.0%). Among asymptomatic individuals, sensitivity was 34.7% (95% CI 29.3-40.4%) and specificity was 98.7% (95% CI: 97.8-99.3%). In persons with onset of symptoms 7 days (157/876, 17.9%). The highest sensitivity was 87.0% (95% CI: 80.9-91.8%) in symptomatic individuals with cycle threshold (Ct) values ≤30.ConclusionThe overall sensitivity and NPV of the Panbio™ Ag RDT were much lower than expected. The specificity of the Ag RDT was high and satisfactory; therefore, a positive result may not require confirmation by rRT-PCR. The kit may be useful as a rapid screening tool only for symptomatic patients in high-risk settings with limited access to rRT-PCR. A negative result should be interpreted based on clinical and epidemiological information and may require retesting by rRT-PCR.

Robust data on the impact of the COVID-19 pandemic on mortality in Africa are relatively scarce. Using data from two well-characterized populations in Kenya we aimed to estimate excess mortality during the COVID-19 pandemic period. The mortality data arise from an ongoing population-based infectious disease surveillance (PBIDS) platform, which has been operational since 2006 in rural western Kenya (Asembo, Siaya County) and an urban informal settlement (Kibera, Nairobi County), Kenya. PBIDS participants were regularly visited at home (2-3 times a year) by field workers who collected demographic data, including deaths. In addition, verbal autopsy (VA) interviews for all identified deaths are conducted. We estimated all-cause and cause-specific mortality rates before and during the height of the COVID-19 pandemic, and we compared associated mortality rates between the periods using incidence rate ratios. Excess deaths during the COVID-19 period were also estimated by modelling expected deaths in the absence of COVID-19 by applying a negative binomial regression model on historical mortality data from January 2016. Overall and monthly excess deaths were determined using the P-score metric. Spearman correlation was used to assess whether there is a relationship between the generated P-score and COVID-19 positivity rate. The all-cause mortality rate was higher during the COVID-19 period compared to the pre-COVID-19 period in Asembo [9.1 (95% CI, 8.2-10.0) vs. 7.8 (95% CI, 7.3-8.3) per 1000 person-years of observation, pyo]. In Kibera, the all-cause mortality rate was slightly lower during the COVID-19 period compared to the pre-COVID-19 period [2.6 (95% CI, 2.2-3.2 per 1000 pyo) vs. 3.1; 95% CI, 2.7-3.4 per 1000 pyo)]. An increase in all-cause mortality was observed (incidence rate ratio, IRR, 1.16; 95% CI, 1.04-1.31) in Asembo, unlike in Kibera (IRR, 0.88; 95% CI, 0.71-1.09). The notable increase in mortality rate in Asembo was observed among persons aged 50 to 64 years (IRR, 2.62; 95% CI, 1.95-3.52), persons aged 65 years and above (5.47; 95% CI, 4.60-6.50) and among females (IRR, 1.25; 95% CI, 1.07-1.46). These age and gender differences were not observed in Kibera. We observed an increase in the mortality rate due to acute respiratory infection, including pneumonia (IRR, 1.45;95% CI, 1.03-2.04), and a reduction in the mortality rate due to pulmonary tuberculosis (IRR, 0.22; 95% CI, 0.05-0.87) among older children and adults in Asembo. There was no statistically significant change in mortality rates due to leading specific causes of death in Kibera. Overall, during the COVID-19 period observed deaths were higher than expected deaths in Asembo (P-score = 6.0%) and lower than expected in Kibera (P-score = -22.3%).Using well-characterized populations in the two diverse geographic locations, we demonstrate a heterogenous impact of the COVID-19 pandemic on all-cause and cause-specific mortality rates in Kenya. We observed more deaths than expected during the COVID-19 period in our rural site in western Kenya contrary to the urban site in Nairobi, the capital city in Kenya.

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection (LRTI) among infants under 6 months of age. Yet, in Kenya, little is known about healthcare workers’ (HCWs) knowledge, attitudes, and perceptions around RSV disease and the prevention products under development. Between September and October 2021, we conducted a mixed methods cross-sectional survey to assess HCWs’ knowledge, attitudes, and perceptions of RSV disease and RSV vaccinations in two counties. We enrolled HCWs delivering services directly at maternal and child health (MCH) departments in selected health facilities (frontline HCWs) and health management officers (HMOs). Of the 106 respondents, 94 (88.7%) were frontline HCWs, while 12 were HMOs. Two of the HMOs were members of the Kenya National Immunization Technical Advisory Group (KENITAG). Of the 104 non-KENITAG HCWs, only 41 (39.4%) had heard about RSV disease, and 38/41 (92.7%) felt that pregnant women should be vaccinated against RSV. Most participants would recommend a single-dose vaccine schedule (n = 62, 58.5%) for maximal adherence and compliance (n = 38/62, 61.3%), single dose/device vaccines (n = 50/86, 58.1%) to prevent wastage and contamination, and maternal vaccination through antenatal care clinics (n = 53, 50%). We found the need for increased knowledge about RSV disease and prevention among Kenyan HCWs.

A high burden of Salmonella enterica subspecies enterica serovar Typhi (S. Typhi) bacteremia has been reported from urban informal settlements in sub-Saharan Africa, yet little is known about the introduction of these strains to the region. Understanding regional differences in the predominant strains of S. Typhi can provide insight into the genomic epidemiology. We genetically characterized 310 S. Typhi isolates from typhoid fever surveillance conducted over a 12-year period (2007-2019) in Kibera, an urban informal settlement in Nairobi, Kenya, to assess the circulating strains, their antimicrobial resistance attributes, and how they relate to global S. Typhi isolates. Whole genome multi-locus sequence typing (wgMLST) identified 4 clades, with up to 303 pairwise allelic differences. The identified genotypes correlated with wgMLST clades. The predominant clade contained 290 (93.5%) isolates with a median of 14 allele differences (range 0-52) and consisted entirely of genotypes 4.3.1.1 and 4.3.1.2. Resistance determinants were identified exclusively in the predominant clade. Determinants associated with resistance to aminoglycosides were observed in 245 isolates (79.0%), sulphonamide in 243 isolates (78.4%), trimethoprim in 247 isolates (79.7%), tetracycline in 224 isolates (72.3%), chloramphenicol in 247 isolates (79.6%), β-lactams in 239 isolates (77.1%) and quinolones in 62 isolates (20.0%). Multidrug resistance (MDR) determinants (defined as determinants conferring resistance to ampicillin, chloramphenicol and cotrimoxazole) were found in 235 (75.8%) isolates. The prevalence of MDR associated genes was similar throughout the study period (2007-2012: 203, 76.3% vs 2013-2019: 32, 72.7%; Fisher's Exact Test: P = 0.5478, while the proportion of isolates harboring quinolone resistance determinants increased (2007-2012: 42, 15.8% and 2013-2019: 20, 45.5%; Fisher's Exact Test: P

Abstract Background The relationship between antibiotic use and antimicrobial resistance varies with cultural, socio-economic, and environmental factors. We examined these relationships in Kibera, an informal settlement in Nairobi—Kenya, characterized by high population density, high burden of respiratory disease and diarrhea. Methods Two-hundred households were enrolled in a 5-month longitudinal study. One adult (≥ 18 years) and one child (≤ 5 years) participated per household. Biweekly interviews (n = 1516) that included questions on water, sanitation, hygiene, and antibiotic use in the previous two weeks were conducted, and 2341 stool, 2843 hand swabs and 1490 drinking water samples collected. Presumptive E. coli (n = 34,042) were isolated and tested for susceptibility to nine antibiotics. Results Eighty percent of presumptive E. coli were resistant to ≥ 3 antibiotic classes. Stool isolates were resistant to trimethoprim (mean: 81%), sulfamethoxazole (80%), ampicillin (68%), streptomycin (60%) and tetracycline (55%). Ninety-seven households reported using an antibiotic in at least one visit over the study period for a total of 144 episodes and 190 antibiotic doses. Enrolled children had five times the number of episodes reported by enrolled adults (96 vs. 19). Multivariable linear mixed-effects models indicated that children eating soil from the household yard and the presence of informal hand-washing stations were associated with increased numbers of antimicrobial-resistant bacteria (counts increasing by 0·27–0·80 log10 and 0·22–0·51 log10 respectively, depending on the antibiotic tested). Rainy conditions were associated with reduced carriage of antimicrobial-resistant bacteria (1·19 to 3·26 log10 depending on the antibiotic tested). Conclusions Antibiotic use provided little explanatory power for the prevalence of antimicrobial resistance. Transmission of resistant bacteria in this setting through unsanitary living conditions likely overwhelms incremental changes in antibiotic use. Under such circumstances, sanitation, hygiene, and disease transmission are the limiting factors for reducing the prevalence of resistant bacteria.

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

Introduction: Urban informal settlements may be disproportionately affected by the COVID-19 pandemic due to overcrowding and other socioeconomic challenges that make adoption and implementation of public health mitigation measures difficult. We conducted a seroprevalence survey in the Kibera informal settlement, Nairobi, Kenya, to determine the extent of SARS-CoV-2 infection. Methods: Members of randomly selected households from an existing population-based infectious disease surveillance (PBIDS) provided blood specimens between 27th November and 5th December 2020. The specimens were tested for antibodies to the SARS-CoV-2 spike protein. Seroprevalence estimates were weighted by age and sex distribution of the PBIDS population and accounted for household clustering. Multivariable logistic regression was used to identify risk factors for individual seropositivity. Results: Consent was obtained from 523 individuals in 175 households, yielding 511 serum specimens that were tested. The overall weighted seroprevalence was 43.3% (95% CI, 37.4 – 49.5%) and did not vary by sex. Of the sampled households, 122(69.7%) had at least one seropositive individual. The individual seroprevalence increased by age from 7.6% (95% CI, 2.4 – 21.3%) among children (

The distributions and frequencies of individual pneumococcal capsular serotypes among nonpneumococcal strains in the upper respiratory tract are unknown and potentially affect pneumococcal serotype distributions among the population and immunity to circulating pneumococcal strains. Repeated demonstration that these nonpneumococcal strains expressing so-called pneumococcal serotypes are readily recovered from current carriage specimens is likely to be relevant to pneumococcal epidemiology, niche biology, and even to potential strategies of employing commensal live vaccines.

Acute Zika virus (ZIKV) infection has not been confirmed in Kenya. In 2018, we used specimens collected in a 2013 dengue serosurvey study in Mombasa to test for ZIKV IgM. We confirmed specific ZIKV IgM positivity in 5 persons. These results suggest recent ZIKV transmission in the coastal region of Kenya.

Abstract Background Adolescent girls in sub-Saharan Africa are disproportionally vulnerable to sexual and reproductive health (SRH) harms. In western Kenya, where unprotected transactional sex is common, young females face higher rates of school dropout, often due to pregnancy, and sexually transmitted infections (STIs), including HIV. Staying in school has shown to protect girls against early marriage, teen pregnancy, and HIV infection. This study evaluates the impact of menstrual cups and cash transfer interventions on a composite of deleterious outcomes (HIV, HSV-2, and school dropout) when given to secondary schoolgirls in western Kenya, with the aim to inform evidence-based policy to improve girls’ health, school equity, and life-chances. Methods Single site, 4-arm, cluster randomised controlled superiority trial. Secondary schools are the unit of randomisation, with schoolgirls as the unit of measurement. Schools will be randomised into one of four intervention arms using a 1:1:1:1 ratio and block randomisation: (1) menstrual cup arm; (2) cash transfer arm, (3) cups and cash combined intervention arm, or (4) control arm. National and county agreement, and school level consent will be obtained prior to recruitment of schools, with parent consent and girls’ assent obtained for participant enrolment. Participants will be trained on safe use of interventions, with all arms receiving puberty and hygiene education. Annually, the state of latrines, water availability, water treatment, handwashing units and soap in schools will be measured. The primary endpoint is a composite of incident HIV, HSV-2, and all-cause school dropout, after 3 years follow-up. School dropout will be monitored each term via school registers and confirmed through home visits. HIV and HSV-2 incident infections and risk factors will be measured at baseline, mid-line and end-line. Intention to treat analysis will be conducted among all enrolled participants. Focus group discussions will provide contextual information on uptake of interventions. Monitoring for safety will occur throughout. Discussion If proved safe and effective, the interventions offer a potential contribution toward girls’ schooling, health, and equity in low- and middle-income countries. Trial registration ClinicalTrials.gov NCT03051789, 15th February 2017.

Abstract 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.

Abstract 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.

Abstract More than 75% of emerging infectious diseases are zoonotic in origin and a transdisciplinary, multi-sectoral One Health approach is a key strategy for their effective prevention and control. In 2004, US Centers for Disease Control and Prevention office in Kenya (CDC Kenya) established the Global Disease Detection Division of which one core component was to support, with other partners, the One Health approach to public health science. After catalytic events such as the global expansion of highly pathogenic H5N1 and the 2006 East African multi-country outbreaks of Rift Valley Fever, CDC Kenya supported key Kenya government institutions including the Ministry of Health and the Ministry of Agriculture, Livestock, and Fisheries to establish a framework for multi-sectoral collaboration at national and county level and a coordination office referred to as the Zoonotic Disease Unit (ZDU). The ZDU has provided Kenya with an institutional framework to highlight the public health importance of endemic and epidemic zoonoses including RVF, rabies, brucellosis, Middle East Respiratory Syndrome Coronavirus, anthrax and other emerging issues such as anti-microbial resistance through capacity building programs, surveillance, workforce development, research, coordinated investigation and outbreak response. This has led to improved outbreak response, and generated data (including discovery of new pathogens) that has informed disease control programs to reduce burden of and enhance preparedness for endemic and epidemic zoonotic diseases, thereby enhancing global health security. Since 2014, the Global Health Security Agenda implemented through CDC Kenya and other partners in the country has provided additional impetus to maintain this effort and Kenya’s achievement now serves as a model for other countries in the region. Significant gaps remain in implementation of the One Health approach at subnational administrative levels; there are sustainability concerns, competing priorities and funding deficiencies.

Abstract Since 1979, multiple CDC Kenya programs have supported the development of diagnostic expertise and laboratory capacity in Kenya. In 2004, CDC’s Global Disease Detection (GDD) program within the Division of Global Health Protection in Kenya (DGHP-Kenya) initiated close collaboration with Kenya Medical Research Institute (KEMRI) and developed a laboratory partnership called the Diagnostic and Laboratory Systems Program (DLSP). DLSP built onto previous efforts by malaria, human immunodeficiency virus (HIV) and tuberculosis (TB) programs and supported the expansion of the diagnostic expertise and capacity in KEMRI and the Ministry of Health. First, DLSP developed laboratory capacity for surveillance of diarrheal, respiratory, zoonotic and febrile illnesses to understand the etiology burden of these common illnesses and support evidenced-based decisions on vaccine introductions and recommendations in Kenya. Second, we have evaluated and implemented new diagnostic technologies such as TaqMan Array Cards (TAC) to detect emerging or reemerging pathogens and have recently added a next generation sequencer (NGS). Third, DLSP provided rapid laboratory diagnostic support for outbreak investigation to Kenya and regional countries. Fourth, DLSP has been assisting the Kenya National Public Health laboratory-National Influenza Center and microbiology reference laboratory to obtain World Health Organization (WHO) certification and ISO15189 accreditation respectively. Fifth, we have supported biosafety and biosecurity curriculum development to help Kenyan laboratories safely and appropriately manage infectious pathogens. These achievements, highlight how in collaboration with existing CDC programs working on HIV, tuberculosis and malaria, the Global Health Security Agenda can have significantly improve public health in Kenya and the region. Moreover, Kenya provides an example as to how laboratory science can help countries detect and control of infectious disease outbreaks and other public health threats more rapidly, thus enhancing global health security.

Abstract Background Antibiotics are essential to treat for many childhood bacterial infections; however inappropriate antibiotic use contributes to antimicrobial resistance. For childhood diarrhea, empiric antibiotic use is recommended for dysentery (bloody diarrhea) for which first-line therapy is ciprofloxacin. We assessed inappropriate antibiotic prescription for childhood diarrhea in two primary healthcare facilities in Kenya. Methods We analyzed data from the Kenya Population Based Infectious Disease Surveillance system in Asembo (rural, malaria-endemic) and Kibera (urban slum, non-malaria-endemic). We examined records of children aged 2–59 months with diarrhea (≥3 loose stools in 24 h) presenting for care from August 21, 2009 to May 3, 2016, excluding visits with non-diarrheal indications for antibiotics. We examined the frequency of antibiotic over-prescription (antibiotic prescription for non-dysentery), under-prescription (no antibiotic prescription for dysentery), and inappropriate antibiotic selection (non-recommended antibiotic). We examined factors associated with over-prescription and under-prescription using multivariate logistic regression with generalized estimating equations. Results Of 2808 clinic visits with diarrhea in Asembo, 2685 (95.6%) were non-dysentery visits and antibiotic over-prescription occurred in 52.5%. Of 4697 clinic visits with diarrhea in Kibera, 4518 (96.2%) were non-dysentery and antibiotic over-prescription occurred in 20.0%. Antibiotic under-prescription was noted in 26.8 and 73.7% of dysentery cases in Asembo and Kibera, respectively. Ciprofloxacin was used for 11% of dysentery visits in Asembo and 0% in Kibera. Factors associated with over- and under-prescription varied by site. In Asembo a discharge diagnosis of gastroenteritis was associated with over-prescription (adjusted odds ratio [aOR]:8.23, 95% confidence interval [95%CI]: 3.68–18.4), while malaria diagnosis was negatively associated with antibiotic over-prescription (aOR 0.37, 95%CI: 0.25–0.54) but positively associated with antibiotic under-prescription (aOR: 1.82, 95%CI: 1.05–3.13). In Kibera, over-prescription was more common among visits with concurrent signs of respiratory infection (difficulty breathing; aOR: 3.97, 95%CI: 1.28–12.30, cough: aOR: 1.42, 95%CI: 1.06–1.90) and less common among children aged

Abstract Background HIV, syphilis, malaria and anaemia are leading preventable causes of adverse pregnancy outcomes in sub-Saharan Africa yet testing coverage for conditions other than HIV is low. Availing point-of-care tests (POCTs) at rural antenatal health facilities (dispensaries) has the potential to improve access and timely treatment. Fundamental to the adoption of and adherence to new diagnostic approaches are healthcare workers’ and pregnant women’s (end-users) buy-in. A qualitative approach was used to capture end-users’ experiences of using POCTs for HIV, syphilis, malaria and anaemia to assess the appropriateness, acceptability and feasibility of integrated testing for ANC. Methods Seven dispensaries were purposively selected to implement integrated point-of-care testing for eight months in western Kenya. Semi-structured interviews were conducted with 18 healthcare workers (14 nurses, one clinical officer, two HIV testing counsellors, and one laboratory technician) who were trained, had experience doing integrated point-of-care testing, and were still working at the facilities 8–12 months after the intervention began. The interviews explored acceptability and relevance of POCTs to ANC, challenges with testing, training and supervision, and healthcare workers’ perspectives of client experiences. Twelve focus group discussions with 118 pregnant women who had attended a first ANC visit at the study facilities during the intervention were conducted to explore their knowledge of HIV, syphilis, malaria, and anaemia, experience of ANC point-of-care testing services, treatments received, relationships with healthcare workers, and experience of talking to partners about HIV and syphilis results. Results Healthcare workers reported that they enjoyed gaining new skills, were enthusiastic about using POCTs, and found them easy to use and appropriate to their practice. Initial concerns that performing additional testing would increase their workload in an already strained environment were resolved with experience and proficiency with the testing procedures. However, despite having the diagnostic tools, general health system challenges such as high client to healthcare worker volume ratio, stock-outs and poor working conditions challenged the delivery of adequate counselling and management of the four conditions. Pregnant women appreciated POCTs, but reported poor healthcare worker attitudes, drug stock-outs, and fear of HIV disclosure to their partners as shortcomings to their ANC experience in general. Conclusion This study provides insights on the acceptability, appropriateness, and feasibility of integrating POCTs into ANC services among end-users. While the innovation was desired and perceived as beneficial, future scale-up efforts would need to address health system weaknesses if integrated testing and subsequent effective management of the four conditions are to be achieved.

Multidrug-resistant non-typhoidal Salmonella (NTS) infection has emerged as a prominent cause of invasive infections in Africa. We investigated the prevalence of ceftriaxone-resistant invasive NTS infections, conducted exploratory analysis of risk factors for resistance, and described antimicrobial use in western Kenya. We conducted a secondary analysis of existing laboratory, epidemiology, and clinical data from three independent projects, a malaria vaccine trial, a central nervous system (CNS) study, and the International Emerging Infections Program morbidity surveillance (surveillance program) during 2009-2014. We calculated odds ratios (OR) with 95% confidence intervals (CI) for ceftriaxone-resistant NTS infections compared with ceftriaxone-susceptible infections. We surveyed hospitals, pharmacies, and animal drug retailers about the availability and use of antimicrobials. In total, 286 invasive NTS infections were identified in the three projects; 43 NTS isolates were ceftriaxone-resistant. The absolute prevalence of ceftriaxone resistance varied among these methodologically diverse projects, with 18% (16/90) of isolates resistant to ceftriaxone in the vaccine trial, 89% (16/18) in the CNS study, and 6% (11/178) in the surveillance program. Invasive ceftriaxone-resistant infections increased over time. Most ceftriaxone-resistant isolates were co-resistant to multiple other antimicrobials. Having an HIV-positive mother (OR = 3.7; CI = 1.2-11.4) and taking trimethoprim-sulfamethoxazole for the current illness (OR = 9.6, CI = 1.2-78.9) were significantly associated with acquiring ceftriaxone-resistant invasive NTS infection. Ceftriaxone and other antibiotics were widely prescribed; multiple issues related to prescription practices and misuse were identified. In summary, ceftriaxone-resistant invasive NTS infection is increasing and limiting treatment options for serious infections. Efforts are ongoing to address the urgent need for improved microbiologic diagnostic capacity and an antimicrobial surveillance system in Kenya.

Abstract Background Tuberculosis (TB) case finding is an important component of TB control because it can reduce transmission of Mycobacterium tuberculosis (MTB) through prompt detection and treatment of infectious patients. Methods Using population-based infectious disease surveillance (PBIDS) platforms with links to health facilities in Kenya we implemented intensified TB case finding in the community and at the health facilities, as an adjunct to routine passive case finding conducted by the national TB program. From 2011 to 2014, PBIDS participants ≥15 years were screened either at home or health facilities for possible TB symptoms which included cough, fever, night sweats or weight loss in the preceding 2 weeks. At home, participants with possible TB symptoms had expectorated sputum collected. At the clinic, HIV-infected participants with possible TB symptoms were invited to produce sputum. Those without HIV but with symptoms lasting 7 days including the visit day had chest radiographs performed, and had sputum collected if the radiographs were abnormal. Sputum samples were tested for the presence of MTB using the Xpert MTB/RIF assay. TB detection rates were calculated per 100,000 persons screened. Results Of 11,191 participants aged ≥15 years screened at home at both sites, 2695 (23.9%) reported possible TB symptoms, of whom 2258 (83.8%) produced sputum specimens. MTB was detected in 32 (1.4%) of the specimens resulting in a detection rate of 286/100,000 persons screened. At the health facilities, a total of 11,762 person were screened, 7500 (63.8%) had possible TB symptoms of whom 1282 (17.1%) produced sputum samples. MTB was detected in 69 (5.4%) of the samples, resulting in an overall detection rate of 587/100,000 persons screened. The TB detection rate was higher in persons with HIV compared to those without at both home (HIV-infected - 769/100,000, HIV-uninfected 141/100,000, rate ratio (RR) – 5.45, 95% CI 3.25–22.37), and health facilities (HIV-infected 3399/100,000, HIV-uninfected 294/100,000, RR 11.56, 95% CI 6.18–18.44). Conclusion Facility-based intensified TB case finding detected more TB cases per the number of specimens tested and the number of persons screened, including those with HIV, than home-based TB screening and should be further evaluated to determine its potential programmatic impact.

Summary: Background: Influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus are the most common viruses associated with acute lower respiratory infections in young children (

BackgroundWorldwide, the number of emerging and re-emerging infectious diseases is increasing, highlighting the importance of global disease pathogen surveillance. Traditional population-based methods may fail to capture important events, particularly in settings with limited access to health care, such as urban informal settlements. In such environments, a mixture of surface water runoff and human feces containing pathogenic microorganisms could be used as a surveillance surrogate.MethodWe conducted a temporal metagenomic analysis of urban sewage from Kibera, an urban informal settlement in Nairobi, Kenya, to detect and quantify bacterial and associated antimicrobial resistance (AMR) determinants, viral and parasitic pathogens. Data were examined in conjunction with data from ongoing clinical infectious disease surveillance.ResultsA large variation of read abundances related to bacteria, viruses, and parasites of medical importance, as well as bacterial associated antimicrobial resistance genes over time were detected. Significant increased abundances were observed for a number of bacterial pathogens coinciding with higher abundances of AMR genes. Vibrio cholerae as well as rotavirus A, among other virus peaked in several weeks during the study period whereas Cryptosporidium spp. and Giardia spp, varied more over time.ConclusionThe metagenomic surveillance approach for monitoring circulating pathogens in sewage was able to detect putative pathogen and resistance loads in an urban informal settlement. Thus, valuable if generated in real time to serve as a comprehensive infectious disease agent surveillance system with the potential to guide disease prevention and treatment. The approach may lead to a paradigm shift in conducting real-time global genomics-based surveillance in settings with limited access to health care.

Streptococcus pneumoniae is a highly impactful bacterial pathogen on a global scale. The principal pneumococcal virulence factor and target of effective vaccines is its polysaccharide capsule, of which there are many structurally distinct forms. Here, we describe four distinct strains of three Mitis group commensal species (Streptococcus infantis, Streptococcus mitis, and Streptococcus oralis) recovered from upper respiratory tract specimens from adults in Kenya and the United States that were PCR-positive for the pneumococcal serotype 5 specific gene, wzy5. For each of the four strains, the 15 genes comprising the capsular polysaccharide biosynthetic gene cluster (cps5) shared the same order found in serotype 5 pneumococci, and each of the serotype 5-specific genes from the serotype 5 pneumococcal reference strain shared 76–99% sequence identity with the non-pneumococcal counterparts. Double-diffusion experiments demonstrated specific reactivity of the non-pneumococcal strains with pneumococcal serotype 5 typing sera. Antiserum raised against S. mitis strain KE67013 specifically reacted with serotype 5 pneumococci for a positive Quellung reaction and stimulated serotype 5 specific opsonophagocytic killing of pneumococci. Four additional commensal strains, identified using PCR serotyping assays on pharyngeal specimens, revealed loci highly homologous to those of pneumococci of serotypes 12F, 15A, 18C, and 33F. These data, in particular the species and strain diversity shown for serotype 5, highlight the existence of a broad non-pneumococcal species reservoir in the upper respiratory tract for the expression of capsular polysaccharides that are structurally related or identical to those corresponding to epidemiologically significant serotypes. Very little is known about the genetic and antigenic capsular diversity among the vast array of commensal streptococcal strains that represent multiple diverse species. The discovery of serotype 5 strains within three different commensal species suggests that extensive capsular serologic overlap exists between pneumococci and other members of the diverse Mitis group. These findings may have implications for our current understanding of naturally acquired immunity to S. pneumoniae and pneumococcal serotype distributions in different global regions. Further characterization of commensal strains carrying homologs of serotype-specific genes previously thought to be specific for pneumococci of known serotypes may shed light on the evolution of these important loci.

Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon.

Non-typhoidal Salmonella (NTS) is a leading cause of bloodstream infections in Africa, but the various contributions of host susceptibility versus unique pathogen virulence factors are unclear. We used data from a population-based surveillance platform (population ~25,000) between 2007-2014 and NTS genome-sequencing to compare host and pathogen-specific factors between individuals presenting with NTS bacteremia and those presenting with NTS diarrhea. Salmonella Typhimurium ST313 and Salmonella Enteritidis ST11 were the most common isolates. Multi-drug resistant strains of NTS were more commonly isolated from patients presenting with NTS bacteremia compared to NTS diarrhea. This relationship was observed in patients under age five [aOR = 15.16, 95% CI (2.84-81.05), P = 0.001], in patients five years and older, [aOR = 6.70 95% CI (2.25-19.89), P = 0.001], in HIV-uninfected patients, [aOR = 21.61, 95% CI (2.53-185.0), P = 0.005], and in patients infected with Salmonella serogroup B [aOR = 5.96, 95% CI (2.28-15.56), P < 0.001] and serogroup D [aOR = 14.15, 95% CI (1.10-182.7), P = 0.042]. Thus, multi-drug-resistant NTS was strongly associated with bacteremia compared to diarrhea among children and adults. This association was seen in HIV-uninfected individuals infected with either S. Typhimurium or S. Enteritidis. Risk of developing bacteremia from NTS infection may be driven by virulence properties of the Salmonella pathogen.

We assessed knowledge and practices related to antibiotic use in Kibera, an urban informal settlement in Kenya. Surveys was employed at the beginning (entry) and again at the end (exit) of a 5-month longitudinal study of AMR. Two-hundred households were interviewed at entry, of which 149 were also interviewed at exit. The majority (>65%) of respondents in both surveys could name at least one antibiotic, with amoxicillin and cotrimoxazole jointly accounting for 85% and 77% of antibiotics mentioned during entry and exit, respectively. More than 80% of respondents felt antibiotics should not be shared or discontinued following the alleviation of symptoms. Nevertheless, 66% and 74% of respondents considered antibiotics effective for treating colds and flu in the entry and exit surveys, respectively. There was a high (87%, entry; 70% exit) level of reported antibiotic use (past 12 months) mainly for colds/flu, coughs and fever, with >80% of respondents obtaining antibiotics from health facilities and pharmacies. Less than half of respondents remembered getting information on the correct use of antibiotics, although 100% of those who did reported improved attitudes towards antibiotic use. Clinicians and community pharmacists were highly trusted information sources. Paired household responses (n = 149) generally showed improved knowledge and attitudes by the exit survey although practices were largely unchanged. Weak agreement (κ = -0.003 to 0.22) between survey responses suggest both that unintended learning had not occurred, and that participant responses were not based on established knowledge or behaviors. Targeted public education regarding antibiotics is needed to address this gap.

The effect of malaria exposure on mortality using health facility incidence data as a measure of transmission has not been well investigated. Health and demographic surveillance systems (HDSS) routinely capture data on mortality, interventions and other household related indicators, offering a unique platform for estimating and monitoring the incidence-mortality relationship in space and time.Mortality data from the HDSS located in Western Kenya collected from 2007 to 2012 and linked to health facility incidence data were analysed using Bayesian spatio-temporal survival models to investigate the relation between mortality (all-cause/malaria-specific) and malaria incidence across all age groups. The analysis adjusted for insecticide-treated net (ITN) ownership, socio-economic status (SES), distance to health facilities and altitude. The estimates obtained were used to quantify excess mortality due to malaria exposure.Our models identified a strong positive relationship between slide positivity rate (SPR) and all-cause mortality in young children 1-4 years (HR = 4.29; 95% CI: 2.78-13.29) and all ages combined (HR = 1.55; 1.04-2.80). SPR had a strong positive association with malaria-specific mortality in young children (HR = 9.48; 5.11-37.94), however, in older children (5-14 years), it was associated with a reduction in malaria specific mortality (HR = 0.02; 0.003-0.33).SPR as a measure of transmission captures well the association between malaria transmission intensity and all-cause/malaria mortality. This offers a quick and efficient way to monitor malaria burden. Excess mortality estimates indicate that small changes in malaria incidence substantially reduce overall and malaria specific mortality.

Influenza and respiratory syncytial virus (RSV) associated mortality has not been well-established in tropical Africa.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.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

Objective Information on adverse pregnancy outcomes is important to monitor the impact of public health interventions. Miscarriage is a challenging end point to ascertain and there is scarce information on its rate in low-income countries. The objective was to estimate the background rate and cumulative probability of miscarriage in rural western Kenya.Design This was a population-based prospective cohort.Participants and setting Women of childbearing age were followed prospectively to identify pregnancies and ascertain their outcomes in Siaya County, western Kenya. The cohort study was carried out in 33 adjacent villages under health and demographic surveillance.Outcome measure Miscarriage.Results Between 2011 and 2013, among 5536 women of childbearing age, 1453 pregnancies were detected and 1134 were included in the analysis. The cumulative probability was 18.9%. The weekly miscarriage rate declined steadily with increasing gestation until approximately 20 weeks. Known risk factors for miscarriage such as maternal age, gravidity, occupation, household wealth and HIV infection were confirmed.Conclusions This is the first report of weekly miscarriage rates in a rural African setting in the context of high HIV and malaria prevalence. Future studies should consider the involvement of community health workers to identify the pregnancy cohort of early gestation for better data on the actual number of pregnancies and the assessment of miscarriage.

BACKGROUND:Enteric fever due to Salmonella Typhi (typhoid fever) occurs in urban areas with poor sanitation. While direct fecal-oral transmission is thought to be the predominant mode of transmission, recent evidence suggests that indirect environmental transmission may also contribute to disease spread. METHODS:Data from a population-based infectious disease surveillance system (28,000 individuals followed biweekly) were used to map the spatial pattern of typhoid fever in Kibera, an urban informal settlement in Nairobi Kenya, between 2010-2011. Spatial modeling was used to test whether variations in topography and accumulation of surface water explain the geographic patterns of risk. RESULTS:Among children less than ten years of age, risk of typhoid fever was geographically heterogeneous across the study area (p = 0.016) and was positively associated with lower elevation, OR = 1.87, 95% CI (1.36-2.57), p

BackgroundFor most rural households in sub-Saharan Africa, healthy livestock play a key role in averting the burden associated with zoonotic diseases, and in meeting household nutritional and socio-economic needs. However, there is limited understanding of the complex nutritional, socio-economic, and zoonotic pathways that link livestock health to human health and welfare. Here we describe a platform for integrated human health, animal health and economic welfare analysis designed to address this challenge. We provide baseline epidemiological data on disease syndromes in humans and the animals they keep, and provide examples of relationships between human health, animal health and household socio-economic status.MethodWe designed a study to obtain syndromic disease data in animals along with economic and behavioral information for 1500 rural households in Western Kenya already participating in a human syndromic disease surveillance study. Data collection started in February 2013, and each household is visited bi-weekly and data on four human syndromes (fever, jaundice, diarrhea and respiratory illness) and nine animal syndromes (death, respiratory, reproductive, musculoskeletal, nervous, urogenital, digestive, udder disorders, and skin disorders in cattle, sheep, goats and chickens) are collected. Additionally, data from a comprehensive socio-economic survey is collected every 3 months in each of the study households.FindingsData from the first year of study showed 93% of the households owned at least one form of livestock (55%, 19%, 41% and 88% own cattle, sheep, goats and chickens respectively). Digestive disorders, mainly diarrhea episodes, were the most common syndromes observed in cattle, goats and sheep, accounting for 56% of all livestock syndromes, followed by respiratory illnesses (18%). In humans, respiratory illnesses accounted for 54% of all illnesses reported, followed by acute febrile illnesses (40%) and diarrhea illnesses (5%). While controlling for household size, the incidence of human illness increased 1.31-fold for every 10 cases of animal illness or death observed (95% CI 1.16-1.49). Access and utilization of animal source foods such as milk and eggs were positively associated with the number of cattle and chickens owned by the household. Additionally, health care seeking was correlated with household incomes and wealth, which were in turn correlated with livestock herd size.ConclusionThis study platform provides a unique longitudinal dataset that allows for the determination and quantification of linkages between human and animal health, including the impact of healthy animals on human disease averted, malnutrition, household educational attainment, and income levels.

Influenza-associated disease burden among children in tropical sub-Saharan Africa is not well established, particularly outside of the 2009 pandemic period. We estimated the burden of influenza in children aged 0-4 years through population-based surveillance for influenza-like illness (ILI) and acute lower respiratory tract illness (ALRI). Household members meeting ILI or ALRI case definitions were referred to health facilities for evaluation and collection of nasopharyngeal and oropharyngeal swabs for influenza testing by real-time reverse transcription polymerase chain reaction. Estimates were adjusted for health-seeking behavior and those with ILI and ALRI who were not tested. During 2008-2012, there were 9,652 person-years of surveillance among children aged 0-4 years. The average adjusted rate of influenza-associated hospitalization was 4.3 (95% CI 3.0-6.0) per 1,000 person-years in children aged 0-4 years. Hospitalization rates were highest in the 0-5 month and 6-23 month age groups, at 7.6 (95% CI 3.2-18.2) and 8.4 (95% CI 5.4-13.0) per 1,000 person-years, respectively. The average adjusted rate of influenza-associated medically attended (inpatient or outpatient) ALRI in children aged 0-4 years was 17.4 (95% CI 14.2-19.7) per 1,000 person-years. Few children who had severe laboratory-confirmed influenza were clinically diagnosed with influenza by the treating clinician in the inpatient (0/33, 0%) or outpatient (1/109, 0.9%) settings. Influenza-associated hospitalization rates from 2008-2012 were 5-10 times higher than contemporaneous U.S. estimates. Many children with danger signs were not hospitalized; thus, influenza-associated severe disease rates in Kenyan children are likely higher than hospital-based estimates suggest.

BackgroundZinc treatment shortens diarrhea episodes and can prevent future episodes. In rural Africa, most children with diarrhea are not brought to health facilities. In a village-randomized trial in rural Kenya, we assessed if zinc treatment might have a community-level preventive effect on diarrhea incidence if available at home versus only at health facilities.MethodsWe randomized 16 Kenyan villages (1,903 eligible children) to receive a 10-day course of zinc and two oral rehydration solution (ORS) sachets every two months at home and 17 villages (2,241 eligible children) to receive ORS at home, but zinc at the health-facility only. Children's caretakers were educated in zinc/ORS use by village workers, both unblinded to intervention arm. We evaluated whether incidence of diarrhea and acute lower respiratory illness (ALRI) reported at biweekly home visits and presenting to clinic were lower in zinc villages, using poisson regression adjusting for baseline disease rates, distance to clinic, and children's age.ResultsThere were no differences between village groups in diarrhea incidence either reported at the home or presenting to clinic. In zinc villages (1,440 children analyzed), 61.2% of diarrheal episodes were treated with zinc, compared to 5.4% in comparison villages (1,584 children analyzed, pConclusionsIn this study, home zinc use to treat diarrhea did not decrease disease rates in the community. However, with proper training, availability of zinc at home could lead to more episodes of pediatric diarrhea being treated with zinc in parts of rural Africa where healthcare utilization is low.Trial registrationClinicalTrials.gov NCT00530829.