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Supplemental Digital Content is available in the text., Background: In resource-limited settings, acute respiratory infections continue to be the leading cause of death in young children. We conducted postmortem investigations in children

Background Maternal immunization is a key strategy for reducing morbidity and mortality associated with infectious diseases in mothers and their newborns. Recent developments in the science and safety of maternal vaccinations have made possible development of new maternal vaccines ready for introduction in low- and middle-income countries. Decisions at the policy level remain the entry point for maternal immunization programs. We describe the policy and decision-making process in Kenya for the introduction of new vaccines, with particular emphasis on maternal vaccines, and identify opportunities to improve vaccine policy formulation and implementation process. Methods We conducted 29 formal interviews with government officials and policy makers, including high-level officials at the Kenya National Immunization Technical Advisory Group, and Ministry of Health officials at national and county levels. All interviews were recorded and transcribed. We analyzed the qualitative data using NVivo 11.0 software. Results All key informants understood the vaccine policy formulation and implementation processes, although national officials appeared more informed compared to county officials. County officials reported feeling left out of policy development. The recent health system decentralization had both positive and negative impacts on the policy process; however, the negative impacts outweighed the positive impacts. Other factors outside vaccine policy environment such as rumours, sociocultural practices, and anti-vaccine campaigns influenced the policy development and implementation process. Conclusions Public policy development process is complex and multifaceted by its nature. As Kenya prepares for introduction of other maternal vaccines, it is important that the identified policy gaps and challenges are addressed.

Although seroprevalence of Middle East respiratory coronavirus syndrome is high among camels in Africa, researchers have not detected zoonotic transmission in Kenya. We followed a cohort of 262 camel handlers in Kenya during April 2018–March 2020. We report PCR-confirmed Middle East respiratory coronavirus syndrome in 3 asymptomatic handlers.

Data on influenza vaccine immunogenicity in children are limited from tropical developing countries. We recently reported significant, moderate effectiveness of a trivalent inactivated influenza vaccine (IIV) in a controlled, cluster-randomized trial in children in rural Senegal during 2009, a year of H3N2 vaccine mismatch (NCT00893906). We report immunogenicity of IIV3 and inactivated polio vaccine (IPV) from that trial. We evaluated hemagglutination inhibition (HAI) and polio antibody titers in response to vaccination of three age groups (6 through 35 months, 3 through 5 years, and 6 through 8 years). As all children were IIV naive, each received two vaccine doses, although titers were assessed after only the first dose for subjects aged 6 through 8 years. Seroconversion rates (4-fold titer rise or increase from

Respiratory pathogens, such as novel influenza A viruses, Middle East respiratory syndrome coronavirus (MERS-CoV), and now, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are of particular concern because of their high transmissibility and history of global spread (1). Clusters of severe respiratory disease are challenging to investigate, especially in resource-limited settings, and disease etiology often is not well understood. In 2014, endorsed by the Group of Seven (G7),* the Global Health Security Agenda (GHSA) was established to help build country capacity to prevent, detect, and respond to infectious disease threats.† GHSA is a multinational, multisectoral collaboration to support countries towards full implementation of the World Health Organization's International Health Regulations (IHR).§ Initially, 11 technical areas for collaborator participation were identified to meet GHSA goals. CDC developed the Detection and Response to Respiratory Events (DaRRE) strategy in 2014 to enhance country capacity to identify and control respiratory disease outbreaks. DaRRE initiatives support the four of 11 GHSA technical areas that CDC focuses on: surveillance, laboratory capacity, emergency operations, and workforce development.¶ In 2016, Kenya was selected to pilot DaRRE because of its existing respiratory disease surveillance and laboratory platforms and well-developed Field Epidemiology and Laboratory Training Program (FELTP) (2). During 2016-2020, Kenya's DaRRE partners (CDC, the Kenya Ministry of Health [MoH], and Kenya's county public health officials) conceptualized, planned, and implemented key components of DaRRE. Activities were selected based on existing capacity and determined by the Kenya MoH and included 1) expansion of severe acute respiratory illness (SARI) surveillance sites; 2) piloting of community event-based surveillance; 3) expansion of laboratory diagnostic capacity; 4) training of public health practitioners in detection, investigation, and response to respiratory threats; and 5) improvement of response capacity by the national emergency operations center (EOC). Progress on DaRRE activity implementation was assessed throughout the process. This pilot in Kenya demonstrated that DaRRE can support IHR requirements and can capitalize on a country's existing resources by tailoring tools to improve public health preparedness based on countries' needs.

On February 22, 2017, Hospital X-Kampala and US CDC-Kenya reported to the Uganda Ministry of Health a respiratory illness in a 46-year-old expatriate of Company A. The patient, Mr. A, was evacuated from Uganda to Kenya and died. He had recently been exposed to dromedary camels (MERS-CoV) and wild birds with influenza A (H5N6). We investigated the cause of illness, transmission, and recommended control. We defined a suspected case of severe acute respiratory illness (SARI) as acute onset of fever (≥38°C) with sore throat or cough and at least one of the following: headache, lethargy, or difficulty in breathing. In addition, we looked at cases with onset between February 1 and March 31 in a person with a history of contact with Mr. A, his family, or other Company A employees. A confirmed case was defined as a suspected case with laboratory confirmation of the same pathogen detected in Mr. A. Influenza-like illness was defined as onset of fever (≥38°C) and cough or sore throat in a Uganda contact, and as fever (≥38°C) and cough lasting less than 10 days in a Kenya contact. We collected Mr. A's exposure and clinical history, searched for cases, and traced contacts. Specimens from the index case were tested for complete blood count, liver function tests, plasma chemistry, Influenza A(H1N1)pdm09, and MERS-CoV. Robust field epidemiology, laboratory capacity, and cross-border communication enabled investigation.

Maternal vaccination coverage remains suboptimal globally and is lowest in low- and middle-income countries. Attitudes toward maternal vaccines have been characterized in middle-high income settings, however data from African countries are limited. We assessed drivers and barriers of vaccine acceptance among pregnant women in Kenya. We conducted a cross-sectional survey among pregnant women aged 15–49 y. We enrolled a convenience sample of women presenting for antenatal care at seven health-care facilities in four diverse counties (Nairobi, Mombasa, Marsabit, Siaya) of Kenya and from the community in two counties (Nairobi, Siaya). We described frequencies of socio-demographic characteristics of participants and their knowledge, attitudes, and beliefs regarding maternal vaccination. We enrolled 604 pregnant women with a median age of 26.5 y, of whom 48.2% had primary education or less. More than 95% agreed that maternal vaccines are “important for my health” and that getting vaccinated is “a good way to protect myself from disease”. The most commonly cited reason in favor of maternal vaccination was disease prevention (53.2%). Fear of side effects to mother/baby (15.1%) was the most frequently reported potential barrier. Influenza vaccine is not in routine use in Kenya; however, 77.8% reported willingness to accept influenza vaccination during pregnancy. Maternal vaccination is well accepted among Kenyan pregnant women. We identified the provision of adequate vaccine information and addressing safety concerns as opportunities to improve maternal vaccine uptake. The expressed willingness to receive a vaccine not currently in routine use bodes well for implementation of new maternal vaccines in Kenya.

Highlights • Willingness to be vaccinated against influenza while pregnant was high. • Willingness to vaccinate was higher among pregnant women who knew about influenza. • Government recommendation for the vaccine may lead to higher rates of acceptance. • Improving disease knowledge and mitigating safety concerns may improve acceptance. • Hesitant mothers should be educated on benefits of the vaccine during pregnancy., Background Influenza vaccination during pregnancy benefits mothers and children. Kenya and other low- and middle-income countries have no official influenza vaccination policies to date but are moving towards issuing such policies. Understanding determinants of influenza vaccine uptake during pregnancy in these settings is important to inform policy decisions and vaccination rollout. Methods We interviewed a convenience sample of women at antenatal care facilities in four counties (Nairobi, Mombasa, Marsabit, Siaya) in Kenya. We described knowledge and attitudes regarding influenza vaccination and assessed factors associated with willingness to receive influenza vaccine. Results We enrolled 507 pregnant women, median age was 26 years (range 15–43). Almost half (n = 240) had primary or no education. Overall, 369 (72.8%) women had heard of influenza. Among those, 288 (78.1%) believed that a pregnant woman would be protected if vaccinated, 252 (68.3%) thought it was safe to receive a vaccine while pregnant, and 223 (60.4%) believed a baby would be protected if mother was vaccinated. If given opportunity, 309 (83.7%) pregnant women were willing to receive the vaccine. Factors associated with willingness to receive influenza vaccine were mothers’ belief in protective effect (OR 3.87; 95% CI 1.56, 9.59) and safety (OR 5.32; 95% CI 2.35, 12.01) of influenza vaccines during pregnancy. Conclusion Approximately one third of pregnant women interviewed had never heard of influenza. Willingness to receive influenza vaccine was high among women who had heard about influenza. If the Kenyan government recommends influenza vaccine for pregnant women, mitigation of safety concerns and education on the benefits of vaccination could be the most effective strategies to improve vaccine acceptance.

BackgroundTo improve early detection of emerging infectious diseases in sub-Saharan Africa (SSA), many of them zoonotic, numerous electronic animal disease-reporting systems have been piloted but not implemented because of cost, lack of user friendliness, and data insecurity. In Kenya, we developed and rolled out an open-source mobile phone-based domestic and wild animal disease reporting system and collected data over two years to demonstrate its robustness and ability to track disease trends.MethodsThe Kenya Animal Biosurveillance System (KABS) application was built on the Java® platform, freely downloadable for android compatible mobile phones, and supported by web-based account management, form editing and data monitoring. The application was integrated into the surveillance systems of Kenya’s domestic and wild animal sectors by adopting their existing data collection tools, and targeting disease syndromes prioritized by national, regional and international animal and human health agencies. Smartphone-owning government and private domestic and wild animal health officers were recruited and trained on the application, and reports received and analyzed by Kenya Directorate of Veterinary Services. The KABS application performed automatic basic analyses (frequencies, spatial distribution), which were immediately relayed to reporting officers as feedback.ResultsOver 95% of trained domestic animal officers downloaded the application, and >72% of them started reporting using the application within three months. Introduction of the application resulted in 2- to 10-fold increase in number of disease reports when compared the previous year (p90% of the reports, with respiratory, gastrointestinal and skin diseases constituting >85% of the reports. Herbivore wildlife (zebra, buffalo, elephant, giraffe, antelopes) accounted for >60% of the wildlife disease reports, followed by carnivores (lions, cheetah, hyenas, jackals, and wild dogs). Deaths, traumatic injuries, and skin diseases were most reported in wildlife.ConclusionsThis open-source system was user friendly and secure, ideal for rolling out in other countries in SSA to improve disease reporting and enhance preparedness for epidemics of zoonotic diseases.Authors SummaryTaking advantage of a recently developed freely downloadable disease reporting application in the United States, we customized it for android smartphones to collect and submit domestic and wild animal disease data in real-time in Kenya. To enhance user friendliness, the Kenya Animal Biosurveillance System (KABS) was installed with disease reporting tools currently used by the animal sector and tailored to collected data on transboundary animal disease important for detecting zoonotic endemic and emerging diseases. The KABS database was housed by the government of Kenya, providing important assurance on its security. The application had a feedback module that performed basics analysis to provide feedback to the end-user in real-time. Rolling out of KABS resulted in >70% of domestic and wildlife disease surveillance officers using it to report, resulting in exponential increase in frequency and spatial distributions of reports regions. Utility of the system was demonstrated by successful detected a Rift Valley fever outbreak in livestock in 2018, resulting in early response and prevention of widespread human infections. For the wildlife sector in Eastern Africa, the application provided the first disease surveillance system developed. This open-source system is ideal for rolling out in other countries in sub-Saharan Africa to improve disease reporting and enhance preparedness for epidemics of zoonotic diseases.

Introduction: In tropical Africa, data about influenza-associated illness burden are needed to assess potential benefits of influenza vaccination among pregnant women. We estimated the incidence of influenza among pregnant women and their infants in Siaya County, Kenya. Methods: We enrolled women at

BackgroundWe report results of years 2 and 3 of consecutive cluster-randomized controlled trials of trivalent inactivated influenza vaccine (IIV3) in Senegal.MethodsWe cluster-randomized (1:1) 20 villages to annual vaccination with IIV3 or inactivated poliovirus vaccine (IPV) of age-eligible residents (6 months–10 years). The primary outcome was total vaccine effectiveness against laboratory-confirmed influenza illness (LCI) among age-eligible children (modified intention-to-treat population [mITT]). Secondary outcomes were indirect (herd protection) and population (overall community) vaccine effectiveness.ResultsWe vaccinated 74% of 12 408 age-eligible children in year 2 (June 2010–April 11) and 74% of 11 988 age-eligible children in year 3 (April 2011–December 2011) with study vaccines. Annual cumulative incidence of LCI was 4.7 (year 2) and 4.2 (year 3) per 100 mITT child vaccinees of IPV villages. In year 2, IIV3 matched circulating influenza strains. The total effectiveness was 52.8% (95% confidence interval [CI], 32.3–67.0), and the population effectiveness was 36.0% (95% CI, 10.2–54.4) against LCI caused by any influenza strain. The indirect effectiveness against LCI by A/H3N2 was 56.4% (95% CI, 39.0–68.9). In year 3, 74% of influenza detections were vaccine-mismatched to circulating B/Yamagata and 24% were vaccine-matched to circulating A/H3N2. The year 3 total effectiveness against LCI was −14.5% (95% CI, −81.2–27.6). Vaccine effectiveness varied by type/subtype of influenza in both years.ConclusionsIIV3 was variably effective against influenza illness in Senegalese children, with total and indirect vaccine effectiveness present during the year when all circulating strains matched the IIV3 formulation.Clinical Trials RegistrationNCT00893906.

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.

Background and objectives Although acute respiratory illness (ARI) is a leading cause of hospitalization among young children, few data are available about cost of hospitalization in middle-income countries. We estimated direct and indirect costs associated with severe ARI resulting in hospitalization among children aged Methods During 2012 and 2013, we surveyed caregivers of children hospitalized with ARI about their direct medical (i.e., outpatient consultation, medications, hospital fees), non-medical (transportation, childcare), and indirect costs (lost wages) at discharge and 7 days after discharge. We multiplied subsidized hospital bed costs derived from administrative data by hospitalization days to estimate provider costs. Results Overall, 638 children were enrolled with a median age of 12 months (IQR 6–23). Their median length of hospitalization was 4 days (IQR 3–6). In El Salvador, caregivers incurred a median of US$38 (IQR 22–72) in direct and indirect costs per illness episode, while the median government-paid hospitalization cost was US$118 (IQR 59–384) generating an overall societal cost of US$219 (IQR 101–416) per severe ARI episode. In Panama, caregivers incurred a median of US$75 (IQR 39–135) in direct and indirect costs, and the health-care system paid US$280 (IQR 150–420) per hospitalization producing an overall societal cost of US$393 (IQR 258–552). Conclusions The cost of severe ARI to caregivers and the health care system was substantive. Our estimates will inform models to estimate national costs of severe ARI and cost-benefit of prevention and treatment strategies.

Summary: Background: Paediatric vaccination against influenza can result in indirect protection, by reducing transmission to their unvaccinated contacts. We investigated whether influenza vaccination of children would protect them and their household members in a resource-limited setting. Methods: We did a cluster-randomised, blinded, controlled study in three villages in India. Clusters were defined as households (ie, dwellings that shared a courtyard), and children aged 6 months to 10 years were eligible for vaccination as and when they became age-eligible throughout the study. Households were randomly assigned (1:1) by a computer-based system to intramuscular trivalent inactivated influenza vaccine (IIV3) or a control of inactivated poliovirus vaccine (IPV) in the beginning of the study; vaccination occurred once a year for 3 years. The primary efficacy outcome was laboratory-confirmed influenza in a vaccinated child with febrile acute respiratory illness, analysed in the modified intention-to-treat population (ie, children who received at least one dose of vaccine, were under surveillance, and had not an influenza infection within 15 days of last vaccine dose). The secondary outcome for indirect effectiveness (surveillance study) was febrile acute respiratory illness in an unvaccinated household member of a vaccine study participant. Data from each year (year 1: November, 2009, to October, 2010; year 2: October, 2010, to October, 2011; and year 3: October, 2011, to May, 2012) were analysed separately. Safety was analysed among all participants who were vaccinated with at least one dose of the vaccine. This trial is registered with ClinicalTrials.gov, number NCT00934245. Findings: Between Nov 1, 2009, to May 1, 2012, we enrolled 3208 households, of which 1959 had vaccine-eligible children. 1010 households were assigned to IIV3 and 949 households were assigned to IPV. In 3 years, we vaccinated 4345 children (2132 with IIV3 and 2213 with IPV) from 1868 households (968 with IIV3 and 900 with IPV) with 10 813 unvaccinated household contacts. In year 1, influenza virus was detected in 151 (10%) of 1572 IIV3 recipients and 206 (13%) of 1633 of IPV recipients (total IIV3 vaccine efficacy 25·6% [95% CI 6·8–40·6]; p=0·010). In year 2, 105 (6%) of 1705 IIV3 recipients and 182 (10%) of 1814 IPV recipients had influenza (vaccine efficacy 41·0% [24·1–54·1]; p

Background Data on pneumococcal conjugate vaccine (PCV) indirect effects in low-income countries with high human immunodeficiency virus (HIV) burden are limited. We examined adult pneumococcal pneumonia incidence before and after PCV introduction in Kenya in 2011. Methods From 1 January 2008 to 31 December 2016, we conducted surveillance for acute respiratory infection (ARI) among ~12 000 adults (≥18 years) in western Kenya, where HIV prevalence is ~17%. ARI cases (cough or difficulty breathing or chest pain, plus temperature ≥38.0°C or oxygen saturation Results Pre-PCV (2008–2010) crude and adjusted ARI incidences were 3.14 and 5.30/100 person-years-observation (pyo), respectively. Among ARI cases, 39.0% (340/872) had both blood culture and UAT; 21.2% (72/340) had pneumococcus detected, yielding a baseline pneumococcal pneumonia incidence of 1.12/100 pyo (95% confidence interval [CI]: 1.0–1.3). In each post-PCV year (2012–2016), the incidence was significantly lower than baseline; with incidence rate ratios (IRRs) of 0.53 (95% CI: 0.31–0.61) in 2012 and 0.13 (95% CI: 0.09–0.17) in 2016. Similar declines were observed in HIV-infected (IRR: 0.13; 95% CI: 0.08–0.22) and HIV-uninfected (IRR: 0.10; 95% CI: 0.05–0.20) adults. Conclusions Adult pneumococcal pneumonia declined in western Kenya following PCV introduction, likely reflecting vaccine indirect effects. Evidence of herd protection is critical for guiding PCV policy decisions in resource-constrained areas.

Background Pregnant women are prioritized for seasonal influenza vaccination, but the evidence on the risk of influenza during pregnancy that is used to inform these policies is limited. Methods Individual-level administrative data sets and active surveillance data were joined to estimate influenza-associated hospitalization and outpatient visit rates by pregnancy, postpartum, and trimester status. Results During 2012-2015, 46 of 260 (17.7%) influenza-confirmed hospitalizations for acute respiratory infection and 13 of 294 (4.4%) influenza-confirmed outpatient visits were among pregnant and postpartum women. Pregnant and postpartum women experienced higher rates of influenza-associated hospitalization than nonpregnant women overall (rate ratio [RR], 3.4; 95% confidence interval [CI], 2.5-4.7) and by trimester (first, 2.5 [95% CI, 1.2-5.4]; second, 3.9 [95% CI, 2.4-6.3]; and third, 4.8 [95% CI, 3.0-7.7]); the RR for the postpartum period was 0.7 (95% CI, 3.0-7.7). Influenza A viruses were associated with an increased risk (RR for 2009 pandemic influenza A[H1N1] virus, 5.3 [95% CI, 3.2-8.7]; RR for influenza A(H3N2) virus, 3.0 [95% CI, 1.8-5.0]), but influenza B virus was not (RR, 1.8; 95% CI, .7-4.6). Influenza-associated hospitalization rates in pregnancy were significantly higher for Māori women (RR, 3.2; 95% CI, 1.3-8.4), compared with women of European or other ethnicity. Similar risks for influenza-confirmed outpatient visits were not observed. Conclusion Seasonal influenza poses higher risks of hospitalization among pregnant women in all trimesters, compared with nonpregnant women. Hospitalization rates vary by influenza virus type and ethnicity among pregnant women.

Rapid detection and response to infectious disease outbreaks requires a robust surveillance system with a sufficient number of trained public health workforce personnel. The Frontline Field Epidemiology Training Program (Frontline) is a focused 3-month program targeting local ministries of health to strengthen local disease surveillance and reporting capacities. Limited literature exists on the impact of Frontline graduates on disease surveillance completeness and timeliness reporting. Using routinely collected Ministry of Health data, we mapped the distribution of graduates between 2014 and 2017 across 47 Kenyan counties. Completeness was defined as the proportion of complete reports received from health facilities in a county compared with the total number of health facilities in that county. Timeliness was defined as the proportion of health facilities submitting surveillance reports on time to the county. Using a panel analysis and controlling for county-fixed effects, we evaluated the relationship between the number of Frontline graduates and priority disease reporting of measles. We found that Frontline training was correlated with improved completeness and timeliness of weekly reporting for priority diseases. The number of Frontline graduates increased by 700%, from 57 graduates in 2014 to 456 graduates in 2017. The annual average rates of reporting completeness increased from 0.8% in 2014 to 55.1% in 2017. The annual average timeliness reporting rates increased from 0.1% in 2014 to 40.5% in 2017. These findings demonstrate how global health security implementation progress in workforce development may influence surveillance and disease reporting.

Summary The failure to mount an antibody response following viral infection or seroconversion failure is a largely underappreciated and poorly understood phenomenon. Here, we identified immunologic markers associated with robust antibody responses after influenza virus infection in two independent human cohorts, SHIVERS and FLU09, based in Auckland, New Zealand and Memphis, Tennessee, USA, respectively. In the SHIVERS cohort, seroconversion significantly associates with (1) hospitalization, (2) greater numbers of proliferating, activated CD4+ T cells, but not CD8+ T cells, in the periphery during the acute phase of illness, and (3) fewer inflammatory monocytes (CD14hiCD16+) by convalescence. In the FLU09 cohort, fewer CD14hiCD16+ monocytes during early illness in the nasal mucosa were also associated with the generation of influenza-specific mucosal immunoglobulin A (IgA) and IgG antibodies. Our study demonstrates that seroconversion failure after infection is a definable immunological phenomenon, associated with quantifiable cellular markers that can be used to improve diagnostics, vaccine efficacy, and epidemiologic efforts.

Background: Maternal immunization is known to be one of the best strategies to protect both mothers and their infants from infectious diseases. Studies have shown that healthcare providers play a critical role in implementation of maternal immunization. However, little is known about providers’ attitudes and beliefs towards vaccination that can influence their vaccine recommendations, specifically in low to middle income countries (LMIC). Methods: A self-administrated knowledge, attitude and behavior (KAB) survey was provided to 150 antenatal care providers across four different regions (Nairobi, Mombasa, Marsabit, and Siaya counties) of Kenya. The research staff visited the 150 clinics and hospitals and distributed a quantitative KAB survey. Results: Nearly all of the antenatal care providers (99%) recommended tetanus maternal vaccination. Similarly, 99% of the providers agreed that they would agree to provide additional vaccinations for pregnant women and reported that they always advise their patients to get vaccinated. Between 80 and 90% of the providers reported that religious beliefs, ethnicity, cultural background and political leaders do not affect their attitude or beliefs towards recommending vaccines. Conclusions: Considering the positive responses of healthcare providers towards vaccine acceptance and recommendation, these results highlight an opportunity to work in partnership with these providers to improve coverage of maternal vaccination and to introduce additional vaccines (such as influenza). In order to achieve this, logistical barriers that have affected the coverage of the currently recommended vaccines, should be addressed as part of this partnership.

Background Influenza is a cause of febrile acute respiratory infection (FARI) in India; however, few influenza vaccine trials have been conducted in India. We assessed absolute and relative efficacy of live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) among children aged 2 to 10 years in rural India through a randomized, triple-blind, placebo-controlled trial conducted over 2 years. Methods and findings In June 2015, children were randomly allocated to LAIV, IIV, intranasal placebo, or inactivated polio vaccine (IPV) in a 2:2:1:1 ratio. In June 2016, vaccination was repeated per original allocation. Overall, 3,041 children received LAIV (n = 1,015), IIV (n = 1,010), nasal placebo (n = 507), or IPV (n = 509). Mean age of children was 6.5 years with 20% aged 9 to 10 years. Through weekly home visits, nasal and throat swabs were collected from children with FARI and tested for influenza virus by polymerase chain reaction. The primary outcome was laboratory-confirmed influenza-associated FARI; vaccine efficacy (VE) was calculated using modified intention-to-treat (mITT) analysis by Cox proportional hazards model (PH) for each year. In Year 1, VE was 40.0% (95% confidence interval (CI) 25.2 to 51.9) for LAIV and 59.0% (95% CI 47.8 to 67.9) for IIV compared with controls; relative efficacy of LAIV compared with IIV was −46.2% (95% CI −88.9 to −13.1). In Year 2, VE was 51.9% (95% CI 42.0 to 60.1) for LAIV and 49.9% (95% CI 39.2 to 58.7) for IIV; relative efficacy of LAIV compared with IIV was 4.2% (95% CI −19.9 to 23.5). No serious adverse vaccine-attributable events were reported. Study limitations include differing dosage requirements for children between nasal and injectable vaccines (single dose of LAIV versus 2 doses of IIV) in Year 1 and the fact that immunogenicity studies were not conducted. Conclusions In this study, we found that LAIV and IIV vaccines were safe and moderately efficacious against influenza virus infection among Indian children. Trial registration Clinical Trials Registry of India CTRI/2015/06/005902., Anand Krishnan and co-workers study the efficacy and safety of influenza vaccines for children in India., Author summary Why was this study done? In recent years, 2 community-based trials of the single-dose Russian-backbone live attenuated influenza vaccine (LAIV) in low- and middle-income countries (LMIC) have been published, with contrasting results. In Senegal, LAIV vaccine efficacy (VE) was demonstrated to be 0.0% (95% confidence interval (CI) −26.4 to 20.9), and in Bangladesh, LAIV VE was demonstrated to be 41.0% (95% CI 28.0 to 51.6) against all influenza virus strains. In addition, observational studies for VE of LAIV such as in the United States and Europe have also shown mixed results. While the World Health Organization (WHO) continues to recommend LAIV use in children, conflicting data on LAIV have led countries to review and reconsider national preferential recommendations for LAIV use in children. Given these gaps in evidence and the potential for indigenously produced LAIV to be used for prevention of influenza virus infection in Indian children, we evaluated the absolute efficacy of LAIV and inactivated influenza vaccine (IIV) and relative efficacy of LAIV versus IIV among children aged 2 to 10 years in rural India. What did the researchers do and find? We conducted a 2-year, triple (participant–observer–analyst) blind, community-based vaccine trial. We randomly assigned 3,041 children aged 2 to 10 years to receive age appropriate doses of LAIV, IIV, or a control vaccine. In Year 1, VE was 40.0% (95% CI 25.2 to 51.9) for LAIV and 59.0% (95% CI 47.8 to 67.9) for IIV compared with controls; relative efficacy of LAIV compared with IIV was −46.2% (95% CI −88.9 to −13.1). In Year 2, VE was 51.9% (95% CI 42.0 to 60.1) for LAIV and 49.9% (95% CI 39.2 to 58.7) for IIV; relative efficacy of LAIV compared with IIV was 4.2% (95% CI −19.9 to 23.5). We found that LAIV and IIV were safe and moderately efficacious against laboratory-confirmed influenza virus infection. In Year 1, LAIV, as a single dose in a vaccine-naïve population, was significantly less efficacious than IIV, whereas in Year 2, VE for LAIV and IIV was similar. This was the first randomized controlled trial to our knowledge in a developing country setting that compared LAIV efficacy with IIV and provided VE by age group and influenza type/subtype across seasons spanning 2 consecutive years. Importantly, during both years, LAIV and IIV were protective against influenza A(H3N2) viruses. However, LAIV had limited efficacy against influenza A(H1N1)pdm09 for both years. What do these findings mean? Influenza vaccination is an important tool for preparedness and response against seasonal epidemics and pandemics. However, decisions on specific vaccine introductions into national immunization platforms depend on multiple factors including effectiveness, presence of existing immunization platforms and cold chain infrastructure, cost, and local production of the vaccines. Availability of indigenous, safe, and moderately efficacious influenza vaccines, including LAIV, should initiate discussion on the optimal use of vaccines for the national strategy for influenza prevention and control in India.

Background Brucellosis occurs globally with highly variable incidence in humans from very low in North America and Western Europe to high in the Middle East and Asia. There are few data in Sub-Saharan Africa. This study estimated the incidence of human brucellosis in a pastoralist community in Kenya. Methods Between February 2015 and January 2016, we enrolled persons living in randomly selected households in Kajiado County. Free health care was offered at three facilities in the study area. Those who met the study clinical case definition completed a standardized questionnaire on demographics, clinical history and presentation. A blood sample was collected and tested by Rose Bengal test (RBT), then later tested at the Kenya Medical Research Institute laboratory for Brucella IgG and IgM by ELISA. Those who tested positive by both RBT and ELISA (IgG or IgM antibodies) were classified as confirmed while those that only tested positive for IgG or IgM antibodies were classified as probable. Further, sera were tested by polymerase chain reaction using a TaqMan Array Card (TAC) for a panel of pathogens causing AFI including Brucella spp. Annual incidence of brucellosis was calculated as the number of confirmed cases in one year/total number in the study population. Results We enrolled a cohort of 4746 persons in 804 households. Over half (52.3%) were males and the median age was 18 years (Interquartile range (IQR) 9 months– 32 years). A total of 236 patients were enrolled at three health facilities; 64% were females and the median age was 40.5 years (IQR 28–53 years). Thirty-nine (16.5%) were positive for Brucella antibodies by IgG ELISA, 5/236 (2.1%) by IgM ELISA and 4/236 (1.7%) by RBT. Ten percent (22/217) were positive by TAC. We confirmed four (1.7%) brucellosis cases giving an annual incidence of 84/100,000 persons/year (95% CI 82, 87). The incidence did not significantly vary by gender, age and location of residence. Conclusion We report a high incidence of brucellosis in humans among members of this pastoralist community. Brucellosis was the most common cause of febrile illness in this community., Author summary Brucellosis is a bacterial disease that affects both humans and animals. Humans get infected via ingestion of unpasteurized animal products from infected animals and direct contact during animal abortions and deliveries. Infected animals shed bacteria for life through milk and during deliveries posing a risk to those with occupational exposure to infected animals. As such, human disease is disproportionately high in regions with high prevalence of animal brucellosis. While human brucellosis is distributed globally, incidence is low in North America and Western Europe and high in Asia and the Middle East where the disease is endemic. Data from Africa are scarce. We set out to estimate the incidence of brucellosis in a pastoralist community with documented high Brucella sero-prevalence in humans and livestock. We followed up a cohort of 804 households for one year and tested household members who became ill in three designated health facilities. We estimated an incidence of 84 cases per 100,000 persons per year in this community. We also found that Brucella was the most common pathogen among persons who had febrile illness highlighting the importance of this pathogen in this rural pastoralist community. No brucellosis intervention measures were being implemented.

Despite high exposure to Middle East respiratory syndrome coronavirus (MERS-CoV), the predictors for seropositivity in the context of husbandry practices for camels in Eastern Africa are not well understood. We conducted a cross-sectional survey to describe the camel herd profile and determine the factors associated with MERS-CoV seropositivity in Northern Kenya. We enrolled 29 camel-owning households and administered questionnaires to collect herd and household data. Serum samples collected from 493 randomly selected camels were tested for anti-MERS-CoV antibodies using a microneutralisation assay, and regression analysis used to correlate herd and household characteristics with camel seropositivity. Households reared camels (median = 23 camels and IQR 16–56), and at least one other livestock species in two distinct herds; a home herd kept near homesteads, and a range/fora herd that resided far from the homestead. The overall MERS-CoV IgG seropositivity was 76.3%, with no statistically significant difference between home and fora herds. Significant predictors for seropositivity (P ⩽ 0.05) included camels 6–10 years old (aOR 2.3, 95% CI 1.0–5.2), herds with ⩾25 camels (aOR 2.0, 95% CI 1.2–3.4) and camels from Gabra community (aOR 2.3, 95% CI 1.2–4.2). These results suggest high levels of virus transmission among camels, with potential for human infection.

Aflatoxins are carcinogenic mycotoxins that contaminate a variety of crops worldwide. Acute exposure can cause liver failure, and chronic exposure can lead to stunting in children and liver cancer in adults. We estimated aflatoxin exposure across Uganda by measuring a serum biomarker of aflatoxin exposure in a subsample from the 2011 Uganda AIDS Indicator Survey, a nationally representative survey of HIV prevalence, and examined its association with geographic, demographic, and socioeconomic variables. We analysed a subsample of 985 serum specimens selected among HIV-negative participants from 10 survey-defined geographic regions for serum aflatoxin B1-lysine (AFB1-lys) by use of isotope dilution LC-MS/MS and calculated results normalised to serum albumin. We used statistical techniques for censored data to estimate geometric means (GMs), standard deviations, and percentiles. We detected serum AFB1-lys in 71.7% of specimens (LOD = 0.5 pg/mg albumin). Unadjusted GM AFB1-lys (pg/mg albumin) was 1.33 (95% CI: 1.21-1.47). Serum AFB1-lys was higher in males (GM: 1.57; 95% CI: 1.38-1.80) vs. females (GM: 1.12; 95% CI: 0.97-1.30) (

Background:There is substantial burden of seasonal influenza in Kenya, which led the government to consider introducing a national influenza vaccination programme. Given the cost implications of a nationwide programme, local economic evaluation data are needed to inform policy on the design and benefits of influenza vaccination. We set out to estimate the cost-effectiveness of seasonal influenza vaccination in Kenya. Methods:We fitted an age-stratified dynamic transmission model to active surveillance data from patients with influenza from 2010 to 2018. Using a societal perspective, we developed a decision tree cost-effectiveness model and estimated the incremental cost-effectiveness ratio (ICER) per disability-adjusted life year (DALY) averted for three vaccine target groups: children 6–23 months (strategy I), 2–5 years (strategy II) and 6–14 years (strategy III) with either the Southern Hemisphere influenza vaccine (Strategy A) or Northern Hemisphere vaccine (Strategy B) or both (Strategy C: twice yearly vaccination campaigns, or Strategy D: year-round vaccination campaigns). We assessed cost-effectiveness by calculating incremental net monetary benefits (INMB) using a willingness-to-pay (WTP) threshold of 1–51% of the annual gross domestic product per capita (USD17–USD872). Results:The mean number of infections across all ages was 2–15 million per year. When vaccination was well timed to influenza activity, the annual mean ICER per DALY averted for vaccinating children 6–23 months ranged between USD749 and USD1385 for strategy IA, USD442 and USD1877 for strategy IB, USD678 and USD4106 for strategy IC and USD1147 and USD7933 for strategy ID. For children 2–5 years, it ranged between USD945 and USD1573 for strategy IIA, USD563 and USD1869 for strategy IIB, USD662 and USD4085 for strategy IIC, and USD1169 and USD7897 for strategy IID. For children 6–14 years, it ranged between USD923 and USD3116 for strategy IIIA, USD1005 and USD2223 for strategy IIIB, USD883 and USD4727 for strategy IIIC and USD1467 and USD6813 for strategy IIID. Overall, no vaccination strategy was cost-effective at the minimum (USD17) and median (USD445) WTP thresholds. Vaccinating children 6–23 months once a year had the highest mean INMB value at USD872 (WTP threshold upper limit); however, this strategy had very low probability of the highest net benefit. Conclusion:Vaccinating children 6–23 months once a year was the most favourable vaccination option; however, the strategy is unlikely to be cost-effective given the current WTP thresholds.

Large-scale serosurveillance of severe acute respiratory syndrome coronavirus type 2 (SARS- CoV-2) will only be possible if serological tests are sufficiently reliable, rapid and inexpensive. Current assays are either labour-intensive and require specialised facilities (e.g. virus neutralization assays), or expensive with suboptimal specificity (e.g. commercial ELISAs). Bead-based assays offer a cost-effective alternative and allow for multiplexing to test for antibodies of other pathogens. Here, we compare the performance of four antigens for the detection of SARS-CoV-2 specific IgG antibodies in a panel of sera that includes both severe (n=40) and mild (n=52) cases, using a neutralization and a Luminex bead-based assay. While we show that neutralising antibody levels are significantly lower in mild than in severe cases, we demonstrate that a combination of recombinant nucleocapsid protein (NP), receptor- binding domain (RBD) and the whole spike protein (S1S2) results in a highly sensitive (96%) and specific (99%) bead-based assay that can detect IgG antibodies in both groups. Although S1-specific IgG levels correlate most strongly with neutralizing antibody levels, they fall below the detection threshold in 10% of the cases in our Luminex assay. In conclusion, our data supports the use of RBD, NP and S1S2 for the development of SARS-CoV-2 serological bead- based assays. Finally, we argue that low antibody levels in mild/asymptomatic cases might complicate the epidemiological assessment of large-scale surveillance studies.

Background Effective public health surveillance systems are crucial for early detection and response to outbreaks. In 2016, Kenya transitioned its surveillance system from a standalone web-based surveillance system to the more sustainable and integrated District Health Information System 2 (DHIS2). As part of Global Health Security Agenda (GHSA) initiatives in Kenya, training on use of the new system was conducted among surveillance officers. We evaluated the surveillance indicators during the transition period in order to assess the impact of this training on surveillance metrics and identify challenges affecting reporting rates. Methods From February to May 2017, we analysed surveillance data for 13 intervention and 13 comparison counties. An intervention county was defined as one that had received refresher training on DHIS2 while a comparison county was one that had not received training. We evaluated the impact of the training by analysing completeness and timeliness of reporting 15 weeks before and 12 weeks after the training. A chi-square test of independence was used to compare the reporting rates between the two groups. A structured questionnaire was administered to the training participants to assess the challenges affecting surveillance reporting. Results The average completeness of reporting for the intervention counties increased from 45 to 62%, i.e. by 17 percentage points (95% CI 16.14–17.86) compared to an increase from 49 to 52% for the comparison group, i.e. by 3 percentage points (95% CI 2.23–3.77). The timeliness of reporting increased from 30 to 51%, i.e. by 21 percentage points (95% CI 20.16–21.84) for the intervention group, compared to an increase from 31 to 38% for the comparison group, i.e.by 7 percentage points (95% CI 6.27–7.73). Major challenges for the low reporting rates included lack of budget support from government, lack of airtime for reporting, health workers strike, health facilities not sending surveillance data, use of wrong denominator to calculate reporting rates and surveillance officers having other competing tasks. Conclusions Training plays an important role in improving public health surveillance reporting. However, to improve surveillance reporting rates to the desired national targets, other challenges affecting reporting must be identified and addressed accordingly.