Use of Sentinel Surveillance Platforms for Monitoring SARS-CoV-2 Activity: Evidence From Analysis of Kenya Influenza Sentinel Surveillance Data.

BACKGROUND: Little is known about the cocirculation of influenza and SARS-CoV-2 viruses during the COVID-19 pandemic and the use of respiratory disease sentinel surveillance platforms for monitoring SARS-CoV-2 activity in sub-Saharan Africa. OBJECTIVE: We aimed to describe influenza and SARS-CoV-2 cocirculation in Kenya and how the SARS-CoV-2 data from influenza sentinel surveillance correlated with that of universal national surveillance. METHODS: From April 2020 to March 2022, we enrolled 7349 patients with severe acute respiratory illness or influenza-like illness at 8 sentinel influenza surveillance sites in Kenya and collected demographic, clinical, underlying medical condition, vaccination, and exposure information, as well as respiratory specimens, from them. Respiratory specimens were tested for influenza and SARS-CoV-2 by real-time reverse transcription polymerase chain reaction. The universal national-level SARS-CoV-2 data were also obtained from the Kenya Ministry of Health. The universal national-level SARS-CoV-2 data were collected from all health facilities nationally, border entry points, and contact tracing in Kenya. Epidemic curves and Pearson r were used to describe the correlation between SARS-CoV-2 positivity in data from the 8 influenza sentinel sites in Kenya and that of the universal national SARS-CoV-2 surveillance data. A logistic regression model was used to assess the association between influenza and SARS-CoV-2 coinfection with severe clinical illness. We defined severe clinical illness as any of oxygen saturation <90%, in-hospital death, admission to intensive care unit or high dependence unit, mechanical ventilation, or a report of any danger sign (ie, inability to drink or eat, severe vomiting, grunting, stridor, or unconsciousness in children younger than 5 years) among patients with severe acute respiratory illness. RESULTS: Of the 7349 patients from the influenza sentinel surveillance sites, 76.3% (n=5606) were younger than 5 years. We detected any influenza (A or B) in 8.7% (629/7224), SARS-CoV-2 in 10.7% (768/7199), and coinfection in 0.9% (63/7165) of samples tested. Although the number of samples tested for SARS-CoV-2 from the sentinel surveillance was only 0.2% (60 per week vs 36,000 per week) of the number tested in the universal national surveillance, SARS-CoV-2 positivity in the sentinel surveillance data significantly correlated with that of the universal national surveillance (Pearson r=0.58; P<.001). The adjusted odds ratios (aOR) of clinical severe illness among participants with coinfection were similar to those of patients with influenza only (aOR 0.91, 95% CI 0.47-1.79) and SARS-CoV-2 only (aOR 0.92, 95% CI 0.47-1.82). CONCLUSIONS: Influenza substantially cocirculated with SARS-CoV-2 in Kenya. We found a significant correlation of SARS-CoV-2 positivity in the data from 8 influenza sentinel surveillance sites with that of the universal national SARS-CoV-2 surveillance data. Our findings indicate that the influenza sentinel surveillance system can be used as a sustainable platform for monitoring respiratory pathogens of pandemic potential or public health importance.

Resilience of routine childhood immunization services in two counties in Kenya in the face of the COVID-19 pandemic.

The recently emerged coronavirus disease 2019 (COVID-19) has caused considerable morbidity and mortality worldwide and disrupted health services. We describe the effect of the COVID-19 pandemic on utilization of childhood vaccination services during the pandemic. Using a mixed methods approach combining retrospective data review, a cross-sectional survey, focus group discussions among care givers and key informant interviews among nurses, we collected data between May and September 2021 in Mombasa and Nakuru counties. Overall, there was a <2 % decline in the number of vaccine doses administered during the pandemic period compared to the pre-pandemic period but this was statistically insignificant, both for the pentavalent-1 vaccine (ß = -0.013, p = 0.505) and the pentavalent-3 vaccine (ß = -0.012, p = 0.440). In government health facilities, there was 7.7 % reduction in the number of pentavalent-1 (ß = -0.08, p = 0.010) and 10.4 % reduction in the number of pentavalent-3 (ß = -0.11, p < 0.001) vaccine doses that were administered during the pandemic period. In non-government facilities, there was a 25.8 % increase in the number of pentavalent-1 (ß=0.23, p < 0.001) and 31.0 % increase in the number of pentavalent-3 (ß = -0.27, p < 0.001) vaccine doses that were administered facilities during the pandemic period. The strategies implemented to maintain immunization services during the pandemic period included providing messaging on the availability and importance of staying current with routine vaccination and conducting catch-up vaccinations and vaccination outreaches. Our findings suggest that the COVID-19 pandemic did not impact childhood vaccination services in Mombasa and Nakuru counties in Kenya. The private health facilities cushioned vaccination services against the effects of the pandemic and the strategies that were put in place by the ministry of health ensured continuation of vaccination services and encouraged uptake of the services during the pandemic period in the two counties in Kenya. These findings provide useful information to safeguard vaccination services during future pandemics.

Correcting for measurement error in assessing gestational age in a low-resource setting: a regression calibration approach.

Introduction: Measurement error in gestational age (GA) may bias the association of GA with a health outcome. Ultrasound-based GA is considered the gold standard and is not readily available in low-resource settings. We corrected for measurement error in GA based on fundal height (FH) and date of last menstrual period (LMP) using ultrasound from the sub-cohort and adjusted for the bias in associating GA with neonatal mortality and low birth weight (< 2,500 grams, LBW). Methods: We used data collected from 01/2015 to 09/2019 from pregnant women enrolled at two public hospitals in Siaya county, Kenya (N = 2,750). We used regression calibration to correct for measurement error in FH- and LMP-based GA accounting for maternal and child characteristics. We applied logistic regression to associate GA with neonatal mortality and low birth weight, with and without calibrating FH- and LMP-based GA. Results: Calibration improved the precision of LMP (correlation coefficient, ρ from 0.48 to 0.57) and FH-based GA (ρ from 0.82 to 0.83). Calibrating FH/LMP-based GA eliminated the bias in the mean GA estimates. The log odds ratio that quantifies the association of GA with neonatal mortality increased by 29% (from -0.159 to -0.205) by calibrating FH-based GA and by more than twofold (from -0.158 to -0.471) by calibrating LMP-based GA. Conclusion: Calibrating FH/LMP-based GA improved the accuracy and precision of GA estimates and strengthened the association of GA with neonatal mortality/LBW. When assessing GA, neonatal public health and clinical interventions may benefit from calibration modeling in settings where ultrasound may not be fully available.

Predictors of severity of influenza-related hospitalizations: Results from the Global Influenza Hospital Surveillance Network (GIHSN).

BACKGROUND: The Global Influenza Hospital Surveillance Network (GIHSN) has since 2012 provided patient-level data on severe influenza-like illnesses from over 100 participating clinical sites worldwide based on a core protocol and consistent case definitions. To our knowledge, this is the first study to analyze multiple years of global, patient-level data generated by prospective, hospital-based surveillance across a large number of countries to investigate geographic differences in influenza severity. METHODS: We used multivariable logistic regression to assess the risk of intensive care unit admission, mechanical ventilation, and in-hospital death among hospitalized patients with influenza and explored the role of patient-level covariates and country income. RESULTS: The dataset included 73,121 patients hospitalized with respiratory illness in 22 countries, with 15,660 laboratory-confirmed for influenza. After adjusting for patient-level covariates we found a 7-fold increase in the risk of influenza-related intensive care unit admission in lower middle-income countries, compared to high-income countries (p = 0.01). The risk of mechanical ventilation and in-hospital death also increases by four-fold in lower middle-income countries, though these values were not statistically significant. We also find that influenza severity increased with older age and number of comorbidities. Across all severity outcomes studied and after controlling for patient characteristics, infection with influenza A/H1N1pdm09 was more severe than with A/H3N2. CONCLUSIONS: Our study provides new information on influenza severity in under-resourced populations, particularly those in lower middle-income countries. Understanding the mechanisms responsible for these disparities will be important to improve management of influenza, optimize vaccine allocation, and mitigate global disease burden.

Assessment of gestational age at antenatal care visits among Kenyan women to inform delivery of a maternal respiratory syncytial virus (RSV) vaccine in low- and middle-income countries.

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.

Respiratory Syncytial Virus (RSV) Disease and Prevention Products: Knowledge, Attitudes, and Preferences of Kenyan Healthcare Workers in Two Counties in 2021.

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.

Age Differences in Comorbidities, Presenting Symptoms, and Outcomes of Influenza Illness Requiring Hospitalization: A Worldwide Perspective From the Global Influenza Hospital Surveillance Network.

Background: The Global Influenza Hospital Surveillance Network (GIHSN) was established in 2012 to conduct coordinated worldwide influenza surveillance. In this study, we describe underlying comorbidities, symptoms, and outcomes in patients hospitalized with influenza. Methods: Between November 2018 and October 2019, GIHSN included 19 sites in 18 countries using a standardized surveillance protocol. Influenza infection was laboratory-confirmed with reverse-transcription polymerase chain reaction. A multivariate logistic regression model was utilized to analyze the extent to which various risk factors predict severe outcomes. Results: Of 16 022 enrolled patients, 21.9% had laboratory-confirmed influenza; 49.2% of influenza cases were A/H1N1pdm09. Fever and cough were the most common symptoms, although they decreased with age (P < .001). Shortness of breath was uncommon among those <50 years but increased with age (P < .001). Middle and older age and history of underlying diabetes or chronic obstructive pulmonary disease were associated with increased odds of death and intensive care unit (ICU) admission, and male sex and influenza vaccination were associated with lower odds. The ICU admissions and mortality occurred across the age spectrum. Conclusions: Both virus and host factors contributed to influenza burden. We identified age differences in comorbidities, presenting symptoms, and adverse clinical outcomes among those hospitalized with influenza and benefit from influenza vaccination in protecting against adverse clinical outcomes. The GIHSN provides an ongoing platform for global understanding of hospitalized influenza illness.

The relative effect of climate variability on malaria incidence after scale-up of interventions in western Kenya: A time-series analysis of monthly incidence data from 2008 to 2019.

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.

Estimates of the national burden of respiratory syncytial virus in Kenyan children aged under 5 years, 2010-2018.

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 < 5 years, the estimated annual incidence of outpatient and non-medically attended RSV-associated ARI was 206 (95% credible interval, CI; 186-229) and 226 (95% CI; 204-252) per 1000 children, respectively. The estimated annual rates of hospitalized and non-hospitalized RSV-associated SARI were 349 (95% CI; 303-404) and 1077 (95% CI; 934-1247) per 100,000 children respectively. The estimated annual number of in- and out-of-hospital deaths associated with RSV infection in Kenya were 539 (95% CI; 420-779) and 1921 (95% CI; 1495-2774), respectively. Children aged < 6 months had the highest burden of RSV-associated severe disease: 2075 (95% CI; 1818-2394) and 44 (95% CI 25-71) cases per 100,000 children for hospitalized SARI and in-hospital deaths, respectively. CONCLUSIONS: Our findings suggest a substantial disease burden due to RSV infection, particularly among younger children. Prioritizing development and use of maternal vaccines and affordable long-lasting monoclonal antibodies could help reduce this burden.

Healthcare-seeking behavior for respiratory illnesses in Kenya: implications for burden of disease estimation.

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 < 5 years, or report of inability to perform routine chores. RESULTS: From August through September 2018, we interviewed 28,072 individuals from 5,407 households. Of those surveyed, 9.2% (95% Confidence Interval [CI] 7.9-10.7) reported an episode of ARI, and 4.2% (95% CI 3.8-4.6) reported an episode of severe pneumonia. Of the reported ARI cases, 40.0% (95% CI 36.8-43.3) sought care at a health facility. Of the74.2% (95% CI 70.2-77.9) who reported severe pneumonia and visited a medical health facility, 28.9% (95% CI 25.6-32.6) were hospitalized and 7.0% (95% CI 5.4-9.1) were referred by a clinician to the hospital but not hospitalized. 21% (95% CI 18.2-23.6) of self-reported severe pneumonias were hospitalized. Children aged < 5 years and persons in households with a higher socio-economic status were more likely to seek care for respiratory illness at a health facility. CONCLUSION: Our findings suggest that hospital-based surveillance captures less than one quarter of severe pneumonia in the community. Multipliers from community household surveys can account for underutilization of healthcare resources and under-ascertainment of severe pneumonia at hospitals.

Diagnostic accuracy of the Panbio COVID-19 antigen rapid test device for SARS-CoV-2 detection in Kenya, 2021: A field evaluation.

BACKGROUND: Accurate 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%. METHODS: This 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. RESULTS: We 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 <5 days (594/876, 67.8%), sensitivity was 67.1% (95% CI: 59.2-74.3%), and 53.3% (95% CI: 40.0-66.3%) among those 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. CONCLUSION: The 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.

Prevalence of microcephaly and Zika virus infection in a pregnancy cohort in Kenya, 2017-2019.

BACKGROUND: Zika virus (ZIKV), first discovered in Uganda in 1947, re-emerged globally in 2013 and was later associated with microcephaly and other birth defects. We determined the incidence of ZIKV infection and its association with adverse pregnancy and fetal outcomes in a pregnancy cohort in Kenya. METHODS: From October 2017 to July 2019, we recruited and followed up women aged ≥ 15 years and ≤ 28 weeks pregnant in three hospitals in coastal Mombasa. Monthly follow-up included risk factor questions and a blood sample collected for ZIKV serology. We collected anthropometric measures (including head circumference), cord blood, venous blood from newborns, and any evidence of birth defects. Microcephaly was defined as a head circumference (HC) < 2 standard deviations (SD) for sex and gestational age. Severe microcephaly was defined as HC < 3 SD for sex and age. We tested sera for anti-ZIKV IgM antibodies using capture enzyme-linked immunosorbent assay (ELISA) and confirmed positives using the plaque reduction neutralization test (PRNT90) for ZIKV and for dengue (DENV) on the samples that were ZIKV neutralizing antibody positive. We collected blood and urine from participants reporting fever or rash for ZIKV testing. RESULTS: Of 2889 pregnant women screened for eligibility, 2312 (80%) were enrolled. Of 1916 recorded deliveries, 1816 (94.6%) were live births and 100 (5.2%) were either stillbirths or spontaneous abortions (< 22 weeks of gestation). Among 1236 newborns with complete anthropometric measures, 11 (0.9%) had microcephaly and 3 (0.2%) had severe microcephaly. A total of 166 (7.2%) participants were positive for anti-ZIKV IgM, 136 of whom became seropositive during follow-up. Among the 166 anti-ZIKV IgM positive, 3 and 18 participants were further seropositive for ZIKV and DENV neutralizing antibodies, respectively. Of these 3 and 18 pregnant women, one and 13 (72.2%) seroconverted with antibodies to ZIKV and DENV, respectively. All 308 samples (serum and urine samples collected during sick visits and samples that were anti-ZIKV IgM positive) tested by RT-PCR were negative for ZIKV. No adverse pregnancy or neonatal outcomes were reported among the three participants with confirmed ZIKV exposure. Among newborns from pregnant women with DENV exposure, four (22.2%) were small for gestational age and one (5.6%) had microcephaly. CONCLUSIONS: The prevalence of severe microcephaly among newborns in coastal Kenya was high relative to published estimates from facility-based studies in Europe and Latin America, but little evidence of ZIKV transmission. There is a need for improved surveillance for microcephaly and other congenital malformations in Kenya.

Development of effective messages to promote maternal immunization in Kenya.

OBJECTIVES: This study evaluated messages and communication approaches for maternal immunization uptake in Kenya. We identified persuasive communication aspects that would inform maternal immunization attitudes, intent, and vaccine uptake. METHODS: We conducted a two-phased mixed methods study with pregnant women and their male partners in three regions of Kenya. Discussions were conducted in English and Swahili languages by trained focus group moderators. Baseline measures included a survey and discussions about potential messages and accompanying visuals. Follow-up focus groups with the same participants included a survey about previously discussed messages, visuals, and communication impressions. The second round of focus groups focused on message preferences developed from the first round, along with rank order discussion for final message selection. Following transcription of focus group discussions, we conducted analyses using NVivo software. Quantitative data analyses included frequencies, factor analyses, reliability assessment, regression modeling, and comparative assessment of rank order. RESULTS: The sample (N = 118) included pregnant women (n = 91) and their partners (n = 27) from diverse Kenyan regions (Bondo/Lwak/Siaya, Mombasa, and Nairobi). A four-factor solution resulted from factor analyses that included subscales "positive ad attitudes" (n = 5 items, α = 0.82), "negative ad attitudes" (n = 4 items, α = 0.75), "ad indifference" (n = 2 items, α = 0.52), and "ad motivation" (n = 4 items, α = 0.71). Overall, the positive ad attitudes factor (ß = 0.61, p = 0.03) was the only significant component in the overall model examining message selections (χ2(6) = 262.87, p = 0.17). Among the tested concepts, we found that source and situational cues had a strong influence on women's attitude formation and intention to obtain recommended maternal vaccinations. With self-acknowledged variations in knowledge, participants were particularly attuned to images of relatable women, providers, and depictions in realistic or actual Kenyan clinical settings. CONCLUSIONS: The results indicated that positive attitudes were shaped by incorporating highly relatable factors in messages. Implications for subsequent campaigns and research directions are discussed.

Clinical and phylogenetic influenza dynamics for the 2019-20 season in the global influenza hospital surveillance network (GIHSN) - Pilot study.

BACKGROUND: The Global Influenza Hospital Surveillance Network (GIHSN) has operated with the aim of investigating epidemiological and clinical factors related to severe influenza-related hospitalisations. STUDY DESIGN: A common GIHSN core protocol for prospective patient enrolment was implemented. Hospital personnel completed a standardized questionnaire regarding the included patients' medical history, compiled a hospitalisation summary, collected an upper respiratory swab sample for laboratory diagnosis, and genome sequencing was performed for a subset of samples. Patient data were compared according to influenza subtype, lineage, and phylogenetic groups using the Fisher's exact test. RESULTS: From September 2019 to May 2020, 8791 patients aged ≥5 years were included. Among them, 3021 (34.4%) had a laboratory-confirmed influenza diagnosis. Influenza A(H1N1)pdm09 dominated the season among all age groups, while the B/Victoria-like lineage accounted for over half of the infections among younger age groups (5-49 years). Sequencing of the hemagglutinin segment was possible for 623 samples and revealed an influenza A and B clade frequency among severe influenza hospitalisations similar to other medically attended surveillance networks, such as the WHO GISRS. No phylogenetic clustering was observed among hemagglutinin substitutions depending on the administration of supplemental oxygen or vaccine failure. CONCLUSIONS: The GIHSN confirms its ability as an international hospital-based active surveillance network to provide valuable information on influenza infection dynamics in hospital settings. Increasing the number of participating sites and compiling more complete data, such as genome sequencing, will allow the exploration of associations between viral factors, vaccine protection, and disease severity.

Comparable Pregnancy Outcomes for HIV-Uninfected and HIV-Infected Women on Antiretroviral Treatment in Kenya.

BACKGROUND: The impact of human immunodeficiency virus (HIV) on pregnancy outcomes for women on antiretroviral therapy (ART) in sub-Saharan Africa remains unclear. METHODS: Pregnant women in Kenya were enrolled in the second trimester and followed up to delivery. We estimated effects of treated HIV with 3 pregnancy outcomes: loss, premature birth, and low birth weight and factors associated with HIV-positive status. RESULTS: Of 2113 participants, 311 (15%) were HIV infected and on ART. Ninety-one of 1762 (5%) experienced a pregnancy loss, 169/1725 (10%) a premature birth (<37 weeks), and 74/1317 (6%) had a low-birth-weight newborn (<2500 g). There was no evidence of associations between treated HIV infection and pregnancy loss (adjusted relative risk [aRR], 1.19; 95% confidence interval [CI], .65-2.16; P = .57), prematurity (aRR, 1.09; 95% CI, .70-1.70; P = .69), and low birth weight (aRR, 1.36; 95% CI, .77-2.40; P = .27). Factors associated with an HIV-positive status included older age, food insecurity, lower education level, higher parity, lower gestation at first antenatal clinic, anemia, and syphilis. Women who were overweight or underweight were less likely to be HIV infected compared to those with normal weight. CONCLUSIONS: Currently treated HIV was not significantly associated with adverse pregnancy outcomes. HIV-infected women, however, had a higher prevalence of other factors associated with adverse pregnancy outcomes.

Malaria hospitalisation in East Africa: age, phenotype and transmission intensity.

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 < 1 to 48.7%. Twelve site-time periods were described as low transmission (PfPR2-10 < 5%), five low-moderate transmission (PfPR2-10 5-9%), 20 moderate transmission (PfPR2-10 10-29%) and 12 high transmission (PfPR2-10 ≥ 30%). The majority of malaria admissions were below 5 years of age (69-85%) and rare among children aged 10-14 years (0.7-5.4%) across all transmission settings. The mean age of all-cause malaria hospitalisation was 49.5 months (95% CI 45.1, 55.4) under low transmission compared with 34.1 months (95% CI 30.4, 38.3) at high transmission, with similar trends for each severe malaria phenotype. CM presented among older children at a mean of 48.7 months compared with 39.0 months and 33.7 months for SMA and RD, respectively. In moderate and high transmission settings, 34% and 42% of the children were aged between 2 and 23 months and so within the age range targeted by chemoprevention or vaccines. CONCLUSIONS: Targeting chemoprevention or vaccination programmes to areas where community-based parasite prevalence is ≥10% is likely to match the age ranges covered by interventions (e.g. intermittent presumptive treatment in infancy to children aged 2-23 months and current vaccine age eligibility and duration of efficacy) and the age ranges of highest disease burden.

The burden of influenza among Kenyan pregnant and postpartum women and their infants, 2015-2020.

BACKGROUND: 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 <31 weeks of gestation and conducted weekly follow-up until 6-month postpartum to identify acute respiratory illnesses (ARIs). We defined ARI among mothers as reported cough, rhinorrhoea or sore throat and among infants as maternal-reported cough, difficulty breathing, rhinorrhoea or clinician diagnosis of respiratory illness. We collected nasal/nasopharyngeal and oropharyngeal swabs from mothers/infants with ARI and tested for influenza A and B using molecular assays. We calculated antenatal incidence of laboratory-confirmed influenza among mothers and postnatal incidence among mothers and infants. RESULTS: During June 2015 to May 2020, we analysed data from 3,026 pregnant women at a median gestational age of 16 weeks (interquartile range [IQR], 13, 18) and followed 2,550 infants. Incidence of laboratory-confirmed influenza during pregnancy (10.3 episodes per 1,000 person-months [95% confidence interval {CI} 8.6-11.8]) was twofold higher than in the postpartum period (4.0 [95% CI 2.6-5.5]; p < 0.01). Incidence was significantly higher among human immunodeficiency virus (HIV)-infected pregnant women (15.6 [95% CI 11.0-20.6] vs. 9.1 [95% CI 7.5-10.8]; p < 0.01). Incidence among young infants was 4.4 (95% CI 3.0-5.9) and similar among HIV-exposed and HIV-unexposed infants. CONCLUSION: Our findings suggest a substantial burden of influenza illnesses during pregnancy, with a higher burden among HIV-infected mothers. Kenyan authorities should consider the value of vaccinating pregnant women, especially if HIV infected.

The Impact of Maternal Human Immunodeficiency Virus Infection on the Burden of Respiratory Syncytial Virus Among Pregnant Women and Their Infants, Western Kenya.

BACKGROUND: Respiratory syncytial virus (RSV) is an important cause of respiratory illness worldwide; however, burden data on mother-infant pairs remain sparse in sub-Saharan Africa, where human immunodeficiency virus (HIV) is prevalent. We evaluated the impact of maternal HIV infection on the burden of RSV among mothers and their infants in western Kenya. METHODS: We enrolled pregnant women (≤20 weeks' gestation) and followed them and their newborns weekly for up to 3-6 months postpartum, to document cases of acute respiratory illness (ARI). Nasal/oropharyngeal swabs were collected and tested for RSV using polymerase chain reaction. Analyses were stratified by maternal HIV status and incidence was computed per 1000 person-months. RESULTS: Compared to RSV-negative ARI cases, RSV-positive cases were associated with cough, apnea, and hospitalization among infants. RSV incidence per 1000 person-months among mothers was 4.0 (95% confidence interval [CI], 3.2-4.4), and was twice that among the HIV-infected mothers (8.4 [95% CI, 5.7-12.0]) compared to the HIV-uninfected mothers (3.1 [95% CI, 2.3-4.0]). Among infants, incidence per 1000 person-months was 15.4 (95% CI, 12.5-18.8); incidence did not differ by HIV exposure or prematurity. CONCLUSIONS: HIV infection may increase the risk of RSV illness among pregnant women. Future maternal RSV vaccines may have added benefit in areas with high HIV prevalence.

Effect of Time Since Death on Multipathogen Molecular Test Results of Postmortem Specimens Collected Using Minimally Invasive Tissue Sampling Techniques.

BACKGROUND: We used postmortem minimally invasive tissue sampling (MITS) to assess the effect of time since death on molecular detection of pathogens among respiratory illness-associated deaths. METHODS: Samples were collected from 20 deceased children (aged 1-59 months) hospitalized with respiratory illness from May 2018 through February 2019. Serial lung and/or liver and blood samples were collected using MITS starting soon after death and every 6 hours thereafter for up to 72 hours. Bodies were stored in the mortuary refrigerator for the duration of the study. All specimens were analyzed using customized multipathogen TaqMan® array cards (TACs). RESULTS: We identified a median of 3 pathogens in each child's lung tissue (range, 1-8; n = 20), 3 pathogens in each child's liver tissue (range, 1-4; n = 5), and 2 pathogens in each child's blood specimen (range, 0-4; n = 5). Pathogens were not consistently detected across all collection time points; there was no association between postmortem interval and the number of pathogens detected (P = .43) and no change in TAC cycle threshold value over time for pathogens detected in lung tissue. Human ribonucleoprotein values indicated that specimens collected were suitable for testing throughout the study period. CONCLUSIONS: Results suggest that lung, liver, and blood specimens can be collected using MITS procedures up to 4 days after death in adequately preserved bodies. However, inconsistent pathogen detection in samples needs careful consideration before drawing definitive conclusions on the etiologic causes of death.

Characterizing the Countrywide Epidemic Spread of Influenza A(H1N1)pdm09 Virus in Kenya between 2009 and 2018.

The spatiotemporal patterns of spread of influenza A(H1N1)pdm09 viruses on a countrywide scale are unclear in many tropical/subtropical regions mainly because spatiotemporally representative sequence data are lacking. We isolated, sequenced, and analyzed 383 A(H1N1)pdm09 viral genomes from hospitalized patients between 2009 and 2018 from seven locations across Kenya. Using these genomes and contemporaneously sampled global sequences, we characterized the spread of the virus in Kenya over several seasons using phylodynamic methods. The transmission dynamics of A(H1N1)pdm09 virus in Kenya were characterized by (i) multiple virus introductions into Kenya over the study period, although only a few of those introductions instigated local seasonal epidemics that then established local transmission clusters, (ii) persistence of transmission clusters over several epidemic seasons across the country, (iii) seasonal fluctuations in effective reproduction number (Re) associated with lower number of infections and seasonal fluctuations in relative genetic diversity after an initial rapid increase during the early pandemic phase, which broadly corresponded to epidemic peaks in the northern and southern hemispheres, (iv) high virus genetic diversity with greater frequency of seasonal fluctuations in 2009-2011 and 2018 and low virus genetic diversity with relatively weaker seasonal fluctuations in 2012-2017, and (v) virus spread across Kenya. Considerable influenza virus diversity circulated within Kenya, including persistent viral lineages that were unique to the country, which may have been capable of dissemination to other continents through a globally migrating virus population. Further knowledge of the viral lineages that circulate within understudied low-to-middle-income tropical and subtropical regions is required to understand the full diversity and global ecology of influenza viruses in humans and to inform vaccination strategies within these regions.