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 >100 participating clinical sites worldwide based on a core protocol and consistent case definitions. 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 level. RESULTS: The data set included 73 121 patients hospitalized with respiratory illness in 22 countries, including 15 660 with laboratory-confirmed 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 (LMICs), compared with high-income countries (P = .01). The risk of mechanical ventilation and in-hospital death also increased by 4-fold in LMICs, though these differences were not statistically significant. We also find that influenza mortality increased significantly with older age and number of comorbid conditions. 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 underresourced populations, particularly those in LMICs.

The cost of care for children hospitalized with respiratory syncytial virus (RSV) associated lower respiratory infection in Kenya.

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 < 5 years admitted to referral hospitals in Kilifi (coastal Kenya) and Siaya (western Kenya) with symptoms of acute lower respiratory tract infection (LRTI) during the 2019-2021 RSV seasons. These children had been enrolled in ongoing in-patient surveillance for respiratory viruses. Household expenditures on direct and indirect medical costs were collected 10 days prior to, during, and two weeks post hospitalization. Aggregated health system costs were acquired from the hospital administration and were included to calculate the cost per episode of hospitalized RSV illness. RESULTS: We enrolled a total of 241 and 184 participants from Kilifi and Siaya hospitals, respectively. Out of these, 79 (32.9%) in Kilifi and 21(11.4%) in Siaya, tested positive for RSV infection. The total (health system and household) mean costs per episode of severe RSV illness was USD 329 (95% confidence interval (95% CI): 251-408 ) in Kilifi and USD 527 (95% CI: 405- 649) in Siaya. Household costs were USD 67 (95% CI: 54-80) and USD 172 (95% CI: 131- 214) in Kilifi and Siaya, respectively. Mean direct medical costs to the household during hospitalization were USD 11 (95% CI: 10-12) and USD 67 (95% CI: 51-83) among Kilifi and Siaya participants, respectively. Observed costs were lower in Kilifi due to differences in healthcare administration. CONCLUSIONS: RSV-associated disease among young children leads to a substantial economic burden to both families and the health system in Kenya. This burden may differ between Counties in Kenya and similar multi-site studies are advised to support cost-effectiveness analyses.

Association between low maternal serum aflatoxin B1 exposure and adverse pregnancy outcomes in Mombasa, Kenya, 2017-2019: A nested matched case-control study.

We examined the association between serum aflatoxin B1-lysine adduct (AFB1-lys) levels in pregnant women and adverse pregnancy outcomes (low birthweight, miscarriage and stillbirth) through a nested matched case-control study of pregnant women enroled at ≤28 weeks' gestation in Mombasa, Kenya, from 2017 to 2019. Cases comprised women with an adverse birth outcome, defined as either delivery of a singleton infant weighing <2500 g, or a miscarriage, or a stillbirth, while controls were women who delivered a singleton live infant with a birthweight of ≥2500 g. Cases were matched to controls at a ratio of 1:2 based on maternal age at enrolment, gestational age at enrolment and study site. The primary exposure was serum AFB1-lys. The study included 125 cases and 250 controls. The median gestation age when serum samples were collected was 23.0 weeks (interquartile range [IQR]: 18.1-26.0) and 23.5 (IQR: 18.1-26.5) among cases and controls, respectively. Of the 375 tested sera, 145 (38.7%) had detectable serum AFB1-lys: 36.0% in cases and 40.0% in controls. AFB1-lys adduct levels were not associated with adverse birth outcomes on multivariable analysis. Mid-upper arm circumference was associated with a 6% lower odds of adverse birth outcome for every unit increase (p = 0.023). Two-fifths of pregnant women had detectable levels of aflatoxin midway through pregnancy. However, we did not detect an association with adverse pregnancy outcomes, likely because of low serum AFB1-lys levels and low power, restricting meaningful comparison. More research is needed to understand the public health risk of aflatoxin in pregnant women to unborn children.

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.

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.

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.

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.

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.

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.

SARS-CoV-2 Infection among Pregnant and Postpartum Women, Kenya, 2020-2021.

We determined incidence of severe acute respiratory syndrome coronavirus 2 and influenza virus infections among pregnant and postpartum women and their infants in Kenya during 2020-2021. Incidence of severe acute respiratory syndrome coronavirus 2 was highest among pregnant women, followed by postpartum women and infants. No influenza virus infections were identified.

The cost of influenza-associated hospitalizations and outpatient visits in Kenya.

BACKGROUND: We estimated the cost-per-episode and the annual economic burden associated with influenza in Kenya. METHODS: From July 2013-August 2014, we recruited patients with severe acute respiratory illness (SARI) or influenza-like illness (ILI) associated with laboratory-confirmed influenza from 5 health facilities. A structured questionnaire was used to collect direct costs (medications, laboratory investigations, hospital bed fees, hospital management costs, transportation) and indirect costs (productivity losses) associated with an episode of influenza. We used published incidence of laboratory-confirmed influenza associated with SARI and ILI, and the national population census data from 2014, to estimate the annual national number of influenza-associated hospitalizations and outpatient visits and calculated the annual economic burden by multiplying cases by the mean cost. RESULTS: We enrolled 275 patients (105 inpatients and 170 outpatients). The mean cost-per-episode of influenza was US$117.86 (standard deviation [SD], 88.04) among inpatients; US$114.25 (SD, 90.03) for children < 5 years, and US$137.45 (SD, 76.24) for persons aged ≥5 years. Among outpatients, the mean cost-per-episode of influenza was US$19.82 (SD, 27.29); US$21.49 (SD, 31.42) for children < 5 years, and US$16.79 (SD, 17.30) for persons aged ≥5 years. National annual influenza-associated cost estimates ranged from US$2.96-5.37 million for inpatients and US$5.96-26.35 million for outpatients. CONCLUSIONS: Our findings highlight influenza as causing substantial economic burden in Kenya. Further studies may be warranted to assess the potential benefit of targeted influenza vaccination strategies.

Patient and provider perspectives on how trust influences maternal vaccine acceptance among pregnant women in Kenya.

BACKGROUND: Pregnant women and newborns are at high risk for infectious diseases. Altered immunity status during pregnancy and challenges fully vaccinating newborns contribute to this medical reality. Maternal immunization is a strategy to protect pregnant women and their newborns. This study aimed to find out how patient-provider relationships affect maternal vaccine uptake, particularly in the context of a lower middle- income country where limited research in this area exists. METHODS: We conducted semi-structured, in-depth narrative interviews of both providers and pregnant women from four sites in Kenya: Siaya, Nairobi, Mombasa, and Marsabit. Interviews were conducted in either English or one of the local regional languages. RESULTS: We found that patient trust in health care providers (HCPs) is integral to vaccine acceptance among pregnant women in Kenya. The HCP-patient relationship is a fiduciary one, whereby the patients' trusts is primarily rooted in the provider's social position as a person who is highly educated in matters of health. Furthermore, patient health education and provider attitudes are crucial for reinstating and fostering that trust, especially in cases where trust was impeded by rumors, community myths and misperceptions, and religious and cultural factors. CONCLUSION: Patient trust in providers is a strong facilitator contributing to vaccine acceptance among pregnant women in Kenya. To maintain and increase immunization trust, providers have a critical role in cultivating a positive environment that allows for favorable interactions and patient health education. This includes educating providers on maternal immunizations and enhancing knowledge of effective risk communication tactics in clinical encounters.

Evaluation of case definitions to detect respiratory syncytial virus infection in hospitalized children below 5 years in Rural Western Kenya, 2009-2013.

BACKGROUND: In order to better understand respiratory syncytial virus (RSV) epidemiology and burden in tropical Africa, optimal case definitions for detection of RSV cases need to be identified. METHODS: We used data collected between September 2009 - August 2013 from children aged <5 years hospitalized with acute respiratory Illness at Siaya County Referral Hospital. We evaluated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of individual signs, symptoms and standard respiratory disease case definitions (severe acute respiratory illness [SARI]; hospitalized influenza-like illness [hILI]; integrated management of childhood illness [IMCI] pneumonia) to detect laboratory-confirmed RSV infection. We also evaluated an alternative case definition of cough or difficulty breathing plus hypoxia, in-drawing, or wheeze. RESULTS: Among 4714 children hospitalized with ARI, 3810 (81 %) were tested for RSV; and 470 (12 %) were positive. Among individual signs and symptoms, cough alone had the highest sensitivity to detect laboratory-confirmed RSV [96 %, 95 % CI (95-98)]. Hypoxia, wheezing, stridor, nasal flaring and chest wall in-drawing had sensitivities ranging from 8 to 31 %, but had specificities >75 %. Of the standard respiratory case definitions, SARI had the highest sensitivity [83 %, 95 % CI (79-86)] whereas IMCI severe pneumonia had the highest specificity [91 %, 95 % CI (90-92)]. The alternative case definition (cough or difficulty breathing plus hypoxia, in-drawing, or wheeze) had a sensitivity of [55 %, 95 % CI (50-59)] and a specificity of [60 %, 95 % CI (59-62)]. The PPV for all case definitions and individual signs/symptoms ranged from 11 to 20 % while the negative predictive values were >87 %. When we stratified by age <1 year and 1- < 5 years, difficulty breathing, severe pneumonia and the alternative case definition were more sensitive in children aged <1 year [70 % vs. 54 %, p < 0.01], [19 % vs. 11 %, p = 0.01] and [66 % vs. 43 %, p < 0.01] respectively, while non-severe pneumonia was more sensitive [14 % vs. 26 %, p < 0.01] among children aged 1- < 5 years. CONCLUSION: The sensitivity and specificity of different commonly used case definitions for detecting laboratory-confirmed RSV cases varied widely, while the positive predictive value was consistently low. Optimal choice of case definition will depend upon study context and research objectives.

Overview of the Global and US Burden of Preterm Birth.

Preterm birth (PTB) is the leading cause of morbidity and mortality in children globally, yet its prevalence has been difficult to accurately estimate due to unreliable methods of gestational age dating, heterogeneity in counting, and insufficient data. The estimated global PTB rate in 2020 was 9.9% (95% confidence interval: 9.1, 11.2), which reflects no significant change from 2010, and 81% of prematurity-related deaths occurred in Africa and Asia. PTB prevalence in the United States in 2021 was 10.5%, yet with concerning racial disparities. Few effective solutions for prematurity prevention have been identified, highlighting the importance of further research.

The effects of climatic and non-climatic factors on malaria mortality at different spatial scales in western Kenya, 2008-2019.

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.

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.

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.

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.

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.