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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.We enrolled women at31 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.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.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.

BACKGROUND Avian influenza (AI) outbreaks occurred frequently in 2022 and continue to pose a health, economic, and food security risk. A comprehensive review of current global AI surveillance information is key to assessing the pandemic risk of AI viruses. OBJECTIVE We provide an analysis of global AI surveillance information from the last decade and identify risk factors of interest and surveillance gaps. METHODS We compared AI reports submitted to animal and public health authorities from January 2013 – June 2022 to January 2005 – December 2012. A multivariable regression analysis was used to evaluate associations between risk factors of interest and reported animal AI outbreaks. RESULTS From 2013–2022, 52% (95/182) of World Organization for Animal Health (WOAH) member-states identified 34 AI virus subtypes during 21,249 outbreaks. The most frequently reported subtypes were high pathogenic AI H5N1 (10,079, 47.4%) and H5N8 (6,722, 31.6%). Ten high pathogenic AI and six low pathogenic AI virus subtypes were reported to WOAH for the first time during 2013–2022. One in four member-states (26/95) did not report an outbreak prior to 2013. AI outbreaks in animals occurred in 26 more countries than reported in the previous eight years. Decreasing World Bank income classification was significantly associated with decreases in reported AI outbreaks. Seventeen (8.8%, 17/194) World Health Organization (WHO) member-states reported 2,000 human AI virus infections of 10 virus subtypes. H7N9 (1,568, 78.4%) and H5N1 (254, 12.7%) viruses accounted for the most human infections. Eight member-states did not report a human case prior to 2013. Of 1,953 human cases with available information, 75% (1,461/1,953) had a known animal exposure. The median time from illness onset to the notification posted on the WHO event information site was 15 days (IQR=21, Average= 23). Seasonality patterns of bird outbreaks and human infections with AI viruses were very similar, occurred year-round, and peaked during November through May. CONCLUSIONS Our analysis suggests that AI outbreaks are more frequent and geographically widespread than in the past. Global surveillance gaps include reporting delays and inconsistent reporting from all regions. Continued monitoring for AI outbreaks in animals and human infections with AI viruses is crucial for pandemic preparedness.

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

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

BackgroundInfluenza viruses undergo rapid evolutionary changes, which requires continuous surveillance to monitor for genetic and potential antigenic changes in circulating viruses that can guide control and prevention decision making.MethodsWe sequenced and phylogenetically analyzed A(H1N1)pdm09 virus genome sequences obtained from specimens collected from hospitalized patients of all ages with or without pneumonia between 2009 and 2018 from seven sentinel surveillance sites across Kenya. We compared these sequences with recommended vaccine strains during the study period to infer genetic and potential antigenic changes in circulating viruses and determinants of clinical outcome.ResultsWe generated and analyzed a total of 383 A(H1N1)pdm09 virus genome sequences. Phylogenetic analyses revealed that multiple genetic groups (clades, subclades, and subgroups) of A(H1N1)pdm09 virus circulated in Kenya over the study period; these evolved away from their vaccine strain, forming clades 7 and 6, subclades 6C, 6B, and 6B.1, and subgroups 6B.1A and 6B.1A1. Several amino acid substitutions among circulating viruses were associated with continued evolution of the viruses, especially in antigenic epitopes and receptor binding sites (RBS) of circulating viruses. Disease severity reduced with increase in age among children aged ConclusionOur study highlights the utility of genomic surveillance to monitor the evolutionary changes of influenza viruses. Routine influenza surveillance with broad geographic representation and whole genome sequencing capacity to inform on the severity of circulating strains could improve selection of influenza strains for inclusion in vaccines.

We describe the epidemiology and clinical features of Kenyan patients hospitalized with laboratory-confirmed influenza compared with those testing negative and discuss the potential contribution of severe acute respiratory illness (SARI) surveillance in monitoring a broader range of respiratory pathogens.We described demographic and clinical characteristics of SARI cases among children (18 years) and adults, separately. We compared disease severity (clinical features and treatment) of hospitalized influenza positive versus negative cases and explored independent predictors of death among SARI cases using a multivariable logistic regression model.From January 2014 to December 2018, 11,166 persons were hospitalized with SARI and overall positivity for influenza was ~10%. There were 10,742 (96%) children (18 years)-median age of 1 year, interquartile range (IQR = 6 months, 2 years). Only 424 (4%) of the SARI cases were adults (≥18 years), with median age of 38 years (IQR 28 years, 52 years). There was no difference in disease severity comparing influenza positive and negative cases among children. Children hospitalized with SARI who had an underlying illness had greater odds of in-hospital death compared with those without (adjusted odds ratio 2.11 95% CI 1.09-4.07). No further analysis was done among adults due to the small sample size.Kenya's sentinel surveillance for SARI mainly captures data on younger children. Hospital-based platforms designed to monitor influenza viruses and associated disease burden may be adapted and expanded to other respiratory viruses to inform public health interventions. Efforts should be made to capture adults as part of routine respiratory surveillance.

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.

BackgroundThe 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 is lacking.MethodsWe isolated, sequenced, and analyzed 383 influenza A(H1N1)pdm09 viral genomes isolated 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.ResultsThe transmission dynamics of influenza A(H1N1)pdm09 virus in Kenya was characterized by: (i) multiple virus introductions into Kenya over the study period, although these were remarkably few, with only a few of those introductions instigating 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 2009-11 and 2018 and low virus genetic diversity with relatively weaker seasonal fluctuations in 2012-17; and (v) virus migration from multiple geographical regions to multiple geographical destinations in Kenya.ConclusionConsiderable influenza virus diversity circulates within Africa, as demonstrated in this report, including virus lineages that are unique to the region, which may be 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.

International audience; BackgroundInfluenza surveillance helps time prevention and control interventions especially where complex seasonal patterns exist. We assessed influenza surveillance sustainability in Africa where influenza activity varies and external funds for surveillance have decreased.MethodsWe surveyed African Network for Influenza Surveillance and Epidemiology (ANISE) countries about 2011-2017 surveillance system characteristics. Data were summarized with descriptive statistics and analyzed with univariate and multivariable analyses to quantify sustained or expanded influenza surveillance capacity in Africa.ResultsEighteen (75%) of 24 ANISE members participated in the survey; their cumulative population of 710 751 471 represent 56% of Africa's total population. All 18 countries scored a mean 95% on WHO laboratory quality assurance panels. The number of samples collected from severe acute respiratory infection case-patients remained consistent between 2011 and 2017 (13 823 vs 13 674 respectively) but decreased by 12% for influenza-like illness case-patients (16 210 vs 14 477). Nine (50%) gained capacity to lineage-type influenza B. The number of countries reporting each week to WHO FluNet increased from 15 (83%) in 2011 to 17 (94%) in 2017.ConclusionsDespite declines in external surveillance funding, ANISE countries gained additional laboratory testing capacity and continued influenza testing and reporting to WHO. These gains represent important achievements toward sustainable surveillance and epidemic/pandemic preparedness.

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.

Influenza vaccination remains the most effective tool for reducing seasonal influenza disease burden. Few Low and Middle-Income Countries (LMICs) have robust, sustainable annual influenza national vaccination programs. The Partnership for Influenza Vaccine Introduction (PIVI) was developed as a public-private partnership to support LMICs to develop and sustain national vaccination programs through time-limited vaccine donations and technical support. We review the first 5 years of experience with PIVI, including the concept, country progress toward sustainability, and lesson learned. Between 2013 and 2018, PIVI worked with Ministries of Health in 17 countries. Eight countries have received donated vaccines and technical support; of these, two have transitioned to sustained national support of influenza vaccination and six are increasing national support of the vaccine programs towards full transition to local vaccine program support by 2023. Nine additional countries have received technical support for building the evidence base for national policy development and/or program evaluation. PIVI has resulted in increased use of vaccines in partner countries, and early countries have demonstrated progress towards sustainability, suggesting that a model of vaccine and technical support can work in LMICs. PIVI expects to add new country partners as current countries transition to self-reliance.

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.

Background Healthcare workers (HCWs) are at high risk of exposure and transmission of infectious respiratory pathogens like influenza. Despite the potential benefits, safety and efficacy of influenza vaccination, vaccines are still underutilized in Africa, including among HCWs. Method From May-June 2018, we conducted a cross-sectional, self-administered, written survey among HCWs from seven counties in Kenya and assessed their knowledge attitudes and perceptions towards pandemic influenza disease and vaccination. Using regression models, we assessed factors that were associated with the HCW’s knowledge of pandemic influenza and vaccination. Results A total of 2,035 HCWs, representing 49% of the targeted respondents from 35 health facilities, completed the question. Sixty eight percent of the HCWs had ever heard of pandemic influenza, and 80.0% of these were willing to receive pandemic influenza vaccine if it was available. On average, Kenyan HCWs correctly answered 55.0% (95% CI 54.0–55.9) of the questions about pandemic influenza and vaccination. Physicians (65.6%, 95% CI 62.5–68.7) and pharmacists (61.7%, 95% CI 57.9–65.5) scored higher compared to nurses (53.1%, 95% CI 51.7–54.5). HCWs with 5 or more years of work experience (55.8, 95% CI 54.5–57.0) had marginally higher knowledge scores compared to those with less experience (53.9%, 95% CI 52.5–55.3). Most participants who were willing to receive pandemic influenza vaccine did so to protect their relatives (88.7%) or patients (85.9%). Conclusion Our findings suggest moderate knowledge of pandemic influenza and vaccination by HCWs in Kenya, which varied by cadre and years of work experience. These findings highlight the need for continued in-service health education to increase the HCW’s awareness and knowledge of pandemic influenza to increase acceptance of influenza vaccination in the case of a pandemic.

Background The impact of influenza B virus circulation in Sub-Saharan Africa is not well described. Methods We analyzed data from acute respiratory illness (ARI) in Kenya. We assessed clinical features and age-specific hospitalization and outpatient visit rates by person-years for influenza B/Victoria and B/Yamagata and the extent to which circulating influenza B lineages in Kenya matched the vaccine strain component of the corresponding season (based on Northern Hemisphere [October–March] and Southern Hemisphere [April–September] vaccine availability). Results From 2012 to 2016, influenza B represented 31% of all influenza-associated ARIs detected (annual range, 13–61%). Rates of influenza B hospitalization and outpatient visits were higher for Conclusions Influenza B causes substantial burden in Kenya, particularly among children aged

Molecular diagnostic methods are becoming increasingly available for assessment of acute lower respiratory illnesses (ALRI). However, nasopharyngeal/oropharyngeal (NP/OP) swabs may not accurately reflect etiologic agents from the lower respiratory tract where sputum specimens are considered as a more representative sample. The pathogen yields from NP/OP against sputum specimens have not been extensively explored, especially in tropical countries. We compared pathogen yields from NP/OP swabs and sputum specimens from patients ≥18 years hospitalized with ALRI in rural Western Kenya. Specimens were tested for 30 pathogens using TaqMan Array Cards (TAC) and results compared using McNemar’s test. The agreement for pathogen detection between NP/OP and sputum specimens ranged between 85–100%. More viruses were detected from NP/OP specimens whereas Klebsiella pneumoniae and Mycobacterium tuberculosis were more common in sputum specimens. There was no clear advantage in using sputum over NP/OP specimens to detect pathogens of ALRI in adults using TAC in the context of this tropical setting.

BackgroundInfluenza is an important contributor to acute respiratory illness, including pneumonia, and results in substantial morbidity and mortality globally. Understanding the local burden of influenza-associated severe disease can inform decisions on allocation of resources toward influenza control programs. Currently, there is no national influenza vaccination program in Uganda.MethodsIn this study, we used data on pneumonia hospitalizations that were collected and reported through the Health Management Information System (HMIS) of the Ministry of Health, Uganda, and the laboratory-confirmed influenza positivity data from severe acute respiratory illness (SARI) surveillance in three districts (Wakiso, Mbarara, and Tororo) to estimate the age-specific incidence of influenza-associated pneumonia hospitalizations from January 2013 through December 2016.ResultsThe overall estimated mean annual rate of pneumonia hospitalizations in the three districts was 371 (95% confidence interval [CI] 323-434) per 100,000 persons, and was highest among children aged ConclusionsThe burden of influenza-associated pneumonia hospitalizations was substantial in Uganda, and was highest among young children aged

OBJECTIVES We compared minimally invasive tissue sampling (MITS) with conventional autopsy (CA) in detection of respiratory pathology/pathogens among Kenyan children younger than 5 years who were hospitalized with respiratory disease and died during hospitalization. METHODS Pulmonary MITS guided by anatomic landmarks was followed by CA. Lung tissues were triaged for histology and molecular testing using TaqMan Array Cards (TACs). MITS and CA results were compared for adequacy and concordance. RESULTS Adequate pulmonary tissue was obtained by MITS from 54 (84%) of 64 respiratory deaths. Comparing MITS to CA, full histologic diagnostic concordance was present in 23 (36%) cases and partial concordance in 19 (30%), an overall 66% concordance rate. Pathogen detection using TACs had full concordance in 27 (42%) and partial concordance in 24 (38%) cases investigated, an overall 80% concordance rate. CONCLUSIONS MITS is a viable alternative to CA in respiratory deaths in resource-limited settings, especially if combined with ancillary tests to optimize diagnostic accuracy.

BACKGROUND In sub-Saharan Africa, where the burden of respiratory disease–related deaths is the highest, information on the cause of death remains inadequate because of poor access to health care and limited availability of diagnostic tools. Postmortem examination can aid in the ascertainment of causes of death. This manuscript describes the study protocol for the Pediatric Respiratory Etiology Surveillance Study (PRESS). OBJECTIVE This study protocol aims to identify causes and etiologies associated with respiratory disease–related deaths among children (age 1-59 months) with respiratory illness admitted to the Kenyatta National Hospital (KNH), the largest public hospital in Kenya, through postmortem examination coupled with innovative approaches to laboratory investigation. METHODS We prospectively followed children hospitalized with respiratory illness until the end of clinical care or death. In case of death, parents or guardians were offered grief counseling, and postmortem examination was offered. Lung tissue specimens were collected using minimally invasive tissue sampling and conventional autopsy where other tissues were collected. Tissues were tested using histopathology, immunohistochemistry, and multipathogen molecular-based assays to identify pathogens. For each case, clinical and laboratory data were reviewed by a team of pathologists, clinicians, laboratorians, and epidemiologists to assign a cause of and etiology associated with death. RESULTS We have enrolled pediatric cases of respiratory illness hospitalized at the KNH at the time of this submission; of those, 14.8% (140/945) died while in the hospital. Both analysis and interpretation of laboratory results and writing up of findings are expected in 2019-2020. CONCLUSIONS Postmortem studies can help identify major pathogens contributing to respiratory-associated deaths in children. This information is needed to develop evidence-based prevention and treatment policies that target important causes of pediatric respiratory mortality and assist with the prioritization of local resources. Furthermore, PRESS can provide insights into the interpretation of results using multipathogen testing platforms in resource-limited settings. INTERNATIONAL REGISTERED REPOR DERR1-10.2196/10854

Item does not contain fulltext BACKGROUND: Little is known about how human immunodeficiency virus (HIV) infection affects influenza transmission within homes in sub-Saharan Africa. METHODS: We used respiratory illness surveillance and HIV testing data gathered in Kibera, an urban slum in Nairobi, Kenya, to examine the impact of HIV status on (1) introducing influenza to the home and (2) transmitting influenza to household contacts. RESULTS: While HIV status did not affect the likelihood of being an influenza index case, household contacts of HIV-infected influenza index cases had twice the risk of developing secondary influenza-like illness than contacts of HIV-negative index cases. CONCLUSIONS: HIV-infected influenza index cases may facilitate transmission of influenza within the home.

BACKGROUND Influenza-associated respiratory illness was substantial during the emergence of the 2009 influenza pandemic. Estimates of influenza burden in the post-pandemic period are unavailable to guide Kenyan vaccine policy. OBJECTIVES To update estimates of hospitalized and non-hospitalized influenza-associated severe acute respiratory illness (SARI) during a post-pandemic period (2012-2014) and describe the incidence of disease by narrow age categories. METHODS We used data from Siaya County Referral Hospital to estimate age-specific base rates of SARI. We extrapolated these base rates to other regions within the country by adjusting for regional risk factors for acute respiratory illness (ARI), regional healthcare utilization for acute respiratory illness, and the proportion of influenza-positive SARI cases in each region, so as to obtain region-specific rates. RESULTS The mean annual rate of hospitalized influenza-associated SARI among all ages was 21 (95% CI 19-23) per 100 000 persons. Rates of non-hospitalized influenza-associated SARI were approximately 4 times higher at 82 (95% CI 74-90) per 100 000 persons. Mean annual rates of influenza-associated SARI were highest in children

Background Respiratory diseases cause substantial morbidity and mortality worldwide, with sub-Saharan Africa bearing the greatest burden. Identifying etiologies of respiratory disease is important to inform cost effective treatment, prevention and control strategies. Testing for all of the different pathogens that are potentially associated with respiratory illnesses is challenging. We piloted the use of a multi-pathogen respiratory Taqman Array Cards (TAC) to identify pathogens in respiratory samples collected from non-fatal and fatal cases and their matched asymptomatic controls. Methods This is a case control study comparing viral and bacterial pathogens detected among non-fatal and fatal cases to those detected among age and time matched asymptomatic controls. We used McNemar’s test to compare proportions of pathogens detected among cases (non-fatal and fatal) to their matched asymptomatic controls. We used Mann-Whitney test to compare the distribution of median Cycle threshold (Ct) values among non-fatal and fatal cases to their corresponding asymptomatic controls. Results There were 72 fatal and 72 non-fatal cases matched to 72 controls. We identified at least one pathogen in 109/144 (76%) cases and 59/72 (82%) controls. For most pathogens, the median Ct values were lower among cases (fatal and non-fatal) compared to asymptomatic controls. Conclusions Similar rates of pathogen detection among cases and controls make interpretation of results challenging. Ct-values might be helpful in interpreting clinical relevance of detected pathogens using multi-pathogen diagnostic tools. Electronic supplementary material The online version of this article (10.1186/s12879-017-2694-0) contains supplementary material, which is available to authorized users.

Background Recent influenza surveillance data from Africa suggest an important burden of influenza-associated morbidity and mortality. In tropical countries where influenza virus transmission may not be confined to a single season alternative strategies for vaccine distribution via antenatal care (ANC) or semiannual campaigns should be considered. Methods Using data on monthly influenza disease burden in women of child-bearing age and infants aged 0–5 months in Kenya from 2010–2014, we estimated the number of outcomes (illnesses, medical visits, hospitalizations, and deaths) that occurred and that may have been averted through influenza vaccination of pregnant women using: 1) a year-round immunization strategy through ANC, 2) annual vaccination campaigns, and 3) semiannual vaccination campaigns. Results During 2010–2014, influenza resulted in an estimated 279,047 illnesses, 36,276 medical visits, 1612 hospitalizations and 243 deaths in pregnant women and 157,053 illnesses, 65,177 medical visits, 4197 hospitalizations, and 755 deaths in infants aged 0–5 months in Kenya. Depending on the mode of distribution and the vaccine coverage achieved, 12.8–31.4% of influenza-associated disease in pregnant women and 11.6–22.1% in infants aged 0–5 months might have been prevented through maternal influenza immunization. In this model, point estimates for influenza-associated disease averted through maternal vaccination delivered year-round in ANC or semiannually in campaigns were higher than vaccination delivered in a single annual campaign, but confidence intervals overlapped. Conclusions Vaccinating pregnant women against influenza can reduce the burden of influenza-associated illness, hospitalization and death in both pregnant women and their young infants. Alternative immunization strategies may avert more influenza-associated disease in countries where influenza virus transmission occurs throughout the year.

BackgroundAlthough health care–associated infections are an important cause of morbidity and mortality worldwide, the epidemiology and etiology of respiratory health care–associated infections (rHAIs) have not been documented in Kenya. In 2010, the Ministry of Health, Kenya Medical Research Institute, and Centers for Disease Control and Prevention initiated surveillance for rHAIs at 3 hospitals.MethodsAt each hospital, we surveyed intensive care units (ICUs), pediatric wards, and medical wards to identify patients with rHAIs, defined as any hospital-onset (≥3 days after admission) fever (≥38°C) or hypothermia (

Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/31513690/ We describe the epidemiological characteristics, pattern of circulation, and geographical distribution of influenza B viruses and its lineages using data from the Global Influenza B Study. We included over 1.8 million influenza cases occurred in thirty-one countries during 2000-2018. We calculated the proportion of cases caused by influenza B and its lineages; determined the timing of influenza A and B epidemics; compared the age distribution of B/Victoria and B/Yamagata cases; and evaluated the frequency of lineage-level mismatch for the trivalent vaccine. The median proportion of influenza cases caused by influenza B virus was 23.4%, with a tendency (borderline statistical significance, p = 0.060) to be higher in tropical vs. temperate countries. Influenza B was the dominant virus type in about one every seven seasons. In temperate countries, influenza B epidemics occurred on average three weeks later than influenza A epidemics; no consistent pattern emerged in the tropics. The two B lineages caused a comparable proportion of influenza B cases globally, however the B/Yamagata was more frequent in temperate countries, and the B/Victoria in the tropics (p = 0.048). B/Yamagata patients were significantly older than B/Victoria patients in almost all countries. A lineage-level vaccine mismatch was observed in over 40% of seasons in temperate countries and in 30% of seasons in the tropics. The type B virus caused a substantial proportion of influenza infections globally in the 21st century, and its two virus lineages differed in terms of age and geographical distribution of patients. These findings will help inform health policy decisions aiming to reduce disease burden associated with seasonal influenza. info:eu-repo/semantics/publishedVersion

Contains fulltext : 175739.pdf (Publisher’s version ) (Open Access) BACKGROUND: Influenza and respiratory syncytial virus (RSV) associated mortality has not been well-established in tropical Africa. METHODS: We used the negative binomial regression method and the rate-difference method (i.e. deaths during low and high influenza/RSV activity months), to estimate excess mortality attributable to influenza and RSV using verbal autopsy data collected through a health and demographic surveillance system in Western Kenya, 2007-2013. Excess mortality rates were calculated for a) all-cause mortality, b) respiratory deaths (including pneumonia), c) HIV-related deaths, and d) pulmonary tuberculosis (TB) related deaths. RESULTS: Using the negative binomial regression method, the mean annual all-cause excess mortality rate associated with influenza and RSV was 14.1 (95% confidence interval [CI] 0.0-93.3) and 17.1 (95% CI 0.0-111.5) per 100,000 person-years (PY) respectively; and 10.5 (95% CI 0.0-28.5) and 7.3 (95% CI 0.0-27.3) per 100,000 PY for respiratory deaths, respectively. Highest mortality rates associated with influenza were among >/=50 years, particularly among persons with TB (41.6[95% CI 0.0-122.7]); and with RSV were among

Contains fulltext : 172815.pdf (Publisher’s version ) (Open Access) BACKGROUND: Information on the timing of influenza circulation remains scarce in Tropical regions of Africa. OBJECTIVES: We assessed the relationship between influenza activity and several meteorological factors (temperature, specific humidity, precipitation) and characterized the timing of influenza circulation and its implications to vaccination strategies in Kenya. METHODS: We analyzed virologically confirmed influenza data for outpatient influenza-like illness (ILI), hospitalized for severe acute respiratory infections (SARI), and cases of severe pneumonia over the period 2007-2013. Using logistic and negative binomial regression methods, we assessed the independent association between climatic variables (lagged up to 4 weeks) and influenza activity. RESULTS: There were multiple influenza epidemics occurring each year and lasting a median duration of 2-4 months. On average, there were two epidemics occurring each year in most of the regions in Kenya, with the first epidemic occurring between the months of February and March and the second one between July and November. Specific humidity was independently and negatively associated with influenza activity. Combinations of low temperature (

BACKGROUND Although children

Background: In sub-Saharan Africa, where the burden of respiratory disease–related deaths is the highest, information on the cause of death remains inadequate because of poor access to health care and limited availability of diagnostic tools. Postmortem examination can aid in the ascertainment of causes of death. This manuscript describes the study protocol for the Pediatric Respiratory Etiology Surveillance Study (PRESS). Objective: This study protocol aims to identify causes and etiologies associated with respiratory disease–related deaths among children (age 1-59 months) with respiratory illness admitted to the Kenyatta National Hospital (KNH), the largest public hospital in Kenya, through postmortem examination coupled with innovative approaches to laboratory investigation. Methods: We prospectively followed children hospitalized with respiratory illness until the end of clinical care or death. In case of death, parents or guardians were offered grief counseling, and postmortem examination was offered. Lung tissue specimens were collected using minimally invasive tissue sampling and conventional autopsy where other tissues were collected. Tissues were tested using histopathology, immunohistochemistry, and multipathogen molecular-based assays to identify pathogens. For each case, clinical and laboratory data were reviewed by a team of pathologists, clinicians, laboratorians, and epidemiologists to assign a cause of and etiology associated with death. Results: We have enrolled pediatric cases of respiratory illness hospitalized at the KNH at the time of this submission; of those, 14.8% (140/945) died while in the hospital. Both analysis and interpretation of laboratory results and writing up of findings are expected in 2019-2020. Conclusions: Postmortem studies can help identify major pathogens contributing to respiratory-associated deaths in children. This information is needed to develop evidence-based prevention and treatment policies that target important causes of pediatric respiratory mortality and assist with the prioritization of local resources. Furthermore, PRESS can provide insights into the interpretation of results using multipathogen testing platforms in resource-limited settings. International Registered Report Identifier (IRRID): DERR1-10.2196/10854

Background The global burden of pediatric severe respiratory illness is substantial, and influenza viruses contribute to this burden. Systematic surveillance and testing for influenza among hospitalized children has expanded globally over the past decade. However, only a fraction of the data has been used to estimate influenza burden. In this analysis, we use surveillance data to provide an estimate of influenza-associated hospitalizations among children worldwide. Methods and Findings We aggregated data from a systematic review (n = 108) and surveillance platforms (n = 37) to calculate a pooled estimate of the proportion of samples collected from children hospitalized with respiratory illnesses and positive for influenza by age group (, The substantial global burden of influenza infections in children is revealed by Lafond and colleagues. Children in developing countries are 3 times more likely to be hospitalised and treatments vary. This study highlights the need for vaccination programs in the young., Editors' Summary Background Acute lower respiratory infections—bacterial and viral infections of the lungs and airways (the tubes that take oxygen-rich air to the lungs)—are major causes of illness and death in children worldwide. Pneumonia (infection of the lungs) alone is responsible for 15% of deaths among children under five years old and kills nearly one million young children every year. Globally, infections with respiratory syncytial virus and with Streptococcus pneumoniae are associated with about 25% and 18.3%, respectively, of all episodes of severe respiratory infection in young children. Another infectious organism that contributes to the global burden of respiratory disease among children is the influenza virus. Every year, millions of people become infected with this virus, which infects the airways and causes symptoms that include a high temperature, tiredness and weakness, general aches and pains, and a dry chesty cough. Most infected individuals recover quickly, but seasonal influenza outbreaks (epidemics) nevertheless kill about half a million people annually, with the highest burden of severe disease being experienced by elderly people and by children under five years old. Why Was This Study Done? Annual immunization (vaccination) can reduce an individual’s risk of catching influenza, but before a country implements this preventative measure, policymakers need reliable estimates of the burden of influenza in their country. Although such estimates have been calculated for resource-rich countries with temperate climates, where influenza largely occurs in the winter, few estimates of influenza burden are available for resource-limited countries, which has hampered informed consideration of vaccination for influenza prevention in many settings. Recently, however, there has been a global expansion of systematic surveillance and testing for influenza virus among patients admitted to hospital for severe respiratory infection. Here, the researchers use this expanded surveillance data to provide an estimate of influenza-associated hospitalizations among children worldwide between 1982 and 2012. Specifically, they undertake a systematic review to identify published research articles on influenza-associated respiratory disease in hospitalized children, and, by aggregating the data from these articles with data collected by hospital-based influenza surveillance, they calculate a pooled estimate of the proportion of children hospitalized with respiratory disease who are positive for influenza. What Did the Researchers Do and Find? Using predefined search criteria, the researchers identified 108 published research articles that provided information on influenza-associated respiratory illness among hospitalized children. In addition, the Global Respiratory Hospitalizations–Influenza Proportion Positive (GRIPP) working group provided 37 hospital-based influenza surveillance datasets. By aggregating the data from these sources using a statistical approach called meta-analysis, the researchers calculated that, overall, influenza was associated with 9.5% of hospitalizations for severe respiratory infection among children under 18 years old worldwide, ranging from 4.8% among children under six months old to 16.4% among children aged 5–17 years. The researchers also calculated that, on average over the study period, influenza resulted in about 374,000 hospitalizations annually among children under one year old (including 228,000 hospitalizations among children less than six months old) and nearly one million hospitalizations annually among children under five years old. Finally, the researchers calculated that influenza-associated hospitalization rates among children under five years old over the study period were more than three times higher in resource-limited countries than in industrialized countries (150 and 48 hospitalizations, respectively, per 100,000 children per year). What Do These Findings Mean? Differences in hospitalization practices, in applications of case definitions, and in influenza testing protocols between settings may affect the accuracy of these findings. Specifically, the approach taken by the researchers may mean that their estimate of the total burden of severe respiratory disease due to influenza is an underestimate of the true situation. Even so, these findings suggest that influenza is an important contributor to hospitalizations for severe respiratory illness among children worldwide. Increasing influenza vaccination coverage among young children and pregnant women could, therefore, reduce the contribution that influenza makes to hospitalizations for respiratory infections among children. Importantly, the estimates of the burden of influenza provided by these findings can now be used by countries considering influenza vaccination programs for children and/or pregnant women to help them investigate the possible health and cost implications of such programs and should also stimulate further research into the development of effective influenza vaccines for young children. Additional Information This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001977. The UK National Health Service Choices website provides information about respiratory infections, seasonal influenza, influenza vaccination, and influenza vaccination in children The World Health Organization provides information on seasonal influenza (in several languages) and on influenza vaccines The US Centers for Disease Control and Prevention also provides information for patients and health professionals on all aspects seasonal influenza, including information about vaccination, and about children, influenza, and vaccination; its website contains a short video about personal experiences of influenza Flu.gov, a US government website, provides access to information on seasonal influenza and vaccination MedlinePlus has links to further information about influenza and about vaccination (in English and Spanish)

Erratum in - Correction: Temporal Patterns of Influenza A and B in Tropical and Temperate Countries: What Are the Lessons for Influenza Vaccination? PLoS One. 2016 May 2;11(5):e0155089. doi: 10.1371/journal.pone.0155089. Introduction: Determining the optimal time to vaccinate is important for influenza vaccination programmes. Here, we assessed the temporal characteristics of influenza epidemics in the Northern and Southern hemispheres and in the tropics, and discuss their implications for vaccination programmes. Methods: This was a retrospective analysis of surveillance data between 2000 and 2014 from the Global Influenza B Study database. The seasonal peak of influenza was defined as the week with the most reported cases (overall, A, and B) in the season. The duration of seasonal activity was assessed using the maximum proportion of influenza cases during three consecutive months and the minimum number of months with 80% of cases in the season. We also assessed whether co-circulation of A and B virus types affected the duration of influenza epidemics. Results: 212 influenza seasons and 571,907 cases were included from 30 countries. In tropical countries, the seasonal influenza activity lasted longer and the peaks of influenza A and B coincided less frequently than in temperate countries. Temporal characteristics of influenza epidemics were heterogeneous in the tropics, with distinct seasonal epidemics observed only in some countries. Seasons with co-circulation of influenza A and B were longer than influenza A seasons, especially in the tropics. Discussion: Our findings show that influenza seasonality is less well defined in the tropics than in temperate regions. This has important implications for vaccination programmes in these countries. High-quality influenza surveillance systems are needed in the tropics to enable decisions about when to vaccinate. The Global Influenza B Study is supported by an unrestricted research grant from Sanofi Pasteur. info:eu-repo/semantics/publishedVersion