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For ethical reasons, we cannot publish the data sets online. However, requests for the data underlying the findings presented in our manuscript can be made to the following persons: Dr. Influenza-associated disease burden among children in tropical sub-Saharan Africa is not well established, particularly outside of the pandemic period. We estimated the burden of influenza in children aged 0—4 years through population-based surveillance for influenza-like illness ILI and acute lower respiratory tract illness ALRI. Household members meeting ILI or ALRI case definitions were referred to health facilities for evaluation and collection of nasopharyngeal and oropharyngeal swabs for influenza testing by real-time reverse transcription polymerase chain reaction.

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During —, there were 9, person-years of surveillance among children aged 0—4 years. The average adjusted rate of influenza-associated hospitalization was 4.

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Hospitalization rates were highest in the 0—5 month and 6—23 month age groups, at 7. The average adjusted rate of influenza-associated medically attended inpatient or outpatient ALRI in children aged 0—4 years was Influenza-associated hospitalization rates from — were 5—10 times higher than contemporaneous U. Many children with danger s were not hospitalized; thus, influenza-associated severe disease rates in Kenyan children are likely higher than hospital-based estimates suggest. The burden of influenza in children in the United States and other temperate countries is well-described.

The epidemiology of influenza may be different in sub-Saharan Africa due to less predictable seasonality and the high prevalence of risk factors for severe influenza including HIV. A study of influenza-associated hospitalizations from Bondo District, reported an estimated 1. Other publications from Kenya included annual rates that were heavily influenced by inclusion of the pandemic period.

We also assessed risk factors for influenza infection and the likelihood of providers to clinically diagnose influenza. The study sites and surveillance methods have been described ly.

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Elizabeth Lwak Mission Hospital. Located along Lake Victoria, malaria transmission is endemic. Kibera, the urban site with a surveillance population of approximately 28, in just 0. Malaria is not endemic due to the high altitude.

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A home-based testing and counseling program in found HIV prevalence among adults was In both sites, participants must have resided in the area for at least 4 months prior to enrollment and can access free healthcare at centrally located clinics. There is no hospital-based surveillance in Kibera due to the large of hospitals in Nairobi that may provide care to enrolled participants. Household surveillance was increased to weekly from September to June following the emergence of the influenza A H1N1 pdm09 strain. The first 5 ILI cases presenting to the study clinic each day were sampled to test for influenza infection.

IMCI danger s include inability to drink, vomiting everything, convulsions, lethargy or unconsciousness.

Associated data

Both nasopharyngeal and oropharyngeal specimens, and clinical data were obtained from patients who met the ILI or ALRI case definition and attended the study outpatient clinic both sites or who met the ALRI case definition and were admitted to the study hospital in Lwak. Malaria co-infection was determined by site smear or rapid diagnostic test. Economic quintile was determined for residents of Lwak only based upon multiple correspondence analysis derived from household assets. These data were not available for the Kibera site.

We examined differences between children who tested kenyan for influenza and those who tested negative. Lastly we compared those children who met the ALRI case definition and were hospitalized with those who also met the ALRI case definition gedeon were not hospitalized.

Population-based rates of influenza-associated hospitalization and medically attended ALRI inpatient and outpatient were calculated for children aged 0—5 months, 6—23 months, 24—59 months, and 0—4 years. Crude inpatient and outpatient rates were adjusted for health-seeking outside the study clinics by age group and year as reported in home visits and the proportion influenza-positive among tested children was applied to those meeting the case definition but from whom no specimen was collected Appendix 1. are presented as events per person-years based on the population under surveillance.

Data analysis was performed using Stata version During —, a total person-time of person-years follow-up was recorded among enrolled children aged 0—4 years. During —, among enrolled children aged 0—4 years in the two study sites, 82, episodes of ILI were reported and Of the saints with ILI who sex study clinics, Of these children, Among these hospitalized children there were also 13 children with ILI or respiratory illness who were hospitalized and tested positive for influenza but did not meet the ALRI case definition. Children with ILI at the urban site were more likely to have influenza than those at the rural site These variables were included in multivariable analysis.

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The average rate of influenza-associated hospitalization was 4. Hospitalization rates were highest in the 6—23 month age group at 8.

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During the pandemic year, an exceptionally high hospitalization rate of The average rate of influenza-associated medically attended ALRI in children 0—4 years old was Rates of medically attended influenza-associated ALRI were highest in the 6—23 month age group at Rates of medically attended influenza-associated ALRI remained high among infants aged 0—5 months at There was no difference between influenza-positive inpatients and influenza-positive ALRI outpatients in gender or age distribution Table 5.

Rates of influenza-associated hospitalizations in Kenyan children aged 0—4 years were higher than U. The prolonged circulation of influenza throughout most of the year and higher prevalence of co-morbid conditions e. HIV, TB, malaria, malnutrition may contribute to these rates. Prior studies have documented the association of HIV and increased severity hospitalizations, deaths of influenza virus infections. Influenza was rarely clinically diagnosed among children with severe laboratory-confirmed influenza by inpatient or outpatient care providers, which implies poor recognition of influenza as a respiratory pathogen.

A study of U. Likewise, sex medically attended outpatient ALRI episodes appeared to have similar severity as determined by the presence of hypoxia and danger s to inpatient episodes, few children in the urban setting were hospitalized with influenza-associated ALRI. From —, annual influenza-associated hospitalization gedeon for Kenyan children aged 0—4 years were 5—10 times higher than estimates in U. EIP estimates ranged from 0. EIP estimates for the same age strata. These estimates fall within the confidence limits of our own annual estimates for all but the pandemic year, but the confidence intervals for the pandemic year still overlap.

Children with influenza-associated outpatient ALRI were equally as likely and be hypoxic as inpatients with influenza infection suggesting similar levels of disease severity; therefore, we conducted additional analyses including all sites who met the ALRI case definition and sought medical care to estimate the prevalence of severe influenza-associated kenyan.

Using this method, rates of severe disease influenza-associated hospitalization and non-hospitalized medically attended influenza-associated ALRI were approximately 4 times greater than hospitalization rates alone. An earlier publication estimated the incidence of influenza-associated SARI during — in Lwak in children 0—4 years old to be 58 per person-years of surveillance.

Our estimates of influenza-associated medically attended ALRI in the pandemic were approximately 3 times higher than non-pandemic years for children aged 6—23 months and children aged 24—59 months. Additional years of surveillance outside the pandemic period may provide greater stability to these estimates. There were several limitations to this saint. Influenza was rarely identified in children 0—5 months old with hospitalized ALRI. The lowest rates of medically attended ILI were also among children 0—5 months of age which may reflect a greater tendency to hospitalize in this age group, or atypical presentation of influenza in young infants.

A study of children hospitalized with laboratory-confirmed influenza from — in Finland found that over half of children 0—5 months old were admitted for suspected sepsis, and nearly half of children 6 months-2 years old and over two-thirds of children 3—6 years old were admitted with non-respiratory primary diagnoses.

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To support this, higher rates of influenza-associated hospitalizations were found among infants aged 0—5 months at Siaya District Hospital where presence of fever was not required to meet the SARI case definition. Many parents cannot afford transport to health facilities or to pay for hospitalization charges, parents may be unable to stay in the hospital to care for young children because they need to work or care for other members of the household, and hospitalization and oxygen administration are frequently associated with death in young children making parents reluctant to seek hospital-based care for a severely ill infant.

Some danger s may be misinterpreted by clinicians or caregivers leading to over estimation of severe disease in children. In this study, the increased reporting of chest wall indrawing may reflect differences in clinical practice at the two sites rather than a real difference in the frequency of respiratory distress but this is difficult to determine without a gold standard physical examination. The higher rate of convulsions reported in the rural area may be partially attributable to the co-circulation of malaria but may also reflect differences in clinical practice at the two study sites.

Severely ill children were often excluded from enrolment because of clinical instability, which may bias our estimates if influenza was more or less common among these children than enrolled children. Likewise, influenza-associated illness may have been more or less severe than other causes of ILI leading to differential care-seeking that could bias the proportion positive. The burden of influenza-associated hospitalization in Kenyan children from — was at least 5—10 times higher than contemporaneous U.

Influenza-associated hospitalizations in infants aged 0—5 months were likely underestimated in our surveillance, due to the atypical presentation of influenza in this age group.

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Few clinicians diagnosed children with influenza despite the presence of a global pandemic during the reporting period. Influenza-associated disease remains under-recognized in Kenyan children.

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In research settings for burden of disease estimates, expanding case definitions for children aged 0—5 months to include history of fever or hypothermia without respiratory symptoms may increase sensitivity of influenza detection.

Expanding case definitions in children 6—59 months of age to include fever and cough in children without a primary respiratory diagnosis may also increase sensitivity of influenza detection. Furthermore, clinicians should be sensitized to recognize influenza as an important cause of severe disease in young children.

Influenza vaccination should be strongly considered. The authors would like to acknowledge the communities of Kibera and Lwak who graciously allow us to conduct these research activities. We would also like to acknowledge the team of field workers who conduct home visits in these communities every 2 weeks. National Center for Biotechnology InformationU. PLoS One. Published online Sep Meredith L.