Global burden of influenza-associated lower respiratory tract infections and hospitalizations among adults: A systematic review and meta-analysis.

BACKGROUND: Influenza illness burden is substantial, particularly among young children, older adults, and those with underlying conditions. Initiatives are underway to develop better global estimates for influenza-associated hospitalizations and deaths. Knowledge gaps remain regarding the role of influenza viruses in severe respiratory disease and hospitalizations among adults, particularly in lower-income settings. METHODS AND FINDINGS: We aggregated published data from a systematic review and unpublished data from surveillance platforms to generate global meta-analytic estimates for the proportion of acute respiratory hospitalizations associated with influenza viruses among adults. We searched 9 online databases (Medline, Embase, CINAHL, Cochrane Library, Scopus, Global Health, LILACS, WHOLIS, and CNKI; 1 January 1996-31 December 2016) to identify observational studies of influenza-associated hospitalizations in adults, and assessed eligible papers for bias using a simplified Newcastle-Ottawa scale for observational data. We applied meta-analytic proportions to global estimates of lower respiratory infections (LRIs) and hospitalizations from the Global Burden of Disease study in adults ≥20 years and by age groups (20-64 years and ≥65 years) to obtain the number of influenza-associated LRI episodes and hospitalizations for 2016. Data from 63 sources showed that influenza was associated with 14.1% (95% CI 12.1%-16.5%) of acute respiratory hospitalizations among all adults, with no significant differences by age group. The 63 data sources represent published observational studies (n = 28) and unpublished surveillance data (n = 35), from all World Health Organization regions (Africa, n = 8; Americas, n = 11; Eastern Mediterranean, n = 7; Europe, n = 8; Southeast Asia, n = 11; Western Pacific, n = 18). Data quality for published data sources was predominantly moderate or high (75%, n = 56/75). We estimate 32,126,000 (95% CI 20,484,000-46,129,000) influenza-associated LRI episodes and 5,678,000 (95% CI 3,205,000-9,432,000) LRI hospitalizations occur each year among adults. While adults <65 years contribute most influenza-associated LRI hospitalizations and episodes (3,464,000 [95% CI 1,885,000-5,978,000] LRI hospitalizations and 31,087,000 [95% CI 19,987,000-44,444,000] LRI episodes), hospitalization rates were highest in those ≥65 years (437/100,000 person-years [95% CI 265-612/100,000 person-years]). For this analysis, published articles were limited in their inclusion of stratified testing data by year and age group. Lack of information regarding influenza vaccination of the study population was also a limitation across both types of data sources. CONCLUSIONS: In this meta-analysis, we estimated that influenza viruses are associated with over 5 million hospitalizations worldwide per year. Inclusion of both published and unpublished findings allowed for increased power to generate stratified estimates, and improved representation from lower-income countries. Together, the available data demonstrate the importance of influenza viruses as a cause of severe disease and hospitalizations in younger and older adults worldwide.

Seasonal Influenza and Avian Influenza A(H5N1) Virus Surveillance among Inpatients and Outpatients, East Jakarta, Indonesia, 2011-2014.

During October 2011-September 2014, we screened respiratory specimens for seasonal and avian influenza A(H5N1) virus infections among outpatients with influenza-like illness and inpatients with severe acute respiratory infection (SARI) in East Jakarta, an Indonesia district with high incidence of H5N1 virus infection among poultry. In total, 31% (1,875/6,008) of influenza-like illness case-patients and 15% (571/3,811) of SARI case-patients tested positive for influenza virus. Influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B virus infections were detected in all 3 years, and the epidemic season extended from November through May. Although 28% (2,810/10,135) of case-patients reported exposure to poultry, only 1 SARI case-patient with an H5N1 virus infection was detected. Therefore, targeted screening among case-patients with high-risk poultry exposures (e.g., a recent visit to a live bird market or close proximity to sick or dead poultry) may be a more efficient routine surveillance strategy for H5N1 virus in these types of settings.

Application of WHO's guideline for the selection of sentinel sites for hospital-based influenza surveillance in Indonesia.

BACKGROUND: A sentinel hospital-based severe acute respiratory infection (SARI) surveillance system was established in Indonesia in 2013. Deciding on the number, geographic location and hospitals to be selected as sentinel sites was a challenge. Based on the recently published WHO guideline for influenza surveillance (2012), this study presents the process for hospital sentinel site selection. METHODS: From the 2,165 hospitals in Indonesia, the first step was to shortlist to hospitals that had previously participated in respiratory disease surveillance systems and had acceptable surveillance performance history. The second step involved categorizing the shortlist according to five regions in Indonesia to maximize geographic representativeness. A checklist was developed based on the WHO recommended attributes for sentinel site selection including stability, feasibility, representativeness and the availability of data to enable disease burden estimation. Eight hospitals, a maximum of two per geographic region, were visited for checklist administration. Checklist findings from the eight hospitals were analyzed and sentinel sites selected in the third step. RESULTS: Six hospitals could be selected based on resources available to ensure system stability over a three-year period. For feasibility, all eight hospitals visited had mechanisms for specimen shipment and the capacity to report surveillance data, but two had limited motivation for system participation. For representativeness, the eight hospitals were geographically dispersed around Indonesia, and all could capture cases in all age and socio-economic groups. All eight hospitals had prerequisite population data to enable disease burden estimation. The two hospitals with low motivation were excluded and the remaining six were selected as sentinel sites. CONCLUSIONS: The multi-step process enabled sentinel site selection based on the WHO recommended attributes that emphasize right-sizing the surveillance system to ensure its stability and maximizing its geographic representativeness. This experience may guide other countries interested in adopting WHO's influenza surveillance standards for sentinel site selection.

Seroprevalence of SARS-CoV-2 antibodies in Bali Province: Indonesia shows underdetection of COVID-19 cases by routine surveillance.

The international tourist destination of Bali reported its first case of Coronavirus Disease 2019 or COVID-19 in March 2020. To better understand the extent of exposure of Bali's 4.3 million inhabitants to the COVID-19 virus, we performed two repeated cross-sectional serosurveys stratified by urban and rural areas. We used a highly specific multiplex assay that detects antibodies to three different viral antigens. We also assessed demographic and social risk factors and history of symptoms. Our results show that the virus was widespread in Bali by late 2020, with 16.73% (95% CI 12.22-21.12) of the population having been infected by that time. We saw no differences in seroprevalence between urban and rural areas, possibly due to extensive population mixing, and similar levels of seroprevalence by gender and among age groups, except for lower seroprevalence in the very young. We observed no difference in seroprevalence between our two closely spaced surveys. Individuals reporting symptoms in the past six months were about twice as likely to be seropositive as those not reporting symptoms. Based upon official statistics for laboratory diagnosed cases for the six months prior to the survey, we estimate that for every reported case an additional 52 cases, at least, were undetected. Our results support the hypothesis that by late 2020 the virus was widespread in Bali, but largely undetected by surveillance.

Quality of National Disease Surveillance Reporting before and during COVID-19: A Mixed-Method Study in Indonesia.

BACKGROUND: Global COVID-19 outbreaks in early 2020 have burdened health workers, among them surveillance workers who have the responsibility to undertake routine disease surveillance activities. The aim of this study was to describe the quality of the implementation of Indonesia's Early Warning and Response Alert System (EWARS) for disease surveillance and to measure the burden of disease surveillance reporting quality before and during the COVID-19 epidemic in Indonesia. METHODS: A mixed-method approach was used. A total of 38 informants from regional health offices participated in Focus Group Discussion (FGD) and In-Depth Interview (IDI) for informants from Ministry of Health. The FGD and IDI were conducted using online video communication. Yearly completeness and timeliness of reporting of 34 provinces were collected from the application. Qualitative data were analyzed thematically, and quantitative data were analyzed descriptively. RESULTS: Major implementation gaps were found in poorly distributed human resources and regional infrastructure inequity. National reporting from 2017-2019 showed an increasing trend of completeness (55%, 64%, and 75%, respectively) and timeliness (55%, 64%, and 75%, respectively). However, the quality of the reporting dropped to 53% and 34% in 2020 concomitant with the SARS-CoV2 epidemic. CONCLUSIONS: Report completeness and timeliness are likely related to regional infrastructure inequity and the COVID-19 epidemic. It is recommended to increase report capacities with an automatic EWARS application linked systems in hospitals and laboratories.

Estimated incidence of influenza-associated severe acute respiratory infections in Indonesia, 2013-2016.

BACKGROUND: Indonesia's hospital-based Severe Acute Respiratory Infection (SARI) surveillance system, Surveilans Infeksi Saluran Pernafasan Akut Berat Indonesia (SIBI), was established in 2013. While respiratory illnesses such as SARI pose a significant problem, there are limited incidence-based data on influenza disease burden in Indonesia. This study aimed to estimate the incidence of influenza-associated SARI in Indonesia during 2013-2016 at three existing SIBI surveillance sites. METHODS: From May 2013 to April 2016, inpatients from sentinel hospitals in three districts of Indonesia (Gunung Kidul, Balikpapan, Deli Serdang) were screened for SARI. Respiratory specimens were collected from eligible inpatients and screened for influenza viruses. Annual incidence rates were calculated using these SIBI-enrolled influenza-positive SARI cases as a numerator, with a denominator catchment population defined through hospital admission survey (HAS) to identify respiratory-coded admissions by age to hospitals in the sentinel site districts. RESULTS: From May 2013 to April 2016, there were 1527 SARI cases enrolled, of whom 1392 (91%) had specimens tested and 199 (14%) were influenza-positive. The overall estimated annual incidence of influenza-associated SARI ranged from 13 to 19 per 100 000 population. Incidence was highest in children aged 0-4 years (82-114 per 100 000 population), followed by children 5-14 years (22-36 per 100 000 population). CONCLUSIONS: Incidence rates of influenza-associated SARI in these districts indicate a substantial burden of influenza hospitalizations in young children in Indonesia. Further studies are needed to examine the influenza burden in other potential risk groups such as pregnant women and the elderly.

Physician's knowledge, attitudes, and practices regarding seasonal influenza, pandemic influenza, and highly pathogenic avian influenza A (H5N1) virus infections of humans in Indonesia.

Indonesia has reported highest number of fatal human cases of highly pathogenic avian influenza (HPAI) A (H5N1) virus infection worldwide since 2005. There are limited data available on seasonal and pandemic influenza in Indonesia. During 2012, we conducted a survey of clinicians in two districts in western Java, Indonesia, to assess knowledge, attitudes, and practices (KAP) of clinical diagnosis, testing, and treatment of patients with seasonal influenza, pandemic influenza, or HPAI H5N1 virus infections. Overall, a very low percentage of physician participants reported ever diagnosing hospitalized patients with seasonal, pandemic, or HPAI H5N1 influenza. Use of influenza testing was low in outpatients and hospitalized patients, and use of antiviral treatment was very low for clinically diagnosed influenza patients. Further research is needed to explore health system barriers for influenza diagnostic testing and availability of antivirals for treatment of influenza in Indonesia.

The Intersection of Care Seeking and Clinical Capacity for Patients With Highly Pathogenic Avian Influenza A (H5N1) Virus in Indonesia: Knowledge and Treatment Practices of the Public and Physicians.

BACKGROUND: Indonesia has the highest human mortality from highly pathogenic avian influenza (HPAI) A (H5N1) virus infection in the world. METHODS: A survey of households (N=2520) measured treatment sources and beliefs among symptomatic household members. A survey of physicians (N=554) in various types of health care facilities measured knowledge, assessment and testing behaviors, and perceived clinical capacity. RESULTS: Households reported confidence in health care system capacity but infrequently sought treatment for potential HPAI H5N1 signs/symptoms. More clinicians were confident in their knowledge of diagnosis and treatment than in the adequacy of related equipment and resources at their facilities. Physicians expressed awareness of the HPAI H5N1 suspect case definition, yet expressed only moderate knowledge in questioning symptomatic patients about exposures. Self-reported likelihood of testing for HPAI H5N1 virus was high after learning of certain exposures. Knowledge of antiviral treatment was moderate, but it was higher among clinicians in puskesmas. Physicians in private outpatient clinics, the most heavily used facilities, reported the lowest confidence in their diagnostic and treatment capabilities. CONCLUSIONS: Educational campaigns can encourage recall of possible poultry exposure when patients are experiencing signs/symptoms and can raise awareness of the effectiveness of antivirals to drive people to seek health care. Clinicians may benefit from training regarding exposure assessment and referral procedures, particularly in private clinics. (Disaster Med Public Health Preparedness. 2016;10:838-847).

Healthcare-seeking behaviors for acute respiratory illness in two communities of Java, Indonesia: a cross-sectional survey.

Understanding healthcare-seeking patterns for respiratory illness can help improve estimations of disease burden and inform public health interventions to control acute respiratory disease in Indonesia. The objectives of this study were to describe healthcare-seeking behaviors for respiratory illnesses in one rural and one urban community in Western Java, and to explore the factors that affect care seeking. From February 8, 2012 to March 1, 2012, a survey was conducted in 2520 households in the East Jakarta and Bogor districts to identify reported recent respiratory illnesses, as well as all hospitalizations from the previous 12-month period. We found that 4% (10% of those less than 5years) of people had respiratory disease resulting in a visit to a healthcare provider in the past 2weeks; these episodes were most commonly treated at government (33%) or private (44%) clinics. Forty-five people (0.4% of those surveyed) had respiratory hospitalizations in the past year, and just over half of these (24/45, 53%) occurred at a public hospital. Public health programs targeting respiratory disease in this region should account for care at private hospitals and clinics, as well as illnesses that are treated at home, in order to capture the true burden of illness in these communities.