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 Methods and findings: We aggregated published data from a systematic review and unpublished data from surveillance platforms to generate global meta-analytic estimates for the proportion of acute respiratory hospitalizations associated with influenza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 The 63 data sources represent published observational studies (n = 28) and unpublished surveillance data (n = 35), from all World Health Organization regions (Africa, n = 8; Americas, n = 11; Eastern Mediterranean, n = 7; Europe, n = 8; Southeast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.

The continuing pandemic threat posed by avian influenza A/H5N1 viruses calls for improved insights into their evolution during human infection. We performed whole genome deep sequencing of respiratory specimens from 44 H5N1-infected individuals from Indonesia and found substantial within-host viral diversity. At nearly 30% of genome positions multiple amino acids were observed within or across samples, including positions implicated in aerosol transmission between ferrets. Amino acid variants detected our cohort were often found more frequently in available H5N1 sequences of human than avian isolates. We additionally identified previously unreported amino acid variants and multiple variants that increased in proportion over time in available sequential samples. Given the importance of the polymerase complex for host adaptation, we tested 121 amino acid variants found in the PB2, PB1 and PA subunits for their effects on polymerase activity in human cells. We identified multiple single amino acid variants in all three polymerase subunits that substantially increase polymerase activity including some with effects comparable to that of the widely recognized adaption and virulence marker PB2-E627 K. These results indicate highly dynamic evolutionary processes during human H5N1 virus infection and the potential existence of previously undocumented adaptive pathways.

We describe the first 11 detected COVID-19 cases in Indonesia, resulting from a local transmission occurring in a club and a restaurant. The virus was detected until an average of 21.3 days (range: 11–25, SD: 4.1) after the onset of illness, and the partial N gene sequences (28,321–28,707 nucleotide position) had 100% similarity with the SARS-CoV-2 sequence from Wuhan. Two subjects were asymptomatic, and one subject has died.

Background. By 30 July 2009, Indonesia had reported 139 outbreaks of avian influenza (AI) H5N1 infection in humans. Risk factors for case clustering remain largely unknown. This study assesses risk factors for cluster outbreaks and for secondary case infection. Methods. The 113 sporadic and 26 cluster outbreaks were compared on household and individual level variables. Variables assessed include those never reported previously, including household size and genealogical relationships between cases and their contacts. Results. Cluster outbreaks had larger households and more blood-related contacts, especially first-degree relatives, compared with sporadic case outbreaks. Risk factors for cluster outbreaks were the number of first-degree blood-relatives to the index case (adjusted odds ratio [aOR], 1.50; 95% confidence interval [CI]: 1.20–1.86) and index cases having direct exposure to sources of AI H5N1 virus (aOR, 3.20; 95% CI: 1.15–8.90). Risk factors for secondary case infection were being aged between 5 and 17 years (aOR, 8.32; 95% CI: 1.72–40.25), or 18 and 30 years (aOR, 6.04; 95% CI: 1.21–30.08), having direct exposure to sources of AI H5N1 virus (aOR, 3.48; 95% CI: 1.28–9.46), and being a first-degree relative to an index case (aOR, 11.0; 95% CI: 1.43–84.66). Siblings to index cases were 5 times more likely to become secondary cases (OR, 4.72; 95% CI: 1.67–13.35). Conclusions. The type of exposure and the genealogical relationship between index cases and their contacts impacts the risk of clustering. The study adds evidence that AI H5N1 infection is influenced by, and may even depend on, host genetic susceptibility.

Since 2003, 200 cases of bird flu (H5N1) cases have been reported with 168 death (case fatality rate: 84%) in Indonesia. Pandemics are unpredictable, but the threat is imminent. Therefore, pandemic preparedness, which includes full simulation exercises, is a key to reduce this threat. Responding to the challenges, Ministry of Health (MoH) Indonesia adopted WHO pandemic risk management guideline, developed contingency plan and conducted full scale epicenter influenza pandemic simulation. The exercise outlines the Government of Indonesia operational plans for Avian Influenza (AI) control from the detection of AI cases (from poultry to human transmission) and containment of human to human transmission of novel influenza virus in influenza pandemic epicenter at Setu village South Tangerang. The simulation covers multiple locations in community, hospitals, point of entry and live bird market. 25 evaluators and around 800 observers involved in the exercise. The full scale pandemic epicenter containment exercise has demonstrated Indonesia capacity in whole of society approach pandemic risk management in the overall national emergency response framework, covering command and coordination, animal health response surveillance, medical response, laboratory, risk communication, perimeter control, pharmaceutical interventions, non-pharmaceutical interventions and civil-military interoperability. It is served as a momentum to improve multisector commitment on pandemic preparedness. The outcome of this exercise has contributed to identification of gaps that require further strengthening of IHR core capacities in the country to reduce the threat of the next influenza pandemic. There is also a critical need for more evidence-based strategies and policy formulation to strengthen pandemic preparedness.