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Background Since their emergence in Indonesia in 2005, 200 human infections with clade 2.1 highly pathogenic avian influenza A/H5N1 virus have been reported, associated with exceptionally high mortality (84%) compared to regions affected by other genetic clades of this virus. To provide potential clues towards understanding this high mortality, detailed clinical virological analyses were performed in specimens from 180 H5N1 patients, representing 90% of all Indonesian patients and 20% of reported H5N1-infected patients globally. Methods H5N1 RNA was quantified in available upper- and lower-respiratory tract specimens as well as fecal and blood samples from 180 patients with confirmed infection between 2005 and 2017. Mutations in the neuraminidase and M2 genes that confer resistance to oseltamivir and adamantanes were assessed. Fatal and nonfatal cases were compared. Results High viral RNA loads in nasal and pharyngeal specimens were associated with fatal outcome. Mortality increased over time during the study period, which correlated with increasing viral RNA loads on admission. Furthermore, the prevalence of amantadine resistance–conferring M2 mutations increased over time, and viral loads were higher in patients infected with viruses that harbored these mutations. Compared to observations from other regions, viral RNA was detected more frequently in feces (80%) and particularly in blood (85%), and antiviral responses to oseltamivir appeared less pronounced. Conclusions These observations confirm the association of viral load with outcome of human H5N1 infections and suggest potential differences in virulence and antiviral responses to oseltamivir that may explain the exceptionally high mortality related to clade 2.1 H5N1 infections in Indonesia. [ABSTRACT FROM AUTHOR]

Global surveillance of antimicrobial resistance (AMR) is a key component of the 68th World Health Assembly Global Action Plan on AMR. Laboratory-based surveillance is inherently biased and lacks local relevance due to aggregation of data. We assessed the feasibility, sensitivity, and affordability of a population-based AMR survey using lot quality assurance sampling (LQAS), which classifies a population as having a high or low prevalence of AMR based on a priori defined criteria. Three studies were carried out in Medan and Bandung, Indonesia, between April 2014 and June 2017. LQAS classifications for 15 antibiotics were compared with AMR estimates from a conventional population-based survey, with an assessment of the cost of a single LQAS classification using microcosting methodology, among patients suspected of urinary tract infection at 11 sites in Indonesia. The sensitivity of LQAS was above 98%. The approach detected local variation in the prevalence of AMR across sites. Time to reach LQAS results ranged from 47 to 138 days. The average cost of an LQAS classification in a single facility was US$466. The findings indicate that LQAS-based AMR survey is a feasible, sensitive, and affordable strategy for population-based AMR surveys, providing essential data to inform local empirical treatment guidelines and antimicrobial stewardship efforts. [ABSTRACT FROM AUTHOR]