METHODS: In-depth individual interviews with thematic saturation were conducted between May and July 2018. The data was analyzed using thematic analysis.
RESULTS: Based on expert opinion, diagnosis of severe dengue is challenging as it depends on astute clinical interpretation of non-dengue-specific clinical and laboratory findings. A specific test that detects impending manifestation of severe dengue could 1) overcome failure in identifying severe disease for referral or admission, 2) facilitate timely and appropriate management of plasma leakage and bleeding, 3) overcome the lack of clinical expertise and laboratory diagnosis in rural health settings. The most important feature of any diagnostics for severe dengue is the point-of-care (POC) format where it can be performed at or near the bedside.
CONCLUSION: The development of diagnostics to detect impending severe dengue is warranted to reduce the morbidity and mortality rates of dengue infection and it should be prioritized.
METHODOLOGY/PRINCIPAL FINDINGS: Sentinel and study sites collected nasopharyngeal specimens for diagnostic detection, virus isolation, antigenic characterization, sequencing and antiviral susceptibility analysis from patients who fulfilled case definitions for influenza-like illness, acute lower respiratory infections and event-based surveillance. Each year in Cambodia, influenza viruses were detected mainly from June to November, during the rainy season. Antigenic analysis show that A/H1N1pdm09 isolates belonged to the A/California/7/2009-like group. Circulating A/H3N2 strains were A/Brisbane/10/2007-like in 2009 before drifting to A/Perth/16/2009-like in 2010 and 2011. The Cambodian influenza B isolates from 2009 to 2011 all belonged to the B/Victoria lineage represented by the vaccine strains B/Brisbane/60/2008 and B/Malaysia/2506/2004. Sequences of the M2 gene obtained from representative 2009-2011 A/H3N2 and A/H1N1pdm09 strains all contained the S31N mutation associated with adamantanes resistance except for one A/H1N1pdm09 strain isolated in 2011 that lacked this mutation. No reduction in the susceptibility to neuraminidase inhibitors was observed among the influenza viruses circulating from 2009 to 2011. Phylogenetic analysis revealed that A/H3N2 strains clustered each year to a distinct group while most A/H1N1pdm09 isolates belonged to the S203T clade.
CONCLUSIONS/SIGNIFICANCE: In Cambodia, from 2009 to 2011, influenza activity occurred throughout the year with peak seasonality during the rainy season from June to November. Seasonal influenza epidemics were due to multiple genetically distinct viruses, even though all of the isolates were antigenically similar to the reference vaccine strains. The drug susceptibility profile of Cambodian influenza strains revealed that neuraminidase inhibitors would be the drug of choice for influenza treatment and chemoprophylaxis in Cambodia, as adamantanes are no longer expected to be effective.