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BackgroundDengue virus (DENV) infection is a major cause of acute febrile illness in Indonesia. Diagnostic inaccuracy may occur due to its varied and non-specific presentation. Characterization of DENV epidemiology, clinical presentation, and virology will facilitate appropriate clinical management and public health policy.Methodology/Principal findingsA multicenter observational cohort study was conducted in Indonesia to assess causes of acute fever requiring hospitalization. Clinical information and specimens were collected at enrollment, 14–28 days, and 3 months from 1,486 children and adults. Total of 468 (31.9%) cases of DENV infection were confirmed by reference laboratory assays. Of these, 414 (88.5%) were accurately diagnosed and 54 had been misdiagnosed as another infection by sites. One hundred initially suspected dengue cases were finally classified as ‘non-dengue’; other pathogens were identified in 58 of those cases. Mortality of DENV infection was low (0.6%). Prior DENV exposure was found in 92.3% of subjects >12 years. DENV circulated year-round in all cities, with higher incidence from January to March. DENV-3 and DENV-1 were the predominant serotypes. This study identified DENV-1 with TS119(C→T) substitution in the serotyping primer annealing site, leading to failure of serotype determination.Conclusions/SignificanceDENV is a common etiology of acute febrile illness requiring hospitalization in Indonesia. Diagnostic accuracy at clinical sites merits optimization since misdiagnosis of DENV infection and over-estimation of dengue can negatively impact management and outcomes. Mutation at the annealing site of the serotyping primer may confound diagnosis. Clinicians should consider following diagnostic algorithms that include DENV confirmatory testing. Policy-makers should prioritize development of laboratory capacity for diagnosis of DENV.

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Background: Reports of human rickettsial infection in Indonesia are limited. This study sought to characterize the epidemiology of human rickettsioses amongst patients hospitalized with fever at 8 tertiary hospitals in Indonesia. Methods: Acute and convalescent blood from 975 hospitalized non-dengue patients was tested for Rickettsia IgM and IgG by ELISA. Specimens from cases with seroconversion or increasing IgM and/or IgG titers were tested for Rickettsia IgM and IgG by IFA and Rickettsia genomes using primers for Rickettsia (R.) sp, R. typhi, and Orientia tsutsugamushi. Testing was performed retrospectively on stored specimens; results did not inform patient management. Results: R. typhi, R. rickettsii, and O. tsutsugamushi IgG antibodies were identified in 269/872 (30.8%), 36/634 (5.7%), and 19/504 (3.8%) of samples, respectively. For the 103/975 (10.6%) non-dengue patients diagnosed with acute rickettsial infection, presenting symptoms included nausea (72%), headache (69%), vomiting (43%), lethargy (33%), anorexia (32%), arthralgia (30%), myalgia (28%), chills (28%), epigastric pain (28%), and rash (17%). No acute rickettsioses cases were suspected during hospitalization. Discharge diagnoses included typhoid fever (44), dengue fever (20), respiratory infections (7), leptospirosis (6), unknown fever (6), sepsis (5), hepatobiliary infections (3), UTI (3), and others (9). Fatalities occurred in 7 (6.8%) patients, mostly with co-morbidities. Conclusions: Rickettsial infections are consistently misdiagnosed, often as leptospirosis, dengue, or Salmonella typhi infection. Clinicians should include rickettsioses in their differential diagnosis of fever to guide empiric management; laboratories should support evaluation for rickettsial etiologies; and public policy should be implemented to reduce burden of disease.

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