Dengue 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. A 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. DENV 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. Dengue is a mosquito-borne viral disease whose global incidence has increased dramatically in recent decades. Infection with any of the four serotypes can cause subclinical to life-threatening illness. Indonesia and other subtropical regions are hyper-endemic, thus are at increased risk of disease impact. We conducted a multicenter observational cohort study of acute febrile illness requiring hospitalization in children and adults in Indonesia from 2013–2016. Epidemiology, clinical course, and virology of dengue were assessed. Dengue infection is the main cause of hospitalized acute febrile illness in Indonesia. DENV serotypes 1–4 circulated throughout the study period, with highest overall rates in January to March. We observed DENV-1 with TS1₁₉(C→T) substitution in the serotyping primer annealing site that caused failure of routine detection. Diagnostic accuracy at clinical sites merits optimization. Clinicians should consider following diagnostic algorithms that include DENV confirmatory testing, while policy-makers should prioritize development of laboratory capacity for diagnosis of DENV.

Dengue disease is still a major health problem in Indonesia. Surabaya, the second largest city in the country, is endemic for dengue. We report here on dengue disease in Surabaya, investigating the clinical manifestations, the distribution of dengue virus (DENV) serotypes, and the relationships between clinical manifestations and the genetic characteristics of DENV. A total of 148 patients suspected of having dengue were recruited during February-August 2012. One hundred one (68%) of them were children, and 47 (32%) were adults. Dengue fever (DF) and Dengue hemorrhagic fever (DHF) were equally manifested in all of the patients. We performed DENV serotyping on all of the samples using real-time RT-PCR. Of 148, 79 (53%) samples were detected as DENV positive, with DENV-1 as the predominant serotype (73%), followed by DENV-2 (8%), DENV-4 (8%), and DENV-3 (6%), while 5% were mixed infections. Based on the Envelope gene sequences, we performed phylogenetic analyses of 24 isolates to genotype the DENV circulating in Surabaya in 2012, and the analysis revealed that DENV-1 consisted of Genotypes I and IV, DENV-2 was of the Cosmopolitan genotype, the DENV-3 viruses were of Genotype I, and DENV-4 was detected as Genotype II. We correlated the infecting DENV serotypes with clinical manifestations and laboratory parameters; however, no significant correlations were found. Amino acid analysis of Envelope protein did not find any unique mutations related to disease severity.

Background: Diphtheria has been reported as an outbreak in some regions in Indonesia, most especially in East Java Province. Resistance to penicillin, erythromycin, and other antibiotics, single or multiple, has been reported in several studies. This study aims to evaluate the first-line antibiotic susceptibility pattern of toxigenic Corynebacterium diphtheriae isolates. Methods: This descriptive observational study was performed from August to November 2018. C. diphtheriae isolates were collected from diphtheria patients and carriers in East Java from 2012 to 2017 and kept at the Balai Besar Laboratorium Kesehatan Daerah Surabaya or the Public Health Laboratory of Surabaya. Sample selection was done by random cluster sampling. The sensitivity test by E-test®of the five antibiotics (penicillin, oxacillin, erythromycin, azithromycin, and clarithromycin) was done to determine the minimum inhibitory concentration (MIC). The Clinical and Laboratory Standards Institute M45A (2015) Corynebacterium spp. for penicillin and erythromycin was used as standard. Results: From 114 targeted isolates, 108 were viable and toxigenic. The E-test was performed on the viable isolates. The majority of the hosts were male (58.3%), with median (range) age of 6.5 (1–14) years. Half of the samples were from the 1 to 5-year-old age group. The isolates were acquired much more from patients (78.7%) than carriers (21.3%) and from pharyngeal swab (74.1%). Most of these isolates were from Madura Island (47.2%) and the northern and eastern parts of the province (horseshoe area). Mitis isolates were the major variant (76.9%). The susceptibility pattern of C. diphtheriae to erythromycin was better than that to penicillin. The E-test result for penicillin was 68.52% susceptible, 31.48% intermediate, and 0% resistant (MIC range, < 0.016 to 2 μg/L) and for erythromycin (MIC range, < 0.016 to > 256 μg/L) was 85.2% susceptible, 12% intermediate, and 2.8% resistant The MIC range for oxacillin was 1 to 96 μg/L, while for both azithromycin and clarithromycin were < 0.016 to > 256 μg/L. Conclusion: The susceptibility rate of C. diphtheriae to erythromycin is higher than that to penicillin. The regular update of antibiotic selection to the national guidelines is recommended. The MIC reference standard to azithromycin and clarithromycin is also needed.

Background: Severe acute respiratory infection (SARI) accounts for a large burden of illness in Indonesia. However, epidemiology of SARI in tertiary hospitals in Indonesia is unknown. This study sought to assess the burden, clinical characteristics, and etiologies of SARI and concordance of clinical diagnosis with confirmed etiology.Methods: Data and samples were collected from subjects presenting with SARI as part of the acute febrile Illness requiring hospitalization study (AFIRE). In tertiary hospitals, clinical diagnosis was ascertained from chart review. Samples were analyzed to determine the “true” etiology of SARI at hospitals and Indonesia Research Partnership on Infectious Diseases (INA‐RESPOND) laboratory. Distribution and characteristics of SARI by true etiology and accuracy of clinical diagnosis were assessed.Results: Four hundred and twenty of 1464 AFIRE subjects presented with SARI; etiology was identified in 242 (57.6%), including 121 (28.8%) viruses and bacteria associated with systemic infections, 70 (16.7%) respiratory bacteria and viruses other than influenza virus, and 51 (12.1%) influenza virus cases. None of these influenza patients were accurately diagnosed as having influenza during hospitalization.Conclusions: Influenza was misdiagnosed among all patients presenting with SARI to Indonesian tertiary hospitals in the AFIRE study. Diagnostic approaches and empiric management should be guided by known epidemiology. Public health strategies to address the high burden of influenza should include broad implementation of SARI screening, vaccination programs, clinician education and awareness campaigns, improved diagnostic capacity, and support for effective point‐of‐care tests.

Background: Measles is a recurrent health problem in both advanced and developed countries. The World Health Organization (WHO) recommends anti-measles immunoglobulin M (Ig M) as the standard method of detecting the virus; however, many areas still present the inability to perform a serology test of anti-measles IgM. Therefore, a typical clinical feature is necessary to establish the diagnosis of measles. The objective of this study was to evaluate hyperpigmented rash and other clinical features as the diagnostic tools with respect to measles, especially in an outbreak setting. Methods: In this observational diagnostic study, the inclusion criteria were as follows: between 6 and 144 months of age, fever, maculopapular rash for 3 days or more, accompanied by a cough, or coryza, or conjunctivitis. Those with a prior history of measles vaccination (1–6 weeks) were excluded, in addition to those with histories of corticosteroid for 2 weeks or more and immunocompromised conditions. The samples were taken from Dr. Soetomo General Academic Hospital in Surabaya, Indonesia. We evaluated the sensitivity, specificity, the positive predictive value, and the negative predictive value of such clinical features. Hyperpigmented rash was validated using Kappa and Mc Nemar tests. Anti-measles Ig M was considered as the gold standard. Results: This study gathered 82 participants. The clinical manifestations of all subjects included fever, cough, coryza, conjunctivitis, Koplik spots, and maculopapular rash (which turns into hyperpigmented rash along the course of the illness). Most maculopapular rashes turn out to be hyperpigmented (89%). Sensitivity, specificity, positive predictive value, and negative predictive values ​​of the combination of fever, maculopapular rash, and hyperpigmented rash were found to be at 90.7, 28.6, 93.2, and 22.2%, respectively. The Mc Nemar and Kappa tests showed p values of 0.774 and 0.119, respectively. Conclusion: The combination of fever, maculopapular rash, and hyperpigmented rash can be used as a screening tool regarding measles infection in an outbreak setting, which can then be confirmed by anti-measles Ig M. Cough, coryza, and Koplik’s spot can be added to this combination, albeit with a slight reduction of sensitivity value.