Underdiagnoses of Rickettsia in patients hospitalized with acute fever in Indonesia: observational study results.

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.

Leptospirosis in Indonesia: diagnostic challenges associated with atypical clinical manifestations and limited laboratory capacity.

BACKGROUND: The burden of leptospirosis in Indonesia is poorly understood. Data from an observational study conducted from 2013 to 2016 in seven cities across Indonesia was used to estimate the incidence of leptospirosis and document its clinical manifestations in patients requiring hospitalization. METHODS: Specimens from patients hospitalized with acute fever were collected at enrollment, 14-28 days, and 3 months. Demographic and clinical information were collected during study visits and/or retrieved from medical records and double-entered into clinical report forms. After initially screening for dengue virus and other pathogens, specimens were tested at a central Reference Laboratory for anti-Leptospira IgM using commercial ELISA kits and for Leptospira DNA using an in-house quantitative real-time PCR assay. RESULTS: Of 1464 patients enrolled, 45 (3.1%) confirmed cases (by PCR and/or sero-coversion or four-fold increase of IgM) and 6 (0.4%) probable cases (by high titer IgM) of leptospirosis were identified by the Reference Laboratory. Disease incidence at sites ranged from 0 (0%) cases in Denpasar to 17 (8.9%) cases in Semarang. The median age of patients was 41.2 years (range of 5.3 to 85.0 years), and 67% of patients were male. Twenty-two patients (43.1%) were accurately diagnosed at sites, and 29 patients (56.9%) were clinically misdiagnosed as having another infection, most commonly dengue fever (11, 37.9%). Clinically, 20 patients (39.2%) did not present with hyperbilirubinemia or increased creatinine levels. Two patients (3.9%) died, both from respiratory failure. Fifteen patients (29.4%) clinically diagnosed with leptospirosis at sites were negative based on IgM ELISA and/or PCR at the Reference Laboratory. CONCLUSIONS: Leptospirosis remains an important cause of hospitalization in Indonesia. It can have diverse clinical presentations, making it difficult to differentiate from other common tropical infections. PCR combined with ELISA is a powerful alternative to the cumbersome gold-standard microscopic agglutination test, particularly in resource-limited settings.

Managing seasonal influenza: oseltamivir treatment policy in indonesia?

To manage cases of avian influenza A/H5N1 virus infection and in anticipation of a pandemic triggered by this virus, Indonesia purchased and distributed oseltamivir to the government health facilities. Oseltamivir is an antiviral drug that was developed for the treatment of influenza infections. Disease surveillance and research suggests that seasonal influenza (A/H1N1, A/H3N2 or B) results in considerable morbidity and mortality in Indonesia, where over 15% of influenza-like illness and severe acute respiratory illness patients test positive for the influenza virus. Indonesia currently limits oseltamivir for the management of avian influenza A/H5N1cases and in anticipation of a pandemic triggered by the A/H5N1 virus. We present the evidence for the use of oseltamivir in the treatment of seasonal influenza infections so that doctors have the option to prescribe the drug. We propose that the benefits of this approach will largely outweigh the risk of antiviral resistance. We recommend that oseltamivir be available for administration to patients with seasonal influenza infections, especially for those hospitalized and for groups with high risk of complications and adverse outcomes. Overall, this will reduce morbidity and mortality of seasonal influenza.

Evaluation of diagnostic assays for hepatitis E virus in outbreak settings.

Hepatitis E virus (HEV) is a major cause of hepatitis. We evaluated five HEV antibody diagnostic assays by using outbreak specimens. The Abbott immunoglobulin G (IgG), Genelabs IgG, and Walter Reed Army Institute of Research (WRAIR) IgM assays were about 90% sensitive; the Abbott IgG and WRAIR total Ig and IgM assays were more than 90% specific.

A large outbreak of probable rotavirus in Nusa Tenggara Timur, Indonesia.

An outbreak of acute diarrheal disease was reported in Kupang, Nusa Tenggara, Indonesia, in August 2002. An investigative team carried out a retrospective historical review of records, and a case-control study involving data and specimen collections. Etiologic determination involving stool specimens was based on an enzyme-linked immunosorbent assay, with a reverse transcriptase-polymerase chain reaction performed for serotyping purposes. Two thousand six hundred probable cases were identified from hospital records during the outbreak months of June, July, August, and September 2002. Previous enteric outbreaks were recognized from the same months in the preceding years and all annual outbreak episodes following a period of prolonged, low rainfall. In contrast to previous outbreaks discerned from trend analysis, the overwhelming burden of disease fell upon the pediatric population versus the young and old in previous outbreak instances. Rotavirus was found to be the causative etiology, with serotype 1 predominating.

Tracking the re-emergence of epidemic chikungunya virus in Indonesia.

Twenty-four distinct outbreaks of probable chikungunya (CHIK) etiology were identified throughout Indonesia from September 2001 to March 2003, after a near 20-year hiatus of epidemic CHIK activity in the country. Thirteen outbreak reports were based on clinical observations alone, and 11 confirmed by serological/virological methods. Detailed epidemiological profiles of two investigated outbreaks in Bogor and Bekasi are presented. Human sera were screened using an ELISA for IgM and IgG anti-CHIK antibodies. Additionally, reverse transcriptase PCR and virus isolation were attempted for virus identification. The mean age of cases was 37 +/- 18 years in Bogor and 33 +/- 20 years in Bekasi. There was no outstanding case-clustering, although outbreak-affected households were observed to be geographically grouped within villages. The attack rates in Bogor and Bekasi were 2.8/1000 and 6.7/1000 inhabitants respectively. Both outbreaks started in the rainy season following increased Aedes aegypti and A. albopictus densities.

Transmission of epidemic dengue hemorrhagic fever in easternmost Indonesia.

In April 2001, a second suspected outbreak of dengue hemorrhagic fever in the easternmost region of Indonesia was investigated in Merauke, a town located in the southeastern corner of Papua, by the Indonesian Ministry of Health and the U.S. Naval Medical Research Unit No. 2. Principal case criteria of hemorrhagic disease provided for a study enrollment of 15 clinically acute and 37 convalescing subjects. Additionally, 32 comparable age/sex controls were selected from neighboring households. Laboratory diagnosis involved three testing methodologies: virus isolation by cell culture, a reverse transcriptase-polymerase chain reaction (RT-PCR) assay, and serologic assays. Antibody (IgM) to dengue virus was detected in 27% of the acute clinical cases, 30% of the convalescing cases, and only 3% of the matched controls. Dengue 3 was the only viral serotype detected from acute serum samples by the RT-PCR. The mean +/- SD age of the acute and convalescing cases was 7.8 +/- 5.4 years. Overall hospital records accounted for 172 suspected outbreak cases, all urban residents of Merauke with no recent travel history outside the area. The estimated outbreak-associated case fatality rate among all suspected dengue cases was 1.2%. A seven-year retrospective review of hospital records in Merauke showed negligible disease reporting involving hemorrhagic disease prior to the outbreak.

The importance of leptospirosis in Southeast Asia.

The importance of leptospirosis in Southeast Asia was assessed in conjunction with other studies supported by the U.S. Naval Medical Research Unit No. 2 (US NAMRU-2), Jakarta, Republic of Indonesia. These included studies of hospital-based, acute clinical jaundice in Indonesia, Lao PDR, and Socialist Republic of Vietnam; nonmalarial fever in Indonesia; and hemorrhagic fever in Cambodia. Background prevalence estimates of leptospiral infection were obtained by a cross-sectional, community-based study in Lao PDR. Laboratory testing methods involved serology, microscopic agglutination test, and reverse-transcriptase polymerase chain reaction. Suggestive evidence of recent leptospiral infections was detected in 17%, 13%, and 3% of patients selected on the basis of non-hepatitis A through E jaundice, nonmalarial fever, and hemorrhagic fever (in the absence of acute, dengue viral infections). Leptospiral IgG antibody, reflective of prior infections, was detected in 37% of human sera, collected in Lao PDR. The predominant leptospiral serogroups identified from cases with clinical jaundice were Hurstbridge, Bataviae, and Icterohaemorrhagiae tonkini LT 96 69. Among the nonmalarial febrile cases, Bataviae was the most frequently recognized serogroup. Pyrogenes and Hurstbridge were the principal serogroups among the hemorrhagic fever case subjects. These findings further attest to the relative importance of clinical leptospirosis in Southeast Asia. The wide spectrum of clinical signs and symptoms associated with probable, acute, leptospiral infections contributes to the potential of significant underreporting.

Short report: hepatitis b infection and severe Plasmodium falciparum malaria in Vietnamese adults.

We investigated the prevalence of infection with hepatitis B virus among adult Vietnamese patients hospitalized for severe Plasmodiumfalciparum malaria. Sera from patients admitted with severe malaria in Ho Chi Minh City, Vietnam, between May 1991 and January 1996 were assayed for hepatitis B surface antigen (HB(s)Ag) by a commercial enzyme-linked immunosorbent assay kit. The overall prevalence of HB(s)Ag was 23.77% (77 of 324). This was higher than reported estimates of prevalence in the general catchment population for the study hospital (mean, 9.8%; range, 9-16%). No association was found between risk of death caused by severe malaria and HB(s)Ag. Patients admitted with cerebral malaria had a slightly greater risk of registering positive for HB(s)Ag (relative risk, 1.28; 95% confidence interval, 1.04-1.58) relative to other manifestations of severe malaria. Chronic infection with hepatitis B virus may be a risk factor for severe malaria.

Hepatitis C among child transfusion and adult renal dialysis patients in Indonesia.

Hepatitis C virus (HCV) prevalence among high-risk pediatric and adult patients was evaluated. The study included 269 adults and 150 children in a case-control research design. Risk factors of HCV exposure in Indonesia were assessed among adult renal dialysis patients and pediatric patients who received multiple blood transfusions. A high prevalence of anti-HCV was found among the adult renal dialysis patients, measured by second-generation electroimmunoassay tests. Family members of dialysis patients, who served as a comparison group for dialysis patients, were found to have a 9.0% seroprevalence. The prevalence of anti-HCV among pediatric patients with hematological disorders was found to be 39.0%. The comparison group seroprevalence (pediatric patients and family members) was 4.3% among sera available for confirmatory testing. Patients with history of hospitalization (odds ratio [OR] = 7.94, 95% confidence interval [CI]: 4.06-15.51, P = 0.0001), blood transfusion (OR = 6.85, 95% CI: 3.95-11.88, P = 0.0001), circumcision (OR = 2.39, 95% CI: 1.43-3.99, P = 0.0001), or marital partner/family member history of jaundice (OR = 3.62, 95% CI: 1.97-6.62, P = 0.0001) were found to have an increased odds of HCV exposure compared with individuals without similar histories.