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

Abstract

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 resourcelimited settings.

Leptospirosis with pulmonary haemorrhage and multiple organ failure: a case report and literature review

“… 11 , 12 As a result, specific laboratory tests for leptospirosis are not available in many units, and the diagnosis can easily be missed. 13 In the present case, we could not diagnose the leptospiral infection in the early stage of the disease because we had an insufficient understanding of leptospirosis, overlooked the risk factors, and obtained no important diagnostic clues from the routine laboratory tests.…”

Leptospiral Infection, Pathogenesis and Its Diagnosis—A Review

“…Conventional diagnostic techniques such as culture can be useful, but most of its resources (if not all) are not available in most countries [ 227 ]. As current diagnostic trends for leptospirosis strongly suggest the use of both serological and molecular techniques for heightened accuracy, the combinatorial use of PCR and ELISA (in place of the cumbersome gold standard MAT) for early diagnosis is a powerful alternative in resource-poor countries [ 228 ], highlighting the significance of combinatorial techniques in diagnoses. Besides that, Koizumi et al [ 229 ] developed a revolutionary loop-mediated isothermal amplification (LAMP) technique to detect a 16S rRNA gene ( rrs ) that are typically found in urines of patients infected with pathogenic leptospires.…”

Going Micro in Leptospirosis Kidney Disease

“…Nested PCR also helps in detecting more specific and sensitive DNA sites with additional sets of primers [ 86 , 87 ]. However, current trends for leptospirosis diagnosis are the use of both serological and molecular techniques, such as PCR and ELISA (easier than the gold standard serological MAT), for resource-limited countries [ 88 , 89 ]. Additionally, the LAMP technique [ 90 ] to detect a 16S rRNA gene (rrs), is a cost-effective, rapid and high-yield for detecting the pathogenic leptospires in the urine.…”