Leptospirosis during Dengue Outbreak, Bangladesh

LaRocque, Regina C.; Breiman, Robert F.; Ari, Mary D.; Morey, Roger E.; Janan, Firdous Ara; Hayes, John M.; Hossain, M. Anowar; Brooks, W. Abdullah; Levett, Paul N.

doi:10.3201/eid1105.041212

Cited by 118 publications

(111 citation statements)

References 15 publications

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“…Leptospiral infection may be clinically inapparent, 24 or may result in undifferentiated fever, fulminant disease, and mimics other tropical diseases such as malaria, 25 dengue, [26][27][28][29] hantaviral syndromes, 18,30-32 scrub typhus, 33,34 and others. During the acute phase of leptospirosis, timely confirmation is an important clinical priority to optimize both specific treatment and supportive management.…”

Section: Discussionmentioning

confidence: 99%

Redefining Gold Standard Testing for Diagnosing Leptospirosis: Further Evidence from a Well-Characterized, Flood-Related Outbreak in Sri Lanka

Agampodi

Dahanayaka

Nöckler

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Abstract. A gap in the leptospirosis field remains the lack of well-characterized sample collections that allow for comparison of new methods to standard ones. In the context of a flood-related outbreak of leptospirosis evaluated in Anuradhapura, Sri Lanka, a specimen bank was obtained with detailed metadata accompanied by gold standard diagnostic test results. Blood samples collected on admission and 14 days later from suspected cases of leptospirosis were tested using microscopic agglutination test (MAT) (17 serovars), an in-house enzyme-linked immunosorbent assay (ELISA) using a locally obtained strain of Leptospira kirschneri as sonicated antigen, a commercially available ELISA based on sonicated Leptospira biflexa, and a quantitative polymerase chain reaction (qPCR) assay targeting the pathogenic Leptospira-specific 16S rRNA gene. Of 62 patients presenting within the first 2 days of illness, 31 had confirmed leptospirosis based either on paired-sample MAT or qPCR. During the acute phase, qPCR was most sensitive, detecting 74% of definitively diagnosed cases; immunoglobulin G (IgG) ELISA (in-house), IgG ELISA (commercial), and MAT had sensitivities of 35.5%, 12.0%, and 22.6%, respectively, in detecting definitively diagnosed cases using acute phase serum. Of 40 patients with paired sera, 10 were qPCR positive. Of these, five samples were negative by paired-sample MAT. Of the 11 MAT-positive samples, only five were detected using qPCR confirming that both tests are needed for maximal sensitivity. Regional leptospiral serovar-specific IgG ELISA was superior to MAT. Knowing the regionally dominant serovars improves serological sensitivity in the analysis of acute specimens by ELISA, but qPCR was most sensitive in this patient population.

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Section: Discussionmentioning

confidence: 99%

Redefining Gold Standard Testing for Diagnosing Leptospirosis: Further Evidence from a Well-Characterized, Flood-Related Outbreak in Sri Lanka

Agampodi

Dahanayaka

Nöckler

et al. 2016

The American Society of Tropical Medicine and Hygiene

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“…We also analyzed immune responses using previously collected acute and convalescentphase serum specimens from patients with culture-confirmed cholera (n ϭ 5) (2) and febrile illnesses due to serologically confirmed dengue (n ϭ 5) and leptospirosis (n ϭ 5) (23). The study and all sample collections and analyses were approved by the ethical and research review committees of the ICDDR,B.…”

Section: Methodsmentioning

confidence: 99%

Salmonella enterica Serovar Typhi-Specific Immunoglobulin A Antibody Responses in Plasma and Antibody in Lymphocyte Supernatant Specimens in Bangladeshi Patients with Suspected Typhoid Fever

Sheikh

Bhuiyan

Khanam

et al. 2009

Clin Vaccine Immunol

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Many currently available diagnostic tests for typhoid fever lack sensitivity and/or specificity, especially in areas of the world where the disease is endemic. In order to identify a diagnostic test that better correlates with typhoid fever, we evaluated immune responses to Salmonella enterica serovar Typhi (serovar Typhi) in individuals with suspected typhoid fever in Dhaka, Bangladesh. We enrolled 112 individuals with suspected typhoid fever, cultured day 0 blood for serovar Typhi organisms, and performed Widal assays on days 0, 5, and 20. We harvested peripheral blood lymphocytes and analyzed antibody levels in supernatants collected on days 0, 5, and 20 (using an antibody-in-lymphocyte-supernatant [ALS] assay), as well as in plasma on these days. We measured ALS reactivity to a serovar Typhi membrane preparation (MP), a formalin-inactivated whole-cell preparation, and serovar Typhi lipopolysaccharide. We measured responses in healthy Bangladeshi, as well as in Bangladeshi febrile patients with confirmed dengue fever or leptospirosis. We categorized suspected typhoid fever individuals into different groups (groups I to V) based on blood culture results, Widal titer, and clinical features. Responses to MP antigen in the immunoglobulin A isotype were detectable at the time of presentation in the plasma of 81% of patients. The ALS assay, however, tested positive in all patients with documented or highly suspicious typhoid, suggesting that such a response could be the basis of improved diagnostic pointof-care-assay for serovar Typhi infection. It can be important for use in epidemiological studies, as well as in difficult cases involving fevers of unknown origin.Salmonella enterica serovar Typhi (serovar Typhi) is the cause of typhoid fever, an illness that affects over 20,000,000 individuals worldwide each year, killing over 200, 000 (5, 8, 16). The largest burden of typhoid fever is borne by impoverished individuals in resource-poor areas of the world. Serovar Typhi is a human-restricted invasive enteric pathogen which, after ingestion, crosses the intestinal mucosa, is taken up by gutassociated lymphoreticular tissues, and enters the systemic circulation. Both mucosal and systemic host immune responses are stimulated after infection. Serovar Typhi is an intracellular pathogen, and antibody and cell-mediated immune responses occur after infection or immunization with live oral attenuated typhoid vaccines (10,25,34).Diagnostic tests for typhoid fever often lack sensitivity and/or specificity, especially in areas of the world that are endemic for typhoid fever, where clinically distinguishing typhoid fever from other febrile illnesses is difficult (5, 17, 39). Microbiologic culturing of blood is approximately 30 to 70% sensitive, with the highest sensitivity being associated with an absence of prior use of antibiotics and the culturing of larger volumes of blood, features that complicate this mode of diagnosis in young children (5,6,8,36). Microbiologic culturing of bone marrow aspirates is more sensitive than bl...

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“…Por ejemplo, se ha documentado ampliamente la asociación de leptospirosis y dengue en diferentes regiones del mundo, algunas veces asociada con brotes después de desastres naturales (25)(26)(27)(28)(29) En Colombia es poco lo que se ha informado sobre leptospirosis en humanos, o sobre su comportamiento epidemiológico y serológico (20,(30)(31)(32)(33)(34)(35)(36). Lo anterior se debe posiblemente a que no existen pruebas serológicas de amplia distribución para confirmar el diagnóstico etiológico.…”

Section: Discussionunclassified

Evaluación de la prueba de inmunofluorescencia indirecta para el diagnóstico de leptospirosis humana.

Agudelo‐Flórez¹,

Restrepo²,

Lotero³

2006

biomedica

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Introducción. El diagnóstico de la leptospirosis es difícil debido al amplio espectro de síntomas clínicos que presenta. Varias pruebas diagnósticas serológicas se han desarrollado, pero su aplicación y utilidad en Colombia no han sido determinadas. Objetivos. Evaluar la prueba de inmunofluorescencia indirecta para el diagnóstico de leptospirosis humana y determinar así los anticuerpos de las clases inmunoglobulina G y M producidos contra Leptospira. Materiales y métodos. Se establecieron tres grupos de estudio. El primero incluyó 19 muestras positivas para leptospirosis de pacientes con diagnóstico clínico y prueba de microaglutinación positiva; el segundo, 40 muestras de personas sin antecedentes de leptospirosis y con microaglutinación negativa, y el tercero con 96 muestras de pacientes con otras enfermedades diferentes a leptospirosis. Todas las muestras fueron procesadas por inmunofluorescencia indirecta. Resultados. Se determinó que la inmunofluorescencia indirecta tiene sensibilidad de 89,47%, especificidad de 100%, valor predictivo negativo de 95,2% (IC95% 82,6 a 99,2) y valor predictivo positivo de 100%. En forma paralela, un estudio exploratorio en 27 muestras de suero que habían sido remitidas para diagnóstico de diferentes síndromes febriles encontró que 11% de ellas fueron positivas por inmunofluorescencia indirecta para anticuerpos IgM contra Leptospira. Conclusiones. La inmunofluorescencia indirecta es una alternativa que complementa el diagnóstico de leptospirosis y los estudios seroepidemiológicos. La presencia de anticuerpos dirigidos contra Leptospira en las muestras de síndrome febril del estudio indica que la leptospirosis es una de las causas de este síndrome que el clínico debe explorar.Palabras clave: Leptospira, leptospirosis, enfermedad de Weil, anticuerpos, serología, técnica del anticuerpo fluorescente indirecta. Evaluation of Indirect Inmunofluorescence assay for diagnosis of human leptospirosisIntroduction. The diagnosis of leptospirosis is difficult because it presents an extremely broad spectrum of symptoms. A number of diagnostic serological assays have been developed, but their performance and utility have not been evaluated in Colombia. Objectives. To evaluate the IgM-IgG-indirect inmunofluorescence assay to detect antibodies against Leptospira in human serum samples and to diagnose leptospirosis. Materials and methods. A panel of 19 sera from leptospirosis cases with clinical diagnosis and positive microscopic agglutination test, 40 samples from individuals without history of leptospirosis and negative microscopic agglutination test, and 96 samples from patients with other infectious diseases were evaluated. Results.The sensitivity of the indirect inmunofluorescence assay was 89.47%, its specificity was 100%, the negative predictive value was 95.2% (CI 95% 82.6-99.2), and its positive predictive value was 100%. At the same time an exploratory study of 27 samples from different febrile syndromes, 11% were positive by IgM-indirect inmunofluorescence assay against Leptospira. Con...

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Leptospirosis during Dengue Outbreak, Bangladesh

Cited by 118 publications

References 15 publications

Redefining Gold Standard Testing for Diagnosing Leptospirosis: Further Evidence from a Well-Characterized, Flood-Related Outbreak in Sri Lanka

Redefining Gold Standard Testing for Diagnosing Leptospirosis: Further Evidence from a Well-Characterized, Flood-Related Outbreak in Sri Lanka

Salmonella enterica Serovar Typhi-Specific Immunoglobulin A Antibody Responses in Plasma and Antibody in Lymphocyte Supernatant Specimens in Bangladeshi Patients with Suspected Typhoid Fever

Evaluación de la prueba de inmunofluorescencia indirecta para el diagnóstico de leptospirosis humana.

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