Pathogen-specific leptospiral proteins in urine of patients with febrile illness aids in differential diagnosis of leptospirosis from dengue

Chaurasia, Reetika; Thresiamma, K C; Eapen, Charu; Zachariah, B. J.; Paul, Regi; Sritharan, Manjula

doi:10.1007/s10096-018-3187-9

Cited by 17 publications

(16 citation statements)

References 42 publications

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“…Clinical diagnosis of leptospirosis is also nonspecific mimicking other common infections, including dengue and malaria, which require further laboratory confirmation (Chaurasia et al 2018). In several places, including Brazil, Hawaii, Korea, New Caledonia, and Seychelles, Plank and Dean (2000) reported that common leptospirosis manifestations were fever, myalgia, headache, jaundice, and conjunctival suffusion.…”

Section: Introductionmentioning

confidence: 99%

Significant Clinical Presentation of Leptospirosis in Relation to Sociodemographic and Risk Factors in a Tertiary Hospital, Malaysia

Taib

Ahmad

Soh

et al. 2020

Vector-Borne and Zoonotic Diseases

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Introduction: Incidence of leptospirosis has increased within the past few years in many countries. Its clinical presentations were generally nonspecific, making it difficult to assist in the diagnosis. Besides the determination of the common clinical features, the sociodemographic background is essential to identify high-risk populations to assist in prevention. Methods: Data for this study were obtained from electronic medical records among patients clinically diagnosed with leptospirosis at a tertiary hospital in Malaysia from the years 2011 to 2015 and were recorded using standard pro forma. Associations between clinical features and sociodemographics were performed using bivariate analysis and logistic regression. Results: Data were collected from 283 patients. Their mean age was 30.71 years old. Out of 283 patients, 206 (72.8%) were male. Involvement in outdoor events and water activities was the highest risk factor of acquiring leptospirosis in 64 (22.7%) patients followed by 59 (20.8%) patients who were staying in crowded housing areas with poor sanitation. Although fever was the main clinical presentation in 274 (96.8%) patients with leptospirosis, gastrointestinal (GIT) symptoms were the second most frequent in 159 (56.2%) patients followed by pulmonary symptoms, myalgia, headache, and jaundice. From the total number of 283 patients, only 21 (92.6%) presented with severe leptospirosis. GIT symptoms were a significant predictor for leptospirosis severity, while the age group was the significant sociodemographic factor toward GIT presentation in leptospirosis. The relationship between GIT symptoms and crowded housing areas with poor sanitation was also significant. Multivariable logistic regression showed that crowded housing areas with poor sanitation (odds ratio [OR] = 3.570, p < 0.001) and age between 20 and 40 years old (OR = 2.056, p = 0.014) were more likely to have GIT symptoms. Conclusions: Information regarding the clinical features of leptospirosis to the public is necessary, while targeted prevention by educational outreach among 20-40 year olds especially those participating in outdoor water activities are crucial to decrease the incidence and complications of leptospirosis.

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Section: Introductionmentioning

confidence: 99%

Significant Clinical Presentation of Leptospirosis in Relation to Sociodemographic and Risk Factors in a Tertiary Hospital, Malaysia

Taib

Ahmad

Soh

et al. 2020

Vector-Borne and Zoonotic Diseases

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“…Because an RDT capable of diagnosing leptospirosis using urine will be useful in remote health centres and large outbreaks situations, several studies have focused on the urine by targeting structural leptospiral antigens, such as lipopolysaccharides [10] ; outer membrane proteins LigA [11] , LipL32 [21] or DNA [22] . More recently, Chaurasia et al., detected additional pathogen specific antigens (LipL41, Fla1, HbpA and sphingomielinase) in the urine of leptospirosis patients collected in Kerala, India [23] . These antigens were also detected in patients with pyrexia of unknown origin with MAT-negative results.…”

Section: Discussionmentioning

confidence: 99%

Leptospiral 3-hydroxyacyl-CoA dehydrogenase as an early urinary biomarker of leptospirosis

Toma

Koizumi

Kakita

et al. 2018

Heliyon

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Leptospirosis, caused by spirochetes of the genus Leptospira, is a globally widespread, neglected and emerging zoonotic disease. The currently used diagnostic tests are time-consuming, require technical expertise or require the use of sophisticated equipment. Clinicians have pointed out the urgent need to develop a rapid test for the diagnosis of acute leptospirosis with a non-invasive and easy sampling method. In this study, we have focused on a leptospiral enzyme, 3-hydroxyacyl-CoA dehydrogenase (3-HADH), as a urinary biomarker of acute leptospirosis. A specific antiserum for pathogenic Leptospira spp. was produced, targeting a peptide corresponding to amino acids 410 to 424 of 3-HADH. The antiserum was used to investigate whether 3-HADH is excreted in the urine by Western blotting. Among 70 suspected leptospirosis patients, 40 were laboratory confirmed by microscopic agglutination test (MAT) using paired sera samples and/or polymerase chain reaction (PCR). In the acute phase of the laboratory-confirmed leptospirosis cases, sensitivity for 3-HADH, blood PCR and urine PCR were 52.5%, 57.5% and 12%, respectively. 3-HADH was detected from 2 days post-onset of illness (p.o) and could be detected at least until 9 days p.o. The combination of PCR and 3-HADH detection increased sensitivity of diagnosis to 100% in samples collected between 1 and 3 days p.o., and to 82% in samples collected between 4 and 9 days p.o. Our results suggested that the detection of 3-HADH can support a clinical diagnosis of leptospirosis, especially when serological methods are negative during the acute phase.

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“…L. interrogans expresses sph2 in dialysis membrane chambers implanted into 41 the peritoneal cavity of rats. Additionally, antisera raised against Sph2 detects antigen in kidney 42 sections from acutely-infected hamsters (11) and in urine obtained from leptospirosis patients 43 (12). Sph2 may contribute to the pathogenesis of leptospirosis by adhering to fibronectin, 44 inducing apoptosis of host cells, and triggering the production of proinflammatory cytokines (13-45 16).…”

Section: Introduction 29mentioning

confidence: 99%

Identification of a cis-acting determinant limiting expression of sphingomyelinase genesph2inLeptospira interroganswith agfpreporter plasmid

Matsunaga

Haake

2018

Preprint

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1Many Pomona strains of the spirochete Leptospira interrogans express the osmotically-2 inducible sphingomyelinase gene, sph2, at much higher levels than non-Pomona strains. We 3 developed a new green fluorescent protein (GFP) reporter plasmid to examine sph2 gene 4 expression determinants. The vector allows fusion of the test promoter to the ribosome-binding 5 site and coding region of gfp. We fused the sph2 promoters from the serovar Lai strain 56601 6 and from the serovar Pomona strain LC82-25 to gfp to examine the molecular determinants of 7 differential sph2 expression between the two strains. Similar to what is observed with the native 8 sph2 genes, introduction of the plasmids into the Lai 56601 strain resulted in near background 9 levels of gfp expression from the Lai sph2 promoter, while expression from the Pomona sph2 10 promoter was high. Expression from both fusions increased at physiologic levels of osmolarity 11 achieved by addition of sodium chloride to the culture medium. We examined the role of a 17 12 bp upstream element found in all L. interrogans strains expressing low basal levels of sph2 and 13 missing from Pomona strains that express sph2 at high levels. When the 17 bp sequence 14 present upstream of the Lai sph2 promoter was deleted or scrambled, fusion expression 15 increased substantially. Conversely, insertion of the 17 bp sequence upstream of the Pomona 16 sph2 promoter diminished fusion expression. In contrast, removal of an insertion sequence-like 17 element that is found only in the Pomona sph2 upstream sequence had no effect on expression 18 from the Pomona sph2 fusion in the Lai strain. These findings demonstrate the utility of the gfp 19 reporter plasmid in analyzing gene expression in L. interrogans. 20 21 IMPORTANCE 22Genetic tools are needed to examine gene expression in the pathogen Leptospira 23 interrogans. We developed a reporter plasmid that replicates in L. interrogans with green 24 fluorescent protein (GFP) as the read out of promoter activity. We demonstrated an application 25 of the new reporter plasmid by identifying an upstream element responsible for the poor basal 26 3 expression of the sph2 sphingomyelinase gene in a serovar Lai strain of L. interrogans. This 27 new tool is useful for discovery of the molecular determinants of L. interrogans gene expression. 28

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Pathogen-specific leptospiral proteins in urine of patients with febrile illness aids in differential diagnosis of leptospirosis from dengue

Cited by 17 publications

References 42 publications

Significant Clinical Presentation of Leptospirosis in Relation to Sociodemographic and Risk Factors in a Tertiary Hospital, Malaysia

Significant Clinical Presentation of Leptospirosis in Relation to Sociodemographic and Risk Factors in a Tertiary Hospital, Malaysia

Leptospiral 3-hydroxyacyl-CoA dehydrogenase as an early urinary biomarker of leptospirosis

Identification of a cis-acting determinant limiting expression of sphingomyelinase genesph2inLeptospira interroganswith agfpreporter plasmid

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