A Diagnostic Scoring Model for Leptospirosis in Resource Limited Settings

Abstract

BackgroundLeptospirosis is a zoonotic infection with significant morbidity and mortality. The clinical presentation of leptospirosis is known to mimic the clinical profile of other prevalent tropical fevers. Laboratory confirmation of leptospirosis is based on the reference standard microscopic agglutination test (MAT), direct demonstration of the organism, and isolation by culture and DNA detection by polymerase chain reaction (PCR) amplification. However these methods of confirmation are not widely available in resource limited settings where the infection is prevalent, and reliance is placed on clinical features for provisional diagnosis. In this prospective study, we attempted to develop a model for diagnosis of leptospirosis, based on clinical features and standard laboratory test results.MethodsThe diagnostic score was developed based on data from a prospective multicentre study in two hospitals in the Western Province of Sri Lanka. All patients presenting to these hospitals with a suspected diagnosis of leptospirosis, based on the WHO surveillance criteria, were recruited. Confirmed disease was defined as positive genus specific MAT (Leptospira biflexa). A derivation cohort and a validation cohort were randomly selected from available data. Clinical and laboratory manifestations associated with confirmed leptospirosis in the derivation cohort were selected for construction of a multivariate regression model with correlation matrices, and adjusted odds ratios were extracted for significant variables. The odds ratios thus derived were subsequently utilized in the criteria model, and sensitivity and specificity examined with ROC curves.ResultsA total of 592 patients were included in the final analysis with 450 (180 confirmed leptospirosis) in the derivation cohort and 142 (52 confirmed leptospirosis) in the validation cohort. The variables in the final model were: history of exposure to a possible source of leptospirosis (adjusted OR = 2.827; 95% CI = 1.517–5.435; p = 0.001) serum creatinine > 150 micromol/l (adjusted OR = 2.735; 95% CI = 1.374–4.901; p = 0.001), neutrophil differential percentage > 80.0% of total white blood cell count (adjusted OR 2.163; 95% CI = 1.309–3.847; p = 0.032), serum bilirubin > 30 micromol/l (adjusted OR = 1.717; 95% CI 0.938–3.456; p = 0.049) and platelet count < 85,000/mm3 (adjusted OR = 2.350; 95% CI = 1.481–4.513; p = 0.006). Hosmer-Lemeshow test for goodness of fit was 0.931. The Nagelkerke R2 was 0.622. The area under the curve (AUC) was noted as 0.762. A score value of 14 reflected a sensitivity of 0.803, specificity of 0.602, a PPV of 0.54, NPV of 0.84, a positive LR of 2.01 and a negative LR of 0.32.ConclusionsThe above diagnostic model for diagnosis of leptospirosis is suggested for use in clinical settings. It should be further validated in clinical practice.

Leptospira interrogans and Leptospira kirschneri are the dominant Leptospira species causing human leptospirosis in Central Malaysia

“…The vast variations in clinical presentations hinder the early accurate diagnosis, hence laboratory confirmation is critically needed to support the manifested signs and symptoms for initiating the treatment. In the present study, 92/165 patients with clinical manifestations suggesting leptospirosis were confirmed https://doi.org/10.1371/journal.pntd.0008197.g001 .07, which is in agreement with several other studies that ranged between 38.9-45 years [23][24][25][26][27]. About two thirds of the patients (n = 60; 65%) were males as observed in most studies [24-26, 28, 29].…”

Leptospirosis: challenges in diagnosis, and predictors of severity

“…13 The following were found to be independently associated with leptospirosis, when compared with other fevers with a similar clinical picture: history of exposure, serum creatinine >150mol/L, neutrophil differential percentage 14 >82.8%, platelet count 14 <85000mm 3 , and serum bilirubin >27U/L (Nagelkerke R square -0.567, Hosmer-Lemeshow test for goodness of fit -chi square = 2.898, p = 0.941). Notably, very few clinical or investigation characteristics reliably differentiate leptospirosis from non-leptospirosis fevers.…”

Jarisch–Herxheimer Reaction Among Patients with Leptospirosis: Incidence and Risk Factors

“…This clinical observation may usefully complete a model recently elaborated for diagnosis of leptospirosis, based on clinical features and standard laboratory test results. 19 Our study has several major limitations. First, the retrospective design exposed to misclassification bias, including patients with early recovery, or compensated severe sepsis, a prospective data collection for our definition would be more rigorous.…”