title: A Diagnostic Scoring Model for Leptospirosis in Resource Limited Settings.
abstract: Leptospirosis 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.
  
  
  
  The 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.
  
  
  
  A 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.
  
  
  
  The above diagnostic model for diagnosis of leptospirosis is suggested for use in clinical settings. It should be further validated in clinical practice.
authors.affiliation: Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Sri Lanka.
authors.forename: Senaka
authors.initials: S
authors.lastname: Rajapakse
authors.affiliation: University Medical Unit, National Hospital of Sri Lanka, Colombo.
authors.forename: Praveen
authors.initials: P
authors.lastname: Weeratunga
authors.affiliation: Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Sri Lanka.
authors.forename: Roshan
authors.initials: R
authors.lastname: Niloofa
authors.affiliation: Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Sri Lanka.
authors.forename: Narmada
authors.initials: N
authors.lastname: Fernando
authors.affiliation: Sir John Kotelawala Defence University, Sri Lanka.
authors.forename: Nipun Lakshitha
authors.initials: NL
authors.lastname: de Silva
authors.affiliation: Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Sri Lanka.
authors.forename: Chaturaka
authors.initials: C
authors.lastname: Rodrigo
authors.affiliation: Ministry of Health, Sri Lanka.
authors.forename: Sachith
authors.initials: S
authors.lastname: Maduranga
authors.affiliation: Ministry of Health, Sri Lanka.
authors.forename: Nuwanthi
authors.initials: N
authors.lastname: Nandasiri
authors.affiliation: Department of Zoology, Faculty of Science, University of Colombo, Sri Lanka.
authors.forename: Sunil
authors.initials: S
authors.lastname: Premawansa
authors.affiliation: Medical Research Institute, Colombo, Sri Lanka.
authors.forename: Lilani
authors.initials: L
authors.lastname: Karunanayake
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka.
authors.forename: H Janaka
authors.initials: HJ
authors.lastname: de Silva
authors.affiliation: Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Sri Lanka.
authors.forename: Shiroma
authors.initials: S
authors.lastname: Handunnetti
mesh_terms: D000328:Adult; D000818:Animals; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D019411:Clinical Laboratory Techniques; D005260:Female; D006801:Humans; D007922:Leptospirosis / Q000175:diagnosis* / Q000473:pathology*; D008297:Male; D016017:Odds Ratio; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013188:Sri Lanka / Q000453:epidemiology; D015047:Zoonoses
chemical_list: D015415:Biomarkers