The non-linear and lagged short-term relationship between rainfall and leptospirosis and the intermediate role of floods in the Philippines.

BACKGROUND: Leptospirosis is a worldwide bacterial zoonosis. Outbreaks of leptospirosis after heavy rainfall and flooding have been reported. However, few studies have formally quantified the effect of weather factors on leptospirosis incidence. We estimated the association between rainfall and leptospirosis cases in an urban setting in Manila, the Philippines, and examined the potential intermediate role of floods in this association. METHODS/PRINCIPAL FINDINGS: Relationships between rainfall and the weekly number of hospital admissions due to leptospirosis from 2001 to 2012 were analyzed using a distributed lag non-linear model in a quasi-Poisson regression framework, controlling for seasonally varying factors other than rainfall. The role of floods on the rainfall-leptospirosis relationship was examined using an indicator. We reported relative risks (RRs) by rainfall category based on the flood warning system in the country. The risk of post-rainfall leptospirosis peaked at a lag of 2 weeks (using 0 cm/week rainfall as the reference) with RRs of 1.30 (95% confidence interval: 0.99-1.70), 1.53 (1.12-2.09), 2.45 (1.80-3.33), 4.61 (3.30-6.43), and 13.77 (9.10-20.82) for light, moderate, heavy, intense and torrential rainfall (at 2, 5, 16, 32 and 63 cm/week), respectively. After adjusting for floods, RRs (at a lag of 2 weeks) decreased at higher rainfall levels suggesting that flood is on the causal pathway between rainfall and leptospirosis. CONCLUSIONS: Rainfall was strongly associated with increased hospital admission for leptospirosis at a lag of 2 weeks, and this association was explained in part by floods.

Diagnostic Accuracy of Recombinant Immunoglobulin-like Protein A-Based IgM ELISA for the Early Diagnosis of Leptospirosis in the Philippines.

BACKGROUND: Leptospirosis is an important but largely under-recognized public health problem in the tropics. Establishment of highly sensitive and specific laboratory diagnosis is essential to reveal the magnitude of problem and to improve treatment. This study aimed to evaluate the diagnostic accuracy of a recombinant LigA protein based IgM ELISA during outbreaks in the clinical-setting of a highly endemic country. METHODOLOGY/PRINCIPAL FINDINGS: A prospective study was conducted from October 2011 to September 2013 at a national referral hospital for infectious diseases in Manila, Philippines. Patients who were hospitalized with clinically suspected leptospirosis were enrolled. Plasma and urine were collected on admission and/or at discharge and tested using the LigA-IgM ELISA and a whole cell-based IgM ELISA. Sensitivity and specificity of these tests were evaluated with cases diagnosed by microscopic agglutination test (MAT), culture and LAMP as the composite reference standard and blood bank donors as healthy controls: the mean+3 standard deviation optical density value of healthy controls was used as the cut-off limit (0.062 for the LigA-IgM ELISA and 0.691 for the whole cell-based IgM ELISA). Of 304 patients enrolled in the study, 270 (89.1%) were male and the median age was 30.5 years; 167 (54.9%) were laboratory confirmed. The sensitivity and ROC curve AUC for the LigA-IgM ELISA was significantly greater than the whole cell-based IgM ELISA (69.5% vs. 54.3%, p<0.01; 0.90 vs. 0.82, p<0.01) on admission, but not at discharge. The specificity of LigA-IgM ELISA and whole cell-based IgM ELISA were not significantly different (98% vs. 97%). Among 158 MAT negative patients, 53 and 28 were positive by LigA- and whole cell-based IgM ELISA, respectively; if the laboratory confirmation was re-defined by LigA-IgM ELISA and LAMP, the clinical findings were more characteristic of leptospirosis than the diagnosis based on MAT/culture/LAMP. CONCLUSIONS/SIGNIFICANCE: The newly developed LigA-IgM ELISA is more sensitive than the whole cell-based IgM based ELISA. Although the final diagnosis must be validated by more specific tests, LigA-IgM ELISA could be a useful diagnostic test in a real clinical-setting, where diagnosis is needed in the early phase of infection.