Early Indicators of Fatal Leptospirosis during the 2010 Epidemic in Puerto Rico

Abstract

Background: Leptospirosis is a potentially fatal bacterial zoonosis that is endemic throughout the tropics and may be misdiagnosed as dengue. Delayed hospital admission of leptospirosis patients is associated with increased mortality.

Methodology/principal findings: During a concurrent dengue/leptospirosis epidemic in Puerto Rico in 2010, suspected dengue patients that tested dengue-negative were tested for leptospirosis. Fatal and non-fatal hospitalized leptospirosis patients were matched 1:1-3 by age. Records from all medical visits were evaluated for factors associated with fatal outcome. Among 175 leptospirosis patients identified (4.7 per 100,000 residents), 26 (15%) were fatal. Most patients were older males and had illness onset during the rainy season. Fatal case patients first sought medical care earlier than non-fatal control patients (2.5 vs. 5 days post-illness onset [DPO], p < 0.01), but less frequently first sought care at a hospital (52.4% vs. 92.2%, p < 0.01). Although fatal cases were more often diagnosed with leptospirosis at first medical visit (43.9% vs. 9.6%, p = 0.01), they were admitted to the hospital no earlier than non-fatal controls (4.5 vs. 6 DPO, p = 0.31). Cases less often developed fever (p = 0.03), but more often developed jaundice, edema, leg pain, hemoptysis, and had a seizure (p ≤ 0.03). Multivariable analysis of laboratory values from first medical visit associated with fatal outcome included increased white blood cell (WBC) count with increased creatinine (p = 0.001), and decreased bicarbonate with either increased WBC count, increased creatinine, or decreased platelet count (p < 0.001).

Conclusions/significance: Patients with fatal leptospirosis sought care earlier, but were not admitted for care any earlier than non-fatal patients. Combinations of routine laboratory values predictive of fatal outcome should be considered in admission decision-making for patients with suspected leptospirosis.

Fig 1. Date of illness onset of fatal (n = 26) and non-fatal (n = 147) leptospirosis patients identified in Puerto Rico, 2010*.

*If date of illness onset was unavailable, date of first specimen collection was used instead. Two non-fatal patients had no available date of illness onset or date of specimen collection.

Fig 2. Age group of fatal (n = 26) and non-fatal (n = 146*) leptospirosis patients in Puerto Rico, 2010.

Red bars represent fatal laboratory-positive (n = 21) and suspected (n = 5) leptospirosis patients; blue bars represent non-fatal probable (n = 58) and confirmed (n = 88) leptospirosis patients. *age was unavailable for 1 non-fatal patient.

Fig 3. Rate of leptospirosis patients (N = 155*) and number of fatal patients (n = 26) by municipality of residence, Puerto Rico, 2010.

Rates were calculated by dividing case numbers by municipality-specific populations, and grouped by quintile. *municipality of residence was unavailable for 18 non-fatal patients

Fig 4. Box plots of selected laboratory values of fatal (n = 21) and non-fatal (n = 52) leptospirosis patients included in a case-control study, Puerto Rico, 2010.

Medical records from all health care visits were abstracted, and first and worst laboratory values (S4 Table) were compared. The median value is indicated by the horizontal line within each box; mean value is indicated by the diamond; 25^th and 75^th interquartile range (IQR) are indicated by the bottom and top edges of the box, respectively; whiskers indicate the range of values within 1.5 times the value of the IQR. P values indicate statistical significant differences between fatal and non-fatal patients. Shaded horizontal lines indicate normal reference laboratory values.