Clinical spectrum of pulmonary involvement in leptospirosis in a region of endemicity, with quantification of leptospiral burden

Abstract

Background: Pulmonary involvement in leptospirosis remains poorly recognized in regions where it is endemic, despite reports of recent outbreaks and epidemic disease.

Methods: A prospective, population-based study was carried out to identify febrile patients exposed to Leptospira in urban and rural contexts in Iquitos, Peru. Evidence of exposure to Leptospira was obtained by serologic testing, and diagnosis of leptospirosis was confirmed in pulmonary cases by culture or quantitative real-time PCR assay.

Results: Of 633 consecutively enrolled febrile patients, 321 (50.7%) had antileptospiral IgM antibodies or high titers of antileptospiral antibodies. Seven patients with histories of only urban exposure to leptospires had severe pulmonary manifestations; of these, 5 patients died; 4 of the deaths were caused by pulmonary hemorrhage, and 1 was caused by acute respiratory distress syndrome and multiorgan failure. Real-time, quantitative PCR assay showed high levels of leptospiremia (>or=10(4) leptospires/mL) in most fatal cases; 1 patient, from whom tissue specimens were obtained at autopsy, had >or=10(5) leptospires/g of lung, kidney, and muscle tissue. DISCUSSION. This study demonstrates the underdiagnosis of leptospirosis in a region of high endemicity and the underrecognition of grave pulmonary complications. Pulmonary involvement in leptospirosis was present in urban but not rural areas. Presumptive treatment for leptospirosis should be initiated immediately in the appropriate epidemiological and clinical context.

Figure 1

Chest radiograph (top) and gross appearance of right lower lung (bottom) from patient 4, a 19-year-old man who died from leptospiral pulmonary hemorrhage. The chest radiograph shows diffuse, patchy, alveolar infiltrates with a lower-lobe predominance. The right lower lung was extensively hemorrhagic and friable; the portion shown was obtained through the diaphragm through a peri-umbilical incision because only a partial necropsy was authorized.

Figure 2

Quantification of the leptospiral burden in 7 patients with severe pulmonary manifestations of leptospirosis. Patient numbers correspond to patient descriptions in table 2. Bars show the number of leptospires per milliliter of serum or urine, or (e.g. patient 4) per g of tissue obtained at autopsy, as determined by a real-time polymerase chain reaction assay (see Materials and Methods). The line connecting the data points for patient 6 represents sequential urine samples. D, day; †, fatal case.