Date Published: December 26, 2007
Publisher: Public Library of Science
Author(s): Daniel H. Libraty, Khin S. A. Myint, Clinton K. Murray, Robert V. Gibbons, Mammen P. Mammen, Timothy P. Endy, Wenjun Li, David W. Vaughn, Ananda Nisalak, Siripen Kalayanarooj, Duane R. Hospenthal, Sharone Green, Alan L. Rothman, Francis A. Ennis, Mathieu Picardeau
Abstract: BackgroundLeptospirosis is an emerging zoonosis that is often under-recognized in children and commonly confused with dengue in tropical settings. An enhanced ability to distinguish leptospirosis from dengue in children would guide clinicians and public health personnel in the appropriate use of limited healthcare resources.Methodology/Principal FindingsWe conducted a prospective, hospital-based, study of children with acute febrile illnesses and dengue in Thailand. Among the children without dengue, we identified those with leptospirosis using anti-leptospira IgM and microscopic agglutination titers in paired acute and convalescent blood samples. We then performed a case-control comparison of symptoms, signs, and clinical laboratory values between children with leptospirosis and dengue.In a semi-rural region of Thailand, leptospirosis accounted for 19% of the non-dengue acute febrile illnesses among children presenting during the rainy season. None of the children with leptospirosis were correctly diagnosed at the time of hospital discharge, and one third (33%) were erroneously diagnosed as dengue or scrub typhus. A predictive model to distinguish pediatric leptospirosis from dengue was generated using three variables: the absolute neutrophil count, plasma albumin, and aspartate aminotransferase levels in the first 72 hours of illness.Conclusions/SignificanceUnrecognized leptospirosis can be a significant cause of “dengue-like” febrile illness in children. Increased awareness of pediatric leptospirosis, and an enhanced ability to discriminate between leptospirosis and dengue early in illness, will help guide the appropriate use of healthcare resources in often resource-limited settings.
Partial Text: Leptospirosis is an increasingly recognized cause of acute febrile illness throughout the tropical and sub-tropical regions of the world. Spirochetal infection with Leptospira sp. typically occurs when water or soil contaminated with the urine of an infected animal comes in contact with human skin or mucous membranes ,. The clinical manifestations of leptospirosis range from a mild self-limited febrile illness to a severe and potentially fatal illness characterized by jaundice, renal failure, thrombocytopenia, and hemorrhage (Weil’s disease). Early in illness, leptospirosis is often indistinguishable from other common causes of acute febrile illnesses in the tropics- e.g. dengue, malaria, scrub typhus, typhoid, and others ,. Children in particular often bear the brunt of these tropical diseases, and pose the greatest diagnostic challenges to clinicians. In the pediatric population, leptospirosis and dengue often have similar clinical manifestations and are among the most common diagnostic dilemmas. Both typically occur during the rainy season, and rapid laboratory confirmation of the infecting pathogen is generally not available. Several studies have shown that leptospirosis is often confused with dengue and under-diagnosed in endemic regions –.
Leptospirosis in children is often under-diagnosed, especially in those who do not present with the severe icteric form of disease. In a semi-rural region of north central Thailand, we found that leptospirosis accounted for at least 6% of all acute undifferentiated febrile illnesses, and 19% of the non-dengue illnesses, among children presenting to hospital during the rainy season. As expected, the prevalence of leptospirosis was much lower in the metropolitan environment of Bangkok. We used the PanBio IgM ELISA to screen for leptospirosis in well-timed acute and convalescent blood samples, and performed MAT on any equivocal or positive samples. It is unlikely that a large number of leptospirosis cases were missed, since the sensitivity of the PanBio IgM ELISA as used in this study has been reported as high (76–90%) ,. Some characteristics of the children we identified with leptospirosis were similar to what has been previously reported. There was a male predominance, cases peaked during times of flooding (i.e. late rainy season), and illness was generally less severe than what is typically reported in adults –. Our cohort of children with leptospirosis had self-limited and even milder disease than what has been reported from studies of pediatric leptospirosis in Brazil, Reunion Island, and India –,,. One reason may be differences in the predominant circulating Leptospira serovars. Serovars that have been reported to be associated with severe illness in children are Icterhemorrhagiae, Copenhageni, Canicola, and Sejroe ,. In our cohort of Thai children with leptospirosis, we noted predominant seroreactivity to serovars Autumnalis and Andamana (serogroups Autumnalis and Andamana, respectively). However, others have reported different serovar associations with disease severity  or none at all . Another reason for the mild disease seen here could be the slightly younger age distribution of the children in our study. An age-dependent association with the severity and case-fatality rate of leptospirosis has been observed across many regions of the world ,. Host factors that may contribute to this association could include higher organism loads with increasing age, or age-dependent changes in innate and adaptive immune responses to leptospiral infection. Finally, 39% of the children received antibiotics, but not because leptospirosis was suspected. We cannot determine if early antibiotic therapy played a role in ameliorating the severity of some pediatric leptospiral disease.