Volume 91, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Co-infection with pathogens that cause acute febrile illness creates a diagnostic challenge as a result of overlapping clinical manifestations. Here, we describe four fatal cases of species/dengue virus co-infection in Puerto Rico. Although all patients sought care early, antibiotic administration was delayed for most. Steroids were administered to all patients, in most cases before antibiotics. These cases show the need for clinicians evaluating patients in or recently returned from the tropics with acute febrile illness to consider both dengue and leptospirosis. Furthermore, they illustrate the need for nucleic acid- or antigen-based rapid diagnostic tests to enable timely patient diagnosis and management. In particular, antibiotic therapy should be initiated early for patients with suspected leptospirosis, and steroids should not be administered to patients with suspected dengue.


Article metrics loading...

Loading full text...

Full text loading...



  1. World Health Organization, 2009. Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control. Geneva: WHO.
  2. Brandling-Bennet D, Pinheiro F, , 1996. Infectious diseases in Latin America and the Caribbean: are they really emerging and increasing? Emerg Infect Dis 2: 3.[Crossref]
  3. San Martin JL, Brathwaite O, Zambrano B, Solorzano JO, Bouckenooghe A, Dayan GH, Guzman MG, , 2010. The epidemiology of dengue in the Americas over the last three decades: a worrisome reality. Am J Trop Med Hyg 82: 128135.[Crossref]
  4. Bharti AR, Nally JE, Ricaldi JN, Matthias MA, Diaz MM, Lovett MA, Levett PN, Gilman RH, Willig MR, Gotuzzo E, Vinetz JM, , 2003. Leptospirosis: a zoonotic disease of global importance. Lancet Infect Dis 3: 757771.[Crossref]
  5. Levett PN, , 2001. Leptospirosis. Clin Microbiol Rev 14: 296326.[Crossref]
  6. Lam PK, Tam DT, Diet TV, Tam CT, Tien NT, Kieu NT, Simmons C, Farrar J, Nga NT, Qui PT, Dung NM, Wolbers M, Wills B, , 2013. Clinical characteristics of dengue shock syndrome in Vietnamese children: a 10-year prospective study in a single hospital. Clin Infect Dis 57: 15771586.[Crossref]
  7. United States Census Bureau, 2011. American FactFinder. Available at: http://factfinder2.census.gov/faces/nav/jsf/pages/index.xhtml. Accessed January 9, 2012.
  8. Neff JM, Morris L, Gonzalez-Alcover R, Coleman PH, Lyss SB, Negron H, , 1967. Dengue fever in a Puerto Rican community. Am J Epidemiol 86: 162184.[Crossref]
  9. Sharp TM, Hunsperger E, Santiago GA, Munoz-Jordan JL, Santiago LM, Rivera A, Rodriguez-Acosta RL, Gonzalez Feliciano L, Margolis HS, Tomashek KM, , 2013. Virus-specific differences in rates of disease during the 2010 Dengue epidemic in Puerto Rico. PLoS Negl Trop Dis 7: e2159.[Crossref]
  10. Koppisch E, Suarez RM, Kohlschūter E, Hernandez-Morales F, , 1942. Weil's disease in Puerto Rico: report of five cases, one of them with post-mortem findings. PR J Public Health Trop Med 17: 36.
  11. Centers for Disease Control and Prevention, 2012. Investigation of leptospirosis underreporting- Puerto Rico, 2010. Morbidity and Mortality Weekly Report 61: 421.
  12. Sanders EJ, Rigau-Perez JG, Smits HL, Deseda CC, Vorndam VA, Aye T, Spiegel RA, Weyant RS, Bragg SL, , 1999. Increase of leptospirosis in dengue-negative patients after a hurricane in Puerto Rico in 1996 [correction of 1966]. Am J Trop Med Hyg 61: 399404.
  13. Bruce MG, Sanders EJ, Leake JA, Zaidel O, Bragg SL, Aye T, Shutt KA, Deseda CC, Rigau-Perez JG, Tappero JW, Perkins BA, Spiegel RA, Ashford DA, , 2005. Leptospirosis among patients presenting with dengue-like illness in Puerto Rico. Acta Trop 96: 3646.[Crossref]
  14. Karande S, Gandhi D, Kulkarni M, Bharadwaj R, Pol S, Thakare J, De A, , 2005. Concurrent outbreak of leptospirosis and dengue in Mumbai, India, 2002. J Trop Pediatr 51: 174181.[Crossref]
  15. Flannery B, Pereira MM, Velloso L d F, Carvalho C d C, De Codes LG, Orrico G d S, Dourado CM, Riley LW, Reis MG, Ko AI, , 2001. Referral pattern of leptospirosis cases during a large urban epidemic of dengue. Am J Trop Med Hyg 65: 657663.
  16. Dircio Montes Sergio A, Gonzalez Figueroa E, Maria Saadia VG, Elizabeth SH, Beatriz RS, Altuzar Aguilar Victor M, Navarrete Espinosa J, , 2012. Leptospirosis prevalence in patients with initial diagnosis of dengue. J Trop Med 2012: 519701.[Crossref]
  17. Levett PN, Branch SL, Edwards CN, , 2000. Detection of dengue infection in patients investigated for leptospirosis in Barbados. Am J Trop Med Hyg 62: 112114.
  18. Chaudhry R, Pandey A, Das A, Broor S, , 2009. Infection potpourri: are we watching? Indian J Pathol Microbiol 52: 125.[Crossref]
  19. Kaur H, John M, , 2002. Mixed infection due to Leptospira and dengue. Indian J Gastroenterol 21: 206.
  20. Rele MC, Rasal A, Despande SD, Koppikar GV, Lahiri KR, , 2001. Mixed infection due to Leptospira and dengue in a patient with pyrexia. Indian J Med Microbiol 19: 206207.
  21. Behera B, Chaudhry R, Pandey A, Mohan A, Dar L, Premlatha MM, Gupta E, Broor S, Aggarwal P, , 2009. Co-infections due to Leptospira, dengue and hepatitis E: a diagnostic challenge. J Infect Dev Ctries 4: 4850.
  22. Singh RK, Ghatak T, Baronia AK, Garg P, , 2013. Intracranial hemorrhage in a patient coinfected with dengue and leptospirosis. J Neurosci Rural Pract 4: 366367.[Crossref]
  23. Yong LS, Koh KC, , 2013. A case of mixed infections in a patient presenting with acute febrile illness in the tropics. Case Rep Infect Dis 2013: 562175.
  24. Lindo J, Brown PD, Vickers I, Brown M, Jackson ST, Lewis-Fuller E, , 2013. Leptospirosis and malaria as causes of febrile illness during a dengue epidemic in Jamaica. Pathog Glob Health 107: 329334.[Crossref]
  25. Sharp TM, Bracero J, Rivera A, Shieh WJ, Bhatnagar J, Rivera-Diez I, Hunsperger E, Munoz-Jordan J, Zaki SR, Tomashek KM, , 2012. Fatal human co-infection with Leptospira spp. and dengue virus, Puerto Rico, 2010. Emerg Infect Dis 18: 878880.[Crossref]
  26. Stoddard RA, Gee JE, Wilkins PP, McCaustland K, Hoffmaster AR, , 2009. Detection of pathogenic Leptospira spp. through TaqMan polymerase chain reaction targeting the LipL32 gene. Diagn Microbiol Infect Dis 64: 247255.[Crossref]
  27. Dikken H, Kmety E, Bergan T, Norris J, , 1978. Serological typing methods of leptospires. , eds. Methods in Microbiology. London: Academic Press, 259307.
  28. Zaki SR, Shieh WJ, , 1996. Leptospirosis associated with outbreak of acute febrile illness and pulmonary hemorrhage, Nicaragua, 1995. The Epidemic Working Group at Ministry of Health in Nicaragua. Lancet 347: 535536.[Crossref]
  29. Musso D, Scola BL, , 2013. Laboratory diagnosis of leptospirosis: a challenge. J Microbiol Immunol Infect 46: 8.[Crossref]
  30. Brett-Major DM, Coldren R, , 2012. Antibiotics for leptospirosis. Cochrane Database Syst Rev 2: CD008264.
  31. Vinetz JM, , 2003. A mountain out of a molehill: do we treat acute leptospirosis, and if so, with what? Clin Infect Dis 36: 15141515.[Crossref]
  32. Tomashek KM, Gregory CJ, Rivera Sanchez A, Bartek MA, Garcia Rivera EJ, Hunsperger E, Munoz-Jordan JL, Sun W, , 2012. Dengue deaths in Puerto Rico: lessons learned from the 2007 epidemic. PLoS Negl Trop Dis 6: e1614.[Crossref]
  33. Kularatne SA, , 2005. Survey on the management of dengue infection in Sri Lanka: opinions of physicians and pediatricians. Southeast Asian J Trop Med Public Health 36: 11981200.
  34. Rajapakse S, Ranasinghe C, Rodrigo C, , 2010. Corticosteroid therapy in dengue infection—opinions of junior doctors. J Glob Infect Dis 2: 199200.[Crossref]
  35. Panpanich R, Sornchai P, Kanjanaratanakorn K, , 2006. Corticosteroids for treating dengue shock syndrome. Cochrane Database Syst Rev (3): CD003488.
  36. Tam DT, Ngoc TV, Tien NT, Kieu NT, Thuy TT, Thanh LT, Tam CT, Truong NT, Dung NT, Qui PT, Hien TT, Farrar JJ, Simmons CP, Wolbers M, Wills BA, , 2012. Effects of short-course oral corticosteroid therapy in early dengue infection in Vietnamese patients: a randomized, placebo-controlled trial. Clin Infect Dis 55: 12161224.[Crossref]
  37. Tassniyom S, Vasanawathana S, Chirawatkul A, Rojanasuphot S, , 1993. Failure of high-dose methylprednisolone in established dengue shock syndrome: a placebo-controlled, double-blind study. Pediatrics 92: 111115.
  38. Niwattayakul K, Kaewtasi S, Chueasuwanchai S, Hoontrakul S, Chareonwat S, Suttinont C, Phimda K, Chierakul W, Silpasakorn S, Suputtamongkol Y, , 2010. An open randomized controlled trial of desmopressin and pulse dexamethasone as adjunct therapy in patients with pulmonary involvement associated with severe leptospirosis. Clin Microbiol Infect 16: 12071212.[Crossref]

Data & Media loading...

  • Received : 10 Apr 2014
  • Accepted : 26 May 2014

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error