Research Article: Fatal Leptospira spp./Zika Virus Coinfection—Puerto Rico, 2016

Date Published: October 11, 2017

Publisher: The American Society of Tropical Medicine and Hygiene

Author(s): Paige Neaterour, Aidsa Rivera, Renee L. Galloway, Myriam Garcia Negrón, Brenda Rivera-Garcia, Tyler M. Sharp.


Coinfection with pathogens that cause acute febrile illness (AFI) can complicate patient diagnosis and management. This report describes a fatal case of Leptospira spp./Zika virus (ZIKV) coinfection in Puerto Rico. The patient presented with a 5-day history of AFI; reported behavioral risk factors for leptospirosis; was diagnosed with possible leptospirosis, dengue, chikungunya, or ZIKV disease; and received appropriate treatment for leptospirosis and dengue. Following a 3-day hospitalization, the patient died due to acute gastrointestinal hemorrhage, and kidney and liver failure. Serologic diagnostic testing for leptospirosis and ZIKV disease was negative; however, molecular diagnostic testing performed postmortem was positive for detection of Leptospira spp. and ZIKV nucleic acid. This case demonstrates the need for continued clinical awareness of leptospirosis in areas experiencing outbreaks of pathogens that cause AFI and the need for evaluation of coinfection with AFI-causing pathogens as a risk factor for increased severity of disease.

Partial Text

Co-circulation of pathogens that cause acute febrile illness (AFI) complicates clinical diagnosis of patients, which can result in delays in initiating lifesaving medical interventions.1,2 Leptospirosis is a tropical AFI that is the result of infection with Leptospira species bacteria, which are spread through contact with the urine of infected animals including rodents, dogs, cattle, pigs, and sheep.3 Risk factors for infection with Leptospira spp. bacteria include exposure to open sewers and contaminated water, and close contact with rats or other animals.3 Common manifestations of leptospirosis include fever, headache, myalgia, vomiting, and thrombocytopenia.4 Roughly 10% of patients with leptospirosis will progress to life-threatening manifestations including pulmonary and gastrointestinal hemorrhage, and renal and hepatic failure.4 The annual worldwide burden of leptospirosis is estimated to exceed 1 million cases and 58,000 deaths.5 Recommended management of patients with suspected leptospirosis focuses on early administration of antibiotics, which can be lifesaving.1,2

In July 2016, a 48-year-old obese (body mass index = 31.2) male with no significant past medical history presented to the emergency department with a 5-day history of subjective fever, nausea and vomiting, diarrhea, headache, and myalgia. The patient denied the use of home medications, and reported growing banana plants at home, household exposure to rats, and exposure to a stray dog. On evaluation, the patient was afebrile, tachycardic (heart rate = 112 beats per minute), and normotensive (blood pressure [BP] = 111/74 mmHg). Physical examination was notable for scleral icterus and jaundice. Initial laboratory results revealed thrombocytopenia and elevated serum creatinine (Figure 1). The patient was given intravenous (IV) fluids, ranitidine, and promethazine, oral acetaminophen, and admitted to the hospital with a differential diagnosis of dengue, Zika, leptospirosis, and chikungunya.

This case demonstrates the importance for providers in Puerto Rico and throughout the tropics to be aware of the possibility of coinfection with the multiple pathogens that cause AFI, including Leptospira spp. and ZIKV. The patient described herein experienced a disease course consistent with severe leptospirosis including gastrointestinal hemorrhage and hepatic and renal failure.4 Although the patient did not demonstrate rash, which is a common sign of ZIKV disease,6 the proportion of patients with ZIKV infection who experience fever, myalgia, and headache in the absence of rash has varied between reports.12 Nonetheless, we cannot rule out that the patient was asymptomatically infected with ZIKV and that all observed signs and symptoms were attributable to infection with Leptospira spp. bacteria. Similarly, although the CT values corresponding to detection of Leptospira spp. and ZIKV nucleic acid observed in the patient’s serum specimen were within expected ranges, we cannot rule out the possibility of ZIKV infection altering the patient’s immune response to result in increased bacteremia or vice versa. Overall, it is difficult to confidently assess the relative contribution of ZIKV infection to the patient’s clinical course or fatal outcome.




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