Multi-organ failure, weeks after being exposed to murky water - rule out leptospirosis.

Leptospirosis is a rare zoonotic disease which occurs in people exposed to contaminated water or/and animal urine. We report two cases of moderate to severe leptospirosis. The first case was a healthy middle-aged biology professor who recently visited his family in Jamaica and presented with multi-organ failure. The second case was a 27-year-old police officer who was admitted for acute liver injury and thrombocytopenia after helping people evacuate during a flood/disaster situation.

Case 1

A 51-year-old male, biology professor presented to our emergency department with complaints of subjective fevers, worsening fatigue, abdominal pain, and jaundice. He recently had traveled to Jamaica to visit with family members, stayed there for two weeks and returned back to the USA in January 2017. He, along with family members, went to the beach, swam in the ocean, did some cliff diving and rested under a waterfall which was apparently murky because of a recent storm. He started to feel poorly seven to ten days after coming back from Jamaica with the onset of fatigue, generalized muscle aches, fevers, and night sweats. His symptoms gradually worsened and subsequently he started to have abdominal pain and yellowish discoloration of his skin. Throughout this time, he had been taking acetaminophen and ibuprofen occasionally, but did not feel better. His primary care physician did some basic blood work which revealed hyperbilirubinemia and thrombocytopenia. He waited for five days but as he was no longer able to work he decided to go the hospital for further evaluation.

On physical exam, the patient appeared toxic, uncomfortable, and was restlessly lying on the bed. He was severely jaundiced. Left eye conjunctival suffusion was present. The abdomen was tense, more tender on the right upper quadrant, and had hepatomegaly up to 18 cm. He had no rashes. Neurologically, he had no focal findings.

Some significant initial lab values were: WBC: peaked at 20.82 /UL, hgB: as low as 8.1 gm/dl; platelets: 87 000, serum sodium: lowest 126 mEq/L; creatinine: 1.4 mg/dl; alkaline phosphatase: 184 IU/L, AST: 69 IU/L, ALT 105 IU/L; total bilirubin: 10.4 mg/dl, direct: 8.8 mg/dl; procalcitonin: 2.10 ng/ml. Urinalysis – specific gravity of 1.013; proteinuria: 75 mg/dl on repeated samples and no evidence of urinary tract infection. A CT scan of the abdomen revealed an enlarged liver measuring up to 22 cm in length. No evidence of intrahepatic biliary dilatation was seen on abdominal ultrasound. Patient was admitted and started on intravenous fluids. Given strong suspicion for leptospirosis, he was empirically started on IV penicillin G. Interestingly hyponatremia did not improve on IV fluid resuscitation even though his urine sodium on admission was 14 mEq/l. He was eventually kept on fluid restrictions and a rise in serum sodium levels was noted. His symptoms gradually started to improve on the fifth day of his hospitalization and he was discharged on Day seven on oral penicillin V for four more days.

Leptospira DNA, Qual-PCR came back negative following his discharge. But due to strong suspicion, IgM antibodies were sent as an outpatient, which were positive, confirming our provisional diagnosis of leptospirosis.

Case 2

A 27-year-old police officer without any PMH who was working in standing flood water as part of a flood/disaster relief two weeks earlier presented with two days of vomiting and diarrhea and was found to have thrombocytopenia with a platelet count of 51 000, creatinine of 1.9, and acute liver injury (bilirubin 3.7, AST 137 and ALT 97). Physical exam was remarkable for conjunctival suffusion. Initial diagnostic workup which included hepatitis panel, blood and stool cultures, monoscreen, legionella IgM (Ag and Ab), and Anaplasma IgM and IgG were negative. A CT Scan was remarkable for hepatomegaly (22 cm) and splenomegaly (13 cm). US abdomen was negative for any biliary duct dilatation. He was started on Doxycycline while waiting for leptospira DNA PCR to come back, given the high suspicion for leptospirosis. The patient improved clinically and was discharged. On follow up, leptospira DNA PCR was reported positive.

Discussion

Leptospirosis is a zoonotic disease caused by pathogenic spirochetes of the genus Leptospira. Over 350 000 cases of leptospirosis are estimated to occur each year worldwide and are generally underreported. In the USA, around 100 to 200 leptospirosis cases are identified each year. Leptospira frequently infects wild and domestic mammals. Humans are infected directly by contact with infected animals or indirectly through contact with urine-contaminated soil or water. Disease severity ranges from mild and self-limiting to severe with life-threatening manifestations, including massive pulmonary hemorrhage and Weil’s syndrome (the triad of jaundice, acute renal failure, and bleeding) [1].

Leptospirosis has two main clinical phases. The first phase is a septicemic phase which is characterized by fever, myalgia, headache, fever, and conjunctival suffusion (seen in both our cases). The second phase is an immunological phase during which organ damage occurs. Our cases had classical presentation of leptospirosis presenting with jaundice, thrombocytopenia, hyponatremia (Case 1 only), acute renal failure, and conjunctival suffusion. Hyponatremia is caused after the leptospira inhibits the Na-K-Cl cotransporter in the loop of Henle, leading to a potassium and sodium wasting. In case 1, the patient had environmental exposure likely from water (including turbulent muddy water) during his recent visit to Jamaica. In case 2, the patient had exposure to contaminated water during floods while helping evacuate people. Another case diagnosed with leptospirosis was reported in 2011, after exposure to Baltimore alley rats [2].

ELISA allows detection of specific IgM class antibodies. IgM may remain detectable for several months or even years. The need for rapid diagnostics at the time of admission has led to the development of numerous PCR assays. The advantage lies in the ability to obtain a definitive diagnosis during the acute stage of the illness prior to antibodies being detected [3]. PCR detects DNA in blood in the first five to ten days after the onset of the disease and can be detected up till the 15th day [4]. Our hypothesis is that case 1 presented to the hospital after two weeks of the onset of disease which explains why the patient was negative for PCR and positive for IgM ELISA. Case 2 patient presented within days of onset of symptoms and thus PCR was positive. Next generation sequencing was used in one case to diagnose neuro-leptospirosis when PCR and ELISA were negative.

Most cases of leptospirosis are self-limiting and do not require admission. Our first case was treated with penicillin 1.5 million units IV every six hours, while our second case was treated with IV doxycycline 100 mg IV every 12 hours. Both patients showed clinical improvement 24 hours after starting antibiotics. Many authors prefer doxycycline over penicillin, especially when suspicion for leptospirosis is high but rickettsial disease cannot be ruled out [5].

According to the CDC, around 100–200 cases of leptospirosis are diagnosed in US yearly. Most of these cases are from Hawaii. Many of these cases are return travelers from endemic countries but some cases are seen during floods or incidental exposure to animal urine or contaminated water. These cases are more difficult to diagnose given low suspicion and prevalence. A detailed history focusing on recent travel and in identifying risk factors could suggest such exposure, along with some specific clinical findings like conjunctival suffusion, can give an important clue towards the diagnosis. Case 2 is an example of this disease affecting first responders during floods and raises the question for the need of protection/prophylaxis during such disaster situations.