Abstract

Leptospirosis, an infection of worldwide distribution, has come to international attention as a re-emerging infectious disease. It is caused by spirochetes of the genus Leptospira, which infect most of the domestic and wild animals and spread to humans by the infected urine of animals. Patients with leptospirosis may present with acute febrile illness to life-threatening multiorgan failure. Here we present the case of a 25-year-old female with fever, jaundice and altered sensorium, admitted as a case of sepsis with multiple organ dysfunction syndrome who was later diagnosed as a case of leptospirosis.

Case Report

A 25-year-old female presented with complaints of fever for 7 days; there was continuous high-grade fever, nochills or rigor, with generalized body pain. Patient had altered sensorium since 1 day. Patient had one episode of seizure (generalized tonic-clonic seizure [GTCS]) with frothing from mouth and post-ictal confusion a few hours prior to admission in the hospital. There was no history of vomiting or cough with expectoration.

No history of decreased urine output or abdominal pain was given. Patient was not a diabetic and had no history of pulmonary tuberculosis in the past. Patient was married, had 2 children and had no menstrual irregularities at present. On examination, patient was irritable, not obeying oral commands, responded to pain. Patients general physical examination revealed patient febrile - 100.6°F with pallor++; icterus+ and subconjunctival hemorrhage. Pulse - 126/min and regular; blood pressure (BP) -100/60 mmHg; cardiac examination - normal; respiratory system - patient tachypneic, normal vesicular breath sounds present with scattered crepitations and per abdomen - soft, hepatomegaly present. Central nervous system - patient had altered sensorium, agitated, responded to pain, moved all limbs, reflexes diminished bilaterally and bilateral plantars extensor. Bilateral pupils equal and reacting to light and terminal neck rigidity was present. Patient was admitted with the provisional diagnosis of meningitis with multiorgan dysfunction syndrome and was evaluated. Her complete hemogram revealed anemia with hemoglobin - 9.9 g/dL, total leukocyte count - 8,400/mm3, differential count: polymorphs - 67% and lymphocytes -24%, with severe thrombocytopenia – platelets 24,000/mm3. She had hypoglycemia with random blood glucose of 60 mg/dL. Her renal function tests and serum electrolytes were normal. Her liver function was deranged: total bilirubin - 4.6 mg/dL, SGOT - 430 IU/L,SGPT - 190 IU/L, ALP - 190 IU/L, total protein -7.0 g/dL and albumin - 3.7 g/dL. Her urine examination showed microalbuminuria with plenty of RBCs and hemogranular casts suggestive of acute tubular necrosis. Arterial blood gas analysis revealed metabolic acidosis. ECG showed sinus tachycardia but was otherwise normal and chest X-ray revealed increased bronchovascular markings.

Patient was started on intravenous (IV) fluids, Ryle’stube feeding, nasal O2, antipyretics and IV antibiotics (injection ceftriaxone 1 g IV b.i.d. and injection vancomycin 1 g IV b.i.d.). Treatment was continued with glucose and platelet monitoring in intensive care unit. Since, patient had altered sensorium, a computed tomography (CT) brain was done that showed multiple small calcifications, but was otherwise normal. Alumbar puncture was done for cerebrospinal fluid (CSF) analysis - cytology showed moderate cellularity with 240 cells predominant of neutrophils - 70% and monocytes - 20%. However, CSF protein was normal - 25 mg/dL, glucose - 55 mg/dL and lactate dehydrogenase (LDH) - 80. Dengue serology, scrub typhus and viral markers were negative. Blood, urine and CSF culture were negative and peripheral smear was normal. On Day 2 of admission, her platelets decreased to 12,000/mm3 and prothrombin time was prolonged. The patient was transfused with 4 units of platelet concentrate and 2 units of fresh frozen plasma. On Day 3 of admission, we had a suspicion of leptospirosis and serum leptospirosis antibody test (IgM) was negative. A serum microagglutination test (MAT) for leptospirosis was positive - 1:160 dilution (significant >1:80 dilution). Patient was continued on injection ceftriaxone 1 g IV b.i.d. and injection vancomycin 1 g IV b.i.d. for 7 days. Patient gradually improved over a period of 7 days; sensorium improved, no fever spikes, platelets returned to normal and liver function improved. After 10 days of intensive care treatment patient was discharged. Final diagnosis -Leptospirosis with multiorgan failure.

Discussion

Leptospirosis is a re-emerging infectious disease of worldwide distribution but more commonly seen in the tropical countries and outbreaks occur in the rainy season. The causative organism is Leptospira interrogans, a Gram-negative, thin and motile bacterium, 6-20 μmin length with flagella and it includes around 250 serovars. It is the most common zoonosis and humans are accidental hosts, infected from body fluids, especially urine, of infected animal and rodents are the most common source worldwide.

Leptospirosis presents after an incubation period of 5-14 days. Often a good clinical history is needed to suspect and diagnose leptospirosis. Studies have shown that most of the patients (around 90%) present with acute febrile illness due to bacteremia (anicteric leptospirosis), which is often self-limiting. Patients typically present with fever associated with headache and muscle ache (typically calf pain) and conjunctival suffusion. Also, patients may have symptoms of vomiting, diarrhea and pharyngitis. Inspite of fever being the cardinal symptom, studies have shown that about 5% of cases have no history of fever.

The second phase (immune stage) of illness occurs after 1-3 days of symptom free period or after the initial bacteremic phase. The exact pathogenesis of this immune phase remains unclear. This is probably due to the host immune response to the leptospiral antigens and protein. The two phases are often indistinguishable in icteric leptospirosis. Renal manifestations include oliguric acute tubular necrosis due to hypovolemia and decreased renal perfusion, direct tissue injury, presence of vasoconstrictor agents and some studies suggest rhabdomyolysis, but could not prove it. Acute renal failure is associated with increased mortality. Patients present with jaundice and deranged liver function because of hepatic necrosis. Acalculous cholecystitis, though rare, is clinically significant. Weil’s syndrome, the severe form of leptospirosis, manifests with hepatic, renal and pulmonary dysfunction and is associated with increased mortality. The pulmonary complications are life-threatening; these include acute respiratory distress syndrome and massive hemoptysis. Aseptic meningitis is seen in patients in anicteric immune stage and cranial nerve palsies, encephalitis and altered sensorium are uncommon. Our patient had meningitis with icterus and altered sensorium. Conjunctival hemorrhage is common in immune stage and uveitis may be observed and persist for a year.

The complications of leptospirosis are Weil’s disease, disseminated intravascular coagulation, meningoencephalitis, massive hemoptysis, acute renal failure, myocarditis, acalculous holecystitis and pancreatitis. Thus, leptospirosis can involve most of the vital organs in the body.

Diagnosis is made by rapid diagnostic kits by detecting antibodies IgM and IgG but are negative during first week of illness. Limitation of serology is that antibodies are lacking in the acute phase of the disease. In recent years, several real-time polymerase chain reactionas says have been described. Culturing the bacteria in the blood during first week of illness and in urine from Day 7 of illness is diagnostic but it takes weeks for diagnosis. The MAT represents growth of battery of serovars of 26 leptospiral groups. Detection of agglutination by dark field microscopy is definitive of diagnosis but it usually is negative in first week ofillness and is done in specialized centers. Most of the antibiotics are sensitive in leptospirosis and the drugs commonly used are doxycycline, penicillins and macrolides. Some studies suggest no definiterole of antibiotics in milder form of disease. But early antibiotic treatment has been found to reduce mortality in some studies. Patients with Weil’s disease require IV antibiotics. Cefotaxime and ceftriaxone have replaced penicillin in the treatment of leptospirosis. Patients with Weil’s disease should be treated in intensive care unit. Renal failure requires dialysis and other supportive care should be given. Patients should be carefully monitored for the pulmonary complications, which are life-threatening. Few studies showed that oliguria, hypotension and abnormal chest auscultations were important prognostic factors in leptospirosis. There are few case reports of patients with Weil’s disease managed successfully with plasma exchange.

Conclusion

To conclude, physicians should be aware of complicated leptospirosis. A high-degree of clinical suspicion is required to diagnose leptospirosis. If any patient presents with multiorgan dysfunction, leptospirosis should be ruled out as earlier the diagnosis and treatment, better the prognosis.

Suggested Reading

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