Introduction

Leptospirosis is a zoonotic disease caused by bacteria that belongs to the genus Leptospira. Leptospira interrogans is pathogenic for humans. The genus can be separated into more than 200 serovars belonging to 23 serogroups[1].  The median global incidence of endemic human lept­ospirosis, excluding cases due to outbreaks, was 5 cases per 100,000 population, but in some areas the inci­dence was as high as 975 cases per 100,000. The mean annual global incidence of epidemic leptospirosis, as reported in outbreak reports, was 14 cases per 100,000 population. Some concern was expressed at the signifi­cant lack of data, especially from Africa and the Eastern Mediterranean Region, and at the substantial hetero­geneity in the data[2].

Case Report

A 68 year old male was brought to our hospital with chief complaints of decreased level of consciousness, breathing difficulty and decreased urine output. The patient had a past medical history of asthma and hypertension. He was a non-smoker and non-alcoholic. Two weeks prior to presentation at our hospital, he had an episode of vomiting while running his daily errands and subsequently developed breathing difficulty. He was taken to a nearby hospital where his chest X-Ray (Figure:1a) showed right upper zone patch. During his stay there, he was treated with bronchodilators and antibiotics. He progressively became drowsy and his urine output decreased and further evaluation showed a deranged liver and renal functions. He was then referred to our hospital for higher level of care.

Vitals in the emergency room at our hospital were notable for a normal temperature, pulse rate of 93/min and a blood pressure of 150/100 mmHg. The patient was drowsy but obeying commands with a GCS of 10/15 (E4 V2 M4). He did not have neck stiffness. He did not have a history of fever, headache, body pain, abdominal pain, hematuria or melena Ocular examination was notable for scleral icterus. The chest on auscultation revealed crepitation which were greater on the right side and the abdomen was soft and non-tender.

Initial laboratory study revealed a white blood count of 23,000/ul, which was polymorphonuclear predominant (poly 78.4%), hemoglobin of 11.3 gm%, platelet of 17,000/ul, creatinine of 8.2 mg/dl, BUN of 194 mg/dl, total bilirubin of 8.4 mg/dl, direct bilirubin of 5.7 mg/dl, AST of 60 U/L, ALT of 84 U/L, alkaline phosphatase of 67 U/L, serum cortisol level was 39.88 ug/dl and LDH was 1053 U/L. CT scan of his chest showed patchy-diffuse bilateral ground glass attenuation with minimal right side pleural effusion(Figure:2). Ultrasound of his abdomen showed bulky and hypoechoic kidneys. 

The patient was admitted to intensive care unit because of multi-organ dysfunction. The possibility of sepsis was considered for which the patient was started meropenem and fluid resuscitation. As the patient was afebrile, leptospirosis was an unlikely diagnosis but given his clinical presentation, doxycycline was also added to the treatment regimen. The following day, the patient’s urine output and level consciousness decreased further and he was in uremic encephalopathy with a serum creatinine of 9.2 mg/dl and a BUN of 229mg/dl. CT-brain showed diffuse age related cerebral and cerebellar atrophy and small vessel ischemic disease. The patient was started on dialysis considering his poor renal function. By then his leptospirosis serology test returned positive, dengue serology was negative, blood culture and urine culture were sterile. The patient was dialysed thrice during this period and there was gradual improvement in his urine output along with improvement in his renal function, liver function and platelet counts (Figure 3a, 3b, 3c respectively). Patient was also transfused 2 units of PRBC. Repeat chest X-Ray was taken which showed good resolution.   Patient was transferred to the wards on the 7^th day with improving urine output, a progressively improving renal function and a GCS of 15/15.   

In wards the same line of management was continued with no further need of dialysis.  At discharge patient was symptomatically better with a hemoglobin of 8.0 gm%, platelet count of 181,000/ul, serum creatinine of 2.2 mg/dl, AST of 41 U/L, ALT of 56 U/L, total bilirubin of 2.2 mg/dl, indirect bilirubin or 1.0 mg/dl, direct bilirubin of 1.2 mg/dl and normal Chest X-ray (Figure 1b). One week after discharge from the hospital, the patient’s serum creatinine was 1.8 mg/dl and hemoglobin was 9.3 gm% on follow up visit.

Discussion

Leptospirosis is the most widespread zoonosis in the world. Tropical countries and low socioeconomic conditions with poor sanitation have particularly been identified as favorable for disease transmission.

Human leptospiral infections result primarily from direct or indirect exposure to the urine of infected animals. Rats are the most common reservoir in India. Human infections can occur either by direct contact with infected urine of the infected animal[4].

A retrospective study reported that in patients with leptospirosis, the common clinical features included fever (100%), headache (75%), myalgia (55%), arthralgia (45%) and vomiting (39%)[5].Leptospirosis is usually biphasic. The first phase is the septicemic phase that usually lasts a week. The patient presents with fever, headache, conjunctival congestion, nausea, vomiting, joint pain and myopathy. This phase is followed by a brief afebrile period of variable duration that, in turn, is followed by the immune phase of illness.  During this phase, the patient has multi-organ involvement. This severe form of leptospirosis is called Weil’s disease. The common organs involved during this phase are the liver, kidneys and lungs. Liver involvement leads to elevated liver enzymes and a high total bilirubin. Kidney involvement can give rise to azotemia, hematuria, uremia and pyuria The patients with lung involvement can present with cough, hemoptysis, chest pain and shortness of breath, pulmonary haemorrhage or ARDS[6,7]. Leptospirosis can present atypically with predominant pulmonary manifestation, which normally results in misdiagnosis and hence delayed appropriate treatment[8].

Some of the common differential diagnosis of leptospirosis include dengue, malaria, encephalitis and scrub typhus.

Diagnosis of leptospirosis is based on clinical suspicion and laboratory investigations. The commonly ordered laboratory investigation in a suspected case of leptospirosis at our hospital is detection of leptospirosis IgM antibody by ELISA test. A confirmatory test is microscopic agglutination test (MAT), although this is not commonly done when there is high suspicion of leptospirosis based on clinical presentation and a positive leptospirosis IgM by ELISA.

Leptospirosis can be treated with antibiotics like penicillin, doxycycline and ceftriaxone. A Jarisch-Herxheimer reaction can occur during the treatment but it is usually mild[1]. It is important to start the treatment early to shorten the hospital stay.

A retrospective case control study identified predictors of mortality as - age > 40 years, development of oliguria, platelet count < 70,000/ μL, creatinine > 3 mg/dl, and pulmonary involvement[9]. Mortality rate of Weil’s disease is 5-15%.

Conclusion

Our patient did not present with fever and he did not have the classic symptoms of the septicemic phase of leptospirosis either, but because of pulmonary, hepatic and renal involvement, we had leptospirosis as one of our main differential diagnosis. We wish to emphasize that leptospirosis should be considered as a differential diagnosis in tropical countries when a  patient presents with multi-organ failure or fever of greater than 3 days duration without an obvious cause.

Reference:

1. 20^th Edition of Davidson’s Principles and Practise of Medicine, Page no. 321
2. WHO-Report of the Second Meeting of the Leptospirosis Burden Epidemiology Reference group- Page no. 12
3. Elizabeth F. Daher, Rafael S.A. Lima, Geraldo B. Silva Júnior, Eveline C. Silva, Nahme N.N. Karbage, Raquel S. Kataoka, Paulo C. Carvalho Júnior, Max M. Magalhães, R osa M.S. Mota, Alexandre B. Libório- The Brazilian Journal of Infectious Diseases, Volume 14, Issue 1, Pages 3-10
4. Indian J Crit Care Med. 2013 Jan-Feb; 17(1): 43–45- Multivisceral organ failure related to leptospirosis in pregnant patient-Sbai Hicham, Mellouki ihsane,¹ El Bouazzaoui Abderahim, Boukatta Brahim, Smail Labib, Harrandou Mustapha, Khatouf Mohamed, Ibrahimi Adil,¹ Melhouf Abdelilah,² and Kanjaa Nabil
5. 5. Postgrad Med 2005;51:179-83- Unusual Clinical Manifestations of Leptospirosis- Bal AM
6. J Postgrad Med 2005; 51:179-83- Unusual Clinical Manifestations of Leptospirosis by Bal AM
7. Journal of Medical Case Reports 2011, 5:7- Fulminant Leptospirosis (Weils disease) in an urban setting as an overlooked cause of multiorgan failure: a case report Elias Maroun^*, Anurag Kushawaha, Elie El-Charabaty, Neville Mobarakai and Suzanne El-Sayegh
8. Gulati S, Gulati A. Pulmonary manifestations of leptospirosis. Lung India 2012;29:347-53
9. Marotto PC, Nascimento CM, Eluf-Neto J, Marotto MS, Andrade L, Sztajnbok J, et al. Acute lung injury in leptospirosis: Clinical and laboratory features, outcome, and factors associated with mortality. Clin Infect Dis 1999;29:1561-3