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Year : 2020  |  Volume : 11  |  Issue : 3  |  Page : 102-107

Clinicolaboratory profile of leptospirosis: Observations from a tertiary care hospital

1 Father Muller Research Centre, Father Muller Medical College Hospital, Mangalore, Karnataka, India
2 Department of Microbiology, Father Muller Medical College Hospital, Mangalore, Karnataka, India

Date of Submission08-Feb-2020
Date of Decision25-Mar-2020
Date of Acceptance06-Apr-2020
Date of Web Publication16-Sep-2020

Correspondence Address:
Dr. Ramakrishna Pai Jakribettu
MES Medical College Hospital, Perinthalmanna - 679 338, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/joah.joah_11_20

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BACKGROUND: Leptospirosis is a neglected tropical disease caused by spirochete Leptospira interrogans. It is one of the notifiable diseases. It is under-reported and under-diagnosed in tropical countries, including India.
AIM: The aim of this study is to compare the clinico-laboratory profile of leptospirosis patients with healthy individuals and survived with dead patients.
MATERIAL AND METHODS: This was a retrospective study carried out in people diagnosed with leptospirosis. All the clinical features and laboratory parameters were studied and analyzed as per the Student's t-test.
RESULTS: A total of 467 patients were diagnosed with leptospirosis during the study period 2013–2018. Males were majority, and most of the patients belonged to the age group of 31–45 years. Seventy-two patients (15.41%) succumbed to leptospirosis. Fever, vomiting, abdominal pain, jaundice were common symptoms. Leptospirosis patients had significant anemia, leukocytosis, thrombocytopenia, elevated liver, and renal parameters. Among the dead patients, significant neutrophilia, lymphocytopenia, hyperbilirubinemia, hyperuremia, and raised creatinine were observed compared with alive patients.
CONCLUSION: Leptospirosis should be strongly suspected in male, working-age groups presenting with fever and jaundice. Anemia, leukocytosis, thrombocytosis were hematological changes in leptospirosis patients. Hepatic and renal dysfunctions with neutrophilia are the risk factors with increased mortality in patients with leptospirosis.

Keywords: Biochemical, clinical hematological, dead, leptospirosis

How to cite this article:
George T, J. Pais ML, Adnan M, Pereira R, Jakribettu RP, Baliga MS. Clinicolaboratory profile of leptospirosis: Observations from a tertiary care hospital. J Appl Hematol 2020;11:102-7

How to cite this URL:
George T, J. Pais ML, Adnan M, Pereira R, Jakribettu RP, Baliga MS. Clinicolaboratory profile of leptospirosis: Observations from a tertiary care hospital. J Appl Hematol [serial online] 2020 [cited 2021 Jun 23];11:102-7. Available from: https://www.jahjournal.org/text.asp?2020/11/3/102/295113

  Introduction Top

Leptospirosis, a neglected bacterial zoonosis, is an important public health problem associated with significant morbidity and mortality. It is caused by pathogenic spirochetes Leptospira interrogans, is endemic mainly in tropical and sub-tropical countries. In tropics, the burden of the disease is estimated to around >1 million cases and ~ 60,000 deaths occur annually.[1],[2] Even though, it was considered to be the rural disease, nowadays, rampant urbanization, unhygienic sanitary conditions expose the city dwellers to rats. The incidence is more in young- and middle-aged men, compared to older men and women, as these get exposed in more frequently with contaminated water.

The species L. interrogans has been studied extensively, and presently classified into 26 serogroups and around 240 serovars.[3] The disease is transmitted from the urine of the wide range of rodent and nonrodent reservoirs, including cattle. The pathogen, after getting excreted in urine, contaminates the water body, especially during monsoon or natural calamities such as cyclone and flood, leading in outbreaks. It is also called “Rice field fever” or “mud fever,” which reflects the mode of transmission of the disease, i.e., humans, especially farmers, come in contact with contaminant water, the pathogens invade the abraded skin, mucous membrane including conjunctiva. Following the entry of the pathogen into the tissue, the Leptospira enter into the lymphatics and blood vessels, leading to leptospiremia and finally spreading to all major organs. Thus, the incubation period can vary from 2 to 30 days, with an average of around 10 days. Within 3–7 days of onset of the disease, humoral immunity gets activated and produces specific anti-Leptospira antibodies. Mainly, IgM serovars specific antibodies are produced, which protects the individual from re-infection from the specific serovars as long as the titers of these antibodies are high. The IgG type of antibodies when produced, may not be detectable or detectable for a short duration but may persist for a longer duration.[3]

Leptospirosis has been explained in three forms ranging from milder anicteric, icteric, and severe Weil's disease with multi-organ failure. Leptospirosis, being one of the differential diagnoses of acute febrile illness, patients present with fever, myalgia, headache, and conjunctival suffusion, in milder anicteric (septicaemic) phase. If not diagnosed and treated appropriately, disease progresses to the icteric phase in were patients present with fever, severe calf muscle tenderness, acute renal failure, hypotension, and circulatory collapse. Weil's disease (immune phase), the severe form with high mortality rate, is the other end of the spectrum, with severe hepato-renal dysfunction with bleeding tendency, finally leading to multi-organ failure. The hepatic function is severely deranged, causing hepatomegaly, tenderness in the right hypochondrium, and severe jaundice. The renal dysfunction sets in 7–14 days and starts improving, and with total recovery by the 4th week of illness, in severe cases, patients may require few cycles of hemodialysis.

Acute renal failure is attributed to immunological response leading to acute tubular necrosis and interstitial nephritis, and the patient may even develop haematuria, decreased urine output, and generalized edema. When the lungs are involved mildly, cough chest pain, and blood-tinged sputum is seen, but when severity increases, the mortality rate are can rise as high as 90%. The main pathophysiological changes that occur in lungs are hemorrhage, both interstitial and alveolar, with pneumonitis, and severe respiratory distress, leading to death within 48 h. When Leptospira affects the myocardium, various types of arrhythmias especially may be seen caused by myocarditis and shock, may be seen when the cardiovascular system is involved. Aseptic meningitis is the common presentation when the central nervous system is affected, with few cases of encephalitis, peripheral neuropathies, myelitis also been reported.[3]

The severity of the illness depends on the serovars of Leptospira infecting and old age, nutritional status, and presence of other comorbid conditions in the patients. Prognosis of the disease depends on the timely diagnosis and initiation of effective antibacterials, in the early stage, is very crucial. In anicteric stage, oral doxycycline on an outpatient basis is suffice, whereas, in the icteric phase, intravenous penicillin or 3rd generation cephalosporins like ceftriaxone are effective.[4] However, atypical presentation in leptospirosis is not uncommon, rendering it a diagnostic challenge for the clinicians.

The case fatality rate can range from <5% to 30%. The National Center for Disease Control has well defined the warning signs of leptospirosis.[5],[6] The early diagnosis can prevent the progression of the disease into the fatal stage. Early diagnosis is possible only with appropriate diagnostic tests only, as the clinical features are nonspecific and can occur in our infections also. In this study, we have compared the clinico-laboratory profile of leptospirosis patients with healthy individuals. We have correlated the various parameters of the survived patients with the dead.

  Material and Methods Top

This was a retrospective study, conducted at the Department of Microbiology at Department of Microbiology at Father Muller Medical College Hospital, Mangalore, India. The study was undertaken following approval by the institutional ethics committee (FMMC/IEC/345/2018). All patients above the age of 18 years, who got admitted with the history of fever and confirmed to be affected by leptospirosis during the study period (January 2013– to June 2018), were included in the study. A probable case was defined as the patient presenting with acute febrile illness with headache, myalgia and prostration associated with one or more of the following symptoms like calf muscle tenderness, conjunctival effusion, anuria or oliguria and/or proteinuria, jaundice, hemorrhagic manifestations (intestines, lung), meningeal irritation, nausea, vomiting, abdominal pain, diarrhea with a positive result in IgM based immune-assays or immunochromatographic test.[5]

The serological assays for leptospirosis were performed using a standard kit (J. Mitraand Co. Pvt. Ltd., New Delhi, India). Patients with positive results for lepto IgM antibodies were considered lepto-positive group, while those that were not positive were considered lepto-negative. All adults confirmed with other differential diagnoses of febrile illness such as confirmed reports of malaria, tuberculosis, HIV, and bacterial and parasitic illness were excluded from the study. All the clinical, laboratory profile, and treatment details during the study period were considered. For control, we considered the hematological and biochemical data of age-matched healthy individuals who had come for their health checkups during the study period. The data from individual patients satisfying the inclusion and exclusion criteria were noted down from individual files and entered into Microsoft Excel. The demographic details were categorized into frequency, while the haematological and biochemical data were calculated to obtain mean ± standard deviation. All these details are represented in the tables. For overall comparison, results were compared as healthy individuals and lepto patients and subjected to the Student's t-test. A P value of 0.05 was considered statistically significant.

  Results Top

A total of 467 cases were clinically suspected for leptospirosis and were tested positive for IgM ELISA were included in the study. The male patients formed the majority, accounting for 348 (74.52%) of the cases. The highest number (163, 34.9%) of patients belonged to the age group of 31–45 years, least was observed in the age group of >75 years, i.e., 3 (0.64%), as shown in [Table 1]. Of the 467 patients, 72 (15.41%) patients expired. Among the expired patients, 21/72 (29.17%) were admitted to the intensive care unit [Table 1]. Most of the patients were from the Mangalore region [Table 1]. With regard to the clinical symptoms most common symptom were fever (89.08%), vomiting (36.19%), abdominal pain (26.34%), yellowish discoloration of eyes (20.99), headache (19.06), body ache (17.99), diarrhea (15.85), and cough (3.06) [Table 2].
Table 1: Demographic details of the patients with Leptospirosis

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Table 2: Symptoms in the patients with leptospirosis studied (n=467)

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The hematological parameters among the patients with leptospirosis were deranged grossly compared to healthy individuals. The patients had severe anemia, raised erythrocyte sedimentation rate (ESR), leucocytosis, neutrophilia, monocytosis, and thrombocytopenia [Table 3]. The liver function tests (LFTs), mainly serum total bilirubin, liver enzymes serum glutamate oxaloacetate transaminase, and serum glutamate pyruvate transaminase were deranged. Similarly, renal function parameters, i.e., blood urea, and serum creatinine had significantly increased. When the same parameters were compared with the patients who succumbed to leptospirosis and alive, significant neutrophilia, lymphocytopenia, monocytopenia were observed in dead patients. No significant difference was observed in LFT, but in RFT, blood urea and serum creatinine were deranged significantly in dead patients compared to alive patients [Table 4].
Table 3: Comparison of hematological and biochemical parameters among the healthy individuals and patients with leptospirosis

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Table 4: Comparison of hematological and biochemical parameters among the people who survived and succumbed to leptospirosis

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  Discussion Top

Leptospirosis is a differential diagnosis in a patient presenting with fever, especially in tropical and subtropical countries. The patients can present with a range of clinical features which may overlap with other tropical diseases such as dengue, malaria, typhoid.[3] The patient may manifest with the mild form to severe, Weil's disease, associated with hematological and biochemical abnormalities. In our study, we have studied the variation in hematological and biochemical parameters in the patients diagnosed with Leptospirosis. In our study, majority of the patients affected were male (74.52%). Similar high incidence of leptospirosis has been reported in this geographical area, especially in South India[7],[8] and Srilanka.[9],[10] Most of our patients belonged to the age group of 31–45 years i.e., 34.9%. Such clustering of the cases in this age group has been observed by many studies.[6],[7],[8],[9],[10]

In our patients, the hemoglobin was significantly low compared to a healthy individual.[11],[12] As leptospirosis being a bacterial infection, leukocytosis with neutrophilia is seen.[11],[12] The thrombocytopenia was significant in patients with leptospirosis, which is observed in various Indian studies.[13],[14],[15],[16],[17] Various studies have reported hepatic dysfunction in patients admitted with leptospirosis, similarly, we have seen LFT deranged significantly in our patients.[18],[19],[20],[21] The renal dysfunction was noted in our study with raised blood urea and serum creatinine, which is also observed in other studies.[13],[19]

The mortality rate in our patients was as high as 15.41% i.e., 72/467 patients. There was statistically significant leucocytosis, neutrophilia, lymphopenia, monocytopenia, among the patients who succumbed to Leptospirosis. A death audit of 13 patients in Gujarat, who had succumbed to leptospirosis, had severe anemia, thrombocytopenia and leukocytosis.[6] Even, a study which included 130 cases from Mangalore, concluded the same finding.[7] However, in our study, there was no much of thrombocytopenia that was observed and even the patients didn't present with bleeding tendencies. Lymphopenia, which was observed in our patients, was also reported by a referral center of Coastal Karnataka and North Kerala.[8] Hyperbiliruninemia was observed in our dead patients, which was considered as high-risk factor in patients with leptospirosis.[6],[8] Acute renal failure is one of the complications seen in leptospirosis. Among the dead patients, we have observed a significant hyperuricemia and elevated creatinine level, similar to other studies.[6],[8]

  Conclusion Top

Leptospirosis is a re-emerging zoonosis, is one of the neglected tropical diseases. Hence, it is a disease of public health globally. It affects mainly the working-age group with a predominance toward male. Fever is the commonest symptoms and depending on the organ system involved, the symptoms may vary. Severe anemia, leucocytosis, raised ESR, deranged LFT and RFT are very much evident in patients with leptospirosis. Significant leucocytosis, neutrophilia, elevated Bilirubin, urea, creatinine are observed in patients who succumbed to leptospirosis. Hence, these parameters need to be monitored, and effective, timely intervention can reduce the mortality and morbidity, especially in endemic areas.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Ko AI, Goarant C, Picardeau M. Leptospira: The dawn of the molecular genetics era for an emerging zoonotic pathogen. Nat Rev Microbiol 2009;7:736-47.  Back to cited text no. 1
Costa F, Hagan JE, Calcagno J, Kane M, Torgerson P, Martinez-Silveira MS, et al. Global morbidity and mortality of leptospirosis: A systematic review. PLoS Negl Trop Dis 2015;9:e0003898.  Back to cited text no. 2
Human Leptospirosis: Guidance for Diagnosis, Surveillance and Control. Geneva: World Health Organization, International Leptospirosis Society; 2003. Available from: http://whqlibdoc.who.int/hq/2003/WHO_CDS_CSR_EPH_2002.23.pdf. [Last accessed on 2020 Jan 22].  Back to cited text no. 3
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Daher EF, Lima RS, Silva GB Jr., Silva EC, Karbage NN, Kataoka RS, et al. Clinical presentation of leptospirosis: A retrospective study of 201 patients in a metropolitan city of Brazil. Braz J Infect Dis 2010;14:3-10.  Back to cited text no. 14
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  [Table 1], [Table 2], [Table 3], [Table 4]

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