|Ahead of print publication
A study of clinical profile of 100 icteric leptospirosis cases
Mohit Sethia1, Rahul Jain2, Santosh Kumar Singh3, Rina Tilak4, Arun Kumar Yadav4
1 Department of Gastroenterology, Army Hospital R and R, New Delhi, India
2 Department of Gastroenterology, R and R Hospital, New Delhi, India
3 Department of Internal Medicine, AFMC, Pune, Maharashtra, India
4 Department of Community Medicine, AFMC, Pune, Maharashtra, India
|Date of Submission||22-Oct-2021|
|Date of Decision||14-Dec-2021|
|Date of Acceptance||14-Dec-2021|
Arun Kumar Yadav,
Department of Community Medicine, AFMC, Pune - 411 040, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Leptospirosis is a widespread zooanthroponosis prevalent in tropical regions due to its etiologic agent's favorable environmental survival conditions. The disease has protean clinical manifestation. The present study was conducted to describe clinical signs, symptoms, and outcomes in severe icteric leptospirosis cases. Materials and Methods: This observational study was carried out in Surat from r 2012–2014. A total of 100 confirmed cases of icteric Leptospirosis was included in the study. Clinico-socio-demographic profile of the cases was noted. The symptoms and signs were described. The clinical outcome was described in terms of laboratory and other findings. Results: Fever was seen as the most common presenting symptom in 100% patients. Icterus (100%) crepts (86%) and tachypnea (80%) were the most common presenting signs. Breathlessness and hemoptysis were significantly more common in nonsurvivors than survivors. Mortality was more common in cases who had not taken chemoprophylaxis, platelet count <50,000/mm3, serum creatinine more than three mg%, international normalized ratio less than two, and multiorgan dysfunction. Conclusion: The study brought out common sign and symptoms of icteric leptospirosis. Sociodemographic and clinical parameters associated with poor outcome were also delineated. Smoking and alcohol seemed to be important contributory factors in aggravation of the disease. Chemoprophylaxis was preventive in adverse outcome. The clinical parameter may help in prediction of the course of the disease.
Keywords: Clinical profile, icterus, leptospirosis
|How to cite this URL:|
Sethia M, Jain R, Singh SK, Tilak R, Yadav AK. A study of clinical profile of 100 icteric leptospirosis cases. Med J DY Patil Vidyapeeth [Epub ahead of print] [cited 2022 Nov 30]. Available from: https://www.mjdrdypv.org/preprintarticle.asp?id=337099
| Introduction|| |
Leptospirosis is a zooanthroponosis caused by a pathogenic spirochete of genus Leptospira. It is more prevalent in tropical regions than temperate climates due to the favorable environmental survival conditions of its etiologic agent. Outbreaks mainly occur as a result of heavy rainfall and consequent flooding.
Cases of leptospirosis have been reported in India since 1931. However, the cases have been on the rise in the last few years. The disease has been reported from all regions of the country. Leptospirosis is seen in the occupation of farmers, agriculture workers, those engaged in recreational activities involving contact with inland natural waterways, and less frequently of sewer men, miners, and fish workers. Most of the population of India still are involved in agricultural practices, including fisheries in rural areas, thus making them vulnerable to the disease.
Humans become infected through the skin and mucous membrane contact with infected animal urine or water and soil contaminated with infected animal urine. Leptospirosis causes a wide spectrum of diseases ranging from asymptomatic infection or influenza-like symptoms to classical Weil's disease with fever, jaundice, hemorrhagic episodes, aseptic meningitis, hepatitis, and nephritis. The syndrome of icteric leptospirosis with renal involvement is referred to as Weil's disease. Another recognized clinical form is that presenting with severe pulmonary hemorrhage. Other complications include acute respiratory failure, myocarditis, meningitis, and renal failure. Uveitis has recently been recognized as a late complication of leptospirosis. There are also hemorrhagic manifestations due to thrombocytopenia.
In the countries where leptospirosis is more prevalent, there is a lack of awareness among medical personnel and minimal availability of laboratory support for diagnosis. So, frequently it is misdiagnosed or under-diagnosed. Chemoprophylaxis using Doxycycline is one of the preventive measures in absence of any vaccines. According to NCDC the chemoprophylaxis is recommended during peak season using Doxycycline 200 mg once a week to the high-risk groups like agricultural, sanitary workers vicenarian, etc. The duration of chemoprophylaxis should not exceed more than 6 weeks.
Leptospirosis is endemic in Southern Gujrat and has witnessed outbreaks during the monsoon season for the past decade. Gujrat saw the highest number of leptospirosis cases in the year 2011. Leptospirosis has protean clinical manifestation, which makes it difficult to diagnose if there is no suspicion. Hence, the present study was conducted to describe sociodemographic, clinical, laboratory factors of confirmed icteric leptospirosis cases admitted to a hospital in south Gujrat.
| Materials and Methods|| |
This observational study was carried out in New Civil Hospital, Surat, during the monsoon period (July to October) of leptospirosis from 2012 to 2014. All consecutive suspected cases were screened as per the case definition given by NCDC guidelines. All patients who were meeting the clinical case definition of a confirmed case of icteric (Total bilirubin >2 mg/dl) leptospirosis as per NCDC were included in the present study. In the present study, positive polymerase chain reaction (PCR) and serology on microscopic agglutination test (MAT) was taken as confirmed case, which is in congruence with NCDC definition of the confirmed leptospirosis. Patients having smear-positive Malaria, Viral Hepatitis (Hepatitis A/B/C/E), Dengue (immunoglobulin M enzyme-linked immunosorbent assay [ELISA]/NS1 Ag/PCR positive), chronic renal failure patients, heart disease patients, chronic diseases, Age ≤12 years, and nonicteric were excluded from the study. The first consecutive 100 confirmed cases of Icteric Leptospirosis were included in the study.
Sociodemographic and clinical data was collected on a case record form. Patients were subjected to detailed clinical examination and thorough investigations, which included routine investigations like complete blood workup, Viral markers, electrocardiogram (ECG), and chest X-ray. Specific investigations ELISA, MAT, PCR, and rapid diagnostic test were carried out to reach the diagnosis. The study was given institutional ethical clearance vide their letter number 129/12 dated December 2012.
Statistical analysis was done by software Epi Info version 6.0. Descriptive statistics such as percentages, mean, and standard deviation were used. Chi-square test was applied to test the association between categorical variables and P < 0.05 was considered statistically significant.
| Results|| |
During the period, we enrolled 100 participants. Among the study participants, 60 were in the age group 13–40 years, whereas 40 participants were >40 years of age. Majority of the participants were male (80, 80%). The prevalence of smoking and alcohol among participants was 40% and 48%, respectively [Table 1]. There was mortality of 50% among study participants.
It was seen that fever was most common presenting symptom, present in 100% of patients followed by breathlessness (90%), myalgia (86%), headache (78%), oliguria (70%), and cough (66%). Hematemesis and convulsions were the least presenting symptoms seen in 12% and 5% patients respectively. Various symptoms among the survivors and nonsurvivors are as shown in [Figure 1].
Various signs associated with leptospirosis and their distribution in survivor and nonsurvivor group is presented in [Figure 2]. It was seen that the most common presenting sign was icterus (100%) crepts on ausculation (86%) and tachypnea (80%) whereas raised Juglar Venous Pulse and signs of meningeal irritation were seen only in 12% and 3% patients, respectively [Figure 2].
Various features of multiorgan involvement were studied and they were characterized on the basis of their survivorship as shown in [Table 2]. It was seen that multiorgan involvement was present in 58 patients which consisted of 34.48% survivors and 65.51% nonsurvivors (P = 0.04). Pulmonary hemorrhage was seen in 64 patients: 26.56% survivors and 73.43% nonsurvivors (P < 0.0001).
Out of 100 cases, 90 patients had acute respiratory distress syndrome (ARDS), of which 04 had mild ARDS, 82 patients had moderate ARDS and 04 patients had severe ARDS. Patient with severe ARDS had 100% mortality while patient with mild ARDS and without ARDS had 100% survival. Among them 56.09% were nonsurvivors and 43.90% were survivors in those having moderate ARDS.
Lab investigations revealed an equal distribution of study participants in survivor and nonsurvivor group with low Hb levels (36 each), hyponatremia (10 each) and leukocytosis (20 in survivor and 22 in nonsurvivor group). An unequal distribution among the two groups was seen in lab parameters like international normalized ratio (INR) >2 (90.90% in nonsurvivor group), Creatine phosphokinase (CPK) >500 (75% in nonsurvivor group) and platelet count <50,000/cm3 (73.07% in nonsurvivor group). ST-T changes, repolarization abnormalities were seen in total 20 patients of which 75% were nonsurvivors whereas ejection fraction <40 and myocarditis was seen in 04 patients of which 03 were nonsurvivors. Chest X-ray showing B/L infiltrates suggestive of ARDS was seen in 55 patients of which 39 were nonsurvivors, whereas other findings suggestive of consolidation and pleural effusion was seen in 14 patients of which 64.28% were nonsurvivors.
Only 50 (50%) patients had received the chemoprophylaxis for leptospirosis. A total of 38, (76%) cases among survivors had received chemoprophylaxis while only 24% cases among nonsurvivors had received chemoprophylaxis (P = 0.0023). Total 86 patients were put on Mechanical Ventilation, out of which 40 were on invasive while 46 were put on noninvasive ventilation. Among them, 75% of those on invasive ventilator were nonsurvivors while 43.47% of those on noninvasive ventilators were nonsurvivors. Renal Failure (S. Creatinine >3.0 mg %) was present in 72 patients out of which in 16 patients' hemodialysis was done. About 62.5% of patients were survivors among those in which dialysis was done.
| Discussion|| |
During the past decade in south Gujarat Leptospirosis has emerged and resulted in outbreaks causing significant morbidity and mortality in South Gujarat. Key reasons of disease in these regions are: (i) Leptospira microorganism require three conditions for its survival, namely a reservoir host (Rodents, Cattle, Goats, Pigs etc.) alkaline soil and wetness (heavy rainfall and water logging conditions). All these factors viz., alkaline soil, presence of leptospira serovars in domestic animals, and wetness are present in South Gujarat. When the agricultural workers pass through or work in these waterlogged conditions, they become susceptible to the disease. (ii) The areas from where the disease is being reported are agriculturally advanced areas and the main crops cultivated here are paddy, sugarcane, and banana.
In our study, maximum number of patients were found in 13–40 years age group who are commonly going to farm for work, thus having more chances of exposure to contaminated water and soil during work in farm after rainfall. Findings of our study are consistent with those of who found that maximum number of patients (55%) were in age group of 13–40 years. In our study, we found that 80% of the patients were males which can be attributed to the frequent visit by them to the farm for work and thus increased risk of exposure. As per our study, chronic smoking and alcohol history was more common in nonsurvivor than survivor group (P < 0.001) thus being important predictors of mortality. Chronic alcohol intake leads to liver damage thus manifesting hepatic involvement and smoking leads to lung damage complicating the disease in patients with pulmonary leptospirosis. Thus, smokers and alcoholics are more prone to complications and mortality than nonsmokers and nonalcoholic. Lebreton et al. also show that chronic alcohol was a important predictor of mortality in icteric leptospirosis patients.
As brought out in our study, multiorgan dysfunction is an important predictor of mortality which correlates with Edilane et al. and Trivedi et al., in which mortality is common in cases with multiorgan involvement. There is significant difference in mortality in both survivor and nonsurvivor group in mild, moderate, and severe ARDS as well as without ARDS. Patients with mild to moderate ARDS can be managed without ventilator support or need only noninvasive ventilation, thus associated with less mortality than severe ARDS which needs invasive ventilation. These findings are in concordance with those of Marotto et al. in which PAO2/FIO2 ratio <200 was an important predictor of mortality.
There is no difference in survivor and nonsurvivor group regarding anemia which is in sync with the findings of Edilane et al., Marotto et al. and Holla et al. depicting anemia not being an important predictor of mortality. There is significant difference among survivor and nonsurvivor group for thrombocytopenia (Platelet count < 50,000, P < 0.001), thus being a predictor of mortality in leptospirosis patient. Similar results were seen in studies by Spichler et al. and Holla et al. All patients with raised S. bilirubin level had direct bilirubinemia. Clerke AM et al. found in their study that most of the participants had direct hyperbilirubinemia, which closely correlates with our study. INR >2.0 present in 90.90% patients among nonsurvivor which is significant (P value 0.01061). So, it is an important predictor of mortality which correlates with Storck et al., in which also prolonged INR was an important predictor of mortality. There is not significant difference in survivor and nonsurvivor group for both hyponatremia and hypernatremia. So, serum sodium level may not important predictor of mortality in pulmonary leptospirosis patient correlating with the findings of Storck et al. and Trivedi et al. About 60% mortality was seen in patients with hyperkalemia (>5.5) which is significant. Mortality rate was 75% among patient with raised CPK (>500) being an important predictor of mortality in leptospirosis patients. This result is similar as of Marotto et al. in which raised CPK was present in 82% patients. Mortality was significantly higher in those with abnormal X-ray chest suggestive of pulmonary involvement being an important predictor of mortality.
Mortality is more common in cases who had not taken chemoprophylaxis than who had taken chemoprophylaxis. Hence, chemoprophylaxis leads to less severe disease. So, this finding indicate that chemoprophylaxis for leptospirosis during rainy season may be helpful in decreasing the mortality. As per NCDC guidelines also, the population at risk should take chemoprophylaxis with Doxycycline (200 mg once a week). ECG changes s/o cardiac involvement were more common in nonsurvivor group (75%) than survivor (30%) group. Myocarditis changes on echo was seen in only in 04 patients out of which 03 were nonsurvivor. These findings correlate with Trivedi et al. in which myocarditis was an important cause of mortality in leptospirosis patients.
The study has certain limitation. The molecular studies could not be done due to resource constraints and nonavailability. The genus Leptospira is classified into 19 genospecies, of which 13 are known pathogenic strains. The major pathogenic species include Leptospira interrogans, Leptospira noguchi, Leptospira borgpetersenii, Leptospira santarosai, Leptospira krischneri, Leptospira weilii, Leptospira alexanderi, Leptospira fainei eptospira meyeri. Based on antigenic similarities, pathogenic Leptospira are further classified into more than 250 serovars and antigenically similar serovars are grouped into serogroups. Some genospecies and servars of Leptospira cause more severe disease than others, e. g., L. interrogans serovar Icrerohaemorrhagiae is highly pathogenic, through such an association cannot always be demonstrated. Another limitation of the study was that we could not follow up the cases after they were discharge from the hospital so some late complication may not be known.
This descriptive study of cases brought about the sign and symptoms of icteric leptospirosis. The study also highlights important factors associated with mortality. These factors need to be further studied in higher design study. Since we have taken described cases of icteric leptospirosis, it is possible that anicteric cases may have different presentations.
| Conclusion|| |
The study brought out common sign and symptoms of icteric leptospirosis. Sociodemographic and clinical parameters associated with poor outcome were also delineated. Smoking and alcohol seemed to be important contributory factors in aggravation of the disease. Chemoprophylaxis was preventive in adverse outcome. The clinical parameter may help in prediction of the course of the disease.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Carvalho CR, Bethlem EP. Pulmonary complications of leptospirosis. Clin Chest Med 2002;23:469-78.
Gubler DJ, Reiter P, Ebi KL, Yap W, Nasci R, Patz JA. Climate variability and change in the United States: Potential impacts on vector- and rodent-borne diseases. Environ Health Perspect 2001;109 Suppl 2:223-33.
Sambasiva RR, Naveen G, Bhalla P, Agarwal SK. Leptospirosis in India and the rest of the world. Braz J Infect Dis 2003;7:178-93.
Victoriano AF, Smythe LD, Gloriani-Barzaga N, Cavinta LL, Kasai T, Limpakarnjanarat K, et al.
Leptospirosis in the Asia Pacific region. BMC Infect Dis 2009;9:147.
Tangkanakul W, Tharmaphornpil P, Plikaytis BD, Bragg S, Poonsuksombat D, Choomkasien P, et al.
Risk factors associated with leptospirosis in northeastern Thailand, 1998. Am J Trop Med Hyg 2000;63:204-8.
Hill MK, Sanders CV. Leptospiral pneumonia. Semin Respir Infect 1997;12:44-9.
Budihal SV, Perwez K. Leptospirosis diagnosis: Competancy of various laboratory tests. J Clin Diagn Res 2014;8:199-202.
Clerke AM, Leuva AC, Joshi C, Trivedi SV. Clinical profile of leptospirosis in South Gujarat. J Postgrad Med 2002;48:117-8.
] [Full text]
Chand PT, Garg VR, Wadia MZ. A study on cardiovascular manifestation in leptospirosis cases in a tertiary care hospital of Surat city. Headache 2016;60:20.
Lebreton T, Aubrun F, Mabrut JY, Heyer L, Perrin C. Liver transplantation for acute liver failure attributed to leptospirosis: A report of two cases. Case Rep Crit Care 2019;2019:5189542.
Gouveia EL, Metcalfe J, de Carvalho AL, Aires TS, Villasboas-Bisneto JC, Queirroz A, et al.
Leptospirosis-associated severe pulmonary hemorrhagic syndrome, Salvador, Brazil. Emerg Infect Dis 2008;14:505-8.
Trivedi SV, Chavda RK, Wadia PZ, Sheth V, Bhagade PN, Trivedi SP, et al.
The role of glucocorticoid pulse therapy in pulmonary involvement in leptospirosis. J Assoc Physicians India 2001;49:901-3.
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.
Holla R, Darshan B, Pandey L, Unnikrishnan B, Kumar N, Thapar R, et al.
Leptospirosis in coastal south India: A facility based study. Biomed Res Int 2018;2018:1759125.
Spichler AS, Vilaça PJ, Athanazio DA, Albuquerque JO, Buzzar M, Castro B, et al.
Predictors of lethality in severe leptospirosis in urban Brazil. Am J Trop Med Hyg 2008;79:911-4.
Storck CH, Postic D, Lamaury I, Perez JM. Changes in epidemiology of leptospirosis in 2003-2004, a two El Niño Southern Oscillation period, Guadeloupe archipelago, French West Indies. Epidemiol Infect 2008;136:1407-15.
[Figure 1], [Figure 2]
[Table 1], [Table 2]