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Table of Contents   
ORIGINAL ARTICLE  
Year : 2012  |  Volume : 5  |  Issue : 3  |  Page : 240-244
Predictors of the development of myocarditis and acute renal failure in patients with leptospirosis


1 Consultant Physician, Teaching Hospital, Kandy, Sri Lanka
2 Department of Community Medicine, Faculty of Medicine and Allied Sciences, Saliyapura, Anuradhapura, Sri Lanka
3 Registrar in Medicine, Teaching Hospital, Kandy, Sri Lanka
4 Teaching Hospital, Kandy, Sri Lanka

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Date of Web Publication17-Jul-2012
 

   Abstract 

Background: Leptospirosis has a varied clinical presentation with complications such as myocarditis and acute renal failure. There are various predictors of severity and mortality, including clinical and laboratory parameters. Early detection and treatment can reduce complications. Therefore, recognizing the early predictors of the complications of leptospirosis is important in patient management. Aims: This study was aimed at determining the clinical and laboratory predictors of myocarditis and acute renal failure. Setting and Design: This is a prospective descriptive study carried out in medical wards of our hospital from July 1, 2007, to July 31, 2008. Materials and Methods: Patients with clinical features compatible with leptospirosis case definition were confirmed using the Microscopic Agglutination Test (MAT). Clinical features and laboratory investigations done on admission were recorded. The patients were observed for the development of acute renal failure and myocarditis. Statistical Analysis: Chi-square statistics, Fisher's exact test, and Student's t test were used to compare patients with and without complications. A logistic regression model and backward stepwise elimination of variables was carried out to select final variables. Results: Sixty-two confirmed leptospirosis patients were included in the study. Six patients (9.6%) developed acute renal failure and five (8%) developed myocarditis, while three (4.8%) had acute renal failure and myocarditis together. Conjunctival suffusion - 40 (65%), muscle tenderness - 28 (45%), oliguria - 20 (32%), jaundice - 12 (19%), hepatomegaly - 10 (16%), arrhythmias (irregular radial pulse) - 8 (13%), chest pain - 6 (10%), bleeding - 5 (8%), and shortness of breath (SOB) - 4 (6%) were the common clinical features present in the patients. Of these, only oliguria {Odds Ratio (OR) = 4.14, 95% Confidence Interval (CI) = 1.003 - 17.261}, jaundice (OR = 5.13, 95% CI = 1.149 - 28.003), and arrhythmias (OR = 5.774, 95% CI = 1.001 - 34.692), were predictors of myocarditis and acute renal failure and none of the laboratory investigations could predict the two complications. Conclusion: This study shows that out of clinical and laboratory variables, only oliguria, jaundice, and arrhythmia are strong predictors of development of acute renal failure and myocarditis.

Keywords: Acute renal failure, leptospirosis, myocarditis

How to cite this article:
Dassanayake D, Wimalaratna H, Agampodi S B, Nandadewa D, Nugaliyadda A, Ratnatunga C N. Predictors of the development of myocarditis and acute renal failure in patients with leptospirosis. Ann Trop Med Public Health 2012;5:240-4

How to cite this URL:
Dassanayake D, Wimalaratna H, Agampodi S B, Nandadewa D, Nugaliyadda A, Ratnatunga C N. Predictors of the development of myocarditis and acute renal failure in patients with leptospirosis. Ann Trop Med Public Health [serial online] 2012 [cited 2018 May 22];5:240-4. Available from: http://www.atmph.org/text.asp?2012/5/3/240/98627

   Introduction Top


Leptospirosis is endemic in both urban and rural areas of Sri Lanka, and there have been several outbreaks in the recent past. A total of 2,187 cases were reported in 2007 in Sri Lanka, while 147 cases were reported from the Kandy District. [1] In the recent epidemic of leptospirosis in 2008, the number of cases have increased to 7,099 and the number of deaths has gone up to 204 (sixfold increase as compared to 2007). [2]

Leptospirosis can vary from a mild non-specific influenza-like infection to Weil's disease, where serious complications can occur. In various publications, mortality rates are reported between 3% and 54% according to the affected organ system. [3],[4]

Common complications of leptospirosis are acute renal failure, myocarditis, aseptic meningitis, pulmonary hemorrhage, myositis, uveitis, and bleeding. [5] Cardiac and renal involvement are two of the most dreaded complications of leptospirosis. Some studies have shown that 70% of the patients with serologically proven leptospirosis had electrocardiographic abnormalities, with atrial fibrillation being the most common major arrhythmia noted. [6] Thirty-six percent of the patients had conduction system abnormalities and 30% had T-wave changes. Another series has reported atrioventricular block in 44% of patients with leptospirosis. [7] A glycoprotein fraction of the leptospiral cell wall has been incriminated in the pathogenesis of these rhythm disturbances. Other reported cardiac abnormalities include myocarditis and endocarditis. [8]

Renal involvement is the most serious complication in leptospirosis and the most common cause of death. [9] Two mechanisms have been postulated in the production of leptospiral renal failure: (1) direct nephrotoxicity brought about by various endotoxins or endotoxin-like substances, and (2) anoxic effect due to disturbances in renal circulation. The typical lesion is tubulointerstitial nephritis, characterized by interstitial edema and dense focal infiltration of predominantly mononuclear cells. Tubular changes are degenerative in nature and affect, primarily, the proximal tubules. Intravascular volume depletion causing the vasomotor nephropathy in this disease has been postulated to occur from capillary leakage with associated loss of fluid and protein, hence the proteinuria. [9]

Severe leptospirosis may carry high mortality if treatment is not instituted early. Poor prognostic markers in leptospirosis reported in various studies include hypotension, oliguria, and hyperkalemia. [10] Other studies have reported dyspnea, white blood cell count greater than 12,900/mm 3 , [11] repolarization abnormalities on electrocardiogram, alveolar infiltrates, [12] hemoptysis, metabolic acidosis, and thrombocytopenia. In hospitals that have adequate facilities, patients with these risk factors should preferably be treated in an intensive care unit. [13]

The beginning of early pertinent antimicrobial therapy within 4-5 days after the onset of illness, proper supportive therapy and use of dialysis to treat renal failure has reduced the leptospirosis-related mortality. [14] Therefore, early predictors of complications are helpful in detecting and managing patients with leptospirosis and also in minimizing the mortality.

This study was aimed at determining which clinical and laboratory findings can predict the development of myocarditis and acute renal failure.


   Materials and Methods Top


Study Setting

This study was carried out in the medical ward of our hospital, which is a tertiary care (Teaching) hospital. This medical unit treats about 10,000 patients per year and 10% of the admissions are due to fever, of which substantial proportion is due to leptospirosis. Ethical approval was granted by the Ethics Committee of the Teaching Hospital {No: AB (II)/ETHICAL/2007}. The study population constituted patients with leptospirosis who were admitted to wards 33 and 35, from July 1, 2007, to July 31, 2008, for a period of one year. As the study was carried out only for a year, all patients who were confirmed as having leptospirosis by serology were included in the study. Patients without a serological proof or those who died before serologically proving leptospirosis were excluded.

Procedure

Patients with clinical features of leptospirosis were screened using a symptom checklist and interviewer administered questionnaire to diagnose leptospirosis according to the leptospirosis case definition. Surveillance case definition for diagnosis of leptospirosis, which was published by the Epidemiology Unit, was used for the present study. [15] Nine clinical features thought to predict complications were recorded. The clinical features were chest pain, Shortness Of Breath (SOB), oliguria, jaundice, bleeding, conjunctival suffusion, arrhythmias (irregular radial pulse), muscle tenderness, and hepatomegaly. Blood samples were taken on admission for Hemoglobin (Hb), Packed Cell Volume (PCV), White Blood Cell (WBC) count, bilirubin, Platelet Count (PLC), Blood Urea (BU), serum Potassium (K), and creatinine.

Leptospirosis was confirmed using the genus specific Microscopic Agglutination Test (MAT) done on blood samples drawn on the seventh day of fever. Informed written consent was obtained from patients before they participated in the study as well as before blood sampling. The MAT was done at Medical Research Institute (MRI), Colombo, which uses the non-pathogenic Patoc strain of Leptospira biflexa. A positive MAT test was defined as a titer of ≥1:800 in acute phase serum. This is the titer specified by MRI, which is the national reference laboratory. [16] Reported sensitivity and specificity of MAT are as high as 92% and 95%, respectively. Positive predictive values of 95% and negative predictive values of 100% also have been documented. [17]

Only the laboratory confirmed patients were included in the study. The patients were observed for the development of acute renal failure or myocarditis alone or in combination.

Acute renal failure was defined as the presence of one of the following criteria:

  • An increase in serum creatinine of >0.5 mg/dl
  • An increase in serum creatinine of >50% from baseline
  • A reduction in calculated creatinine clearance of >50%
  • Need for dialysis


Myocarditis was defined as reduction in systolic blood pressure below 100 mm Hg with one of the following criteria:

  • Presence of transient ST segment changes, T-wave changes, or conduction abnormalities in the absence of electrolyte imbalances
  • Reduction of ejection fraction <40% with characteristic echocardiographic evidence of myocarditis
  • Need for ionotropic support


Statistical analysis

Descriptive analyses of patients with and without complications were done using proportions and percentages. Chi-square statistics, Fisher's exact test, and Student's t test were used to compare patients with and without complications. All variables with P<0.1 were selected for the predictor model. A logistic regression model was used to evaluate the predictor variables. A backward stepwise elimination of variables was carried out to select final variables included in the model. Results were analyzed using SPSS software.


   Results Top


Sixty-two confirmed leptospirosis patients were included in the study. Mean age of the confirmed cases of leptospirosis was 39 years with a standard deviation of 19. The male to female ratio was 3:1. Six patients (9.6%) developed acute renal failure and five (8%) developed myocarditis, while three (4.8%) had acute renal failure and myocarditis together. [Table 1] shows distribution of confirmed cases of leptospirosis by clinical features and complications.

Of the eight patients who had arrhythmias, five (62.5%) developed complications, and among 54 patients without arrhythmias, only 10 (18.5%) developed complications. This observed difference was statistically significant.
Table 1: Distribution of confirmed cases of leptospirosis by clinical features and complications

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[Table 2] shows distribution of confirmed cases of leptospirosis by investigation findings and complication.
Table 2: Distribution of confirmed cases of leptospirosis by investigation findings and complications

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In the univariate analysis, patients with complications had lower Hb, PCV, and platelet count with higher WBC counts, blood urea, and creatinine levels as compared to those without complications.

These clinical features and investigations were then entered into a logistic regression model to assess the predictor values of each variable. [Table 3] shows the results of logistic regression model. In the backward stepwise elimination process, only three variables were retained in the model. Oliguria, jaundice, and arrhythmia on admission were shown as predictors of acute renal failure and myocarditis.
Table 3: Variables included in the final model that predicts leptospirosis complications

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   Discussion Top


Clinical presentation of leptospirosis can be varied and nonspecific; hence, recognition of red flags of complications is of paramount importance. The aim of our study was to determine such red flags and formulate a risk predictor model. Of the many clinical and laboratory predictors of mortality that have been described, we assessed nine clinical and eight laboratory variables in our study. Furthermore, several studies have been conducted to determine the predictors of mortality, but studies determining the predictors of complications were not found in Sri Lankan literature. [18] Of the 17 variables assessed, only oliguria, jaundice, and arrhythmias were the predictors of leptospirosis complications. Previous studies have shown 70% of leptospirosis patients having arrhythmias, but in our study, only 13% had arrhythmias. [6] In another study, acute renal failure was found in 40% of patients, which is a higher value as compared to that in our study. In the same study, oliguria was shown to be a sensitive sign of severe leptospirosis; this finding is somewhat similar to the finding of our study. The reason for such high variations in clinical severity of leptospirosis so far remains unexplained, but differences in serovars could be a good reason. Although univariate analysis showed a significant difference in most of the laboratory variables, none of them were significant as predictors in multivariate analysis. Similarly, oliguria and jaundice showed a significant difference as predictors in multivariate analysis despite having no significant difference in univariate analysis. This finding could be due to the confounding effects of the variables. All three variables included in the predictor model were strong predictors and are included in surveillance case definition of leptospirosis in Sri Lanka as well as other countries. Many previous studies have shown leukocytosis, thrombocytopenia, and blood urea as early predictors. [8] Interestingly, none of the investigation findings were shown any value as early predictors of renal or cardiac complications in our study.

This is a valuable finding as most patients present to rural or district hospitals, which lack laboratory facilities; therefore, predicting their complications and need for transfer could be decided using the three clinical criteria alone.

Although many previous studies have shown pulmonary involvement with hemoptysis as a major complication, [14] it was not found in our study. A possible reason for this could be a different pathogenic serovar existing in the area, but this could not be confirmed as we did not analyze for serotypes.

Thrombocytopenia was a common finding in our patients. Despite this, bleeding was uncommon and unlike in other studies, it did not predict the development of myocarditis or acute renal failure. Similarly, leukocytosis was also a common finding, and it is a valuable investigation in differentiating leptospirosis from dengue fever, which is deadlier than leptospirosis. It was also not proven to be effective as a predictor of complications.

As seen with other similar studies, [19] acute renal failure was a major complication in our patients. Oliguria has shown to predict acute renal failure but not BU, K, and creatinine. It is possible that serum biochemical markers lag behind the clinical presentation of acute renal failure in leptospirosis, but the exact mechanism is unknown. How jaundice and arrhythmias predict acute renal failure cannot be explained pathophysiologically. Similarly, although it is possible to explain how arrhythmias predict myocarditis, how jaundice and oliguria does that is unexplainable. An explanation could be that all three clinical features herald multi-organ involvement in the severe condition, with different organs involved in different levels of severity.

Many outcome prediction scores have been developed for critically ill patients, eg, APACHE 11, but none of them have been validated for leptospirosis. [13] According to our study, presence of the three clinical variables-oliguria, jaundice, and arrhythmias-predicts acute renal failure, and hence myocarditis can be used to decide which patient should receive intensive/high dependency care.

Limitations of the study

Although none of the laboratory confirmed cases died, three patients suspected of having leptospirosis died before serology could be performed, and were not included in the study; this could have resulted in bias in the sample.

Duration from the onset of the illness to admission was varied, which could have had some confounding effect on the investigations done on admission. This could be a reason why laboratory investigations were poor in predicting complications.

Due to lack of facilities we could not confirm myocarditis histologically, and it was done with clinical, electrocardiographic and echocardiographic evidence. However, histological confirmation would not change the management of a leptospirosis patient with myocarditis.


   Conclusion Top


This study shows that out of 17 variables, only oliguria, jaundice, and arrhythmia are strong predictors of development of acute renal failure and myocarditis, and none of the laboratory variables could predict these complications.

 
   References Top

1.Dassanayake DL, Wimalaratna H, Agampodi SB, Liyanapathirana VC, Piyarathna TA, Goonapienuwala BL. Evaluation of surveillance case definition in the diagnosis of leptospirosis, using the Microscopic Agglutination Test: A validation study. BMC Infect Dis 2009;9:48.  Back to cited text no. 1
[PUBMED]  [FULLTEXT]  
2.Epidemiology Unit. An interim analysis of leptospirosis outbreak in Sri Lanka - 2008. Colombo: Epidemiology Unit, Ministry of Health Care and Nutrition, Sri Lanka; 2008.  Back to cited text no. 2
    
3.Lee MG, Char G, Dianzumba S, Prussia P. Cardiac involvement in severe leptospirosis. West Indian Med J 1986;35:295-300.  Back to cited text no. 3
[PUBMED]    
4.Ko AI, Galvao Reis M, Ribeiro Dourado CM, Johnson WD, Riley LW. Urban epidemic of severe leptospirosis in Brazil. Salvador Leptospirosis Study Group. Lancet 1999;354:820-5.  Back to cited text no. 4
    
5.Levett PN. Leptospirosis. Clin Microbiol Rev 2001;14:296-326.  Back to cited text no. 5
[PUBMED]  [FULLTEXT]  
6.Rajiv C, Manjuran RJ, Sudhayakumar N, Haneef M. Cardiovascular involvement in leptospirosis. Indian Heart J 1996;48:691-4.  Back to cited text no. 6
[PUBMED]    
7.Trivedi SV, Bhattacharya A, Amichandwala K, Jakkamsetti V. Evaluation of cardiovascular status in severe leptospirosis. J Assoc Physicians India 2003;51:951-3.  Back to cited text no. 7
[PUBMED]    
8.Shah K, Amonkar GP, Kamat RN, Deshpande JR. Cardiac findings in leptospirosis. J Clin Pathol 2010;63:119-23.   Back to cited text no. 8
[PUBMED]  [FULLTEXT]  
9.Irma CL, Orpilla B, Mario M. Panaligan, predictors of mortality among patients with leptospirosis admitted at the JRRMMC. Phil J Microbiol Infect Dis 2002;31:145-9.  Back to cited text no. 9
    
10.Panaphut T, Domrongkitchaiporn S, Thinkamrop B. Prognostic factors of death in leptospirosis: A prospective cohort study in Khon Kaen, Thailand. Int J Infect Dis 2002;6:52-9.  Back to cited text no. 10
    
11.Katz AR, Ansdell VE, Effler PV, Middleton CR, Sasaki DM. Assessment of the clinical presentation and treatment of 353 cases of laboratory-confirmed leptospirosis in Hawaii, 1974-1998. Clin Infect Dis 2001;33:1834-41.  Back to cited text no. 11
[PUBMED]  [FULLTEXT]  
12.Dupont H, Dupont-Perdrizet D, Perie JL, Zehner-Hansen S, Jarrige B, Daijardin JB. Leptospirosis: Prognostic factors associated with mortality. Clin Infect Dis 1997;25:720-4.  Back to cited text no. 12
[PUBMED]  [FULLTEXT]  
13.Bal AM. Unusual clinical manifestations of leptospirosis. J Postgrad Med 2005;51:179-83.  Back to cited text no. 13
[PUBMED]  Medknow Journal  
14.Kobayashi Y. Human leptospirosis: Management and prognosis. J Postgrad Med 2005;51:201-4.  Back to cited text no. 14
[PUBMED]  Medknow Journal  
15.Epidemiology Unit. Leptospirosis. Surveillance Case Definitions for Notifiable Diseases in Sri Lanka. Colombo: Epidemiology Unit, Ministry of Health; 2005. p. 19-20.  Back to cited text no. 15
    
16.Somarathna P. Leptospirosis-re-emerging in a changing pattern? Bull Sri Lanka Coll Microbiol 2008;6:59-62.  Back to cited text no. 16
    
17.Available from: http://www.emedicine.com/PED/topic1298.htm#section~bibliography. [Last accessed on 2010 Dec 1].  Back to cited text no. 17
    
18.Gunawardhana SA, Sellahewa KH. Clinical features of leptospirosis: A prospective descriptive study at the National Hospital of Sri Lanka (NHSL) in 2007. Ceylon Med J 2008;53:155-6.  Back to cited text no. 18
[PUBMED]    
19.Seguro AC, Lomar AV, Rocha AS. Acute renal failure of leptospirosis: Nonoliguric and hypokalemic forms. Nephron 1990;55:146-51.  Back to cited text no. 19
[PUBMED]    

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Correspondence Address:
Dinesh Dassanayake
Registrar in Medicine, Teaching Hospital, Kandy
Sri Lanka
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1755-6783.98627

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