Significant Clinical Presentation of Leptospirosis in Relation to Sociodemographic and Risk Factors in a Tertiary Hospital,Malaysia

Abstract

Introduction:

Incidence of leptospirosis has increased within the past few years in many countries. Its clinical presentations were generally nonspecific, making it difficult to assist in the diagnosis. Besides the determination of the common clinical features, the sociodemographic background is essential to identify high-risk populations to assist in prevention.

Methods:

Data for this study were obtained from electronic medical records among patients clinically diagnosed with leptospirosis at a tertiary hospital in Malaysia from the years 2011 to 2015 and were recorded using standard pro forma. Associations between clinical features and sociodemographics were performed using bivariate analysis and logistic regression.

Results:

Data were collected from 283 patients. Their mean age was 30.71 years old. Out of 283 patients, 206 (72.8%) were male. Involvement in outdoor events and water activities was the highest risk factor of acquiring leptospirosis in 64 (22.7%) patients followed by 59 (20.8%) patients who were staying in crowded housing areas with poor sanitation. Although fever was the main clinical presentation in 274 (96.8%) patients with leptospirosis, gastrointestinal (GIT) symptoms were the second most frequent in 159 (56.2%) patients followed by pulmonary symptoms, myalgia, headache, and jaundice. From the total number of 283 patients, only 21 (92.6%) presented with severe leptospirosis. GIT symptoms were a significant predictor for leptospirosis severity, while the age group was the significant sociodemographic factor toward GIT presentation in leptospirosis. The relationship between GIT symptoms and crowded housing areas with poor sanitation was also significant. Multivariable logistic regression showed that crowded housing areas with poor sanitation (odds ratio [OR] = 3.570, p < 0.001) and age between 20 and 40 years old (OR = 2.056, p = 0.014) were more likely to have GIT symptoms.

Conclusions:

Information regarding the clinical features of leptospirosis to the public is necessary, while targeted prevention by educational outreach among 20–40 year olds especially those participating in outdoor water activities are crucial to decrease the incidence and complications of leptospirosis.

Introduction

Worldwide cases of leptospirosis are estimated to occur more in people living in tropical climates than in temperate climates (WHO 2010). Studies had shown an emerging concern of leptospirosis in Malaysia from a total of 263 cases in 2004 to 3665 and 4457 cases in 2012 and 2013, respectively (Vke 2011, Tan et al. 2016). This may impose a significant health impact and a burden to the nation in the coming years if the disease is not appropriately diagnosed and controlled.

The transmission circle of leptospirosis involves a complex interaction between humans, animal reservoirs, and the environment. Changes of human involvement in the environment such as deforestation and rapid urbanization might cause flooding, which was significantly associated with the incidence of leptospirosis (Naing et al. 2019). In more developed countries, outdoor activities facilitate leptospirosis infection through activities such as wading, swimming, and rafting, especially among travelers participating in “adventure tourism” and water-related activities (Plank and Dean 2000, Lau et al. 2010).

Migration of populations from rural to urban has resulted in the formation of urban slum communities, which is frequently linked to poor hygiene, overcrowding, and poverty infection (Plank and Dean 2000, Lau et al. 2010, Thayaparan et al. 2013). As one of the developing countries, Malaysia is also affected by urbanization resulting in urban population growth and urban decay. Besides that, we have seasonal heavy rainfall with occasional flooding that assists the movement of infectious leptospires from soil or sewers into water surface leading to leptospirosis outbreak (Radi et al. 2018, Naing et al. 2019).

In addition, human behavior and ecological factors influence the dynamics of rodent populations, which serve as a common reservoir for leptospirosis. These factors differ among various households or communities (Munoz-Zanzi et al. 2014). The variability of sociodemography and risk factors for leptospirosis may be different in this country and should be determined.

Although leptospirosis cases have been reported in Malaysia since the 1920s, the actual disease burden in the country remains underestimated. This is partly because it was not in the list of notifiable diseases under the Prevention and Control of Communicable Diseases Act until recently. In addition, notified cases only cover cases diagnosed in the hospital (Rafizah et al. 2013). A study in Northeastern Malaysia showed that only 31.0% of leptospirosis cases were diagnosed as leptospirosis upon discharge, whereas 38.1%, 14.3%, and 7.1% were diagnosed as dengue fever, pneumonia, and typhoid, respectively (Rafizah et al. 2013). Other countries also reported misdiagnosed cases of leptospirosis (Levett et al. 2000, Kishimoto et al. 2004).

Clinical diagnosis of leptospirosis is also nonspecific mimicking other common infections, including dengue and malaria, which require further laboratory confirmation (Chaurasia et al. 2018). In several places, including Brazil, Hawaii, Korea, New Caledonia, and Seychelles, Plank and Dean (2000) reported that common leptospirosis manifestations were fever, myalgia, headache, jaundice, and conjunctival suffusion. Furthermore, untreated cases can progress to more fulminant presentations such as Weil's syndrome involving organs such as kidney which increase the mortality rate (Haake and Levett 2015, Wang et al. 2016).

Herein, we describe findings from our 5-year retrospective data to identify high risk populations and provide common clinical feature information, which may assist in early laboratory confirmation and treatment for leptospirosis.

Materials and Methods

The study was a cross-sectional study using retrospective medical data in Hospital Serdang, a tertiary hospital in the West Coast of Peninsular Malaysia from 2011 to 2015. The hospital was selected because it is in Serdang, a district in the state of Selangor, the most populous state in Malaysia (Department of Statistic Malaysia 2015). In July 2015, the Selangor state had the fourth highest number of reported cases after Kuala Lumpur, Negeri Sembilan, and Sarawak (Garba et al. 2017). Khairani-Bejo et al. (2004) reported 3.1% prevalence of leptospirosis among rats that were caught in Serdang residential area. Based on statistical estimation, the ratio between person and rat population is 1:8 rats indicating that leptospirosis incidence in this region is present (Vke Lim 2011).

A random list of medical record numbers of clinically suspected leptospirosis patients between 2011 and 2015 was generated from the hospital integrated information system. Systematic random sampling was used whereby every second number from the list was chosen and included in this study. Repeated patients, inadequate data from the medical notes, and incorrect clinical diagnosis were excluded. The medical records were retrieved from the system and documented in a standard pro forma.

The pro forma was composed of sections which were demographic information (age, sex, and race) and risk factors (involvement in outdoor and water activities such as triathlon, white water rafting, fishing, recreational water activities; crowded housing with poor sanitation; high risk occupation such as gardener, sewage worker, and veterinary; and involvement with animals and exposure to flood).

Clinical presentation records included the clinical features presented by each patient during hospital admission, which were asymptomatic, fever, headache, myalgia (particularly associated with the calf muscles and lumbar region), jaundice, conjunctival suffusion without purulent discharge, skin rash (maculopapular or petechial), meningitis, gastrointestinal (GIT) symptoms such as nausea, vomiting, abdominal pain, pulmonary complications (cough and breathlessness), cardiac arrhythmia or failure, electrocardiogram (ECG) abnormalities, renal insufficiency (anuria or oliguria), hemorrhages from the intestines and lungs, hematuria, and hematemesis. Data for severe leptospirosis were also collected.

Severe leptospirosis was defined as the presence of at least one of these criteria: Acute kidney injury (increase in serum creatinine >3 fold from baseline or >300 μmol, passing urine <0.3 mL/kg/day or anuric for >12 h, or requiring renal replacement therapy); severe hepatitis (alanine aminotransferase (ALT) >1,000 μmol/L); severe jaundice (bilirubin >70 μmol/L); pulmonary hemorrhage [frank hemoptysis or frank blood from endotracheal tube with at least two of the following: (1) drop of hemoglobin with no other explainable source of bleeding, (2) no clinical signs of fluid overload, and (3) Chest X-ray showing alveolar infiltration pattern]; patient on mechanical ventilation; cardiovascular collapse requiring inotropic support; thrombocytopenia (<70,000/μL); cardiac rhythm disorders (atrial fibrillation, atrial flutter, heart blocks); hemorrhagic manifestations; and neurological involvement (facial palsies, altered Glasgow Coma Scale (GCS), meningeal syndrome).

Laboratory data collected include laboratory methods used to diagnose leptospirosis using serology, PCR, and microscopic agglutination test (MAT) methods and interpreted based on CDC Leptospirosis case definition (CDC 2013). Other tests included were platelet count and liver function test on the day of admission.

We examined descriptive statistics for sociodemographic factors and clinical outcomes in this study. The age was divided into three arbitrary age groups, which were <21, 21–40, and >40 years old, respectively. We conducted chi-squared tests and multivariable logistic regression to assess associations between sociodemographic factors and clinical outcomes at a significance level of 0.05.

Ethical approval

Ethical approval was obtained from the Medical Research and Ethics Committee (MREC) Malaysia (NMRR-15-2148-27536).

Results

The total number of clinically suspected leptospirosis patients was 678, and among them, 122 (16.5%) of the cases were excluded due to repetition, inadequate medical data, and incorrect diagnosis of leptospirosis. Among 283 patients included in the study, 275 (97.1%) were diagnosed as supportive leptospirosis through the detection of IgM against leptospira and by leptospira agglutination titer of >200 but <800 by MAT in an acute serum specimen. Confirmed leptospirosis was diagnosed by PCR from blood samples in three patients (1.1%) and one patient (0.4%) by MAT with agglutination titer >800. Another four clinically diagnosed leptospirosis patients were not supported by laboratory test (CDC 2013). The mean age of the leptospirosis cases was 30.71 years old (range 1–85 years old). There were 206 (72.8%) males and 77 (27.2%) females. The main ethnicity was Malay 175 (61.7%) followed by Chinese and Indian, 32 (11.3%) and 25 (8.8%), respectively. Other ethnicity was 51 (18.0%).

The highest risk of acquiring leptospirosis cases in this study was an outdoor event and water activity 64 (22.7%), followed by staying in a crowded housing area with poor sanitation 59 (20.8%). Nineteen (7.9%) leptospirosis cases were due to high risk occupations, while only six (2.5%) of the patients reported had exposure to floods.

The main clinical presentation at admission was fever in 274 patients (96.8%) followed by GIT symptoms in 159 patients (56.2%). Nearly half of the patients had pulmonary symptoms (cough and breathlessness), and about one quarter manifested with myalgia (particularly associated with calf muscle and lumbar region). About 20.0% of patients presented with headache, while <5.0% had jaundice and skin rash. Cardiac arrhythmia or failure was present in six (2.1%), while eight (2.8%) showed ECG abnormalities. Features of conjunctival suffusion and renal insufficiency were noted in six (2.1%) patients and four patients (1.4%), respectively. Three patients (1.1%) presented with hemorrhages and meningitis, correspondingly. Only one patient was asymptomatic (0.4%) (Table 1). This study also showed that the mean length hospital stay was 6.9 days.

Table 1.

Sociodemographics, Risk Factor, and Sign and Symptoms of Patients with Leptospirosis in Tertiary Hospital (n = 283)

	n = 283	%
Age	Mean 30.71, SD 19.97
Gender
Male	206	72.8
Female	77	27.2
Ethnicity
Malay	175	61.8
Indian	25	8.8
Chinese	32	11.3
Others	51	18
Risk factor
Involvement with outdoor and water activity	64	22.7
Crowded housing area with poor sanitation	59	20.8
High risk occupation (gardener, sewage worker, veterinary etc.)	19	6.7
Involvement with animals	19	6.7
Exposure to flood	6	2.1
Sign and symptoms
Asymptomatic	1	0.4
Fever	274	96.8
Gastrointestinal symptoms such as nausea, vomiting, abdominal pain	159	56.2
Pulmonary symptoms (e.g., cough, breathlessness)	124	43.8
Myalgia particularly associated with the calf muscles and lumbar region	79	27.9
Headache	55	19.4
Jaundice	14	4.9
Meningitis	3	1.1
Skin rash (maculopapular or petechial)	11	3.9
Conjunctival suffusion without purulent discharge	6	2.1
Renal insufficiency (anuria or oliguria)	4	1.4
Cardiac arrhythmia or failure	6	2.1
ECG abnormalities	8	2.8
Hemorrhages (from the intestines and lungs, hematuria, hematemesis)	4	2.1

SD, standard deviation.

Severe leptospirosis manifestation

Severe leptospirosis was diagnosed in 21 out of 283 patients (7.4%). Among severe leptospirosis cases (n = 21), acute kidney injury was found in 17 patients (81.0%), and 10 patients (47.6%) were on mechanical ventilation. Six (28.6%) of the patients had thrombocytopenia. Five cases (23.8%) developed severe jaundice and cardiovascular failure. Pulmonary hemorrhage was found in four patients (19.0%). Only 1 case (4.8%) presented with cardiac arrhythmia on admission (Table 2), and 13 cases (61.9%) succumbed to death.

Table 2.

Distribution of Leptospirosis Patient with Severe Leptospirosis in Tertiary Hospital (n = 21)

Severe leptospirosis marker	n = 21	%
Acute kidney injury	17	81.0
Required assisted mechanical ventilation	10	47.6
Neurological involvement	2	9.5
Severe hepatitis (ALT >1,000 μmol/L)	2	9.5
Severe jaundice (bilirubin >70 μmol/L)	5	23.8
Pulmonary hemorrhage	4	19.0
Cardiovascular collapse requiring inotropic support	5	23.8
Thrombocytopenia (<70,000/μL)	6	28.6
Cardiac arrhythmia	1	4.8

ALT, alanine aminotransferase.

Association between clinical presentation and age group and demographic factors

We found no significant association between clinical presentations with other sociodemographic except that there was a significant association between GIT symptoms and age group (p < 0.05). The study also showed a significant association between leptospirosis severity and age group (p < 0.05). In relation to the risk factors there was only a significant relationship between crowded housing areas with poor sanitation (p < 0.05) and GIT symptoms as shown in Table 3.

Table 3.

Association Between the Age Group and Gastrointestinal Symptoms (n = 283)

Sociodemographic characteristic	Gastrointestinal symptoms				Severe leptospirosis
	Yes	No	χ²	p	Yes	No	χ²	p
	n (%)	n (%)	χ²	p	n (%)	n (%)	χ²	p
Age
<21	41 (45.1)	50 (54.9)	7.205	0.027^*	0 (0)	91 (100.0)	16.255	0.000^*
20–40	76 (63.3)	44 (36.7)	7.205	0.027^*	9 (7.5)	111 (92.5)
>41	42 (58.3)	30 (41.7)			12 (16.7)	60 (83.3)
Gender
Male	120 (58.3)	86 (41.7)	1.316	0.251	14 (6.8)	192 (93.2)	0.43	0.512
Female	39 (50.6)	38 (49.4)			7 (9.1)	70 (90.9)
Ethnicity
Malay	97 (55.4)	78 (44.6)	1.124	0.771	12 (6.9)	163 (93.1)		0.076^a
Chinese	15 (60.0)	10 (40.0)			4 (16.0)	21 (84.0)
Indian	16 (50.0)	16 (50.0)			4 (12.5)	28 (87.5)
Others	31 (60.8)	20 (39.2)			1 (2.0)	50 (98.0)
Crowded housing with poor sanitation
Yes	46 (78.0)	13 (22.0)	14.367	<0.001^*	4 (6.8)	55 (93.2)	0.45	1.000
No	113 (50.4)	111 (49.6)			17 (7.6)	207 (92.4)

Fisher exact test.

Significant at p < 0.05.

Using the multivariable logistic regression analysis, factors with a significant association with GIT symptoms in the bivariate analyses were entered into the multivariable model. Staying in crowded housing areas with poor sanitation (odds ratio [OR] = 3.570, p < 0.001) and age from 20 to 40 (OR = 2.056, p = 0.014) were more likely to have GIT symptoms compared to their counterparts (Table 4).

Table 4.

Multivariable Logistic Regression Analysis for Factors Associated with Gastrointestinal Symptoms (n = 283)

Variable	Gastrointestinal symptoms			Multivariable logistic regression
	Yes	No	p	OR (95% CI)
	n (%)	n (%)	p	OR (95% CI)
Age			0.027^*
<21	41 (45.1)	50 (54.9)		Ref.
20–40	76 (63.3)	44 (36.7)		2.056 (1.16–3.65)^*
>41	42 (58.3)	30 (41.7)		1.972 (1.04–3.75)^*
Crowded housing with poor sanitation			<0.001^*
Yes	46 (78.0)	13 (22.0)		3.570 (1.803–7.069)^*
No	113 (50.4)	111 (49.6)		Ref.

Significance level p < 0.05.

CI, confidence interval; OR, odds ratio.

Discussion

The outcomes of this study provide recent information on the influence of sociodemographic factors on clinical presentation of leptospirosis in the West Coast region of Peninsular Malaysia. We found that the involvement of water and outdoor activities contributed to the highest leptospirosis frequency. Despite efforts from the local authorities (Nicholas 2016), the recurrent incidence of water-related leptospirosis had been reported since the outbreak among international participants in the Eco-Challenge in 2000 in East Malaysia followed by series of cases in Lubuk Yu Pahang (2010), in Kedah (2011), and also in Sungai Siput Malaysia (2012) (Thayaparan et al. 2013). The most common age group acquiring leptospirosis in this study was among middle age group and in view of the increasing popularity of water adventures among them; education about the risk of leptospirosis should be emphasized to this group.

Crowded housing with poor sanitation showed the second risk factor of leptospirosis, which may be contributed by rapid urbanization and increase in slum areas due to squatters' houses (Plank and Dean 2000, Shuid 2010). The slum environments will favor the increase of the rat population. Close encounters between rats and humans can lead to leptospirosis transmission. A better understanding within the community level of how to prevent the uncontrolled growth in rat population in the areas can potentially lead to a decline of these zoonotic diseases (Philip et al. 2013).

High risk occupation, including gardener, sewage worker, and veterinary, and involvement with animals carried minimal risk of getting leptospirosis disease in this study. They are mainly carriers or immune to the disease as shown by high leptospirosis seroprevalence among healthy municipal employees (Samsudin et al. 2015). We also noted that in this study, minimal leptospirosis cases were exposed to flood, which differ from North-eastern Peninsular Malaysia whereby the higher leptospirosis was suggested to attribute to higher rainfall especially during monsoon season (Ridzlan et al. 2010).

Our study also showed that more leptospirosis cases involve men, which was similar to other studies (Ko et al. 1999, Katz et al. 2011). We found that there was no significant association between gender and risk factors, which include exposure to flood, involve in water and outdoor activities, and involve with animals and high-risk occupation (Table 5) which differ from Philip et al. (2013) who found that men were participating more in riskier jobs like harvesting and animal handling in India.

Table 5.

Association Between Gender and Risk Factors (n = 283)

Risk factors	Gender
	Male	Female	χ²	p
	n (%)	n (%)	χ²	p
Risk factors
Exposure to flood
Yes	4 (66.7)	2 (33.3)	0.116	0.665
No	202 (72.9)	75 (27.1)	0.116	0.665
Outdoor activities
Yes	33 (84.6)	6 (15.4)	3.121	0.083
No	172 (71.1)	70 (28.9)	3.121	0.083
Involve with animal
Yes	17 (89.5)	2 (10.5)	2.862	0.112
No	189 (71.6)	75 (28.4)	2.862	0.112
Crowded housing with poor sanitation
Yes	43 (72.9)	16 (27.1)	0.000	1.000
No	163 (72.8)	61 (27.2)	0.000	1.000
High risk group
Yes	16 (84.2)	3 (15.8)	1.341	0.298
No	190 (72.0)	74 (28.0)	1.341	0.298

Significant at p < 0.05.

From the findings, staying in areas of crowded housing with poor sanitation and involvement in outdoor water activities increased the odds of leptospirosis for those individuals. Information about leptospirosis should be disseminated to them to increase their knowledge, attitude, and practice toward the prevention of leptospirosis.

Clinical presentation of leptospirosis

The spectrum of human disease caused by leptospires is extremely wide, ranging from subclinical infection to severe syndrome of multiorgan infection with high mortality. Fever was found to be the main clinical presentation followed by GIT symptoms, pulmonary symptoms, myalgia, headache, and jaundice. However, the majority of other studies showed minimal or no gastrointestinal presentation in leptospirosis (Abgueguen et al. 2008, Svarch et al. 2017, Pakoa et al. 2018, Sukmark et al. 2018). Only a few studies showed similar finding whereby nausea, vomiting, and abdominal pain occurred in up to 60% of patients, after fever and headache by Tique et al. (2018) in Columbia and about 70% in Brazil by Daher et al. (2010) after fever, jaundice, myalgia, and headache.

We also found that there was a significant correlation between GIT symptoms and the age group between 20 and 40 years. Furthermore, crowded housing with poor sanitation had a significant association with the GIT symptoms. This study suggests that besides fever, GIT symptoms could be a clinical indicator to diagnose leptospirosis especially in patients coming from crowded housing areas.

Symptoms of nonproductive cough had been reported in 20–57% of leptospirosis patients (Haake and Levett 2015). This was similar to this study whereby nearly half (43.8%) of the cases were found to have pulmonary symptoms. Although pneumonia was not commonly associated with leptospirosis, pulmonary involvement in leptospirosis varies from atypical symptoms to severe pulmonary hemorrhage. In Semarang Indonesia, a study reported four cases of laboratory-confirmed leptospirosis presenting with community-acquired pneumonia (Gasem et al. 2016).

Although myalgia represents a common presentation of leptospirosis especially on calf muscle and lumbar region (Daher et al. 2010), we found that myalgia (27.9%) was an uncommon presentation. Less than half of leptospirosis patients presented with headache (19.4%), which was different from another study in which headache was a much more common symptom for up to 74.0% of cases (Daher et al. 2010). Although conjunctival suffusion serves as a specific diagnostic sign for leptospirosis (Plank and Dean 2000), we found that only 2.1% of patients in this study had the symptom.

Percentages of leptospirosis patients presented with jaundice and rash in this study were low, which were 4.9% and 3.9%, respectively. Jaundice frequency varies widely among case series, due, in part, to the virulence and serogroup of the causative organism (Haake and Levett 2015). Rash is uncommon in leptospirosis generally, and clinical presentation of rash in dengue fever and leptospirosis is considerably overlapping, leading to misdiagnosis or underdiagnoses in cases of mixed infection (Pan et al. 2016, Priya et al. 2017).

Although the length of stay in hospital is similar to other study as 6.9 ± 3.6 days (Hartskeerl et al. 2011, Traxler et al. 2014), leptospirosis-associated hospitalizations in Malaysia are slightly longer than dengue 4.2 ± 2.1 days (Mallhi et al. 2015). This indicates that the economic burden is higher in leptospirosis than dengue based on the days of hospital stay. In addition, a longer stay in hospital is significantly associated with other complications such as nosocomial infection that further increases the cost burden (Dasgupta et al. 2015).

Study limitations

The main limitations of this study are its retrospective design, limited sociodemographic factors were included in the pro forma, incomplete required data in few patient records, and the study was only conducted in one region of Malaysia.

Conclusion

In this study, leptospirosis cases were mostly found among individuals who had a history of water and outdoor activities and among those who were 20- to 40-year old. Attention to GIT symptoms should not be ignored to avoid misdiagnosis of leptospirosis. Leptospirosis education and awareness for those who participate in outdoor water activities are essential. Leptospirosis prevention should also incorporate improvement of sewage system maintenance and redevelopment of overcrowding housing areas.

Footnotes

Acknowledgment

The authors thank the Director General of Health Malaysia for his permission to publish this article.

Author Disclosure Statement

The authors declare that they have no competing interests.

Funding Information

This study was supported by Long Term Research Grant Scheme (LRGS) grant number UPM/700-2/1/LRGS/5526400.

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