|Year : 2015 | Volume
| Issue : 1 | Page : 29-33
Clinical profile, epidemiology and prognostic factors of scrub typhus in a tertiary care centre
Priyadarshini Balasubramanian1, Anitha Puduvail Moorkoth2, Udayabhaskaran Valuvil1, Jayesh Kumar1, Jahana Thottathil2, Kalpana George2
1 Department of Medicine, Government Medical College, Kozhikode, Kerala, India
2 Department of Microbiology, Government Medical College, Kozhikode, Kerala, India
|Date of Web Publication||16-Jun-2015|
Anitha Puduvail Moorkoth
Department of Microbiology, Government Medical College, Kozhikode, Kerala
Source of Support: None, Conflict of Interest: None
Background: There has been a gross under diagnosis of scrub typhus cases in India due to its non-specific and diverse clinical presentations, limited awareness, lack of high index of suspicion, and limited number of clinical studies. An early diagnosis and prompt institution of treatment can avert significant morbidity and mortality. Materials and Methods: This was an observational study of prospective design conducted in the Department of General Medicine, Government Medical College, Kozhikode over a period of 1½ years from 1 st January 2012 to 31 st June 2013. Patients with clinical features suggestive of scrub typhus with positive Weil-Felix OXK ≥160 or 4 fold increase in titre and/or positive IgM ELISA for scrub typhus were included in the study. Results: Out of 70 patients with clinical features suggestive of scrub typhus, 39 (56%) were males, and 31 (44%) were females. Most cases occurred during the cooler months of the year (October to February). Fever was the most prominent symptom (100%) followed by headache in 68 (98.6%) patients. The most common physical sign was lymphadenopathy in 44 (62.8%) cases, eschar was present in 32 (45.7%) cases with groin being the most common site (31.3%). Leucocytosis was observed in 28 (40%) and was associated with statistically significant mortality rate and increased complications like meningoencephalitis. Mortality rate was also higher in the patients with erythrocyte sedimentation rate >100 (46.2%) (P = 0.002) and in patients with serum albumin <2 g% (66.7%) (P = 0.001). An association between low serum albumin (<2 g%) and myocarditis was also observed. The complications observed in our study were myocarditis in 17.1%, meningoencephalitis in 14.3%, acute kidney injury in 44.3%, and adult respiratory distress syndrome in 8.5%. Totally, 62 (88.6%) patients responded to Doxycycline whereas 8 (11.4%) showed no response and were treated with Azithromycin or Chloramphenicol. There is an emerging resistance to Doxycycline in the community. The case fatality rate was 14.3%.
Keywords: Clinical profile, India, Kerala, prognostic factors, rickettsial infections, scrub typhus
|How to cite this article:|
Balasubramanian P, Moorkoth AP, Valuvil U, Kumar J, Thottathil J, George K. Clinical profile, epidemiology and prognostic factors of scrub typhus in a tertiary care centre. J Acad Clin Microbiol 2015;17:29-33
|How to cite this URL:|
Balasubramanian P, Moorkoth AP, Valuvil U, Kumar J, Thottathil J, George K. Clinical profile, epidemiology and prognostic factors of scrub typhus in a tertiary care centre. J Acad Clin Microbiol [serial online] 2015 [cited 2022 Oct 5];17:29-33. Available from: https://www.jacmjournal.org/text.asp?2015/17/1/29/158799
| Introduction|| |
Scrub typhus is a zoonosis, which causes vasculitis that involves multiple-organs including the lungs, heart, kidney, spleen, and central nervous system (CNS). The disease is caused by infection with Orientia tsutsugamushi, and is transmitted by the bite of larval stage (chiggers) of trombiculid mite. Disseminated vasculitis with perivasculitis is the pathologic hallmark of scrub typhus. The clinical manifestations of this disease range from sub-clinical disease to fatal multi-organ disease with varied symptoms. Scrub typhus is an underdiagnosed disease that is potentially treatable when there is a high index of suspicion. Death is most commonly due to late presentation, delayed diagnosis, and drug resistance. Considering the fatality if under diagnosed or misdiagnosed and the threat of scrub typhus as a major public health problem, this study has a significant place in the field of public health as it throws light on the clinical features and prognostic factors of scrub typhus.
| Materials and methods|| |
The aim was to study the clinical profile, epidemiology, and prognostic factors of scrub typhus.
Period and study population
This was an observational study of prospective design conducted in the Department of General Medicine, Government Medical College, Kozhikode over a period of 1½ years from 1 st January 2012 to 30 th June 2013.
- Age >13 years. (2) Patient satisfying any 3 of the 4 criteria defined below was included.
- Clinical features suggestive of Scrub typhus (2) presence of eschar (3) either positive Weil-Felix OXK ≥160 OR a four-fold increase in titre (4) positive IgM ELISA for scrub typhus.
Patients with established chronic renal disease, chronic infections, chronic liver disease or connective tissue disorders
Definitions of complications
(1) Myocarditis: Defined as severe cardiac dysfunction, haemodynamic compromise requiring vasopressors, with electrocardiogram (ECG) changes consistent with myocarditis, positive cardiac biomarkers with evidence on two-dimensional echo with no previous history of structural or ischemic heart disease. (2) Adult respiratory distress syndrome (ARDS): Defined as the acute onset of respiratory failure, with bilateral infiltrates on chest radiograph and hypoxemia defined as PaO 2 /FIO 2 ratio <200. (3) Meningoencephalitis: Defined as clinical features of headache, altered sensorium with or without seizures or focal neurological deficits with consistent cerebrospinal fluid (CSF) findings and abnormal electroencephalogram (EEG) with consistent findings on magnetic resonance imaging (MRI). (4) Acute kidney injury (AKI): Defined as any of the following. (a) Increase in serum creatinine (SCr) by 0.3 mg/dL within 48 h or (b) Increase in SCr to 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days or (c) urine volume of <0.5 mL/kg/h for 6 h.
Response to Doxycycline is defined as the patient becoming afebrile within 48 h of starting Doxycycline.
Written informed consent was obtained from all the patients or their legal surrogates before enrolment.
A thorough history was obtained from all patients regarding their symptoms, occupational behaviour, and the area of residence. A detailed clinical examination was done in all patients.
Weil-Felix tube agglutination test (multiple micro 3) using IVD FAR diagnostic kit for OXK, OX2 and OX19, and IgM ELISA for scrub typhus using Scrub Typhus Detect™ IgM ELISA system manufactured by InBios International Inc., USA was done to identify cases based on the defined criteria. Positive and negative controls were run for each test.
Routine investigations that were done, included complete blood count with erythrocyte sedimentation rate (ESR), urine routine and microscopy, renal function tests, liver function tests, coagulation parameters in all patients. Other diagnoses like enteric fever, leptospirosis, and malaria were excluded in all cases with blood culture, Widal test, peripheral smear for the malarial parasite, IgM Dengue, and IgM Leptospira. Lumbar puncture and CSF study were done in cases where CNS involvement was suspected. Pure tone audiometry was done to assess hearing, in patients with complaints of hearing loss. ECG was taken in all cases and EEG was done in cases where meningoencephalitis was suspected. Chest X-ray, ultrasound abdomen, MRI brain, and echocardiography were done in relevant cases.
Doxycycline was used as the first-line drug in the treatment. In cases with no response to Doxycycline either Chloramphenicol or Azithromycin was used.
Data were analysed with SPSS software (SPSS Inc., USA). The statistical significance of different variables was calculated using Chi-square test and Pearson's correlation co-efficient wherever needed. P < 0.05 was considered significant.
| Results|| |
A total of 70 patients satisfying the inclusion and exclusion criteria were included in the study. Of these, 39 (56%) were males and 31 (44%) were females. Majority of the patients 46 (65.7%) belonged to the age group 21-50 years. There were 49 (70%) manual labourers and 95.7% patients belonged to the lower socioeconomic strata. In our study, 39 that is, 55.7% cases occurred during the period from October to February [Figure 1].
Of the 70 patients in our study, 18 (25.7%) were from Malapuram district and 14 (20%) from Wayanad district. The rest of the patients hailed from in and around Kozhikode district.
Fever was the most prominent symptom and was seen in all (100%) with rigors and chills in 33 patients (47.1%) and intermittent fever in 91.4% patients. Most patients, that is, 44 (62.9%) had a duration of fever between 8 and 14 days at presentation. The next common symptom was a headache, which was present in 69 (98.6%) patients [Figure 2].
The most common physical sign was lymphadenopathy [Figure 3], which was present in 44 patients (62.8%) of which 34 (77.3%) had localised lymphadenopathy and 10 (22.7%) had generalised lymphadenopathy. Eschar was present in 32 (45.7%) cases [Figure 4]. The most common site of eschar in 10 (31.3%) cases was groin, and the next common site was eight (25%) cases with eschar on the shoulder [Figure 5]. There was no difference in the distribution of eschar in males and females.
|Figure 3: Number of patients in whom the various signs were elicited HM: Hepatomegaly, SM: Splenomegaly, LNE: Lymphadenopathy|
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The complications observed in the study were myocarditis in 12 (17.1%), meningoencephalitis in 9 (12.8%), AKI in 31 (44.3%), and ARDS in 6 (8.5%) patients. Among females, 9 (29%) had myocarditis while only 3 (7.7%) males had myocarditis. Of the 9 patients with meningoencephalitis, 5 (55.6%) had CSF TC in the range 50-100 cells with lymphocyte predominance. CSF sugar/RBS ratio was <2/3 rd in 7 (77.8%) patients. CSF protein was <60 mg% in 5 (55.6%) patients and between 60 and 100 mg% in 4 (44.4%).
Of 70 patients, 28 (40%) had leucocytosis (TC >11,000) and it showed significant association with complications and mortality. Other parameters that were analysed for association with complications and mortality are given in [Table 1]. Thrombocytopenia (platelet count <1 lakh) was seen in 21 (30%) patients. In this study, no correlation between thrombocytopenia and prognosis was seen.
|Table 1: Biochemical parameters with associated complications and mortality rates|
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Association of elevated serum glutamic oxaloacetic transaminase (SGOT) with complications were not analysed as it is seen to be increased in other conditions as well.
All the cases had Weil-Felix titre of ≥160. Of 70, 41 (58.6%) cases had titre 160; 26 cases (37.1%) had titre of 320; and 3 cases (4.3%) had titre of 640. IgM scrub ELISA was positive in all the cases tested.
Of the total 70 patients, 62 (88.6%) responded to Doxycycline whereas 8 (11.4%) showed no response. These patients were treated with either Azithromycin or Chloramphenicol. Chloramphenicol was used in three patients and Azithromycin in six patients.
Of 70, 60 patients (85.7%) survived and 10 patients expired. The case fatality rate was 14.3%.
| Discussion|| |
Of the 70 patients included in the study after satisfying the inclusion criteria, 39 (56%) were males and 31 (44%) were females. This is consistent with results of study by Gurung et al. with a male preponderance of the disease.  This may be due to the fact that men are more involved in outdoor activities compared to women and are more exposed to chigger bites. Majority of the patients 46 (65.7%) belonged to the age group 21-50 years which corresponds to working population in our country. Totally, 49 patients (70%) were manual labourers. Of 67 (95.7%) patients belonged to poor socioeconomic status.
Scrub typhus is an infectious disease with seasonal variation. Most cases are known to occur during the cooler months of the year. In our study, 39 (55.7%) cases occurred during the period from October to February consistent with the study by Mathai et al.  The clinical illness may vary from mild, self-limiting to severe fatal disease. Fever and headache were the most common symptoms seen in this study.
The most common physical sign was lymphadenopathy and localised regional lymphadenopathy was more common than generalised. Similar observations were made by Ogawa et al.  Eschar is generally seen in <50% of cases and in this study eschar was present in 32 (45.7%) cases consistent with the study by Chrispal et al.  The most common site of eschar was groin and the next common site was a shoulder. Study by Vivekanandan et al. had similar results with eschar in 46% cases and the most common sites being axilla, breast, and the groin. 
Leucocytosis is known to be one of the parameters associated with poor clinical outcome in scrub typhus. In the present study, leucocytosis was seen to be poor prognostic marker and leucopenia good prognostic factor in scrub typhus (P = 0.036). This result is similar to the study by Lee et al. according to which leucocytosis is an independent predictor of complications and mortality. 
Hypoalbuminemia was also seen to be a poor prognostic indicator. Severe hypoalbuminemia was associated with increased mortality and a higher risk of complications like myocarditis and encephalitis. Similar result was obtained in a study by Lee et al. in Korea where hypoalbuminemia in scrub typhus was closely related to the frequency of various complication and longer hospital stay.  Totally, 41 (58.6%) of patients had albuminuria probably related to the endothelial damage and as a part of capillary leakage.
Other blood parameters associated with complications and poor prognosis included higher TC (>20,000), ESR >100 mm/1 st h, hyponatraemia serum Na <120 mEq/L, elevated serum transaminases especially more than 2 times the normal elevation of SGOT, and of serum glutamic pyruvic transaminase [Table 1]. Association of higher total blood count with encephalitis was also noted in a study by Viswanathan et al. 
Majority of patients with meningoencephalitis had CSF TC in the range 50-100 cells with lymphocyte predominance, CSF sugar/RBS ratio less than 2/3 rd , and CSF protein <60mg%.
In the present study, myocarditis was seen more in females. The reason for this female predisposition is not known and requires further study.
Cases of scrub typhus resistant to Doxycycline have been reported from Thailand.  In this study, 8 patients (11.4%) showed no response to Doxycycline. These patients were treated with either Azithromycin or Chloramphenicol. This shows that resistance to Doxycycline is emerging in our society, and we need to consider the possibility of scrub typhus in the appropriate clinical setting even in the absence of response to Doxycycline.
Of the 70 patients, 60 (85.7%) survived and 10 patients (14.3%) expired. The case fatality rate was 14.3% consistent with the study by Varghese et al. 
Scrub typhus is an emerging infectious disease in Northern Kerala and is important to have a high degree of clinical suspicion for early diagnosis and prompt treatment. Awareness of Prognostic indicators will help recognise the impending complications and appropriate management, which can reduce the associated mortality.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]