Scrub typhus is an acute febrile illness endemic to the ‘tsutsugamushi triangle’, which encompasses broad areas of south and southeastern Asia, the Asian Pacific Rim, and northern Australia, with a population of over one billion people. This infection is caused by Orientia tsutsugamushi, which is an obligate intracellular Gram-negative bacterium, transmitted to humans by the bite of the larval stage of trombiculid mites. It is a seasonal infectious disease occurring between August to December. A clear re-emergence of the disease has been documented in the southern part of India and some states of north India like Rajasthan, is more prevalent in Hadoti region of Rajasthan. As scrub typhus is more prevalent in this region of the state, we conducted a cross-sectional study to study epidemiology, clinical manifestations, and laboratory parameters of scrub typhus.
The disease mainly presented with fever, headache, myalgia, cough, breathlessness, generalized body swelling, seizures, and altered sensorium, in which fever is the most common presenting symptom. In a highly variable percentage (10%-92%) of patients an eschar mark can be found at the inoculation site. The infection can range from a self-limiting disease to a fatal illness in 35%-50% of cases, with multiorgan dysfunction, if not promptly diagnosed and appropriately treated. Complications including acute respiratory distress syndrome, hepatitis, renal failure, meningoencephalitis, and myocarditis with circulatory collapse may present in a varying percentage of patients.
The disease is presented with various abnormal laboratory parameters including thrombocytopenia, deranged liver function test with transaminitis, reported in the majority of cases (66.7% to > 90%)[2,5,6], renal dysfunction as evidenced by elevated serum creatinine, most studies have reported it to be presented in 10%-20%[2,6], and hypoalbuminemia, increased triglyceride levels, increased lactate dehydrogenase (LDH), hypocalcemia in variable proportion.
2. Patients and methods
2.1. Study design
This cross-sectional study was conducted from August 2022 to November 2022. Patients over the age of 14 years with acute febrile illness, admitted to the Medicine Department of Government Medical College & Attached Hospitals, Kota were included in the study. The sample was collected using a nonprobability convenience sampling technique.
During the time of admission, a structured questionnaire was administered to assess the demographic variable. Data were collected regarding demographics, occupation, clinical presentation, delay in presentation to hospital, complications, and laboratory data (complete blood counts, urine complete, blood urea, serum creatinine, liver function tests, lipid profile, serum LDH, creatine kinase isoenzyme, serum calcium), requirement of oxygen, ventilatory support, vasopressor support, duration of illness before hospital admission, and duration of hospital admission. All patients underwent complete history, general physical & systemic examination. Specific emphasis was given to patient’s vitals and the presence of an eschar mark. The diagnosis was confirmed by serum IgM ELISA scrub typhus. The presence of an eschar mark provided supportive evidence.
2.3. Ethical statement
Ethical clearance was taken from Institutional ethical committee of GMC, Kota, India. Written informed consent was obtained for each patient before their enrollment in the study.
2.4. Statistical analysis
After initiating treatment, the primary outcomes were the number of days required for complete recovery of the patient and mortality. Data were presented as numbers and percentages and analyzed using Microsoft Excel.
A total of 89 patients presented with acute febrile illness and were potentially eligible candidates for the study. Out of which 63 candidates were confirmed eligible as scrub typhus IgM was positive in these patients. Out of these 63 candidates, 9 patients lost to follow up and 4 patients did not consent for study. Finally 50 patients completed the follow up and all of them were included in the study (Figure 1).
3.1. Demographic and basic characteristics
Most of the patients were admitted in September 2022 and after September, there was a steep decline in the number of cases. Very few cases were reported in November 2022. Out of the total patients admitted, 92% of the patients were from a rural background, 86% were farmers, and the majority were females (female/male=6:4) (Table 1).
3.2. Clinical symptoms and complications
Out of the 50 patients included in the study, all of them complained of fever and myalgia. Majority of them had headache, nausea, vomiting, cough, shortness of breath, generalized body swelling. Few of them also developed seizures, altered sensorium, hepatosplenomegaly and eschar mark. Complications like pneumonia and multi organ dysfunction syndrome were seen in majority of patients and some of them developed hepatitis, acute kidney injury, and shock (Table 2).
3.3. Laboratory results
Anemia (<10 g/dL) was observed in 26% of patients and thrombocytopenia in 90% of patients, out of which 4 patients required packed cell volume transfusion and 7 patients required platelets transfusion. Bilirubin>2.5 mg/dL was seen in 32% of patients and serum glutamic-oxaloacetic transaminase/serum glutamic pyruvic transaminase more than 4 times of upper limit was seen in 38% of patients, creatinine ≥1.5 mg/dL was seen in 42% of patients, triglyceride >200 mg/dL was in 80% of patients, high-density lipoprotein<30 mg/dL in 76% of patients, low-density lipoprotein (LDH)>480 IU/L in 90% of patients, albumin<3.5 g/dL in 98% of patients. Hypocalcemia (<8 mg/dL) was observed in 56% of patients (Table 3).
It was observed that in critically ill patients, triglyceride levels and LDH level was high while serum albumin and serum calcium levels were decreased. With the improvement in clinical status, levels of these indexes became near normal without any intervention.
3.4. Treatment and outcomes
The average duration of illness before hospital admission was 8 days and the average duration of hospital stay was 6.5 days. It was observed that patients who presented late in hospital during course of illness were found more critically ill and their hospital stay was also long.
Oxygen support was required in 64% of patients and they were put on either a simple oxygen mask or a nonrebreathing face mask according to oxygen requirement. A total of 12% required invasive ventilatory support and 4% required non-invasive ventilatory support. Vasopressor support was required in 40% of patients and 56% of patients required ICU admission. Mortality was 18%.
Scrub typhus is a potentially fatal infection that affects about one million people every year. In our study, most of the patients were from a rural area (92%), which is slightly higher compared to the study of Saha et al(78.6%). A total of 86% of patients were farmers or engaged in animal husbandry.
Patients were between 15 to 80 years old but most of the cases were between the age of 40 to 60 years old. More patients were female, which is similar to the study by Takhar et al. It is because most of the work related to farming and husbandry is carried out by females in this region.
In this study, cases of scrub typhus occurred between August to November and more occurred in September, which is similar to other studies as well[8,9,10]. In this study, mean duration of illness before the hospital visit was 8 days, and patients presented with fever (100%), myalgia (100%), headache (82%), nausea/vomiting (62%), cough (68%), shortness of breath (60%), seizure (10%), altered sensorium (20%), and body swelling (80%).
Skin lesion eschar mark was present in 24% of patients. The incidence varies from 10% to 70% in various studies[7,11]. The variation in the incidence of an eschar may represent the different geographic distribution of the various strain of the organism or inadequate search for the eschar; further research is warranted in this area.
In this study, pulmonary dysfunction was the most common complication (64%) and it varied from mild pneumonia to acute respiratory distress syndrome, in which 16% of patients required ventilatory support. In the study by Varghese et al, the most common complication was also pulmonary dysfunction and 69% of patients required ventilatory support. Other complications include shock (40%), hepatitis (44%), multiple organ dysfunction syndrome (62%), and acute renal failure (42%). The incidence of renal impairment is higher than the 18% reported by Varghese et al and 23.2% reported by Attur et al, and 66.4% reported by Mahajan et al. Higher mortality was seen in the patients who presented with acute respiratory distress syndrome and hypotension and required vasopressor support. In this study, thrombocytopenia was seen in 90%, increased triglyceride was seen in 80%, decreased albumin levels in 98%, and increased LDH in 90% of patients.
Fatality rate varies from 0% to 25% in various studies conducted in India[8,11,13], while in this study, it was 18%.
Scrub typhus is a serious acute febrile illness that can lead to multiorgan dysfunction and is associated with significant mortality. Mortality is significantly higher in a patient with pulmonary dysfunction or renal failure and in those who required vasopressor support for hypotension. Because of increasing awareness and early diagnosis, mortality is decreasing over several years. By increasing awareness regarding disease in endemic regions, early screening of patients, and treatment as early as possible we can prevent the patient from severe life-threatening complications.
Conflict of interest statement
The authors report no conflict of interest.
This study received no extramural funding.
PJ developed the concept and design of the study. M Sharma contributed with literature search, data acquisition. Data analysis, statistical analysis, manuscript preparation and editing was done by M Sharma and M Seval. PM and All authors have reviewed and approved the final version of the manuscript.
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