Acute Febrile Illness (AFI) is defined as a patient with fever of 38°C or higher at presentation or history of fever that persisted for 2–7 days with no localizing source [1]. Acute febrile illness is a common cause of patients seeking health care settings posing a diagnostic and therapeutic challenge to the health care workers. Field studies on fever etiology in India are few and surveillance is limited by lack of accessibility to health facilities [2]. 

Some fever syndromes have a clearer localization to skin and soft tissue (abscess or cellulitis), meninges or neural tissue (headache, neck-stiffness, altered sensorium with or without focal neurological signs), respiratory tract (cough, breathlessness), or urinary tract (dysuria, hematuria). These syndromes have better developed guidelines for their management. On the other hand, AUF-syndromes (such as fever-rash, fever-myalgia, fever-arthralgia, fever-hemorrhage and fever-jaundice) have overlapping etiologies, which makes their diagnosis and management even more challenging [3].

In this article we describe the clinical, laboratory, serological and radiological features of Scrub typhus as a cause of Acute Undifferentiated Febrile Illness among the patients admitted in the Department of Medicine at Indira Gandhi Medical College, Shimla, Himachal Pradesh, India.

It was a hospital-based cross-sectional observational study that was conducted in the Department of Internal Medicine at Indira Gandhi Medical College, Shimla, Himachal Pradesh, India. The study was conducted over a period of one year. All patients who were admitted with the scrub typhus as a cause of Acute Undifferentiated Fever were defined as temperature ≥100°F and history of febrile illness of 2–14 days duration, with no other localized cause were included in the study. The data was collected, cleaned and entered into Microsoft Excel spreadsheet and transferred to Epi info version 7.2.1.0 software. The categorical variables were expressed in terms of   frequencies, proportions, and percentages with 95% confidence intervals. The continuous variables were expressed as means± standard deviation.

There were 54 patients who were admitted for Scrub typhus. We found that the mean age of the study participants suffering from scrub typhus was found to be 38.1 years with a standard deviation of 9.2 days. The duration of the stay in the hospital in these study participants was found to be 8.2 days with a standard deviation of 1.4 days. The duration of fever was also found to be 5.1 days with a standard deviation of 2.6 days. (Table 1) The cases of scrub typhus were presented to the department of general medicine at Indira Gandhi medical college Shimla in the month of September, October, November and December (Figure 1).

Table 2 gives a description of clinical parameters of the study participants who presented with scrub typhus as an acute undifferentiated illness. In the cases of scrub typhus 50% of the individuals were found to have eschar, 52% of the individuals presented with arthralgia. 54% of the individuals presented with myalgia. 19% of the individuals had lymphadenopathy 24% and 9% of the individuals were found to have hepatomegaly and splenomegaly respectively. Pain abdomen was found in only 13% of the individuals. No patient presented with seizures or neck stiffness or cranial nerve palsies.

Among 54 patients of scrub typhus 30% anemia coma 48% had leukocytosis whereas 46% had thrombi cytopenia. Hematocrit and serum creatinine were raised in nearly one fourth of the individuals scrub typhus while nearly one third of the individuals had elevated liver function tests. Nearly one fourth of the individuals had raised serum albumin while 33% of the patients presented with azotemia. Among all the cases, 52% had abnormal chest X-ray while half of the individuals had abnormal ultrasonographic findings in the abdomen (Table 3). 

Table 1: Epidemiological Profile of Patients with Scrub Typhus (n = 54)

Table 2: Clinical parameters associated with Acute Undifferentiated Febrile Illness Due to Scrub Typhus (n = 54)

Illness in scrub typhus varies from mild and self-limiting to fatal. After an incubation period of 6-21 days, onset is characterized by fever, headache, myalgia, cough and gastrointestinal symptoms [4]. The classic case description includes a primary popular lesion (where the chigger has fed and can occur anywhere on the body), which enlarges, undergoes central necrosis and crusts to form a flat black eschar. This is associated with regional and later generalized lymphadenopathy (enlarged and tender nodes). The symptoms gradually increase in severity and a macular rash may appear on the trunk. These findings correspond to the study conducted by Kim et al. and are in concordance with our study [5]. If untreated, the patient may become stuporous as meningoencephalitis develops. Various cranial nerve deficits have been noted in untreated patients [6]. Pulmonary findings are often absent despite radiographic evidence of interstitial pneumonia. Signs of cardiac dysfunction, including minor electrocardiographic abnormalities - first-degree heart block and inverted T waves - can appear. In patients with myocarditis, there may be a gallop rhythm, poor-quality heart sounds and systolic murmurs [7]. Sometimes, palpable spleen (and occasionally liver) may also be present. Deafness, dysarthria and dysphagia may occur but are usually transient, although deafness can last for several months. Patients with untreated disease remain febrile for about 2 weeks and have a long convalescence of 4 to 6 weeks thereafter as suggested by Mahajan et al. [8].

Table 3: Laboratory, Serological and Radiological Parameters Associated with Acute Undifferentiated Febrile Illness Due to Scrub Typhus (n = 54)

Figure 1: Monthly Distribution of Cases of Scrub Typhus

Scrub typhus may be mild or severe. Most patients present with fever and regional/generalized lymphadenopathy. A single painless eschar, maculopapular rash, hepatomegaly, splenomegaly and gastrointestinal symptoms (abdominal pain, vomiting and diarrhoea) may be present. Case fatality rate in untreated patients may be as high as 30%, although deaths are infrequent. 

It is necessary to determine the predictors that identify markers of severe disease in order to reduce the mortality, complications and the delay in treatment. The potential markers for developing complications were age (≥60 years); scrub typhus patients who presented to the hospital without an eschar; laboratory findings such as WBC counts >10, 000/mm and serum albumin level ≤3.0 g/dL [9]. 

Laboratory studies revealed leukocytosis and thrombocytopenia with subsequent increase of white blood cell counts to normal levels. Leukocyte and platelet counts are usually within normal ranges, although thrombocytopenia and leukocytosis may also occur. Coagulopathy, elevation of liver enzymes and bilirubin - indicating hepatocellular damage, proteinuria, elevation of creatinine, Reticulonodular infiltrates (most common finding on chest radiograph) were some of clinical features found in our study which is in similar lines with the study conducted by Kim et al. [5].

Scrub typhus is a growing and emerging disease, which is grossly under-diagnosed in under developed/developing countries due to its non-specific clinical presentation, limited awareness and low index of suspicion among clinicians and lack of diagnostic facilities. Hence, early diagnosis and treatment are imperative to reduce the mortality and the complications associated with the disease.

1. A. Chrispal et al."Acute undifferentiated febrile illness in adult hospitalized patients the disease spectrum and diagnostic predictors - an experience from a tertiary care hospital in South India." Trop. Dr., vol. 40, no. 4, 2010, pp. 230–234.

2. N. Acestor et al."Mapping the aetiology of non-malarial febrile illness in Southeast Asia through a systematic review--terra incognita impairing treatment policies." PLoS One, vol. 7, no. 9, 2012, e44269.

3. P. Ray et al. "Chikungunya infection in India results of a prospective hospital based multi-centric study." PLoS One, vol. 7, no. 2, 2012, e30025.

4. R.B. Hornick "Rickettsial diseases." In: Bennett J.C. and Plum F. (eds). Goldman Cecil textbook of medicine, 21st ed., Philadelphia, USA: W.B. Saunders Company, 2000, pp. 1911–1912. (Chapter 371).

5. D. Kim et al. "Clinical and laboratory findings associated with severe scrub typhus." BMC Infect. Dis., vol. 10, 2010, 108.

6. W.H. Chang "Current status of tsutsugamushi disease in Korea." J. Korean Med. Sci., vol. 10, 1995, pp. 227–238.

7. Mahajan S.K. "Scrub typhus." J. Assoc. Physicians India, vol. 53, 2005, pp. 954–958.

8. S.K. Mahajan et al."Relevance of Weil-Felix test in diagnosis of scrub typhus in India." J. Assoc. Physicians India, vol. 54, 2006, pp. 619–621.

9. D. Kim et al. "Usefulness of nested PCR for the diagnosis of scrub typhus in clinical practice a prospective study." Am. J. Trop. Med. Hyg., vol. 75, 2006, pp. 542–545.