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From the Department of Biochemistry, Sree Balaji Medical College & Hospital, Chromepet, Chennai, Tamil Nadu, India.

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Scrub typhus is an acute, febrile, infectious illness which was first described in China in 313 AD. The characteristic findings of this illness are high fever, eschar, maculopapular rash, lymphadenopathy, headache, and myalgia. Non-specific clinical presentations, limited awareness with low index of suspicion among doctors makes scrub typhus under-diagnosed disease.

Scrub typhus leads to generalized vasculitis which may involve the tissues of any organ system [2,3]. Complications of scrub typhus include interstitial pneumonia, acute renal failure, meningoencephalitis, gastrointestinal bleeding and multiorgan failure. Since patients with scrub typhus may die from such complications, clinicians need to be aware of the severity markers of the disease.  Few studies done in the past have reported that hypoalbuminemia and multiorgan failure could be used as markers of severity of the disease [4,5]. We report a case of scrub typhus and the consequences of multiorgan dysfunction and hypoalbuminemia.

A 23 year old male was referred to our department with complaint of headache for last 2 weeks. He was running high grade fever since last 5 days. There was no history of bleeding from any site, oral or genital ulcers, seizures, joint pains, swelling or drug intake. 

On examination, patient was found to be febrile with GCS of E2M2V1. His pulse rate was 120/min, and blood pressure was 150/90 mm Hg. There were no palpable lymph nodes or clinical signs of jaundice. Dermatological examination revealed an eshar in right infraaxillary region. He did not have any skin rashes. Abdomen examination was suggestive of hepatomegaly. Central nervous system examination revealed an asymmetrical pupil and neck stiffness. Other systems were within normal limits.

Blood counts revealed a total leucocyte count of 23,500/µL with 84% neutrophils and 16% lymphocytes. The hemoglobin, platelet count and serum bilirubin were normal. Smears for malarial parasite were negative.  The liver transaminases were elevated: SGOT 170 IU/L, and SGPT 86 IU/L with total protein - 4.0 g/dL, Albumin - 2.1g/dL and Globulin - 1.9 g/dL. Urine examination revealed 2+ albumin, bile salts and bile pigments. The blood urea was 64 mg% with serum creatinine 1.3 mg/dL. There was marked prolongation of Prothrombin time (PT), Partial thromboplastin time (APTT),and INR [PT was 20 seconds with control of 14 seconds,  INR - 1.7, APTT was 50 seconds with control of 30 seconds]. The D-dimer [11.15 µgm/ml FEU (< 0.5)], which indicated lysis of fibrin clot, was also raised suggesting disseminated intravascular coagulation.

The patient was diagnosed as a case of scrub typhus on basis of serology (Positive IgM ELISA) and was treated with doxycycline and additional supportive treatment for DIC, acute respiratory distress syndrome, hepatitis and renal involvement. Inspite of aggressive and appropriate treatment the patient could not be saved.

Scrub typhus is endemic in ‘Tsutsugamushi triangle’ which extends from northern Japan and far-eastern Russia in the north, to northern Australia in the south, and to Pakistan and Afghanistan in the west. Scrub typhus is acquired during agricultural exposure, with rice fields serving a reservoir for transmission [1]. It is transmitted to humans by infected chigger, the larval stage of trombiculid mites. The natural reservoir for the chiggers is wild rats and when the chiggers feed on humans, infection occurs.

Our patient of scrub typhus was admitted with a GCS (Glasgow coma scale) of 5 and multiorgan failure- acute renal failure, adult respiratory distress syndrome, hepatic dysfunction, disseminated intravascular coagulation. The root cause of all the complications in scrub typhus is due to the destruction of endothelial cell lining of small vessels which leads to vasculitis. Usually, the cause for hypoalbuminemia in any acute infectious illness is due to poor oral intake of protein, decreased hepatic synthesis and increase protein catabolism. However, in scrub typhus the mechanism of hypoalbuminemia seems to be vasculitis leading to increased vascular permeability and thus protein leakage from blood vessels causing hypoalbuminemia [6]. 

It has been reported in the past that hepatic dysfunction and septic shock more often occurred in patients of scrub typhus with hypoalbuminemia [7,8]. This shows the close association of hypoalbuminemia with severity of the disease. Vasculitis and perivasculitis of small blood vessels may also lead to multiorgan dysfunction like hepatic dysfunction, cardiac dysfunction, interstitial pneumonia, renal failure, myocarditis and disseminated intravascular coagulation [9]. Few studies have shown that in patients with scrub typhus, hypoalbuminemia, thrombocytopenia and leukocytosis represented the severity of disease. In this case there is leukocytosis, which might show the severity of the disease.

Acute renal failure may be due to direct invasion by Orientia tsutsugamushi causing acute tubular necrosis. Chang-Seop Lee et al emphasized the role of hypoalbuminemia as a marker for severity of the disease [5]. Hepatic and renal involvement as a part of multiorgan involvement could also contribute to hypoalbuminemia in scrub typhus. It has been shown by Song et al that pulmonary edema, interstitial pneumonia and pleural effusion were more often reported in scrub typhus patients with hypoalbuminemia than in scrub typhus without hypoalbuminemia [10].

Our study also reemphasizes the fact that hypoalbuminemia associated with multi organ failure could be a marker of the severity of scrub typhus. 

This case report establishes the close relationship of hypoalbuminemia and multiorgan failure with scrub typhus to fatal outcome of the disease.

1. Sharma PK, Ramakrishnan R, Hutin YJ, Barui AK, Manickam P, Kakkar M, et al. Scrub typhus in Darjeeling, India: opportunities for simple, practical prevention measures. Trans R Soc Trop Med Hyg. 2009;103:1153-1158. 
2. Yi KS, Chong Y, Covington SC, Donahue BJ, Rothen RL, Rodriguez J, et al. Scrub typhus in Korea: importance of early clinical diagnosis in this newly recognized endemic area. Mil Med. 1993;158:269-273.  
3. Ogawa M, Hagiwara T, Kishimoto T, Shiga S, Yoshida Y, Furuya Y, et al. Scrub typhus in Japan: epidemiology and clinical features of cases reported in 1998. Am J Trop Med Hyg. 2002;67:162-165.
4. Chi WC, Huang JJ, Sung JM, Lan RR, Ko WC, Chen FF. Scrub typhus associated with multiorgan failure: A case report. Scand J Infect Dis. 1997;29:634-635. 
5. Chang-Seop Lee, In-Suk Min, Jeong-Hwan Hwang, Keun-Sang Kwon, Heung-Bum Lee. Clinical significance of hypoalbuminemia in outcome of patients with scrub typhus. BMC Infect Dis. 2010;10:216. 
6. Kim YO, Jeon HK, Cho SG, Yoon SA, Son HS, Oh SH, et al. The role of hypoalbuminemia as a marker of the severity of disease in patients with tsutsugamushi disease. Korean J Internal Med. 2000;59:516–521
7. Chanta C, Triratanapa K, Ratanasirichup P, Mahaprom W. Hepatic dysfunction in pediatric scrub typhus. Role of liver function test in diagnosis and marker of disease severity. J Med Assoc Thai. 2007; 90:2366-2369.  
8. Thap LC, Supanaranond W, Treeprasertsuk S, Kitvatanachai S, Chinprasatsak S, Phonrat B. Septic shock secondary to scrub typhus: Characteristics and complications. Southeast Asian J Trop Med Public Health. 2002;33:780-786.   
9. Cracco C, Delafosse C, Baril L, Lefort Y, Morelot C, Derenne JP, et al. Multiple organ failure complicating probable scrub typhus. Clin Infect Dis. 2000;31:191–192. 
10. Song SW, Kim KT, Ku YM, Park SH, Kim YS, Lee DG, et al. Clinical role of interstitial pneumonia in patients with scrub typhus: A possible marker of disease severity. J Korean Med Sci. 2004;19:668–673.