Tsutsugamushi Disease

Tsutsugamushi disease is transmitted through a mite bite. During the inoculation period, which typically lasts for 6 to 20 days, the patient usually remains asymptomatic. Approximately at the tenth day following the initial infection, high fever, headaches, myalgia and fatigue emerge. The non-specificity of the symptoms constitutes a diagnostic obstacle at the early disease phase. During this initial period, a papule begins to form at the region of the mite bite, gradually progressing to form a necrotic localized spot, referred to as an eschar.

Despite the diagnostic challenge due to the non-specificity of the symptoms, the existence of an eschar is pathognomonic of tsutsugamushi disease; it is observed in half of the patients with a primary infection and is well-defined by the time that an individual develops fever [1] [2] [3]. Other symptoms associated with tsutsugamushi disease are lymphadenopathy, regional or generalized, ocular pain, a productive cough and infected conjunctiva [4] [5]. A characteristic symptom is also the centrifugal macular rash that appears after approximately a week following the infection. The erythema develops on the torso, may gradually assume papular characteristics and may not be observed due to its transient nature [6].

As the disease progresses, pneumonia, encephalitis, delirium and splenomegaly may be added to the clinical picture.

The complete workup for scrub typhus encompasses a multitude of tests and procedures, including routine blood tests, serology, and PCR.

More specifically, laboratory blood tests including a complete blood count and biochemical studies usually yield the following results:

• Lymphopenia, early in the course of the disease
• Lymphocytosis, during the progressed stage
• Decreased CD4:CD8 ratio
• Thrombocytopenia [7]
• Augmented SGOT/SGPT levels in up to 95% of the patients
• Hypoalbuminemia, in 50% of the patients

The aforementioned findings may also suggest a potential dengue fever or leptospirosis infection; the latter is known to often coexist with scrub fever [8].

Serologic tests are further carried out, as they constitute the primary diagnostic procedures. A direct immunoperoxidase test and an immunofluorescent assay are used to establish the diagnosis and are expected to yield a result displaying a 4-fold augmentation of antibody titers between acute and convalescent serum specimens [9]. All potential O. tsutsugamushi subtypes should be considered as a possibility and should, therefore, be separately investigated serologically. A dot immunoassay can also be employed in order to diagnose tsutsugamushi disease, whereas the immunochromatographic test, aimed at the detection of immunoglobulin (Ig) M and IgG antibodies exhibit a considerably greater sensitivity for an early diagnosis when compared to the standard immunofluorescence assay.

The polymerase chain reaction tests (PCR) has proven a valuable diagnostic tool, on eschar samples, early in the course of the disease. In third world countries, the method of choice is the Weil-Felix OX-K strain agglutination reaction; when more advanced medical facilities are available, this test is not opted for due to its decreased sensitivity.

1. Watt G, Walker DH. Scrub typhus. Guerrant RL, Walker DH, Weller PF, eds. Tropical Infectious Diseases Principles, Pathogens and Practice. 2nd ed. Philadelphia, PA: Elsevier Churchill Livingstone; 2006. Vol 1: Chapter 52.
2. Raoult D. Scrub typhus. Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. 6th ed. Philadelphia, PA: Elsevier Churchill Livingstone; 2005. Vol 2: 2309-10.
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5. Chanta C, Chanta S. Clinical study of 20 children with scrub typhus at Chiang Rai Regional Hospital. J Med Assoc Thai. 2005 Dec. 88(12):1867-72.
6. Sirisanthana V, Puthanakit T, Sirisanthana T. Epidemiologic, clinical and laboratory features of scrub typhus in thirty Thai children. Pediatr Infect Dis J. 2003 Apr. 22(4):341-5.
7. Edwards MS, Feigen RD. Rickettsial and Erlichial Diseases. Feigin RD, Cherry JD, Demmler-Harrison GJ, Kaplan SL. Feigin and Cherry's Textbook of Pediatric Infectious Diseases. 6th ed. Philadelphia, PA: Elsevier Saunders; 2009. Vol 2: 2677-2678.
8. Phimda K, Hoontrakul S, Suttinont C, Chareonwat S, Losuwanaluk K, Chueasuwanchai S. Doxycycline versus azithromycin for treatment of leptospirosis and scrub typhus. Antimicrob Agents Chemother. 2007 Sep. 51(9):3259-63.
9. Phetsouvanh R, Blacksell SD, Jenjaroen K, Day NP, Newton PN. Comparison of indirect immunofluorescence assays for diagnosis of scrub typhus and murine typhus using venous blood and finger prick filter paper blood spots.