Scrub typhus (ORPHA:83317)
Scrub typhus is a rare dust mite-borne infectious disease caused by the Orientia tsutsugamushi bacterium and characterized clinically by an eruptive fever which is potentially serious.
Epidemiology
Precise prevalence and incidence rates of scrub typhus are not known. An estimated 1 billion people worldwide are at risk for scrub typhus, and an estimated 1 million cases occur each year. The disease is widespread in rural South and South-East Asia and the Western Pacific (Korea to Australia) as well as from Japan to India and Pakistan. In these regions its annual incidence is approximately 1/4,000. Scrub typhus occurs preferentially in spring and autumn in rural areas and has frequently been reported in individuals who traveled to endemic regions.
Clinical description
After a silent incubation period of 10 days or more, onset is sudden with constant high fever, headache, obtundation, cough, myalgia and nausea. A pale macular rash is common and an inoculation eschar at the site of the mite bite is found in many cases, often with painful satellite lymph nodes. Splenomegaly is observed in 1/3 of cases. Most cases are mild, but pneumonitis, meningoencephalitis, multiorgan failure, bleeding and even death may occur, especially in untreated patients. Relapses after recovery may occur but are usually less severe than the inaugural episode.
Etiology
Scrub typhus is caused by Orientia tsutsugamushi, an obligate intracellular Gram-negative rod bacteria belonging to the genus Orentia, which is transmitted to humans by the bites of larval thrombiculid mites (chiggers).
Diagnostic methods
Diagnosis is based on clinical signs (fever, headache, eschar at the bite site, rash) in an endemic rural zone. Non-specific laboratory test results include increased transaminase levels, thrombocytopenia, leucopenia and CD4/CD8 lymphocyte ratio inversion. A definitive diagnosis can be made by culture of O. tsutsugamushi in a shell vial or molecular biology analysis of sampling (skin, lymph nodes, EDTA blood) using PCR amplification. The organisms stain poorly with the Gimenez method but easily with Giemsa staining. Immunohistochemistry of skin lesions may reveal an O. tsutsugamushi infection. Later serological confirmation is possible by indirect immunofluorescence.
Differential diagnosis
Differential diagnosis includes typhoid fever, leptospirosis, malaria, and dengue (see these terms), as well as HIV seroconversion and rickettsial diseases (see this term).
Management and treatment
Treatment usually involves drug therapy with doxycycline and chloramphenicol. Doxycycline is administered for a short time (3-7 days) in adults (200 mg/day) and children (2.2 mg/kg, twice daily). All patients with a suspected infection should be treated. Patients with poor response to doxycycline and chloramphenicol, as well as pregnant women, can be treated with rifampicin (600-900 mg/day) or azithromycin (500 mg on the first day, then 250 mg/day).
Prognosis
The disease course may be severe. However, the mortality rate depends on the geographic areas and varies from 3% in Taiwan up to 30% in Northern Japan. The exact reasons for the variable mortality in these regions are not known, but it is likely that different serotypes may account for the varying manifestations of the disease.

                            Last update: 
                            March 2013


                            - Expert reviewer(s): 
                            Dr Senaka RAJAPAKSE