Scrub typhusA75.3

Tsutsugamushi fever is a rickettsial disease transmitted by mites and may be severe. It is transmitted by the larvae of mites that live in the soil in the wild. The disease is widespread in parts of Southeast and Far East Asia and northern Australia, where it is a serious public health problem (Xu G et al. 2017). Caused by Orientia tsutsugamushi, scrub typhus can lead to severe multi-organ failure with a mortality rate of up to 70% without appropriate treatment.

Orientia tsutsugamushi (formerly: Rickettsia tsutsugamushi)

Endemic to some countries in Asia, South America (Chile), and the Southwest Pacific including Australia. In these regions, the annual incidence is approximately 1/4,000. Scrub typhus occurs preferentially in rural areas in spring and fall and has been frequently observed in persons who have traveled to endemic regions. Exact prevalence and incidence rates of the disease are not known. Globally, an estimated 1 billion people are at risk for scrub typhus, and an estimated 1 million cases occur each year (Xu G et al. 2017).

Infestation by Orientia tsutsugamuschi infected larval stages of trombiculid mites, mainly Leptotrombidium deliense u. Leptotrombidium (Trombicula) acamushi (predominantly living in low shrubs).

The antigenic heterogeneity of O. tsutsugamushi precludes generic immunity and allows reinfection. Being a neglected disease, there is still a large knowledge gap about this disease, as evidenced by the sporadic epidemiological data and other related public health information regarding scrub typhus in endemic areas (Xu G et al. 2017).

At the primary lesion (= eschar): Hard inflammatory nodule in about half of the patients. Regional or generalized lymph node swelling. Transformation of the primary lesion into a multilocular vesicle, later ulceration with crust formation. If the causative agent is generalized, fever, headache, limb pain, conjunctivitis, and splenomegaly may occur. Maculopapular exanthema on the 6th to 10th day of illness, possibly enanthema of the soft palate, CNS symptomatology (neck stiffness, drowsiness, speech disturbance).

In some cases, scrub typhus leads to severe disease symptomatology that can result in multiple organ involvement and death. This course is thought to result from systemic vasculitis caused by both direct effects of the organisms and an exuberant immune response (cytokine storm) (Rajapakse S et al. 2017).

Diagnosis is based on clinical symptoms (fever, headache, bite site scab, rash) in an endemic rural area. Nonspecific laboratory test results include elevated transaminase levels, thrombocytopenia, leukopenia, and inversion of the CD4/CD8 lymphocyte ratio. A definitive diagnosis can be made by culture of O. tsutsugamushi or by molecular biology analysis of specimens (skin, lymph nodes, EDTA blood) using PCR amplification.

The organisms are readily stained using Giemsa stain.

Immunohistochemistry of skin lesions may reveal O. tsutsugamushi infection. Subsequent serological confirmation is possible by indirect immunofluorescence.

Serology, pathogen detection by PCR or cultivation.

Treatment usually includes drug therapy with doxycycline and chloramphenicol. Doxycycline is given for a short time (3-7 days) in adults (200 mg/day) and children (2.2 mg/kg, twice daily). All patients with suspected infection should be treated. Patients with poor response to doxycycline and chloramphenicol and pregnant women may be treated with rifampicin (600-900 mg/day) or azithromycin (500 mg the first day, then 250 mg/day).

The course of the disease can be severe. However, the mortality rate depends on the geographical areas and varies from 3% in Taiwan to 30% in northern Japan. The exact reasons for the variation in mortality in these regions are not known, but it is likely that different serotypes are responsible for the different manifestations of the disease.

1. Rajapakse S et al (2017) Clinical manifestations of scrub typhus. Trans R Soc Trop Med Hyg 111:43-54.
2. Weitzel T et al. (2019) Scrub typhus in Continental Chile, 2016-20181. Emerg Infect Dis 25:1214-1217.
3. Xu G et al (2017) A review of the global epidemiology of scrub typhus. PLoS Negl Trop Dis 11:e0006062.