Clinical Overview of Scrub Typhus

Background

Scrub typhus is distributed throughout the Asia-Pacific region. It is endemic to Korea, China, Taiwan, Japan, Pakistan, India, Bangladesh, Thailand, Laos, Malaysia, Vietnam, Sri Lanka, and Australia. In 1999, the World Health Organization listed scrub typhus as one of the most underdiagnosed and underreported causes of febrile illness in Asia and Oceania.

Scrub typhus is transmitted to humans through bites from infected larval trombiculid mites, commonly known as chiggers. The following species are known vectors of scrub typhus: Leptotrombidium pallidum, L. fuji, L. scutellare, and L. akamushi.

Seasonality of the disease is determined by the appearance of larvae. In temperate zones, scrub typhus season is observed mainly in the fall, but also occurs in the spring. If a person is bitten by an infected mite, disease occurs within 7–10 days and typically lasts 14–21 days without appropriate treatment. Transmission is year-round in tropical and sub-tropical regions, with seasonal peaks determined by rainy and dry seasons.

The majority of cases of scrub typhus occur in rural areas where mite-harboring vegetation is common. Interestingly, studies have described focal areas of scrub vegetation as small as a few square meters that are infested with these mites. If people enter one of these hot spots, their risk of infection increases dramatically.

Clinical characteristics

Symptoms of scrub typhus begin abruptly, 7 or more days after infection. Scrub typhus causes an acute febrile illness that can range from mild and self-limited to severe or fatal. Typical signs and symptoms include:

• Fever and chills
• Headache
• Myalgia
• Eschar
• Altered mental status, ranging from confusion to coma or delirium
• Lymphadenopathy
• Rash

Most patients have thrombocytopenia and may also show elevated levels of hepatic transaminases, bilirubin, and/or creatinine. Splenomegaly and hepatomegaly may be observed. Severe manifestations usually develop after the first week of untreated illness and may include multiple organ dysfunction syndrome with hemorrhaging, acute respiratory distress syndrome, encephalitis, pneumonia, renal or liver failure, and death. During pregnancy, scrub typhus frequently leads to spontaneous abortion. Relapses may occur following apparent recovery in cases where inadequate treatment has occurred. Relapse is usually less severe than the initial presentation.

Eschar

The area around the bite may develop a necrotic skin lesion known as an eschar [PDF – 2 pages]. The eschar may appear before the individual develops systemic symptoms. Common sites of eschars are axillae, under the breast, and groin, and less often on the abdomen, back, and extremities. Multiple eschars have been reported.

Rash

About 25–50% of scrub typhus patients develop a rash. The rash is usually macular or maculopapular. Typically, it will begin on the abdomen of an infected individual and then spread to the extremities. Petechiae are uncommon.

Diagnosis

It is important to treat scrub typhus early in the course of the disease in order to avert life-threatening complications. A reliable diagnostic laboratory test in the early phase of illness is not readily available; therefore, diagnosis is based on clinical findings and epidemiologic setting. Treatment should never be withheld pending diagnostic tests.

Laboratory confirmation

Serologic assays are the most frequently used methods for confirming cases of scrub typhus. The indirect fluorescent antibody (IFA) test is generally considered the reference standard, but is usually not available in developing countries where this disease is endemic. Other serological tests include ELISA and indirect immunoperoxidase (IIP) assays.

Weil-Felix OX-K agglutination assays have very low sensitivity and specificity and are not recommended as a diagnostic assay.

Diagnosis is typically confirmed by documenting a four-fold rise in antibody titer between acute and convalescent samples. Acute specimens are taken during the first week of illness and convalescent samples are taken 2–10 weeks later. IgG antibodies are considered more accurate than IgM, but detectable levels of IgG antibody generally do not appear until 7–10 days after the onset of illness.

Because antibody titers may persist in some individuals for years after the original exposure, only demonstration of recent changes in titers between paired specimens can be considered reliable confirmation of an acute scrub typhus infection. The most rapid and specific diagnostic assays for scrub typhus rely on molecular methods like polymerase chain reaction (PCR), which can detect DNA in a whole blood, eschar swab [PDF – 1 page], or tissue sample. Immunostaining procedures can also be performed on formalin-fixed tissue samples.

Since scrub typhus is not common in the United States, confirmatory tests are not typically available at state and local health departments. Nonetheless, serologic and molecular assays can be performed at the CDC through submission from state health departments.

Treatment

Doxycycline is the treatment of choice for suspected scrub typhus in persons of all ages. Patients should be treated for at least 3 days after the fever subsides and until there is evidence of clinical improvement. Single-dose or short courses of doxycycline may lead to a relapse in illness.

Recommended dosages of doxycycline:

• Adults over 45 kg (100 lbs): 100 mg twice per day
• Children under 45 kg (100 lbs): 2.2 mg/kg body weight twice per day

Treatment for pregnant people should be determined in consultation with an expert in infectious diseases. Treatments for patients with severe doxycycline allergy may include azithromycin or rifampin. Chloramphenicol is an alternative treatment, but oral formulations are no longer available in the United States and the parenteral formulation has limited availability. Limited clinical reports suggest ciprofloxacin or levofloxacin also might be effective alternatives in adults.