Typhus, Scrub (Tsutsugamushi Fever)

Essentials of Diagnosis

• Exposure to mites in endemic South and East Asia, the western Pacific (including Korea), and Australia

• Black eschar at site of the bite, with regional and generalized lymphadenopathy

• High fever, relative bradycardia, headache, myalgia, and a short-lived macular rash

• Frequent pneumonitis, encephalitis, and myocarditis

General Considerations

• Caused by Orientia tsutsugamushi, which is a parasite of rodents and is transmitted by larval trombiculid mites (chiggers)

• Disease is endemic in Korea, China, Taiwan, Japan, Pakistan, India, Thailand, Malaysia, Vietnam, Laos, and Queensland, Australia, which form an area known as the "tsutsugamushi triangle"

• Cases are also reported in the Middle East, Kenya, and South America

• Risk factors in China include

  • Female sex

  • Ages between 60 and 69 years

  • Farming

• Transmission

  • Occurs more often at higher altitudes

  • Vertical transmission occurs

  • Blood transfusions may transmit the pathogen as well

Symptoms and Signs

• Malaise, chills, severe headache and backache develop after a 1- to 3-week incubation period

• At the site of the bite, a papule evolves into a flat black eschar (the groin and the abdomen being the most common sites followed by the chest and axilla)

• Regional lymph nodes are commonly enlarged and tender, and sometimes a more generalized adenopathy occurs

• Fever rises gradually during the first week of infection

• Rash

  • Usually macular

  • Primarily on the trunk area

  • Can be fleeting or more severe, peaking at 8 days but lasting up to 21 days after onset of infection

• Relative bradycardia

• Gastrointestinal symptoms, including nausea, vomiting, and diarrhea, occur in nearly two-thirds of patients and correspond to the presence of

  • Superficial mucosal hemorrhage

  • Multiple erosions

  • Ulcers in the gastrointestinal tract

• Acute kidney injury and other renal abnormalities are frequently present

Differential Diagnosis

• Leptospirosis

• Typhoid

• Dengue

• Malaria

• Q fever

• Hemorrhagic fevers

• Tuberculous meningitis

• Trigeminal neuralgia

• Thrombocytopenia and elevation of liver enzymes, bilirubin, and creatinine are common

• Indirect immunofluorescent assay (IFA) and indirect immunoperoxidase assays are

  • The gold standard for establishing the diagnosis

  • Expensive and have limited availability

• An ELISA detecting Orientia specific antibodies in serum is available

• PCR (from the eschar or blood)

  • Most sensitive diagnostic test

  • However, it remains positive even after initiation of treatment

• Culture of the organism from blood obtained in the first few days of illness is another diagnostic modality but requires a specialized biological safety level 3 laboratory

• Doxycycline (100 mg orally twice daily) or minocycline (100 mg intravenously twice daily)

  • Should be given until there is evidence of clinical improvement and at least 3 days after the fever subsides

  • Shorter duration of therapy is associated with relapse

• A 2018 randomized controlled trial comparing 5 days of doxycycline 200 mg daily to rifampin 600 mg daily showed that rifampin is noninferior to doxycycline

• Alternative therapy for pregnant women and patients with doxycycline allergy include chloramphenicol, although chloramphenicol- and tetracycline-resistant strains have been reported from Southeast Asia

• Azithromycin

  • Shown to be as effective as doxycycline with fewer side effects but is more expensive

  • May not prevent poor fetal outcomes in infected pregnant women

Complications

• Severe complications may develop during the second or third week, including

  • Pneumonitis

  • Myocarditis

  • Encephalitis or aseptic meningitis

  • Peritonitis

  • Granulomatous hepatitis

  • Hemophagocytic syndrome

  • Immune thrombocytopenia

  • Disseminated intravascular coagulation

  • Cerebrovascular hemorrhage or infarction

  • Cranial nerve palsies

  • Parkinsonian symptoms

  • ARDS

  • Hemophagocytosis

Prevention

• Repeated application of long-acting miticides can make endemic areas safe

• Insect repellents on clothing and skin as well as protective clothing are effective

• Although chemoprophylaxis with doxycycline has been used, the CDC does not recommend prophylaxis with antibiotics for asymptomatic travelers

• No effective vaccines are available

Prognosis

• Without treatment, fever subsides spontaneously after 2 weeks, but the mortality rate may be 10–30%

• Poor prognostic factors include

  • Hypotension requiring vasopressors

  • ICU care

  • Age over 60 years

  • Absence of an eschar (making the diagnosis difficult)

  • Pregnancy

  • Laboratory findings such as leukocytosis or hypoalbuminemia