Typhus, Scrub (Tsutsugamushi Fever)

KEY FEATURES

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 an area known as the "tsutsugamushi triangle" which is formed by

  • Korea

  • China

  • Taiwan

  • Japan

  • Pakistan

  • India

  • Thailand

  • Malaysia

  • Vietnam

  • Laos

  • Queensland, Australia

• 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

  • Case numbers increased with higher temperatures, high humidity, and increased rainfall in a Chinese study

  • Vertical transmission occurs

  • Blood transfusions may transmit the pathogen as well

CLINICAL FINDINGS

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 infection onset

• 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

• Other rickettsial infections

DIAGNOSIS

Laboratory Tests

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

• Severe infections correlate with intermediate and high early immunoglobulin G (IgG) levels and higher levels of proteases (granzymes)

• Indirect immunofluorescent assay and indirect immunoperoxidase assays are

  • The gold standard for establishing the diagnosis

  • Expensive and have limited availability

• An enzyme-linked immunosorbent assay (ELISA) detecting Orientia specific antibodies in serum is available

• Polymerase chain reaction (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

• Combining immunoglobulin M (IgM) detection ...