Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 32-11: Typhus Group + Key Features Download Section PDF Listen +++ +++ 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 + Clinical Findings Download Section PDF Listen +++ +++ 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 + Diagnosis Download Section PDF Listen +++ ++ 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 + Treatment Download Section PDF Listen +++ ++ 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 + Outcome Download Section PDF Listen +++ +++ 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 + References Download Section PDF Listen +++ + +El Sayed I et al. Antibiotics for treating scrub typhus. Cochrane Database Syst Rev. 2018 Sep 24;9:CD002150. [PubMed: 30246875] + +Jung LY et al. Relative bradycardia in scrub typhus. Am J Trop Med Hyg. 2017 Nov;97(5):1316–8. [PubMed: 29016300] + +Kim YS et al. Effects of rifampin and doxycycline treatments in patients with uncomplicated scrub typhus: an open-label, randomized, controlled trial. Clin Infect Dis. 2018 Aug 1;67(4):600–5. [PubMed: 29462266] + +Pathak S et al. Clinical profile, complications and outcome of scrub typhus in children: a hospital based observational study in central Nepal. PLoS One. 2019 Aug 13;14(8):e0220905. [PubMed: 31408484] + +Rajan SJ et al. Scrub typhus in pregnancy: maternal and fetal outcomes. Obstet Med. 2016 Dec;9(4):164–6. [PubMed: 27829876] + +Shelke YP et al. Spectrum of infections in acute febrile illness in central India. Indian J Med Microbiol. 2017 Oct–Dec;35(4):480–4. [PubMed: 29405137] + +Wangrangsimakul T et al. Causes of acute undifferentiated fever and the utility of biomarkers in Chiangrai, northern Thailand. PLoS Negl Trop Dis. 2018 May 31;12(5).e0006477. [PubMed: 29852003] + +Wangrangsimakul T et al. Scrub typhus and the misconception of doxycycline resistance. Clin Infect Dis. 2020 May 23;70(11):2444–9. [PubMed: 31570937]