Tsutsugamushi disease is transmitted through a mite bite. During the inoculation period, which typically lasts for 6 to 20 days, the patient usually remains asymptomatic. Approximately at the tenth day following the initial infection, high fever, headaches, myalgia and fatigue emerge. The non-specificity of the symptoms constitutes a diagnostic obstacle at the early disease phase. During this initial period, a papule begins to form at the region of the mite bite, gradually progressing to form a necrotic localized spot, referred to as an eschar.

Despite the diagnostic challenge due to the non-specificity of the symptoms, the existence of an eschar is pathognomonic of tsutsugamushi disease; it is observed in half of the patients with a primary infection and is well-defined by the time that an individual develops fever [1] [2] [3]. Other symptoms associated with tsutsugamushi disease are lymphadenopathy, regional or generalized, ocular pain, a productive cough and infected conjunctiva [4] [5]. A characteristic symptom is also the centrifugal macular rash that appears after approximately a week following the infection. The erythema develops on the torso, may gradually assume papular characteristics and may not be observed due to its transient nature [6].

As the disease progresses, pneumonia, encephalitis, delirium and splenomegaly may be added to the clinical picture.

• Splenomegaly

  As the disease progresses, pneumonia, encephalitis, delirium and splenomegaly may be added to the clinical picture. [symptoma.com]

  As the eschar heals, there is a sudden onset of headache, malaise, anorexia, weakness, and fever, followed by pneumonia, a macular rash (on the trunk before the limbs), lymphadenopathy, hepato-splenomegaly, and conjunctivitis. [histopathology-india.net]

  Splenomegaly may be present, and interstitial myocarditis is more common than in other rickettsial diseases. In untreated patients, high fever may persist ≥ 2 weeks, then falls gradually over several days. [msdmanuals.com]

  Morbilliform rash, eschar, splenomegaly, and lymphadenopathies are typical signs. Leukopenia and abnormal liver function tests are commonly seen in the early phase of the illness. [en.wikipedia.org]

• Generalized Lymphadenopathy

  All five children had fever, vomiting and generalized lymphadenopathy, but none had eschar or rash. One was cured with doxycycline, remaining four patients treated with azithromycin and one died despite treatment. [ncbi.nlm.nih.gov]

  After an incubation period of 6 to 21 days (mean 10 to 12 days), symptoms of scrub typhus start suddenly and include fever, chills, headache, and generalized lymphadenopathy. [msdmanuals.com]

  The bacteria multiply at the inoculation site, and a papule forms that ulcerates and becomes necrotic, evolving into an eschar, with regional lymphadenopathy that may progress to generalized lymphadenopathy within a few days. [emedicine.com]

• Fever

  […] or leptospirosis infection; the latter is known to often coexist with scrub fever. [symptoma.com]

  Tsutsugamushi tsutsugamushi disease bush typhus Japanese river fever Kedani fever scrub mite-borne typhus Japanese river fever (disorder) Kedani fever (disorder) Scrub mite-borne typhus (& various types) Scrub typhus Scrub typhus (disorder) Scrub typhus [wikidata.org]

  Synonym(s): akamushi disease, flood fever, inundation fever, island disease, island fever, Japanese river fever, kedani fever, mite typhus, scrub typhus, shimamushi disease, tropic typhus, tsutsugamushi fever tsutsugamushi disease (tso͞o′tso͞o-gə-mo͞o [medical-dictionary.thefreedictionary.com]

  Fever clearance time. Median fever clearance 80 hours (Chiang Rai); 30 hours (Maesot). [doi.org]

  The disease was also a problem for US troops stationed in Japan after WWII, and was variously known as "Shichitō fever" (by troops stationed in the Izu Seven Islands) or "Hatsuka fever" (Chiba prefecture). [en.wikipedia.org]

• Lymphadenopathy

  It presents with fever, headache, a macular rash, lymphadenopathy and eschar at the region of the mite bite. Tsutsugamushi disease is transmitted through a mite bite. [symptoma.com]

  Symptoms are fever, a primary lesion, a macular rash, and lymphadenopathy. Scrub typhus is related to rickettsial diseases. [msdmanuals.com]

  All five children had fever, vomiting and generalized lymphadenopathy, but none had eschar or rash. One was cured with doxycycline, remaining four patients treated with azithromycin and one died despite treatment. [ncbi.nlm.nih.gov]

  Tsutsugamushi disease: A mite-borne infectious disease caused by a microorganism, Rickettsia tsutsugamushi, characteristically with fever, headache, a raised (macular) rash, swollen glands (lymphadenopathy) and a dark crusted ulcer (called an eschar or [medicinenet.com]

• High Fever

  Tsutsugamushi disease is characterized by the early appearance of a black crust at the bitten area and the subsequent development of macular or macropapular rush on the whole body with high fever. [ncbi.nlm.nih.gov]

  It features headache, high fever and a rash. [medical-dictionary.thefreedictionary.com]

  Approximately at the tenth day following the initial infection, high fever, headaches, myalgia and fatigue emerge. The non-specificity of the symptoms constitutes a diagnostic obstacle at the early disease phase. [symptoma.com]

• Chills

  After an incubation period of 6 to 21 days (mean 10 to 12 days), symptoms of scrub typhus start suddenly and include fever, chills, headache, and generalized lymphadenopathy. [msdmanuals.com]

  Case report of a 60-year-old woman who complained of fever, chills, headache, lymphadenopathy, and blurred vision in the right eye following an insect bite to the lower right forehead. [ncbi.nlm.nih.gov]

• Malaise

  As the eschar heals, there is a sudden onset of headache, malaise, anorexia, weakness, and fever, followed by pneumonia, a macular rash (on the trunk before the limbs), lymphadenopathy, hepato-splenomegaly, and conjunctivitis. [histopathology-india.net]

  Signs and symptoms include sudden headache, generalized muscle pain, malaise, and macular skin lesions. The infection may affect the central nervous system causing encephalitis. [fpnotebook.com]

  She also complained of malaise, loss of appetite, and dyspnea. Central nervous system symptoms such as headache and confusion were not observed. [tandfonline.com]

  Increasing malaise and confusion led to hospitalization; at presentation, she was febrile (body temperature, 40.0°C) and apathetic. [dx.doi.org]

• Cough

  Other symptoms associated with tsutsugamushi disease are lymphadenopathy, regional or generalized, ocular pain, a productive cough and infected conjunctiva. [symptoma.com]

  Cough is present during the 1st week of fever, and pneumonitis may develop during the 2nd week. In severe cases, pulse rate increases; blood pressure drops; and delirium, stupor, and muscular twitching develop. [msdmanuals.com]

• Pneumonia

  As the eschar heals, there is a sudden onset of headache, malaise, anorexia, weakness, and fever, followed by pneumonia, a macular rash (on the trunk before the limbs), lymphadenopathy, hepato-splenomegaly, and conjunctivitis. [histopathology-india.net]

  As the disease progresses, pneumonia, encephalitis, delirium and splenomegaly may be added to the clinical picture. [symptoma.com]

  Treatment for suspected malignancy and Pneumocystis carinii pneumonia was commenced. [jstage.jst.go.jp]

  Pneumonia is a well-documented complication of rickettsial diseases, but ARDS is rare (6 cases) [3, –7]. [academic.oup.com]

  Death either occurs as a direct result of the disease, or from secondary effects, such as bacterial pneumonia, encephalitis, or circulatory failure. If death occurs, it is usually by the end of the second week of infection. [montana.edu]

• Sore Throat

  Other signs and symptoms include: rash, lymphadenopathy, hepatosplenomegaly, cough, sore throat, abdominal pain, and central nervous system involvement. [kjim.org]

• Severe Clinical Course

  It is generally said that the clinical course of JSF is worse than that of TD despite antibiotic treatment. The precise mechanism underlying the more severe clinical course of JSF is not fully understood. [ncbi.nlm.nih.gov]

• Vomiting

  All five children had fever, vomiting and generalized lymphadenopathy, but none had eschar or rash. One was cured with doxycycline, remaining four patients treated with azithromycin and one died despite treatment. [ncbi.nlm.nih.gov]

  The most common gastrointestinal symptoms of scrub typhus patients included vomiting, nausea, diarrhea and hametamesis or melena. Gastrointestinal signs included hepatomegaly, jaundice and abdominal pain. [histopathology-india.net]

  The most frequent presenting complaints were fever (100%), headache (91.3%), nausea and vomiting (73.9%), altered sensorium and seizures. Cases of scrub typhus that presented with altered sensorium were 14 (60.8%). [amhsr.org]

• Nausea

  The most common gastrointestinal symptoms of scrub typhus patients included vomiting, nausea, diarrhea and hametamesis or melena. Gastrointestinal signs included hepatomegaly, jaundice and abdominal pain. [histopathology-india.net]

  Most patients who developed nausea and/or vomiting after treatment had a history of nausea or vomiting prior to admission. [doi.org]

  The most frequent presenting complaints were fever (100%), headache (91.3%), nausea and vomiting (73.9%), altered sensorium and seizures. Cases of scrub typhus that presented with altered sensorium were 14 (60.8%). [amhsr.org]

• Abdominal Pain

  Gastrointestinal signs included hepatomegaly, jaundice and abdominal pain. Since multiple serotypes exist and cross-immunity is transient, recurrent infections are common. [histopathology-india.net]

  Haug Browse recently published Learning/CME Learning/CME View all learning/CME CME Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis Case 4-2019: An 18-Year-Old Man with Abdominal Pain and Hematochezia Bridging the Gap Challenge Yourself [nejm.org]

  Other signs and symptoms include: rash, lymphadenopathy, hepatosplenomegaly, cough, sore throat, abdominal pain, and central nervous system involvement. [kjim.org]

  Trichuris trichiura infection, abdominal pain, and colonoscopy. Diagnosis of Trichuris trichiura whipworm by colonoscopic extraction. Endoscopic prevalence of whipworm infestation in northern Italy. [julian-g.ro]

  The common symptoms noted were fever (68/68, 100%), myalgia (20/68, 29.41%), vomiting (8/68, 11.76%), abdominal pain (10/68, 14.71%), chills (11/68, 16.17%), rigors, and headache (9/68, 13.23%) cases. [ijpmonline.org]

• Acute Abdomen

  Unusual presentation of acute abdomen in scrub typhus: a report of two cases. Zhonghua Yi Xue Za Zhi (Taipei) 1995; 55: 401–404. PubMed Google Scholar 12. Pai H, Sohn S, Seong Y et al. [doi.org]

• Jaundice

  Gastrointestinal signs included hepatomegaly, jaundice and abdominal pain. Since multiple serotypes exist and cross-immunity is transient, recurrent infections are common. [histopathology-india.net]

  […] thrombocytopenia (6/68, 8.82%), lymphadenopathy (4/68, 5.88%), eschar formation (8/68, 11.76%), diabetic ketoacidosis (1/68, 1.47%), hepatosplenomegaly (1/68, 1.47%), acute appendicitis (5/68, 7.35%), diabetes mellitus (5/68, 7.35%), ARDS (2/68, 2.94%), and jaundice [ijpmonline.org]

  Clinical presentations of these infections vary widely, from acute flu-like syndrome, with or without signs of organ dysfunction, such as jaundice or renal insufficiency, to multiorgan dysfunction mimicking severe sepsis syndrome ( 10 ). [doi.org]

  Symptoms Number of patients (%) Fever =7 days 9 7-10 days 7 =2 weeks 7 Myalgia 19 (82.6) Jaundice 6 (26.0) Breathlessness 7 (30.4) Cough 8 (34.7) Headache 21 (91.3) Nausea/vomiting 17 (73.9) Seizures 6 (26.0) Clinical signs Altered sensorium 14 (60.8) [amhsr.org]

• Conjunctival Injection

  Patient 1 had bilateral conjunctival injection and subconjunctival hemorrhage; patients 2-4 had conjunctival injection and episcleral vessel dilation bilaterally. [ncbi.nlm.nih.gov]

  Headache is severe and common, as is conjunctival injection. A macular rash develops on the trunk during the 5th to 8th day of fever, often extending to the arms and legs. It may disappear rapidly or become maculopapular and intensely colored. [msdmanuals.com]

  Case presentation: We report the case of a 4-year-old boy who presented with fever of 7 days duration and skin rash and bilateral conjunctival injection. He had a history of visiting a rural area with his grandmother. [circ.ahajournals.org]

• Myalgia

  Approximately at the tenth day following the initial infection, high fever, headaches, myalgia and fatigue emerge. The non-specificity of the symptoms constitutes a diagnostic obstacle at the early disease phase. [symptoma.com]

  In comparison to Lao patients, Japanese patients had a substantially lower prevalence of myalgia and hepatomegaly. [doi.org]

  Clinical manifestations of Tsutsugamushi disease include maculopapular skin rashes, fever, and myalgia. This is followed by disseminated systemic vasculitis affecting the lung, liver, and kidney within days or weeks [ 1 ]. [kjim.org]

  Fever was the most common symptom in our group of patients which is similar to a previous report. [20] Narvencar et al. [2] in 2012 reported fever with myalgia as the predominant symptom in 80% of the patients, but in the present study, myalgia was observed [ijpmonline.org]

• Arthralgia

  He reported that his initial symptoms were high fever, chills, night sweats, intense headaches, myalgia, and arthralgia that had started 3 weeks earlier, but his fever and systemic symptoms had resolved spontaneously after 1 week. [dx.doi.org]

• Skin Rash

  An 85-year-old female farmer was admitted to our hospital for fever, general fatigue, and skin rash. Cephalosporin was not effective and minocycline was dramatically effective. An eschar was discovered on her inguinal region after the defervescence. [ncbi.nlm.nih.gov]

  Scrub typhus is transmitted to humans by chiggers infected with Orientia tsutsugamushi that attach to the skin and suck tissue fluid, and it is characterized by eschar, fever, headache, and skin rash ( 1, 3 ). [doi.org]

  However, because of the initial lack of response to ASPC, generalized skin rashes without an ordinary stick wound which had diminished before the hospitalization, and a history of working outdoors in a nearby mountain area, the possibility of new type [jstage.jst.go.jp]

  He had erythematous macular rash on her trunk. Examination of his skin revealed an eschar on penile base of right scrotum. [circ.ahajournals.org]

  Case report An 84-year-old rural-dwelling Japanese woman presented to our clinic in April 2016 with a three-day history of high-grade fever and skin rash. She also complained of malaise, loss of appetite, and dyspnea. [tandfonline.com]

• Pruritic Rash

  Two weeks earlier, she had noticed a transient pruritic rash on her abdomen, which had appeared after she had been collecting firewood in a local forest clearing. [dx.doi.org]

• Night Sweats

  Patient 2 In January 2016, a 40-year-old construction worker had sudden onset of high fever, chills, night sweats, headaches, myalgia, retro-orbital pain, and photophobia. [dx.doi.org]

• Skin Eschar

  Pat = patient's skin eschar; Neg = negative control; Shi = Shimokoshi strain (positive control); Kt = Kato strain; M = marker (100 bp ladder). [ncbi.nlm.nih.gov]

• Headache

  It presents with fever, headache, a macular rash, lymphadenopathy and eschar at the region of the mite bite. Tsutsugamushi disease is transmitted through a mite bite. [symptoma.com]

  After an incubation period of 6 to 21 days (mean 10 to 12 days), symptoms of scrub typhus start suddenly and include fever, chills, headache, and generalized lymphadenopathy. [msdmanuals.com]

  Tsutsugamushi disease: A mite-borne infectious disease caused by a microorganism, Rickettsia tsutsugamushi, characteristically with fever, headache, a raised (macular) rash, swollen glands (lymphadenopathy) and a dark crusted ulcer (called an eschar or [medicinenet.com]

  Case report of a 60-year-old woman who complained of fever, chills, headache, lymphadenopathy, and blurred vision in the right eye following an insect bite to the lower right forehead. [ncbi.nlm.nih.gov]

The complete workup for scrub typhus encompasses a multitude of tests and procedures, including routine blood tests, serology, and PCR.

More specifically, laboratory blood tests including a complete blood count and biochemical studies usually yield the following results:

• Lymphopenia, early in the course of the disease
• Lymphocytosis, during the progressed stage
• Decreased CD4:CD8 ratio
• Thrombocytopenia [7]
• Augmented SGOT/SGPT levels in up to 95% of the patients
• Hypoalbuminemia, in 50% of the patients

The aforementioned findings may also suggest a potential dengue fever or leptospirosis infection; the latter is known to often coexist with scrub fever [8].

Serologic tests are further carried out, as they constitute the primary diagnostic procedures. A direct immunoperoxidase test and an immunofluorescent assay are used to establish the diagnosis and are expected to yield a result displaying a 4-fold augmentation of antibody titers between acute and convalescent serum specimens [9]. All potential O. tsutsugamushi subtypes should be considered as a possibility and should, therefore, be separately investigated serologically. A dot immunoassay can also be employed in order to diagnose tsutsugamushi disease, whereas the immunochromatographic test, aimed at the detection of immunoglobulin (Ig) M and IgG antibodies exhibit a considerably greater sensitivity for an early diagnosis when compared to the standard immunofluorescence assay.

The polymerase chain reaction tests (PCR) has proven a valuable diagnostic tool, on eschar samples, early in the course of the disease. In third world countries, the method of choice is the Weil-Felix OX-K strain agglutination reaction; when more advanced medical facilities are available, this test is not opted for due to its decreased sensitivity.

• Rickettsia Orientalis

  Tsutsugamushi, which is caused by Rickettsia nipponica (Rickettsia orientalis, Rickettsia tsutsugamushi), is widely distributed over an area which includes Japan, Malaya, French Indo-China, Sumatra, the Philippines, other islands of the Pacific and northern [jamanetwork.com]

  The cross-protection test with mice for identification and differentiation of several strains of Rickettsia orientalis newly isolated in Japan. Jpn J Med Sci Biol 1959;12:391–404. [synapse.koreamed.org]

  Strain variation of Rickettsia orientalis in the complement fixation test. Jpn J Med Sci Biol. 1964;17:59–72. View Article PubMed Google Scholar Nakayama K, Yamashita A, Kurokawa K, Morimoto T, Ogawa M, Fukuhara M. [bmcinfectdis.biomedcentral.com]

The clinical response to doxycycline treatment in patients with early, mild scrub typhus in northern Thailand was compared with the results of treatment in Mae Sod, western Thailand. [ncbi.nlm.nih.gov]

No treatment failure was reported. No trials reported deaths or serious complications. There are several trials of scrub typhus treatment with antibiotics. [doi.org]

2: Antibiotic Treatment for Scrub Typhus in Pregnant Women. [antimicrobe.org]

Prognosis Prognosis varies and depends on the severity of illness, which relates to the different strains of O tsutsugamushi, as well as to host factors. Severe disease is uncommon with antimicrobial treatment. [emedicine.com]

The present research throws light on specific etiological agents that may cause AES and have found scrub typhus to be an important etiology. [doi.org]

The etiologic agent of scrub typhus, R. tsutsugamushi, is a natural infection of several trombiculid mites, most commonly L. deliensis. [cambridge.org]

To retrospectively confirm the suspected rickettsial disease (Scrub typhus) using a gold standard diagnostic test i.e. microimmunofluorescence in pediatric patients with acute febrile illness of unknown etiology. [ncbi.nlm.nih.gov]

Commission on Immunization of the Army Epidemiological Board, Washington, D. C. [jci.org]

The current system for Tsutsugamushi disease surveillance is useful for describing epidemiologic patterns by time, prefecture, and demographic characteristics. [ncbi.nlm.nih.gov]

Numerous experts in medicine, epidemiology, and entomology were called upon to examine the problem, and, two major lines of defense against the disease had been developed. [cambridge.org]

Methods Data from the National Infectious Disease Surveillance (NIDS) system were used to analyze the epidemiology of scrub typhus in South Korea. [parasitesandvectors.biomedcentral.com]

The infection and activation of endothelial cells contribute to the pathophysiology of scrub typhus as reported in rickettsioses. [onlinelibrary.wiley.com]

Scrub typhus: pathophysiology, clinical manifestations and prognosis. Asian Pac J Trop Med. 2012 Apr. 5(4):261-4. [Medline]. Watt G, Jongsakul K, Chouriyagune C, Paris R. [emedicine.com]

This study shows the status of scrub typhus in Japan in 1998 and provides important information for diagnosis and prevention. [ncbi.nlm.nih.gov]

This study shows the status of scrub typhus in Japan in 1998 and provides important information for diagnosis and prevention. © The American Society of Tropical Medicine and Hygiene Article metrics loading... [doi.org]

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