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 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]

  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]

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

  Plasma fibrinogen was normal at 312 mg/dL (normal 160–380) and fibrinogen degradation products were slightly elevated at 11.4 μg/mL ( 7 cells (normal Computed tomography revealed mild splenomegaly and small pleural effusion bilaterally, but no significant [tandfonline.com]

  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. [merckmanuals.com]

• 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. [merckmanuals.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.medscape.com]

• Fever

  […] patients given doxycycline monotherapy (fever clearance time 52 h). [ncbi.nlm.nih.gov]

  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]

  Of the numerous tick-borne rickettsioses identified in recent years, African tick-bite fever appears to be of particular importance to travellers. The newly described flea-borne spotted fever caused by Rickettsia felis may be global in distribution. [doi.org]

• 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]

  Other finding werecardiomegaly (10 patients), pleural effusion (6 patients), mediastinal lymphadenopathy(3 patients). [synapse.koreamed.org]

  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]

  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]

• 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]

  Abstract A 47-year-old male was referred to our hospital with persistent high fever. [jstage.jst.go.jp]

• Chills

  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]

  A reddish or pinkish lesion appears at the site of the mite bite, and the person begins to experience headache, fever, chills, and general pains, along with swollen lymph glands. [britannica.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. [merckmanuals.com]

  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]

• 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]

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

  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]

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

• Cough

  The second patient was a 30-year-old rice and corn farmer who presented with fever that had lasted for 10 days accompanied by cough, hearing loss, lymphadenopathy, and conjunctival suffusion. [doi.org]

  Signs and symptoms include fever, headache, muscle pain, cough, and gastrointestinal symptoms. More virulent strains of O. tsutsugamushi can cause hemorrhaging and intravascular coagulation. [en.wikipedia.org]

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

  Scrub typhus is associated with non-specific symptoms, including fever, headache, cough, myalgia, and rash. The rash occurs in about one half of all patients and spreads from the trunk to the extremities; this rash was present in our patient. [tandfonline.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]

  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]

  Mycoplasma pneumonia IgM was negative. R.tsutsugamushi Ab was positive. Echocardiographic findings 1 day after admission was mild dilatation of LCA (RCA 1.8mm, LCA 3mm). [circ.ahajournals.org]

• Sore Throat

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

• Painful Cough

  Signs and symptoms include fever, headache, muscle pain, cough, and gastrointestinal symptoms. More virulent strains of O. tsutsugamushi can cause hemorrhaging and intravascular coagulation. [en.wikipedia.org]

• Severe Clinical Course

  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]

  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]

• 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]

  Its symptoms resemble those of dengue and include fever, headache, muscle pain, nausea, and vomiting 1, 2. It can cause multi-organ failure, haemoptysis, and pneumonitis and is fatal in 1.4–6% of cases 2, 3. [nature.com]

• 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]

  An episode of transient abdominal pain accompanied by vaginal bleeding occurred on the third hospital day. [doi.org]

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

  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]

  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]

  […] 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]

  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) Pedal [amhsr.org]

• Otalgia

  Otalgia and eschar in the external auditory canal in scrub typhus complicated by acute respiratory distress syndrome and multiple organ failure. BMC Infect Dis. 2011 Mar 30. 11:79. [Medline]. [Full Text]. Edwards MS, Feigen RD. [emedicine.medscape.com]

• 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]

  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]

  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. [merckmanuals.com]

  It is characterized by fever with eschar as a pathognomonic sign and accompanied by other non-specific clinical signs such as headache, chills, cough, myalgia, conjunctival injection and skin rash, and sometimes serious complications such as meningitis [synapse.koreamed.org]

• Blurred Vision

  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]

• Retinal Hemorrhage

  To report branch retinal vein occlusion and retinal hemorrhages associated with tsutsugamushi disease. [ncbi.nlm.nih.gov]

• 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]

  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]

  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]

• Myalgia

  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]

  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]

  The clinical picture of scrub typhus typically associates fever, an exanthematous rash, myalgia, and diffuse lymphadenopathy. [academic.oup.com]

  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]

• 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]

• Headache

  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]

  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]

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

  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]

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.

• Pericardial Effusion

  Pericardial effusion in Tsutsugamushi Disease is not a common manifestation, although a high rate of effusion was reported in autopsy in those who had died of the disease. [ncbi.nlm.nih.gov]

• 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]

The distributions of prior antimicrobial treatment were similar in the two treatment groups (data not shown here). [doi.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.medscape.com]

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]

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

A number of microorganisms were hypothesized as an etiology of the illness. This is the first reported case of Kawasaki disease with tsutsugamushi disease. [circ.ahajournals.org]

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

Short Communication Comparative Research on Epidemiological Aspects of Tsutsugamushi Disease (Scrub Typhus) between Korea and Japan Hyeong-Ae Bang, Myeong-Jin Lee 1 and Won-Chang Lee 2 * Faculty of Public Health, The Korean Public Health Association; [web.archive.org]

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]

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.medscape.com]

After preventive measures were implemented, the incidence was descent. So Nan Peng Lie Islands were the natural foci of tsutsugamushi disease. [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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