Acute Cholecystitis in Patients with Scrub Typhus

Acute cholecystitis is a rare complication of scrub typhus. Although a few such cases have been reported in patients with scrub typhus, the clinical course is not well described. Of 12 patients, acute cholecystitis developed in 66.7% (8/12) of patients older than 60 yr. The scrub typhus group with acute cholecystitis had marginal significant longer hospital stay and higher cost than the group without cholecystitis according to propensity score matching. Scrub typhus should be kept in mind as a rare etiology of acute cholecystitis in endemic areas because the typical signs of scrub typhus such as skin rash and eschar can present after the abdominal pain.

A case of Tsutsugamushi disease presenting with nephrotic syndrome

Nephrotic syndrome associated with Tsutsugamushi disease has not been previously reported. We are describing a case of Tsutsugamuchi disease presenting with nephrotic syndrome. A 72-year-old woman presented with fever and generalized edema. Laboratory studies revealed a leukocytosis, hypoalbuminemia, and hypercholesterolemia. Her urine protein excretion was 5.4 g/day. The anti-Tsutsugamushi antibody test was strongly positive (1:2,560). A renal biopsy was performed, and pathologic findings revealed membranous glomerulonephritis. The patient's clinical symptoms improved markedly after treatment with doxycycline.

Persistence of Orientia tsutsugamushi in Humans

We investigated the persistence of viable Orientia tsutsugamushi in patients who had recovered from scrub typhus. Blood specimens were available from six patients with scrub typhus who were at 1 to 18 months after the onset of the illness. The EDTA-treated blood specimens were inoculated into ECV304 cells, and cultures were maintained for 7 months. Sequencing of the 56-kDa type-specific antigen gene of O. tsutsugamushi was performed to ascertain the homology of isolates. O. tsutsugamushi was isolated from all six patients, and nucleotide sequences of isolates serially collected from each patient were identical in all five patients in whom nucleotide sequences were compared. One patient relapsed 2 days after completion of antibiotic therapy; two patients complained of weakness for 1 to 2.5 months after the illness; one patient underwent coronary angioplasty 6 months later; and one patient suffered from a transient ischemic attack 8 months later. This finding suggests that O. tsutsugamushi causes chronic latent infection, which may be associated with certain clinical illnesses, preceded by scrub typhus. Antibiotic therapy abates the symptoms of scrub typhus, but does not eradicate O. tsutsugamushi from the human body.

Incidence and Type of Monoclonal or Biclonal Gammopathies in Scrub Typhus / 대한진단검사의학회지

BACKGROUND: Korea is an endemic area of scrub typhus and it is a common seasonal febrile illness. Although, various humoral immune responses to scrub typhus have been documented, no association between gammopathy and scrub typhus has ever been reported. We analyzed the incidences and types of monoclonal and biclonal gammopathies in scrub typhus for better coping with those gammopathies in scrub typhus. METHODS: Anti-Orientia tsutsugamushi antibody-positive sera identified by indirect immunofluorescence assay were acquired from 40 patients with confirmed scrub typhus. Monoclonal and biclonal gammopathies were screened by protein electrophoresis and were confirmed using immunofixation electrophoresis (IFE). Laboratory findings on admission of the patients with monoclonal or biclonal gammopathy were investigated retrospectively to characterize the gammopathies. RESULTS: Monoclonal or biclonal gammopathies were detected in 30% (12/40) of patients with scrub typhus (IgG-lambda, 40%; IgG-kappa, 30%; IgM-kappa, 10%; IgM-lambda, 10%; IgA-kappa, 5%; IgA-lambda, 5%). Concentrations of clonal immunoglobulin were less than 3 g/dL in all gammopathies, and hypercalcemia was not detected in any of the patients. CONCLUSIONS: Our results suggest possible association between gammopathies and scrub typhus. Further studies in larger series will be needed for exact incidence and clinical course of gammopathies in scrub typhus.

Hepatic dysfunction in pediatric scrub typhus: role of liver function test in diagnosis and marker of disease severity.

OBJECTIVE: Determine the frequency of abnormalities of liver function test in children with scrub typhus and its relation with severity of disease. MATERIAL AND METHOD: Fifty-four children diagnosed with scrub typhus at Chiang Rai Regional Hospitalfrom January 2004 to December 2005 were studied. The diagnosis of scrub typhus in the present study was based on a single indirect immunofluorescent antibody (IFA) titer against O tsutsugamushi of > or = 1:400 or a four fold or greater rise in IFA titer to at least 1:200. Liver function tests (LFT) were done on the first few days of admission in all patients. Abnormalities of LFT were focused on serum AST, ALT albumin and total bilirubin level. All of the patients were divided into two groups based on the presence or absence of complications. RESULTS: Fifty-two patients (96.3%) had abnormal LFT. Evaluation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were detected in 52 (96.3%) and 36 (66.7%) cases, respectively. Hypoalbuminemia and hyperbilirubinemia were detected in 23 (42.6%) and 4 (7.4%) cases, respectively. The higher level of AST, ALT and lower level ofserum albumin correlated significantly with the severity of scrub typhus in children. CONCLUSION: Hepatic dysfunction is common in children with scrub typhus. Elevation of AST level may be used as a screening test for diagnosis of scrub typhus in areas where rapid diagnostic test is not commercially available. Increased AST, ALT and hypoalbuminemia related with severity of disease.

Acute reversible hearing loss in scrub typhus.

Scrub typhus usually presents as pyrexia with or without multiple organ involvement. Acute hearing loss occurs in about one third of cases and is a useful clue toward the diagnosis. We present two cases of scrub typhus with acute reversible hearing loss from an endemic area. The diagnosis was confirmed by nested PCR.

ARDS complicating scrub typhus in Sub-Himalayan region.

Scrub typhus is a febrile illness widely endemic in Asia caused by Rickettsiae tsutsugamushi in which humans are accidental hosts. If there is delay in the initiation of the appropriate antimicrobial therapy patient may present with serious complications. We report three cases that presented in emergency with acute respiratory distress syndrome and history of fever for more than one-week duration. On investigation all the three patients were positive for Weil Felix reaction and showed dramatic response to doxycycline.

Gastrointestinal manifestations of septic patients with scrub typhus in Maharat Nakhon Ratchasima Hospital.

Scrub typhus is an acute febrile illness caused by Orientia induced vasculitis, which is common in Asia and the Pacific Islands and is sometimes also encountered in Western countries. Even though it can cause multi-organ dysfunctions, there is limited information regarding the relationship between scrub typhus infection and gastrointestinal dysfunction. Therefore, a cross-sectional study was conducted to discover the gastrointestinal manifestations of septic patients with scrub typhus infection. During the study period, 80 septic cases were recruited, and according to the results of immunofluorescent antibody testing (IFA), 20 (25%) were found to have scrub typhus infection. The most common gastrointestinal symptoms of scrub typhus patients were vomiting 13 (65%), nausea 12 (60%), diarrhea 9 (45%), and hametamesis or melena 5 (25%). Gastrointestinal signs included hepatomegaly 8 (40%), jaundice 7 (35%), and abdominal pain 4 (20%). Elevation of SGOT, SGPT, and alkaline phosphatase were 16 (80%), 14 (70%), and 16 (80%), respectively. Direct bilirubin was elevated in 19 (95%) of the cases and half of the cases had a low serum protein level. Of scrub typhus cases, 8 (40%) had eschars. The sites of eschars were mostly in hidden areas, such as on the back, genitalia and abdomen. Three of the five patients with eschar had hepatomegaly on ultrasound examination. The significant findings of the scrub typhus septic patients with eschar on endoscopic examination were gastritis in two cases, gastritis with gastric erosion in two cases, and one case showed a duodenal ulcer and erosion. The differentiating point for endoscopic findings in scrub typhus compared to the other causes was that the stomach lesions were more frequent and severe than the duodenal lesions. According to our endoscopic findings, physicians should be aware of gastric and duodenal lesions in febrile patients with gastrointestinal symptoms, such as abdominal pain or discomfort and indigestion. Scrub typhus can cause gastrointestinal and liver dysfunction.

Clinical Role of Interstitial Pneumonia in Patients with Scrub Typhus: A Possible Marker of Disease Severity

Interstitial pneumonia (IP) frequently occurs in patients with scrub typhus, but its clinical significance is not well known. This study was designed to evaluate interstitial pneumonia as a marker of severity of the disease for patients with scrub typhus. We investigated clinical parameters representing the severity of the disease, and the chest radiographic findings for 101 patients with scrub typhus. We then compared these clinical factors between patients with and without IP. We also studied the relationship between IP and other chest radiographic findings. The chest radiography showed IP (51.4%), pleural effusion (42.6%), cardiomegaly (14.9%), pulmonary alveolar edema (20.8%), hilar lymphadenopathy (13.8%) and focal atelectasis (11.8%), respectively. The patients with IP (n=52) had higher incidences in episode of hypoxia (p=0.030), hypotension (p=0.024), severe thrombocytopenia (p=0.036) and hypoalbuminemia (p=0.013) than the patients without IP (n=49). The patients with IP also had higher incidences of pleural effusion (p<0.001), focal atelectasis (p=0.019), cardiomegaly (p<0.001), pulmonary alveolar edema (p=0.011) and hilar lymphadenopathy (p<0.001) than the patients without IP. Our data suggest that IP frequently occurs for patients with scrub typhus and its presence is closely associated with the disease severity of scrub typhus.

Outbreak of Hepatitis by Orientia tsutsugamushi in the Early Years of the New Millenium / 대한간학회지

BACKGROUND/AIMS: Orientia -tsutsugamushi infection is an acute febrile disease due to the accidental transmission through human skin of forest dwelling vector Leptotrombidium larva. The authors observed liver dysfunctions in patients diagnosed with tsutsugamushi disease (Scrub typhus) in the past 3 years and report the data in the hope of bringing attention to this disease in the differential diagnosis of autumn-season hepatitis, especially of non-A, non-B and non-C hepatitis. METHODS: Medical records of 22 patients diagnosed with tsutsugamushi disease by the hemagglutinin method between October 2000 and November 2002 were reviewed. RESULTS: Female gender was dominant in the ratio of 3.4:1. Mean age was 56.4 +/- 2.6. Admission was between 23rd September and 15th November with the peak between mid October and early November. Fever, being the most common symptom, was observed in 21 cases, myalgia in 13, arthralgia in 12, chills in 6, and skin rash in 6. An incubation period of 7-9 days was most common (10 cases), 13-15 days (4), 10-12 days (3), within 3 days (3), and 4-6 days (2). Average ALT, AST and GGTP were increased to 93.2 +/- 17.3 IU/L (18 +/- 345 IU/L), 92.5 +/- 11.7 IU/L (34-255 IU/L) and 132.2 +/- 14.5 IU/L (19-251 IU/L), respectively, but total bilirubin was normal. All the patients improved with doxycycline therapy. CONCLUSIONS: Since it usually shows liver dysfunction, it is important to take Orientia tsutsugamushi into consideration in differential diagnosis of autumn-season, febrile hepatic disease.

Tsutsugamushi Infection-Associated Acute Rhabdomyolysis and Acute Renal Failure

Rhabdomyolysis is a rare complication that emerges in a variety of infectious diseases, such as tsutsugamushi infection. In this study, we report a 71-year-old female patient with tsutsugamushi infection who exhibiting rhabdomyolysis and acute renal failure. On admission, an eschar, which is characteristic of tsutsugamushi infection, was found on her right flank area. Moreover, her tsutsugamushi antibody titer was 1: 40960. The elevated values of serum creatinine phosphokinase (CPK), aldolase, creatinine and dark brown urine secondary to myoglobinuria are consistent with indications of rhabdomyolysis and acute renal failure due to tsutsugamushi infection. Her health improved without any residual effects after treatment with doxycyclin and hydration with normal saline.

Evaluation of a newly developed dipstick test for the rapid diagnosis of scrub typhus in febrile patients.

Scrub typhus is a potentially fatal, febrile disease prevalent in rural Asia. The etiological agent, Orientia tsutsugamushi, is transmitted to humans by the bite of a larval trombiculid mite. No current diagnostic test is sufficiently practical for use by physicians working in rural areas. A new dipstick test using a dot blot immunoassay format has been developed for the serodiagnosis of scrub typhus. We evaluated this test on 83 patients presenting with acute fever of unknown origin at Maharaj Hospital, a tertiary care medical center in Nakhon Ratchasima, Northeast Thailand. The diagnosis of scrub typhus was confirmed in 30 of these patients (36%) by the indirect immunoperoxidase test. The sensitivity of the test was 87% and its specificity was 94%. The dot blot immunoassay dipstick is accurate, rapid, easy to use, and relatively inexpensive. It appears to be the best currently available test for diagnosing scrub typhus in rural areas where this disease predominates.

Acute respiratory distress syndrome associated with scrub typhus: diffuse alveolar damage without pulmonary vasculitis

Pathologic findings of scrub typhus have been characterized by vasculitis of the microvasculature of the involved organ resulting from a direct invasion by Orientia tsutsugamushi. We experienced a case of acute respiratory distress syndrome (ARDS) associated with scrub typhus. The case was proven by eschar and high titer of serum IgM antibody (positive at 1:1280). Open lung biopsy showed diffuse alveolar damage (DAD) in the organizing stage without evidence of vasculitis. Immunofluorescent antibody staining and polymerase chain reaction for O. tsutsugamushi failed to demonstrate the organism in the lung tissue. The patient expired due to progressive respiratory failure despite doxycycline therapy. Immunologic mechanism, without direct invasion of the organism, may participate in the pathogenesis of ARDS associated with scrub typhus.

Seroprevalence of scrub typhus infection in patients with pyrexia at some malaria clinics in three western provinces of Thailand.

In Thailand, the epidemiological data on scrub typhus infection represents only "the tip of an iceberg" especially in malaria clinics where patients come to seek attention because of other febrile illnesses that may have initial clinical signs that are indistinguishable from malaria. The objectives of this study were to determine the prevalence of antibody titers to Orientia tsutsugamushi, and its various strains, among patients at some malaria clinics in three western provinces of Thailand. The sample was represented by 200 patients from 6 malaria clinics in Ratchaburi, Petchaburi and Kanchanaburi provinces between June and November, 1994. Blood specimens were collected with their consent. Immunofluorescent antibody assays (IFA) were used for measuring IgM and IgG antibody titers for scrub typhus infection. The results showed that the prevalence rate for scrub typhus infection (IgM and/or IgG titer > or = 50) was 59.50% (119 cases). The immunofluorescent antibody response to various strains of O. tsutsugamushi showed that co-infections with the Karp, the Gilliam and the Kato strains were the most common (found in 68.10% of cases). Geometric mean antibody titers (GMT) were highest for the Karp strain, followed by the Gilliam then Kato strains. In conclusion, this study indicates that the prevalence rate of scrub typhus is not rare in these areas.

Electrocardiographic changes in scrub typhus patients.

Ninety-eight cases of scrub typhus were examined electrocardiographically. Various findings beyond the normal range were as follows: In the febrile stage, sinus arrhythmia with some beats below 60 per minute, flat or low T waves in the left precordial leads, sinus tachycardia, ST segment elevation of 4-l mm in V2, prominent u waves measuring 1 mm or more in amplitude, tall and peaked T waves in V2-4, incomplete right bundle branch block, T wave inversion in V3-4, first degree A-V block, Q-Tc interval prolongation, notched T waves in V3, AV junctional escapes, prominent Ta waves or depression of PR segments in V2, and right axis deviation; in the convalescent stage, sinus arrhythmia with some beats below 60 per minute, prominent u waves measuring 1 mm or more in amplitude, tall and peaked T waves in V2-4, flat or low T waves in the left precordial leads, incomplete right bundle branch block, sinus tachycardia, first degree A-V block, Q-Tc interval prolongation, T wave inversion in V3-4, ST segment elevation of 4 mm in amplitude in V2, ventricular premature contractions, atrial premature contractions, and right axis deviation. In comparison with the electrocardiographic findings in 101 asymptomatic normal subjects, flat T waves in the precordial leads, tall and peaked T waves in V2-4 in both acute and convalescent stages, and sinus arrhythmia with some beats below 60 per minute in the convalescent stage were more frequent in cases. Electrocardiographic abnormalities were present most commonly in the acute illness, and our findings support the impression that, with few exceptions, prompt treatment of scrub typhus with antibiotics prevents the serious cardiac complications seen prior to the antibiotic era.