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[Scrub typhus--one case report].

Scrub typhus (tsutsugamushi disease) is an acute infectious disease caused by Rickettsia tsutsugamushi transmitted through the bite of larvae of certain trombiculid mites. Geographical distribution in Asian-Pacific region is much of the roughly triangular area bounded by Japan, Pakistan and Australia. It is an endemic illness in the Pescadores Islands, but has scarcely been reported in central Taiwan. An eleven-year-old boy was admitted to Changhua Christian Hospital with the chief complaints of fever, lethargy and skin rash for seven days. On physical examination, he was found to have painless eschar, conjunctivitis, meningoencephalitis, pneumonitis, ascites, jaundice, hepatomegaly, liver function impairment and thrombocytopenia. His Proteus OX-K agglutinin titer increased from 1:160 in the acute sera to 1:640 in the convalescent sera. A greater than four-fold rise (greater than 1:640) in antibody titers to Karp, Gilliam, Kato strains of R. tsutsugamushi between acute and convalescent sera were demonstrated by immunofluorescent antibody. The patient was treated with minocycline and chloramphenicol and was completely recovered.

Child↗

HLA-DR+CD3+ and CD8+ cells are increased but CD4+CD45RA+ cells are reduced in the peripheral blood in human scrub typhus.

Immunological studies on scrub typhus (ST) have been limited mostly to animals despite the possible difference in the immune responses among the species of the hosts. To investigate in vivo cellular immune responses to ST in humans, we characterized T-cell subsets in the peripheral blood samples from 30 healthy control subjects (HC), 11 patients with nonrickettsial acute infections (NRAI), and 6 patients with ST by a dual labeling method of flow cytometry. In ST, HLA-DR+CD3+ cells were greatly increased compared with those in HC and NRAI (HC, 2.3 +/- 1.3%; NRAI, 4.5 +/- 4.4%; ST, 32.5 +/- 14.7% values are means +/- SD). CD8+ cells were also significantly increased (HC, 29.5 +/- 5.9%; NRAI, 30.5 +/- 9.4%; ST, 44.9 +/- 11.5%), while CD4+CD45RA+ cells were significantly reduced (HC, 23.6 +/- 8.2%; NRAI, 23.3 +/- 12.3%; ST, 12.9 +/- 7.1%) in ST. The unique changes in the T-cell subsets in the peripheral blood samples from the patients with ST support the importance of the cellular immune responses to the natural infection of ST in humans.

Adult↗

Pregnancy with scrub typhus and vertical transmission: a case report.

Scrub typhus is a rickettsian disease which is seldom found in pregnancy. A 31-year-old, 34 weeks pregnant woman presented with fever, chill and cough for 6 weeks. Fetal jeopardy was found then a cesarean section was performed to deliver a 2,200 g male with hepatosplenomegaly. The mother's diagnosis was confirmed by positive Weil-Felix (OXK titer 1:320) and scrub typhus (titer 1:1600) tests. Vertical transmission was also demonstrated by a positive scrub typhus IgM in her child.

Adult↗

Life-threatening scrub typhus in a traveler returning from Thailand.

Scrub typhus is not one of the more commonly encountered diseases in travelers returning from Asia, but it deserves more consideration in view of its severity and the availability of specific chemotherapy and chemoprophylaxis. We describe a case of scrub typhus that was associated with coma and multiorgan failure in a traveler returning to the United States from Thailand. The diagnosis was made only retrospectively despite a travel history and clinical signs that suggested infection with Rickettsia tsutsugamushi. No specific therapy was given, and marked neurological impairment persisted 6 months after the beginning of the illness. An increased awareness of scrub typhus is a prerequisite for recommending prophylaxis and instituting prompt therapy.

Coma↗

[Tsutsugamushi disease (scrub typhus) in Japan: clinical features].

Clinical features of tsutsugamushi disease (scrub typhus) were analyzed, based on 416 cases reported in Japan in 1998. Three major clinical symptoms: eschar, fever and rash were found in 87%, 98% and 92% of the cases, respectively. Elevated levels of CRP, GOT, GPT and LDH were observed in 96%, 85%, 78% and 91%, respectively. These clinical and laboratory findings were observed in the majority of the cases and considered important for diagnosis. Disseminated intravascular coagulation developed in 21 cases, indicating that scrub typhus can be life threatening. Lymphadenopathy was observed in 51% of the cases. Enlarged lymph nodes were limited to the local sites in 75% of these lymphadenopathy cases and most of these sites were adjacent to eschars. Most eschars were scabbed and located in the abdomen and the lower half of the body, especially the feet. This suggests that these parts are frequently exposed to tsutsugamushi mites. Furthermore, the skin is soft in these parts and covered by cloth. These factors may make it possible for mites to keep biting without being noticed for several hours, long enough for rickettsial transmission. Interestingly, eschar and rash were absent in 14% and 8% of the cases, respectively. This result suggests that the cases without the unique symptoms may have been misdiagnosed as common cold or other febrile illnesses. One hundred and fifty-four suspected cases were not scrub typhus cases by the serological tests. The three major clinical symptoms were present in approximately a half of these negative cases, eschar being observed in approximately 70%. This may suggest the presence of new type of scrub typhus can not be diagnosed by the present laboratory tests. Clinical features of scrub typhus in Japan were well revealed, and information obtained in the present study is useful for improving clinical diagnosis. It should, however, be stressed that there were cases that could not be correctly diagnosed only by the clinical symptoms, suggesting that it is important to improve the serological tests.

Diagnosis, Differential↗

Differentiating dengue virus infection from scrub typhus in Thai adults with fever.

Dengue fever and scrub typhus are common infections in Asia that often present as acute febrile illness of unclear etiology. We prospectively evaluated febrile adults presenting to the outpatient department of a hospital in northern Thailand to attempt to identify distinguishing characteristics between the two infections. Fifty-four patients were infected with scrub typhus and 35 were infected with dengue virus. Dengue virus infection was associated with hemorrhagic manifestations, particularly bleeding from the gums, which was reported by 27% of the dengue patients, but by none of the scrub typhus patients (P < 0.001, by Fisher's exact test). A low platelet count (< 140,000/mm3) and low white blood cell count (< 5,000/mm3) were strongly associated with dengue infections: odds ratio = 26.3 (95% confidence interval [CI] = 7.4-93.2) for platelet count and 8.2 (95% CI = 2.6-25.5) for leukocyte count. Prospective evaluations of the usefulness of these simple criteria to differentiate scrub typhus from dengue infection are needed in other areas, particularly where rapid confirmatory diagnostic tests are not available.

Adult↗

Doxycycline and rifampicin for mild scrub-typhus infections in northern Thailand: a randomised trial.

BACKGROUND: Some strains of scrub typhus in northern Thailand are poorly responsive to standard antirickettsial drugs. We therefore did a masked, randomised trial to compare rifampicin with standard doxycycline therapy for patients with scrub typhus. METHODS: Adult patients with strictly defined, mild scrub typhus were initially randomly assigned 1 week of daily oral treatment with 200 mg doxycycline (n=40), 600 mg rifampicin (n=38), or doxycycline with rifampicin (n=11). During the first year of treatment, the combined regimen was withdrawn because of lack of efficacy and the regimen was replaced with 900 mg rifampicin (n=37). Treatment outcome was assessed by fever clearance time (the time for oral temperature to fall below 37.3 degrees C). FINDINGS: About 12,800 fever patients were screened during the 3-year study to recruit 126 patients with confirmed scrub typhus and no other infection, of whom 86 completed therapy. Eight individuals received the combined regimen that was discontinued after 1 year. The median duration of pyrexia was significantly shorter (p=0.01) in the 24 patients treated with 900 mg daily rifampicin (fever clearance time 22.5 h) and in the 26 patients who received 600 mg rifampicin (fever clearance time 27.5 h) than in the 28 patients given doxycycline monotherapy (fever clearance time 52 h). Fever resolved in a significantly higher proportion of patients within 48 h of starting rifampicin (900 mg=79% [19 of 24], 600 mg=77% [20 of 26]) than in patients treated with doxycycline (46% [13 of 28]; p=0.02). Severe gastrointestinal events warranted exclusion of two patients on doxycyline. There were two relapses after doxycycline therapy, but none after rifampicin therapy. INTERPRETATION: Rifampicin is more effective than doxycycline against scrub-typhus infections acquired in northern Thailand, where strains with reduced susceptibility to antibiotics can occur.

Adolescent↗

[A clinical analysis of 31 cases with pulmonary damage caused by scrub typhus].

OBJECTIVE: To deepen the understanding of pulmonary damage caused by scrub typhus. METHODS: 31 cases of pulmonary damage caused by scrub typhus from 1993 to 1998 were reviewed with chest radiographs, chest B-ultrasound, etc. RESULTS: 44% cases with scrub typhus showed a pulmonary damage (31/70), in which 66% (20/31) had cough, 53% (16-31) had sputum, 53% (16/31) had rales and the most symptoms were mild. Chest X-rays: 45% (14/31) showed pulmonary interstitial lesion, 53%(16/31) pulmonary effusion lesion and 8 cases pleural lesion. 26% (8/31) of pleural effusion was confirmed by chest B-ultrasound. Respiratory failure was found in 5 cases. All cases were treated with chloramphenicol and(or) doxycyclinum and made a good recovery. CONCLUSION: The pulmonary damage caused by scrub typhus should be paid more attention to for avoiding misdiagnosis.

Adolescent↗

Elevation of serum transcobalamin II in patients with scrub typhus.

Serum transcobalamin II levels were measured in scrub typhus patients. Eighteen out of fifty-two patients admitted to Maharat Nakhon Ratchasima Hospital were diagnosed with scrub typhus infection. The serum unsaturated vitamin B12 binding protein (UBBC) and total vitamin B12 binding protein (TBBC) levels in these patients were significantly higher than in normal subjects (p < 0.001). The mean serum transcobalamin II level in the typhus patients was also significantly higher than in the normal subjects (p=0.004). There was a significant correlation between serum TCII levels and typhus IgM or IgG titers (p < 0.05), but not to total IgM levels. These findings indicate that patients with scrub typhus had stimulation of the recticuloendothelial system as a result of a considerable increase in transcobalamin II levels.

Adolescent↗

[Tsutsugamushi disease (scrub typhus) in Japan: epidemiological aspects].

Epidemiological aspects of tsutsugamushi disease (scrub typhus) in Japan in 1998 were analyzed using questionnaires. Four hundred and sixteen scrub typhus cases were reported in 24 prefectures in 1998. The annual number of the patients in 1998 was similar to those in the preceding three years. There was no sex difference. The patients at the age of 51 or greater accounted for 72% of the total cases. Patients engaged in farming and forestry accounted for 32% and 14% cases, respectively. Fifty-six, 21 and 19% were reported in Kyusyu, Kanto and Tohoku-Hokuriku districts, respectively, 96% of the total cases being reported in these 3 districts. Most cases were reported from April through June with some from October through December in Tohoku-Hokuriku districts, while most cases were reported from October through December in other districts, including Kyusyu and Kanto districts. Thus, there was a difference in epidemic seasons among the districts. Serotypes of scrub typhus rickettsia were analyzed by serum antibody titers in the Kyusyu district. The novel Kawasaki and Kuroki types were major strains; however, no geographical difference was seen within the Kyusyu district. Interestingly, 24 cases were diagnosed only by the new serotypes not by the classical serotypes (Kato, Karp and Gilliam) in serological tests. This result suggests that further investigations are required to determine the prevalent serotypes in each district and to improve the serological tests. This was the first comprehensive report of epidemiology of scrub typus in entire Japan. Information obtained in the present study provides deep insight into prediction, diagnosis, treatment and prevention of scrub typhus in Japan.

Adolescent↗

Scrub typhus in Hong Kong.

A retrospective analysis of cases of scrub typhus in military personnel in Hong Kong during the years 1979-1989 is presented. Fifty-nine cases were identified, most occurring during the hot humid season between May and October. Few civilian cases of scrub typhus are notified to the Hong Kong Medical and Health Department and possible reasons for the disparity in case numbers between military and civilian personnel are discussed. Reports from other areas of South-east Asia have documented a previously unrecognized high incidence of scrub typhus in the indigenous population. It is suggested that a prospective study utilizing specific serological diagnostic techniques would be of value in assessing the importance of scrub typhus as a cause of 'fever of undetermined origin' in the civilian population of Hong Kong.

Doxycycline↗

Scrub typhus: a frequently overlooked cause of acute renal failure.

Acute renal failure associated with scrub typhus infection is not rare as previously thought. The possibility of scrub typhus should be borne in mind when patients present with fever and varying degrees of acute renal failure, particularly if an eschar exists, along with a history of environmental exposure in an area like Taiwan, where scrub typhus is endemic. Prompt diagnosis and the use of appropriate antibiotics can rapidly alter the clinical course of the disease and prevent the development of serious or fatal complications. To illustrate the above point, this study reports 3 cases of scrub typhus associated with acute renal failure. They were seen at Chang Gung Memorial Hospital in a 2-year interval. Case 1 was referred from district hospital with clinical features of multiple organ dysfunctions, including shock, fever, acute respiratory failure, acute renal failure, and acute hepatitis. Case 2 was admitted with the chief problems of shock, fever, acute renal failure, and DIC. Case 3 visited our outpatient clinic due to fever, maculopapular rash and acute renal failure. In all these patients, the diagnosis was confirmed using immunofluorescence techniques, which showed that Orientia tsutsugamushi had an IgM titer of 1:80 or greater. Notably, despite having varying degrees of acute renal deterioration, the patients responded very well to doxycycline therapy and recovered completely. Additionally, a total of 4 similar cases of scrub typhus associated with acute renal failure were reviewed from the past literature.

Acute Kidney Injury↗

Outbreak of scrub typhus in southern India during the cooler months.

Orientia tsutsugamushi, the agent of scrub typhus, is a strict intracellular bacterium which is found in many parts of Asia including India. During the past few years, the number of patients with rickettsial infection and scrub typhus has increased, especially during the cooler months. We report in this study a recent outbreak of scrub typhus recorded during the cooler months (October 2001 to February 2002) in patients admitted to our hospital with acute febrile illness associated with diverse signs and symptoms. Overall, 28 patients were clinically and serologically confirmed to have scrub typhus. Fever for more than one week was the only common manifestation. Myalgias was the next most common feature (52%), and rash was observed in only 22% of the cases. Seventeen patients treated with doxycycline recovered in 1 to 3 days, as well as two patients who received chloramphenicol. In five patients who received ciprofloxacin, fever subsided only after five days. Finally three patients (10.7%) died, including one patient treated with doxycycline. These data indicate that scrub typhus is a reemerging infectious disease in India with a possibility of drug resistance. This reemergence emphasizes the need for further prospective studies to design effective control measures.

Adolescent↗

Possible scrub typhus coinfections in Thai agricultural workers hospitalized with leptospirosis.

Possible coinfections with Orientia tsutsugamushi the causative agent of scrub typhus, were prospectively evaluated in rice farmers hospitalized with leptospirosis in Northeast Thailand. Of 22 adults with leptospirosis diagnosed by the microscopic agglutination test, 9 also had serologic evidence of scrub typhus. Of 9 individuals with possible coinfections, 5 had signs or symptoms typical of scrub typhus and atypical of leptospirosis. Patients who appeared to have mixed infections had significantly higher median platelet counts and significantly lower median serum bilirubin and creatinine concentrations (P < 0.05, Mann-Whitney U test) than did individuals with leptospirosis alone. One patient with serologic evidence of scrub typhus and leptospirosis was treated only with penicillin, to which scrub typhus is not sensitive. Respiratory distress worsened during therapy, and the patient died of respiratory failure. Physicians should consider the possibility of scrub typhus infection in leptospirosis patients who respond poorly to treatment or who have atypical disease manifestations.

Adult↗

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.

Adult↗

Scrub typhus: radiological and clinical findings.

OBJECTIVES: To describe the radiological and clinical findings of scrub typhus. We retrospectively analysed the radiographic, thin-section CT and clinical features of scrub typhus. METHODS: The study included 75 consecutive patients (median age = 47 years, range = 18-81 years) with scrub typhus. Plain chest radiographs were obtained in all 75 patients and 19 underwent thin-section CT within 6 days of initial radiography. The radiographic and thin-section CT findings were retrospectively analysed by three radiologists. RESULTS: Most common clinical symptoms were fever (73/75, 98%), myalgia (61/75, 81%) and headache (60/75%, 80%). Rash (59/75, 79%) and eschar (56/75, 75%) were the most common signs. Radiography showed abnormalities in 54/75 (72%) patients. The most frequent findings were parenchymal abnormalities (53/75, 71%) with lower lung predilection including bilateral reticulonodular opacities (30/75, 40%), ground-glass opacity (19/75, 25%), consolidation (19/75, 25%), septal lines (27/75, 36%) and hilar lymph node enlargement (19/75, 25%). Thin-section CT (n = 19) showed ground-glass opacity (17/19, 89%) predominantly in the lower zones. Bronchial wall thickening (11/19, 58%), centrilobular nodules (9/19, 47%) and interlobular septal thickening (9/19, 47%) were less frequent findings. CONCLUSIONS: Scrub typhus is an acute febrile illness characterized by eschar, which usually has a limited course without serious complication. Diffuse bilateral reticulonodular opacities with lower lung predominance was the most frequent radiographic finding. Chest radiography and thin-section CT show pulmonary interstitial disease which may have a component of pulmonary oedema secondary to cardiac dysfunction.

Adolescent↗

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.

Adult↗

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.

Acute Disease↗