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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↗

Epidemic typhus meningitis in the southwestern United States.

A patient residing in New Mexico had murine typhus diagnosed. A novel molecular assay was performed at the Centers for Disease Control and Prevention, and Rickettsia prowazekii, the agent of epidemic typhus, was found, rather than R. typhi. To our knowledge, this is the first reported case of epidemic typhus confirmed by means of polymerase chain reaction--based testing of cerebrospinal fluid, and it introduces a novel assay for the molecular diagnosis of both epidemic and murine typhus.

DNA, Bacterial↗

A comparative trial of a single dose of azithromycin versus doxycycline for the treatment of mild scrub typhus.

BACKGROUND: Scrub typhus is one of the most important endemic infections in the Asia-Pacific region. Although tetracyclines or chloramphenicol are the recommended drugs of choice for the treatment of scrub typhus, reports of doxycycline-resistant strains have prompted a search for alternative treatments. METHODS: We conducted a prospective, open-label, randomized trial from September 2002 through November 2003 to compare azithromycin with doxycycline for the treatment of mild scrub typhus. The time to defervescence was assessed to compare the efficacy of the 2 treatment regimens. RESULTS: A total of 93 patients were randomly assigned to receive either a single 500-mg dose of azithromycin or a 1-week course of daily oral 200-mg dose of doxycycline. Cure was achieved in 47 (100%) of 47 patients in the azithromycin-treated group and in 43 (93.5%) of 46 patients in the doxycycline-treated group (P=.117). The median time to defervescence was 21 h for the azithromycin-treated group and 29 h for the doxycycline-treated group (P=.097). There were no serious adverse events during the study. No relapses occurred in either group during a 1-month follow-up period. CONCLUSION: The single 500-mg dose of azithromycin was as effective as the 1-week course of daily 200-mg doses of doxycycline for the treatment of mild scrub typhus acquired in South Korea.

Aged↗

Acute hearing loss due to scrub typhus: a forgotten complication of a reemerging disease.

We describe 6 patients with scrub typhus who presented with acute hearing loss, a forgotten complication of this reemerging disease. They were admitted with fever of 10-14 days' duration and had clinical evidence of deafness and pneumonitis. Five patients had eschars, which prompted the diagnosis of typhus fever and led to early institution of treatment. Deafness has been described as a clue to the diagnosis of scrub typhus; awareness of this symptom facilitated early diagnosis in 4 of 5 patients who recovered. Acute hearing loss or hearing impairment in a febrile patient should arouse strong suspicion of scrub typhus.

Acute Disease↗

Infection with human immunodeficiency virus does not influence the clinical severity of scrub typhus.

Infection by Orientia (formerly Rickettsia) tsutsugamushi causes scrub typhus, a severe febrile disease common in Asia. Both scrub typhus and AIDS are prevalent in northern Thailand. Therefore, we prospectively investigated the impact of infection due to human immunodeficiency virus (HIV) on the severity of the clinical syndrome produced by O. tsutsugamushi. The severity of scrub typhus was objectively graded on admission of patients to the hospital, and serologies for antibodies to HIV were performed. Fourteen (16%) of 86 patients with scrub typhus were infected with HIV; the median T helper cell count was 70/mm3. There were no significant differences between HIV-infected patients and non-HIV-infected patients in severity scores or other admission characteristics. O. tsutsugamushi was isolated in blood samples from 48.6% of patients without HIV infection and in blood samples from 14.3% of HIV-infected patients (P < .05 x 2 test). The clinical manifestations of O. tsutsugamushi infection, unlike those due to some other intracellular pathogens, are not unusually severe in immunocompromised patients with AIDS.

AIDS-Related Opportunistic Infections↗

Central nervous system involvement in patients with scrub typhus.

Scrub typhus, which is caused by Orientia tsutsugamushi, is a systemic illness that causes generalized vasculitis. The central nervous system (CNS) is the most crucial target in other rickettsial diseases; however, there have been several reports of encephalitis or meningitis without direct evidence of rickettsial invasion of the CNS in cases of scrub typhus. To investigate CNS involvement in cases of scrub typhus, we analyzed the CSF profiles (cell count and levels of protein and glucose) and amplified rickettsial DNA in CSF specimens by means of nested polymerase chain reaction (PCR) for 25 patients with the infection. Mild pleocytosis was present in 48% of the patients: CSF white blood cell counts ranged from 0 to 110/mm3 (mean [+/- SD] count, 16.3 +/- 27.0/mm3), and the mean (+/- SD) lymphocyte proportion was 51.9% +/- 23.9%. The CSF protein level was increased (>50 mg/dL) in seven patients. Nested PCR amplified six products from the 25 CSF specimens: four of the products were Boryong genotypes, and two were Karp genotypes. The results of this study suggest that O. tsutsugamushi does invade the CSF and that scrub typhus should be considered one of the causes of mononuclear meningitis in areas of endemicity.

Central Nervous System Diseases↗

Roxithromycin treatment of scrub typhus (tsutsugamushi disease) in children.

BACKGROUND: Although chloramphenicol and doxycycline have been used for the treatment of scrub typhus, a difficulty exists in determining which drug to use in treating children because of such potential complications as aplastic anemia or tooth discoloration. We evaluated the effect of roxithromycin, a macrolide antibiotic, on scrub typhus in children. METHODS: A retrospective analysis was conducted on 39 children with scrub typhus who were treated with doxycycline (DC), chloramphenicol (CM) or roxithromycin (RM) between 1991 and 2000. We divided the patients into the DC-treated group (DC group; 16 children), CM-treated group (CM group; 14 children) and RM- treated group (RM group; 9 children) and compared these groups. RESULTS: Most cases (97%) occurred in October and November. Fever and rash were observed in all 39 cases, and an eschar was noted in 36 cases (92%). No statistical differences could be found between the 3 groups in mean age, duration of fever before admission, white blood cell (WBC) count and complications including abnormal liver enzymes. In most cases defervescence after treatment was within 24 h (34 cases, 87%) and during 24 to 48 h in 2 cases in the DC group, 1 case in the CM group and 2 cases in the RM group (no statistical difference). CONCLUSION: Roxithromycin was as effective as conventional doxycycline or chloramphenicol in children with scrub typhus and may be safer to use.

Adolescent↗

Granulomatous hepatitis associated with scrub typhus.

A 56 year old patient with scrub typhus infection having unusual presentation of hepatic injury resembling acute hepatitis is described. The clinical features of fever, headache, eschar, lymphadenopathy, lymphocytosis and high Rickettsia tsutsugamushi immunofluorescence titres confirmed the diagnosis of scrub typhus. Acute hepatitis was proven by hepatic biochemical tests and liver biopsy. The patient had a complete recovery soon after antibiotic treatment. The presentation of this case suggests that scrub typhus infection should be included in the list of differential diagnosis of acute hepatitis or granulomatous hepatitis, at least in the Asian Pacific region where scrub typhus still prevails.

Acute Disease↗

[Murine typhus infected in Oku-etsu area, Fukui Prefecture].

A 15-year-old girl, high school student, became febrile (38-39 degrees C) with chills, sore throat and cough on April 20, 1994. Until the onset, she was healthy and she had been camping with her classmates in a wooded mountainous area in Oku-etsu, Fukui Prefecture. She consulted a local clinic on April 21 and bacampicillin was initially administered and then changed to cefaclor on April 23. However, high body temperature continued and a maclopapular rash appeared on her face on April 24 and gradually spread to her anterior chest and back. Blood examination showed a WBC count of 2,200/microliter, and she was admitted to our hospital on April 25. On admission, peripheral blood data showed leukocytopenia (WBC 2,300/microliter) with 5% atypical lymphocytes. Titers of anti-Rickettsia typhi serum antibodies (IgM, -G) were elevated (1:80, 1:640) and she was diagnosed as having murine typhus. On the second hospital day, 200 mg of minocycline (MINO) was administered per os and her body temperature fell to within the normal limits on the third hospital day. On the 7th hospital day, the skin rash disappeared and she was discharged. Altogether, 320 high school students went camping with this patient. Among them, approximately 30 students had similar symptoms and signs as this case and had been diagnosed suspected viral infection. Twelve students of the 30 were admitted to other hospitals. It was considered that this case was part of an outbreak of murine typhus in the Oku-etsu area, Fukui Prefecture, but no further investigation was performed. Murine typhus is usually a benign disease that is controllable by the administration of MINO. In rare cases, infection can worsen to multiorganic failure, severe complications have been reported in 1-4% of cases, and death has been reported in less than 3%. Recently, it has also been reported that MINO not only has an antibiotic effect, but also play acts as a cytokine modulator in patients with rickettsial infection. Thus, in febrile patients in whom uncommon Rickettsia infection is suspected, serological test for murine typhus should be examined and the immediate administration of MINO is important.

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↗

Early diagnosis of scrub typhus with a rapid flow assay using recombinant major outer membrane protein antigen (r56) of Orientia tsutsugamushi.

The variable 56-kDa major outer membrane protein of Orientia tsutsugamushi is the immunodominant antigen in human scrub typhus infections. We developed a rapid immunochromatographic flow assay (RFA) for the detection of immunoglobulin M (IgM) and IgG antibodies to O. tsutsugamushi. The RFA employs a truncated recombinant 56-kDa protein from the Karp strain as the antigen. The performance of the RFA was evaluated with a panel of 321 sera (serial bleedings of 85 individuals suspected of scrub typhus) which were collected in the Pescadore Islands, Taiwan, from 1976 to 1977. Among these 85 individuals, IgM tests were negative for 7 cases by both RFA and indirect fluorescence assay (IFA) using Karp whole-cell antigen. In 29 cases specific responses were detected by the RFA earlier than by IFA, 44 cases had the same detection time, and 5 cases were detected earlier by IFA than by RFA. For IgG responses, 4 individuals were negative with both methods, 37 cases exhibited earlier detection by RFA than IFA, 42 cases were detected at the same time, and 2 cases were detected earlier by IFA than by RFA. The sensitivities of RFA detection of antibody in sera from confirmed cases were 74 and 86% for IgM and IgG, respectively. When IgM and IgG results were combined, the sensitivity was 89%. A panel of 78 individual sera collected from patients with no evidence of scrub typhus was used to evaluate the specificity of the RFA. The specificities of the RFA were 99% for IgM and 97% for IgG. The sensitivities of IFA were 53 and 73% for IgM and IgG, respectively, and were 78% when the results of IgM and IgG were combined. The RFA test was significantly better than the IFA test for the early detection of antibody to scrub typhus in primary infections, while both tests were equally sensitive with reinfected individuals.

Antibody Specificity↗

Scrub typhus, Republic of Palau.

Scrub typhus, caused by Orientia tsutsugamushi, is a severe febrile illness transmitted to humans by trombiculid mites, which normally feed on rodents. The first known outbreak of scrub typhus in Palau occurred in 2001 to 2003 among residents of the remote southwest islands. To determine the extent of scrub typhus distribution in Palau, we tested serum samples from humans and rodents for antibodies to O. tsutsugamushi. Of 212 Palau residents surveyed in 2003, 101 (47.6%) had immunoglobulin G (IgG) antibody titers >1:64, and 56 (26.4%) had concurrent IgG and IgM antibody titers >1:512 and 1:64, respectively. Of 635 banked serum samples collected from Palau residents in 1995, 34 (5.4%) had IgG antibody titers >1:64. Sera collected from rodents (Rattus norvegicus and R. rattus) in 2003 and 2005 were tested, and 18 (28.6%) of 63 had IgG antibody titers >1:64. These findings suggest that scrub typhus is endemic in Palau.

Adult↗

A suburban focus of endemic typhus in Los Angeles County: association with seropositive domestic cats and opossums.

Thirty-three cases of locally acquired murine typhus were reported in Los Angeles County residents from May 1984 through February 1988. Only eight cases were reported over the previous 20-year period. Thirty (91%) cases resided within a suburban area encompassing approximately 50 km2 in northcentral Los Angeles or had contact with an animal from this area. Serologic testing (complement fixation and indirect fluorescent antibody) of selected animals in close association with human cases revealed a high prevalence of seropositivity among domestic cats and opossums. Nine (90%) of 10 resident cats tested had demonstrable antibody titers compared with none (0%) of 20 cats from a control area (P < 0.001). Suburban typhus cases were more likely than neighborhood controls to own a cat or dog (odds ratio = 6.9, 95% confidence interval = 1.8, 25.9, P = 0.002). Sixteen (42%) of 38 opossums trapped in close proximity to the residences of cases were seropositive versus none (0%) of 36 opossums from control areas (P < 0.001) A low frequency (2.8%) of seropositivity was found in commensal rodents, and the classic vector of murine typhus, Xenopsylla cheopis, was not found. Ectoparasite indices form seropositive opossums revealed heavy infestations with the cat flea, Ctenocephalides felis (mean flea count = 104.7), a species that readily bites humans. These data provide evidence that a suburban focus of murine typhus exists in Los Angeles that differs substantially from the classic transmission cycle, and that cats, opossums and C. felis may play an important role in the occurrence of human cases.

Adolescent↗

Orientia tsutsugamushi in peripheral white blood cells of patients with acute scrub typhus.

Scrub typhus, caused by Orientia tsutsugamushi, is an acute illness that occurs in many parts of Asia. Clinical manifestations range from inapparent to organ failure. Organisms disseminate from the skin to target organs, suggesting that they may enter the peripheral circulation. Here, peripheral blood cell smears from patients with acute scrub typhus were obtained before treatment and for 2 days after treatment and reacted with antibodies specific for O. tsutsugamushi. White blood cells from 3 of 7 patients with acute scrub typhus stained positively for O. tsutsugamushi. Cells containing O. tsutsugamushi were mononuclear and were detected on each day of sampling. The presence of O. tsutsugamushi in peripheral white blood cells of patients with acute scrub typhus is a new finding with clinical and pathogenic implications.

Adult↗

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↗

A case of murine typhus in Queensland.

OBJECTIVE: To present a case of murine (endemic) typhus, the first to be reported within the last 30 years in Australia. CLINICAL FEATURES: A 17-year-old pregnant woman presented with a viral-like illness and later developed a spotted rash, fever and headache. INVESTIGATION AND OUTCOME: Sera taken on Day 7 and Day 30 of the illness showed seroconversion to Proteus OX19 (Weil-Felix) and to Rickettsia typhi (by immunofluorescence), indicating recent infection with Rickettsia of the typhus group. Her illness was clinically compatible with murine typhus. She responded well to erythromycin and delivered a normal infant at term. CONCLUSION: Infection with Rickettsia typhi (murine typhus) still occurs in Australia. It can be diagnosed by means of specific serological tests for rickettsial disease, which are superior to the non-specific Weil-Felix test.

Adolescent↗

Serious complications in scrub typhus.

Scrub typhus, a mite-transmitted zoonosis caused by Orientia tsutsugamushi, is a disease endemic to Taiwan. Serious complications in scrub typhus were more common in the past 4 years than reported previously. Between August 1993 and July 1997, 33 cases of scrub typhus were admitted at Tri-Service General Hospital. Symptoms and signs were: fever (100%), chills (39%), cough (24%), headache (21%), diarrhea (18%), dyspnea (18%), eschar (60%), adenopathy (33%), and rash (21%). Nineteen percent (6/32) had obvious leukopenia (WBC < 4000/ mm3), 34% (11/32) had leukocytosis(WBC > 10,000/mm3) and 44% (14/32) had thrombocytopenia (platelet count < 100,000/mm3). Elevation of aspartate aminotransferase (AST) and elevation of alanine aminotransferase (ALT) were 81% (26/32) and 75% (24/32), respectively. Serious complications included pneumonitis 36% (12/33), acute respiratory distress syndrome (ARDS) 15% (5/33), acute renal failure 9% (3/33), myocarditis 3% (1/33) and septic shock 3% (1/33). One patient died of ARDS due to delay in diagnosis. Other patients recovered after appropriate antibiotic and intensive supportive treatments. Emerging virulent strains of O. tsutsugamushi in Taiwan might be biologically plausible. Scrub typhus should be considered in a patient with fever, varying degree of respiratory distress, particularly if there is an eschar or a history of environmental exposure in endemic areas. Prompt diagnosis, timely antimicrobial therapy and intensive supportive care are important for ARDS and other life-threatening complications.

Adolescent↗

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.

Adolescent↗