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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↗

Epidemiologic, clinical and laboratory features of scrub typhus in thirty Thai children.

BACKGROUND: Scrub typhus, a potentially fatal rickettsial infection, is common in Asia. Although serologic surveys suggested that as many as one-fourth of cases of scrub typhus might be in children, very few reports of childhood scrub typhus are available in the medical literature. OBJECTIVES: To document the clinical, laboratory and epidemiologic characteristics of pediatric patients with scrub typhus. METHODS: From January 1, 2000 to December 31, 2001, all pediatric patients at Chiang Mai University Hospital who had obscure fever for >5 days were tested for indirect immunofluorescent antibody (IFA) against Orientia tsutsugamushi, the causative organism of scrub typhus. Scrub typhus was diagnosed on the basis of either a single IFA titer against O. tsutsugamushi > or =1/400 or a 4-fold or greater rise in IFA titer to at least 1/200. RESULTS: Thirty children with scrub typhus were enrolled. Most were diagnosed during the rainy months of June to November. Common physical signs included lymphadenopathy (93%), hepatomegaly (73%), eschar (68%), conjunctival hyperemia (33%), maculopapular rash (30%) and splenomegaly (23%). Eleven patients had interstitial pneumonitis and 1 patient had meningitis. All patients responded well to doxycycline or chloramphenicol. The average interval to defervescence after treatment was 29 h (range, 6 to 72). CONCLUSIONS: Clinical and epidemiologic features of 30 pediatric patients with scrub typhus are reported in a prospective study. The presence of eschar was helpful in making the diagnosis. Complications included pneumonitis and meningitis. All cases responded well to treatment with antibiotic.

Adolescent↗

The clinical significance of upper gastrointestinal endoscopy in gastrointestinal vasculitis related to scrub typhus.

BACKGROUND AND STUDY AIMS: Scrub typhus is an acute febrile illness caused by Rickettsia tsutsugamushi-induced vasculitis, which is common in Asia and the Pacific islands and is sometimes encountered in Western countries because of increased travel and economic changes spurred by world globalization. Skin rash and eschar are typical physical findings on the trunk and extremities, but endoscopic mucosal changes have not been described in the gastrointestinal tract until now. We aimed to describe different endoscopic characteristics of the gastrointestinal manifestation of scrub typhus, to ascertain the necessity for endoscopy, and to determine correlations between the degrees of endoscopic lesion and clinical severity, including cutaneous manifestation. PATIENTS AND METHODS: Between January 1993 and October 1998, out of 256 scrub typhus patients, we applied esophagogastroduodenoscopy to 58 patients who complained of gastrointestinal symptoms but had no past history of these symptoms. We categorized clinical severity into four grades according to the degree of six clinical indicators of systemic complications, and endoscopic findings were graded from I to IV (I, normal, nonspecific hyperemia; II, distinct hyperemia, petechiae, purpura; II, superficial hemorrhage, erosion; IV, ulcer, active bleeding). RESULTS: Endoscopic findings of scrub typhus were characterized by petechiae, superficial hemorrhage, erosion, ulcers, and vascular bleeding (grade I, 14 patients; grade II, 11 patients; grade III, 16 patients; grade IV, 17 patients). In 83.3% of patients there was multiple occurrence of lesions without any predilection sites. Clinical severity was graded (grade I, 7 patients; grade II, 23 patients; grade III, 22 patients; grade IV, 6 patients). There was a correlation between clinical severity and endoscopic findings (P < 0.01). The grade of lesion was high in patients with cutaneous lesions (r(s) 0.359, P < 0.01). In two cases of gastric vascular bleeding, complete hemostasis was achieved by endoscopic hemoclipping. CONCLUSIONS: The major endoscopic features that can develop in scrub typhus are superficial mucosal hemorrhage, multiple erosions and ulcers without any predilection sites, and unusual vascular bleeding. The endoscopic features are related to cutaneous lesions and severity of the disease. Endoscopy is useful for diagnosis and management of gastrointestinal vasculitis related to scrub typhus.

Endoscopy, Gastrointestinal↗

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.

Adult↗

Scrub typhus in north Queensland.

Scrub typhus was once common in north Queensland, but no reports from this region have been published for nearly 30 years, and the focus has turned to cases from the Northern Territory and Western Australia. In 1996, diagnosis of scrub typhus in a Queensland soldier led to recognition of an earlier outbreak with up to 17 cases. Another outbreak occurred a year later with 11 confirmed cases. All cases were in soldiers who had visited a training area near Innisfail. Review of other laboratory diagnoses of scrub typhus shows it is still prevalent in north Queensland, with several "hot spots".

Adult↗

Ecological considerations in scrub typhus. 1. Emerging concepts.

Scrub typhus infection is now known to occur in geographical and ecological areas where its presence was hitherto unsuspected-north and west of the Indus River and in south-eastern Siberia; in semi-desert, montane desert, and alpine terrain high in the Himalayas, as well as in primary jungle. Additional data are presented to support the hypothesis that "ecological islands", containing basically similar faunas of rodents and ectoparasites, exist on scattered mountains in the Pakistan Himalayas, despite the intervening "barriers" of desert, broad rivers and massive peaks. Since scrub typhus has been demonstrated in some of these isolated areas, it is felt that the infection may exist, unrecognized, in neighbouring countries as well.A number of larval trombiculid mites, largely species of the subgenus Leptotrombidium, are believed to be vectors, in addition to the well-known L. (L.) deliense and L. (L.) akamushi. The host-range of natural infection in ground-dwelling small mammals, especially rodents, is very broad in endemic areas. An important factor of time, and not only of space, may be involved in an endemic locus, the disease undergoing a sequential evolution involving different chiggers and rodents over a period of years. It is pointed out that new irrigation schemes, road construction, and agricultural projects may introduce scrub typhus into an area or greatly increase its endemicity if the infection is already present.

Animals↗

Multi-laboratory evaluation of a scrub typhus diagnostic kit.

Scrub typhus is a major cause of febrile illness throughout the Asia-Pacific region. It is commonly undiagnosed, partly because of the lack of a simple, reliable diagnostic test which can be used in clinical laboratories. The indirect immunoperoxidase technique, configured into a test kit, was provided to technicians who were trained in its use. They used the kit during a 2 year field trial in their respective clinical hospital laboratories throughout Malaysia. In an evaluation using 1,722 consecutive sera tested in those laboratories, the kit was found to have a median sensitivity for IgG detection of 0.85 (range 0.33-0.95), a median specificity of 0.94 (range 0.88-1.00), reproducibility of 0.86, and efficiency of 0.92 when compared to the reference laboratory. In a proficiency survey in which 10 laboratories received 3 coded test samples, all but 2 laboratories had results within 1 dilution of the reference laboratory in quantitating specific IgG, whereas 7 laboratories were within 1 dilution in quantitating IgM. The shelf life of the kit was at least 1 year at 4 degrees C.

Antibodies, Bacterial↗

Activation of cytotoxic lymphocytes in patients with scrub typhus.

Thai patients with scrub typhus caused by the intracellular pathogen Orientia tsutsugamushi displayed elevated plasma concentrations of granzymes A and B, interferon-gamma (IFN)-gamma-inducible protein 10, and monokine induced by IFN-gamma. These data suggest that activation of cytotoxic lymphocytes is part of the early host response to scrub typhus.

Adolescent↗

Case reports: scrub typhus during pregnancy in India.

Scrub typhus, caused by Orientia tsutsugamushi, is a rural zoonosis endemic in the Asian Pacific region. Doxycycline and chloramphenicol, the recommended drugs for treating this infection, may not be safe during pregnancy. We report on 5 patients with scrub typhus during pregnancy who were seen in India between October 2001 and February 2002. Four of the 5 women were treated initially with ciprofloxacin. Three women had stillbirths, 1 an abortion and 1 a low birthweight baby, which suggests that ciprofloxacin should not be used for treating pregnant women and that scrub typhus leads to severe adverse effects during pregnancy. Randomized controlled trials are urgently needed to ascertain the optimal drug choice, given that currently recommended drugs are contraindicated in pregnant women.

Abortion, Spontaneous↗

Comparison of immune response against Orientia tsutsugamushi, a causative agent of scrub typhus, in 4-week-old and 10-week-old scrub typhus-infected laboratory mice using enzyme-linked immunosorbent assay technique.

Using the indirect enzyme-linked immunosorbent assay (ELISA) technique, we compared the immune response of specific antibodies (IgM and IgG) in serum samples of scrub typhus-infected and non-infected mice against Orientia sutsugamushi (a causative agent of scrub typhus). Two different age groups (4-week-old and 10-week-old) of ICR laboratory mice were infected with O. tsutsugamushi by the animal passage procedure. Serum samples were detected for scrub typhus-specific antibodies using ELISA technique. Results from determining the presence of IgM and IgG in the serum samples obtained from scrub typhus-infected mice showed that the IgG was first detected on day-13 after the initial infection in both the 4-week-old and 10-week-old mice. The IgG titer levels of both groups were not significantly different. Although the presence of IgM in the in serum samples obtained from scrub typhus-infected mice was first detected on day 13 in the 4-week-old mice and on day-12 in the 10-week-old mice, the IgM titer in the 4-week-old mice was slightly lower than in the 10-week-old mice. Clinical observations of the scrub typhus-infected mice showed that the older mice become ill on day 9 whereas the younger mice exhibited the symptoms on day 12. Considering the earlier detection and slightly higher level of specific IgM antibody, it could be interpreted that the older mice may appear to have responded against O. tsutsugamushi faster than the younger mice.

Aging↗

[Epidemiology of scrub typhus in Matsu Peikang Island].

A retrospective survey of the epidemiology of scrub typhus in 1990 in Matsu Peikang Island was made at the end of December of 1990. The diagnosis of scrub typhus was based on the presence of escar, typical clinical manifestation and good response to tetracycline treatment. There were 89 cases of scrub typhus studied, and except for one civilian, the other 88 cases were military personnel, occurring in 2.2% of the total military personnel on the island. However it occurred in 0.08% of the civilian population. Seasonal distribution of scrub typhus was limited to between June and October of 1990. The peak incidence occurred in July. Scrub typhus was distributed over the whole island. A higher incidence of scrub typhus occurred in soldiers and sergeants than in officers. A significant different incidence was found in different units. No fatalities were reported. Different units. No fatalities were reported. Different military activities, duties and the location of the military unit may affect the incidence of scrub typhus. The scrub typhus epidemic was also related to temperature.

China↗

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↗

Scrub typhus in the Western Pacific region.

Scrub typhus is widely endemic in Asia. Man's behaviour and climatic changes greatly influenced the occurrence of the disease. Increasing prevalences of scrub typhus have been reported from some Asian countries and may coincide with the widespread use of beta-lactam antibiotics or to improve diagnostic facilities and/or more urbanisation into rural areas. Many cases acquired in Asia surfaced in Europe and America. The disease probably is overlooked among paediatric patients. Most patients with scrub typhus present with acute fever of unknown origin (acute FUO). Eschars are rare among Southeast Asian patients. Complications usually develop after the first week of illness. The complications include pneumonitis, meningoencephalitis, renal failure and jaundice. Improved serologic and molecular diagnostic tests are now available. Although drug-resistant strain of Orientia tsutsugamushi has been reported, the infection usually responds to simple but unpopular drugs such as doxycycline or chloramphenicol.

Asia, Southeastern↗

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↗

Scrub typhus during pregnancy and its treatment: a case series and review of the literature.

Although scrub typhus is uncommon in pregnant women, when present, it can have serious repercussions for the mother and developing fetus. Since it is uncommon, the clinical impact of scrub typhus on pregnancy has not been elucidated and an effective and safe therapeutic regimen has not been validated. The medical records of pregnant women whose scrub typhus were treated at Chungnam National University Hospital were reviewed and their clinical outcomes were evaluated. A review of the literature was also performed on pregnant women with scrub typhus and their clinical outcomes. Eight pregnant women with scrub typhus were treated successfully with a single 500-mg dose of azithromycin, and no relapses were reported. They all delivered healthy babies at term, without congenital or neonatal complications. In the reviews, azithromycin was effective against scrub typhus and had favorable pregnancy outcomes. Ciprofloxacin and cefuroxime failed to treat scrub typhus and fetal loss resulted. A single 500-mg dose of azithromycin may be a reasonable treatment regimen for pregnant women with scrub typhus. Ciprofloxacin might not be advisable for the treatment of scrub typhus during pregnancy. Scrub typhus itself seems to have serious adverse effects on pregnancy if not appropriately controlled.

Adult↗

Sensitive microplate enzyme-linked immunosorbent assay for detection of antibodies against the scrub typhus rickettsia, Rickettsia tsutsugamushi.

A microtiter enzyme-linked immunosorbent assay (ELISA) has been developed for the titration of antibodies against scrub typhus in human and animal sera. Scrub typhus rickettsiae were grown in monolayers of irradiated mouse LM3 cells and separated from host cell materials by differential centrifugation, filtration through a glass filter (AP-20, Millipore Corp.), and isopycnic banding in Renografin density gradients. The scrub typhus ELISA antigens were obtained from the purified viable rickettsiae by French pressure cell disruption and addition of 0.2% Formalin to the soluble extract. Antisera prepared in rabbits against the prototype Karp, the Kato, and the Gilliam strains of scrub typhus were used to standardize the ELISA and to compare its sensitivity and specificity to that of the indirect fluorescent antibody test (IFA). ELISA titers were measured as the greatest serum dilution showing an optical density 0.25 above controls or by the optical density achieved at a fixed serum dilution. The IFA and ELISA end point titers were quite similar, and all three measures of titer had comparable specificity for the strains of scrub typhus. No cross-reactions between the typhus and scrub typhus wera were observed by ELISA. Both the immunoglobulin M (IgM) and IgG antibody titers of 12 sequential sera from four patients with scrub typhus were obtained by IFA and ELISA. The IFA and ELISA end point titers for IgM and IgG had correlation coefficients of 0.91 and 0.97, respectively, whereas the ELISA optical density values at a serum dilution of 1:100 had slightly lower correlations with IFA titers (0.80 and 0.94). Early rising IgM titers followed by rising IgG titers were demonstrated by ELISA in three patients with primary scrub typhus infections, whereas the IgG response predominated in a patient with a reinfection. It is concluded that the ELISA for scrub typhus is a very satisfactory alternative to the IFA test.

Animals↗

Outbreak investigation of scrub Typhus in Himachal Pradesh (India).

Scrub Typhus outbreak investigation was undertaken during September 2003 in the three worst affected districts Shimla, Solan and Sirmaur in Himachal Pradesh (India). A total of 113 cases and 19 deaths (17.27 percent case fatality rate) were reported from the eight districts, which were reporting cases. Cases were prevalent in all age groups and in both the sexes among the persons frequenting forest for occupational work. 35.7 percent of the patients serum samples showed a titer of > 1: 80 against OX 19 and OXK antigen is suggestive of Scrub Typhus. Entomologically Rattus rattus (39.5 per cent) was the most prevalent species followed by Suncus murinus (22.91 percent), Bandicoota bengalensis (29.16 percent) and Bandicoota indica and Mus musculus (4.16 percent each). Vector species Leptotrombidium deliense and Gahrliepia (schoengastilla) sp. were recorded. The chigger index 23.0 was found to be highest in Vill. Baldian and 5.0 in Vill. Bhatakuffer (Shimla) and 1.0 in Vill. Rebon (Solan), which is above the critical limit of 0.69 per rodents. Other mite species, ixodid ticks, fleas and lice have been recorded.

Adolescent↗

Doxycycline propylaxis for human scrub typhus.

The use of doxycycline, as a prophylactic antibiotic against scrub typhus was investigated in a prospective, randomized, double-blind study. Twenty volunteers were divided into two similar groups. Beginning three days before exposure to Leptotrombidium fletcheri chiggers infected with Rickettsia tsutsugamushi, and continuing for six weeks after exposure, one group received weekly 200-mg oral doses of doxycycline and the other group received a placebo. Nine of 10 doxycycline-treated subjects remained well during prophylaxis but developed antibody to scrub typhus, whereas nine of 10 subjects given the placebo required treatment for scrub typhus. Therefore, the efficacy of the regimen in preventing scrub typhus was 89% (eight cases prevented of nine expected). Ten days after successfully completing prophylaxis, eight of nine subjects reported minor self-limiting symptoms. A single dose of doxycycline was given on day 3 of illness to volunteers who developed scrub typhus. Such therapy was initially effective but was frequently followed by relapse and cannot be recommended.

Adult↗