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PubMed1990

Scrub typhus in suburban Bangkok: first cases.

Three patients, two of whom had eschars, were admitted with fulminant febrile disease suggestive of scrub typhus. Elevated IgG and IgM to Rickettsia tsutsugamushi were detected in all three by IFA. The cases lived in widely separated areas of western Bangkok where fruit trees are grown and claimed not to have left the areas of their homes during the estimated incubation periods. A field survey collected rodents, treeshrews, and mites fro around the homes of each case. R. tsutsugamushi was isolated from one rat and known vector species of mites were found. These are the first confirmed cases of scrub typhus transmission in Metropolitan Bangkok. It is suggested that typhus incidence around Bangkok may be substantial but has been unreported because of widespread self-medication with antibiotics and the difficulties of laboratory diagnosis.

Adult↗
PubMed1976

Scrub typhus: a common cause of illness in indigenous populations.

An explanation was sought for the disparity between the low reported incidence of scrub typhus and the high prevalence of antibody to Rickettsia tsutsugamushi in the rural population of Malaysia. A combination of isolation of the organism, titration of antibody by indirect immunofluorescence, and the Weil-Felix test was used to confirm infections. Scrub typhus was found to be very common, causing 23% of all febrile illnesses at one hospital. The infection was particularly prevalent in oil-palm workers, causing an estimated 400 cases annually in a population of 10,000 people living on one plantation. The clinical syndrome, whether mild or severe, was difficult to distinguish from that due to other infections. Eschars, rashes and adenopathy were uncommon. When used to examine early sera, the Weil-Felix test failed to confirm the diagnosis in most infections.20

Adolescent↗
PubMed1998

Recovery and viability of Orientia tsutsugamushi from packed red cells and the danger of acquiring scrub typhus from blood transfusion.

BACKGROUND: The purpose of this study was to determine whether infective Orientia tsutsugamushi, the etiologic agent of scrub typhus, could survive normal blood banking processing and storage procedures. STUDY DESIGN AND METHODS: Mononuclear cells isolated from whole blood by density gradient centrifugation were inoculated with O. tsutsugamushi, Karp strain. Infection of the mononuclear cells was confirmed by Giemsa stain, direct fluorescent antibody assay, and polymerase chain reaction using primers specific for the groESL operon of O. tsutsugamushi. The quantity of rickettsial particles in each preparation was determined by direct counts from the Giemsa-stained preparations. Infected mononuclear cells were returned to their respective aliquots of packed red blood cells, which were then either stored at 4 degrees C or glycerolized and frozen at -70 degrees C. RESULTS: Rickettsiae survived up to 10 days (but not 30 days) of refrigerated storage and 45 days of frozen storage, as determined by inoculation of mice with 0.5-mL aliquots of the blood components. Infection of the mice was determined by illness, death, direct fluorescent antibody assay of peritoneal smears, polymerase chain reaction of blood, and enzyme-linked immunosorbent assay detection of antibodies in plasma. CONCLUSION: Because the quantity of rickettsiae injected into the mice was comparable to the quantity reported in the literature for human blood during natural infections, scrub typhus could present a risk in blood collected from donors in endemic areas. This may especially be true, because people can be rickettsemic before illness, after successful antibiotic treatment, and chronically after resolution of disease.

Animals↗
PubMed1978

Single dose doxycycline therapy for scrub typhus.

A single dose of 200 mg of doxycycline was shown to be as effective as a seven day course of tetracycline, in patients suspected of having scrub typhus. 65 (44%) of the 149 patients studied fulfilled the criteria for definite diagnosis of scrub typhus; 10 had an additional diagnosis. Rickettsia tsutsugamushi was isolated from 49 (75%) patients. There was no difference between the two treatment groups in time to defervescence, abolition of cough and headache, or in the time taken to recover well-being. There were no relapses in either group. Of the remaining 84 patients, a causal diagnosis was achieved in 52. Irrespective of a diagnosis there was no difference in apparent response to either doxycycline or tetracycline.

Adolescent↗
PubMed1979

Forecasting the onset of a scrub typhus epidemic in the Pescadores Islands of Taiwan using daily maximum temperatures.

Daily maximum atmospheric temperatures were used to forecast the seasonal onset of scrub typhus in the Pescadores Islands of Taiwan. The day of the year on which the temperature first reached 30 degrees C was selected as the predictive base. Predictions for 1977 closely matched observed events. The model provides an easy and effective means to forecast the start of scrub typhus epidemics in the Pescadores Islands and could be used for such practical purposes as determining when prophylactic antibiotics should be administered to subjects whose risk of infection with Rickettsia tsutsugamushi is high.

Disease Outbreaks↗
PubMed2006

Scrub typhus among hospitalised patients with febrile illness in South India: magnitude and clinical predictors.

OBJECTIVES: To derive a clinical algorithm for diagnosis of scrub typhus among patients hospitalized with febrile illness and to determine predictors of bad prognosis. METHODS: Patients hospitalized with febrile illness of 5-30 days duration were evaluated for common aetiologies. Sera were tested for antibodies (IgM and IgG) to Orientia tsutsugamushi using ELISA kit. RESULTS: Among 207 patients, 50 had elevated levels of IgM antibodies. The data of these patients were compared with that of 16 controls having febrile illnesses in whom rickettsial infection was ruled out. Transaminase elevation (>twice normal) was present in 90% and was significantly (P=0.004) more common in those with scrub typhus. If a combination of elevated transaminases, thrombocytopenia and leukocytosis is used, the specificity and positive predictive value are about 80%. Case fatality rate was 14%. Univariate analysis showed that hyperbilirubinemia (>1.5mg%) has a RR of 9 (95% CI=1.48-58.5) and elevated creatinine level (>1.4 mg%) had a RR of 43.99 (95% CI=3.65-530.5) for death. Elevated creatinine level was found to be an independent predictor of mortality (P=0.02). CONCLUSION: In developing countries with limited diagnostic facilities, it is prudent to recommend empiric therapy in patients with undifferentiated febrile illness having evidence of multiple system involvement especially if there is transaminase elevation. Elevated creatinine may predict bad outcome.

Adolescent↗
PubMed2003

Scrub typhus and tropical rickettsioses.

PURPOSE OF REVIEW: Recent developments in molecular taxonomic methods have led to a reclassification of rickettsial diseases. The agent responsible for scrub typhus (Orientia tsutsugamushi ) has been removed from the genus Rickettsia and a bewildering array of new rickettsial pathogens have been described. An update of recent research findings is therefore particularly timely for the nonspecialist physician. RECENT FINDINGS: An estimated one billion people are at risk for scrub typhus and an estimated one million cases occur annually. The disease appears to be re-emerging in Japan, with seasonal transmission. O. tsutsugamushi has evolved a variety of mechanisms to remain viable in its intracellular habitat. Slowing the release of intracellular calcium inhibits apoptosis of macrophages. Subsets of chemokine genes are induced in infected cells, some in response to transcription factor activator protein 1. Cardiac involvement is uncommon and clinical complications are predominantly pulmonary. Serious pneumonitis occurred in 22% of Chinese patients. Dual infections with leptospirosis have been reported. Standardized diagnostic tests are being developed and attempts to improve treatment of women and children are being made. 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. SUMMARY: Rash and fever in a returning traveler could be rickettsial and presumptive doxycycline treatment can be curative. Recent research findings raise more questions than answers and should stimulate much needed research.

Animals↗
PubMed1980

Gamma-irradiated scrub typhus immunogens: analysis for residual, replicating rickettsiae.

Scrub typhus immunogens that received inadequate gamma radiation contained residual, viable rickettsiae. The presence of these organisms in the host was masked by the rapid immune response elicited by the large number of inactivated rickettsiae. Transfer of homogenized spleen cells from immunized mice to normal syngeneic recipients provided a sensitive technique for the detection of these viable, replicating organisms.

Animals↗
PubMed2006

Relevance of Weil-Felix test in diagnosis of scrub typhus in India.

OBJECTIVE: To study the relationship of Weil-Felix test and microimmunofluorescence test. METHODS: Sera of 21 patients with clinical diagnosis of scrub typhus were subjected to Weil-Felix and Microimmunofluorescence tests. RESULTS: On Weil-Felix test, 13 (62%) sera showed titers 1: > or = 40-320. 7 patients showed titers 1: > or = 320, 3 showed titers 1 : 160, 2 showed titers 1 : 80 and 1 patients showed titers 1 : 40, to Proteus OXK antigen. All 21 sera showed significant titers to O. tsutsugamushi on microimmunofluorescence. CONCLUSION: Weil-Felix test is not a very sensitive test in diagnosis of scrub typhus but due to of lack of availability of definitive tests in India it canbe a useful tool when used and interpreted in the correct clinical context.

Adolescent↗
PubMed1970

Plaque assay for Q fever and scrub typhus rickettsiae.

The plaque assay procedure developed for spotted fever and typhus group rickettsiae is also appropriate for scrub typhus and Q fever rickettsiae. The plaque titers of suspensions of Rickettsia tsutsugamushi and Coxiella burnetii compared favorably with end points obtained by titrations in mice.

Animals↗
PubMed1995

Effectiveness of a dot-blot immunoassay of anti-Rickettsia tsutsugamushi antibodies for serologic analysis of scrub typhus.

We compared a commercially available dot-blot immunoassay system with the indirect immunofluorescence assay (IFA) in tests of known negative and known positive sera from scrub typhus cases. Using a panel of 100 sera from patients with various rickettsial and nonrickettsial infections, we observed that the IFA was 99% specific and the dipstick assay was 98% specific. In tests of 91 sera (30 negative and 61 positive for scrub typhus antibodies) from a study of febrile patients in Malaysia, using the standard of an IFA titer < 1:64 as negative, an IFA titer > 1:128 as positive, and an IFA titer = 1:64 as either positive or negative (supported by clinical records), dipsticks were 83% specific and 90% sensitive. The quantitative correlation of the dipsticks to IFA titers was confirmed by significant differences in geometric means of inverse IFA titers corresponding to the number of positive dipstick spots (no dots = 8.5, one dot = 43.3, two dots = 206.7, and three dots = 676.9). The assay would enable physicians and public health workers who deal with patients to quickly diagnose and appropriately treat most cases of the disease, especially in areas of high prevalence where the proportion of false-positive results to true-positive results would be low.

Antibodies, Bacterial↗
PubMed2003

Scrub typhus in the Torres Strait islands of north Queensland, Australia.

Scrub typhus, caused by Orientia tsutsugamushi, occurs throughout Southeast Asia. We descript ten cases that occurred in the Torres Strait islands of northern Australia during 2000 and 2001. Preceding heavy rain may have contributed to the outbreak. The successful use of azithromycin in two pediatric patients is also reported.

Adolescent↗
PubMed1977

Plaque assay and cloning of scrub typhus rickettsiae in irradiated L-929 cells.

It was demonstrated that gamma-irradiated L-929 cells support plaque formation by three strains of Rickettsia tsutsugamushi and representative species of the spotted fever and typhus group rickettsiae. Sensitivity of the plaque assay for detection of viable scrub typhus rickettsiae was similar to that achieved with intraperitoneal inoculation of random-bred mice. The concentration of irradiated cells and the temperature and length of incubation were all found to affect plaque size. A technique combining terminal dilution and plaque purification was used to obtain clones of three strains of scrub typhus rickettsiae.

Gamma Rays↗
PubMed1968

Ecological considerations in scrub typhus. 2. Vector species.

Certain features, characteristic of outbreaks of scrub typhus, can be explained by the behaviour of the chigger vectors which are remarkably hardy and can survive weeks of freezing or immersion in water. The established vectors are all species of the genus Leptotrombidium (Leptotrombidium), i.e., L. (L.) akamushi (Brumpt, 1910), L. (L.) deliense (Walch, 1922), L. (L.) pallidum (Nagayo et al., 1919), and L. (L.) scutellare (Nagayo et al., 1921). These chiggers (i.e. larval mites) infest a broad variety of birds and mammals, and tend to be found in clusters on certain specific sites on the host. However, the precise site for any species of mite varies with the host, and it is believed that the grooming habits of the infested animal account for this "site preference". The degree of infestation cannot validly be ascribed to the size of the host. L. (L.) pavlovskyi (Schluger, 1948), L. (L.) orientale (Schluger, 1948), L. (L.) arenicola Traub, 1960, and L. (L.) tosa (Sasa & Kowashima, 1951) are regarded as probable vectors. Other species, some belonging to other genera, are under suspicion in this regard.L. (L.) subintermedium (Jameson & Toshioka, 1954) and certain other chiggers were found in "ecological islands" in all montane habitats studied in West Pakistan, despite the intervening high mountains, broad rivers and belts of semi-desert. The infection-rate of Rickettsia tsutsugamushi in vector species in nature is believed to be low, and chiggers may be serving as reservoirs of infection and not just as vectors.

Animals↗
PubMed2004

Evaluation of nested PCR for the diagnosis of scrub typhus among patients with acute pyrexia of unknown origin.

A nested PCR technique was performed to detect a specific 483 bp DNA fragment of Orientia tsutsugamushi, the aetiological agent of scrub typhus, in 53 blood samples from 36 patients with acute pyrexia of unknown origin in southern Thailand. The specific primers could amplify the specific DNA from all 10 prototype strains of O. tsutsugamushi and all nine seropositive patients and three seronegative patients, while no DNA amplification was obtained with DNAs from other rickettsiae or from healthy persons or from patients with murine typhus. The specific PCR product was detectable in the blood for as long as 22 days after the onset of disease in patients without specific treatment and 27 days after receiving a single dose of doxycycline. Thus, nested PCR may be more sensitive than the serological test for diagnosis of scrub typhus and prolonged persistence of O. tsutsugamushi DNA in patients' blood was demonstrated despite clinical recovery of the patients.

Adult↗
PubMed2001

Investigation of the role of Blankaartia acuscutellaris (Acari: Trombiculidae) as a vector of scrub typhus in central Thailand.

Monthly collections of rodents were conducted in Phitsanulok Province, central Thailand in 1993 to investigate the role of the mite Blankaartia acuscurellaris as a vector of scrub typhus. Overall, a total of 41 rodents were collected and examined for the presence of the red colored larvae of B. acuscutellaris and yellow larvae of Leptotrombidium deliense and Ascoshoengastia sp. A total of 787 B. acuscutellaris and 1390 yellow larvae were placed into pools, triturated and isolation of Orientia tsutsugamushi attempted in laboratory mice. The sera of 8 of the collected rodents had elevated antibodies to O. tsutsugamushi indicating active infections; however, O. tsutsugamushi was not isolated from rodent tissues or pools of larvae. The results of this survey suggest that B. acuscutellaris may not be an important vector of scrub typhus, but more studies are needed in endemic areas.

Animals↗
PubMed2003

In vitro reactivation of human immunodeficiency virus-1 upon stimulation with scrub typhus rickettsial infection.

While a number of microbial infections induce a transient burst in viral load in individuals infected with human immunodeficiency virus-1 (HIV-1), a recent study has suggested that scrub typhus may suppress HIV-1 infection. We investigated the effects of Orientia tsutsugamushi on HIV-1 infection. In vitro HIV-1 infection experiments were conducted using peripheral blood mononuclear cells (PBMC) acutely infected with R5 and X4 HIV-1 or PBMC derived from patients receiving highly active antiretroviral therapy (HAART) whose plasma viral load was undetectable. Stimulation of PBMC with O. tsutsugamushi induced production of proinflammatory cytokines and beta-chemokines, and markedly down-regulated expression of CCR5. Although pretreatment with O. tsutsugamushi rendered PBMC resistant to R5 HIV-1, it otherwise enhanced HIV-1 replication. Stimulation by O. tsutsugamushi induced HIV-1 replication in PBMC from patients receiving HAART. These findings suggest that scrub typhus does not necessarily suppress HIV-1 infection and does have potential to enhance HIV-1 replication.

Cytokines↗
PubMed2005

Protection against scrub typhus by a plasmid vaccine encoding the 56-KD outer membrane protein antigen gene.

The 56-kD outer membrane protein of Orientia tsutsugamushi has previously been shown to be the immunodominant antigen in scrub typhus infections. Its gene was cloned into the DNA vaccine vector pVR1012 as a vaccine candidate (pKarp56). The in vitro expression of this 56-kD antigen by pKarp56 was confirmed in tissue culture by an indirect fluorescence assay and Western blot analysis. The initial antibody responses of mice immunized with varied doses of the pKarp56 were barely detected, but increases were observed after each of three subsequent booster immunizations. Although no protection was observed with a single immunization of pKarp56, after four immunizations, 60% of the mice survived a 1,000 x 50% lethal dose (LD(50)) challenge. These results specifically confirm the importance of the 56-kD protein antigen in protective immunity against O. tsutsugamushi and demonstrate the feasibility of DNA vaccines for the prevention of scrub typhus.

Animals↗