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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↗

Vectors of scrub typhus and their hosts on a mature oil palm estate.

L. (L.) deliense was the predominant vector of scrub typhus in a mature oil palm estate, but a small number of L. (L.) fletcheri (0.1% from rodents) and L. (L.) vivericola (0.02% from rodents and 8.0% from black plates) was also collected. Although good correlation between L. (L.) deliense collected from rodents and from black plates was not established, either method may serve as a general indicator of population fluctuations over a period of time. For the most part, the vectors of scrub typhus were limited to litter piles, and thus, the possibility of contracting scrub typhus within this type of habitat was minimal.

Animals↗

Epidemic typhus in the United States associated with flying squirrels.

Between July 1977 and January 1980, seven cases of sporadic, nonepidemic "epidemic" typhus (Rickettsia prowazekii) were discovered in Virginia, West Virginia, and North Carolina. The reservoir seemed to be the southern flying squirrel (Glaucomys volans), an animal indigenous to the eastern United States; however, the vector or mode of acquisition was not evident. Diagnosis was established principally through complement fixation, indirect immunofluorescence, and toxin neutralization tests. Patients' ages were 11 to 81 years. Most were white women. Six had abrupt onset of illness. Headaches, fever, myalgias, and exanthems were among the presenting complaints. The disease seemed milder than classic louse-born epidemic typhus, but in some instances, it was life-threatening. All patients responded to tetracycline or chloramphenicol. This entity probably is more common than reported, is difficult to recognize, and is produced by an organism seemingly identical to that producing louse-born epidemic typhus.

Adolescent↗

Murine typhus in Kuwait in 1978.

Murine typhus occurred in 254 individuals in Kuwait between April and August 1978; 81% of patients were aged between 15 and 44 years, and 63% were male. The highest attack rate occurred among people in the lowest socioeconomic class. The outbreak coincided with a period of high rat and flea density. A study of the first 104 cases suggested that infection was acquired in the home, but a case - control study revealed no significant differences between patients and control subjects in terms of exposure to rats or domestic animals, and other factors. This suggests that murine typhus is hyperendemic rather than epidemic in Kuwait. The disease is being controlled through reduction of both flea and rat populations. Murine typhus may be much more common in many areas than is generally realized, and its status should be re-evaluated regularly in all known and potential foci.

Adolescent↗

Unusual presentation of acute abdomen in scrub typhus: a report of two cases.

Two young soldiers presented with acute abdomens, then received surgical procedures under initial impression of acute cholecystitis and acute appendicitis respectively. Operative findings did not confirm the initial diagnosis, and the clinical condition did not improve after operation. Scrub typhus was suggested later by clinical manifestations of fever, chills, headache, lymphadenopathy, skin rash and presence of eschar formation; this diagnosis was finally confirmed by positive serologic results of high Weil-Felix OXK agglutination and/or Rickettsia tsutsugammushi immunoflorescence titers in paired sera. Both patients rapidly became afebrile after administration of tetracycline. This unusual presentation with acute abdomen in scrub typhus is emphasized, with caution that the possibility of scrub typhus should be taken considered, especially in patients coming from hyperendemic areas.

Abdomen, Acute↗

Scrub typhus in Korea: importance of early clinical diagnosis in this newly recognized endemic area.

Scrub typhus became a well recognized infectious disease threat to military operations in the Pacific Theater during World War II. Early diagnosis and treatment with tetracycline or chloramphenicol dramatically reduces the mortality and morbidity of this disease. Korea is a newly recognized scrub typhus endemic country. We report our experience with 189 scrub typhus patients seen at a civilian outpatient clinic in Chinhae, Republic of Korea, from 1985 through 1990, and verify the accuracy of clinical diagnosis by serologic tests.

Adolescent↗

Scrub typhus complicating acute respiratory distress syndrome: a report of two cases.

Scrub typhus is a zoonotic disease, caused by Rickettsia tsutsugamushi, in which humans are accidental hosts. Although it is an acute febrile illness, severe complications of this disease are very rare since the introduction of specific antibiotic therapy. The authors report two cases of scrub typhus complicating acute respiratory distress syndrome. The first case progressed to multiple organ failure, and the patient expired. In the second case, the patient recovered and was discharged. These two cases were proved to be scrub typhus by their travel history or their having lived in endemic area, clinical manifestations, an eschar and indirect immunofluorescent antibody test. For a good prognosis, early diagnosis and early treatment of this disease are important.

Female↗

Diagnosis of scrub typhus in Malaysian aborigines using nested polymerase chain reaction.

A rapid diagnostic system for scrub typhus using nested polymerase chain reaction (PCR) was applied to clinical samples from Malaysian Aborigines. Whole blood from twenty-four patients suspected of scrub typhus infection were tested using nested polymerase chain reaction and sera were evaluated by the indirect immunoperoxidase test. Antibody responses towards Rickettsia tsutsugamushi were observed in seventeen patients with the majority having high titers of IgG antibodies. Seven patients were seronegative. The nested PCR amplified R. tsutsugamushi DNA from six patients, of which two were negative serologically and four had high titers of IgG antibodies. Second samples collected seven days after treatment were negative by PCR testing. Nested PCR is highly sensitive and specific and may be used to provide rapid confirmation of scrub typhus cases in endemic region.

Adolescent↗

[Endemic typhus imported to Norway].

Murine typhus, caused by Rickettsia typhi, is an important zoonosis in all parts of the world. The disease is transmitted from rodents to humans by fleas. In this article we describe the first three cases of serologically proven murine typhus imported into Norway during the 1990s. The patients were Norwegian tourists who had visited respectively Guinea-Bissau, Crete and Thailand. They all became acutely ill with fever, chills and severe headache 1-10 days after return to Norway. None of them had a rash. Two patients were admitted to hospital, and one was treated with ciprofloxacin for suspected typhoid fever. All the patients recovered without sequelae. The diagnosis of murine typhus was based on detection of IgM-anti-bodies against R typhi in serum samples during reconvalescence.

Adult↗

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↗

Flying squirrels and their ectoparasites: disseminators of epidemic typhus.

Information gathered during the past decade indicates that the eastern flying squirrel, Glaucomys volans, is a zoonotic reservoir of Rickettsia prowazekii - causative agent of louse-borne (epidemic) typhus. The sporadic cases o f typhus that have occurred in the USA in association with flying squirrels provide evidence that flying squirrels can transmit R. prowazekii infection to humons. Strains of R. prowazekii, isolated from flying squirrels multiply readily in human body lice, but flying squirrel lice, although readily infected, are very host specific and tend not to bite humans. It may be that the infection is spread to humans in infective ectoporasite faeces aerosolized when the flying squirrels groom themselves. As Joseph McDade emphasizes in this article, current concepts of typhus epidemiology and control must be re-evaluated to take into account this zoonotic aspect.

Journal Article↗

Endothelial prostaglandin secretion: effects of typhus rickettsiae.

Cultured human umbilical vein-derived endothelial cells were incubated with typhus rickettsiae, and supernatants were examined for the presence of prostaglandins I2 (PGI2) and E2 (PGE2). Cells incubated with metabolically active rickettsiae secreted significantly more PGI2 and PGE2 than did those incubated with buffer alone or with killed rickettsiae. The amount of PGI2 secreted was directly related to the number of hemolytically active rickettsiae present; abolishing rickettsial hemolytic activity abolished their effect on PGI2 secretion. Mice injected with a lethal dose of native typhus rickettsiae exhibited a rapid rise in circulating PGI2 levels; mice given hemolytically inactive rickettsiae survived and exhibited no rise in plasma PGI2 levels. Finally, endothelial cells were infected with rickettsiae, and secretion of prostaglandins was monitored during rickettsial multiplication; intracellular accumulation of rickettsiae resulted in endothelial destruction and a dramatic increase in endothelial secretion of PGI2 and PGE2. Therefore, typhus rickettsiae can increase endothelial secretion of arachidonate-derived autocoids.

Cells, Cultured↗

Detection of murine typhus infection in fleas by using the polymerase chain reaction.

Polymerase chain reaction (PCR) amplification of DNA was used to detect the etiologic agent of murine typhus, Rickettsia typhi, in experimentally infected adult fleas. A primer pair derived from the 17-kilodalton antigen sequence of typhus and spotted fever group rickettsiae was used to amplify a 434-base-pair (bp) fragment of the genome of the murine typhus rickettsiae. The amplified 17-kilodalton protein antigen-specific sequence was detected in ethidium bromide-stained agarose gels in individual fleas as early as 2 days after exposure to rickettsemic rats (two of six tested). The 434-bp sequence was not detected in uninfected control fleas. A dot hybridization assay used to detect the 434-bp fragment was also specific and about 100-fold more sensitive than the agarose gel PCR assay. Since the PCR assay employed a boiled extract of triturated fleas, both PCR and an antigen capture enzyme-linked immunosorbent assay (ELISA) could be performed on the same individual flea homogenate. The ELISA identified 12 infected fleas out of 29 randomly selected fleas, compared with 14 specimens which were positive by PCR. The PCR assay detected rickettsiae in samples in which no viable rickettsiae were detected by plaque assay. Like the ELISA, the PCR assay sensitivity was due in part to its suitability for detecting small numbers of both live and dead R. typhi in fleas.

Animals↗

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↗

Spotted fever group and typhus group rickettsioses in humans, South Korea.

The presence of the nucleic acid of the spotted fever group (SPG) and typhus group (TG) rickettsiae was investigated in 200 serum specimens seropositive for SFG rickettsiae by multiplex-nested polymerase chain reaction with primers derived from the rickettsial outer membrane protein B gene. The DNA of SFG, TG, or both rickettsiae was amplified in the 24 serum specimens, and sequence analysis showed Rickettsia conorii, R. japonica, and R. felis in the specimens. R. conorii and R. typhi were found in 7 serum specimens, which indicated the possibility of dual infection in these patients. These findings suggest that several kinds of rickettsial diseases, including boutonneuse fever, rickettsialpox, R. felis infection, and Japanese spotted fever, as well as scrub typhus and murine typhus, are occurring in Korea.

Antigens, Bacterial↗

Lysis of cells infected with typhus group rickettsiae by a human cytotoxic T cell clone.

Cytolytic human T cell clones generated in response to the intracellular bacterium Rickettsia typhi were characterized. Growing clones were tested for their ability to proliferate specifically in response to antigens derived from typhus group rickettsiae or to lyse targets infected with R. typhi or Rickettsia prowazekii. Two clones were able to lyse targets infected with typhus group rickettsiae. One of these clones was more fully characterized because of its rapid growth characteristics. This cytolytic clone was capable of lysing an autologous infected target as well as a target matched for class I and II histocompatibility leukocyte antigens (HLA). It was not capable, however, of lysing either a target mismatched for both class I and II HLA or a target partially matched for class I HLA. In addition, the clone exhibited specificity in that it was able to lyse an autologous target infected with typhus group rickettsiae, but did not lyse an autologous target infected with an antigenically distinct rickettsial species, Rickettsia tsutsugamushi. These results demonstrate, for the first time, that cells infected with intracellular bacteria can be lysed by human cytotoxic T lymphocytes.

Antigens, Bacterial↗

[Immunoenzyme analysis in a system of serologic evaluation of louse-borne typhus vaccines].

The blood sera of persons immunized with different typhus vaccines have been studied in the complement fixation test, the indirect hemagglutination test and the enzyme immunoassay. The data thus obtained indicate that the enzyme immunoassay is highly sensitive and can be universally used for the determination of antibodies to Rickettsia prowazekii after primary and booster immunization with different typhus vaccines. This method detects specific antibodies both at an early period and, which is of particular importance, at a remote period after immunization (3 years later) when complement-binding and hemagglutinating antibodies are absent. This is seemingly indicative of the two-phase character of postvaccinal immunity induced by live typhus vaccine.

Antibodies, Bacterial↗

[Cellular immunity factors of tick-borne typhus patients in northern Asia].

In patients with North Asian tick-borne typhus fever the deficiency of the T-system of immunity, most pronounced in the acute period of the disease, is observed, which is manifested by low values of lymphocyte blast-transformation and rosette-formation. A decrease in the number of active E-rosette-forming cells depends on the severity of the disease. The shifts in the T-system of immunity, appearing in patients with North Asian tick-borne typhus fever, are compensated for comparatively quickly, the normalization of the functional activity of T-lymphocytes occurring sooner than the restoration of their number. The specific dynamics of the characteristics of cell-mediated immunity in patients with North Asian tick-borne typhus fever is accompanied by a comparatively mild course of the disease and its favorable outcome.

Adult↗