Charles Nicolle (1866-1936) postal stamps released on Nicolle in France - 1969, Gambia - 1989, on "Scrub typhus" - Malaysia 1976.
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We conducted serodiagnostic testing for dengue virus infection, murine typhus, scrub typhus and leptospirosis in Plasmodium falciparum-infected individuals in Thailand. Sera from 194 malaria patients with a median age of 24 years were tested. No antibody titers diagnostic of dengue virus infection were demonstrated, but 29 (15%) of patients had serological evidence of scrub typhus, 45 (23.2 %) patients had evidence of murine typhus, and 15 (7.7%) sera tested positive for leptospirosis. Our serological results suggested that duel infections are not uncommon in malaria that is acquired in Thailand. However, our results must be confirmed by prospective studies aimed at describing the causative organisms. Mixed infections would have multiple implications for clinicians, including unexpected clinical findings and apparent poor responses to antimalarial treatment in patients thought only to have malaria.
Monoclonal antibodies were produced from mice infected with Rickettsia akari (the etiologic agent of rickettsialpox) and evaluated for specificity in indirect fluorescent-antibody tests with 23 different rickettsial antigens. Of the nine antibodies that were evaluated, two were specific for R. akari and four reacted with R. akari and all other spotted fever group rickettsiae. The remaining three antibodies reacted with some, but not all, members of the spotted fever group. None of the antibodies reacted with typhus, scrub typhus, trench fever, or Q fever rickettsiae. Adding these antibodies to the list of available diagnostic reagents will facilitate identification of rickettsial diseases, particularly those caused by members of the spotted fever group, where the clinical presentations are similar and the etiologic agents are closely related antigenically.
Case histories of boutonneuse fever are described in order to exemplify major characteristics of most rickettsioses: recent travel history, feverish illness with severe headache, skin eruptions and histological findings. Up-to-date informations concerning the epidemiologic situation of typhus, scrub typhus and Rocky Mountain spotted fever are given. The characteristics of Q fever and the possibility of rickettsial laboratory infections are pointed out.
In Nepal, many infections remain poorly characterized, partly due to limited diagnostic facilities. We studied consecutive febrile adults presenting to a general hospital in Kathmandu, Nepal. Of the 876 patients enrolled, enteric fever and pneumonia were the most common clinical diagnoses. Putative pathogens were identified in 323 (37%) patients, the most common being Salmonella enterica serotype Typhi and S. enterica serotype Paratyphi A (117), Rickettsia typhi (97), Streptococcus pneumoniae (53), Leptospira spp. (36), and Orientia tsutsugamushi (28). Approximately half of the Salmonella isolates were resistant to nalidixic acid. No clinical predictors were identified to reliably distinguish between the different infections. These findings confirm the heavy burden of enteric fever and pneumonia in Kathmandu, and highlight the importance of murine typhus, scrub typhus, and leptospirosis. Given the lack of reliable clinical predictors, the development of cheap and accurate diagnostic tests are likely to be of great clinical utility in this setting.
Murine typhus and scrub typhus are important human rickettsial diseases in Thailand. Small mammals, including many species of rodents and shrews, serve as the reservoir host of rickettsial diseases. Rickettsia typhi can be transmitted to humans by fleas causing murine typhus, while infection with Orientia tsutsugamushi causing scrub typhus in humans is transmitted by chiggers. The prevalence of rickettsial infection depends on the geographic area. The seroprevalence of antibody to R. typhi and O. tsutsugamushi was studied in commensal rodents and shrews trapped in markets in the Bangkok Metropolitan Area (BMA). R. typhi and O. tsutsugamushi antigen prepared in the yolk sac of embryonated eggs were used to determine the specific antibody in trapped animals' sera by using fluorescein isothiocyanate (FITC)-anti rat immunoglobulins as a second antibody. Antibody to R. typhi was found in 25 (5%) of 500 sera tested and no antibody to O. tsutsugamushi was detected. R. typhi antibody titer ranged from 40-1280 and was found in Rattus norvegicus (4.2%), Rattus rattus (0.4%), Rattus exulans (0.2%), and Mus musculus (0.2%) trapped in 8 of 47 markets in the BMA. R. typhi antibody was commonly found in R. norvegicus. The authors concluded that murine typhus is an important rickettsial disease and R. norvegicus is an important reservoir species of rodents found in markets of the BMA.
A patient was admitted to our hospital with fever of unknown origin, lymphadenopathy and moderate anemia. The diagnosis of scrub typhus (tsutsugamushi disease) was established on specific serologic demonstration of antibodies to the cross-reacting proteins OX-K antigen and reaffirmed by successful treatment with doxycycline. The diagnosis of hemophagocytic syndrome (HPS) was made on the cytologic findings of many histiocytes containing phagocytosed blood cells in the marrow aspirate. The hemophagocytosis phenomenon disappeared after the scrub typhus was successfully treated, thus suggesting the relationship between scrub typhus and hemophagocytosis. In a patient with rickettsial diseases including scrub typhus, associated with HPS, it is important to understand the relationship between the two disorders since the prognosis for HPS, if untreated, is very poor.
Since 1949, information on rickettsial diseases in the People's Republic of China has been virtually nonexistent in the West. This is the first comprehensive review of the ecology and epidemiology of Chinese rickettsial diseases to be published outside the People's Republic. At least five rickettsioses exist in China: scrub typhus, murine typhus, epidemic typhus, Q fever, and one or more spotted fever-group (SFG) rickettsioses. Although epidemic typhus has been controlled and scrub typhus has abated in many areas, murine typhus, Q fever, and SFG rickettsiosis are important public health problems. Serologic surveys indicate high prevalences of antibodies to Coxiella burnetii, Rickettsia tsutsugamushi, and SFG rickettsiae in some regions; these rickettsiae have been isolated from humans, arthropods, and animals. Doxycycline has emerged as the best treatment for murine typhus, epidemic typhus, and scrub typhus. China offers both opportunities and challenges for the investigation and alleviation of the problems of rickettsial diseases.
BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a monophasic demyelinating disease of the central nervous system, typically occurring after infections or vaccinations. To our knowledge, scrub typhus has not been described in association with ADEM. CASE REPORT: A 77-year-old man was admitted with fever, convulsions and an altered level of consciousness. On neurological examination, the patient was stuporous and had nuchal rigidity and left hemiparesis. A generalized tonic-clonic seizure was observed. Serum and cerebrospinal fluid samples were positive for anti-Orientia tsutsugamushi antibody. Despite a 10-day course of parenteral minocycline, his clinical condition deteriorated. Serial cranial magnetic resonance images demonstrated progressively extensive areas of signal hyperintensity on conventional T2-weighted and fluid attenuated inversion recovery sequence images, mainly affecting the periventricular white matter. After administration of intravenous high-dose corticosteroids, the patient had limited improvement. CONCLUSIONS: This is the first identifiable case of ADEM temporally associated with scrub typhus alone.
BACKGROUND AND PURPOSE: Taiwan is an endemic area for scrub typhus. Recent increases have been noted in two other infectious diseases caused by obligate intracellular organisms, Q fever and murine typhus. These diseases usually present as an acute febrile illness with non-specific symptoms and are difficult to distinguish. This study describes the clinical manifestations and complications of cases of rickettsial infections treated at a medical center in southern Taiwan. METHODS: Serum samples from patients with acute febrile illness with or without shock, but without a clinical diagnosis of localized bacterial infection after a preliminary work-up, were collected for serologic study. Medical records of cases with serologic evidence of infection were reviewed and their clinical manifestations were analyzed. RESULTS: From October 1992 to July 2000, 51 serologically diagnosed cases of rickettsiosis were studied. Q fever predominated (28 cases). All cases of acute Q fever presented with hepatitis during the course of the illness and more than half (54%) reported an animal contact history. Most patients with Q fever (96%) and murine typhus (86%) were male, Serious complications, especially pneumonitis, occurred more frequently with scrub typhus than with acute Q fever. Spontaneous remission frequently occurred with acute Q fever. Administration of tetracycline or its analogues usually resulted in defervescence by the third day of treatment of scrub typhus. CONCLUSIONS: In our study, serious complications including pneumonitis, meningitis/meningoencephalitis, shock, acute renal failure, and disseminated intravascular coagulation were not uncommon in patients with scrub typhus. Physicians should include scrub typhus in the differential diagnosis of suspected cases of community-acquired febrile illness with multiple organ dysfunction in this endemic area. As Q fever is an emerging infectious disease in southern Taiwan, further large-scale epidemiologic surveillance and clinical data are needed.
Indonesian peacekeepers in Cambodia provided a unique study population to estimate the threat of rickettsial exposure to Rickettsia typhi (murine typhus), Orientia tsutsugamushi, (scrub typhus), and R. conorii (spotted fever) for the region. Prescreening prevalence measure showed a large proportion (36%) of soldiers with antibodies to R. typhi. Predeployment prevalence for antibodies to O. tsutsugamushi was 8%, with no evidence of background R. conorii infections. Actual seroconversions of R. typhi (3) and O. tsutsugamushi (1), attributed to exposure(s) in Cambodia, translated into annualized incidence rates of 24 and 8 per 1,000 per year, respectively. Surveillance of rickettsial infections and/or disease is particularly warranted in Cambodia with recent recognition of drug-resistant scrub typhus in neighboring Thailand.
Rickettsial diseases have affected the military throughout history. Efforts such as those of the Joint U.S. Typhus Commission near the beginning of World War II and of military researchers since have reduced the impact of these diseases on U.S. and Allied forces. Despite the postwar development of effective antibiotic therapies, the newly emerging antibiotic-resistant scrub typhus rickettsial strains of the Asian Pacific region mandate continued research and surveillance. Similarly, tick-infested training areas in the United States and similar exposure abroad render the spotted fevers and the ehrlichioses problematic to deployed troops. The military continues to work on countermeasures to control the arthropod vectors, as well as actively participating in the development of rapid accurate diagnostic tests, vaccines, and improved surveillance methods. Several rickettsial diseases, including epidemic typhus, scrub typhus, the ehrlichioses, and the spotted fevers, are reviewed, with emphasis on the military historical significance and contributions.
Orientia tsutsugamushi infection causes scrub typhus, a common zoonosis of rural Asia. Orientia tsutsugamushi was recently detected by a real-time quantitative polymerase chain reaction (qPCR) assay in animal specimens. We evaluated the same qPCR assay in specimens obtained from patients with serologically proven scrub typhus infections. The 47-kDa qPCR assay was more sensitive than was mouse inoculation; it was reactive in whole blood specimens from all 10 isolate-positive patients and in 7 of 17 isolate-negative individuals (P = 0.003, Fisher's two-tailed exact test). As few as 1,076 O. tsutsugamushi copies/microL were detected in whole blood. Four of 7 sera from isolate-proven scrub typhus infections were also reactive by qPCR. The assay was unreactive in all 12 individuals without scrub typhus infection. This is the first demonstration of a sensitive and specific real-time qPCR assay for human scrub typhus infection.
An indirect immunoperoxidase test was compared with an indirect fluorescent antibody test and the Weil-Felix OXK test for serodiagnosis of scrub typhus by measuring the rickettsial antigen specific activity of IgG, IgM, and whole globulin. Acute and convalescent sera from 50 Rickettsia tsutsugamushi isolate-positive scrub typhus patients and from 45 febrile patients diagnosed as having diseases other than scrub typhus were tested. The receiver operating characteristic for each test showed that the indirect immunoperoxidase and indirect fluorescent antibody tests were more sensitive and specific than the Weil-Felix test using convalescent and acute as well as paired sera. The indirect immunoperoxidase test showed no cross-reactivity when R. tsutsugamushi antigen was tested against sera collected from patients living outside the scrub typhus-endemic area with diseases other than scrub typhus. The indirect immunoperoxidase and indirect fluorescent antibody tests were comparable in measured response to R. tsutsugamushi, R. typhi, and TT-118 (spotted fever group) antigen. Thus the indirect immunoperoxidase test represents a sensitive, specific, reproducible, and practical semiquantitative test for rickettsial disease diagnosis.