Genotyping of<i>Orientia tsutsugamushi</i>from Humans with Scrub Typhus, Laos

Parola, Philippe; Blacksell, Stuart D.; Phetsouvanh, Rattanaphone; Phongmany, Simaly; Rolain, Jean‐Marc; Day, Nicholas P. J.; Newton, Paul N.; Raoult, Didier

doi:10.3201/eid1409.071259

Cited by 37 publications

(20 citation statements)

References 9 publications

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“…The majority of our patient group would be predicted to have been infected with strains related to the Karp or Gilliam serotype (2). A study of O. tsutsugamushi strains isolated from patients in Vientiane, Laos, on the opposite side of the Mekong river from Udon Thani reported a comparable pattern of genotypes (16). Although the O. tsutsugamushi strains circulating in Chiang Rai may be similar to those found in Thailand and Laos, it is also conceivable that they differ.…”

Section: Discussionmentioning

confidence: 92%

Association of High Orientia tsutsugamushi DNA Loads with Disease of Greater Severity in Adults with Scrub Typhus

et al. 2009

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Orientia tsutsugamushi, the cause of scrub typhus, is a major pathogen in the Asia-Pacific region. The severity of infection ranges from mild features to multiorgan failure and death. The aim of this prospective study was to define the O. tsutsugamushi loads in the blood samples of patients with scrub typhus on the day of hospital admission and to determine whether this was associated with disease severity. Quantitation was performed using a real-time PCR Orientia tsutsugamushi, the cause of scrub typhus, is a major pathogen in the Asia-Pacific region, where it accounts for up to 23% of all febrile episodes (4). Infection commonly presents as an acute febrile illness 7 to 10 days after the bite of an infected larval trombiculid mite (chigger). The major presenting features are fever, severe headache, and myalgia. Other signs and symptoms include rash, lymphadenopathy, hepatosplenomegaly, cough, sore throat, abdominal pain, and central nervous system involvement. The severity of infection ranges from mild features to multiorgan failure and death, which occurs for around 4% of patients presenting to a hospital (10, 21). Severity of illness has been reported to show geographical variability (10), although the basis for this is unknown and has multiple explanations, including differences in host genetic susceptibility or response to infection and variability in the virulence of the organism. A relationship between magnitude of bacteremia and severity of clinical picture has been reported for a range of bacterial infections in both adults and children, based on quantitative bacterial culture (25) and, more recently, molecular techniques (5, 8). A previous study reported the O. tsutsugamushi DNA loads in 7 patients with scrub typhus, as defined by quantitative real-time PCR targeting a gene encoding a 47-kDa protein (20). This ranged from 1,076 to 28,812 DNA copies/l in blood, but clinical features and outcomes were not described (20).The aim of this study was to define the O. tsutsugamushi loads in blood samples taken on the day of hospital admission from a large, unselected population of patients with scrub typhus in northeast Thailand and to compare this with disease severity. MATERIALS AND METHODSPatients with scrub typhus were identified during a prospective study of acute febrile illness in Udon Thani hospital, northeast Thailand, between October 2000 and December 2001, as described previously (21). In brief, the inclusion criteria were an age of Ն15 years, the presence of a fever (Ͼ37.8°C) of unknown cause, and agreements to participate and to attend an outpatient follow-up for a convalescent-phase serum sample at 2 weeks. The exclusion criterion was a blood smear positive for malaria parasites or the presence of other definable infections, such as pneumonia or urinary tract infection. Blood was drawn on admission for aerobic blood culture, serological testing, and molecular diagnostics. The duration of symptoms prior to admission, antibiotic treatment at presentation, and clinical features, including the prese...

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Section: Discussionmentioning

confidence: 92%

Association of High Orientia tsutsugamushi DNA Loads with Disease of Greater Severity in Adults with Scrub Typhus

et al. 2009

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“…The different strains were closely related based upon the 56-kDa TSA gene sequences determined in previous work (3,23) and clustered within new genotypes. The occurrence of antibodies cross-reactive to different serotypes has been observed in many studies (9,19); however, this may not always be the case when infection occurs with diverse strains that are not included in the antigen panel (9). Therefore, specific antigens, including the three prototypes, i.e., Karp, Kato, and Gilliam, and new genotypes that were observed in this study should be considered for testing against any Thai patient sera to ensure the detection of antibodies produced against different O. tsutsugamushi serotypes in the future.…”

Section: Resultsmentioning

confidence: 99%

Genotype Diversity and Distribution of Orientia tsutsugamushi Causing Scrub Typhus in Thailand

et al. 2011

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Scrub typhus, caused by antigenically disparate isolates of Orientia tsutsugamushi, is a widely distributed mite-borne human disease in the Asia Pacific region. Information regarding the heterogeneity of the immunodominant 56-kDa type-specific antigen (TSA) gene is crucial for the design and evaluation of scrub typhusspecific diagnostic assays and vaccines. Using indirect immunofluorescence assays (IFA) and PCR assays, O. tsutsugamushi was detected samples from rodents and patients with fever of unknown origin obtained from six provinces of Thailand during 2004 to 2007. Sequences were determined for a fragment of the 56-kDa TSA gene, and the relationship between these sequences and those previously determined were assessed. The phylogenetic analyses of partial 56-kDa TSA gene sequences demonstrated wide diversity and distribution of O. tsutsugamushi genotypes in Thailand. Furthermore, the genetic diversity grouped the scrub typhus agents into two commonly and five infrequently found genotypes within six provinces of Thailand. The two most commonly found genotypes of O. tsutsugamushi described in this study do not associate with the prototype strains that are widely used for the design and evaluation of diagnostic assays and vaccine candidates. Thus, these new genotypes should be considered for future scrub typhus assay and vaccine development.

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“…Expanding the panel of antigens used to test scrub typhus and to take into account local antigenic diversity would improve sensitivity of serologic diagnosis. 28 However, even though O. tsutsugamushi infection can be identified by serologic diagnosis, patient sera often cross-react with the antigens from different strains. 27 In our study, crossreactions among Boryong, Gilliam, Karp, and Kato antigen were observed in most patients.…”

Section: Discussionmentioning

confidence: 99%

Phylogenetic Analysis of the 56 kDa Protein Genes of Orientia tsutsugamushi in Southwest Area of Korea

Lee

Kim²,

Lee³

et al. 2011

The American Journal of Tropical Medicine and Hygiene

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Genotyping ofOrientia tsutsugamushifrom Humans with Scrub Typhus, Laos

Cited by 37 publications

References 9 publications

Association of High Orientia tsutsugamushi DNA Loads with Disease of Greater Severity in Adults with Scrub Typhus

Association of High Orientia tsutsugamushi DNA Loads with Disease of Greater Severity in Adults with Scrub Typhus

Genotype Diversity and Distribution of Orientia tsutsugamushi Causing Scrub Typhus in Thailand

Phylogenetic Analysis of the 56 kDa Protein Genes of Orientia tsutsugamushi in Southwest Area of Korea

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