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Scrub typhus in the Northern Territory: exceeding the boundaries of Litchfield National Park.

Scrub typhus is recognised as an important differential diagnosis of fever, rash and sepsis in patients with a history of travel to Litchfield National Park in the Top End of the Northern Territory. All confirmed scrub typhus cases to date from the Northern Territory have visited the Park, but the presence of similar rainforest pockets elsewhere in the Top End suggested further infectious locations might be identified with increased tourism. We report a case of serologically confirmed Orientia tsutsugamushi infection in a man who had not been within Litchfield Park, but had visited another discrete Top End rainforest area.

Adult↗

Scrub typhus imported to Scandinavia.

We present the first 3 cases of confirmed scrub typhus imported to Scandinavia. The patients were infected in Thailand, Laos and Sri Lanka, respectively. Treatment with ciprofloxacin and doxycycline lead to rapid cure in 2 of the patients, while the third patient, who was not treated, had a prolonged convalescence. Specific antibodies against Orientia tsutsugamushi, the causative agent of scrub typhus, were detected in all 3 cases.

Adult↗

Variation in populations of chigger vectors of scrub typhus in developing oil palm areas of different ages.

The populations of scrub typhus vector chiggers were compared in two developing oil palm areas, one 5 years old and the other 7 years old at the inception of the study. Both areas were located within the same oil palm scheme in central Peninsular Malaysia. Leptotrombidium (L.) deliense, a principal vector of scrub typhus in Malaysia, was found in reduced numbers in the older oil palm habitat. This reduction is attributed to changes in the microhabitat, specifically the elimination of grasses between the oil palm trees due to canopy shading and to cultural practices.

Animals↗

Induction of protective immunity against scrub typhus with a 56-kilodalton recombinant antigen fused with a 47-kilodalton antigen of Orientia tsutsugamushi Karp.

A partial gene sequence encoding the 56-kD scrub typhus antigen (Sta56) was amplified from genomic DNA of the Orientia tsutsugamushi Karp strain by a polymerase chain reaction (PCR). The PCR product was ligated with the 47-kD scrub typhus antigen (Sta47) gene in the pQE30/47 expression vector, and the resulting recombinant expression vector was designated pQE30/56-47. A fusion antigen (Sta56-47) was expressed in Escherichia coli cells transformed with pQE30/56-47 after induction with isopropyl-beta-d-thiogalactopyranoside. The Sta56-47 antigen was recognized by both Sta47 and Sta56 immune sera and by immune serum to Sta56-47 in an immunoblot assay. This antigen was purified and used to immunize BALB/c mice. The animals immunized with Sta56-47 exhibited profound humoral and cellular immune responses, as well as increased resistance to O. tsutsugamushi Karp compared with mice immunized with Sta56 or Sta47. These results strongly suggest that Sta56-47 contains antigenic epitopes of the Sta56 and Sta47 antigens of O. tsutsugamushi Karp, and is a more suitable candidate for replacing whole-cell antigen of O. tsutsugamushi Karp to induce protective immunity against scrub typhus.

Animals↗

Rickettsia tsutsugamushi infection and scrub typhus incidence among Chinese military personnel in the Pescadores Islands.

Personnel assigned to infantry units of the army of the Republic of China (Taiwan) stationed in the Pescadores Islands experienced the highest incidence rate of scrub typhus (4%) and the highest rate of Rickettsia tsutsugamushi infection (12%) of the units studied during 1976. The ratio of scrub typhus to infection with R. tsutsugamushi was 30%. Non-immune personnel, when infected, were more likely to develop scrub typhus than were those who had previously been infected. There was a correlation between clinical illness and high antibody titers developed in response to the infection.

Humans↗

Scrub typhus serologic testing with the indirect immunofluorescence method as a diagnostic gold standard: a lack of consensus leads to a lot of confusion.

A review was performed to determine the evidence base for scrub typhus indirect immunofluorescence assay (IFA) methodologies and the criteria for positive results. This review included a total of 109 publications, which comprised 123 eligible studies for analysis (14 publications included 2 substudies). There was considerable underreporting of the IFA methodology and seropositivity criteria used, with most studies using a defined cutoff titer rather than an increase in the titer in paired samples. The choice of positivity cutoff titer varied by country and purpose of the IFA test. This variation limits the comparability of seroprevalence rates between studies and, more seriously, raises questions about the appropriateness of the cutoffs for positive IFA results chosen for diagnosis of acute scrub typhus infection. We suggest that the diagnosis of scrub typhus using IFA should be based on a > or =4-fold increase in the titer in paired serum samples and should only be based on a single sample titer when there is an adequate local evidence base.

Fluorescent Antibody Technique, Indirect↗

Diagnostic criteria for scrub typhus: probability values for immunofluorescent antibody and Proteus OXK agglutinin titers.

The sensitivities and specificities of the indirect microimmunofluorescent antibody (IFA) and Weil-Felix (OXK) tests for scrub typhus were established for a range of titers using groups of diseased and control (other febrile illnesses) patients diagnosed by other methods. At a cut-off point of greater than or equal to 1:400, the IFA test was 0.96 specific, and at greater than or equal to 1:320, the OXK was 0.97 specific. Using either these highly specific levels of antibody or other rigorous diagnostic criteria (isolation or 4-fold rising titers), the prevalence of scrub typhus infection was determined to be 0.22 in an unselected population of febrile patients in a rural Malaysian hospital. Probability values (Pr) for the correct diagnosis of scrub typhus were then calculated from the specificity, sensitivity and prevalence determination for a range of titers. The Pr for an OXK titer of greater than or equal to 1:320 was 0.79, and the Pr for an IFA titer of greater than or equal to 1:400 was 0.78. When both these titers were present in a single specimen, the Pr increased to 0.96.

Agglutination Tests↗

Scrub typhus associated with multiorgan failure: a case report.

The spectrum of clinical severity for scrub typhus ranges from inapparent, mild, to severe or fatal. The pathologic changes are focal or disseminated multiorgan vasculitis of the small blood vessels, a fact that helps explain the great diversity of clinical manifestations that can be encountered. We reported a case of scrub typhus with unusual and serious multiorgan involvement, including tubulointerstitial nephritis (TIN) with acute renal failure (ARF), interstitial pneumonitis with adult respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC), liver function impairment, upper gastrointestinal bleeding, prolonged hyperamylasaemia and hyperlipasaemia. Chloramphenicol administration rapidly altered the clinical course, but with sequelae of renal impairment and prolonged hyperamylasaemia and hyperlipasaemia for 10 months.

Anti-Bacterial Agents↗

Rapid diagnosis of scrub typhus in rural Thailand using polymerase chain reaction.

The aim of this study was to evaluate the use of polymerase chain reaction (PCR) amplification of the O. tsutsugamushi 16S rRNA gene for the diagnosis of scrub typhus in rural Thailand. A prospective study of acute febrile illness in Udon Thani, northeast Thailand, identified 183 patients as having scrub typhus on the basis of immunofluorescent antibody testing (IFA) of paired sera. A further 366 febrile patients admitted concurrently with a range of other diagnoses acted as negative controls. Diagnostic sensitivity and specificity of 16S rRNA PCR was 44.8% and 99.7%, respectively, compared with IFA. PCR positivity was related to duration of symptoms and presence of eschar (P < 0.001, both cases). PCR using primers to amplify a fragment of the 56-kd gene had a sensitivity and specificity of 29.0% and 99.2%, respectively. PCR has a high specificity but low sensitivity for the rapid diagnosis of scrub typhus in this endemic setting.

Humans↗

Short- and long-term immune responses of CD-1 outbred mice to the scrub typhus DNA vaccine candidate: p47Kp.

Orientia tsutsugamushi is an obligate intracellular bacterium that is the causative agent of scrub typhus. To develop an effective vaccine to prevent or ameliorate scrub typhus, knowledge of the protective immune response to O. tsutsugamushi needs to be ascertained. Our laboratory has demonstrated that the DNA vaccine vector pVR1012 carrying the O. tsutsugamushi Karp strain 47-kDa protein gene (p47Kp) consistently provides outbred mice protection against homologous challenge.

Animals↗

[Report on first finding an epidemic of Scrub typhus in north rural areas].

In the autumn of 1989 and 1990, an epidemic of Scrub typhus occurred in north rural areas in Tianjin. The authors investigated the epidemic on clinical, epidemiological, serological and etiological features, 44 patients were diagnosed serologically or clinically as Scrub typhus and 42 of them (95.5%) were diagnosed serologically by IFA method. 10 sera specimens collected from the patients were determined distinctively by CF method, 8 of them were > or = 1:20 titre to Gilliam type antigen of tsutsugamushi. The try for isolating pathogens failed of success. The epidemic areas is situated in 39.45'-40.05' north latitudes and showed it was the new epidemic area in the north of China.

Adolescent↗

Multiple organ failure complicating probable scrub typhus.

This report describes a case of life-threatening acute respiratory distress syndrome with multiple organ failure complicating probable scrub typhus. Favorable outcome was associated with fluoroquinolone therapy. Scrub typhus should be suspected in travelers returning from Southeast Asia presenting with unexplained respiratory manifestations.

Adult↗

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↗

Paediatric scrub typhus in Thailand: a study of 73 confirmed cases.

We studied 73 Thai children with scrub typhus (median age 9 years, range 3-14 years, male:female ratio 1.8:1). Most patients (86%) lived in rural areas. They presented with subacute fever (median, 9 d) with vomiting (35%), hepatomegaly (59%), splenomegaly (18%), and tachypnea (26%). Skin rash (7%), eschar (7%), and history of mite bite were rare. Blood leucocyte counts were usually normal but 19% of patients were thrombocytopenic. Twenty (22%) patients had pneumonia and six (8%) had neurological involvement. Defervescence occurred a median of 1 d and 3 d after initiation of doxycycline and chloramphenicol, respectively, and these responses were more rapid than in those who received other antibiotics or no treatment (P < 0.001). There was one death. Only 55% of the patients were initially diagnosed as having scrub typhus.

Adolescent↗

Differential expression of interferon-gamma and interferon-gamma-inducing cytokines in Thai patients with scrub typhus or leptospirosis.

Interferon (IFN)-gamma plays an important role in the induction of a type 1 immune response against intracellular pathogens. We compared the plasma levels of IFN-gamma and IFN-gamma-inducing cytokines in adult Thai patients with scrub typhus, caused by the obligate intracellular bacterium Orientia tsutsugamushi, and leptospirosis, caused by extracellular Leptospira interrogans. IFN-gamma, interleukin (IL)-18, and IL-15 levels were elevated only in patients with scrub typhus, whereas IL-12p40 and tumor necrosis factor-alpha concentrations were elevated in both patient groups, although more so in scrub typhus. These data suggest a role for a cell-mediated immune response in host defense against O. tsutsugamushi.

Adolescent↗

Acute renal failure associated with scrub typhus: report of a case.

We report on a 25-year-old man who had scrub typhus with the unusual complication of acute renal failure. The clinical features of fever, headache, high Weil-Felix OX-K agglutination and Rickettsia tsutsugamushi immunofluorescence titers confirmed the diagnosis of scrub typhus. Acute renal failure was proven by oliguria, urinary diagnostic indices and renal biopsy. The patient had a complete recovery after adequate medical treatment.

Acute Kidney Injury↗

Brachial plexus neuropathy associated with scrub typhus: report of a case.

We report on a 20-year-old man who had scrub typhus with the unusual neurologic complication of brachial plexus neuropathy. The clinical features of fever, headache, pneumonitis, eschar, high Weil-Felix OX-K agglutination and Rickettsia tsutsugamushi immunofluorescence titers confirmed the diagnosis of scrub typhus. Brachial plexus neuropathy was proven by an electrophysiologic examination. He had a nearly complete recovery after adequate medical treatment.

Adult↗

Temporal changes in prevalence of scrub typhus rickettsia (Orientia tsutsugamushi) infecting the eggs of Leptotrombidium imphalum (Acari: Trombiculidae).

Eggs from seven colony lines of the chigger mite Leptotrombidium imphalum (Vercammen-Grandjean & Langston) were examined for infection with Orientia tsutsugamushi (Hyashi), the etiologic agent of scrub typhus. The polymerase chain reaction (PCR) using primers OtP 56.809 and OtM 56.1221, which amplify a 291 bp region of the P56 gene of O. tsutsugamushi, was used to detect scrub typhus within single eggs. All seven chigger mite lines produced infected eggs with varying rates of infection (Li1 = 8.1%, n = 124; Li2 = 45.6%, n = 90; Li3 = 30.1%, n = 144; Li4 = 31.7%, n = 145; Li5 = 21.3%, n = 136; Li6 = 41.6% n = 77; Li7 = 22.5%, n = 110). The 3 wk with the highest infection rates for each line using Fourier analysis were as follows: Li1 = 2, 7, 14; Li2 = 4, 6, 12; Li3 = 3, 6, 12; Li4 = 4, 6, 12; Li5 = 5, 7, 14; Li7 = 4, 6, 12. Li6 only had nine measurements over time; therefore, Li6 was excluded from individual analysis. Infection rates of scrub typhus in eggs occurred in a 2-wk 2-d cycle, using Fourier analysis of combined data. Not only did infection rates vary among the progeny of females, but temporal variation also occurred.

Animals↗