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[Degree of purification of a chemical epidemic typhus vaccine of the heterogeneous ballast proteins].

The degree of purification of chemical typhus vaccine from the ballast proteins of the substrate has been studied by chemical and immunochemical methods. The analysis of 11 production batches of the vaccine and a number of model preparations has revealed that chemical typhus vaccine is completely free from nonprotein nitrogen-containing components and, to a considerable extent, purified from ballast protein, its concentration being 0.033-0.242 mg per vaccination dose, and also possesses a high specific activity (198-1454 antigenic units per mg of protein. Ballast proteins include at least 5 egg antigens. The concentration of one of them varies between 0 and 5 micrograms per dose. A number of recommendations is made; their realization will make it possible to increase the degree of purification of chemical typhus vaccine.

Animals↗

Scrub Typhus antibody in cynomolgus monkeys (Macaca fascicularis) in Malaysia.

Using an indirect immunofluorescence technique, sera from 113 cynomolgus monkeys (Macaca fascicularis), trapped in Peninsular Malaysia, were screened for the presence of antibody to six prototype strains of Rickettsia tsutsugamushi combined into three polyvalent groupings: I--Karp, TA716, and TA763; II--Gilliam; and III--TA678 and TH1817. Fifteen percent (17/113) of the monkeys had antibody titers greater than or equal to 1:50 to one or more of the antigenic groups. Although a titer greater than or equal to 1:150 is generally considered indicative or prior Rickettsia tsutsugamushi infection, we selected a less than 1:25 titer as a conservative standard to insure non-infected animals. Using this criterion, 62 (55%) of the 113 monkeys were accepted for use in scrub typhus studies. The high prevalence of antibody to scrub typhus in the semi-arboreal cynomolgus monkey is in marked contrast to the low prevalence reported in the strictly arboreal silvered leaf monkeys (Presbytis cristatus). The results of this study indicate that cynomolgus monkeys should be rigorously screened for evidence of prior infection before they are included in experimental scrub typhus studies.

Animals↗

Detection of a typhus group Rickettsia in Amblyomma ticks in the state of Nuevo Leon, Mexico.

The state of Nuevo Leon, Mexico has had outbreaks of typhus group rickettsiosis, most recently recognized in 1997. Evaluation of the sera of 345 patients with a dengue-like illness revealed that 25.5% had antibodies reactive with typhus group rickettsiae and 16% had antibodies to Rickettsia parkeri. Rickettsiae were detected by PCR and shell-vial isolations in the field-collected Amblyomma ticks. Molecular characterization by DNA sequence analysis of the gltA, ompB, and 17-kDa gene identified the organisms to be R. prowazekii.

Animals↗

Seroepidemiologic evidence for murine and scrub typhus in Malang, Indonesia.

Indonesian military personnel stationed in Malang, East Java were among troops deployed to central Cambodia as part of the United Nations' Transition Authority Cambodia peace-keeping operation in 1992. Predeployment blood samples obtained from a cohort of Indonesian soldiers indicated a high prevalence of antibodies to antigens of Rickettsia typhi or Orientia (formerly Rickettsia) tsutsugamushi, the etiologic agents for murine and scrub typhus, respectively. To evaluate the potential risk of these rickettsial diseases in the Malang area, a subsequent seroepidemiologic survey was conducted. This study involved civilian personnel residing within one of three Malang kelurahans (neighborhoods) representing urban, suburban, and rural communities. The heads-of-households from 197 homes completed a detailed epidemiologic survey. In addition, blood samples were collected from 464 individuals residing within the households surveyed. Examination of civilian blood samples disclosed that 34.7% and 1.3% of the study participants were seroreactive to R. typhi and O. tsutsugamushi, respectively. These results were similar to those obtained earlier from the military samples. In addition, assessment of 78 blood samples obtained from peridomestic rodents trapped from within or near the households surveyed showed that 28 were reactive to R. typhi antigens and four were reactive to O. tsutsugamushi antigens. These data indicate that military and civilian personnel living in the Malang area of East Java are at risk of infection with rickettsiae that are antigenically indistinguishable from those that cause murine and scrub typhus.

Adolescent↗

A survey of scrub and murine typhus in the Ancol section of Jakarta, Indonesia.

Rickettsia tsutsugamushi was isolated from L. (L.) arenicola chiggers and three species of rats in an area of scrub and sedge along the Bay of Jakarta. This is the only finding in Indonesia of a cycle of the agent of scrub typhus associated with L. (L.) arenicola. A serologic survey of nearly 300 persons living in two kampungs near the site at which rickettsiae were recovered revealed one individual with antibodies to R. tsutsugamushi. Murine typhus, with a seropositivity rate of 6.5%, may be endemic at low levels.

Animals↗

[3Autochthonous cases of murine typhus in France?].

Three men native from Northern Africa, aged more than 40 years, but by their profession in France with narrow contacts to rats, present clinical signs of typhus. Serology (FCT and FAT) gives positive results with R. prowazeki and R. typhi which have a strait antigenic community. Following assays of absorption of the sera by the two antigens and light differences of titers we conclude that two cases are Brill-Zinsser illnesses, but one is really an autochtone case of murin typhus. The last affirmation is confirmed by the detection of specific IgM-antibodies.

Adult↗

Murine typhus as a common cause of fever of intermediate duration: a 17-year study in the south of Spain.

BACKGROUND: Fever of intermediate duration (FID), characterized by a febrile syndrome lasting from 7 to 28 days, is a frequent condition in clinical practice, but its epidemiological and etiologic features are not well described. Murine typhus (MT) is a worldwide illness; nevertheless, to our knowledge, no studies describing its epidemiological and clinical characteristics have been performed in the south of Spain. Also, its significance as a cause of FID is unknown. OBJECTIVE: To determine the epidemiological features, clinical characteristics, and prognosis of MT and, prospectively, its incidence as a cause of FID. DESIGN: Prospective study of cases of MT over 17 years (1979-1995) and of all cases of FID treated in a tertiary teaching hospital in Seville, Spain. RESULTS: One hundred and four cases of MT were included, and MT was the cause in 6.7% of 926 cases of FID. Insect bites were reported in only 3.8% of the cases of MT previous to the onset of illness. Most cases (62.5%) occurred in the summer and fall. A high frequency of rash (62.5%) was noted. Arthromyalgia (77%), headache (71%), and respiratory (25%) and gastrointestinal (23%) symptoms were also frequent. Laboratory findings were unspecific. Organ complications were uncommon (8.6%), but they were severe in 4 cases. The mean duration of fever was 12.5 days. Cure was achieved in all cases, although only 44 patients received specific treatment. CONCLUSIONS: Murine typhus is prevalent in the south of Spain and is a significant cause of FID. Clinical signs are benign, but some patients may develop severe complications. A high degree of clinical suspicion is required for diagnosis.

Adolescent↗

Clinical, laboratory, and epidemiologic features of murine typhus in 97 Texas children.

OBJECTIVE: To document the clinical, laboratory, and epidemiologic characteristics of pediatric patients with murine typhus. DESIGN: Pediatric patients were diagnosed using serologic testing, and clinical, laboratory, and epidemiologic data were retrospectively reviewed. SETTING: Of 97 patients, 77 (79%) were identified and treated as inpatients and 20 (21%) were treated as outpatients; most resided in south Texas. PATIENTS: Between 1979 and 1996, medical records and patient-physician interviews were available for 97 patients aged 16 years and younger with murine typhus. MAIN OUTCOME MEASURES: The frequency of clinical symptoms and signs, abnormal laboratory findings, epidemiologic findings, and measures of disease severity were determined. RESULTS: The clinical triad of fever, headache, and rash occurred in only 43 (49%) of 87 pediatric patients throughout the illness. Musculoskeletal symptoms were experienced by 43% of patients, whereas gastrointestinal tract symptoms (nausea, vomiting, anorexia, and diarrhea) occurred in 77%. Systemic involvement was evident by the frequent occurrence of abnormal laboratory findings referable to multiple organ systems, including the liver, kidney, blood, and central nervous system. CONCLUSIONS: Pediatric infection by Rickettsia typhi usually causes mild to moderate systemic illness. In children, the median duration of illness was 12 days (range, 5-29 days), but severe complications were rare. Length of illness was significantly related to the initial diagnosis, whereas the interval to defervescence was related to therapy with a tetracycline or chloramphenicol. Early recognition and treatment is important to prevent prolonged morbidity.

Adolescent↗

Clinicoepidemiological study of murine typhus on the Greek island of Evia.

Cases of murine typhus were described in Chalkis, capital town of the island Evia in Greece. In the present work a prospective study on murine typhus was carried out in Chalkis General Hospital in 1985, is presented. During this year 49 cases, serologically confirmed using indirect fluorescence assay, were diagnosed. Signs and symptoms of the patients as well as preliminary epidemiological data are reported in this paper.

Adolescent↗

Scrub typhus pneumonitis acquired through the respiratory tract in a laboratory worker.

We report a case of scrub typhus pneumonitis in a laboratory worker who apparently acquired it through the respiratory tract. The patient was suffering from fever, cough and dyspnea. He had both cervical and axillary lymphadenopathy, and hepatomegaly. A chest X-ray showed interstitial infiltrates. A diagnosis of scrub typhus was established upon isolation of Orientia tsutsugamushi. 12 days before the patient showed symptoms, he had purified O. tsutsugamushi proteins from infected cells using an ultrasonication method which could generate aerosols containing O. tsutsugamushi.

Adult↗

Interferon-gamma in cerebrospinal fluid without pleocytosis in scrub typhus.

We detected immunoreactive interferon-gamma (IFN-gamma) both in cerebrospinal fluid (CSF) and in serum of 5 patients with scrub typhus, one with meningitis and 4 other cases with neither CSF pleocytosis nor blood-CSF barrier dysfunction. Our data suggest intrathecal synthesis of IFN-gamma without pleocytosis which implies occult cerebral involvement in scrub typhus.

Adult↗

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↗

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↗

Rapid, simple serodiagnosis of murine typhus.

The dot-blot enzyme-linked immunosorbent assay (dot-ELISA) was compared to latex agglutination (LA) and the Weil-Felix OX-19 test for the diagnosis of murine typhus using the indirect immunofluorescent antibody (IFA) test as the 'gold standard'. With a panel of 74 positive and 47 negative sera, the dot-ELISA was 98% specific and 74% sensitive at a cut-off value of the second dot. With acute sera, latex agglutination was 100% specific and 74% sensitive at a cut-off titre of > or = 1:64. Both tests were more sensitive than the OX-19 test, which was 98% specific and 56% sensitive at a titre of > or = 1:320. Both dot-ELISA and latex agglutination were comparable and the results were available within one hour of testing. The rapidity, ease in performance and minimal requirement for electrical instruments made these 2 tests suitable for the diagnosis of murine typhus in countries where sophisticated laboratory facilities are lacking.

Acute Disease↗

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↗

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↗

Epidemic typhus in a prison in Burundi.

The International Committee of the Red Cross investigated an outbreak of fever of unknown origin in Ngozi prison, Burundi, which resulted in a crude mortality rate of 2.61% in January 1996. A definite diagnosis of epidemic typhus caused by Rickettsia prowazekii was established by enzyme-linked immunosorbent assay using specific antigens. Control measures included complete cleansing of the prison with cyfluthrine, shaving and dusting all prisoners with permethrin 0.5% dusting powder, and replacement of all mattresses and clothes. All prisoners and guards received a single dose of doxycyline (100 mg) simultaneously. The crude mortality rate dropped abruptly to 1.27% in February 1996 and remained at or below 0.5% from March onwards. Health authorities and medical agencies working in Burundi need to consider epidemic typhus in the differential diagnosis of fever of unknown origin in order to be able to take appropriate control measures in time.

Anti-Bacterial Agents↗

Comparative evaluation of four serodiagnostic tests for scrub typhus in Thailand.

The commercial dot-blot enzyme-linked immunosorbent assay Dip-S-Ticks dipstick test was compared with the indirect immunoperoxidase (IIP) and Weil-Felix (WF) tests for the diagnosis of scrub typhus, using the indirect immunofluorescent antibody test (IFA) as the reference standard. With a panel of 117 positive and 75 negative sera, the dipstick test was 94% sensitive and 98.7% specific at a cut-off value of one or more positive dots. The IIP was 90.6% sensitive and 100% specific at a cut-off titre of 1:400, and was more sensitive than the IFA with acute sera (79.6% vs. 68.5% at a titre > or = 1:400). All 3 were superior to the WF, which lacked sensitivity. The dipstick assay was easy to perform and did not require sophisticated electrical equipment, and the results were available within one hour. It is therefore suitable for use in rural Thailand, where scrub typhus is common.

Agglutination Tests↗