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Biomedical subjects

A Shirai

Publications and source records attributed to A Shirai.

At least 73 records · Page 4Linked to original sources

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↗

Serological analysis of Rickettsia tsutsugamushi isolates from North Queensland.

Fifty-two Rickettsia tsutsugamushi isolates from humans, rodents and chiggers in North Queensland were serologically characterized by the direct immunofluorescence test. A majority (71%) of the isolates was a mixture of two or more strains. The most frequently detected strains in the 52 isolates were TA716 (84%), TA763 (42%), TA686 (33%), and Karp (31%). The Gilliam strain was detected in only 4% of the isolates.

Animals↗

Doxycycline propylaxis for human scrub typhus.

The use of doxycycline, as a prophylactic antibiotic against scrub typhus was investigated in a prospective, randomized, double-blind study. Twenty volunteers were divided into two similar groups. Beginning three days before exposure to Leptotrombidium fletcheri chiggers infected with Rickettsia tsutsugamushi, and continuing for six weeks after exposure, one group received weekly 200-mg oral doses of doxycycline and the other group received a placebo. Nine of 10 doxycycline-treated subjects remained well during prophylaxis but developed antibody to scrub typhus, whereas nine of 10 subjects given the placebo required treatment for scrub typhus. Therefore, the efficacy of the regimen in preventing scrub typhus was 89% (eight cases prevented of nine expected). Ten days after successfully completing prophylaxis, eight of nine subjects reported minor self-limiting symptoms. A single dose of doxycycline was given on day 3 of illness to volunteers who developed scrub typhus. Such therapy was initially effective but was frequently followed by relapse and cannot be recommended.

Adult↗

Characterization of Rickettsia tsutsugamushi strains in two species of naturally infected, laboratory-reared chiggers.

The strains of Rickettsia tsutsugamushi found in naturally infected, laboratory-reared Leptotrombidium (Leptotrombidium) arenicola and L. (L.) fletcheri chiggers were characterized by direct immunofluorescence (FA) and by mouse and monkey virulence tests. The strains existing in the L. (L.) arenicola chiggers consisted of different combinations of TA716, TA763, TA686, Karp, and Kato. In addition to these five strains, Gilliam was found in the L. (L.) fletcheri chiggers. Results indicate that individual chiggers can be simultaneously infected with several antigenic strains of R. tsutsugamushi. Although these antigens appear to remain stable within familial lines when several generations were viewed, the antigenic patterns observed in two succeeding generations did not always correlate. This variable expression of antigens was considered to be due to a quantitative fluctuation from one generation to the next in the strains of rickettsiae combined with a lack of sensitivity of the direct FA test in detecting small numbers of antigenically different rickettsiae. Phenotypic variation was considered to be a less probable explanation. Morbidity and mortality were minimal in ICR mice fed upon by individual chiggers of either species, but infection rates were 85-99%. Tissue suspensions prepared from mice infected by L. (L.) arenicola produced higher mortality and longer duration of illness in mice than those prepared from L. (L.) fletcheri-infected mice. Silvered leaf and cynomolgus monkeys were fed upon by the two species of chiggers or inoculated with the mouse tissue suspensions. In both cases, minimal clinical responses were observed.

Animals↗

Transmission of scrub typhus to human volunteers by laboratory-reared chiggers.

Laboratory-reared, Rickettsia tsutsugamushi-infected Leptotrombidium arenicola and L. fletcheri chiggers were fed on 1 and 2 human volunteers respectively. All subjects developed typical clinical signs and symptoms of scrub typhus beginning days 8-10 post chigger attachment (PCA); these included fever, severe headache, myalgia, regional lymphadenopathy, and eschar. The two L. fletcheri subjects developed a transient generalized rash on days 3-4 after the onset of fever, and these two individuals also appeared to suffer a more severe clinical disease. Rickettsemias were detected in all three volunteers beginning on day 7 PCA, 1-3 days before the onset of clinical disease. Rises in indirect fluorescent antibody titers occurred starting on days 13-19 PCA (day 4-11 post fever) and in Weil-Felix OXK titers starting on days 26-22 PCA (days 7-14 post fever). These results strongly suggest that the use of laboratory-reared chiggers is a reliable means of transmitting scrub typhus infections to volunteers.

Adult↗

Rickettsia tsutsugamushi strains found in chiggers collected in Thailand.

R. tsutsugamushi strains found in chiggers collected from 3 different sites throughout Thailand were antigenically characterized. Monotypic infections were observed in 76.7% of the chiggers. Karp was the most predominant strain, followed by TA716, TA763, TA686 and Kato. This study represents the first confirmed report of R. tsutsugamushi infection in 8 different chigger species in Thailand.

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↗

Test of carcinogenicity of quercetin, a widely distributed mutagen in food.

The carcinogenicity of quercetin, a flavonol, was tested in six-week-old ddY mice of both sexes. Groups of 38 males and 35 females were given pellet diet containing 2% quercetin throughout their life span. As controls, 16 males and 15 females were given basal diet. Animals in both test and control groups developed leukemia and tumors of the lung, forestomach, mammary gland, adrenal, and soft part tissues. In addition, some animals in groups treated with quercetin developed tumors of the heart, liver, salivary gland, ovary, and uterus. The incidences of these tumors in test and control groups were not statistically different.

Animals↗

Enhancement of the mutagenicities of N-methyl-N'-nitro-N-nitrosoguanidine and N-methyl-N-nitrosourea by glucose.

The mutagenicity of N-methyl-N'-nitro-N-nitrosoguanidine to Salmonella typhimurium hisG46 was enhanced by pre-incubating the chemical with bacteria in sodium phosphate buffer. Addition of glucose (to 15 mM) to the pre-incubation mixture further enhanced the mutagenicity. Pre-incubation with glucose also increased the mutagenicity of N-methyl-N-nitrosourea. Fructose, galactose, pyruvate and succinate also enhanced the mutagenicity of N-methyl-N'-nitro-N-nitrosoguanidine. The effect of glucose was observed with S. typhimurium strains hisG46, TA1975, TA1950, TA1535 and TA100.

Biotransformation↗

The longevity of antibody to Rickettsia tsutsugamushi in patients with confirmed scrub typhus.

Serological surveillance for up to two years of 114 patients with laboratory confirmed scrub typhus showed that antibody to Rickettsia tsutsugamushi as demonstrated by the indirect fluorescent antibody test is short-lived. The mean reversion time from mean peak titre (1:499) was 48.9 weeks and the calculated annual reversion rate to a titre less than 1:50 was 61%. This can be used to estimate attack rates based on point prevalence of antibody. The relationship between antibody prevalence and attack rates observed by other workers was confirmed using this model. The possible uses of the finding and its implications in Malaysia are briefly discussed.

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↗

Mutagenicity of pyrrolizidine alkaloids in the Salmonella/mammalian-microsome test.

The mutagenicities of 7 pyrrolizidine alkaloids to Salmonella typhimurium TA100 were demonstrated by a modified Ames's method. The pyrrolizidine alkaloids found to be mutagenic were clivorine, fukinotoxin, heliotrine, lasiocarpine, ligularidine, LX201 and senkirkine. Pre-incubation of these alkaloids with S9 mix and bacteria in a liquid medium was essential for demonstration of their mutagenicities.

Animals↗