Biomedical subjects
Publications and source records attributed to T Pang.
Four recent cases of dengue fever with severe, unusual clinical manifestations are described. Two of these cases had features of fulminant hepatitis and encephalopathy; one of these cases was fatal. The two remaining cases showed hepatitis with renal impairment. The significance and importance of these unusual manifestations of dengue disease are discussed.
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Studies were performed on a cytotoxin (CT) from human strains of Campylobacter jejuni isolated in Malaysia. CT was detected by cytopathic effect (CPE) on HeLa cells at titres from 8 to 32, in culture filtrates from 14 (48%) of 29 human isolates. The CPE correlated well with a quantitative 51Cr-release assay where a specific release of 54-68% was noted. CT production was lost after 5-7 subcultures. CT activity was also detected in 5 (26%) of 19 faecal filtrates from which CT-producing isolates were subsequently obtained. The mol. wt of CT was estimated by Sephadex G-50 chromatography to be greater than 30,000. In a suckling-mouse assay, CT consistently failed to demonstrate fluid accumulation after intragastric inoculation of culture filtrate. The Removable Intestinal Tie Adult Rabbit Diarrhoea (RITARD) assay was also used. Rabbits given CT-producing strains of C. jejuni developed bacteraemia and severe watery mucus-containing diarrhoea for the duration of the experiment with death of some animals. Rabbits given CT non-producing strains had less severe disease and none died. Rabbits given partially-purified CT had diarrhoea for 3 days but none died.
Studies were carried out into the immunopathogenesis and laboratory diagnosis of dengue virus infections. Using an experimental system it was shown that cell-mediated immunity (CMI), as measured by delayed-type hypersensitivity (DTH) was induced in mice infected with dengue virus. The nature of the DTH response satisfies most criteria for a classical DTH reaction. In addition, it was also shown that infection with dengue virus causes a transient immunosuppression as measured by the immune response to other, unrelated antigens. With regard to the laboratory diagnosis of dengue infections, it was found that mosquito cells were a sensitive system for the isolation of dengue viruses and that the success of isolation was related to the antibody content of the serum. A new method for the rapid isolation of dengue viruses was also developed involving the intracerebral inoculation of mosquito larvae. By the use of this method viral antigens can be detected as early as 2-3 days after specimen inoculation. The significance of these findings in relation to the immunopathogenesis, prevention and control of disease syndromes due to dengue viruses is discussed.
A modification of the IgM-capture ELISA which can provide an early diagnosis for dengue infection is presented. The test is technically simple compared to HI and appears to be more sensitive. It has the advantage over HIT for the detection of specific IgM in that it is more sensitive and the reading of the result is not subjective. There is the possibility of the test being able to replace HI and HIT in the future.
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The isolation of dengue viruses from clinical specimens has always posed a particularly difficult problem. The use of invertebrate cell cultures such as AP-61 and C6/36 has reduced the time required for definitive diagnosis to within a week. More recently, inoculation of adult mosquitoes has been used but it requires more than a week to reach a confirmed laboratory diagnosis. We describe a method using intracerebral inoculation of immobilized fourth instar of Toxorhynchites splendens larvae for the isolation of dengue viruses from clinical specimens which yields results within a few days following incubation at 32 degrees C.
We developed a highly specific, sensitive, and economical hemadsorption immunosorbent technique for the detection of dengue-specific immunoglobulin M (IgM) antibody. The technique is based on the reaction of human sera with anti-human IgM immobilized onto a solid phase followed by the detection of dengue-specific IgM by the addition of a known quantity of dengue virus hemagglutinin and goose erythrocytes. Dengue-specific IgM-positive sera showed hemadsorption. IgM antibody specific for dengue virus was detected in 22 of 39 (56%) convalescent-phase sera from primary dengue infections and 8 of 10 (80%) convalescent-phase sera from secondary dengue infections. Additionally, 32 of 76 single sera from patients were positive for dengue IgM; these sera were previously uninterpretable by the hemagglutination inhibition test, as only a single serum specimen was available. No false-positive results were obtained with sera that were negative by the hemagglutination inhibition test for dengue virus. Crude dengue virus hemagglutinin preparations could be used without purification. Dengue-specific IgG did not interfere with the results, nor was there any cross-reactivity between dengue hemagglutinins and IgM specific for other viruses. Some cross-reactivity of the dengue-specific IgM was observed with Japanese encephalitis virus hemagglutinins, but this did not present any problems in the interpretation of results. This test is specific, inexpensive, highly reproducible, and simple to perform.
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Inbred mice fed with a 40% mixture of palmyrah flour pellets showed a significantly reduced capacity to mount a delayed-type hypersensitivity (DTH) response to sheep red blood cells (SRBC). Maximal suppression of DTH was noted after 6 days of feeding but was detectable even after 2 days. Maximal suppression occurred when flour feed was maintained into the sensitization period (with SRBC). The suppressive effect was transferable to normal mice fed with pellets ad libitum by viable spleen cells from mice fed with the 40% flour pellet mixture for a period of 2 days. Further characterization of the cells which were able to transfer suppression showed them to be T cells, some of which possess the Ly-1 surface antigen. The cells appear to be negative for Ly-2 surface antigen. Histologically, no evidence of lesions was noted in the liver and other organs of recipient mice which received cells from flour-fed donors. We thus favour the interpretation that oral feeding of mice with palmyrah flour induced the generation of T suppressor cells which were able to suppress the DTH response to SRBC. The significance and implications of these findings are discussed.
The nature of effector cells which mediate delayed-type hypersensitivity (DTH) to dengue type 2 virus and the influence of the H-2 complex on the cellular transfer of DTH was investigated. The DTH effector cells appeared to consist of two types of T cells, one Lyt-1.1+, the other Lyt-2.1+ or, alternatively, an interaction between these two T cell subsets may be required for maximal expression of DTH. Cellular transfer of DTH reactivity also required compatibility at the K and D or I region of the H-2 complex. Compatibility at the D region alone was not sufficient for transfer of DTH. The significance and implications of these findings are discussed.
Infection of mice with dengue-4 virus produced a significant, transient immunosuppression of the delayed-type hypersensitivity (DTH) response to sheep red blood cells (SRBC). Suppression was noted on day 3 after infection, was maximal on day 5 and was no longer evident on day 13 after infection. The suppressive effect was transferable to normal mice by viable spleen cells from immune mice but not by immune serum. These cells appeared to be present in the spleens of infected mice as early as day 1 after infection and were still detectable on day 7. No evidence was obtained that suppression was mediated by a soluble factor. Further characterization of the cells which could transfer suppression showed them to be T cells possessing both Ly-1 and Ly-2 surface antigens. These data suggest that there may exist two types of T suppressor cells or that, alternatively, an interaction between Ly-1+ and Ly-2+ cells was required to produce suppression. The significance and implications of these findings are discussed.
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