1. A strain of the urban form of tropical typhus has been established in guinea-pigs, and maintained in them for more than one hundred generations. The history and characteristics of the strain are given. The clinical criteria of infection are febrile and scrotal reactions.
2. Methods of demonstration of Rickettsia in material from infected guinea-pigs and rabbits are described. In morphology, distribution and staining characteristics these Rickettsia do not appear to differ from R. prowazeki.
3. The infection of rabbits by intra-ocular inoculation of virus has met with only partial success ; the strains rapidly lose virulence, and do not survive beyond the third generation. The results are closely similar to those reported by Nagayo et al., in corresponding infections of rabbits with the virus of typhus exanthematicus, and to those obtained by the authors in corresponding infections with a strain of Rocky Mountain spotted fever.
4. Infection of white rats has been readily secured, and has been of the "inapparente" form.
5. Two monkeys, inoculated intradermally with infected material, showed a mild general reaction only; no lesion developed at the site of inoculation.
6. The results of the Weil-Felix reactions of sera from rabbits and monkeys convalescent from the infection are summarized. Agglutination is of the OX19 type of Proteus X strains, never of the OXK type.
7. The experimental data obtained indicate that the guinea-pig is the laboratory animal of choice for the study of the urban form of tropical typhus.
1. A strain of the rural form of tropical typhus has been established and maintained in guinea-pigs, and is now in its 97th generation. The history and characteristics of this strain are given. The clinical criterion of infection is a well-marked febrile reaction. Scrotal swelling does not occur. Ascites invariably follows intra-peritoneal inoculation of passage virus.
2. In more than one hundred other such attempts made in this laboratory it has proved impossible to maintain a strain beyond a few generations. Similarly all attempts to maintain the virus of the tsutsugamushi disease in guinea-pigs have failed. The guinea-pig must, therefore, be regarded as very insusceptible to the viruses of the rural typhus and tsutsugamushi group of fevers of Malaya.
3. Infection of rabbits by the intra-ocular inoculation of the virus of rural typhus and of the tsutsugamushi disease has been readily secured. The method, based on that of Nagayo et al., and the criteria of infection, are described in detail.
4. The white rat is readily infected with the virus of rural typhus, the infection being of the "inapparente" form. That the virus could be maintained with unabated virulence for 21 generations indicates, by the criterion of Nicolle, that rural typhus is a murine strain.
5. Monkeys have been successfully infected by the intradermal route with the virus of rural typhus and of the tsutsugamushi disease. At the sites of inoculation, in the case of both viruses, necrotic ulcers have developed that appear to be identical with one another, and with the initial lesion of the tsutsugamushi disease in man; in all other features the experimental infections in the monkey appear to be identical. Rabbits have been similarly infected.
6. The results of the Weil-Felix reactions of sera from rabbits and monkeys convalescent from experimental infection with rural typhus and the tsutsugamushi disease are summarized.
7. Methods of demonstration of Rickettsia from infected guinea-pigs and rabbits are described. In morphology, distribution and staining characteristics the Rickettsia demonstrable in material from animals infected with rural typhus and with the tsutsugamushi disease are identical, and do not appear to differ from the Rickettsia orientalis of Nagayo.
8. The experimental data secured indicate that, provided that intra-ocular inoculation is practised, the rabbit is the laboratory animal of choice in the case of the rural typhus and tsutsugamushi group of fevers (it being assumed that
expense and scarcity make extensive use of monkeys impracticable). Further, these data stress the remarkable similarity of the behaviour of these two viruses in experimental laboratory animals-a similarity that, as will be set forth in a later paper, is fully supported by cross-immunity experiments.
1. Cross-immunity tests between strains of rural typhus and tsutsugamushi in the guinea-pig, rabbit and monkey were made. Complete cross-immunity between the strains was demonstrated.
2. The problem of the absence of a primary ulcer in rural typhus and its presence in tsutsugamushi is discussed. Experimental findings are recorded; from consideration of these and certain clinical and epidemiological observations, the conclusion is drawn that one and the same virus may cause gradations of dermal lesion that vary greatly in extent and duration.
3. Correlation of the results of cross-immunity tests and experimental infections with clinical, aetiological, epidemiological and serological findings indicates that the two diseases are identical. Rural typhus is not a disease sui generis, and the term should be discarded, the older designation, "tsutsugamushi disease ", being retained.
(1) Two strains of tropical typhus have been isolated from wild rats trapped in endemic areas.
(2) Both were isolated and maintained in guinea-pigs.
(3) One could be isolated in rabbits by the intra-ocular inoculation of virus, and maintained thus indefinitely. The features of this infection appeared to be identical with corresponding infections obtained with the viruses of rural typhus and the tsutsugamushi disease of human origin. Repeated attempts to isolate the other rat strain in rabbits in the same manner failed.
(4) Rickettsia were found with ease and in abundance in infected material from guinea-pigs infected with either strain, and from rabbits infected with the one-strain.
(5) The sera of rabbits infected with the two rat strains gave positive Weil-Felix reactions of significant titre.
(6) Cross-immunity tests in rabbits between one rat strain and six strains of huinan origin of rural typhus and tsutsugamushi showed a cross-immunity to exist, complete in five strains and partial in the sixth strain.
(7) A concomitant infection with sodoku was present in the guinea-pigs of botlh strains ; although this may have modified the clinical signs, the infection by a typhus virus could be determined by four decisive criteria.
(8) The conclusion is drawn that the murine origin of the virus of the rural typhus-tsutsugamuslhi group of diseases is now firmly established.
Part VIII.
1. Cross-immunity experiments in the guinea-pig, rabbit and monkey were carried out with the viruses of the tsutsugamushi disease (including rural typhus) and the urban typhus of Malaya; they showed that immunogenically the two viruses are distinct.
2. The characteristics of setiology, epidemiology, serology and experimental infections are compared, and the conclusion drawn that the two diseases belong to entirely separate groups of rickettsial disease.
Part IX.
1. Cross-immunity experiments in the guinea-pig and rabbit were carried out with the viruses of Rocky Mountain spotted fever, tsutsugamushi (including rural typhus) and urban typhus. They showed that, immunologically, tsutsugamushi
and spotted fever are entirely distinct; whereas urban typhus and spotted fever, though more distinct than alike immunologically, do possess a minor degree of reciprocal cross-immunity.
2. Spotted-fever vaccine was found to have no protective value against the viruses of tsutsugamushi and urban typhus.
1. Transmission of the virus of urban typhus under experimental conditions from rat to rat by the rat flea (X. cheopis) by feeding has been effected. Collateral attempts to transmit the virus of rural typhus by precisely the same procedure failed.
2. Transmission of the virus of urban typhus was also achieved by the inoculation of faeces or crushed tissue of infected fleas into the scarified skin of guinea-pigs.
3. Multiplication of the virus of urban typhus occurs within the rat flea.
4. Infection with the virus of urban typhus is not hereditary in the rat flea.
5. Attempts to transmit the virus of urban or rural typhus by two species of ticks failed. In the case of rural typhus a lessened mortality in the experimental guinea-pigs following test inoculation with passage virus makes it, however, difficult to exclude ticks entirely as a minor factor in the epidemiology of rural typhus.
The immunological characteristics of 26 strains of Japanese encephalitis virus (JEV) isolated in Japan and Malaya between 1935 and 1966 have been investigated mainly by the antibody-absorption variant of the haemagglutination-inhibition test, and to a certain extent also by conventional haemagglutination-inhibition and complement-fixation tests. The antibody-absorption technique shows promise as a routine method for the immunotyping of JEV.At present, two immunotypes can be distinguished. One comprises 2 strains, Nakayama-NIH and I-58, and is designated as the I-58 immunotype. The other immunotype, JaGAr 01, comprises 17 strains which share the characteristics of the JaGAr 01 strain, including one subline of the Nakayama strain, Nakayama-Yakken. The Nakayama-RFVL strain was found to have the characteristics of both immunotypes. The I-58 immunotype differs more markedly from related arboviruses, such as the Murray Valley encephalitis virus and the West Nile Eg101 strain, than does the JaGAr 01 immunotype.Evidence is presented which suggests that a given JEV strain can change immunotype on repeated passage through mice.
The report summarizes a one year period of investigation of death losses in West Malaysian livestock. Lesions and etiological agents are mentioned for cattle, sheep, goats, swine, poultry and companion animals as well as some miscellaneous species. Special observations related to a common paramphistome induced hepatic biliary infestation in cattle, a serious malignant head catarrh outbreak in which possible cattle to cow aerosol transmission occurred. Trismus observed in some cattle with malignant head catarrh was associated with arteriolitis and ganglioneuritis of the V cranial nerve. Parasitic, bacterial, viral toxic and neoplastic diseases are recorded in the various species. The occurrence of fatal chronic fluorosis in laboratory guinea pigs and cerebral nematodiasis in a Thoroughbred racehorse are documented.
The effects of phentolamine and propranolol on contractural responses of guinea-pig superior mesenteric-portal vein to adrenaline and isoprenaline were investigated. Phentolamine was capable of completely abolishing the response to adrenaline and to isoprenaline while propranolol had no effect on responses to either agonist. It is suggested that Alpha receptors are the only type of adrenoceptor involved in adrenergic control of contraction of this vein and that isoprenaline is capable of stimulating these receptors.
The immunomodulatory effects of morphine and the active components of marijuana, particularly tetrahydrocannabinol, on various aspects of the host immune parameters include alterations in humoral, cell-mediated and innate immunity. Most studies have shown immunosuppressive effects due to use of these abused substances, although there are reports that they may not produce any deleterious effect and may even enhance some aspects of host immunity. They reduce resistance to cancer growth and microbial pathogens in animals.