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Present knowledge on reservoir hosts of Trypanosoma rhodesiense, T. gambiense and T. brucei in Africa and T. cruzi and T. rangeli in America and experimental transmission studies of T. cruzi in mammalian hosts and in lizards is discussed. The difficulty in differentiating the African species of human trypanosomes, which appear not to be host specific, is a major obstacle to epizootiological studies.

Repeated exposures of Australorbis glabratus of Venezuelan origin to miracidia of Schistosoma mansoni indicate that all members of a given group of snails eventually will become infected. It is concluded that resistance to infection with miracidia of Schistosoma mansoni is not developed by these snails. Studies on the infectivity of Schistosoma mansoni confirm previous reports on the susceptibility of the albino mouse and confirm the observation that gradual adaptation of human strains of Schistosoma mansoni to mice is unnecessary in order to infect them. Mice infected with female Schistosoma mansoni are not protected against subsequent exposures to cercariae of both sexes. A vaccine made from cercariae does not protect mice against a challenging dose of cercariae. When mice are exposed to cercariae of Schistosoma mansoni more than three times and if the intervals between exposures range from a week to a month, immunity develops that manifests itself by causing cessation of development of new larval worms. “Immunity” is used in the sense of “resistance” and refers to immunity acquired from a challenging dose and not to that derived from the already acquired infection. This does not eradicate the disease and the animal dies as rapidly as from a single infection. Re-exposure of two highly susceptible types of animals, the mouse and the hamster, and of two highly resistant types of animals, the guinea pig and the albino rat, after development of mature worms from an initial infection has taken place, results in the recovery of worms after the second exposure in the same percentage as after initial infections. Thus, no immunity is developed. Splenectomy in mice and rats does not affect the course of initial infections or reinfections. Failure of guinea pigs and rats to die after massive initial infection and reinfection evidently is caused by natural resistance, which produces destruction of eggs in the tissues and worms in the vessels. Of the two animals, the rat is more effective in this regard than the guinea pig. The mouse and the hamster lack this mechanism. Multiple re-exposures in guinea pigs and rats produce no indication of immunity but the process of destruction of eggs and worms continues throughout the life of the animals. This process saves their lives but it is not a reflection of acquired immunity.

My partners in this research, Dr Honor B. Fell of the Strangeways Research Laboratory, Cambridge, and Dr V. E. Cosslett of the Cavendish Laboratory, Cambridge, appreciate with me this opportunity to report on experiments which we have made jointly in order to examine certain problems in the mechanism of tuberculous infection, which hitherto have resisted the single-handed attempts of pathologists unaided by research workers of other branches of Science. I consider myself very fortunate that Professor Boyd is in the Chair, because I shall take the text of my lecture from his 'Textbook of Pathology', where he gives a most concise description of one of the crucial problems in tuberculous infection: 'The epithelioid cell may be regarded as a large mononuclear which has partially digested tubercle bacilli, and its distinctive cytoplasmic state seems to be the result of destruction of many bacilli with progressive emulsification of their lipoid (Long, Lurie). It is evident that by the time the mononuclears have become transformed into epithelioid cells the bacilli have undergone extensive destruction. This explains the difficulty which is experienced in demonstrating bacilli in the ordinary type of lesion in man, in which they are few and far between and may only be found after prolonged search, although in acute fulminating lesions such as tuberculous caseous pneumonia they may be present in great numbers. The mononudears do not always have the power of destroying the bacilli which they engulf. Thus, in the rat the bacilli thrive and multiply within the phagocytes, and the latter also multiply with the remorselessness of a malignant growth, until finally the animal succumbs to the cellular accumulation.' With these words the ambiguous nature of the phenomenon known as 'Phagocytosis' is expressed as far as the mononuclear macrophages the mother cells of the epithelioid t u b e r c l e a r e concerned. There are two

Experimental pneumonia was produced with a highly virulent strain of type III pneumococcus which synthesizes, during rapid growth, large amounts of capsular polysaccharide. The type III pneumonia differed from that caused by pneumococcus I in that (a) death occurred more promptly in the type III infection, (b) the local pulmonary lesion became more heavily infected, and (c) frank suppuration was common even after otherwise effective chemotherapy. The greater pathogenicity of the type III organism was shown by special histologic techniques to be due primarily to its capsular slime layer which interferes with surface phagocytosis. Capsular polysaccharide shed from the organism during growth was also demonstrated in high concentration in certain parts of the pneumonic lesion. Removal of the excess polysaccharide from the alveoli resulted from (a) lymphatic drainage to regional lymph nodes and (b) phagocytosis, particularly by macrophages. The possible relationship of the free carbohydrate to the malignancy and the characteristically viscous exudate of type III pneumonia was discussed. The lung abscesses which resulted from type III infection were observed to occur in those areas in which the maximum number of organisms had accumulated. Evidence was obtained that suppuration was due, not to necrotoxic products peculiar to the type III pneumococcus, but rather to the survival of large numbers of bacteria in the tissues, brought about primarily by the antiphagocytic effect of the slime layer. When pneumonia was produced with an intermediate type III mutant lacking the protective slime layer, back mutation to the mucoid parent occurred during the course of the infection, and the mucoid form eventually predominated in the lung as a result of selective phagocytosis of the intermediate organisms. Similar mutation to the maximally virulent type III form was noted with a transformed intermediate type III strain grown from single cell preparations.

1. The suckling 10-day-old mouse harboured fewer worms than the weanling 15-day-old mouse after both 5 and 10 days' infection.2. The adult male mouse, however, harboured significantly more worms when fed on milk than when fed on rat cake after both 5 and 10 days' infection.3. These results were discussed in relation to the effects of diet and gut length on the susceptibility of the host.This work was done during the tenure of a Department of Scientific and Industrial Research Studentship. My thanks are due to Dr E. T. B. Francis for his helpful and critical supervision, and to Professor I. Chester Jones, in whose department the work was done, for the facilities he provided.

The study compares parasite prevalence in two geographically separated populations of white-tailed deer in central Pennsylvania. Differences in prevalence were found for certain of the parasites studied. Characteristics of curves comparing prevalence with host-age group, however, were remarkably similar for individual parasites from both populations. Prevalence increased with host age for certain species of parasite and decreased or remained constant for others. Some of the underlying biological properties of the infections which may be responsible for the characteristics of the age specific prevalence curves are discussed.

The studies presented in this paper describe the effects of control exerted by the immunological response of the host (sheep) on the developmental stages and fecundity of the parasite Nematodirus spathiger. Thirty Merino lambs, maintained worm-free, were randomly divided among three treatment groups each containing ten animals. The group 1 lambs were each given a single dose of 50,000 infective larvae, the group 2 animals were given a single dose of 130,000 infective larvae, and the group 3 animals were given twenty-five consecutive daily doses of 2000 infective larvae. Group fecundity was estimated by performing worm egg counts on daily faecal samples and development of the parasite burden was followed by carrying out differential worm counts on animals slaughtered at crucial stages during the infections. Total fecundity was greatest in group 1 and least in group 3 with group 2 intermediate. An inverse relationship between total fecundity and percentage retardation of development (percentage of 4th-stage larvae in the total worm burden) was demonstrated between the three treatment groups.The results of the studies also show that control of the parasitic infection is mediated about threshold levels of immunological responsiveness and is expressed by (1) elimination at the infective (L3) stage, (2) retardation of development at the L4 stage, (3) reduction in egg production of the adult female, (4) elimination of adult worms, and (5) discrimination against the female in both the degree of retardation in the L4 stage and the extent of elimination in the adult stage.Great variation in response was observed between individuals within treatment groups. The source of variation is attributed to differences in degree of antigenic disparity of the parasite with individual members of the heterozygous host population in which antigenic characters are not uniformly segregated.The concept of ‘fitness’ of the parasitic species was introduced into the discussion to provide a rational interpretation of the results.We are indebted to Dr S. S. Y. Young, Division of Animal Genetics, C.S.I.R.O., for advice and assistance with the statistical analyses, which were performed by Mrs M. Tonkin, and to Dr D. F. Stewart for his constructive criticism of the manuscript. Careful technical assistance was given by Mr E. Teleki and Misses Helen Giller and Berenice Merchant.

Morello, Josephine A. (Boston University School of Medicine, Boston, Mass.), Teresa A. DiGenio, and Edgar E. Baker . Significance of salmonellae isolated from apparently healthy mice. J. Bacteriol. 89: 1460–1464. 1965.—Three species of Salmonella were isolated from three groups of apparently healthy laboratory mice. The host-parasite relationship of one of these, a mutant S. typhimurium (lacks I and i antigens), was studied to determine the significance of these pathogens. Mice were fed undiluted broth cultures, and the infection was followed by means of fecal and organ cultures and a hemolytic serological test. Tissue invasion occurred during the early stages of the disease, but, within 1 week, the organism usually was localized in the intestinal tract. After 1 month, most of the mice had eliminated the organism completely. Antibody response to this organism was generally variable. Conditions of stress, including heat, cold, and cortisone administration, did not precipitate more severe disease in infected animals. The infection was maintained for longer periods of time in animals housed in groups than in those in individual cages. The presence of such salmonellae in laboratory animals appears to be of limited significance.

1. The following new species were encountered in this investigation:Haemogregarina hamata in Lacerta jacksoni;Hepatozoon minchini in Crotaphopeltis degeniPirhaemocyton granosa in Agama colonorumAtoxoplasma argyae n.gen. n.sp. in Argya rubi-ginosaSpirochaeta harveyi in Cercopithecus aethiops.2. Further information is given in regard to the following known species, including new host records:Plasmodium pitmani in Mabuia striata and M. maculilabrisTrypanosoma martini in Mabuia maculilabrisPlasmodium vaughani in Othyphantes reichenowiPlasmodium relictum in Othyphantes reichenowi and Passer iagoensisHaemoproteus wenyoni in Passer griseusLeucocytozoon sp. in nine species of birdsHepatocystes epomophori in Epomophorus labiatusHepatocystes kochi in Cercopithecus, etc.Babesia pitheci in Cercopithecus mitis.3. Exo-erythrocytic schizogony is described in Plasmodium pitmani of the skink (from spleen and heart preparations).

The techniques of infrared spectrophotometry, paper electrophoresis and paper chromatography applied to whole and fractionated tissues of cestodes are used to show: 1. 1. Fixed samples of the laminated membrane of E. granulosus , of the cyst wall of T. hydatigena and of the coenurus M. multiceps give infrared spectra which have readily distinguishable, species-characteristic features. 2. 2. A mucopolysaccharide, with a characteristic infrared spectrum and containing only galactose and glucosamine as the sugar units, can be isolated by a number of methods from the laminated membrane, the scolices and the cyst fluid of E. granulosus . The electrophoretic mobility of the mucopolysaccharide isolated from the laminated membrane or the cyst fluid is, however, quite different from that isolated from the scolices. 3. 3. Evidence is presented that the mucopolysaccharide isolated constitutes the principal structural material of the laminated membrane of hydatid cysts. It may be produced in the scolices prior to incorporation into the non-living laminated membrane. 4. 4. Glycogen is observed by infrared spectrophotometry, electrophoresis, chromatography and histochemical analysis to be present in the larval scolices, in the cyst fluid and in the adult tapeworms of E. granulosus . These same techniques, when applied to the laminated membrane, give negative tests for glycogen. 5. 5. Extracts of lipide materials from the scolices and from the laminated membrane give infrared spectra characteristic of lecithin, in association with a variable fraction of cholesterol. 6. 6. The antigen of Dennis is shown to be a relatively pure protein.

1. It has been shown that there is a difference between the resistance of male and female mice to infection withNematospiroides dubius.2. More parasites were harboured, during both the larval and adult parasitic phases, by male mice.3. These worms were found to occupy a similar relative length of the intestine between the stomach and the caecum in male and female mice infected for either 5 or 10 days.4. The relative length of the intestine infected on the fifth day was significantly greater than that infected on the tenth day.This investigation was carried out during the tenure of a Research Studentship from the Department of Scientific and Industrial Research. I should like to thank Professor I. Chester Jones, in whose department the work was done, for the facilities provided and Dr E. T. B. Francis for his helpful and critical supervision.

Willoughby, Donald S. (University of Minnesota, Minneapolis), and Dennis W. Watson . Host-parasite relationships among group A streptococci. II. Influence of sex on the susceptibility of inbred mice toward streptococcal infection. J. Bacteriol. 87: 1457–1461. 1964—BALB/Sy mice showed marked sex differences in susceptibility to a strain of Streptococcus pyogenes type 18. Castration of the highly susceptible normal adult male increased their resistance 1,000-fold, which approximated that of normal female mice. Treatment of male mice with estrogen and stilbestrol did not affect their resistance significantly. Young, sexually immature male mice, 4 weeks old, were more resistant than mature males. Susceptibility of the resistant females was not affected by age or bilateral ovariectomy, but testosterone injections caused an increase in susceptibility. Treatment of male mice with estrogen and stilbestrol did not modify their resistance. Smears of peritoneal exudates from normal male mice after intraperitoneal injection of streptococci revealed rapid multiplication of the organisms. There was no evidence of multiplication in the resistant normal female and castrated male mice.

The present studies were designed to characterize the response of sheep infected with N. spathiger to challenge infection with the same species.The results showed that: (1) the level of worm counts attained on secondary infection with the parasite was much reduced compared with the counts recorded following initial infection; (2) the relative fecundities of parasite populations which developed in individual hosts following challenge infection, ranked in magnitude in an order which was similar to that established following initial infection; (3) as fecundity was highly correlated with the number of egg-laying females and the number of males and females was nearly equal in individual specimens, it was concluded that worm burdens were also ranked for individual animals on primary infection and following challenge; and (4) the animals of the control group remained as susceptible as the animals of groups 1 and 3 at the time of their primary infection; consequently, in the absence of previous immunological experience due to infection, there was no apparent change in susceptibility of the animals due to an effect of age during the course of the 17 weeks of the experiment.We are greatly indebted to Dr Michael Tallis, Division of Mathematical Statistics, C.S.I.R.O., for advice and assistance with the statistical analyses, and to Dr D. F. Stewart for his interest and constructive criticism during the course of these studies. Our thanks are also due to Mr E. Teleki and Misses Helen Giller and Lindy Stothart for their valuable technical assistance.

1. (1) A specific acetylcholinesterase is present in homogenates of hydatid scolices and brood capsules of Echinococcus granulosus . The rate of hydrolysis of acetylcholine is 45 times that of butyrycholine. Enzyme activity is partially inhibited by physostigmine and hexaethyltetraphosphate (HETP). 2. (2) The reducing substance (“glucose”) contents of fluids of 22 hydatid cysts of the bovine lung ranged from 9·2–102·5 mg per cent, of 24 cysts of the bovine liver, from 13·9–101·1 mg per cent. The cyst fluid “glucose” level is higher in cysts from sheep than in cysts from cattle. 3. (3)In hydatid daughter cysts suspended in isotonic Krebs-Ringer's solution for 4 hr, the outward passage of “glucose” occurs very slowly. Passage is accelerated by the addition of small amounts of certain acetylcholinesterase inhibitors to the suspending solution and markedly by the addition of both HETP and either choline or acetylcholine. 4. (4) Accelerated outward passage of “glucose” also occurs when daugther cysts are suspended in hypotonic salt solutions of 0.04 M concentration or less. 5. (5) The weight changes of hydatid daughter cysts suspended in a variety of salt solutions of from 0·039 M to 0·616 M for 2·5 hr are slow, regular and predictable. In solutions similar chemically but more hypotonic, permeability control in the cyst wall appears to break down following a period of water imbibition at the expected rate. Acetylcholine chloride (0·01 M) maintains permeability control to a greater degree than does NaCl at the same molar concentration. 6. (6) Hydatid daughter cysts lose weight more rapidly when suspended in a hypertonic glucose-saline solution for 3 hr than they do in the same glucose-saline which contains small amounts of acetylcholinesterase inhibitors. 7. (7) Extracts of hydatid cyst fluid and hydatid tissues contian one or more unidentified quaternary ammonium compounds.