Infections by the protozoan parasite Toxoplasma gondii are widely prevalent world-wide in animals and humans. This paper reviews the life cycle; the structure of tachyzoites, bradyzoites, oocysts, sporocysts, sporozoites and enteroepithelial stages of T. gondii; and the mode of penetration of T. gondii. The review provides a detailed account of the biology of tissue cysts and bradyzoites including in vivo and in vitro development, methods of separation from host tissue, tissue cyst rupture, and relapse. The mechanism of in vivo and in vitro stage conversion from sporozoites to tachyzoites to bradyzoites and from bradyzoites to tachyzoites to bradyzoites is also discussed.

Structures of Toxoplasma gondii Tachyzoites, Bradyzoites, and Sporozoites and Biology and Development of Tissue Cysts

In an effort to unify the nomenclature of Trypanosoma cruzi, the causative agent of Chagas disease, an updated system was agreed upon at the Second Satellite Meeting. A consensus was reached that T. cruzi strains should be referred to by six discrete typing units (T. cruzi I-VI). The goal of a unified nomenclature is to improve communication within the scientific community involved in T. cruzi research. The justification and implications will be presented in a subsequent detailed report.

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A new consensus for Trypanosoma cruzi intraspecific nomenclature: second revision meeting recommends TcI to TcVI.

Recent epidemiologic studies indicate that leishmaniasis in the Americas is far more abundant and of greater public health importance than was previously recognized. The disease in the New World is caused by a number of different parasite species that are capable of producing a wide variety of clinical manifestations. The outcome of leishmanial infection in humans is largely dependent on the immune responsiveness of the host and the virulence of the infecting parasite strain. This article reviews current concepts of the clinical forms, immunology, pathology, laboratory diagnosis, and treatment of the disease as well as aspects of its epidemiology and control. Recommendations for future research on the disease and its control are made.

Leishmaniases of the New World: current concepts and implications for future research.

Lipids of the insect cuticle: origin, composition and function

DNA markers define two major phylogenetic lineages of Trypanosoma cruzi

CHAGAS' disease, in which the aetiological agent is Trypanosoma cruzi, is a principal cause of morbidity and mortality on the South American continent; at least 10 million people are said to be infected1. There is no vaccine or acceptable chemotherapy2, and insecticide control of domiciliated triatomine vectors (Hemiptera, Reduviidae) remains problematical. Human survivors of the acute phase of infection commonly develop electrocardiographic abnormalities, chronic cardiomyopathy and singular chagasic syndromes consisting of cardiomegaly, megacolon and megaoesophagus. T. cruzi from diverse mammals and vectors are morphologically indistinguishable3, and are prudently treated as a single entity pathogenic to man. However, heterogeneity has been suspected4 from behaviour in experimental hosts, discordant therapeutic trials, and, most notably, from both the enigmatic, disparate geographical distribution of chagasic syndromes among infected populations5 and the different descriptions of the pathogenesis of the heart disease6,7. By means of enzyme electrophoresis, we show here, for the first time, the heterogeneity of T. cruzi infecting man.

Isozymic heterogeneity of Trypanosoma cruzi in the first autochthonous patients with Chagas' disease in Amazonian Brazil.

1. 1) During a 3-year study on the epidemiology of dermal leishmaniasis in British Honduras, about 150 human cases were seen among which 46 were examined in detail. The parasite, Leishmania mexicana , was isolated in NNN cultures in 27 instances. 2. 2) Race, sex, age and physical condition of the individual appear to have little bearing on the susceptibility of human beings to the disease which is strictly sylvatic in origin and principally restricted to chicleros, mahogany hunters, and other forest workers. 3. 3) The disease is almost always limited to a single dermal lesion. No evidence could be found of any cutaneous spread of infection or visceral involvement. The ear is the most commonly affected part of the body (40 per cent. of the 50 lesions studied), but the hands and arms are also frequently involved (28 per cent.). Lesions on the torso and legs are uncommon. This differential distribution of lesions is thought due to a combination of at least three main factors: firstly the head and arms are the most frequently exposed parts of the body, secondly there is a marked tendency for body lesions to heal spontaneously, and finally L. mexicana appears to proliferate more readily in ear tissue than in that of other parts of the body. 4. 4) Development of the human lesion is described from a study of experimental insect transmission by Phlebotomus , natural infections of known duration and syringe-induced infections in volunteers. The incubation period following the introduction of leptomonads into the skin varied from 2 to 4 weeks. An account of the histology of the developing lesion is given. 5. 5) Three men with infections of short duration resisted attempts to super-infect them with massive intradermal inoculations of leptomonads of L. mexicana . This early premunition contrasts with the much more slowly developed immunity in the case of L. tropica infection. 6. 6) The culture of material from lesions in NNN medium proved the most reliable method of diagnosis. Hamsters and white mice are readily infected both with leptomonads from cultures and L.D. bodies taken directly from human lesions. In one instance the Montenegro skin-test was shown to give equally good reactions with antigens prepared from leptomonads of L. mexicana and L. tropica . 7. 7) Three human volunteers were readily infected with strains of L. mexicana isolated from the wild forest rodents, Ototylomys, Nyctomys and Heteromys species. 8. 8) Sixteen human cases of “Bay-Sore” were successfully treated with Stibophen (pentasodium antimony-biscatechol-3: 5-disulphonate). 9. 9) The medical and economic importance of dermal leishmaniasis in British Honduras is discussed. Two-thirds of the Colony is still under forest from which the main natural resources of chicle, timber and some agricultural products are derived, and one-third of the working population is employed in forest work of some kind. As we have clearly indicated dermal leishmaniasis in British Honduras to be a zoonosis, with the infected animals acting as reservoirs for the human disease, it follows that a large proportion of the population will remain constantly exposed to infection.

Leishmania mexicana: The epidemiology of dermal leishmaniasis in British Honduras

1. 1) Dermal leishmaniasis (“Bay-sore”) in British Honduras is restricted to people who penetrate the forested regions. This suggests the disease to be a zoonosis, with wild animals acting as a source of infection for man. 2. 2) A variety of wild and laboratory animals were tested for susceptibility to Leishmania mexicana in attempts to indicate potential reservoir-hosts. Of the wild animals, only the cotton-rat (Sigmodon hispidus) was readily infected. Among laboratory animals the most susceptible were hamsters, mice, gerbils and rats, in that order. It was concluded, therefore, that the reservoir-hosts of L. mexicana would best be sought among the sub-Order Myomorpha of the Order Rodentia. 3. 3) A focus of infection in the forest was pin-pointed by the isolation of L. mexicana from a batch of sand-flies trapped in a selected area. About 300 insects were triturated together in Locke's solution and inoculated into the skin of a hamster. A lesion containing LD bodies developed at the inoculation site. 4. 4) L. mexicana was isolated from three different species of forest rodents trapped in this same area: the incidence of infection was as follows: The “tree-rat”, Ototylomys phyllotis Merriam (Cricetidae, Rodentia), eight of 20 (40 per cent.) examined. The “spiny-pocket-mouse”, Heteromys desmarestianus Gray (Heteromyidae, Rodentia), six of 58 (10.34 per cent.). The “vesper-rat”, Nyctomys sumichrasti Saussure (Cricetidae, Rodentia), one of eight (12.5 per cent.). No infections could be found in a variety of other mammalian species from this and other areas of the forest. 5. 5) Infection of the reservoir-hosts appeared to be purely cutaneous and restricted to lesions on the tails. Abundant LD bodies were usually evident in stained smears from such lesions and the histology of the lesions is described. 6. 6) In all respects the strains of L. mexicana from the three rodent species appear identical with the parasite causing the human disease. Leptomonads inoculated into human volunteers produced long-lasting, cutaneous lesions containing abundant LD bodies. 7. 7) It is concluded that dermal leishmaniasis in British Honduras is a zoonosis. L. mexicana is primarily a parasite of forest rodents among which Ototylomys phyllotis, Heteromys desmarestianus and Nyctomys sumichrasti figure prominently. Other rodent species are probably also involved. Man is to be regarded as an accidental host. 8. 8) Evidence is presented to indicate that transmission among the wild animals, and to man, is by the agency of Phlebotomus species biting at ground level. 9. 9) The need is indicated for further research on the distribution and life histories of the reservoir-hosts throughout the forests. In particular a study must be made of their nesting habits to determine the possibility of a specific Phlebotomus—rodent association within the nests. 10. 10) The significance of the present findings is discussed with regard to cutaneous leishmaniasis in other parts of Central and South America. Similar investigations should be made on the epidemiology of muco-cutaneous leishmaniasis, due to L. braziliensis. There are a number of apparently distinct clinical forms of cutaneous and muco-cutaneous leishmaniasis in the New World. The possibility is considered that these might be due to infection of man with different leishmanial parasites which are normally found in different wild animal hosts.

The epidemiology of dermal leishmaniasis in British Honduras: Part II. Reservoir-hosts of Leishmania mexicana among the forest rodents

1. 1) Various opinions as to the mode of reproduction of Toxoplasma have been discussed. The general opinion exists that schizogony does not form part of the organism's life cycle as we know it, but there is considerable confusion regarding the nature of the membrane which is frequently to be demonstrated about masses of toxoplasms. Particularly confusing is the loose use of such terms as “pseudocyst” and “cyst” by many authors to describe almost any aggregation of toxoplasms in both acute and chronic infections. 2. 2) The behaviour of toxoplasms of three different, highly virulent strains was studied in mice, guinea-pigs, multi-mammate rats and canaries : no evidence of schizogonic division of Toxoplasma was seen in the study of the parasites in a wide variety of tissues from different animals at all stages of the acute disease. The sole mode of reproduction appears to be by longitudinal binary fission. On no occasion was any structure other than the membrane of the enclosing host cell seen to surround the masses of parasites in any tissue and at any stage of the acute infection. During such infections the host-cell membrane of heavily parasitized cells undergoes no apparent modification other than extreme stretching ; the resulting mass of parasites is essentially of a temporary nature and soon breaks down to liberate the toxoplasms. 3. 3) A study was made of the behaviour of Toxoplasma in asymptomatic, chronic infections using 11 strains of negligible pathogenicity in mice, rabbits and one young dog. There is an initial, low grade proliferation of the parasites (acute infection) — particularly within the cells of the lymphoid-macrophage system (e.g. peritoneal exudate). This phase is soon replaced by a much more prolonged period of binary fission in the deeper tissues. It is characterized by the formation of a highly elastic, tough membrane about the parasites and this was shown to be distinctly separate from that of any enclosing host cell. The resulting structures may persist in the host tissues for at least 5 years and probably longer. Their development was studied from the 8th day of infection up to 102 months in the central nervous system of mice and rabbits : similar bodies were studied in the lungs of mice and rabbits where their development was a constant feature of the chronic infection.They were sometimes found in the lumen of alveoli and bronchioles and were demonstrated in the lungs of a chronically infected dog. 4. 4) The terms “cyst” and “pseudocyst” are defined : evidence is offered to suggest that true cysts of Toxoplasma are produced in the chronic disease as distinct from the pseudocysts associated with the acute infection. 5. 5) The significance of the invariable presence of these cysts in association with the natural type of Toxoplasma infection (the chronic infection) is discussed — in particular the presence of the cysts in the lungs. It is suggested that they may play an important role in the natural transfer of the parasite from host to host.

Observations on the development and nature of pseudocysts and cysts of Toxoplasma gondii.

SYNOPSIS. All of 99 adult English house-sparrows, examined in the St. Albans area of Hertfordshire, England, were found to be infected with the organism previously defined by Garnham (1950) as Atoxoplasma. Young birds were found to become infected while still in the nests and as early as 6 days after hatching; there was no evidence to suggest that the parasite was transmitted through the egg. Within a few weeks of leaving the nests, all of 150 fledgling sparrows examined were heavily infected and several trapped birds died from massive infections.

All stages of schizogony were found in the lymphoid-macrophage cells of the spleen, bone marrow and liver of these birds; later, as the schizogonic cycle abated, gametocytes developed in similar cells of the liver, lungs and kidney. These gametocytes are of the Eimeria type: the zygote nucleus divides to produce an asporous and polyzoic oocyst containing a large number of sporozoites, and after the rupture of the oocyst these sporozoites invade the lymphocytes and monocytes of the peripheral blood.

Transmission of the parasite in the sparrow is thought to take place after the ingestion of infected mites (Dermanyssus gallinae) by the young birds in the nests: unchanged sporozoites were found in smears of these mites that had been fed on infected sparrows. Transmission experiments were impossible due to the complete lack of clean sparrows.

The taxonomic status of Atoxoplasma is discussed. The type of life cycle and the production of asporous, polyzoic oocysts indicate inclusion of this parasite in the Order Coccidiida, Family Eimeriidae, Sub-Family Cryptosporidiinae Hoare, 1933. After comparison of the two genera, the author concludes that Atoxoplasma must be regarded as a synonym for Lankesterella. Some previously described species of Atoxoplasma are, therefore, transferred to the genus Lankesterella.

The name Lankesterella garnhami nov. sp., is proposed for the parasite in the English sparrow (Passer domesticus domesticus), and Lankesterella serini nov. sp., for that in the canary (Serinus canarius).

Ralph Lainson

Papers

Isozymic heterogeneity of Trypanosoma cruzi in the first autochthonous patients with Chagas' disease in Amazonian Brazil.

Leishmania mexicana: The epidemiology of dermal leishmaniasis in British Honduras

The epidemiology of dermal leishmaniasis in British Honduras: Part II. Reservoir-hosts of Leishmania mexicana among the forest rodents

Observations on the development and nature of pseudocysts and cysts of Toxoplasma gondii.

Atoxoplasma Garnham, 1950, as a synonym for Lankesterella Labbé, 1899. Its life cycle in the English sparrow (Passer domesticus domesticus, Linn.)