Toxoplasma Gondii

Synonyms: Toxoplasma cuniculi, T. caviae, T. canis, T. musculi, T. ratti, T. laidlawi, T. sciuri, T. pyrogenes, T. hominis.

Disease: Toxoplasmosis.

Hosts: T. gondii was first found in the gondi (Ctenodactylus gondi), a North African rodent, but it has since been found in many species of mammals and birds. Its host list includes the gondi, house mouse, Norway, black, climbing and water rats, squirrel, ground squirrel, vole, guinea pig, chinchilla, marmot, the Chilean rodent, Octodon degus, the Uruguayan rodent, Ctenomys torquatus, rabbit, hare, mole, shrew, hedgehog, dog, cat, fox, weasel, ferret, mink, wombat, bandicoot, brushtail possum, marsupial rat, pig, sheep, ox, baboon, chimpanzee, macaque (Macaca tantala), whiteface monkey (Cebus capucinus), cotton-topped marmoset (Oedipomidas oedipus), squirrel monkey (Saimiri sciurea), man, pigeon, chicken, crow, canary, penguin and partridge (Perdrix perdrix) (Ratcliffe and Worth, 1951; Christen and Thiermann, 1953; Talice, Perez-Moreira and Mossera, 1954; Jacobs, 1956; Finlay and Manwell, 1956; Van den Akker, Bool and Spitseshuis, 1959; Cook and Pope, 1959; Benirschke and Richart, 1960). In addition, organisms which resemble Toxoplasma morphologically have been seen in reptiles; and turtles, lizards, geckos and chameleons can be infected experimentally (Jacobs, 1956). On the other hand, most of the organisms reported as Toxoplasma from the blood of various wild birds are probably Lankesterella.

Location: Toxoplasma is an intracellular parasite of many types of cells, including neurons, microglia, endothelium, reticulum, liver parenchyma cells, lung and glandular epithelial cells, cardiac and skeletal muscle cells, fetal membranes and leucocytes. In acute infections, the parasites may be found free in the blood and peritoneal exudate.

Geographic Distribution: Worldwide.


Toxoplasmiasis is apparently extremely common in man and also in many domestic animals. As Jacobs (1956) said, there is a sea of Toxoplasma infection around us. However, toxoplasmosis is far less common. Most infections are inapparent, and the disease itself appears only under special circumstances, many of which are still unknown.

Most of the surveys which have been made for Toxoplasma have been serologic and indicate either previous or present infections. In some cases, particularly in sheep and other domestic animals in which Sarcocystis infection is common and in which the Sabin-Feldman dye test was used, they may indicate merely the presence of cross-reacting antibodies (Muhlpfordt, 1951; Awad, 1954; Awad and Lainson, 1954). Hence surveys in which the organism itself was isolated are more reliable, altho much more time-consuming and expensive.

The prevalence of antibodies varies widely in man in different geographic locations. For instance, according to Jacobs (1957), there is relatively less infection in California than in the eastern United States. Feldman and Miller (1956a) observed positive dye tests in 68% of 121 persons on Tahiti, 64% of 266 in Honduras, 36% of 104 in Haiti, 35% of 144 in Pittsburgh, Penn., 31% of 270 in New Orleans, 26% of 184 in St. Louis, 17% of 293 in Portland, Ore., 11% of 108 on Iceland, 4% of 236 Navajo Indians in Arizona, and none of 21 Eskimos in Alaska. In a study of 1072 urban and rural Negroes 11 to 19 years old in the region of Memphis, Tennessee, Gibson (1956) found that the Sabin-Feldman dye test was positive in 20.4% of the urban and 18.9% of the rural group. Balozet (1955) found that 12% of 125 humans in Algiers were positive to the complement fixation test. Thiermann and Naquira (1958) found that the dye test was positive in 43% and the complement fixation test in 11% of 284 normal medical students in Santiago, Chile; the dye test was positive in 48% and the complement fixation test in 2% of 131 blood donors, mostly over 30 years old. Orio et al. (1957) found that the sera of 10.2% of 1139 Africans in Middle Congo were positive to the complement fixation test. The above results give some idea of the range of positive reactions which may be expected in different surveys.

Among domestic animals, the first spontaneous case of toxoplasmosis in the dog was reported by Mello (1910) in Turin, Italy. In reviewing the animal reservoir of toxoplasmosis, Habegger (1953) stated that only something more than 50 cases had been reported in dogs thruout the world. However, more recent reports have raised this figure considerably.

Miller and Feldman (1953) found dye test antibodies in 59% of 51 dogs in Pennsylvania. Feldman and Miller (1956a) found them in 28% of 51 dogs from New York, 30% of 23 dogs from Arizona and 86% of 7 dogs from Honduras. Siim (1950) found that 18.5% of 54 dogs in Copenhagen had dye test titers of 1:250 or more. Otten, Westphal and Kajahn (1950) found that 36% of 84 dogs in Hamburg, Germany were positive to the dye test. Borgen and Berg (1957)found that 44.5% of 20 dogs in Norway were positive to the dye test. De Roever-Bonnet (1957) found that 1 of 75 dogs in Amsterdam was positive to the dye test at a titer above 1:100. Makstenieks and Verlinde (1957) found that 14% of 29 dogs from households in the Netherlands where human toxoplasmosis existed were positive to the dye test at 1:64 or above. Eyles et al. (1959) found that 8.3% of 809 dogs from the Memphis pound or slums were positive to the dye test at a titer of 1:64 or above, and they isolated Toxoplasma by mouse inoculation from 3 of 200 of the dogs. Gibson and Jumper (1960) found that the sera of 16% of 800 dogs from the Memphis pound were positive to the dye test at a titer of 1:16 or above; they found Toxoplasma by mouse inoculation in only 2 out of 75 of these animals.

Morris, Aulisio and McCown (1956) found that 25% of 180 dogs in the Middle Atlantic stages were positive to the complement fixation test. Lainson (1956) found that 42.5% of 113 dogs in London were positive to the complement fixation test. Balozet (1955) found that 30% of 104 pound dogs in Algiers were positive to the complement fixation testa

In the United States, Cole et al. (1953) described an outbreak of toxoplasmosis in a kennel of 104 dachshunds, in which 69 pups and 17 adults (of which 14 were bitches) died. In another outbreak in a kennel of 47 chihuahuas, 14 pups and 15 adults died. They also found toxoplasmosis in 11 pet dogs, each owned by a different family. Langham and Sholl (1949) reported a case in a young fox terrier in Michigan. Moulton and Linton (1953) reported a fatal canine case in California. Krause (1954) found Toxoplasma in 1 out of 30 dogs by inoculating mice with brain tissue. Seibold and Hoerlein (1955) reported a case of renal toxoplasmosis associated with distemper in a puppy.

Hulland (1956) described 8 fatal cases of canine toxoplasmosis in Canada. Wickham and Carne (1950) reported 3 cases in Australia. Grocott (1950) reported a case from the Canal Zone. Sjolte (1948) reported the first case of canine toxoplasmosis in Denmark. Fankhauser (1950, 1951) found it in 6 dogs in Switzerland. Kardevan and Kapp (1957) found Toxoplasma in 2 of 20 dogs in Hungary. Bonser (1950) described a case of toxoplasmatal intussusception in a 3-year-old bitch in England. Campbell, Martin and Gordon (1955) found it by histological examination in 6% of 268 dogs in Glasgow, Scotland. Flir (1954) described 3 cases in dogs in Germany. Van den Akker, Bool and Spitseshuis (1959) found it in a dog in Holland. Blanc and Hintermann (1948) reported it in a dog in Morocco. Orio et al. (1959) found Toxoplasma in a dog in Brazzaville, Middle Congo.

Toxoplasmosis has been reported in single cats by Wickham and Carne (1950) in Australia, Holzworth (1954) in Massachusetts, Jones (1955) in the U.S. and Hulland (1956) in Canada. Jones, Eyles and Gibson (1957) found T. gondii by mouse inoculation in 24% of 140 cats in Memphis, Tennessee, and in 11% of 35 cats in Columbia, South Carolina. They reviewed the literature on isolation of Toxoplasma from the cat; theirs was the tenth report. Gibson and Eyles (1957) found T. gondii by mouse inoculation of brain tissue in 20% of 35 cats from the neighborhood of a house in Memphis where a newborn child had died of congenital toxoplasmosis.

Feldman and Miller (1956a) found that 33% of 79 cats from Massachusetts and New York were positive to the dye test for Toxoplasma. Makstenieks and Verlinde (1957) found that 15% of 33 cats from households in the Netherlands where human toxoplasmosis existed were positive to the dye test at a titer of 1:64 or above. Havlik and Hubner (1959) found that 34% of 200 cats in central Bohemia were positive to the dye test at a titer of 1:16 or above; they isolated Toxoplasma by mouse inoculation from 2 out of 23 of the positive cats.

The first cases of toxoplasmosis in swine were reported by Farrell et al. (1952) in Ohio. They found the disease in 8 pigs from a farm where an undiagnosed disease had recurred for many years. Sanger and Cole (1955) isolated T. gondii from 2 newborn pigs collected aseptically from the vagina as well as from the milk and heart of a naturally infected sow which showed no signs of disease. They also isolated Toxoplasma from the milk and from 3 of 4 pigs from another apparently healthy, naturally infected sow. Momberg-Jorgensen (1956) isolated Toxoplasma from a litter of 8-day-old pigs in Norway, 6 of which had died of pneumonia, enteritis, hepatitis, nephritis and splenitis; he also found Toxoplasma in tissue sections of some 18-day-old pigs that had died of a similar pneumonia.

In a serologic survey of hog sera from a slaughterhouse in New Haven, Conn., Weinman and Chandler (1956) found that 42% of 88 sera were positive to the dye test. Most of the positive pigs were from one farm where the pigs were fed uncooked garbage. Feldman and Miller (1956a) found that 30% of 73 pigs from the midwest and New York were positive to the dye test. De Roever-Bonnet (1957) found that 12% of 25 hogs from an Amsterdam slaughterhouse were positive to the dye test at a titer above 1:1000. Eyles et al. (1959) found that 2% of 178 pigs from Memphis, Tenn. slaughterhouses were positive to the dye test at a titer of 1:64 or above, and isolated Toxoplasma by mouse inoculation from 1 out of 129 of them. By inoculation of mice with peptic digests of diaphragm samples, Jacobs, Remington and Melton (1960a) found Toxoplasma infection in 24% of 50 pigs from a Baltimore slaughterhouse.

Toxoplasmosis was first reported from sheep by Olafson and Monlux (1942) in New York. It was later found in sheep in Australia by Wickham and Carne (1950) and Osborne (1959), in Ohio by Cole et al. (1954) in New Zealand by Hartley and Marshall (1957), and in England by Beverley and Watson (1959). It was associated with abortions and perinatal mortality in the last 4 reports; indeed, Hartley and Marshall considered toxoplasmosis to be the most wide-spread and probably the most important cause of ovine perinatal mortality in New Zealand. It may be important in England, too; Beverley and Watson (1959) found it in 6 of 39 aborted lambs from a number of flocks in that country, and found dye test titers of 1:128 or above in 43 of 549 ewes from 93 flocks, including 22 of 158 ewes which had aborted from causes other than viral or bacterial.

Feldman and Miller (1956a) found that 5% of 66 sheep from Arizona, 56% of 9 sheep from Kentucky and 43% of 65 goats from New York were positive to the dye test for Toxoplasma. De Roever-Bonnet (1957) found that 35% of 23 sheep from an Amsterdam slaughterhouse were positive to the dye test at a titer above 1:100. He also (1957a) isolated Toxoplasma by mouse inoculation from the brains of 4 out of 30 slaughtered sheep picked at random. Rawal (1958) found that 3 of 100 sheep sera from a Sheffield, England slaughterhouse were positive to the dye test at a titer of 1:64 or above. He found Toxoplasma by mouse inoculation in the brains of 6 out of 21 sheep whose sera had reacted to the dye test at a titer of 1:4 or above. Jacobs, Remington and Melton (1960a) found Toxoplasma infection in 9% of 86 sheep from a Baltimore slaughterhouse.

Sanger et al. (1953) found Toxoplasma in 4 herds of cattle in Ohio. Miller and Feldman (1953) and Feldman and Miller (1956) found that 19% of 132 cattle from New York were positive to the dye test. De Roever-Bonnet (1957) found that 6% of 31 cattle from an Amsterdam slaughter house were positive to the dye test at a titer above 1:100. Jacobs, Remington and Melton (1960a) found Toxoplasma infection in 2% of 60 beef cattle from a Baltimore slaughterhouse.

Toxoplasma has been found in lagomorphs not infrequently. Perrin (1943) found it in a laboratory rabbit in Bethesda Md., Christiansen (1948) found it in 8.75% of 2411 hares in Denmark, Lainson (1955) found it in the brains of 5% of 113 domestic rabbits in England, and Orio et al. (1959) isolated it from 57% of 14 rabbits from Brazzaville, Middle Congo, either from the Pasteur Institute animal colony there or from the environs of the city itself. Miller and Feldman (1953) found that 5% of 22 laboratory rabbits were positive to the dye test, and Morris, Aulisio and McCown (1956) found that 19% of 107 cottontails from the Middle Atlantic states were positive to the same test.

Toxoplasma has been found several times in guinea pigs. Among others, Mariani (1941) found it in guinea pigs sent from Italy to Ethiopia. De Rodaniche (1949) found it in guinea pigs purchased in the suburbs of the city of Panama. Varela, Martinez and Trevino (1953) found it in a guinea pig in Mexico. Orio et al. (1959) found it in 23% of 31 adult guinea pigs in the Pasteur Institute animal colony at Brazzaville, Middle Congo. Miller and Feldman (1953) found that 27% of 51 laboratory guinea pigs in the U.S. were positive to the dye test. Makstenieks and Verlinde (1957) found that 33% of 174 guinea pigs from animal dealers in the Netherlands were positive to the dye test at a titer of 1:64 or above.

Toxoplasma was found by mouse or guinea pig inoculation of brain tissue in over 3% of the wild Norway rats in Memphis by Eyles (1952). He also found that the dye test was positive in 20% of 100 rats, but observed no correlation between the dye test and the results of tissue inoculation. Lainson (1957) found Toxoplasma  in 1 of 99 wild Norway rats in England. Miller and Feldman (1953) found no positive dye test reactors among 54 albino rats which they studied.

Toxoplasma has been found in laboratory mice by Nicolau and Balmus (1934) and Mooser (1950). Gibson and Eyles (1957) found it by mouse inoculation of brain tissue in 6% of 121 wild house mice captured in the neighborhood of a house in Memphis where a new-born infant had died of congenital toxoplasmosis. Lainson (1957) failed to find it in 399 wild house mice in England. Makstenieks and Verlinde (1957) found that none of 4097 laboratory mice from animal dealers in the Netherlands was positive to the dye test even at a titer of 1:4.

Toxoplasmosis is so common in voles (Microtus agrestis) in England that it is said to be a population-limiting factor (Findlay and Middleton, 1934; Elton, Davis and Findlay, 1935).

Toxoplasma Gondii trophozoites from mouse peritoneal exudate Giemsa stain

Among other mammals, toxoplasmosis has been reported in mink by Hulland (1956) and Pridham and Belcher (1958) in Canada, and by Momberg-Jorgensen (1956a) in Norway. In the last case, a severe outbreak of distemper was also present. Lainson (1957) found it in a weasel (Mustela nivalis), a ferret, and 2 ferret-polecat hybrids in England. Toxoplasma was reported in 3 chinchillas in Washington by Gorham and Farrell (1956), and in 3 chinchilla ranches in Canada by Hulland (1956).

Among domestic birds, Toxoplasma was found in a hen in Switzerland by Fankhauser (1951a), in a flock of chickens in Norway by Erichsen and Harboe (1954), and in 35 hens from 21 flocks in Denmark by Biering-Sorensen (1956).

Manwell and Drobeck (1951) isolated T. gondii from a pigeon caught in Syracuse, N.Y., while Jacobs, Melton and Jones (1952) isolated it from 4 of 80 wild pigeons caught in Washington, D. C.; the dye test was positive in 7 of these birds, including 1 of those from which the organism was isolated.

Rosenbusch (1931) found T. gondii in a canary in Argentina, and Sergent and Poncet (1954) found it in one in Algeria. Finlay and Manwell (1956) have reviewed the literature on Toxoplasma in birds.


The trophozoites of T. gondii are crescentic or banana-shaped, with one end pointed and the other rounded, and measure 4 to 8 by 2 to 4 u. The nucleus is vesicular and more or less central. There are no flagella, cilia or pseudopods. Locomotion is by body flexion whereby the protozoa follow a corkscrew path, rotate on their longitudinal axis or somersault (Manwell and Drobeck, 1953), or by gliding.

The morphology of the trophozoites has been studied following silver protein staining by Goldman, Carver and Sulzer (1957, 1958) and with the electron microscope by Gustafson, Agar and Cramer (1954), Bringmann and Holz (1954), Ludvik (1956) and Meyer and Mendonca (1957). They resemble the trophozoites of Sarcocystis in a number of ways. At the anterior end within the pellicle is a short, truncate, hollow cone 0.15 to 0.25 u in diameter and 0.2 to 0.3 u long, called a conoid. There is sometimes a distinct, spike-like extension at the anterior end. A number of fine, longitudinal fibrils run posteriorly in the pellicle from the region of the conoid; they extend for about 1/5 of the body length according to Ludvik (1956) or 2/3 of it according to Bringmann and Holz (1954). Running longitudinally in the body from the conoid are 5 to 18 cylindrical or club-shaped structures known as toxonemes. They are of variable length, some extending nearly to the posterior end and others not reaching the level of the nucleus; they become very slender and tortuous as they approach the conoid, and seem to enter its base. They are 0.02 u in diameter when they leave the conoid and then thicken to form a club or sausage-shaped structure 0.08 to 0.2 u in diameter. In addition to these, there are 1 or 2 central fibrils which frequently form a large loop or run posteriorly in a zigzag.

The cytoplasm is somewhat vacuolated and contains a number of osmiophilic granules about 0.5 u in diameter, mitochondria and often a cluster of fine granules around the nucleus. Goldman, Carver and Sulzer (1958) found a mass of argyrophilic granules at the very posterior end. The nucleus is usually round or oval, but lobed and horseshoe shapes have also been seen in electron micrographs. In the latter, the open end faces anteriorly as in Sarcocystis. The nucleus is about 1.0 to 1.5 u in diameter when circular and up to 2 u in diameter when elongated. Inside the nucleus is a large endosome which can be seen both in electron micrographs and after silver protein staining.

In addition to the above structures, Goldman, Carver and Sulzer (1958) described long, thread-like appendages in trophozoites treated with dilute (0.1 to 1.0%) formalin in saline before fixation. These may have been detached pellicular fibrils.

The parasites occur within vacuoles in their host cells. According to Gustafson, Agar and Cramer (1954), there is a definite space between the parasite and the vacuole wall. The space often contains a filamentous or granular precipitate, and concentrations of mitochondria are often present in the host cell at the edge of the vacuole.

As the parasites multiply, they form a cyst-like structure. Frenkel (1956a) emphasized that there is a difference between the terminal colonies which represent the final stage of parasitization in the leucocytes and the cysts which are found in the central nervous system, eye and myocardium. The wall of the latter is argyrophilic and weakly positive to the periodic acid-Schiff stain (PAS), while that of the former is not. Some authorities believe that the wall is formed by the host, so that the "cyst" is actually a pseudocyst, but Frenkel and Friedlander (1951) considered it likely that the wall is derived from the parasite. Lainson (1958), too, distinguished between the cyst-like structures formed in the acute and chronic stages of the infection. The former he considered to be pseudocysts and the latter true cysts.

The trophozoites in the cysts differ slightly from the proliferative ones in the pseudocysts. They contain large glycogen granules, are more resistant to external agents, and multiply slowly. Dasgupta and Kulasiri (1959) found that PAS-positive granules were abundant in the stages in the "pseudocysts" from the brains of mice, but that they were not universally present in the intracellular and extracellular trophozoites at all days of infection.

Life Cycle

Reproduction in Toxoplasma has generally been considered to take place by binary fission. However, Goldman, Carver and Sulzer (1958) reported on the basis of silver protein staining that T. gondii reproduces by a process of internal budding which they named endodyogeny. In this process, 2 daughter cells are formed within the parent cell. They are small at first, but grow until they destroy the parent cell and are released.

The natural mode of infection is unknown except in congenital toxoplasmosis, but experimental infections can be established by intravenous, intraperitoneal or any other type of parenteral inoculation or even by feeding. Weinman and Chandler (1954) transmitted toxoplasmosis to swine and rodents, and Makstenieks and Verlinde (1957) transmitted it to mice and a cynomolgus monkey by feeding infected tissue or peritoneal fluid. However, Schmidtke (1956) and van Thiel and van der Waaij (1956) considered that infection by feeding can occur only when there are epithelial lesions in the mouth or esophagus.

Jacobs, Remington and Melton (1960) found that the cysts of T. gondii are not able to survive freezing and drying, but they survive as long as 68 days at 4° C. Proliferative forms are destroyed within a few minutes by artificial gastric juice, but the cysts remain infective in tissue up to 3 hours, while trophozoites liberated by peptic juice from isolated cysts survive 2 hours. Trypsin destroys the cyst wall immediately, but the liberated trophozoites survive at least 6 hours; proliferative forms survive at least 3 but less than 6 hours. Thus, parasites encysted in tissues could survive the normal digestive period in the stomach and should survive even longer in the duodenum.

Following experimental inoculation, the protozoa proliferate for a time at the site of injection and then invade the blood stream and cause a generalized infection. Susceptible tissues all over the body are invaded, and the parasites multiply in them, causing local necrosis. The parasitemia continues for some time, until antibodies appear in the serum, after which the parasites disappear from the blood and more slowly from the tissues. They finally remain only in pseudocysts or cysts, and only in the most receptive tissues. In general, the spleen, lungs and liver are cleared of parasites relatively rapidly, the heart somewhat more slowly and the brain much more slowly. These residual infections may persist for a number of years.

Following experimental infection of rats, Ruchman and Fowler (1951) reported that Toxoplasma could be found in the blood regularly for the first week and then occasionally during the next 9 days. It could be found in the spleen for 2 weeks, in the liver and lungs for 10 weeks and in the brain for 2 years after infection. Other workers found it as long as 3 years after infection in the brain of rats, mice and pigeons, and 10 months after infection in that of the dog (Jacobs, 1956).

Toxoplasma trophozoites have been found in the urine and feces of mice and dogs with acute toxoplasmosis, in the milk of mice, dogs, cows and sows, in a serous exudate from the conjunctiva of a pigeon, and in the saliva of mice, rabbits and man. However, these are the proliferative forms and are very delicate. They are rarely able to infect other animals. Mice can be raised in the same jar with infected mice without becoming infected. Olafson and Monlux (1942) reported transmission to uninfected puppies caged with a littermate dying of toxoplasmosis, but Jacobs (1957) was unable to repeat this observation under similar circumstances. He was also unable to infect rabbits by spraying large numbers of proliferative forms into a confined space with them.

Transmission via the placenta occurs in congenital toxoplasmosis. It is generally considered to be an accidental complication of an inapparent primary infection of a pregnant female (Feldman and Miller, 1956). Foci of infection are set up in the placenta, and the fetus is infected from them. Koestner and Cole (1960) reported the occurrence of congenital toxoplasmosis in 2 consecutive litters whelped by the same bitch.

Other than placental transmission, as mentioned above, the natural mode of transmission is unknown. Weinman and Chandler (1954) suggested that toxoplasmosis might be acquired in the same way as trichinosis, by eating infected pork. However, the epidemiological evidence does not appear to support this, altho there is suggestive evidence that dogs might perhaps become infected by eating chronically infected rodents (Jacobs, 1957). Arthropod transmission has been postulated without any substantiation.

One possibility which deserves investigation is that a concurrent disease of some sort may be required for infection to succeed. Campbell, Martin and Gordon (1955) found T. gondii in 6% of 268 dogs in Glasgow, Scotland with clinical evidence of distemper or its neurological sequellae. They found distemper virus inclusion bodies in all these dogs, mentioned that the association of distemper with toxoplasmosis had been noted by several earlier workers, and remarked that they themselves had never seen a case of "pure" canine toxoplasmosis or of canine toxoplasmosis associated with any infection other than distemper.

Jacobs, Melton and Cook (1955) studied experimental T. gondii infections in dogs and found that only young puppies given relatively large inocula succumbed. Since it is hardly likely that dogs are exposed to such enormous numbers of parasites, they considered that canine toxoplasmosis is most frequently subclinical or asymptomatic. They believed that the chance of dogs spreading the disease to man under ordinary circumstances is small. On the other hand, Cole et al. (1953), in a study of 37 people in a household containing Toxoplasma-infected dogs, found that the sera of 9 of them were serologically positive and 5 of them ranged in titer from 1:80 to 1:1024. Of these 5 persons, 2 had toxoplasmic encephalitis and neuroretinitis, while 1 had Toxoplasma parasitemia. Makstenieks and Verlinde (1957) found evidence of concurrent infection in man and cats or dogs in a number of households in the Netherlands. These results suggest that there is a relationship between toxoplasmosis in man, dogs and cats, altho there is no proof of communicability.

Kimball et al. (1960) found that 44% of their obstetrical patients who had lived on farms were positive to the dye test as compared with only 21% of those who had never lived on farms. They observed a significant association between a positive dye test and contact with farm animals (cattle, chickens, ducks and geese), and suggested that domesticated fowls may be an important source of human Toxoplasma infections.


Toxoplasmosis may vary from an inapparent infection to an acutely fatal one. Asymptomatic toxoplasmiasis is the most common type.

In man, the most common form of the disease is the congenital type found in newborn infants. It is characterized by encephalitis, rash, jaundice and hepatomegaly, usually associated with chorioretinitis, hydrocephalus and microcephaly, and the mortality rate is high (Feldman, 1953; Feldman and Miller, 1956).

Acquired (i.e., non-congenital) human toxoplasmosis has many different manifestations. Siim (1956) divided them into 4 main types. The most common is characterized by lymphadenopathy. It may be febrile, non-febrile or subclinical. In the first, the onset may be acute, with chills and fever, or gradual. The temperature may last for 2 to 4 weeks or even longer. The lymph nodes are enlarged, the throat is often sore, and the patients suffer from malaise. Fatigue may persist for some time following recovery, and the lymph nodes remain enlarged for months.

The main characteristic of the non-febrile form is lymphadenitis. Its course is benign, but the lymph nodes remain enlarged for months. In the subclinical form, the only characteristic is the presence of swollen but not tender lymph nodes.

The second type of acquired human toxoplasmosis is a typhus-like, exanthematous disease. In addition to the exanthema, there may be atypical pneumonia, myocarditis and meningoencephalitis, and the termination is often fatal. Lymphadenopathy may or may not be present.

The third type is a cerebrospinal form, characterized by fever, encephalitis, convulsions, delirium, lymphadenopathy and a mononuclear pleocytosis, followed by death. This form is quite rare.

The fourth type is an ophthalmic form, characterized by chronic chorioretinitis. Hogan (1950) described ocular toxoplasmosis in detail.

Remington, Jacobs and Kaufman (1960) reviewed toxoplasmosis in the human adult.

The disease in domestic animals is similar to that in man. In dogs (cf. Cole et al., 1953), the disease is most serious in puppies altho adults may also die. Signs include fever, cough, anorexia, weakness, depression, ocular and nasal discharges, pale mucous membranes, dyspnea, premature birth and abortion. The resistance of dogs to experimental infection (Jacobs, Melton and Cook, 1955) and the possible association of the disease with distemper (Campbell, Martin and Gordon, 1955) have already been mentioned.

At necropsy, lesions of pneumonitis are common. The liver may be swollen and contain grey, necrotic foci. There may be ulcers in the oral, gastric and intestinal mucosa; this ulceration is perhaps more common in dogs than in other animals. Lymphadenitis, hydrothorax, ascites, nephritis, pancreatitis and vaginitis may also be present.

None of the 16 cases described by Campbell, Martin and Gordon (1955) had clinical signs which could be regarded as specific for Toxoplasma infection, altho the effects of this parasite may have been masked by intercurrent distemper. They found Toxoplasma in the lungs of 7 dogs, the mediastinal lymph nodes of 6, the mesenteric lymph nodes of 2, the heart muscle of 8, the liver of 4, the pancreas of 3, the spleen of 4, the kidneys of 3, the urinary bladder of 3 and the brain of 10.

Makstenieks and Verlinde (1957) reported encephalitis in one infected cat and abortions in another. However, Simitch et al. (1960) reported that the cat is relatively refractory to infection. They could not infect adult cats with 3 strains of T. gondii by either intravenous, intraperitoneal, subcutaneous or oral inoculation, and only part of the kittens less than 2 to 3 months old which were exposed by these routes became infected.

The disease in swine is similar to that in dogs. Pneumonitis, ulcerative enteritis, focal hepatitis, nephritis and splenitis have been described. Young pigs are much more susceptible than adults.

The disease in cattle is similar to that in dogs, and may vary considerably in its manifestations. In 1 herd described by Sanger et ah (1953), 3 cows developed nervous signs and died, and a fourth, asymptomatic cow which reacted positively to the toxoplasmin skin test was found to have the organisms in her colostrum, uterine wall, spleen and lung. In addition, 3 of 31 calves in this herd were born dead, and 4 developed an obscure disease of which 2 died. In a second herd, 45 of 78 calves died between the ages of 1 day to 6 months with signs of dyspnea, coughing, sneezing, nasal discharge, frothing at the mouth, trembling, head-shaking, dehydration and occasionally diarrhea with blood and mucus. Toxoplasma was recovered from the lungs of 1 calfo In a third herd, a bull died a week after the onset of illness characterized by anorexia, weakness, ataxia, prostration, chewing movements and bicycling; Toxoplasma was found in his brain. In a fourth herd, Toxoplasma was found in various tissues of a 7-year-old cow which had died 2 weeks after parturition with signs of anorexia, diarrhea, depression, fever and mastitis. Some calves in this herd later died of an undiagnosed disease.

In sheep, Olafson and Monlux (1942) and Wickham and Carne (1950) described cases of non-suppurative encephalomyelitis with nervous signs. Cole et ah (1954) isolated Toxoplasma from a flock of sheep in which several ewes and lambs died of a disease with respiratory and nervous signs. Hartley and Marshall (1957) found that toxoplasmosis is an important cause of perinatal mortality in sheep in New Zealand. The overall perinatal mortality rate in sheep in this country is 10 to 15% and at least 1/5 of the deaths are due to potentially pathogenic organisms. Of these Toxoplasma is considered the most widespread and important. In a study of 30 lambs which died of toxoplasmosis on 15 farms, Hartley and Marshall considered that 2/3 died before birth and the other third died either at the end of an apparently normal parturition or a few hours afterwards. The cotyledons of the fetal membranes bore small, necrotic foci which contained clumps of proliferative trophozoites.

Ratcliffe and Worth (1951) described an epidemic of toxoplasmosis in squirrel monkeys (Saimiri sciurea) in the Philadelphia Zoo, and Benirschke and Richart (1959) described a fulminating acute case in a young cotton-topped marmoset (Oedipomidas oedipus).

In naturally affected chickens, Biering-Sorensen (1956) reported that emaciation and central nervous system signs were the principal signs. Necrosis of the optic chiasma and of the retina with cellular infiltration were characteristic. Erichsen and Harboe (1954) described lesions of necrotizing pneumonitis, peri- and myocarditis, necrotizing hepatitis, focal necrotizing encephalitis and ulcerative gastroenteritis.

Altho natural infections occur in the chicken, Jones et al. (1959) found that this bird is remarkably tolerant to the parasite. Disease can be produced experimentally only by large inocula in mature birds, and even very young chicks can survive inoculation of enough parasites to kill rabbits, guinea pigs and hamsters. Parasitemia appears in 2 to 3 days after inoculation and disappears spontaneously, seldom persisting longer than 2 weeks. Even when enormous numbers of parasites were injected into large birds, Toxoplasma was rarely found in the tissues more than 40 days later.

The histopathology of toxoplasmosis has been reviewed by Frenkel (1956a) and Smith and Jones (1957). In the brain, Toxoplasma multiplies in the neurons and other cells and may cause cellular and interstitial necrosis. Sometimes infarction necrosis causes extensive lesions. Whenever aqueductal obstruction and internal hydrocephalus are present, periventricular vasculitis and necrosis are generally observed; these constitute a lesion unique for toxoplasmosis.

Koestner and Cole (1960) studied the neuropathology of canine toxoplasmosis in detail. They found lesions attributed to Toxoplasma in the central nervous systems of 47 out of 63 experimentally or naturally infected dogs with confirmed toxoplasmosis, and they found Toxoplasma itself microscopically in the central nervous systems of 25 of the animals. The parasites themselves were found in the cerebral cortex and basal ganglia of 17 dogs, in the midbrain of 12, the cerebellum of 9, the pons of 8, the medulla of 13 and the spinal cord of 4. Lesions were found in the cerebral cortex and basal ganglia of 47, the midbrain of 28, the cerebellum of 21, the pons of 20, the medulla of 29 and the spinal cord of 9. In acute cases, the lesions consisted of vascular damage and focal necrosis; extracellular trophozoites were found associated with the necrotic foci. In chronic cases, glial nodules and repair were seen, and intracellular parasites and cysts were present. In reactivated latent toxoplasmosis, ruptured cysts and a hyperergic response were present.

The lesions in the liver consist of small, sharply delimited areas of coagulation necrosis in any part of the hepatic lobules. The hepatic cells surrounding them are apparently normal, and there is little or no cellular reaction. The lungs contain small, grey, tumor-like nodules scattered thru 1 or all the lobes. These consist of alveoli filled with large mononuclear cells and leucocytes; the cells of the alveolar walls are cuboid or columnar and contain aggregations of Toxoplasma. The lymph nodes are usually involved. They are enlarged to several times their normal size and contain extensive areas of coagulation necrosis. These areas are irregular in outline, with sharply demarcated boundaries and slight leucocytic infiltration around their margins. Toxoplasma is present around these areas, in the endothelial cells of the veins, in monocytes or free in the tissues. There may be ulcers in the intestine. These may invade the muscularis, producing chronic, necrotizing lesions followed by granulation. Granulomatous chorioretinitis is sometimes seen in man, but ocular infections are apparently rare in animals.

Weinman and Klatchko (1950) found that a toxin which they called toxotoxin is produced in the peritoneal fluid of animals infected with Toxoplasma. It is heat stable and usually kills mice in 1 or 2 minutes following intravenous injection. Cook and Jacobs (1958), however, found no evidence of toxin production in tissue cultures of the organism.


There is a definite age immunity against toxoplasmosis. Congenital infections are the most common, and the mothers usually do not show signs of disease themselves. Young animals are more susceptible than adults.

In infections acquired after birth, humoral antibodies appear at the time that the parasitemia disappears and are probably responsible in part for clearing the blood of parasites. Humoral antibodies are not effective against intracellular parasites, however.

At least 2 types of humoral antibodies, complement fixing and cytoplasm modifying, are produced against Toxoplasma. The latter are revealed by the Sabin-Feldman dye test. They appear earlier in the course of the disease than complement fixing antibodies and persist much longer.

The dye test was introduced by Sabin and Feldman (1948) and has been described in detail by Sabin et al. (1952). It is based on the fact that both the cytoplasm and nucleus of Toxoplasma trophozoites stain deeply with alkaline methylene blue after incubation with normal serum, but that after incubation with antibody-containing serum only the nuclear endosome will stain. According to Lelong and Desmonts (1952), the dye test antibodies act by producing partial lysis of the organisms thru a modified Pfeiffer phenomenon in which the parasites lose those cytoplasmic constituents which are ordinarily stained by methylene blue. Kulasiri and Basgupta (1959) found that ribonucleic acid disappears during incubation in a positive reaction, and suggested that this is the reason the organisms no longer stain.

The antibody itself is heat stable, but a fairly large amount of a heat-labile, complement-like "accessory" factor is also necessary. This is apparently a mixture of the C2, C3 and C4 factors of complement plus properdin (Gronroos, 1956).

In carrying out the dye test, a series of serum dilutions is used, and a titer of 1:16 is considered diagnostic. The dye test titer usually reaches a high level by the end of the second week after infection; in active disease, titers above 1:1000 are found in a month or more. These antibodies usually persist for a number of years, probably for more than a decade, altho their titer declines slowly.

The trophozoites used in the dye test can be obtained from peritoneal exudate or tissue culture. These fluids sometimes contain a soluble antigen in sufficiently high titer to block the test partly or completely (Jacobs and Cook, 1954). Antibody in mouse peritoneal fluid may give rise to false positive tests (Frenkel, 1956). In addition, a prozone phenomenon may often occur, so that a full range of dilutions up to 1:1024 at least must be tested.

The dye test is not necessarily specific for Toxoplasma. Muhlpfordt (1951) and Awad and Lainson (1954) reported cross reactions with Sarcocystis tenella, and Awad (1954) even developed a modified dye test for Toxoplasma, using S. tenella trophozoites.

On the other hand, Cathie and Cecil (1957) were unable to confirm this latter test. Moscovici (1954) found no dye test cross reaction between T. gondii and S. tenella. Jacobs (1956) found no dye test cross reaction between Toxoplasma and Trypanosoma cruzi, Plasmodium berghei, P. gallinaceum, Eimeria tenella, Hepatozoon sp. in squirrels, or Sarcocystis in rhesus monkeys, but did observe cross reactions at titers up to 1:4 between Toxoplasma and Encephalitozoon in rats and up to 1:16 between Toxoplasma and Besnoitia jellisoni in rabbits. Cathie (1957) found the dye test to be specific for Toxoplasma, for human sera at least; the test sera should be inactivated.

The complement fixation test was developed by Warren and Sabin (1943) and Sabin (1949). Complement fixing antibodies rarely appear earlier than 1 month after infection, and decrease relatively rapidly with time. In 60 children with congenital toxoplasmosis studied by Eichenwald (1956), complement fixing antibodies had disappeared from 44 at 5 years of age and from 8 more at 7 years, altho all but 3 still had dye test antibodies. In 15 cases of active toxoplasmosis studied by Makstenieks and Verlinde (1957), the complement fixation reaction became negative in 6 to 9 months while the dye test was still positive at the end of 4 years.

A positive complement fixation titer of 1:32 or above is considered to indicate relatively recent infection.

The antigen for this test may be prepared from protozoa in chicken embryos, mouse brain, peritoneal exudate or tissue cultures. Eichenwald (1956) preferred chorioallantoic membrane or tissue culture because peritoneal exudate has a strong anticomplementary activity.

Jacobs and Lunde (1957) and Lunde and Jacobs (1958) reported on a hemagglutination test for toxoplasmosis. It agreed very closely with the dye test in a survey of 12 human serum specimens from Trinidad; 54.5% were positive by both tests. They considered that the hemagglutination test was adequate for survey purposes but that more work must be done to determine its usefulness in the diagnosis of acute infections.

A skin test using "toxoplasmin" was developed by Frenkel (1948, 1949). Positive reactions appear in man, rhesus monkeys and guinea pigs 3 to 4 weeks after infection. However, they do not appear in about 10% of the individuals, and the test remains negative in most infected rodents and in humans with highly active disease.

Hook and Faber (1957) found that antigenic activity in both the dye and complement fixation tests is associated with a protein component of sonically fragmented T. gondii which was precipitated by 30% saturated ammonium sulfate at pH 7.


The most certain method of diagnosis of toxoplasmosis is by isolation of the parasites themselves by inoculation of experimental animals. Eichenwald (1956) considered mice, hamsters and guinea pigs the most sensitive animals in his experience, and recommended the administration of cortisone to the test animals for 3 to 5 days before inoculation in order to increase the chance of isolating the organisms. Jones et al. (1958), however, found no advantage in using cortisone. They recommended intraperitoneal inoculation of mice. Simitch, Petrovitch and Brodjochki (1956) considered the ground squirrel, Citellus citellus, to be the animal of choice, while Lainson (1957) found that the multimammate rat (Mastomys coucha) is more susceptible than the house mouse and suggested that it might prove more suitable0 After isolation, the organism should be identified serologically.

Despite the disadvantages discussed above, the dye test still appears to be the most satisfactory serological test available at present. Eichenwald (1956) considered the complement fixation test useful only as an adjunct to it, and the hemagglutination test requires further study. A neutralization test was introduced by Sabin and Ruchman (1942). It is now carried out chiefly in tissue cultures. However, according to Eichenwald (1956), it is of use primarily as a research tool to study cell-parasite relationships.

Serologic studies with fluorescein-labelled Toxoplasma antibody have also been carried out (Goldman, Carver and Sulzer, 1957). This technic shows promise. The antibody does not agglutinate Besnoitia.

Toxoplasma can also be found in stained smears and sections of tissues and exudates. It must be differentiated from similar organisms, including Sarcocystis, Besnoitia and Encephalitozoon, and this is not always possible on morphological grounds alone.


Toxoplasma grows reaily in chicken embryos and tissue culture. It was first cultivated in both by Levaditi et al. (1929). Cook and Jacobs (1958) cultivated it in a wide variety of mammalian and avian tissue cultures, including various human, monkey, mouse, rabbit, guinea pig, rat, ox and chick normal tissues, and in human and mouse cancer cells. They also reviewed the literature on the subject.

Eyles, Coleman and Cavanaugh (1956) preserved T. gondii for as long as 209 days by freezing it in the presence of 5% glycerol and storing it at -70° C. They used the technic routinely for preservation of their strains.


No satisfactory treatment for toxoplasmosis is known. Promising results have been obtained by the use of pyrimethamine and sulfonamides simultaneously; the two drugs act synergistically (Eyles, 1956).

For treatment of human ocular toxoplasmosis, Remington, Jacobs and Kaufman (1960) recommended that the patients receive 2 oral loading doses of 200 mg pyrimethamine and 2 g triple sulfonamides each on the first day of therapy, and that thereafter they be given 25 mg pyrimethamine and 2 g triple sulfonamides twice a day for 5 weeks.

Prevention and Control

In the absence of solid information regarding the mode of spread of toxoplasmosis, specific preventive measures cannot be recommended. The measures customarily employed to control infectious diseases should be used. In addition, since many wild mammals are apparently reservoir hosts, contact with them should be avoided and rodents should be controlled. Man and his domestic animals apparently receive their infections from the same source, but it is not clear whether they can give it to each other.