Synonyms: Schizotrypanum cruzi.
Disease: American human trypanosomosis, Chagas' disease.
Hosts: Many species of wild and domestic animals have been found naturally infected with Trypanosoma cruzi, and probably most mammals are susceptible. Man is also susceptible, infants and young children being most often affected. The most important wild reservoir hosts are probably armadillos (Dasypus) in South America, opossums (Didelphis) in South and Central America and the United States, and woodrats (Neotoma) and possibly raccoons (Procyon) in the United States. The dog, cat and possibly the pig are considered of some importance as reservoirs of infection for man in South America.
Location: The trypanosomes are found in the blood early in an infection. Later, they invade the cells of the reticuloendothelial system, heart and striated muscles and other tissues. In central nervous system infections, they are found in the neuroglial cells. Trypanosome forms occur in the blood, and leishmanial forms within the cells.
Geographic Distribution: T. cruzi occurs in South America from Argentina north, in Central America and in southern United States. Dias (1953) published maps of the distribution of Chagas’ disease in South and Central America together with climatologic and other information.
In the United States, T. cruzi had been thought until recently to be confined to the southwestern states, including Texas, Arizona, New Mexico and southern California, but Walton et al. (1956) discovered it in raccoons in Maryland, and it appears that it may be rather widely distributed in the southeastern states. McKeever, Gorman and Norman (1958) found it in 17% of 552 opossums, 2% of 118 grey foxes (Urocyon cinereoargenteus), 1.5% of 608 raccoons and 1% of 306 striped skunks (Mephitis mephitis) from Georgia and Florida. Walton et al. (1958) found it in 5 of 400 raccoons from Maryland. Norman et al. (1959) reported that their strains were typical T. cruzi of relatively low virulence for mice.
Morphology: The forms in the blood are monomorphic, 16 to 20 u long, with a pointed posterior end and a curved, stumpy body. The kinetoplast is subterminal and larger than that of any other trypanosome of domestic animals or man, often causing the body to bulge around it. The undulating membrane is narrow, with only 2 or 3 undulations. There is a moderately long free flagellum. The leishmanial forms in the muscle and other tissue cells are 1.5 to 4.0 u in diameter and occur in groups. Electron microscope studies of this species have been made by Meyer and Porter (1954), Meyer, Musacchio and Mendonca (1958) and Meyer and Queiroga (1960).
Life Cycle: Altho the trypanosome form of T. cruzi is common in the blood in the early stages of Chagasf disease, it does not multiply in this form. The trypanosome forms enter the cells of the reticulo-endothelial system, striated muscles and especially of the heart muscle, where they round up and turn into leishmanial forms. These multiply by binary fission, destroying the host cells and forming cyst-like nests of parasites. There does not appear to be conclusive proof that they turn into the crithidial form in mammals, as was once believed. The leishmanial forms turn into trypanosome forms which re-enter the blood. Among recent studies or reviews of the life cycle of T. cruzi in the vertebrate host are those of Elkeles (1951), Noble (1955), Romana (1956) and Wood (1951, 1951a, 1953).
The vectors of T. cruzi are kissing bugs or conenose bugs, members of the hemipteran family Reduviidae. Natural infections have been found in at least 36 species of these bugs. They get their first name from the fact that in sucking blood they prefer to attack the thinner parts of the skin such as the lips or eyelids.
The most important vector in South America is probably Panstrongylus (syn., Triatoma) megistus. Other important vectors in South and Central America are P. geniculatus, Eutriatoma sordicla, Triatoma infestans, Rhodnius prolixus and Eratyrus cuspidatus.
According to Faust (1949), 15 naturally infected species of reduviids have been found in the United States. Dias (1951, 1951a) listed Triatoma protracta, T. sanguisuga (= T. gerstaeckeri), T. lectularius, T. longipes, T. neotomae and T. rubida as having been found infected in the U. S. Mehringer and Wood (1958) found T. cruzi in 24% of 383 Triatoma protracta collected in the Boy's and Girl's Camp areas in Griffith Park, Los Angeles, Calif. Most of the conenose bugs were taken in human habitations.
Both the nymphs and adults of these reduviids can be infected and can transmit the disease. In addition, it is possible to infect sheep keds (Rodhain and Brutsaert, 1935), ticks (Ornithodoros)(Brumpt, 1939) and bedbugs (Wood, 1951a) experimentally.
After they have been ingested by the triatomids along with a blood meal, the trypanosomes pass to the midgut. Here they turn into leishmanial forms which multiply by binary fission and turn into either metacyclic trypanosomes or crithidial forms. The crithidial forms multiply further by binary fission, and extend into the rectum. Here they turn into metacyclic trypanosomes, which are unable to divide until they enter a vertebrate host. The life cycle in the invertebrate host takes 6 to 15 days or longer, depending on the insect species or stage and on the temperature.
The infective trypanosome forms pass out in the feces. They can penetrate the mucous membranes or skin actively. Triatomids commonly defecate after feeding, and most human infections occur when feces are rubbed into the eyes or mucous membranes following a bite. Animals can become infected by licking their bites or by eating infected bugs or rodents.
Epidemiology: Human infections with T. cruzi are common in many parts of tropical America, including Brazil, Bolivia, northern Chile, northern Argentina, French Guiana, Paraguay, Uruguay and Venezuela. In some localities 10 to 20% or even 50% of the inhabitants are positive to the complement fixation (Machado) test, but in other localities where exposure to the vectors is minimal, there are very few positive reactions. As mentioned below, acute Chagas' disease occurs primarily in infants and children, and the number of acute cases is far lower than the numbers of chronic and unrecognized infections.
Chagas' disease becomes increasingly uncommon to the north of the endemic area even tho infected reservoir hosts and vectors may be common. Less than 140 cases of Chagas' disease had been reported from Guatemala, Salvador, Nicaragua, Costa Rica and Panama according to Dias (1952a) while only 9 cases were known from Mexico (Mazzotti and Dias, 1950). Only a single indigenous case has been reported from the United States, by Woody and Woody (1955) in Texas.
Chagas' disease is a zoonosis, infections occurring widely in animals and man. The armadillo is thought by Hoare (1949) to be the original source of the human disease in South America, but the opossum and many other wild animals are also infected. The most important wild reservoirs in the United States are woodrats of the genus Neotoma. Natural infections have been found in the southwestern states and southern California in N. fuscipes, N. albigula, N. micropus, in the deer-mouse, Peromyscus boylii, and also in the opossum, house mouse and nine-banded armadillo (Dasypus novemcinctus). The recent discovery of T. cruzi infections in raccoons (Procyon lotor), opossums, gray foxes and skunks in Maryland, Georgia and Florida (Walton et al., 1956, 1958; McKeever, Gorman and Norman, 1958) raises the question how widespread the infection is in these animals.
Cats and dogs are often naturally infected in South America, and, because of their closer association with man, are probably more important as sources of human infection than wild animals. NaturNaturally infected pigs have been found in South America, and sheep and goats can be infected experimentally with these South American strains.
In a study of the possible role of farm animals as reservoirs of North American strains of T. cruzi, Diamond and Rubin (1958) established low-grade infections in young pigs, lambs, kids and calves with a strain isolated from a raccoon in Maryland. The infections persisted at least 57 days in the pigs, 53 to 85 days in the lambs, 38 days in a kid and 21 days in a calf.
Infection is common in the triatomid vectors of Chagas' disease. In the endemic regions of South and Central America, 40 to 60% of them are infected, while 20 to 25% are infected in Mexico and southwestern United States. The triatomids infest armadillo burrows and woodrat nests, and thus maintain the infection in these animals. They also infest houses, where they live like bedbugs; it is these triatomids which are responsible for the vast majority of human infections.
Because triatomids are rare in southeastern U. S. where T. cruzi is common in the opossums, and because they isolated the organism from the urine of infected opossums, McKeever, Gorman and Norman (1958) believed that infections may be passed from mammal to mammal by contact with infected urine.
For further information on the epidemiology of T. cruzi infections see Dias (1951, 1951a, 1951b, 1952, 1952a, 1952b), Dias and Chandler (1951), Dias and Laranja (1948), Dias, Laranja and Nobrega (1946) and other papers by these authors. For information on the epidemiology of T. cruzi in southwestern United States, see Elkins (1951) and particularly Wood (1950, 1953a, 1958), and Mehringer and Wood (1958).
Pathogenesis: Chagas' disease may be either acute or chronic in man. The great majority of acute cases occur in infants and young children. The first sign of disease is often swelling of the eyes and conjunctiva. This swelling may affect either one or both sides of the face. The tear glands become inflamed, and the cervical lymph nodes swell. Later on, swellings may appear in other parts of the body. Each swelling, known as a chagoma, is due to an inflammatory exudate in the region where the parasites are invading the tissue cells. In addition to this edema, there may be anemia, more or less continuous fever, prostration and severe headache.
If the patient survives the acute phase, the disease becomes more or less chronic. Some authorities believe that it persists for life. The lymph nodes are edematous and inflamed, and the liver and spleen are enlarged. The heart is affected in many cases. Electrocardiographic abnormalities are common. Inflammatory infiltration by phagocytes, fibrosis, separation of the muscle cells and partial destruction of the fibers by the multiplying parasites are present. The death rate due to cardiac conditions is increased in endemic areas.
T. cruzi may cause an acute or chronic disease in laboratory animals, depending on the strain of the parasite and the age of the host. Puppies and kittens are most susceptible, followed in order by mice and guinea pigs. The reservoir hosts are apparently not seriously affected, nor are farm animals. No clinical signs were observed in the infected young pigs, lambs, kids and calves studied by Diamond and Rubin (1958).
Diagnosis: In the acute stage of the disease, T. cruzi can be found in thick blood smears. In chronic or light infections, other methods must be used. One of the most important is xenodiagnosis, the inoculation of susceptible vector hosts. Laboratory-reared, parasite-free triatomids are allowed to feed on suspected individuals, and their droppings or intestines are examined 7 to 10 days later for developing trypanosomes. Rhodnius prolixus is often used for this purpose (Pifano, 1954a).
Laboratory animals can also be inoculated. In descending order of susceptibility, these are puppies, kittens, mice and guinea pigs. The trypanosomes can be cultivated in NNN medium, Weinman’s (1946) medium, Diamond and Herman’s (1954) SNB-9 (serum-neopeptone-blood) medium, or in a number of other media. The trypanosomes can also be found in biopsy examinations of affected lymph glands or, on necropsy, in sections of heart muscle.
A complement fixation test, the Machado reaction, has been used, but it is also positive in Leishmania infections and weakly positive in a number of other conditions. Other serologic tests which have been used are the precipitin reaction, an intradermal skin test and a slide agglutination test. T. cruzi can be differentiated from the non-pathogenic T. rangeli by its smaller size and large kinetoplast.
Treatment: No satisfactory drug is known for the treatment of T. cruzi infections, altho Bayer 7602 Ac is used.
Control: Prevention of human T. cruzi infection depends upon eliminating triatomids from houses. This will also largely prevent infections among domestic dogs and cats. Dusting or spraying houses with residual lindane or dieldrin has given good results.