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A cohort of more than 500 children from Panama City, Panama was studied prospectively over five years for acquisition of antibody to Toxoplasma gondii. The direct agglutination test showed that 72 of 571 children seroconverted between one and six years of age, for a cumulative incidence of 12.6%. Children were examined by pediatricians quarterly, and illnesses that had occurred in the interval and their activities were noted on questionnaires. Thirty-eight variables were examined for their role as risk factors for seroconversion. There was a higher correlation between children's seroconversion and contact with dogs than with cats. Combinations of significant predictors without dogs explained only 67% of the seroconversions, but the same factors with dogs explained 90%. On the other hand, ingestion of raw or rare meat or eggs appeared to play no role in transmission. Cats were examined and 110 (45.6%) of 241 had Toxoplasma antibody on the first bleeding. Only two (0.5%) of 383 cat fecal specimens, when tested in mice, resulted in seroconversion. Ten (1.1%) of 924 soil samples resulted in seroconversion in mice that had been injected. Antibody to Toxoplasma was found in 52 (23.3%) of 226 rats (Rattus norvegicus) and two (0.035%) of 571 mice (Mus musculus). Two hundred sixteen birds of 16 different species were bled. Antibody to Toxoplasma was found in 13.4% of these birds, mostly in grackles, blue-gray tanagers, and doves. The rate of isolation of Toxoplasma was low: one of 23 in rats and three of 201 in birds. High relative risks (RRs) of transmission to children were predicted by contact histories with nursing dogs (RR = 5.8), weaned dogs (RR = 4.7), many flies (RR = 3.6), 6–12-month-old dogs (RR = 3.4), weaned cats (RR = 3.0), 6–12-month-old cats (RR = 2.7), nursing cats (RR = 2.5), much garbage (RR = 2.4), and many roaches (RR = 2.2). The high statistical correlation of dog contact with seroconversion in children suggests the possibility that dogs, by eating and rolling in cat feces, are instrumental in mechanically transmitting Toxoplasma infection. In addition, flies, and to a lesser extent, cockroaches, may have practically important roles in transmission.