Biomedical subjects
Publications and source records attributed to J K Frenkel.
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We studied Aotus lemurinus, Panamanian night monkeys, for susceptibility to Toxoplasma infection and for their capacity to develop immunity using either sufadiazine prophylaxis or the non-persistent ts-4 vaccine. The animals were highly susceptible to infection with a mouse pathogenic (T265) and a mouse nonpathogenic (T163) Toxoplasma isolate. A calculated single bradyzoite by mouth gave rise to infection which was fatal in nine to 12 days. Chemoprophylaxis with 60-300 of sulfadiazine mg per day for up to 40 days protected the animals; however this was followed by fatal reactivation of infection between 11 and 70 days after treatment was stopped. Vaccination was carried out in two or three doses subcutaneously. Challenge was performed in 26 animals using both Toxoplasma isolates. Five monkeys (19%) survived for over a year, 10 died after a prolonged illness, and 11 died as rapidly as the seven controls. Safety tests showed the vaccine to be nonpathogenic in 111 adults except for slight fever and local inflammation, although one of four juveniles died from disseminated infection. Vaccination of 25 pregnant monkeys was non-pathogenic; however two of 25 fetuses were aborted, one of which was infected and one newborn had microphthalmia, retinitis and a cataract; four of the offspring were not tested. When six lactating monkeys were vaccinated, Toxoplasma was not transmitted to the infants. The high susceptibility to Toxoplasma and the low immunizability was circumstantially attributed to absence of exposure and lack of selection by Toxoplasma of these arboreal monkeys even though about 50% of terrestrial animals from the same area were infected.(ABSTRACT TRUNCATED AT 250 WORDS)
A 24-year-old homosexual man with acquired immunodeficiency syndrome presented with intractable diarrhea and fever. Examination of a rectal biopsy specimen and stool revealed Cryptosporidium. Approximately 4 months after admission he developed respiratory failure and died. Postmortem examination revealed cryptosporidiosis involving the entire gastrointestinal tract as well as the tracheobronchial tree. To our knowledge, this is one of the rare presented cases of tracheobronchial cryptosporidiosis documented histologically.
Kittens are the principal disseminators of Toxoplasma gondii. They can shed greater than 10(8) oocysts in the feces after initial infection with bradyzoites in tissue cysts. Thereafter, most kittens develop protective immunity and do not shed oocysts again if they are reinfected. Bradyzoites of a T gondii mutant, designated T-263, were used to vaccinate kittens. Their use did not result in oocyst shedding, but successfully prevented 84% (31/37) of the kittens from shedding oocysts when challenge exposed with a normal isolate of T gondii. Vaccination of outdoor-roaming cats and kittens would be a useful public health measure to prevent transmission of toxoplasmosis near homes, on farms, and in zoos. It is anticipated that several years will be required for a lyophilized bradyzoite vaccine to be ready for licensing and possible commercial availability.
Toxoplasmosis is a common infection of animals and man, yet remains a rare disease. The disease appears in the offspring of mothers first infected during pregnancy and by relapse of chronic infection in immunodeficient animals and man. Toxoplasmosis can be prevented by the simplest of hygienic measures, such as handwashing. Further control can be achieved by widespread education of the public about the dangers of toxoplasmosis and the methods of prevention. Education of veterinary and zoo workers would reduce transmission in an environment where it is most likely to occur because of high concentrations of cats and cat feces. Toxoplasmosis of sheep and pigs on farms may be amenable to vaccination with the ts-4 strain of Toxoplasma. Finally, the new T-263 toxoplasmosis vaccine for cats offers the possibility of drastically reducing environmental contamination with oocysts, especially on farms. The reduction in numbers of viable oocysts in the environment would eventually reduce the infection of bird and rodent intermediate hosts, and ultimately, the infection of humans.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
To investigate the oocyst-induced cycle with a 21+ day prepatent period, 32 cats were fed 5 x 10(5) to 2 x 10(7) sporulated oocysts of Toxoplasma gondii and necropsied between 4 hr and 41 days thereafter. The presence of the earliest stages in 7 cats was tested in mice. The tissues of 25 cats were studied histologically; 17 were bioassayed by feeding them to cats to determine, by the length of the prepatent period, whether bradyzoites were present. Based on previous studies, a short (3-10 days) prepatent period indicated that bradyzoites were present in an oral inoculum and a long (greater than 21 days) prepatent period indicated the presence of tachyzoites only. Tissues from 14 cats were also bioassayed in mice for the presence of bradyzoites, using their resistance to pepsin as indicator. Six were studied by both methods. Based on these criteria, tachyzoites predominated in extraintestinal organs during the first 14 days after infection. They were found as early as 4 hr in mesenteric lymph nodes where their number reached 10(4) after 6 and 9 days; they were present after 1 day in all levels of the small intestine and after 6 days in the liver, lung, and blood. Bradyzoites were first detected 10 days after oocyst feeding; they predominated by the third week of infection and were present up to 41 days. Enteroepithelial stages were found histologically only in 2 cats, 24 and 41 days after inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)
Mice were immunized s.c. or intraintestinally with two injections of a temperature-sensitive mutant of Toxoplasma gondii (ts4). Nonpersistence of the vaccine strain was documented by subinoculation of tissues of a subgroup of mice 3 mo or more after the second immunization. Mice were immune to other-wise lethal parenteral challenges with tachyzoites of the M7741 strain or to peroral challenge with bradyzoites of the Me49 strain of T. gondii. Although two s.c. or intraintestinal immunizations did not completely protect against development of T. gondii in the brains of mice, fewer cysts developed in the s.c. immunized mice than in control mice (2 +/- 3 cysts/0.01 ml in immunized mice compared with 75 +/- 48 cysts/0.01 ml in controls (p less than 0.002)). Reduction in cyst number after intraintestinal immunization was more variable, but also statistically significant (p less than 0.02). Female mice were first immunized, then mated, and then challenged perorally. Neonates of the s.c. immunized mice were not protected. Neonates of intraintestinally immunized mice were protected in part (36% of 115) against congenital infection compared with controls (7% of 107).
Toxoplasma infection in most adult animals and humans is asymptomatic because of effective protective immunity; this involves antibody acting extracellularly, and T-cell factors acting intracellularly. Whenever immunity is not acquired in a timely fashion, tachyzoites continue to multiply, destroying an excessive number of cells, producing lesions in several organs, with pneumonia and encephalitis the prominent causes of illness and death. However, immunity is insufficient to destroy the slowly multiplying bradyzoites persisting in tissue cysts in many organs - a parasite adaptation to await ingestion of one host by another. Toxoplasma cysts produce lesions when they disintegrate, because of the delayed type of hypersensitivity accompanying infections. In the presence of immunity, the released bradyzoites are destroyed, but when protective immunity fails, the bradyzoites can develop again into actively multiplying tachyzoites parasitizing and destroying cells in expanding foci, usually in the brain. In this review J.K. Frenkel discusses the complex interplay of immunological and parasite factors participating in the various lesions associated with acute and chronic Toxoplasma infections.
We studied the prevalence of Toxoplasma antibody over a 10-year period in a rural population of 326 people in Chorrera Province of Panama using the dye test. Fifty-five seroconversions were found in 108 people at risk, and 48 (87%) in children between 2 and 13 years with a mean incidence rate of 8.6% per year. Antibody prevalence rose from 25% at 5 years to 50% at 10 years of age, and increased gradually, reaching 90% by 60 years. Mean antibody levels after seroconversion were 1:6,000 in the dye test; they fell to 1:1,000 after 1 year, 1:800 after 2 years, 1:200 after 3 years, and 1:333 after 7-9 years. About 10% of antibody titers ranged between 1:4 and 1:32. Toxoplasma antibody prevalence was also studied in the metropolitan Panama City population using 590 sera collected in the fall of 1981. Age-specific incidence rates were similar in the urban and rural setting (correlation coefficient 0.71). The number of cats observed in the rural area and in the city and the degree of soil contact appeared compatible with a hypothesis of transmission by oocysts.
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We studied the specificity of protection conferred by Toxoplasma gondii immune lymphocytes and their supernatants on infected hamster kidney cells, using Besnoitia jellisoni immune lymphocytes as a nonspecific control. The intracellular growth of the organisms was measured by [3H]uracil incorporation, and inhibition of multiplication was used as a measurement of immunity. Although the immune lymphocytes restricted principally the multiplication of homologous organisms, partial protection, expressed against the heterologous organism, was found. This was true for either parasite with intact lymphocytes or their supernatants. Exposure of immune lymphocytes to antigen for 18 to 24 h and treatment of kidney cells with supernatant fluids for 18 to 24 h were required for maximal protection. The specific protective mediator in supernatants of immune lymphocytes was characterized by dialysis as having a molecular weight between 3,000 and 12,000 and was found in the 3,000 to 5,000 peak after Sephadex G-50 chromatography. Nonspecific protective activity was greater than 12,000 by dialysis; it chromatographed in the excluded peak, measuring over 43,000, and was destroyed by exposure to pH 2. In vitro production of lymphokines from toxoplasma immune lymphocytes was first detected 7 to 10 days after vaccination of hamsters. At about the same time, hamsters began to resist challenge infection with the pathogenic RH strain of T. gondii and were able to prevent its multiplication in lungs, liver, spleen, and the subcutaneous infection site. The expression of tissue immunity and the production of toxoplasma-immune lymphokines appear to be time-related events.
Seemingly intact cysts and sequential stages of disintegrating cysts of Toxoplasma were identified immunohistologically within developing microglial nodules in a Panamanian night monkey (Aotus lemurinus). This monkey had been successfully immunized and challenged 5 months earlier. This supports the hypothesis that glial nodules unassociated with Toxoplasma tachyzoites may represent the tombstone of a Toxoplasma cyst. Disintegration of cysts may give rise to clinical encephalitis in the presence of apparently adequate immunity.
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