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Twice-weekly maintenance therapy with sulfadiazine-pyrimethamine to prevent recurrent toxoplasmic encephalitis in patients with AIDS. Spanish Toxoplasmosis Study Group.

OBJECTIVE: To evaluate the efficacy of twice-weekly maintenance therapy with sulfadiazine-pyrimethamine to prevent toxoplasmic encephalitis relapse in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Randomized, open, multicenter trial. Patients were randomly assigned to receive sulfadiazine (500 mg) four times per day plus pyrimethamine (25 mg) plus folinic acid (15 mg) either daily (n = 60) or twice weekly (n = 45). SETTING: 8 university teaching hospitals. PATIENTS: Between February 1990 and June 1993, 105 patients with HIV infection were enrolled after each had had resolution of an acute episode of toxoplasmic encephalitis treated with sulfadiazine (1 g four times per day) plus pyrimethamine (50 mg/d) plus folinic acid (15 mg/d) for 4 to 8 weeks. MEASUREMENTS: Clinical and biological evaluations done every 30 to 60 days. End points were toxoplasmic encephalitis relapse, death, and interruption of therapy due to adverse reactions. RESULTS: After a median follow-up period of 11 months (range, 1 to 39 months), patients receiving the twice-weekly regimen had a higher rate of relapse then patients receiving the daily regimen (19.5 compared with 4.4 per 100 patient-years; incidence rate ratio, 4.36 [95% CI, 1.05 to 25.5]; P = 0.024). The estimated cumulative percentages of relapse at 12 months were 30% and 6%, respectively (P = 0.029), with an adjusted risk ratio (adjusted for age, sex, risk behavior, previous diagnosis of AIDS, Pneumocystis carinii pneumonia prophylaxis before initial episode of toxoplasmosis, CD4 cell count, baseline number of brain lesions, radiologic sequelae, and antiretroviral therapy during follow-up) of 5.6 (CI, 1.2 to 25.6; P = 0.028). Patients receiving the twice-weekly regimen had 1.6 times (CI, 0.9 to 2.9 times; P = 0.11) the adjusted risk for death of patients receiving the daily regimen. No statistical differences were found in the patients who stopped receiving the regimens due to adverse effects. No patient developed P. carinii pneumonia during the study period, even though 17 patients (10 receiving the daily regimen and 7 receiving the twice-weekly regimen) had had an episode of P. carinii pneumonia before study entry. CONCLUSIONS: At the given doses, a combination of sulfadiazine, pyrimethamine, and folinic acid was less effective when administered twice weekly than when administered daily, although the twice-weekly regimen was much more effective than historic controls.

AIDS-Related Opportunistic Infections↗

Adult toxoplasmosis presenting as polymyositis and cerebellar ataxia.

A patient with toxoplasmosis had cerebellar, spinal cord, nerve root, and skeletal muscle symptoms. Toxoplasma gondii was isolated from skeletal muscle, and toxoplasma antibody titers were persistently elevated. The disease has been recurrent during a 3-year period with only temporary response to specific antimicrobial therapy.

Antigens↗

Toxoplasmosis: a serological survey in Ontario wildlife.

Sera from seven species of wild animals in Ontario were examined for antibody to Toxoplasma gondii using the Sabin-Feldman dye test. Of 158 sera tested, 53% of the red foxes (Vulpes vulpes), 56% of the striped skunks (Mephitis mephitis), 78% of the coyotes (Canis latrans), 33% of the black bears (Ursus americanus), 18% of the short tailed shrews (Blarina brevicauda) and none of the field voles (Microtus pennsylvanicus) had antibody. Antibody to T. gondii was present in sera from wild animals captured throughout southern Ontario. A positive linear correlation between prevalence of toxoplasmosis and age of fox pups was calculated (p < 0.005).

Animals↗

An outbreak of toxoplasmosis in wallaroos (Macropus robustus) in a California zoo.

Four wallaroos (Macropus robustus) from a central California zoo colony of 22 died within a three week period. Histopathologic findings in all four cases were suggestive of toxoplasmosis. Brain, lung and heart were the most frequently involved organs. Within 4 months of the last death sera from nine colony members were tested for antibodies against Toxoplasma gondii using the indirect hemagglutination test. All nine had serological titers ranging from 1:64 to 1:131,072.

Animals↗

Toxoplasmosis, distemper, and herpesvirus infection in a skunk (Mephitis mephitis).

A striped skunk (Mephitis mephitis) showing abnormal behavior had histopathologic lesions of toxoplasmosis and canine distemper in addition to intranuclear, eosinophilic inclusions in the reticuloendothelial cells of the spleen, liver and lung. The inclusions, on electron microscopic examination, were compatible with herpesvirus infection.

Animals↗

Survey for rabies, leptospirosis, toxoplasmosis and tularemia in striped skunks (Mephitis mephitis) from three public use areas in northwestern Arkansas.

During a skunk eradication program in late August, 1979, 53 striped skunks (Mephitis mephitis) were removed from three public use areas on Beaver Lake, Benton and Carroll counties in northwestern Arkansas. None of the 53 animals were positive for rabies (fluorescent antibody technique) and only one of 45 (2.2%) was positive for rabies antibodies. Twenty-one of 45 animals (46.6%) tested were positive for leptospirosis; 10 of 45 (22.2%) were positive for toxoplasmosis; and none were positive for tularemia. High populations of striped skunks in public use areas could be a potentially important reservoir for several diseases affecting both humans and other animals.

Animals↗

Fatal neonatal toxoplasmosis in a bobcat (Lynx rufus).

Toxoplasma gondii was found in tissues of a captive 1-week-old bobcat (Lynx rufus) that died of myocarditis, hepatitis and encephalitis. Although infection is common in wild Felidae, clinical toxoplasmosis is rarely seen. In this case, the infection was apparently congenitally acquired.

Animals↗

Acute disseminated toxoplasmosis in a red fox (Vulpes vulpes).

A red fox (Vulpes vulpes) with signs of neurological disease was captured in Fairmount Park, Philadelphia, Pennsylvania (USA). The animal died in captivity and was examined because of suspected rabies. The liver had pale foci up to 4 mm in diameter. Foci of necrosis were associated with Toxoplasma gondii tachyzoites in several organs including liver, lungs and adrenal glands. Rabies antigen and distemper virus inclusions were not detected. The diagnosis of acute disseminated toxoplasmosis was confirmed by immunohistochemical staining.

Acute Disease↗

Toxoplasmosis in Atlantic bottle-nosed dolphins (Tursiops truncatus).

A female Atlantic bottle-nosed dolphin (Tursiops truncatus) and her calf were found beached on Picnic Island in Tampa Bay, Florida, USA. Despite therapy the animals died. Necropsy revealed severe pneumonia and lymphadenopathy in the mother and the calf, gastric ulcers and infection with the stomach digenean Braunina cordiformis in the mother, and a large, pale liver in the calf. Toxoplasma gondii was identified by light and electron microscopy and by immunohistochemistry in tissues of both animals. Toxoplasma gondii was associated with interstitial pneumonia, necrotizing adrenalitis, and cardiac myonecrosis in the mother and with lymphoid necrosis in both dolphins. The source of infection and the relationship to the recent dolphin beachings along the eastern seacoast of North America are unknown. This is the first report of toxoplasmosis in cetaceans.

Animals↗

Antibody prevalence of toxoplasmosis in Arabian gazelles and oryx in Saudi Arabia.

We determined the antibody prevalence of toxoplasmosis (Toxoplasma gondii infections) in antelopes in Saudi Arabia. Serum samples from 324 Gazella subgutturosa marica, 202 Gazella gazella, 70 Gazella dorcas, and 12 Arabian oryx (Oryx leucoryx) were tested by the indirect hemagglutination test. Antibodies to T. gondii were detected in 13(4.0%) G. subgutturosa marica, 12(5.9%) G. gazella, 3(4.3%) G. dorcas, and in none of the Arabian oryx sampled. More adult gazelles were seropositive than juveniles; males and females were similar. The highest reciprocal antibody titer recorded (262,144) was in a G. subgutturosa marica serum.

Animals↗

Toxoplasmosis in a bobcat (Felis rufus).

A bobcat (Felis rufus) estimated to be 6-mo old exhibited head pressing, stupor, intermittent seizures, and vocalization. Based on gross and histopathologic features, it was diagnosed to have severe focally extensive protozoal meningoencephalitis. Toxoplasma gondii was confirmed as the etiologic agent by an avidin-biotin immunohistochemical test. This is the first report of clinical toxoplasmosis in a free-ranging bobcat.

Animals↗

Serodiagnosis of toxoplasmosis in a common wombat.

An 8-yr-old captive, female common wombat (Vombatus ursinus) from Victoria, Australia was euthanased after an illness of 36 days manifested by lethargy, inappetance and terminal coma with respiratory failure. Toxoplasmosis was diagnosed during life by the Toxoplasma direct agglutination test (DAT) which showed a positive initial titre of 1:1,024 at 22 days after onset of illness and a four fold rise in titre to 1:4,098 2 wk later, just prior to death. The Toxoplasma modified agglutination test (MAT) remained negative over this time period. The serological diagnosis was confirmed by histological diagnosis of granulomatous encephalitis, focal myocarditis, interstitial pneumonia and severe adrenal cortical necrosis and the presence of tachyzoites of Toxoplasma gondii in large numbers within the focal necrotic lesions in the brain, myocardium and adrenal cortices. The serological response in the wombat differed from that of the typical eutherian which exhibits a reaction in both the DAT and MAT within 2 wk of infection with T. gondii. An incidental finding was calcification in the media of the ascending aorta and proximal parts of the major arteries.

Adrenal Glands↗

Toxoplasmosis in wild mammals from the Czech Republic.

The prevalence of Toxoplasma gondii was determined in wild mammals in the Czech Republic from 1981 to 1990. The biological prevalence of T. gondii was < 1% in insectivores (n = 578), 12% in carnivores (n = 112), 1% in rodents except muskrats (Ondatra zibethicus) (n = 5,163), 24% in muskrats (n = 437), 5% in lagomorphs (n = 293), 0% in ruminants (n = 456), and 2% in wild boars (Sus scrofa) (n = 136). The seroprevalence (Sabin-Feldman dye test, titre > or = 1:4) of T. gondii was 15% in ruminants (n = 421), and 15% in wild boars (n = 124). Antibodies to T. gondii also were found in four of 10 carnivores. Toxoplasmosis is a common infection in wild mammals from the Czech Republic, but its prevalence varies considerable according to taxonomic groups and different localities where wild mammals live.

Animals↗

Earthworms as paratenic hosts of toxoplasmosis in eastern barred bandicoots in Tasmania.

An experimental feeding study was designed to assess the role of earthworms in the transmission of Toxoplasma gondii infection to eastern barred bandicoots (Perameles gunnii). Six animals with no agglutinating antibodies to T. gondii were fed artificially cultured earthworms that had been maintained in autoclaved nutrient-enriched soil. Two animals were given earthworms that had been maintained in soil contaminated with T. gondii oocysts (P89/VEG strain); two animals were fed on earthworms, which initially had been exposed to soil containing T. gondii oocysts then transferred through three changes of sterile soil; two control bandicoots were fed earthworms maintained in sterile soil. Both bandicoots fed earthworms maintained in T. gondii contaminated soil died 11 and 14 days after feeding. The necropsy findings were consistent with acute toxoplasmosis. Bandicoots fed earthworms exposed to oocysts but then transferred through changes of sterilized soil remained healthy as did control animals. All surviving animals remained seronegative over the 6 wk observation period after feeding. These findings confirm that earthworms, a major component of the natural diet of P. gunnii, can transmit T. gondii infection. It appears that oocysts present in the alimentary tracts of the worms, rather than infective stages of T. gondii in worm somatic tissues, are responsible for these infections.

Animals↗

Acquired toxoplasmosis in Malaysia.

Two cases of acquired toxoplasmosis in asymptomatic Malaysian patients are described. In both instances the diagnosis was first made on the finding of the Piringer-Kuchinka reaction in excised lymph nodes from these patients and serological studies further confirmed the presence of hihg toxoplasmic antibody titres. The characteristic histological features of toxoplasmic lymphadenitis are discussed. Diagnosis and management of the disease are briefly reviewed with emphasis that the importance of diagnosing this disease goes beyond the establishment of a mostly self-limiting, clinically unimportant protozoan infection.

Adult↗

The effect of minocycline, doxycycline and oxytetracycline on experimental mouse toxoplasmosis.

This is a comparative study of the effect of oral and parenteral administration of oxytetracycline, doxycycline and minocycline on experimental acute toxoplasmosis in mice. Two different inocula were used. All the antibiotics were ineffective orally. Doxycycline and minocycline were effective intraperitoneally, curing 90% of the mice who received the smaller inoculum. However, cerebral cysts of T. gondii were more common in the survivors treated with doxycycline.

Administration, Oral↗

Congenital transmission of experimental chronic toxoplasmosis in rats.

A 10% transplacental transmission rate was observed in litters from 89 Wistar rats chronically infected with Toxoplasmosis gondii, as judging from bioassays. The rats had been fed T. gondii 2 mo prior to mating. Six of 7 isolates of T. gondii were transplacentally transmitted. The frequency of transmission did not appear to be affected by the strain of T. gondii or the size of the inoculum.

Animals↗