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Focal encephalitis occurred in a girl with activation of chorioretinitis which on clinical and serological grounds was taken to be caused by toxoplasma. The encephalitis and acute ocular inflammation resolved with treatment with pyrimethamine and sulphadiazine. This is presumably an example of reactivation of congenital cerebral toxoplasmosis.
Three types of antibody curve have been demonstrated by testing sera during the course of acquired toxoplasmosis by six different techniques. These three types are due to cell-wall antibody, (demonstrated by four of the techniques), to antibody to soluble antigen, and to IgM antibody to the cell wall. These findings have been supported by absorption experiments. A scheme is presented for testing single sera by two or three different tests to indicate the stage and duration of the infection.
Although many of the fundamental biological features of toxoplasmosis are today well appreciated, the practical problem of prevention of its most serious consequence--disabling congenital disease, remains unsolved. The reasons vary in different communities, but are concerned with detection of the chief mode of spread, assessment of incidence, delineation of vulnerable antenatal women in latently infected populations, and assessment of the risks of therapeutics. The results of some of the approaches to these problems in Scotland are reported and discussed.
PURPOSE: To evaluate the effects of sulfamethoxazole (SMX) on experimental ocular toxoplasmosis by quantitative competitive polymerase chain reaction (QC-PCR) assay. METHODS: Wild-type (WT) C57BL/6 and WT BALB/c mice and interferon-gamma knockout (GKO) mice were infected orally with Toxoplasma gondii of the Fukaya strain. Mice were classified into groups. The first group (G1) remained untreated, the second group (G2) had a short SMX treatment period, and the third group (G3) received treatment continuously. WT and GKO mice were divided into G1 and G3, and G1, G2, and G3, respectively. T. gondii burdens were evaluated by QC-PCR assay. The effect on stage distribution was analyzed by reverse transcription-PCR. RESULTS: SMX significantly decreased mortality among the infected WT C57BL/6 and GKO mice. In WT G1 mice, T. gondii DNA was detected in all organs and tissues, although in G3 mice it was detected only in the brain. In GKO C57BL/6 G1 mice, the protozoan proliferated much more actively than in the WT mice. In the GKO C57BL/6 G2 mice, the number of T. gondii was less than in G1 during the treatment, although the protozoan reappeared after cessation of treatment. In GKO C57BL/6 G3 mice, T. gondii DNA was detected in the brain, optic nerve, and retina, but not in the iris, choroid, sclera, and blood. In GKO BALB/c mice, the patterns of the kinetics of protozoan abundance in various organs were similar or were milder than those in GKO C57BL/6 mice. In SMX-treated GKO mice, the percentage of bradyzoites increased and that of tachyzoites decreased in the organs and tissues. CONCLUSIONS: SMX decreased the parasitic load in both WT and GKO mice. SMX decreased the tachyzoite load but did not completely eliminate bradyzoites in GKO mice. The present mouse model was used successfully to assess treatment effects in a quantitative fashion.
The kinetics of the nucleoside triphosphate hydrolase (NTPase) of Toxoplasma gondii was examined using an avidin-biotin sandwich-ELISA (ABS-ELISA) based on an anti-NTPase monoclonal antibody, 6C6. The RH and ME49 strains of the parasite were used to produce acute and chronic infections in mice, respectively. In the acute model, detectable serum concentrations of NTPase were observed from day 1 post-infection and gradually increased until the death of the mice. They were associated with parasitaemia (as estimated by bioassay). No anti-T. gondii antibody could be detected at any time. In the chronic model, in which 20 T. gondii ME49 cysts were given to each mouse per os, the NTPase concentration generally increased from day 3, peaked between days 7 and 14 and then declined. However, one of the four mice used still had a high serum concentration of NTPase on day 35. Again, detectable NTPase concentrations occurred when the mice had parasitaemias. Antibody to T. gondii was detected from day 7 (IgM) or 10 (IgG) and brain cysts were observed from day 14. Since detectable serum concentrations of NTPase appear to be associated with parasitaemia in both acute and chronic toxoplasmosis, the ABS-ELISA of the enzyme may make a useful diagnostic tool.
ELISA IgG, IgM antibodies and PCR for toxoplasmosis were performed on 55 women with complicated gestation and their babies. Besides, ELISA IgG and IgM were applied on 27 uncomplicated gestation (mothers & babies) and 152 randomly selected individuals. Seropositivity to specific IgG antibodies was 36.4%, 59.2% and 57.9% and for IgM was 27.3%, 7.4% and 10.5% in complicated gestation. uncomplicated gestation and random population respectively. PCR was positive in 20%, 50% and 60% of mothers with abortion, premature deliveries and deliveries of babies with congenital anomalies respectively. 55.5% and 40% were found seropositive for IgG from normal full term babies and abnormal babies. 13% of abnormal babies were IgM positive and 46.6% were PCR positive from the same group.
The paper presents a review of different treatment regimens employed for 25 years to prevent and treat congenital toxoplasmosis. Unfortunately, no well-controlled, randomized trials have been performed to evaluate the efficacy of different therapies of pregnant women or infected neonates. Treatment in pregnancy may be effective since transplacental passage of parasites is delayed. Spiramycin, a complete safe drug which concentrates in the placenta, may reduce the risk of materno-fetal transmission by 60%, but is in the present doses without influence on an already infected fetus. Pyrimethamine in combination with sulfonamides erradicates more effectively parasites in the placenta, and also in the fetus. Today a combination of both regimens is recommended in pregnancy. As for the infected neonates, intensive treatment of pyrimethamine/sulfonamides alternating with spiramycin until one year of age seems to prevent development of late appearing sequelae. There is obviously a need for international multicenter studies to settle the optimal schedules and duration of therapy which again is highly dependent on the performance of an appropriate serological screening during pregnancy.
In 1975 Austria introduced an obligatory serological screening of pregnant women for toxoplasmosis. Every woman is tested for antibodies at the beginning of her pregnancy and, in case of seronegativity, again in the second and third trimester. Basic tests are--alternatively--Dye test (SFT) and Indirect Fluorescent Antibody test IFAT); for further clarification, complement fixation test (CFT) and, particularly, various tests for detection of specific IgM and IgA antibodies and, in certain cases, for circulating antigen are carried out. If a primary Toxoplasma gondii infection of the pregnant woman is suspected, immediate therapy--with spiramycin before the 16th week of gestation and with pyrimethamin plus sulfadiazin after the 15th week of gestation--is carried out. Before the introduction of the screening programme, the incidence of prenatal toxoplasma infections was 50-70 per 10,000 births, presently it is below 1 per 10,000 births. Seropositivity among pregnant woman has decreased from almost 50% at the end of the seventies, to 36.7% in recent years (1989-1991). The percentage of suspected primary infection during pregnancy has, however, in the same period increased from less than 0.4% to 0.83%.
The results of the screening programme (including the examination of fetal IgM) in East-Germany, related to the efficiency of therapy (pyrimethamine/sulfonamid) of the fetal infection risk are presented. For comparison the results of a prospective study of toxoplasmosis in pregnancy (n = 1697) without therapy, and follow up of the connatal infected infants to the age of 9/10 years old are shown. Recommendations for the diagnostic and therapeutical management in Germany for the future are presented.
Cord blood screening is a helpful tool for the detection of infants probably infected with Toxoplasma gondii, if serological data of the mothers are not available. Testing for toxoplasma specific IgM and IgG antibodies of about 30,000 cord blood sera gave information about the changes in prevalence and incidence of toxoplasmosis in pregnant women in Basel between 1983 and 1991. The follow up and treatment of the infected children revealed the need of a randomized study comparing high and low dose treatment schedules.
The control congenital toxoplasmosis mainly relies on preventive measures, that can be applied on an individual basis as well as within the scope of a collective preventive programme. Several strategies can be adopted, each with its possibilities and impossibilities: primary prevention (health education), secondary prevention (serological screening) or a combination of primary and secondary prevention. Whatever strategy is chosen, decisions have to be taken with respect to the procedures. This paper lists the choices to be made and their consequences. The debate in international literature on the desirability of preventive programmes is summarized.
Between 1966 and 1987, in Liége--Belgium, 20,901 pregnant women were screened for toxoplasmosis. In this period an increase in seronegative women from 30% to 53% and a decrease in the seroconversion rate from 6.4% to 1.2% was observed. This decrease could be the result of advice and prophylactic measures. Due to the low rate of seroconversion (actually less than 1%), the cost/effectiveness of a systematic screening and fetal diagnosis should be investigated.
A case of congenital toxoplasmosis was observed in an infant aged 6 weeks with fatal outcome. Histological changes produced by Toxoplasma gondii in the brain are described.
The seroprevalence of toxoplasmosis among 505 of human immunodeficiency virus (HIV)/AIDS patients was 226 (44.8%; 95% CI 42.64-51.76): 27 (47.4%) and 199 (44.4%) showed Toxoplasma seropositivity with and without toxoplasmic encephalitis (TE), respectively (P <0.05). The majority of these patients were in the 25-34 age group (44 versus 39%), male (86 versus 76%), and Chinese (49 versus 53%), though no statistical significance was found between the two. Significant differences between these two groups were noted, however, in terms of marital status, occupation, and present address. The heterosexual exhibited the most frequent behavior at risk for HIV infection, and accounted for 51 and 59% of patients with and without TE, respectively. Only 17/260 (6.5%) and 1/137 (0.7%) of them later acquired TE after receiving primary chemoprophylaxis (cotrimoxazole) and antiretroviral therapy including HAART (P <0.05). Fifty-seven (11.3%) out of those 505 patients were diagnosed with AIDS-related TE. The most common clinical manifestation was headache (56%). The computed tomography scan findings showed most lesions to be multiple (96.4%), hypodense (66.7%), and in the parietal region (39.3%). Twenty-seven (47.4%) patients had chronic (latent) Toxoplasma infection as evidenced by seropositivity for anti-Toxoplasma (IgG) antibody. At the time of diagnosis, the range of CD4 cell count was from 0-239 with a median of 25 cells/cumm. We also found that a CD4 count of less than 100 cells/cumm was significantly associated with development of TE (P <0.05). Clinical outcomes showed that among those who survived, 21 (36.8%), 16 (28.1%), and 2 (3.5%) of patients had completed treatment, transferred out, and were lost to follow up, respectively. Unfortunately, 18 (31.6%) of the cases were officially pronounced dead. Overall, 7 (12.3%) patients were detected as recurrent TE in this study.
Turkish literature published between 1980-2000 were reviewed from the point of the epidemiology of toxoplasmosis in Turkey. The data obtained from this review were collected at five different tables: 1. Hospital patients, 2. People who had close contact with animals or working in meat industry, 3. Apparently healthy people, 4. Special groups such as homosexuals, hemodialysis patients, and 5. The prevalence in animals of live-stocks and domestic animals. The prevalence rates in these groups were as follows: 13.9% -85.3%; 20.7% -57.6%; 23.0% -43.7%; 16.3% - 76.6%; 39.5% -78.0%. The role of meat eating habits of people and living in close contact with cats were emphasized on these high rates.
A total of 9661 persons, mainly from southern region of Poland, were tested by using Sabin-Feldman dye test and ELISA test to determine the IgG class in the years 1991-2000. The tests were positive in 5297 persons (54.8%). The study included 320 pregnant women: 141 with low and mean titres of IgG class antibodies: 8-300 UM/ml and 62 with high titres, exceeding 300 UM/ml, who were tested only once. There were 117 seronegative pregnant women; the test was performed only once in 108 of them and twice in 9. The test was not repeated third time in any women of this group. According to the guidelines of congenital toxoplasmosis prophylaxis, the tests do not meet the expectations.
Congenital toxoplasmosis has been confirmed in Indonesia. Many newborn children in Indonesia have congenital anomalies attributable to Toxoplasma gondii. The parasite is widespread, with seroprevalence rates of 2-63% in humans, 35-73% in cats, 75% in dogs, 11-36% in pigs, 11-61% in goats, and less than 10% in cows. The prevalence of Toxoplasma antibodies in pregnant women in the Dr Cipto Mangunkusumo Hospital in Jakarta is 14.3%, and in 50 abortions it is 67.8%. In patients with a history of one or more abortions or stillbirths, the prevalence is 21.5% and 22.8%, respectively. No significant difference has been found in women with or without histories of habitual abortions or stillbirths. In adults and children with chorioretinitis, the prevalence of antibody is 60%; in patients with other eye lesions, it is 17%. The prevalence in hydrocephalic children is 10.6%; in children with mental retardation, 44.6%; in children with eye lesions, 44.6%; and in children with signs of systemic diseases, 9.5%. The diagnosis of an acute Toxoplasma infection using the ELISA should be based on a significant increase in IgG levels in paired sera or on detection of IgM.
Studies of congenital toxoplasmosis in twins confirm the definite role of the placenta in the modalities and mechanism of fetal contamination. In single-chorion twin pregnancies, clinical manifestations are generally identical in both infants. Conversely, twins from double-chorion pregnancies usually have different clinical patterns; occasionally, only one of the twins is affected (1 case). The diagnosis can be ascertained antenatally by sampling blood from each of the fetuses (2 cases). The cases reported herein illustrate some of the diagnostic pitfalls that may lead to inappropriate discontinuation of monitoring and treatment: negative placental studies, absence of specific IgM antibodies, transient fall in IgG antibody titers, delayed fetal contamination after a negative fetal blood study, and need for routine tests for increased CSF albumin levels.