[Pulmonary infections in the newborn: diagnostic and therapeutic aspects].
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The molecular mechanisms underlying migration of pathogens across biological barriers remain poorly characterized. Following oral infection, the apicomplexan parasite Toxoplasma gondii actively crosses non-permissive biological barriers such as the intestine, the blood-brain barrier and the placenta, thereby gaining access to tissues where it causes severe pathology. Recently, enhanced migration was found to be associated with virulent strains of Toxoplasma, suggesting that this phenotype contributes to pathogenesis. The migratory machinery appears to be morphologically and functionally well conserved within the phylum of apicomplexan parasites, however, the mechanisms for cellular traffic to breach biological barriers remain to be elucidated. As penetration of host tissue is a prerequisite for the establishment of infections by most apicomplexan parasites, understanding parasite migration is crucial for the development of new approaches to combat disease.
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Sera from 1661 persons in 12 age groups from 0 to 79 years were titrated for toxoplasma antibodies in the indirect immunofluorescence test. The sera were collected from patients with symptoms suggestive of acute, mainly respiratory, viral infections. After the first year of life, the prevalence of antibodies started to rise, reaching 59% between 40 and 79 years of age. From the prevalence of antibodies in different age groups the annual infection risk, i.e, the risk of a non-immune person acquiring toxoplasma infection, was estimated for successive age periods. The estimated annual infection risk increased from 0 . 5% in early childhood to 3% during adolescence and early adult life. Approximately 70--80% of females entered the age of reproduction without evidence of seroimmunity to toxoplasma. The risk of primary infection during pregnancy was estimated from the age distribution of parturient women in The Netherlands in 1975 and the age-specific incidence of primary infections, i.e. the incidence in the total population of susceptible and immune persons. This incidence of primary infection decreased from 1 . 62% per 9 months at the age of 17 1/2--20 years to 0 . 37% at the age of 37--45 years. The incidence of primary infections in pregnant women was estimated to be 1 . 25%.
Age-stratified data on toxoplasma seroprevalence in pregnant women in Stockholm, Sweden for the years 1969, 1979 and 1987 provide the basis for an analysis of temporal patterns of Toxoplasma gondii infection, and estimation of the risk of maternal toxoplasmosis, in this population. A catalytic infection model, in which the rate or force of infection is assumed to be a function of time (and not, as is more usual, age), was employed to describe the observed changes in levels of toxoplasma seropositivity. A range of simple incidence functions (up to 3 parameters) were fitted using a method of maximum likelihood. The data were significantly better described by a linear or an exponential decay in the rate of infection through time compared with a constant level. More complex incidence functions gave no better data description. Thus, whilst there is strong evidence for declining incidence in Stockholm over the past 4-5 decades, the data do not allow discrimination between different possibilities for the nature of this decline. Based on these modelling results, best estimates of the force of infection in 1987 acting on susceptible women are within the range 0 to 0.0045/susceptible/year (95% confidence limits), yielding a possible risk of maternal toxoplasmosis of between 0 and 2.7 cases/1000 pregnancies. These values are shown to be significantly lower than estimates based upon an assumption of temporal stability in toxoplasma incidence, which may be of practical significance to public health policy.
The diagnosis of maternal infection in early pregnancy depends on tests which are sensitive to recent infection, such as specific IgM. Two types of test are considered: those where the response persists for a period following infection and then declines, such as IgM, and those whose response increases with time since infection, such as IgG-avidity. However, individuals vary in their response to infection, and it may not always be possible to determine whether an infection occurred during pregnancy or before it. Mathematical methods are developed to evaluate the performance of these tests, and are applied to the diagnosis of toxoplasmosis in pregnancy. It is shown that, based on existing information, tests of recent infection are unlikely to be both sensitive and predictive. More data on these tests are required, before they can be reliably used to determine whether infection has occurred during pregnancy or before it.
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Rare forms of incompatibility were observed over a period of 20 years in 41 (2%) of 2088 new-borns with haemolytic disease. Antibodies involved were anti-c (n = 27), anti-E (n = 6) and anti-K (n = 4), as well as one case each of anti-E + Fya, -C, -Fya and -Jka. Amniotic fluid was examined during pregnancy in nine cases, three children were given intra-uterine infusions, while in the remainder the haemolytic process was mild or only moderately severe. One infant died of toxoplasmosis, another one of immaturity and respiratory distress syndrome. Kernicterus was always prevented. In haemolytic disease of the newborn caused by anti-c and anti-E, prenatal damage is markedly rarer than with D erythroblastosis, but must be considered during the pregnancy. In anti-K haemolytic disease the severity of the disease is similar to that of D erythroblastosis. All three incompatibilities may lead to kernicterus in the first few days after birth so that exchange transfusions are often necessary. In most of the other incompatibilities the course is similar to that seen with ABO erythroblastosis.
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This is a report on a rare incident of an intrauterine foetal death with toxoplasmosis in the 25th week of pregnancy. The diagnosis could be made serologically as well as pathologically. The issues connected with serological screening for toxoplasmosis are discussed on the basis of this case.
A general serological screening of pregnant women for toxoplasmosis was carried out by means of an IgG-ELISA in Greifswald and its surroundings from October 1986 to the end of 1990. Anti-toxoplasma gondii antibodies were detected in 72.8% of 4355 pregnant women. Since 1987, the prevalence of antibodies has decreased from 76% to 68%. The incidence of acquired toxoplasmosis in pregnancy was 2.53 per 1000. Seroconversion occurred in 11 women, but only 8 of them were treated with combined pyrimethamine and sulphamerazine. Despite treatment we observed 3 connatal infections. No newborn infant had clinical symptoms. With regard to the epidemiological situation, a toxoplasmosis screening is recommendable, at least in our area, from an ethical, moral, medical and economical point of view. To ensure, that toxoplasmosis screening is adequately effective, treatment of the pregnant women and their infants must be guaranteed both organisationally and professionally. It must also comprise health education measures, especially for non-immunised women to avoid the well-known main sources of infection.
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In the course of prenatal care, the sera from 5670 pregnant women were investigated. The average infection rate in the population was 39.22%; 60.39% were seronegative. To minimise the risk involved in toxoplasmosis infection, toxoplasma-antibodies must be definitely determined during prenatal care. This should be carried out simultaneously with the determination of antibodies to the rubella virus.
Even today, toxoplasmosis infection during pregnancy is an unsolved problem. In studies of 2206 pregnant women, toxoplasmosis specific IgM-antibodies have been detected in 69 cases (3.1%). Using more sophisticated serological techniques only 12 active toxoplasmosis cases needing therapy remained. Decisive discrimination criteria of the various tests were exact time of the examination as well as the level of the antibody titer. Although only 12 toxoplasmosis infections were treated, no connatal infections have been observed. On the other hand, in some outpatients, referred to our clinic, cases of severe connatal toxoplasmosis infections were found although they had undergone therapy. To solve the problem of toxoplasmosis, we recommend a general screening before pregnancy if possible. For optimal results of this screening, serologic reference laboratories and efficient sonography units must be established to obtain, when required, umbilical venous blood.
Toxoplasmosis is a special prenatal infection because it is susceptible to medication. Serologic screening and early diagnosis of a new infection is a prerequisite for successful treatment, which protects the fetus from infection. A case of a twenty-two year old gravida-II shows, that infection is possible despite negative initial screening. A new infection was diagnosed because of seroconversion at a routine screening at the end of the second trimester. An ultrasound scan showed severe hydrocephalus, hepatomegaly, and ascites. Labor was induced in the 33rd gestational week. Conatal toxoplasmosis was confirmed by histologic and microbiologic studies of the placenta and membranes. We discuss the difficulties resulting from negative primary serology.
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