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EFFECT OF PREVENTIVE MEASURES: The development of reliable routine serology tests and the demonstration of the high prevalence of toxoplasmosis in France led to mandatory prospective screening of pregnant women in 1978, followed by prenatal screening in 1985. In addition, in utero diagnosis, first on fetal blood and now with the reliable and safe method using polymerase chain reaction on amniotic fluid, formally identifies the parasite. THE SITUATION TODAY: A comparison of the experience of a specialized center in Paris during three different periods over the last 40 years showed that currently 71% of all cases of congenital toxoplasmosis are infraclinical at birth and only 5% are severe. Mean incidence of seroconversion during pregnancy is 1.48%, with a 40% risk of fetal contamination if no treatment is given. The risk of overt fetopathy predominantly concerns maternal infections occurring prior to 26 weeks gestation. IN UTERO TREATMENT: Positive PCR diagnosis on amniotic fluid imposes serial ultrasound examinations to identify any fetopathy and an in utero treatment by giving the mother the pyrimethamine-sulfadiazine combination. Biological results are favorable. POST-NATAL TREATMENT: Post-natal treatment is indicated even in latent forms and should be continued for the first year of life. The pyrimethamine-sulfadiazine combination is the only pharmaceutical regimen with well-proven efficacy. New compounds should allow better prophylaxis against maternofetal contamination or improved post-natal treatment. RECURRENCE: In 70% of the cases, serology tests become positive again, but are not associated with significantly increased risk of ocular recurrence.

Objectives: Over a period of 13 years (1982-1995), 49 cases of acquired toxoplasmosis complicated with ocular and/or neurologic or meningeal involvement were observed in our toxoplasmosis laboratory. This series includes 43 cases of isolated ocular lesions, 3 cases of meningoencephalitis (associated with retinochoroiditis in 1 case), 1 case of meningitis with uveitis, 1 case of polyradiculoneuritis and 1 case of facial nerve palsy., Methods: The patients were aged 1 to 62 years. None had either spontaneous or iatrogenic immunodeficiency. There were two steps in the diagnosis. First congenital infection was eliminated on one or several of the following criteria: any possibility of maternal infection during pregnancy ruled out in 26 cases, evidence of recent acquired infection (i.e. clinical and/or serological evidence of recent acquired toxoplasmosis in 17 cases, retinochoroiditis in non-twin siblings in 3 cases). The second step was to confirm the diagnosis of toxoplasma infection. Apart from serological evidence of recent infection, confirmation included specific local antibody synthesis in the aqueous humor of the eye and/or in cerebro-spinal fluid or ocular lesions characteristic of toxoplasmosis and absence of other etiology., Results: Ocular lesions were unilateral in 43 cases among 45. A mean follow-up of 37.9 months revealed relapses in 14 among 36 patients (39%). As routine serological examination for toxoplasmosis is compulsory in France since 1978, it was possible to document retrospectively the immune status of the mothers of many of the patients of the present series during pregnancy and to rule out congenital toxoplasmosis in a number of cases. This might explain the discrepancy between the relatively large number of cases in the present series and the fact that complicated acquired toxoplasmosis has been considered hitherto as relatively rare in immunocompetent patients., Conclusion: Based on the epidemiology of ocular toxoplasmosis and the data obtained here, it is suggested that the acquired pattern of ocular toxoplasmosis might be more frequent than estimated up to now.

Background: Postnatally acquired toxoplasmosis is relatively common as an unapparent infection. When there are severe clinical manifestations such as encephalitis, pneumonia and myocarditis, the patient should be checked for immunocompetence deficiencies., Case Report: A two-year old girl living in French Guyana suffered from acute respiratory distress due to interstitial pneumonia plus pericarditis that was treated by closed pericardial aspiration. Palsies of four limbs and chorioretinitis gradually appeared. The CSF protein content was elevated, 1 g/l, but the number of cells was normal. Serologic tests indicated a recent toxoplasma infection; she was given sulfadoxine, pyrimethamine and spiramycin. Her neurologic condition and the persistent antibodies, indicating active disease, led to her transfer to our Department 3 months after the onset of the disease. The CSF contained 47 cells/mm3 and 0.8 g/l proteins. Measurement of both IgM and IgG classes of toxoplasma antibodies showed persistent high titers in the blood and CSF. The CT scan showed numerous calcifications in the brain and hypodense areas in the frontal and parietal lobes. The MRI showed extensive changes. The severity of the disease in this girl led us to study her immune system. It was normal. The girl was given 6-week treatments with pyrimethamine-sulfadiazine for 2 years. This treatment stabilized the disease, but her titers of toxoplasma antibodies remained high., Conclusion: The initial clinical presentation of the disease in this patient and persistent high titers of toxoplasma antibodies, especially of the IgM class, argue against the possibility of congenital toxoplasmosis and favor the diagnosis of acquired disease in a patient who has no immune deficiency.

Eighty to ninety percent of pathogens responsible for acute respiratory infections in children are viruses, but despite advances in virology these organisms are isolated in only 20 to 45 percent of the cases. Studies conducted outside hospitals have provided epidemiological data. The virus most frequently encountered is the respiratory syncytial virus. The main clinical feature of these respiratory viral infections is obstruction of the bronchioles, and their immediate or delayed danger is the risk of chronic obstructive bronchitis. Treatment is symptomatic, but specific antiviral agents, notably ribavirin, are useful in severe infections.

Among all organ transplantations, those of heart or heart-lung carry the greatest risk of toxoplasmosis. The disease is observed mainly when the donor is seropositive and the recipient seronegative. In these mismatched couples the risk may be as high as 57 percent. Cardiac tissue transplants are responsible for most contaminations. A subclinical serological reactivation can be observed in seropositive recipients. Patent forms are associated with seroconversion in seronegative subjects. Toxoplasmosis is often severe with multivisceral foci; interstitial pneumonia is possible. The serological diagnosis is easy in cases with significant antibody movements, but it may be difficult if the titre is low or stable. The parasitological diagnosis rests on the isolation of toxoplasma in blood, cerebrospinal fluid, bronchoalveolar lavage fluid and cardiac or cerebral biopsy. Immune defence against toxoplasmosis is primarily cellular, with lymphocytosis and inversion of the CD4/CD8 ratio. Macrophages play a crucial role. Interferon-gamma is the major mediator of cellular resistance. In spite of its immunosuppressive action, cyclosporin clearly has an antiparasitic action in vitro and in vivo. A cytomegalovirus infection might facilitate toxoplasma reactivation. Prevention of toxoplasmosis in transplant recipients includes systematic serology of the recipient and, if possible, the donor, detection of mismatched couples and systematic treatment with pyrimethamine of recipients at risk (in seronegative recipients, this drug has reduced the risk from 57 to 14 percent). Cyclosporin should be used as immunosuppressant in preference to other drugs of this kind. Corticosteroids administered in rejections increase the risk of toxoplasmosis.

Background: Respiratory problems in neonates and infants may be the result of a variety of neuromuscular dysfunctions. Neurologic evaluation of functions, such as sucking and swallowing, may be difficult in these very young infants and can be helped by neurophysiological studies., Methods: 12 infants admitted because of repeated episodes of respiratory obstruction due to difficulties of sucking and/or swallowing took part in the study. The neurophysiological studies included electromyography of the facial, lingual and pharyngeal muscles, brain stem auditory evoked potentials and measurement of the blink reflexes. The results were correlated with events during the perinatal period and those that occurred during the follow-up., Results: Dysphagia was evident from the neonatal period; it was complicated by nasal reflux and aspiration bronchopneumopathy. Facial diplegia was observed in 8 patients. 9 patients failed to thrive. The electromyographic patterns showed partial denervation of the facial, lingual and pharyngeal muscles in all cases; the blink reflex was altered in 11 cases, and the brain stem evoked potentials were abnormal in 3 of the 8 cases tested. 7 of the infants had histories of pregnancy and obstetrical abnormalities, and/or fetal distress. The swallowing function partially improved within several months., Conclusions: Neurophysiological studies indicate neurofunctional alterations in the VII, IX, X and XII cranial nerve nuclei, V and VII pathways and the auditory tract. These lesions and the time course of improvement suggest that they are due to pre- or perinatal anoxo-ischemic brain stem injury.

In two infants with recurrent lower respiratory tract infections starting within a few weeks of birth, dynamic electromyographic studies of sucking and swallowing evidenced a disorder of lingual and pharyngeal activities responsible for the episodes of aspiration. The central location of the anomaly was demonstrated by the absence of peripheral neuromuscular anomalies and by the presence of impaired blinking reflexes and brain stem potential anomalies. These neurofunctional anomalies improved over time and magnetic resonance imaging failed to disclose and structural anomalies of the central nervous system. The occurrence of the swallowing disorder as an isolated manifestation and its long duration, with follow-ups of 23 months and 4 years, are two unique features in these cases. Neurophysiologic investigations are essential for documenting the neurologic etiology of the swallowing disorders, demonstrating their location above or within the medulla oblongata, and differentiating functional and organic anomalies.

Compliance with treatment is a crucial factor in the management of asthmatic children which depends on the understanding of the disease and its treatment. The understanding of, and compliance with treatment were evaluated by means of a questionnaire in 50 parents of asthmatic children. 50% of these parents used anti-histamines as maintenance treatment and 30% also used these drugs during attacks. Half the parents knew about the bronchodilator effects of theophylline and B2-agonists. 42% and 30% respectively of the parents thought that the side-effects of theophylline or corticosteroids were few or inexistent; 86% claimed regular attendance to out-patient clinics, but 30% confessed that they had forgotten such drugs as theophylline and antihistamines. 50% took the appropriate therapeutic measures when confronted with a moderate or severe attack of asthma. Each child received 2.3 drugs on average for his or her asthma. This study shows that parents have an insufficient knowledge of asthma treatments, and this may partially explain the poor compliance with therapy as well as the morbidity and mortality associated with childhood asthma.

The mothers of 52 cases of toxoplasmic fetopathy diagnosed in utero by fetal blood and/or amniotic fluid sampling were treated with the combination pyrimethamine-sulfadiazine (or sulfisoxazole) and by spiramycine. The infants were compared with 51 other infants with congenital toxoplasmosis whose mothers had received spiramycine alone. Patients of both groups received the same pyrimethamine-sulfadiazine and spiramycine treatment after birth. Parasitologic examination of the placenta was positive in 42 and 76.6% of patients, in group I and group II respectively. The newborns had specific IgM in 17.4 and 69.2% of cases respectively in both groups. These differences were significant. The mean specific IgG titer was significantly reduced at birth and 4 to 6 months of age in the first group. Patients in group I had more often subclinical infection than patients of the comparison group: 57% vs 33.3%. They had less often a high cerebro-spinal protein content during the first week. Prenatal treatment with pyrimethamine-sulfadrugs resulted in a less progressing infection at birth. However in cases with clinically patent toxoplasmosis, the frequency of overt localizations and their sequellae was not significantly altered. This might be related to a relatively late onset of the treatment. The pyrimethamine-sulfadrug combination given to mothers of proved infected fetuses can be rewarding. The indication might be extended to well-documented seroconverted mothers if, in the future, the acquired experience and necessary pharmacological studies bring the proof of its innocuousness.

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.

We report the follow-up of 13 infants aged 2.5 to 24 months in whom cystic fibrosis disease presented as respiratory distress. All infants received an intensive treatment. Mean clinical, radiological and microbiological follow-up was 3.1 years. Ten children aged 1.5 to 8.5 years are still alive. One of them presents with serious respiratory failure, with a Shwachman score of 50. The Shwachman score is between 85 and 70 for 8 of 13 and 65 for one. The prognosis of this group did not differ from the one usually observed in the disease. It depends partially on early intensive care management and is not altered by mechanical ventilation.

Five cases of congenital toxoplasmosis consecutive to a maternal toxoplasma infection that had preceded pregnancy were observed. One woman with normal immune system had developed a well-documented lymph node toxoplasmosis 2 months before conceiving. Four women had chronic toxoplasmosis diagnosed in the course of an immunosuppressive disease: Hodgkin's disease in 1 case, systemic lupus erythematosus in 2 cases and pancytopenia in 1 case. Toxoplasmosis had been recognized 3, 5 and 10 years respectively before conception in 3 women, and at an uncertain date in 1 woman. Three women had received corticosteroids during pregnancy, and 2 had undergone splenectomy. Among the 6 children (2 were twins), 1 presented with severe foetal disease at birth, 1 developed lethal systemic toxoplasmosis after birth, 1 showed hydrocephalus with therapeutically well-controlled chorioretinitis, 1 had isolated eye lesion and 2 had asymptomatic infection. The parasite seems to have been transmitted after the 20th week of pregnancy in all cases. The physiopathology of mother-to child toxoplasma transmission, the role played by maternal immunodeficiency and the practical implications of these exceptional cases are discussed.

Case report of a Liebow's desquamative interstitial pneumonia in a 3 week-old infant. The disease resulted in permanent respiratory failure. Steroid therapy had no durable effect and death occurred at 4 1/2 months of age.

100 cases of bronchial foreign body seen over a period of 4 years represent 1.2% of the admissions of a paediatric pneumology unit; 73% of the children were aged between 6 months and 3 years. The foreign body was vegetable in 61% of cases (a peanut in 44% of cases). The time between the inhalation and the endoscopic diagnosis was greater than 7 days in 70% of cases and greater than 30 days in 37% of cases. Removal of the foreign body was possible in all but one case. In particular, the authors studied the pneumological implications of a foreign body: the value of a quantitative bacteriological study of the bronchial secretions, which was significant in 43% of cases, and detection of the sequelae by prospective clinical and functional surveillance with a follow-up of 3 to 24 months. After 6 months, persistent radiological abnormalities were found in 40% of cases, perfusion disorders were found in 35% and ventilation disorders were found in 64%. A surgical operation was performed in 7 cases: one case of bronchotomy for extraction of the foreign body and 6 cases of parenchymal excision, including 2 total pneumonectomy for a destroyed lung. These were no death. The pathophysiology of the complications of functional disorders and of dilatation of the bronchi is discussed in the context of the experience gained from this series.

The early onset of the disease (between the 13th and 15th days of life) and its long duration in 2 out of 3 cases, the absence of infectious symptoms and the efficacy of erythromycin treatment were characteristic features. The diagnosis was confirmed by positive (greater than 1/32th) serological tests in both infants and parents. Chlamydia trachomatis lung infection should be suspected in infants presenting, during the first weeks of life, with cough and dyspnoea unaccompanied by fever, radiological evidence of interstitial pneumonia, blood eosinophilia and raised immunoglobulin levels. The disease results from intranatal contamination and might represent, in France as in the U.S.A., an important percentage of respiratory infections occurring during the early months of life.

A 4 1/2 month-old infant presented with severe alveolo-interstitial pneumonitis needing intubation and mechanical ventilation. Legionella pneumophila infection was established by a significant increase in antibody titers. The clinical picture was consistent with that of legionnaires' disease. No immune defect could be proven.

Needle biopsy was performed in 100 children with diffuse interstitial pneumopathy. Severe histological lesions were noted in the biopsy sections in 4 out 5 cases. Those most frequently observed (57 cases) were non-specific lesions of diffuse interstitial pneumopathy (DIP) or idiopathic fibrosis, the course of which was followed, in some cases, by repeating the biopsy. Specific lesions, especially idiopathic pulmonary hemosiderosis (8 cases), were noted in 22 children, either associated with interstitial fibrosis or apparently better tolerated. The other 16 cases included the lipoidoses (Niemann-Pick, histiocytosis X), alveolar microlithiasis, and some specific inflammatory diseases (tuberculosis, syphilis) or those related to inhalation of a foreign body.

Four children aged between 7 and 19 months with severe bronchopneumonia due to adenovirus type 7, proved by virology and/or serology developed severe hyponatraemia. One of them is reported in detail: it was possible to estimate plasma ADH levels and thereby prove the existence of reversible hypersecretion of the hormone. Whilst the syndrome of hyponatraemia with inappropriate secretion of ADH has not yet been reported in association with severe pneumonia in the child, it is known in adults. The limits of the syndrome and its physiopathology are discussed. It may be due either to vagal stimulation as a result of a fall in left aressure, or to central involvement. Therapeutic implications of the problem are emphasized.

Chlamydia trachomatis now has an important place in infantile respiratory pathology. In neonates, it is transmitted in utero, which explains one quarter of the cases of interstitial pneumonia seen during the first months of life. In children, the number of carriers of antibodies increases with age and may be more than 40 p. cent by the age of 7 years. The mode of contamination and the pathological significance remain uncertain in this age group. Chlamydia trachomatis can be a cause of pneumonia in immuno-depressed patients. A survey conducted in a Paediatric Respiratory Medicine Unit showed that 22 p. cent of patients were carriers of the antibody and at least 7.8 p. cent were infected.