[The significance of rare viral infections and the etiology of fetal damage]. / Die Bedeutung seltener Virusinfektionen für die Entstehung kindlicher Schäden.

Viral infections of the mother during pregnancy are responsible for approximately 10% of birth defects. Infections with Rubella-, Cytomegalo-, Mumps-, Measles- and Chickenpox-Virus in early pregnancy are associated with abortion or abnormal development of the fetus. While infection with Chickenpox, Hepatitis B, Herpes simplex and Enterovirusinfection at the end of pregnancy may affect the newborn. - It is estimated that birth defects due to viral infections in the pregnancy are accounting for ca. 2500 clinically affected newborns among 100,000 deliveries. The number of children well at birth but developing late onset of disease due to intrauterin viral infections is presently difficult to estimate. - It is difficult to make an aetiological diagnosis of birth defects on the basis of clinical symptoms but laboratory methods have improved considerably during the last years and they are helpful in improving the aetiology and can be used as a guide line in taking care of the patients. - In case a woman has contact during pregnancy with one of the above mentioned virus infections the immunstatus can be determined rapidly and a diagnosis of primary or recurrent infection may be established. Women at risk for primary infections may be given hyper immun globulin, vaccinated or treated with anti-viral drugs. Interruption of pregnancy may also be considered for those who run a high risk of delivering a damaged child.

[New methods for demonstration of antigens and antibodies (author's transl)]. / Neuere Methoden zum Nachweis von Antigenen und Antikörpern

With the improvement of diagnostic procedure for the demonstration of antigens and antibodies it has been possible to increase the sensitivity and the specificity of antigen/antibody reactions, to introduce microtechniques and to apply a certain degree of automation and standardization, to allow a better interpretation of the results, and to cope with the ever increasing load of serological reactions.

Solid phase immunosorbent technique (SPIT) for the demonstration of specific IGM antibodies by hemagglutination inhibition and passive hemagglutination.

The adsorption of protein to glass and plastic has been well documented. It has also been demonstrated that the absorbed antigen or antibodies retain their activity in as much as they are able to react with a specific antibody respective specific antigen(1). Furthermore the adsorbed antignene or antibody complex may also react with a later added antigen. Anti IgM is adsorbed to the solid phase and will retain IgM from the patient's serum. If the patient's serum contains specific IgM this will react with the specific antignene. If the antigen is a hemagglutinin it will combine with the specific IgM and therefore added erythrocytes will not hemagglutinate. If the antigen is coated on erythrocytes the coated erythrocytes will combine with the specific IgM and hemagglutination will take place. The reaction is schematically demonstrated in Fig. 1.

Complement-fixing antibodies against cytomegalovirus in different parts of the world.

A WHO cooperative study in which 27 laboratories participated showed that the distribution of cytomegalovirus antibodies in healthy blood donors varies widely, ranging from 40% in highly industrialized areas to 100% in developing countries. Climatic factors did not appear to play an important role in the spread of the virus.

[Clinical data on Legionnaires' disease. Report on 8 sporadic cases of Legionella pneumonia]. / Zur Klinik der Legionellose. Bericht über 8 sporadische Fälle von Legionella-Pneumonie.

In 1978 and 1979, eight sporadic cases of Legionella pneumonia were observed in the Berne and Ticino areas of Switzerland. In all cases the diagnosis was established serologically using indirect immunofluorescence. Seroconversion was observed in five patients. In three cases initially high antibody titers decreased progressively. The clinical picture was characterized by acute onset with high fever, frequent chills, and dry cough. Occasional concomitant symptoms included muscular pains, headache, thoracic pain, dyspnea, hemoptysis, and gastrointestinal and central nervous symptoms. Laboratory findings showed markedly increased BSR as well as slightly increased WBC with a pronounced shift to the left. In all cases, X-ray examinations demonstrated extended, mainly unilateral and often remarkedly peripheral infiltrations of the lung. On the basis of the clinical course, two groups could be distinguished: (a) non-complicated cases of pneumonia with rapid improvement within 2-3 weeks; and (b) cases with a protracted sometimes severe course with persistence of the infiltrations up to 4 months and more. All patients with a protracted course suffered from concomitant symptoms. Whereas none of the patients died of legionellosis, two patients died six months later from their underlying disease. Most patients were treated with several antibiotics. In three patients definite improvement occurred only after therapy had been changed to doxycycline. Erythromycin, currently recommended as the drug of choice, was used in none of these cases.

A collaborative study of cytomegalovirus antibodies in mothers and young children in 19 countries.

Regional variations in the incidence of cytomegalovirus (CMV) injections in mothers and young children were investigated by testing cord blood and serum samples from infants and children up to four years old for the presence of CMV antibodies in 19 different regions of the world. The samples were tested by both the local virus laboratory and the reference laboratory, using the same batch of complement-fixing CMV antigen and techniques which were validated by comparison of the titres recorded for samples of coded sera sent to each laboratory. The incidence of CMV antibodies varied from 44-100% in mothers and from 3-95% in young children. The number of children with CMV antibodies increased with age in five areas; suggesting that there was some child to child transmission of CMV infection between children in these regions. In the other regions, the absence of any significant age-related increase indicated that the main pathway of CMV infection in early life was by transmission from mothers to their infants. The significance of these findings is discussed.

Differentiation of recent and past infections with Legionella pneumophila by determination of specific IgM.

The ELA-IgM antibody test as used in viral diseases can also be applied to infections with Legionella pneumophila and is yielding similar results as the IgM determination by immunofluorescence. Complement-fixation and microagglutination are yielding also positive results in IgM-positive sera. IgM antibodies appear relative late after beginning of the disease and are persisting for several months. There is evidence that IgM antibodies as detected by the use of a Legionella pneumophila antigen are also cross-reacting to a number of other antigens.

[Legionnaire's disease in Switzerland]. / "Legionnaires' disease" in der Schwiez.

The sera from 2453 patients suffering from pneumonia were investigated for antibodies against the agent causing "Legionnaires' disease". A complement-fixing antigen developed in this institute was used for the screening of these sera, and the positive results were confirmed with the IF-test developed by CDC Atlanta. Antibodies were found in 23 Swiss patients. The clinical details from one of these patients are presented.

A solid-phase immunosorbent technique for the rapid detection of rubella IgM by haemagglutination inhibition.

The rubella haemagglutination inhibition (HAI) test has been modified for the detection of rubella-specific IgM. The rubella HAI test is performed in microtitre plate wells in which IgM from patients' sera has been selectively retained by anti-human IgM bound to the polystyrene surface. The test requires only anti-human IgM-coated microtitre plates, in addition to the standard rubella HAI reagents. The results obtained in this test, a solid-phase immunosorbent technique (SPIT), are in good agreement with results obtained by the sucrose density gradient centrifugation technique (DGCT). Advantages include the essentially unrestricted number of sera which can be tested daily, the availability of results within 24 h and the lack of interference by rheumatoid factor and by rubella-specific IgG.

Congenital cytomegalovirus infection in newborn infants of mothers infected before pregnancy.

The rate of congenital cytomegalovirus (CMV) infection was studied in newborn infants in an African population in which all adults had experienced primary CMV infection during childhood. Viruria within the first 12 hours after delivery was taken as evidence of prenatal CMV infection. 28 of 2032 newborn infants examined had viruria, giving a rate of 1.4% congenital CMV infection. The presence of meternal serum antibody therefore appears not to protect the fetus from intrauterine infection. Either reactivation of latent maternal CMV infection or recurrence of infection during pregnancy despite the presence of serum antibodies may explain these findings. Whether the long-term effects of CMV infection acquired in utero differ in cases of primary maternal infection from those due to reactivated or recurrent infection in seropositive mothers, remains undecided. Thus, the value of a live CMV vaccine to prevent prenatal CMV infection may be questioned.

[Microbiological aspects of Legionnaires' disease]. / Mikrobiologische Aspekte der Legionärskrankheit.

Legionella pneumophila was isolated in 1947 but its etiological role was only recognized after the Philadelphia outbreak in 1976. Since then, infections with Legionella pneumophila in patients with so-called atypical pneumonia have been found in different parts of the world in sporadic cases and outbreaks affecting up to several hundred patients. The etiological agent is a bacterium which can be found in dust, mud and water. Transmission to the human most likely occurs through water-cooled air condition units or showers. Air conditioning in hotels, hospitals and offices may transmit the organism and lead to infection which, moreover, is more frequent during the warm season. The diagnosis is based on clinical data and the demonstration of specific antibodies. Isolation of the agent is technically difficult and up to now only approximately 3% of the cases have been confirmed by isolation of the agent. Evidence of Legionella pneumophila infection in Switzerland was obtained by testing stored blood samples from transplanted patients in 1970. Sporadic cases were observed in the period 1977 to 1980. Acute infection was considered in 141 patients on the basis of serological results. Approximately 3% of all pneumonias in 1979 were caused by Legionella pneumophila. Isolation of the etiological agent has been achieved in 3 patients only.

The preparation of a reference serum for the determination of IgG and IgM antibodies against cytomegalovirus and its evaluation in a collaborative trial.

It is now generally accepted that laboratory data produced by different laboratories using different techniques can be better compared if the results are related to a reference preparation. Even within one laboratory the use of a stable reference preparation helps to reduce the day to day variation of the results. Although this idea has been firmly established for many years the introduction of reference preparations so far has met only with limited success. One of the reasons for this development may be the lack of adequate preparation to be used for this purpose. Recently, diagnostic virology has introduced new serological methods in an effort to make a rapid diagnosis and to differentiate between acute and past infection by the determination of specific antibodies in the IgM, IgA or IgE fraction of the patient's serum. In such a situation, a reference IgM serum of low activity would help to differentiate between persistent or past and recent infection. It was therefore attempted to establish such a reference serum containing antibodies against CMV in the IgM fraction.