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Biomedical subjects

D Germann

Publications and source records attributed to D Germann.

36 records · Page 2Linked to original sources

Inhibition of syncytia-inducing (SI) virus by autologous serum from HIV-1-infected individuals.

BACKGROUND: Progression from HIV infection to AIDS is often accompanied or even predicted by a switch of the virus to a more pathogenic or syncytia-inducing (SI) phenotype concomitant with the development of HIV variants escaping neutralizing antibodies. OBJECTIVE: Here we studied the capacity of sera to neutralize autologous SI-HIV or the laboratory strain III(B) and compared these data to the viral load in HIV-1-infected patients. METHODS: The SI phenotype of HIV was detected by co-cultivation of peripheral blood mononuclear cells (PBMCs) with MT2 cells in 112 patients stratified by their CD4 cell counts. Sera at dilutions of 1 : 15 and 1 : 75 were added to MT2 co-cultures with autologous PBMCs as well as with HIV-1/IIIB-infected H9 cells to study the inhibitory capacity. The p24 antigenemia was detected by enzyme-linked immunosorbent assay (ELISA) and the circulating HIV RNA was determined using the polymerase chain reaction (PCR). RESULTS: The SI virus was detected in PBMCs from 31/65 patients with < or = 200 CD4+ cells, 8/28 patients with 201-499 CD4+ cells, and 1/19 patients with > or = 500 CD4+ cells. Sera from 16/40 patients inhibited the autologous SI-HIV. In sera from patients with < or = 200 CD4+ cells, p24 antigen could be detected in 17/34 (50%) patients with non-syncytia-inducing (NSI) phenotype and in 7/19 (37%) patients carrying SI-HIV without serum inhibition. In contrast, all 12 sera with inhibitory activity to the autologous SI-HIV were negative for p24 antigen. A similar tendency was seen in patients with higher CD4+ T-cell counts. The mean load of circulating HIV RNA did not differ among groups of patients. Independently of their neutralizing activity to the autologous SI virus, the majority of sera were able to neutralize the laboratory HIV-1/III(B). CONCLUSIONS: While most of the patients' sera neutralized the laboratory HIV-1/III(B) strain, only some sera were able to inhibit the autologous SI-HIV. In these cases, the detectable SI-HIV may still be controlled by the immune system in vivo, which is consistent with a low p24 antigenemia.

Journal Article↗

Aerosolized immunoglobulin treatment of respiratory syncytial virus infection in infants.

BACKGROUND: Recent studies in animals with experimental respiratory syncytial virus (RSV) infection indicate that passive immunization by intranasal or intratracheal application of gamma-globulins (immunoglobulins) may be beneficial for treatment of infants with lower respiratory tract infection caused by RSV. METHODS: We conducted a placebo-controlled, randomized multicenter study involving 68 infants with proven RSV infection admitted to 5 pediatric centers in Switzerland from November 1, 1992, through April 30, 1993. Treatment was carried out with aerosolized human IgG (Sandoglobulin) by assisted ventilation. On the day of hospital admission a single dose of 0.1 g of IgG per kg of body weight in a 5% solution or an identical amount of placebo, each delivered in 2 parts, was given. RESULTS: The two groups did not differ substantially in their response to the aerosol received. The rate of improvement for symptoms of respiratory tract infection, oxygen requirement and length of hospital stay were comparable for both groups. There was a significant reduction (P < 0.05) in the frequency of apneic spells observed in the treatment group by Day 3 posttreatment. Aerosol therapy was generally well-tolerated in nonintubated infants, but some severe side effects (increased oxygen requirements in two patients, pneumothorax in one patient) were observed in two of three intubated and ventilated infants treated with IgG. CONCLUSIONS: Aerosolized immunoglobulin in the dosage used had no substantial beneficial effect on RSV bronchiolitis. Despite these findings passive immunotherapy for treatment of RSV-induced lower respiratory tract infection deserves further evaluation before being discarded as ineffective.

Aerosols↗

Diagnostic implications of kinetics of immunoglobulin M and A antibody responses to Toxoplasma gondii.

We evaluated immunoglobulin M (IgM) and IgA assays that could improve the predictive value for recently acquired toxoplasma infection for patients with positive screening test results. Follow-up sera were collected from 82 patients whose initial serum specimen had a reactive anti-Toxoplasma gondii IgM result. According to the evolution of the immune response, patients were divided retrospectively into two groups: one in which a recent infection was unlikely and the other one with an evolving immune response suggestive of recent toxoplasma infection. All IgM and one of three IgA assays used in the study are suitable for screening pregnant patients, with a negative predictive value of 100%. The predictive value of positive results is much lower because of the low prevalence of acute toxoplasmosis in pregnant women and the long persistence of IgM after acute infection. In the present study, all except one IgM enzyme immunoassay remained positive well beyond 6 months after the initial sample was tested. The IgM immunofluorescence test had the shortest persistence of positivity in most cases. IgA tests were either too insensitive or remained reactive too long to be useful for screening pregnant patients. Interpreting enzyme immunoassays with modified cutoff values and the combination of two tests could improve the predictive value of positive results to about 80% in terms of recent infection.

Adolescent↗

An outbreak of mumps in a population partially vaccinated with the Rubini strain.

Since 1991, 6 years after the recommendation of universal childhood triple vaccination against measles, mumps and rubella (M + M + R), Switzerland has been confronted with an increasing number of mumps cases affecting both vaccinated and unvaccinated children. The M + M + R vaccine mainly used in the Swiss population after 1986 contains the highly attenuated Rubini strain of mumps virus. We analysed an outbreak of 102 suspected mumps cases by virus isolation, determination of IgM antibodies to mumps virus in 27 acute phase sera, and verification of vaccination histories. Mumps was confirmed by virus isolation in 88 patients, of whom 72 had previously received the Rubini vaccine strain. IgM antibodies to mumps virus were detected in 24/27 acute phase serum samples. A group of 92 subjects from the same geographic area without signs of mumps virus infection served as controls. IgG antibodies to mumps virus and vaccination status were assessed in these children. The vaccination rate in these controls was 61%, with equal seropositivity for unvaccinated and Rubini-vaccinated subjects. These data support other recent reports which indicate an insufficient protective efficacy of current mumps vaccines.

Adolescent↗

[Mumps vaccines: virological basis].

The prevention of mumps virus infection relies on the application of live, attenuated mumps virus vaccines. The process of attenuation from a wildtype mumps isolate to a safe vaccine has been empirical. A lower degree of attenuation results in solid immunity but carries an increased risk of post-vaccination meningitis due to the vaccine strain. Currently used vaccine strains are highly attenuated and essentially free of vaccine strain induced disease. However, their immunogenicity may be lower than previously reported.

Humans↗

The incidence of rubella virus infections in Switzerland after the introduction of the MMR mass vaccination programme.

We have collected data on the incidence of rubella in Switzerland from 1987 to 1992 to help evaluating the impact of the measles, mumps and rubella (MMR) mass vaccination programme which started in 1985 in this country. We used detailed informations on samples submitted for diagnostic testing in conjunction with anonymous laboratory notifications to the Swiss Federal Office for Public Health, and data from the Swiss sentinel network of general practitioners to find trends in the incidence of rubella after the introduction of mass vaccination. We observed an unabated seasonal oscillation without decreasing trend during the observation period and were unable to detect a shift in the age distribution of cases. An important proportion of laboratory-confirmed rubella occurred in women of childbearing age. Immigrants from regions with low endemicity of rubella were at increased risk of contracting rubella and transmitting it to their offspring. We conclude, that MMR mass vaccination has not interrupted the circulation of rubella virus in Switzerland, and that improvements in the implementation and surveillance of the MMR vaccination campaign are necessary in order to avoid untoward effects of it.

Adolescent↗

Detection of human immunodeficiency virus (HIV) type 1 antibodies by new automated microparticle enzyme immunoassay for HIV types 1 and 2.

We compared an automated microparticle double-antigen sandwich enzyme immunoassay (EIA) for the IMx test system recently developed by Abbott with two established assays (the automated indirect Vidas IgG EIA and the double-antigen sandwich EIA from Murex/Wellcome) devised for the detection of human immunodeficiency virus type 1 (HIV-1) and HIV-2 antibodies. A total of 1,078 consecutive serum samples were tested prospectively with the three assays. In addition, we used retrospectively selected panels of serum samples with discrepant results in two different screening tests and with indeterminate or positive Western immunoblot (WB) results, as well as five commercially available HIV-1 seroconversion panels. The new assay showed excellent discriminatory characteristics for the separation of samples from HIV-1-positive and HIV-1-negative persons according to Centers for Disease Control and Prevention WB criteria. The sensitivities were 98.1, 92.9, and 96.1% for the new test and the two other assays, respectively, and the specificities were 99.7, 97.9, and 98.1%, respectively. With the seroconversion panels this new test was positive several days earlier than the two other assays; i.e., seroconversion was evident at the peak of p24 antigenemia and often several weeks before WB became positive by the most stringent criteria.

HIV Antibodies↗

[Epidemiology of HIV-1 infection in Bern--application of molecular methods].

Systematic application of molecular techniques for epidemiology may serve as a useful tool in the evaluation of HIV transmission in small populations, and allows for better targeting of prevention programs while complementing classical epidemiological methods and preserving the privacy of individuals. Coded serum samples from 24 randomly chosen patients belonging to the HIV cohort of Berne were investigated by direct assessment of partial env gene sequences. This information was used to construct a preliminary sequence database. Thereafter, nine couples, amongst whom HIV transmission was thought possible, were assessed in a blind and coded fashion. Sequence data demonstrated that the main viral subtype circulating in Berne has the characteristics of the American-European HIV-1 strain (96% amino acid homology). 4 of 9 couples were shown to share viral strains. Other potential couples carried strains with sequence characteristics that did not support the possibility of transmission. These data provide a basis for future epidemiological studies in our community.

Acquired Immunodeficiency Syndrome↗

Comparison of four enzyme immunoassays for detection of immunoglobulin M antibodies against rubella virus.

We evaluated four tests for the detection of rubella virus-specific immunoglobulin M antibodies. Primarily, consecutive serum samples were tested by two different assays. Selected panels of sera from patients with proven or likely recent rubella and false-positive and true-negative results in the two primary assays were further tested with two recently developed, fully automated techniques. The four tests were comparable in overall accuracy, but their dynamic ranges may differ considerably. Ways to optimize the predictive values are discussed. We conclude that automated assays may be used without causing significant changes in diagnostic accuracy or distortions in notifications of the incidence of rubella compared with the use of established tools.

Adolescent↗

Epstein-Barr virus infection in HIV-positive patients.

The relationship between Epstein-Barr virus (EBV) viral load in peripheral blood and HIV infection was determined in 103 HIV-infected patients. Epstein-Barr virus was detected by polymerase chain reaction in 75% of the patients, 21% of whom had the more uncommon EBV subtype 2. The highest levels of EBV were found in patients with 100-400 CD4+ cells/mm3 and not in those with more profound immunosuppression. An association was identified between EBV load and HIV proviral levels (p < 0.001), an IgM response to EBV early antigens (p < or = 0.01) and p24 antigenemia (p < 0.01 in patients with > 100 CD4+ cells), but not with other clinical or laboratory parameters. Combinations of different EBV and HIV parameters identified a subgroup of patients with a 2.2- to 4.8-fold risk of > or = 35% decline in CD4+ counts over six months. The association between EBV and HIV markers may reflect a significant pathogenic interaction between the two viruses.

Adult↗

Adult bacterial nasopharyngitis: a clinical entity?

OBJECTIVE: To investigate bacterial nasopharyngitis as a cause of adult upper respiratory infection. DESIGN: Prospective case series. SETTING: Walk-in medical clinic of a university hospital. PATIENTS: 507 patients with cold or flu symptoms, sore throat, or recent cough; 21 control subjects without symptoms of upper respiratory infection. MEASUREMENTS AND MAIN RESULTS: After thorough history and physical examination, the patients underwent nasopharyngeal aspiration and throat culture. Nasopharyngeal specimens were cultured for both bacteria and viruses; antigens for influenza, parainfluenza, and respiratory syncytial virus were sought by enzyme-linked immunosorbent assay (ELISA); serum antibodies to viral respiratory pathogens were determined. Group A beta-hemolytic streptococci grew from the throat specimens of 39 of the 507 patients (8%) or 38 of 334 patients (11%) who had clinical diagnoses of pharyngitis. Thirty-three cases of influenza A, 20 cases of influenza B, and seven cases of parainfluenza infections were diagnosed. Bacteria were cultured from the nasopharyngeal secretions of 284 patients (56%). In contrast to pharyngeal culture, commensal mixed flora were rarely found in nasopharyngeal culture. Nasopharyngeal culture of bacteria usually considered to be respiratory pathogens was significantly associated with the presence of leukocytes. Streptococcus pneumoniae (odds ratio 6.0, 95% confidence interval 2.6-14.2), Moraxella catarrhalis (odds ratio 12.9, 95% confidence interval 3.1-79.5), and Hemophilus influenzae (odds ratio 3.0, 95% confidence interval 1.2-7.4) were all associated with the presence of leukocytes. In contrast, nasopharyngeal culture of coagulase-negative staphylococci, mixed flora, and the documentation of a viral infection were not associated with the presence of leukocytes. For none of 21 control subjects were "pathogenic" bacteria found. CONCLUSIONS: These data suggest that potentially pathogenic bacteria may have a causal role in adult nasopharyngitis, although further data are needed to confirm this hypothesis.

Adolescent↗

Competitive polymerase chain reaction using an internal standard: application to the quantitation of viral DNA.

A general strategy for the construction of an internal standard for the polymerase chain reaction (PCR) is described together with its application in the evaluation of clinical samples. This internal standard is a plasmid containing a modified target sequence that is co-amplified with the native target using the same set of primers. The co-amplification reaction will generate two fragments of different size that are readily separated without the need for restriction enzyme digestion. Thereafter, they are detected and quantitated by hybridization to the same probe. Detection of HIV proviral DNA was chosen as a model for this competitive PCR. The assay proved to be a sensitive tool for the detection of PCR inhibitors and allowed quantitation of HIV with a 20-30% variation coefficient. Despite limitations that appear inherent to the amplification process, internal standards appear to be useful tools for quantitative analysis by PCR.

Base Sequence↗

Virus inactivation during production of intravenous immunoglobulin.

The effect of pepsin treatment at pH 4 on the infectivity of several enveloped viruses was assessed under the conditions used during the production of intravenous immunoglobulins. It was shown that the prototypes of four virus families--human immunodeficiency virus (Lentivirinae), herpes simplex virus type 1 and human cytomegalovirus (Herpesviridae), Semliki Forest virus (Togaviridae), and vesicular stomatitis virus (Rhabdoviridae)--were inactivated by this procedure. With vesicular stomatitis virus as a model, the contributions of both low pH and pepsin were demonstrated, and pepsin had a synergistic or additive action.

Animals↗

[Carotid artery dissection. Case examples and review].

"Spontaneous" dissection of the internal carotid artery is a not unusual cause of stroke, particularly in younger subjects. Initial signs are typical, whereas the spectrum of neurological deficits is wide. Three selected case records are presented which demonstrate the spectrum of symptoms and the management of this disease.

Adult↗

[Viral respiratory infections in children: new diagnostic methods for early detection. Initial results of a pilot project in Switzerland].

The new methods of rapid viral diagnosis make it possible to specify a number of the most prevalent agents of respiratory tract infections within 24 hours. The techniques are based on the immunological detection of antigens of respiratory syncytial (RSV), adeno, parainfluenza type 1, 2 and 3, as well as of influenza A and B viruses in nasopharyngeal secretions. During a one-year period we have used these methods to evaluate diagnostically 1541 outpatients presenting with upper and lower respiratory tract infections. The patients included babies, infants and children under 16. In about 50% of all sick babies below the age of three months a definite viral infection could be established, and in approximately 30% of infants and children aged up to 4 years. RSV was most frequently observed, accounting for 53.6% of all infections (80% of all babies below the age of 3 months, in whom specified agents could be identified, had RSV infection). The next most frequent pathogens were parainfluenza type 3 (18,8%), influenza A (11,3%) and, finally, adenoviruses (10.2%). The epidemiological and clinical characteristics of these infections are summarized. In addition, the results of these antigen detecting assays have been compared with those of concomitantly conducted virus isolation techniques in cell cultures. This comparative analysis most impressively revealed the time saved by attempting an etiological diagnosis using the antigen detecting system: in only 6% was a specific diagnosis established on the basis of virus isolation, whereas the delay was equal or more than 8 days in 36% of all patients enroled.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoviridae↗