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Biomedical subjects

L Matter

Publications and source records attributed to L Matter.

At least 19 recordsLinked to original sources

Age-specific seroprevalence to varicella-zoster virus: study in Swiss children and analysis of European data.

Up to date epidemiological data provide the rationale for potential varicella immunization strategies in Europe. The scope of this study was: (1) to generate new seroprevalence data by evaluating sera of 970 individuals aged 0-16 years for the presence of IgG against Varicella-zoster virus (VZV); and (2) to review existing seroprevalence data. Of 256 individuals >12 years of age, 96.1% (95% confidence interval [CI], 93.7-98.5) were seropositive. Swiss citizens > 12 years of age were less likely to be seronegative than foreign citizens (2.3 vs. 15.4%; odds ratio, 0.17; CI, 0.05-0.58). The age-specific seroprevalence curve demonstrated a peak at 7 years of age (84.9%; CI, 75.2-94.5) followed by lower rates at 8 and 9 years. A peak at 7-10 years of age was found in all previously reported seroprevalence curves (chi(2)-test for trend of pooled data, P = 0.09; Poisson analysis, P < 0.001). It is concluded that: (1) > 90% of individuals in Europe acquire immunity against VZV before adolescence; (2) there is no evidence for a recent upward shift of the age at primary varicella; and (3) there may be a north-to-south gradient of seroprevalence. The peak at 7-10 years may represent a transient loss of detectable antibody by some individuals.

Adolescent↗

Community-acquired pneumonia. A prospective outpatient study.

We initiated a prospective study with a group of practitioners to assess the etiology, clinical presentation, and outcome of community-acquired pneumonia in patients diagnosed in the outpatient setting. All patients with signs and symptoms suggestive of pneumonia and an infiltrate on chest X-ray underwent an extensive standard workup and were followed over 4 weeks. Over a 4-year period, 184 patients were eligible, of whom 170 (age range, 15-96 yr; median, 43 yr) were included and analyzed. In 78 (46%), no etiologic agent could be demonstrated. In the remaining 92 patients, 107 etiologic agents were implicated: 43 were due to "pyogenic" bacteria (39 Streptococcus pneumoniae, 3 Haemophilus spp., 1 Streptococcus spp.), 39 were due to "atypical" bacteria (24 Mycoplasma pneumoniae, 9 Chlamydia pneumoniae, 4 Coxiella burnetii, 2 Legionella spp.), and 25 were due to viruses (20 influenza viruses and 5 other respiratory viruses). There were only a few statistically significant clinical differences between the different etiologic categories (higher age and comorbidities in viral or in episodes of undetermined etiology, higher neutrophil counts in "pyogenic" episodes, more frequent bilateral and interstitial infiltrates in viral episodes). There were 2 deaths, both in patients with advanced age (83 and 86 years old), and several comorbidities. Only 14 patients (8.2%) required hospitalization. In 6 patients (3.4%), the pneumonia episode uncovered a local neoplasia. This study shows that most cases of community-acquired pneumonia have a favorable outcome and can be successfully managed in an outpatient setting. Moreover, in the absence of rapid and reliable clinical or laboratory tests to establish a definite etiologic diagnosis at presentation, the spectrum of the etiologic agents suggest that initial antibiotic therapy should cover both S. pneumoniae and atypical bacteria, as well as possible influenza viruses during the epidemic season.

Adolescent↗

HAART in HIV-infected patients: restoration of antigen-specific CD4 T-cell responses in vitro is correlated with CD4 memory T-cell reconstitution, whereas improvement in delayed type hypersensitivity is related to a decrease in viraemia.

OBJECTIVE: To analyse prospectively the effect of highly active antiretroviral treatment (HAART) on CD4 T-cell responses in vitro and in vivo in HIV-infected patients. DESIGN: Prospective study with 49 protease inhibitor-naive adult patients. Data were collected at baseline and after 3 and 6 months of HAART. METHODS: In vitro CD4 T-cell reactivity was analysed by stimulation of peripheral blood mononuclear cells with several antigens. In vivo CD4 T-cell reactivity (delayed type hypersensitivity) was assessed by Multitest Merieux. Both measurements were correlated to CD4 (memory) T-cell count and HIV-1 viraemia. RESULTS: Restoration of specific CD4 T-cell proliferation was observed in most patients. The in vitro T-cell response was restored more frequently against antigens to which the immune system is constantly exposed (Candida albicans, Mycobacterium tuberculosis, M. avium) as compared with a low-exposure antigen (tetanus toxoid). Overall, delayed type hypersensitivity detection rate increased under HAART. Multivariate analysis showed improvement of antigen-specific T-cell proliferation to be significantly associated with an increase in memory CD4 T-cells, whereas improvement of the delayed type hypersensitivity response was associated with a decrease in plasma HIV-1 RNA. CONCLUSIONS: HAART for 6 months restored antigen-specific CD4 T-cell response to several antigens. In vitro immune reconstitution was closely correlated with an increase in memory CD4 cells. Restoration of delayed type hypersensitivity was associated with suppression of viraemia. It appears that in addition to expansion of memory CD4 cells, suppression of viraemia following HAART may allow an improved inflammatory reaction, thus providing even stronger immune reconstitution.

Adult↗

High frequency of non-B subtypes in newly diagnosed HIV-1 infections in Switzerland.

HIV-1 subtypes were determined in newly diagnosed residents of Switzerland. Blood was anonymously collected from patients with a first confirmed positive HIV-1 test result. Viral DNA from the env V3-V5 region was amplified by nested polymerase chain reaction (PCR) and screened for subtype B by heteroduplex mobility assay. All amplicons not identified as B were sequenced. From November 1996 to February 1998, 206 samples were analyzed. Main transmission risks were unprotected heterosexual (55.7%) or homosexual (27.1%) sexual contact or intravenous drug use (12.9%). Subtype B dominated in patients of Swiss, other European, American, or Asian citizenship; particularly high frequencies were found in homosexuals (97%) and drug users (94%). Non-B subtypes including A, C, D, E, F, G, H, a possible B/F recombinant, and a sequence related to J were present in 28.2% (95% confidence interval [CI], 22.9%-35.0%). Non-B were frequent in African citizens (95%), heterosexually infected individuals (44%), and women (43%). Heterosexually infected Swiss males harbored non-B strains in 18% and females in 33%. The results document a change in the epidemiology of newly diagnosed HIV-1 infections in Switzerland: predominance of heterosexual transmission and a high frequency of non-B subtypes.

Adult↗

[Increasing the immunization rate against measles, mumps, and rubella in medical students at the University of Berne].

From 1992 to 1997 the seroprevalence of antibodies against measles, mumps and rubella (MMR) in Swiss medical students was between 77.3% and 86.2%, which is clearly below the target of > 95%. To prevent MMR infections in doctors and possible transmission to their patients, in 1994 we started a project in which MMR vaccination was offered to non-immune students. During three courses in medical school, 82 of 87 (94.3%) non-immune students were vaccinated, thus increasing the immunization rate to more than 96%. We have developed a spread sheet allowing calculation of the direct costs of two different strategies: 1. Determination of immunity followed by MMR vaccination of non-immune students; 2. Universal MMR immunization. Screening before vaccination was less expensive if the immunity level was higher than 73.5% and the calculation was based on prices for mass screening and mass vaccination. Universal immunization was favoured when prices for individual antibody determinations and vaccinations were used for the calculation. A targeted programme of MMR vaccination was successful in increasing the immunization rate of medical students against MMR to > 96%.

Adult↗

Diagnosis by polymerase chain reaction of pneumonia caused by Legionella pneumophila in an immunocompetent child.

A 10-year-old, previously healthy child with pneumonia caused by Legionella pneumophila diagnosed by polymerase chain reaction (PCR) of serum is presented. Diagnostic methods were PCR of serum using two different primer sets, and the detection of specific antibody in paired sera using an indirect immunofluorescence assay. Legionella DNA was amplified from serum obtained before and on day 6, but not after completion of a 14-day course of oral clarithromycin. The etiologic role of L. pneumophila was confirmed by seroconversion. The report illustrates that L. pneumophila PCR of serum may contribute to the identification of this microorganism as a cause of severe pneumonia in immunocompetent children.

Anti-Bacterial Agents↗

Outbreak of echovirus 30 meningitis in Switzerland.

This study includes 80 patients (38 children and 42 adults) who contracted aseptic meningitis in the summer of 1996 in Fribourg, Switzerland. Virological studies revealed an enteroviral infection in 65 out of 70 (93%) investigated patients. In 47 out of the 53 cases (89%) where a precise virus could be identified, the causative agent was an Echovirus 30. More than 50 patients lived in an area within a 5-km radius. The patients presented with the classic symptoms and signs of aseptic meningitis. In contrast, polymorphonuclear leukocytes predominated in the cerebrospinal fluid in the first 24 h and 32% of the cases had a left shift in their peripheral blood smear. The patients' age did not influence white blood cell count, the proportion of polymorphonuclear leukocytes or protein concentration in the cerebrospinal fluid. Thirty-three patients (41%) received antibiotic treatment, and 38 patients (48%) left the hospital within 24 h. Only 2 neuroradiological procedures and 1 electroencephalographic recording were performed. The outcome was favourable in all patients.

Adolescent↗

Decay of passively acquired maternal antibodies against measles, mumps, and rubella viruses.

The decay of maternally derived antibodies to measles, mumps, and rubella viruses in Swiss infants was studied in order to determine the optimal time for vaccination. A total of 500 serum or plasma samples from infants up to 2 years of age were tested by enzyme-linked immunosorbent assay and fluorescent-antibody testing. The decline of antibody prevalence was slowest against the measles virus. By 9 to 12 months of age, only 5 of 58 (8.6%; 95% CI, 2.9 to 19.0) infants were antibody positive for the measles virus, and only 2 had levels above 200 mIU/ml. Mumps and rubella virus antibody seropositivity was lowest at 9 to 12 months of age with 3 of 58 (5. 2%; 95% CI, 1.1 to 14.4) infants and at 12 to 15 months with 1 of 48 (2.1%; 95% CI, 0.1 to 11.1) infants, respectively. Concentrations of passively acquired antibodies decreased rapidly within the first 6 months of life. We observed no significant differences in antibody prevalence or concentration according to gender in any age group. In conclusion, MMR vaccination at 12 instead of 15 months of age could reduce the pool of susceptible subjects in infancy and support the efforts to eliminate these infections, particularly in combination with a second vaccine dose before school entry.

Antibodies, Viral↗

Distinct serum cytokine levels in drug- and measles-induced exanthema.

BACKGROUND: Macular or maculopapular skin reactions are frequent events in drug allergy as well as in viral infections. Clinically, the differentiation may be difficult in the absence of a clear relationship to drug intake or failure to detect virus-specific antibodies of the IgM class. Studies on drug-specific T cell lines and T cell clones isolated from drug-allergic patients have suggested that these cells may represent a significant source of IL-5. On the other hand, viral infections are frequently associated with elevated IFN-gamma levels. OBJECTIVE: Determination of serum-cytokine levels to differentiate between drug- and virally induced skin eruptions. PATIENTS: 18 patients suffering from acute drug allergy and 19 patients with acute measles, rubella or parvovirus infection. MEASUREMENTS: Cytokine-ELISA (IL-5, IL-4 and IFN-gamma) of sera collected during acute drug allergy or during acute measles, rubella or parvovirus infection. RESULTS: In 12/18 patients with drug allergy, IL-5 and/or IL-4 were elevated. A significant correlation (r(Spearman) = 0.84) between IL-5 serum levels and eosinophil counts in the blood was found. No correlation was detected between IL-4 and blood eosinophilia or between IL-4 and IL-5 levels. After remission, IL-5 and IL-4 decreased to undetectable levels. IFN-gamma on the other hand was not measurable in patients with drug allergy while elevated IFN-gamma serum levels were detected in 17/19 patients with measles, rubella or parvovirus infection; 2 patients with acute virus infection had elevated IL-5, and/or IL-4 and IFN-gamma levels. CONCLUSION: These data underline the distinct pathogenesis of these morphologically similar exanthemas and suggest that the combined analysis of eosinophilia in the blood, IL-4 and IFN-gamma might help in differentiating skin eruptions.

Adolescent↗

[Age-related seroprevalence of measles, mumps and rubella antibodies in 1996].

In 1996 the effects on the immunity profile of a Swiss population exposed to MMR vaccination, which has been recommended since 1985, were evaluated with an age-stratified seroprevalence study for measles, mumps and rubella (MMR). At the age of 1.5-2.5 years, seroprevalence attained 76% for measles and rubella, which is respectively 17% and 24% above the values observed in 1992. The seroprevalence for mumps attained only 55% at the same age, which could reflect the poor immunogenicity of this component of the MMR vaccine. The seroprevalence for measles IgG showed a slow but steady increase from vaccination age to adulthood, attaining nearly 100%. The concentrations of measles IgG were about 700 IU/l into adolescence and rose to a plateau at about 1500 IU/l during young adulthood. These observations are compatible with low endemic activity of measles in the last 20 years and a predominance of vaccine-induced immunity up to about 20 years of age. This corresponds to the time period when measles vaccines--single or as MMR--have been in use. In 1992, at the peak of epidemic activity, seroprevalence for mumps rose substantially faster than in 1996. In addition, the rapid increase in quantitative values during preschool age mirrors the ongoing wild virus circulation with minimal vaccine effect. In the vaccine cohort (2-12 years of age) the seroprevalence of rubella IgG reached 70-80%. That there is no rise in the curve during school age shows that the recommended catch-up vaccinations before or during school age have been neglected. The median concentrations of rubella IgG were about 65 IU/ml at vaccination, declined to 40-50 IU/ml during preschool age, and rose again during school age, suggesting wild virus circulation. These data show that the MMR vaccine cover in Swiss children is insufficient to interrupt virus circulation, and administration of a second dose of MMR for catch-up immunisation has been omitted. The poor efficacy of the mumps component of the MMR vaccine that has mainly been used in Switzerland is also evident. The average age at infection is therefore expected to rise, thus involving a risk of increasing age-dependent complications. Efforts to implement the MMR vaccination program in Switzerland should be improved.

Adolescent↗

A critical assessment of the prognostic value of HIV-1 RNA levels and CD4+ cell counts in HIV-infected patients. The Swiss HIV Cohort Study.

OBJECTIVE: To determine to what extent human immunodeficiency type 1 (HIV-1) RNA levels and CD4+ cell counts predict clinical outcomes in a general HIV-1-infected population. METHODS: Community-based prospective study (Swiss HIV Cohort Study) including 394 HIV-1-infected patients, randomly selected from 4 strata of CD4+ cell counts (0 to < 0.05, 0.05 to < 0.20, 0.20 to < 0.50, and > or = 0.50 x 10(9)/L). Levels of HIV-1 RNA, CD4+ cell counts, and other variables were evaluated from samples collected between 1991 and 1993 for their ability to predict death and clinical progression. RESULTS: Patients were followed up on average for 29 months. Baseline HIV-1 RNA levels, CD4+ cell counts, clinical stage, and beta 2-microglobulin levels independently predicted survival, whereas only HIV-1 RNA levels and CD4+ cell counts independently predicted clinical progression. Multivariate relative hazards (RHs) for death ranged from 1.0 to 5.4 across quartiles of CD4+ counts, but only from 1.0 to 1.8 across quartiles of HIV-1 RNA. For clinical progression, gradients of risk were similar for CD4+ counts (1.0-4.2) and for HIV-1 RNA (1.0-3.1). In patients with CD4+ cell counts less than 0.05 x 10(9)L, HIV-1 RNA levels predicted neither death nor clinical progression. Finally, the number of HIV-1 RNA copies per CD4+ cell was the best predictor of death (multivariate RH, 1.0-9.7 across quartiles) and clinical progression (multivariate RH, 1.0-4.1). CONCLUSIONS: Levels of HIV-1 RNA and CD4+ cell counts provided independent and complementary information on clinical outcomes. The RNA/CD4+ ratio was the best single predictor. In patients who had fewer than 0.05 x 10(9)/L CD4+ cells, HIV-1 RNA levels had little prognostic value.

Adult↗

Detection of mumps virus in clinical specimens by rapid centrifugation culture and conventional tube cell culture.

Conventional tube cell culture was compared with a 2 day and 5 day spin-amplified shell vial indirect immunofluorescence assay for the detection of mumps virus in swabs from the area of Stensen's duct. The sensitivity and specificity of the shell vial assay were 95.9 and 100%, respectively. The shell vial detected 66.3% of the positive cultures within 2 days of inoculation while the first positive results were available by conventional tube cell culture after 3 days (1.6%) reaching 72.4% of all culture positive specimens after 7 days. These data suggest that a centrifugation shell vial indirect immunofluorescence assay may be useful for rapid detection of mumps virus in clinical specimens.

Animals↗

Detection of human immunodeficiency virus type 1 (HIV-1) RNA in pools of sera negative for antibodies to HIV-1 and HIV-2.

A total of 234 pools were prepared from 10,692 consecutive serum samples negative for antibodies to human immunodeficiency virus type 1 (HIV-1) and HIV-2 collected at five virological laboratories (average pool size, 45 serum samples). Pools were screened for the presence of HIV-1 RNA by a modified commercial assay (Amplicor HIV-1 Monitor test) which included an additional polyethylene glycol (PEG) precipitation step prior to purification of viral RNA (PEG Amplicor assay). The sensitivity of this assay for HIV-1 RNA detection in individual serum samples within pools matches that of standard commercial assays for individual serum samples, i.e., 500 HIV-1 RNA copies per ml. Five pools were identified as positive, and each one contained one antibody-negative, HIV-1 RNA-positive serum sample, corresponding to an average of 1 infected sample per 2,138 serum samples. Retrospective analysis revealed that the five HIV-1 RNA-positive specimens originated from individuals who had symptomatic primary HIV-1 infection at the time of sample collection and who were also positive for p24 antigenemia. We next assessed the possibility of performing the prepurification step by high-speed centrifugation (50,000 x g for 80 min) of 1.5-ml pools containing 25 microl of 60 individual serum samples, of which only 1 contained HIV-1 RNA (centrifugation Amplicor assay). The sensitivity of this assay also matches the sensitivities of standard commercial assays for HIV-1 RNA detection in individual serum samples. The results demonstrate that both assays with pooled sera can be applied to the screening of large numbers of serum samples in a time- and cost-efficient manner.

Centrifugation↗

Detection by PCR of enteroviruses in cerebrospinal fluid during a summer outbreak of aseptic meningitis in Switzerland.

Enteroviruses (EV) are among the most common causes of aseptic meningitis. Standard diagnostic techniques are often too slow and lack sensitivity to be of clinical relevance. EV RNA can be detected within 5 h by a commercially available reverse transcription-PCR (RT-PCR) test kit. Cerebrospinal fluid (CSF) samples from 68 patients presenting with aseptic meningitis during a summer outbreak in Switzerland were examined in parallel with cell culture and commercial RT-PCR. RT-PCR was positive in all 16 CSF specimens positive by cell culture (100%). In addition, 42 of 52 (80%) CSF samples negative by cell culture were PCR positive. In 26 of these 42 (62%) patients, viral culture from other sites (throat swab or stool) was also positive. The CSF virus culture took 3 to 7 days to become positive. Echovirus 30 was the type most often isolated in this outbreak. The sensitivity of CSF RT-PCR based on clinical diagnosis during this aseptic meningitis outbreak in patients with negative bacterial culture results was 85%, i.e., considerably higher than the sensitivity of CSF virus culture (24%). We conclude that this commercial RT-PCR assay allows a positive diagnosis with minimal delay and may thus influence clinical decisions.

Adolescent↗

[HIV diagnosis 1998].

Due to considerable technical progress during the last few years the diagnosis of HIV-infection has been substantially improved. Third generation antibody screening assays, which also detect antibodies of the IgM and IgA type, have considerably narrowed the immunological window. The determination of the viral load in peripheral blood employing nucleic acid amplification techniques is now generally available and used for diagnostic and prognostic purposes as well as for the monitoring of antiviral therapy. To detect a HIV-infection the antibody screening assay is primarily used and complemented by the HIV-1 p24 antigen assay provided an early primary infection is suspected. In the latter case the antibody screening assay is often negative or indeterminate, while the p24 antigen assay is positive. According to the 1998 guidelines of the Federal Office for Public Health, the physician will be informed of the screening assay result without the need to await a confirmatory test in case of a reactive screening assay in the first sample. Confirmation, e.g. by immunoblot, will be done in a second blood sample which should be sent to the laboratory as soon as possible. EDTA-blood is recommended for this purpose, because it is best suited for quantification of plasma viremia, which has become a prerequisite for the institution and follow-up of antiretroviral treatment. The second sample will also serve to exclude false positive results due to clerical errors, and to determine the type of HIV, i.e. HIV-1 or HIV-2. The concept outlined should accelerate the availability of reactive test results to the physician and should reduce the cost of the diagnostic procedure.

AIDS Serodiagnosis↗

[Mumps epidemic in vaccinated children in West Switzerland].

Since 1991, 6 years after the recommendation of universal childhood vaccination against measles, mumps, and rubella (MMR triple vaccine), Switzerland is confronted with a large number of mumps cases affecting both vaccinated and unvaccinated children. Up to 80% of the children suffering from mumps between 1991 and 1995 had previously been vaccinated, the majority with the Rubini vaccine strain. On the basis of a case-control study including 102 patients and 92 controls from the same pediatric population, a study of the humoral immune-response following vaccination with the Rubini vaccine in 6 young adult volunteers, and two different genetic studies, we investigated the complex problem of large scale vaccine failure in Switzerland. We conclude that the recently reported large number of Swiss mumps cases was caused by at least four interacting factors: 1. A vaccine coverage of 90-95% at the age of 2 years is necessary to interrupt mumps wild virus circulation. The nationwide vaccine coverage in Switzerland of some 80% in 27-36 month-old children is too low. 2. Primary vaccine failures (absence of seroconversion or unprotective low levels of neutralizing antibodies), as well as secondary vaccine failures due to the rapid decline of antibodies to mumps virus in our volunteers and controls, seem to be frequent after vaccination with the Rubini strain. 3. Despite its reported Swiss origin, the Rubini strain does not belong to the mumps virus lineages recently circulating in this area but is closely related to American mumps virus strains. 4. Differences in protein structure between the vaccine strain and the circulating wild type strains, and in particular a different neutralization epitope in the hemagglutinin neuraminidase protein, may additionally contribute to the lack of protection in vaccinated individuals.

Adolescent↗