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Biomedical subjects

P Goubau

Publications and source records attributed to P Goubau.

At least 19 recordsLinked to original sources

Evaluation of a cytomegalovirus glycoprotein B recombinant enzyme immunoassay to discriminate between a recent and a past infection.

Fetal damage following cytomegalovirus (CMV) intrauterine infection is mostly linked to primary infection. To differentiate primary infection from nonprimary infection, immunoglobulin M (IgM) tests are not reliable enough, and measurement of the IgG avidity appears to be the method that is the most widely used at present. In the present study the performance of the Vidas (bioMérieux) avidity assay was compared with that of a new enzyme immunoassay based on the use of a recombinant CMV glycoprotein B protein (Biotest).

Cytomegalovirus Infections↗

Is anti-hepatitis B virus (HBV) immunization successful in elderly hemodialysis (HD) patients?

BACKGROUND: The success rate of anti-hepatitis B virus (HBV) immunization is known from the early 80s to be markedly lower in hemodialysis (HD) patients (around 60%) than in non-uremics (over 90%). It is also known to be inversely correlated with age in non-uremics, but the rate of successful immunization in the currently prevalent elderly HD patients is unknown. METHODS: We therefore reviewed our experience in patients vaccinated soon after starting HD in 1997-2000. A recombinant vaccine (Engerix 20 microg) was administered monthly in the deltoid muscle until anti-HBs titer was > or = 100 IU/l or up to 10 doses or death, whichever occurred first. Conventional serological tests for anti-HBc, anti-HBs and HBs Ag were performed 5, 6, 9 and 12 months after the first dose of vaccine. RESULTS: Ninety-six patients started HD during this period. Sixty-five of them were excluded for the following reasons: evidence of past HBV infection (n = 20, 21%), previous anti-HBV vaccination (n = 13, 14%), rapid transfer to another HD unit (n = 30, 31%), early death (n = 2, 2%). In the remaining 31 patients, with a median age of 73 (range 35-95) years, the vaccination schedule induced seroconversion in 13/31 (42%) and 16/23 (70%) after 5 and 12 months, respectively. The seroconversion rate after 12 months was 3/3 (100%), 9/12 (75%) and 4/8 (50%) in patients aged < 60 years, 60-75 years and > 75 years, respectively. Patients with seroconversion were younger (66 +/- 14 years) than those without seroconversion (76 +/- 9 years) (p = 0.048, unpaired t-test). In the whole cohort, evidence of past HBV infection was more common in patients originating from outside Northern Europe (mainly Africa or Mediterranean countries) (14/26, 54%) than in patients from Northern Europe (6/70, 9%) (p < 0.001, Fisher exact test). CONCLUSION: Up to 50% of elderly (> 75 years) HD patients can be successfully immunized with a reinforced anti-HBV vaccination schedule, a proportion still much lower than in younger HD patients. The ultimate decision to vaccinate elderly HD patients more or less intensively, or not at all, should depend on the local epidemiology of HBV infection and the individual risk of acquiring HBV (e.g. through holiday dialysis in high prevalence countries). Before vaccinating, serological screening of patients originating from countries with high HBV prevalence is recommended.

Adult↗

Ability of three IgG-avidity assays to exclude recent cytomegalovirus infection.

At present, the measurement of IgG avidity appears to be the best method for differentiating primary from nonprimary cytomegalovirus (CMV) infection. This study compared the performances of three denaturation assays for the measurement of CMV IgG avidity: an in-house method and the commercially available assays Enzygnost (Dade-Behring, Germany) and Vidas (bioMérieux, France). The ability of these assays to exclude or to detect a recent CMV infection were calculated according to the results obtained in two control groups of pregnant women: 49 who had seroconverted and 80 with past infections. All three assays demonstrated a good ability to detect a recent infection (98-100%). The Dade-Behring test, in its present form, appears to be ineffective in excluding a recent CMV infection (exclusion ability: 30%), while the in-house method (exclusion ability: 96%) and the bioMérieux method (exclusion ability: 82%) performed better. The practical use of the in-house and the bioMérieux assays was evaluated in 80 women with CMV-specific IgG and a positive IgM result but without documented seroconversion. At the recommended diagnostic thresholds, the concordance between these two tests was 70%. Larger studies will allow more precise determination of the capacities of both assays and specification of the diagnostic thresholds or grey areas to be used.

Antibodies, Viral↗

Favorable outcome of orthotopic liver transplantation in a patient with subacute liver failure due to the emergence of a hepatitis B YMDD escape mutant virus.

BACKGROUND/AIMS: Patients with end-stage liver disease due to chronic hepatitis B infection in whom a YMDD escape hepatitis B virus (HBV) mutant has emerged under lamivudine treatment are generally denied liver transplantation (OLT). METHODS: We report the case of a male patient who was started on prophylactic treatment with lamivudine in the context of recurrent episodes of HBV reactivation during high dose immunosuppressive therapy for relapsing severe pulmonary sarcoidosis. RESULTS: Following the emergence of a YMDD escape mutant virus under lamivudine treatment, he developed subacute liver failure requiring liver transplantation. The patient was treated with a combination of intravenous hepatitis B immune globulin (HBIG) which was started perioperatively and also continued lamivudine after OLT. Twelve months after OLT, there was no evidence of HBV reinfection of the liver graft with the use of HBIG and lamivudine. CONCLUSIONS: This observation suggests that emergence of the YMDD mutation is not a contra-indication to OLT, providing adequate immunoprophylaxis using HBIG and lamivudine combination therapy.

Adult↗

Wide variety of genotypes and geographic origins of hepatitis B virus in Belgian children.

BACKGROUND: Belgium is a country with low endemicity for hepatitis B virus (HBV) infection. Few data are available on genotypes or serotypes of HBV among infected children. METHODS: The S region of the hepatitis B virus genome was amplified and sequenced in 23 children treated with interferon-alpha in Belgium. Nucleotide sequences were aligned and compared with other known sequences in a phylogenetic analysis. RESULTS: A high stability of the S gene was observed during treatment. Four genotypes were represented in this sample of Belgian patients (A, B, D, and E), reflecting the geographic diversity of origins. CONCLUSIONS: In this series, the wide variety of geographic origins is confirmed by the molecular characteristics of HBV. In Belgium, HBV infection of children is currently essentially an imported infection.

Antiviral Agents↗

False-positive IgM antibody tests for cytomegalovirus in patients with acute Epstein-Barr virus infection.

The diagnosis of acute cytomegalovirus (CMV) infection is frequently based on a positive IgM result. False-positive reactions due to interfering infections may exist. Between August 1998 and May 1999, 62 patients were found to be IgM positive and IgG negative with the Axsym assay (Abbott, Germany). Serological testing for Epstein-Barr virus (EBV) was performed in these patients to detect any cross-reactivity due to acute mononucleosis. Additionally, the results of the CMV Axsym was evaluated in 40 patients with acute EBV infection. The results suggest that the CMV-IgM Axsym assay shows a lack of specificity due to acute EBV infection. Precautions must be taken when CMV-IgM Axsym results are interpreted. It seems necessary to confirm equivocal results with another technique and to take into account other clinical and biological observations.

Acute Disease↗

Characteristics of Epstein-Barr virus primary infection in pediatric liver transplant recipients.

BACKGROUND/AIM: Pediatric liver transplant recipients are at high risk of Epstein-Barr virus infection. However the incidence of clinical symptoms and the graft function at the time of acute infection remains poorly documented. The aim of this study was to monitor the clinical and biochemical events associated with primary Epstein-Barr virus infection. METHODS: Clinical and biological patterns associated with Epstein-Barr virus infection were prospectively searched in 38 liver transplanted children. Polymerase chain reaction and anti-Epstein-Barr virus IgM antibodies were used at regular intervals to detect the timing of primary infection. RESULTS: Five children (13%) had pretransplant immunity, 26 (68.5%) developed primary Epstein-Barr virus infection 15 to 90 days after transplantation and seven (18.5%) remained Epstein-Barr virus negative. The four patients with clinical symptoms at the time of infection subsequently developed post-transplant lymphoproliferative disease. A single post-transplant lymphoproliferative disease occurred in non-symptomatic patients (overall incidence 13%). No mortality was associated with post-transplant lymphoproliferative disease. Two asymptomatic patients had abnormal liver function tests possibly related to primary Epstein-Barr virus infection. CONCLUSION: Epstein-Barr virus primary infection occurs in 80% of seronegative patients within 3 months after OLT. Clinical symptoms are rare and closely associated with post-transplant lymphoproliferative disease. Outside post-transplant lymphoproliferative disease, the consequences of infection are marginal.

Adolescent↗

Human herpes virus 8 infection in kidney transplant patients in Belgium.

BACKGROUND: Kaposi sarcoma (KS) may arise as a complication of kidney transplantation. In the Saint Luc Teaching Hospital in Brussels, patients of both Belgian and foreign origin are treated. The prevalence of human herpes virus 8 (HHV-8) infection differs in different geographical settings. We wanted to estimate the background infection rate and the risk of infection in our transplant population: a first step towards evaluating the necessity of HHV-8 screening. METHODS: Serum samples were taken from 210 organ donors over a period of 7 years (30 per year) and from 200 kidney recipients from whom two sera were tested, one pre-transplant and the second 6-12 months post-transplant. All sera were screened for HHV-8 by an enzyme-linked immunosorbant assay using recombinant ORF 65 and ORF 73 antigens and an immunofluorescence assay for the latent antigen. Reactive samples were confirmed by western blotting. RESULTS: Seven donors (3.3%) were positive for HHV-8 antibodies. Of 198 pre-transplant sera available for evaluation, 15 were positive (7.6%). Post-transplantation 18/199 (9%) were positive: four (2.1% of negatives) had a documented seroconversion and one lost the antibodies. No patients developed KS. CONCLUSIONS: A substantial number of kidney transplant patients already had antibodies to HHV-8 at the time of transplantation. A further 2.1% of seronegative patients had seroconversion, which could have been acquired through the transplanted organ (3.3% of donors were positive) or through transfusion.

Antibodies, Viral↗

Reactivity to p52 and CM2 recombinant proteins in primary human cytomegalovirus infection with a microparticle agglutination assay.

We evaluated the reactivities of sera against p52 and CM2 recombinant antigens of human cytomegalovirus (HCMV), coated on microparticles, for the differentiation of primary HCMV infection from an established infection. Two different test formats of the CMV Multiplex Copalis assay were evaluated. The 214 serum samples tested were immunoglobulin M (IgM) positive or equivocal by our reference assay. Reactivities against p52 and CM2 antigens were tested for sera from 37 patients with a well-documented seroconversion within the preceding 3 months (119 serum specimens), 31 patients known to have had a seroconversion at least 8 months earlier (31 serum specimens), and 57 patients without a documented seroconversion (64 serum specimens). The assay had a sensitivity for the detection of a primary infection of 70 or 86% by the first test format and a sensitivity of 88 or 94% by the second test format, according to the criteria used to indicate a primary infection by this test. A good correlation of the results of the assay with our in-house avidity index was found. The specificity of the assay warrants further evaluation. With IgM-positive sera, the assay was not sufficiently specific to make a distinction between a primary infection and an established infection.

Agglutination Tests↗

High prevalence of GB virus C/hepatitis G virus in Kinshasa, Democratic Republic of Congo: a phylogenetic analysis.

A prevalence of 10.3% of GB virus C (GBV-C)/hepatitis G virus (HGV) carriers was found in 97 pregnant women from Kinshasa, Congo (formerly Zaire), while prevalences of 1%, 4.1%, and 0% were found for hepatitis C virus, human immunodeficiency virus, and human T-lymphotropic virus respectively. Phylogenetic analysis of the ten GBV-C/HGV positives based on the 5' non-coding region using three different methods identified consistently three GBV-C/HGV genotypes. Four main clades were found within the type 1 sequences. All the Congolese isolates are GBV-C/HGV type 1 in two different clades. The clustering of seven Congolese isolates was inconsistent in different methods. Further likelihood-mapping analysis showed a well-resolved phylogeny, confirming the clustering of the seven Congolese isolates with a Belgian strain representing a new clade in the GBV-C/HGV type 1 sequences.

Deltaretrovirus Infections↗

Influence of CD4+ lymphocyte counts on GB virus C/hepatitis G virus carriership in HIV-positive individuals.

The duration of the GB virus C or hepatitis G virus (GBV-C/HGV) carriership varies according to the patient group studied. The immune competence of the host may be important. GBV-C/ HGV was studied in human immunodeficiency virus (HIV)-infected persons and an attempt was made to correlate the presence of viral RNA or E2 antibodies with CD4+ lymphocyte counts. Of 138 HIV-positive subjects, 30 were GBV-C/HGV RNA-positive and 20 others were E2 antibody-positive, whereas in healthy GBV-C/HGV-infected persons, the proportion of E2 antibody carriers was much higher. On the other hand, a relationship was not found between CD4+ lymphocyte counts and the presence of GBV-C/HGV RNA in the HIV-infected persons. This result does not necessarily imply that the CD4+ lymphocyte count does not affect viral clearance, but the results could be due to the trans-sectional nature of this study. A longitudinal assessment should clarify this point.

CD4 Lymphocyte Count↗

Prenatal diagnosis of human cytomegalovirus by culture and polymerase chain reaction: 98 pregnancies leading to congenital infection.

Human cytomegalovirus (HCMV) is the most common cause of viral intra-uterine infection. The experience with prenatal diagnosis remains limited and is based on few reports of small numbers of cases. It is thus difficult to compare the accuracy of the different tests because the groups studied were small and heterogeneous. We describe here our experience on a series of 98 pregnancies leading to HCMV congenital infection, among which 71 have been tested by amniotic fluid (AF) sampling followed by culture and/or polymerase chain reaction (PCR). Independently of the delay between AF sampling and the first HCMV IgM positive result, the mean sensitivity of both culture and PCR was around 70 per cent. The best sensitivity (95.5 per cent) was obtained after a delay > or = 6 weeks in late pregnancy (> or = 23 weeks). The present study demonstrated clearly that the delay between AF puncture and the presumed date of seroconversion is more important for sensitivity than the technique used for the diagnosis (PCR or culture). However, even in the best diagnostic conditions, negative results of HCMV culture or PCR in AF cannot formally exclude intra-uterine infection.

Amniocentesis↗

The discovery of two new divergent STLVs has implications for the evolution and epidemiology of HTLVs.

We have isolated and characterised two divergent simian T-lymphotropic viruses (STLV), not belonging to the established human and simian T-lymphotropic virus lineages HTLV-1/STLV-1 and HTLV-2. STLV-L, from an Eritrean sacred baboon (Papio hamadryas), has been typed as a third type of simian T-lymphotropic virus, distinct from HTLV-1/STLV-1 and HTLV-2. The other virus, isolated from Congolese bonobos (Pan paniscus), is a distinct member of the HTLV-2 clade and has been designated STLV-2. The isolation of these two simian viruses shows that the spectrum of HTLVs/STLVs is larger than previously expected. Our data indicate that the two lineages STLV-L and HTLV-2/STLV-2 are of African origin, while the HTLV-1/STLV-1 lineage has been shown to be of Asian origin. These data, together with our phylogenetic analyses, suggest an African origin of the HTLV/STLV ancestor, which provides new clues about virus dissemination. Furthermore, the atypical serological profiles exhibited by STLV-L or STLV-2 infected animals in western blot, raise questions about the efficiency of current screening methods to type highly divergent HTLVs/STLVs. Considering the growing interest in xenotransplantations, more epidemiological and biological knowledge of simian and human T-lymphotropic viruses is necessary to estimate the risk of interspecies transmissions.

Animals↗

Predictive value of maternal-IgG avidity for congenital human cytomegalovirus infection.

BACKGROUND: Human cytomegalovirus (HCMV) is now the most common cause of viral intrauterine infection. Fetal damage is mostly linked to maternal primary infection. It is therefore important to differentiate primary from recurrent or persistent HCMV infection in pregnant females. For this purpose, IgM tests are not reliable enough and the measurement of the IgG avidity appears to be presently the best method. OBJECTIVE: To evaluate the performance of the measurement of HCMV-IgG avidity by a 8 M urea denaturation assay in predicting congenital infection in the offspring. STUDY DESIGN: Seventy-eight women were included in this study on the basis of a HCMV IgM positive or equivocal result on a first serum during pregnancy, but without a documented seroconversion history. The IgG avidity was measured and correlated with the outcome of the pregnancy. RESULTS: In eight cases of HCMV in utero infection the maternal HCMV-IgG avidity index was below 50%. One case of HCMV in utero infection was observed despite a high avidity index during the second trimester of the pregnancy. High or intermediate HCMV-IgG avidity indexes during the first trimester of pregnancy were not associated with a congenital infection. CONCLUSIONS: Even in the presence of an IgM positive result, an HCMV IgG avidity index above 65% on a serum obtained during the first trimester of pregnancy could reasonably be considered as a good indicator of past HCMV infection. In these conditions invasive prenatal diagnosis is not necessary.

Antibodies, Viral↗

Prevalence of GB virus C/hepatitis G virus among blood donors in north-eastern Brazil.

We tested 70 blood donors from Fortaleza (Ceara state, Brazil) for GB virus C/hepatitis G virus (GBV/HGV) infection by polymerase chain reaction and detection of antienvelope antibodies. Twenty-seven (38.6%) showed signs of an active or resolved infection. Sixty-four percent of those with indications of other blood-borne viral infections showed signs of GBV-C/HGV infection also.

Blood Donors↗

Epstein-Barr virus infection in sixty pediatric liver graft recipients: diagnosis of primary infection and virologic follow-up.

BACKGROUND: Epstein-Barr virus (EBV) is an important cause of infection after pediatric liver transplantation. Earlier detection of EBV could result in shortening the delay in diagnosis and allow better management of a pediatric high risk population. OBJECTIVES: To determine the timing of EBV primary infection after graft and to compare the performances of different assays for an early detection of the virus. METHODS: Sixty pediatric liver graft recipients were followed. Kinetics of appearance of different EBV serologic parameters (anti-EBV-IgG, -IgM and -IgA, and anti-EBV nuclear antigen-IgG) and of the viral DNA in peripheral blood lymphocytes by PCR were compared. RESULTS: Thirty-six patients had a primary EBV infection. The first PCR and IgM positive result appeared after a mean delay of 56 and 61 days, respectively, and preceded the IgG response (mean delay, 143 days). Most of the studied patients (13 of 16) developed anti-EBV-IgA and only 3 developed anti-EBNA-IgG during the follow-up period. CONCLUSIONS: EBV primary infection occurred in most cases during the first 2 months after graft. The IgG response was delayed. The best performance was obtained by PCR. However, the IgM test compared well with the PCR and could be a more widely accessible measure to follow regularly.

Adolescent↗

Increased risk of cytomegalovirus transmission in utero during late gestation.

OBJECTIVE: To determine whether the rate of human cytomegalovirus transmission in utero is related to the gestational age at the time of maternal infection. METHODS: One hundred twenty-three pregnant women followed in our units between 1988 and 1998 were studied retrospectively. Each had developed a primary infection with cytomegalovirus evidenced by a seroconversion, confirmed by specific enzyme immunoassays. Infants were diagnosed by urine culture. RESULTS: Regardless of gestational age at the time of maternal cytomegalovirus seroconversion, the mean rate of intrauterine transmission was 57.5%. There was a statistically significant difference between early seroconversion (during the first trimester) and late seroconversion (during the third trimester) (36.0% versus 77.6%; P < .001). The risk of transmission calculated for seroconversion during the second trimester was intermediate (44.9%). CONCLUSION: A statistically significant difference in the rate of intrauterine cytomegalovirus transmission was observed according to the duration of pregnancy at which primary infection occurred. The rate of transmission increased with gestational age.

Adult↗