Measles resurgence in Belgium from January to mid-April 2011: a preliminary report.

From 1 January to 14 April 2011, a total of 155 measles cases were notified in Belgium, whereas throughout 2010, there were only 40. Of the 103 cases with known vaccination status, 87% had not been vaccinated with measles-mumps-rubella vaccine. The resurgence of measles is the consequence of insufficient vaccine coverage in previous years. Efforts to communicate the benefits of measles vaccination to the public and to advise health professionals on control measures and outbreak management are ongoing.

Genotypic evaluation of etravirine sensitivity of clinical human immunodeficiency virus type 1 (HIV-1) isolates carrying resistance mutations to nevirapine and efavirenz.

BACKGROUND: Etravirine is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with a pattern of resistance mutations quite distinct from the current NNRTIs. METHODS: We collected all routine samples of HIV-1 patients followed in the AIDS reference laboratory of UCLouvain (in 2006 and 2007) carrying resistance-associated mutations to nevirapine (NVP) or efavirenz (EFV). The sensitivity to Etravirine was estimated using three different drug resistance algorithms: ANRS (July 2008), IAS (December 2008) and Stanford (November 2008). We also verified whether the mutations described as resistance mutations are not due to virus polymorphisms by the study of 58 genotypes of NNRTI-naive patients. RESULTS: Sixty one samples harboured resistance to NVP and EFV: 41/61 had at least one resistance mutation to Etravirine according to ANRS-IAS algorithms; 42/61 samples had at least one resistance mutation to Etravirine according to the Stanford algorithm. 48 and 53 cases were fully sensitive to Etravirine according to ANRS-IAS and Stanford algorithms, respectively. Three cases harboured more than three mutations and presented a pattern of high-degree resistance to Etravirine according to ANRS-IAS algorithm, while one case harboured more than three mutations and presented high degree resistance to Etravirine according to the Stanford algorithm. The V1061 and V179D mutations were more frequent in the ARV-naive group than in the NNRTI-experienced one. CONCLUSIONS: According to the currently available algorithms, Etravirine can still be used in the majority of patients with virus showing resistance to NVP and/or EFV, if a combination of other active drugs is included.

HIV-1 proviral resistance mutations: usefulness in clinical practice.

OBJECTIVES: Transmitted HIV strains may harbour drug resistance mutations. HIV-1 drug resistance mutations are currently detected in plasma viral RNA. HIV-1 proviral DNA could be an alternative marker, as it persists in infected cells. METHODS: This was a prospective study assessing the prevalence and persistence of HIV-1 drug resistance mutations in DNA from CD4 cells before and after protease inhibitor (PI)- or nonnucleoside reverse transcriptase inhibitor (NNRTI)-based therapy initiation in 69 drug-naïve patients. RESULTS: Before therapy, 90 and 66% of detected mutations were present in CD4 cells and plasma, respectively. We detected seven key mutations, and four of these (M184M/V, M184M/I, K103K/N and M46M/I) were only found in the cells. When treatment was started, 40 patients were followed; the mutations detected at the naïve stage remained present for at least 1 year. Under successful treatment, new key mutations emerged in CD4 cells (M184I, M184M/I and Y188Y/H). CONCLUSIONS: The proportion of mutations detected in the DNA was statistically significantly higher than that detected in standard RNA genotyping, and these mutations persisted for at least 1 year irrespective of therapy. The pre-existence of resistance mutations did not jeopardise treatment outcome when the drug concerned was not included in the regimen. Analysis of HIV-1 DNA could be useful in chronic infections or when switching therapy in patients with undetectable viraemia.

Evaluation of the new architect cytomegalovirus immunoglobulin M (IgM), IgG, and IgG avidity assays.

A panel of new cytomegalovirus (CMV) assays for use on the Architect instrument has been developed, including a CMV avidity assay based on a new technology. The purpose of this study was to compare the performance characteristics of the fully automated CMV immunoglobulin M (IgM), IgG, and IgG avidity tests on the Architect instrument with those of other available assays. A total of 503 consecutive fresh patient serum specimens (routine serum specimens) and 96 serum specimens from 33 pregnant women with a recent CMV primary infection (seroconversion serum specimens) were tested for CMV IgM and IgG by the Architect (Abbott), Vidas (BioMérieux), and Enzygnost (Siemens) assays. The seroconversion sera and 100 preselected serum specimens IgM negative and IgG positive by the AxSYM assay were also tested by the IgG avidity tests on the Architect and Vidas instruments. The relative agreements for CMV IgM determination with routine sera between the Architect assay and the Vidas, Enzygnost, and AxSYM assays were 97%, 94%, and 93%, respectively, for the CMV IgM tests and 99%, 98%, and 98%, respectively, for the CMV IgG tests. The specificities of the CMV IgG avidity test were 98% for the Architect assay and 76% for the Vidas assay. No high CMV IgG avidity test results were found within the first 3 months after seroconversion by either of those assays. The correlation between the results of the newly developed CMV IgM and IgG tests on the Architect instrument with the Vidas and Enzygnost assays was excellent (> or = 94%). The CMV IgG avidity test reliably excluded patients with recent infections and showed an excellent specificity (98%).

Definition of clinical threshold for CMV real-time PCR after comparison with PP65 antigenaemia and clinical data.

BACKGROUND: pp65 antigenaemia and real-time PCR are two methods that are used to diagnose CMV infection in its early stages and, thereby, to facilitate initiation of pre-emptive therapy. OBJECTIVES: Firstly, to compare PCR with antigenaemia and clinical outcome in order to define a clinical threshold for starting pre-emptive therapy. Secondly, to study the impact of the transplant recipient's serological status on the viral load and on the cut-offs. STUDY DESIGN: Sixty-two patients were analysed using antigenaemia (APAAP method) and real-time PCR. ROC curves were established with antigenaemia or clinical outcome as reference. Patients were divided into primo-infection or reactivation on the basis of the serological status. RESULTS: PCR correlated better with the clinical data (AUC closer to 1 and best sensitivity, PPV and NPV) than antigenaemia. Furthermore, the performance of qPCR was even better in the reactivation patients. CONCLUSIONS: This work suggests that transplant recipients should be divided according to their serological status. Indeed, replacing antigenaemia by real-time PCR for decisions regarding initiation of pre-emptive therapy is of particular appeal in patients with positive serology. As a result of this work, we have set our clinical threshold at 1500 copies/ml for reactivation.

[Clinical aspects of human infection by the avian influenza virus]. / Aspects cliniques de l'infection humaine par le virus de l'influenza aviaire.

The species barrier is not perfect for Influenza A and numerous transmissions of the virus from pigs or poultry to humans have been described these years. Appearing in 1997 and becoming epidemic in 2003, influenza A/H5N1 provoked many deadly enzootics in poultry batteries (highly pathogenic avian influenza of HPAI). Starting in Asia, many countries throughout Africa and Europe were affected. Sporadic human cases were described in direct contact with diseased chicken or other poultry. Half of the cases are lethal, but human to human transmission occurs with difficulty. From January 2003 to August 11th 2009, 438 cases were declared worldwide with 262 deaths. Many countries declared cases, but recently most cases occurred in Egypt. Measures in hospital were taken which were copied from the measures for SARS (Severe Acute Respiratory Syndrome), but these were probably excessive in this case, considering the low rate of secondary cases with A/H5N1. In many human infections, signs of severe respiratory distress develop and multi organ failure. It was feared that this deadly virus could become easily transmitted between humans, leading to a new pandemic. This was not the case up to now. The strong pathogenicity of the virus is still not completely explained, but the deep location of infection in the lungs and the deregulation of cytokine production by the target cells, particularly macrophages, may be part of the explanation.

Human bocavirus, a newly discovered parvovirus of the respiratory tract.

Human Bocavirus is a newly discovered parvovirus. This virus is the fourth most frequently detected virus among symptomatic children with respiratory infection. Human Bocavirus is present worldwide and is a probable cause of symptomatic respiratory infection, although Koch's postulates are not all fulfilled. In this article, we propose an overview of the main clinical data about this virus, two years after its discovery. In addition, we discuss some hypotheses about its tropism for the lung in young children.

Dual infection with polyomavirus BK and acyclovir-resistant herpes simplex virus successfully treated with cidofovir in a bone marrow transplant recipient.

A hematopoietic stem cell transplant recipient developed a mucosal herpes simplex virus-1 (HSV-1) infection while under acyclovir (ACV) treatment (HSV was later shown to be resistant to ACV). Concomitantly, the patient presented a hemorrhagic cystitis (HC) due to polyomavirus BK, for which intravenous cidofovir (CDV) was prescribed. The patient benefited from the broad-spectrum anti-DNA virus activity of CDV, and not only the HC resolved without signs of nephrotoxicity but also the HSV-1 lesions disappeared. This is the first report describing the effect of CDV on 2 simultaneous and unrelated DNA viral infections in an immunosuppressed transplant recipient. In addition, we describe here that this HSV-1 isolate possesses a unique phenotype and genotype.

Practical use of hepatitis C and B molecular tools: Belgian guidelines.

This article discusses the use of virologic assays in the diagnosis and management of hepatitis C virus (HCV) and hepatitis B (HBV) infection. The use of virologic tests has become essential in the management of HCV and HBV infection to diagnose viral infection, guide treatment decisions, and assess the virologic response to antiviral therapy. The continuing development of test systems accompanied by new antiviral drugs and novel therapeutic approaches should lead to an optimization of the treatment of HCV infection. Molecular methods for viral testing have become an integral part of the diagnostic and therapeutic management of infections with hepatitis C virus (HCV) and hepatitis B virus (HBV).

Adult liver transplantation at UCL: update 2002.

The authors present the results of a single centre study of 587 liver transplants performed in 522 adults during the period 1984-2002. Results have improved significantly over time due to better pre-, peri- and post-transplant care. One, five, ten and fifteen year actuarial survivals for the whole patient group are 81.2; 69.8; 58.9 and 51.2%. The high incidence of de novo tumors (12.3%), of cardiovascular diseases (7.5%) and of end-stage renal function (3.6%) should be further incentives to tailor the immunosuppression to the individual patient and to direct the attention of the transplant physician to the long-term quality of life of the liver recipient.

Hospital outbreak of gastroenteritis due to Norovirus in Belgium.

We report an outbreak of gastroenteritis due to Norovirus in a care unit in a Belgian hospital involving thirty-three people. The origin of the outbreak was traced to one nursing assistant. The virus strain identified by reverse transcription polymerase chain reaction and electron microscopy belonged to the genogroup II.

Seroepidemiology of herpes simplex type 2 in pregnant women in Belgium.

OBJECTIVE: The objective of this study was to study the prevalence of herpes simplex virus (HSV) type 2 in pregnant women in Belgium. STUDY DESIGN: The serum of 1000 consecutive women was collected. HSV-1 and HSV-2 control sera were added to the study. HSV-2 antibodies were tested with the HerpeSelect 2 enzyme-linked immunosorbent assay (ELISA; Focus) based on the use of the recombinant gG-2 antigen. RESULTS: The 21 HSV-2 control subjects were positive. Among the HSV-1 control subjects, 18 were negative and 4 were positive. Among the pregnant women, 80.3% were negative, 1.5% had equivocal results, and 18.2% were positive. No statistical difference was observed according to the origin (European or African) of the women. CONCLUSIONS: The results obtained with the control sera indicate a high sensitivity of the Focus ELISA, as well as a capacity to discriminate between HSV-1/HSV-2 infection. The HSV-2 prevalence in the studied population raises the question of the possible benefit of a specific preventive program in pregnant women.

The low evolutionary rate of human T-cell lymphotropic virus type-1 confirmed by analysis of vertical transmission chains.

The evolutionary rate of the human T-cell lymphotropic virus type-1 (HTLV-1) is considered to be very low, in strong contrast to the related human retrovirus HIV. However, current estimates of the HTLV-1 rate rely on the anthropological calibration of phylogenies using assumed dates of human migration events. To obtain an independent rate estimate, we analyzed two variable regions of the HTLV-1 genome (LTR and env) from eight infected families. Remarkable genetic stability was observed, as only two mutations in LTR (756 bp) and three mutations in env (522 bp) occurred within the 16 vertical transmission chains, including one ambiguous position in each region. The evolutionary rate in HTLV-1 was then calculated using a maximum-likelihood approach that used the highest and lowest possible times of HTLV-1 shared ancestry, given the known transmission histories. The rates for the LTR and env regions were 9.58 x 10(-8)-1.25 x 10(-5) and 7.84 x 10(-7) -2.33 x 10(-5)nucleotide substitutions per site per year, respectively. A more precise estimate was obtained for the combined LTR-env data set, which was 7.06 x 10(-7)-1.38 x 10(-5)substitutions per site per year. We also note an interesting correlation between the occurrence of mutations in HTLV-1 and the age of the individual infected.

Anticytomegalovirus IgG avidity in pregnancy: a 2-year prospective study.

OBJECTIVES: To analyze the practical use of the anticytomegalovirus IgG avidity and its impact on the follow-up of pregnancy. To evaluate the performance of IgG avidity to exclude the risk of congenital infection. METHODS: 409 IgM-positive women without a documented seroconversion were prospectively followed. Data concerning the follow-up of the pregnancies were collected (amniotic fluid puncture and samples from the offspring). These observations were compared to those of 76 seroconversions during the same period. RESULTS: High avidity excluding a primary infection within the past 3 months was observed in 270 women. As the gestational age was less than 3 months for 121 women, exclusion of a primary infection was achieved in 30% of the cases. The rate of amniotic fluid puncture was influenced by the serological result: high avidity (9%), low avidity (42%) and seroconversion (65%). CONCLUSIONS: A high avidity index during the first trimester of pregnancy could reasonably be considered as a good indicator of past infection and invasive prenatal diagnosis is not necessary. Nearly 70% of the IgM-positive women could be reassured if the first serology was systematically performed before 12 weeks of gestation.

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).

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.

Hepatitis C virus: the burden of the disease.

Chronic hepatitis C infection affects approximately 3% of the world population and is responsible for a large proportion of patients with cirrhosis, end-stage liver diseases, hepatocellular carcinoma and for those who are candidates for liver transplantation or die of liver-related complications. The health care burden of this infection, whose epidemic peaked in the 1980s, is expected to significantly increase in the next 15 years in the absence of an organized national strategy. On the other hand, hepatitis C infection can be easily diagnosed with third generation enzyme immunoassay and indications for molecular biology-based assay are well defined. Composite scores and non-invasive markers of fibrosis may in the future replace liver biopsy which is still recommended in the presence of chronically elevated transaminases and indications for antiviral treatment.

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.

Age trend in hepatitis C virus genotype distribution as seen in a Brussels teaching hospital.

The hepatitis C virus genotype distribution was studied among age groups in 501 referred patients with chronic hepatitis C by INNO-LiPA HCV II (Innogenetics, Belgium). Ten patients had coinfection with several genotypes. Two hundred seventy of 491 singly infected individuals (57%) had 1b, 66 (13.4%) 3a, 57 (11.6%) 1a. HCV subtype 1b was predominant but its prevalence increased with age (76.5% of patients born in the '20s, 39.3% in the '70s) (P < 0.0001). Three possibilities could explain the shift towards a wider variety of genotypes in younger age. (1) 1b could be the original subtypes in this population, (2) the non-1b subtypes could give less chronic carriers, (3) the non-1b subtypes could have a higher mortality, which seems improbable. The 1b genotype seems the oldest subtype in our country while others were imported later through increased population movements and changing habits.

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.