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.

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%).

[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.

Familial transmission and minimal sequence variability of human T-lymphotropic virus type I (HTLV-I) in Zaire.

Our group previously reported a strong familial clustering of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Zaire, suggesting a familial transmission of the virus together with the presence of cofactors. In the present study among 84 relatives of 16 HTLV-I-positive or HAM/TSP index cases, we found that all 15 seropositive children had a seropositive mother and that all 15 children with a seropositive father but a seronegative mother were seronegative. Lymphocytes of 17 relatives from 2 families with a familial HTLV-I-associated neuropathy were tested in 2 polymerase chain reaction (PCR) assays amplifying pol and tax/rex gene fragments. The 10 seropositive individuals were PCR positive for HTLV-I and the 7 seronegatives were negative in both PCR assays. The PCR results showed no evidence for a long lag period between infection with HTLV-I and seroconversion. The HTLV-I long terminal repeat (LTR) of these 10 individuals, related in the first to the fourth degree, was amplified and sequenced. Identical sequences were found within the families except for one woman infected with two variants, one being the familial strain and the other a mutated one with a single nucleotide substitution in the 755 sequenced nucleotides of the LTR region. The family strain and the mutant were both present in two samples taken 1 year apart. Together, the HTLV-I serology, PCR, and sequencing results point toward mother-to-child transmission as the main mode of HTLV-I infection in this population. Comparison of the LTR sequences of the two families with other HTLV-I strains from different geographical regions shows that the Zairean HTLV-I strains form a separate cluster.(ABSTRACT TRUNCATED AT 250 WORDS)

HTLV-II seroprevalence in pygmies across Africa since 1970.

HTLV-II-specific antibodies, with patterns similar to those in the Americas, were present in sera collected about 1970 from Bambuti pygmies in Zaire (14/102; 14%) and from pygmies in Cameroon (5/214; 2.3%), and were more prevalent than HTLV-I. In the Central African Republic, 504 pygmies were HTLV negative. After finding of 4 HTLV-II seropositives among 12 Bambuti pygmies sampled in 1991, this established that HTLV-II or a related retrovirus is present as an ancient endemic in some, but not all, insulated groups of African pygmies, similar to the HTLV-II distribution in Amerindian populations. The endemic among the oldest inhabitants of central Africa, and the occasional and scattered occurrence of apparent HTLV-II among predominant HTLV-I in other Africans, fit well with an ancient African virus and not with importation from the New World. Theories on the origin and evolution of the primate T-lymphotropic viruses (PTLVs) should take into account the longstanding presence of HTLV-II-type viruses in both the Old and New World. Present serology suggests identity of the African viruses with HTLV-II, but their assignment to a new HTLV type is open should genetic analysis show strong divergence from American HTLV-II. Clinical expression, if any, remains to be studied.

HTLV-negative and HTLV type I-positive tropical spastic paraparesis in northeastern Brazil.

A type-specific serological survey among 1042 random nonneurological outpatients in two cities in the state of Ceara (northeastern Brazil) shows a low prevalence of HTLV-I (0.34% in Fortaleza; 0.44% in Crato) and of HTLV-II (0.34% in Fortaleza; 0% in Crato). Among 62 chronic myelopathic patients seen in Fortaleza 27 patients were found with clinical features of tropical spastic paraparesis (TSP); 10 of 27 were found HTLV-I seropositive (37%; 95% confidence limits, 19-58%). Proviral genome detection by polymerase chain reaction in 5 seropositive and 12 seronegative patients confirmed the serological findings. This excludes HTLV-I or -II infection as a cause in the seronegative TSP patients. The HTLV-positive and -negative patients did not differ clinically and by history, except that seropositives had a longer mean disease duration, a female predominance, and a higher proportion of white Caucasians. In this population with low HTLV-I and HTLV-II prevalences, HTLV-negative TSP is at least as frequent as the HTLV-I-associated TSP.

Characterization of HIV-1 strains isolated from patients treated with TIBO R82913.

The drug sensitivities of human immunodeficiency virus type 1 (HIV-1) isolates from a group of four untreated and seven TIBO R82913-treated patients were determined in a reverse transcriptase (RT) assay. Five of the treated patients harbored HIV-1 isolates with R82913 sensitivity comparable to that of the isolates of untreated patients, ranging from almost 2-fold higher sensitivity to 13-fold lower sensitivity than that of recombinant p66 RT. From one of the seven treated patients, an HIV-1 strain with a 20-fold reduced sensitivity to R82913 could be isolated; and from another patient, a strain with 100-fold reduced sensitivity (resistance) was isolated. The drug-resistant strain in this patient emerged after 3 weeks of treatment and was due to the Y188L mutation in its RT. On passaging the virus in cord blood lymphocytes, but not in CEM cells, the resistant virus was lost in favor of a different HIV-1 strain harboring the wild-type Y188 with a sensitivity to R82913 comparable to that of wild-type p66 RT. In several HIV-1 isolates (from treated and untreated patients), some HIV-2- and CIVgab-specific amino acids were found. One of these substitutions, that is, I/V179D (from an untreated patient), conferred a sevenfold reduced RT sensitivity to R82913.

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.

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.

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.

Detection of HIV-1 RNA in plasma and serum samples using the NASBA amplification system compared to RNA-PCR.

The presence of HIV-1 RNA in the plasma and serum of European and African patients was monitored using RNA-polymerase chain reaction (RNA-PCR) and the new isothermal NASBA nucleic acid amplification system encompassing a gel-based detection assay (ELGA). Identical RNA extraction procedures, provided by the NASBA amplification system, were used for both methods. The detection limit for HIV-1 RNA, measured on a 10-fold dilution series of spiked HIVIIIB in negative plasma, was about 0.05 CCID50 per test for both methods. Both NASBA and RNA-PCR were more sensitive than a p24 assay for the detection of circulating HIV-1 virus in blood: 17 of the 34 (50%) p24 antigen-tested seropositives were p24-positive while 32 (94%) were positive by NASBA and 30 (88%) by RNA-PCR. Among the 45 seropositives, 34 of which were tested for p24 antigen, 43 (96%) were positive by NASBA and 41 (91%) by RNA-PCR. Almost all seropositives had a detectable viral load in 100 microliters plasma. Lower viral loads were only encountered in some healthy seropositives with a higher CD4 count. There was no cross-reactivity with HIV-2 or HIV-I with both the RNA-PCR and NASBA. The extraction method used permitted the detection of HIV-1 RNA equally well in serum and in plasma with heparin or EDTA.

Sensitive and rapid assay on MT-4 cells for detection of antiviral compounds against the AIDS virus.

Human immunodeficiency virus (HIV) infection of MT-4 cells, an HTLV-I-transformed T-cell line, proved to be a rapid and sensitive assay system for the detection of potential antiviral drugs effective against the acquired immune deficiency syndrome (AIDS). Four days after HIV inoculation of the MT-4 cells, viral antigen expression was monitored in parallel with indirect immunofluorescence microscopy and laser flow cytofluorography. When 3'-azido-2',3'-dideoxythymidine (AzddThd, AZT) and 2',3'-dideoxycytidine (ddCyd) were evaluated under these conditions, they inhibited viral antigen expression at a minimum (33% inhibitory) concentration of 0.0004 and 0.02 microM, respectively. Similar minimum effective concentrations were found for AzddThd and ddCyd in assays where inhibition of viral cytopathogenicity was based on cell survival. While laser flow cytofluorography could be best adapted for quantitative measurements, cell survival and reconstitution of disrupted cell aggregates gave an equally rapid and sensitive endpoint; and the latter may be ideally suited for preliminary drug screening.

HTLV seroepidemiology in a central African population with high incidence of tropical spastic paraparesis.

In Lisala (Equateur region, Zaire), where a cluster of tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM) was described, 28/200 (14%) out-patients and hospital personnel were HTLV antibody positive. No differences in prevalences were observed between out-patients and hospital personnel or between ethnic groups. The annual attack rate of TSP/HAM is estimated at 0.15-0.3 per 1000 infected. The ethnic and familial clustering of TSP/HAM together with the high attack rate suggests the presence of co-factors for the progression to disease. This high prevalence of HTLV antibodies contrasts with the low prevalence in another part of the Equateur region.

Prevalence of hepatitis C virus and other blood-borne viruses in Pygmies and neighbouring Bantus in southern Cameroon.

The prevalences of antibodies to hepatitis C virus (anti-HCV), human immunodeficiency virus (anti-HIV), human T lymphotrophic virus (anti-HTLV) and of hepatitis B surface antigen (HbsAg) were determined in 168 subjects aged 12 years and over (108 Pygmies, 60 Bantus) living in south Cameroon. In 167 subjects, we found an estimated minimal anti-HCV prevalence of 13%. The prevalence was significantly higher in Bantus (31.7%) than in Pygmies (11.1%) and increased with age in both groups, albeit more rapidly in Bantus. The overall prevalence of HBsAg was 7.2% and correlated with neither sex nor ethnic group. No association was found between anti-HCV and HbsAg prevalence rates. No subject was confirmed to be positive for HTLV or HIV. These findings confirm the high prevalence of HCV infection in south Cameroon and indicate that even secluded population groups are affected.

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.

Brazilian studies on tropical spastic paraparesis. A meta-analysis.

Tropical spastic paraparesis (TSP) is a chronic progressive myelopathy and in most of the cases has a retroviral (HTLV-1) etiology, when it is denominated HTLV-1 associated-mielopathy (HAM/TSP). Around 433 cases of TSP have been described in Northeast and Southeast Brazil. Among these cases, 157 (36.2%) are HTLV-1 positive and 276 (63.7%) are negative. Their mean age is 43.8 years with a slight predominance of females and mulattoes, although white patients are also numerous. Clinically all patients exhibit a spastic paraparesis with variable sphincter and sensory disturbance. Pain and autonomic symptoms seem to be expressive in the HTLV-1 positive HAM/TSP Brazilian patients.

[Tropical spastic paraparesis in the tropics and Brazil. A historical analysis]. / Paraparesia espástica tropical nos trópicos e Brasil. Análise histórica.

The tropical spastic paraparesis (TSP) is a chronic myelopathy, predominant in the tropics, recently known to be of retroviral origin (HTLV-I). This paper aims at delineating the clinico-etiological evolution of this entity. The historical analysis of it showed that the TSP has had, along decades, many different denominations and the discovery of the retroviral origin for some of them has stimulated new paths of research and epidemiological interest in the tropics and Brazil.

Retinal vasculitis in Lyme borreliosis.

We observed retinal vasculitis in seven patients with clinical and serologic evidence of Borrelia burgdorferi infection. Three patients presented with abrupt loss of vision due to acute retinal vasculitis. Funduscopy demonstrated engorged veins, hemorrhages, perivenous infiltrates and retinal white spots. Fluorescein angiography showed leakage from the veins, from the white spots and from the optic disc. Moreover arterial occlusions were observed in two patients. Four patients had signs of chronic uveitis with vitritis, cystoid macular oedema and retinal vasculitis, which was associated with neovascularization and vitreous hemorrhage in one patient, and with optic neuritis in another patient. Six patients received antibiotic treatment and three patients received systemic corticosteroids. Marked improvement in the three acute retinal vasculitis cases occurred within several weeks, the fundus changes disappeared in another few months, and no recurrences were observed. The final visual acuity was excellent in these patients, although optic disc pallor and visual field loss persisted in one case. In the four patients with chronic uveitis visual blurring improved following antibiotic treatment and the retinal vasculitis and vitritis slowly regressed. The proliferative retinopathy of one patient required panretinal laser treatment.