Measles Sclerosing Subacute PanEncephalitis (SSPE), an intriguing and ever-present disease: Data, assumptions and new perspectives.

BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a rare, non-treatable and fatal neurological complication of measles, still present due to the return of the epidemic linked to the loosening of vaccination policies. Its mechanism remains unexplained. OBJECTIVE: The main objective was to investigate explanatory variables relating to the risk of developing SSPE and its pathophysiology. METHODS: Literature analysis was focused on different varieties of SSPE: perinatal forms, short-incubation forms similar to acute measles inclusion body encephalitis (MIBE), rapidly evolving forms, forms occurring in the immunosuppressed, adult forms, and family forms. In addition, several studies on the parameters of innate immunity and interferon responses of patients were analyzed. RESULTS: Two main data were highlighted: a relationship between the so-called fulminant forms and the prescription of corticosteroids was established. In familial SSPE, two groups were individualized according to the duration of the latency period, prompting an analysis of patient exomes. CONCLUSION: Treatment with corticosteroids should be banned. Knowledge of the genes involved and epigenetics should be useful for understanding the pathophysiology of SSPE and other late-onset neurological infections with RNA viruses.

Unusual cause of dyspnea: Cardiac fusiform cells carcinoma.

This manuscript illustrates an unusual cause of dyspnea. Cardiac tumor are uncommon, especially fusiform cells carcinoma.

Clinical severity and molecular characteristics of circulating and emerging rotaviruses in young children attending hospital emergency departments in France.

Group A rotavirus (RVA) is the leading cause of acute gastroenteritis in young children worldwide. A prospective surveillance network has been set up to investigate the virological and clinical features of RVA infections and to detect the emergence of potentially epidemic strains in France. From 2009 to 2014, RVA-positive stool samples were collected from 4800 children <5 years old attending the paediatric emergency units of 16 large hospitals. Rotaviruses were then genotyped by RT-PCR with regard to their outer capsid proteins VP4 and VP7. Genotyping of 4708 RVA showed that G1P[8] strains (62.2%) were predominant. The incidence of G9P[8] (11.5%), G3P[8] (10.4%) and G2P[4] (6.6%) strains varied considerably, whereas G4P[8] (2.7%) strains were circulating mostly locally. Of note, G12P[8] (1.6%) strains emerged during the seasons 2011-12 and 2012-13 with 4.1% and 3.0% prevalence, respectively. Overall, 40 possible zoonotic reassortants, such as G6 (33.3%) and G8 (15.4%) strains, were detected, and were mostly associated with P[6] (67.5%). Analysis of clinical records of 624 hospitalized children and severity scores from 282 of them showed no difference in clinical manifestations or severity in relation to the genotype. The relative stability of RVA genotypes currently co-circulating and the large predominance of P[8] type strains may ensure vaccine effectiveness in France. The surveillance will continue to monitor the emergence of new reassortants that might not respond to current vaccines, all the more so as all genotypes can cause severe infections in infants.

Markers of a recent bocavirus infection in children with Kawasaki disease: "a year prospective study".

BACKGROUND: Retrospective studies and case-reports have suggested the possible role of various viruses in the pathogenesis of the Kawasaki disease. OBJECTIVES: To determine prospectively the incidence of Kawasaki diseases associated with a recent bocavirus infection in the course of a year. STUDY DESIGN: Thirty-two children with Kawasaki disease were enrolled in a 13 months prospective study to assess the frequency of human bocavirus type 1 infections. Seasonal shedding of virus, markers of recent infection such as viraemia, viral load, and serum interferon alpha were analyzed. RESULTS: Three of 32 (9%) children had HBoV-DNA in the serum suggesting a recent infection. HBoV-DNA was detected in naso-pharyngeal aspiration of 7/32 (21.8%) children with Kawasaki Disease and six of them (18%) had an increased viral load. No common respiratory viruses were isolated from the 32 patients with the exception of one adenovirus. The seven bocaviruses were identified during the winter-spring season. In addition, 4 of 7 of Kawasaki disease patients shedding bocavirus had detectable interferon alpha in the blood, indicating a possible active or recent viral infection. CONCLUSIONS: This study shows that a recent bocavirus infection is concomitant with the onset of some cases of Kawasaki disease. Bocavirus may be a cofactor in the pathogenesis of this disease as previously reported for other infectious agents.

Low immunogenicity of seasonal trivalent influenza vaccine among patients receiving docetaxel for a solid tumour: results of a prospective pilot study.

BACKGROUND: Patients receiving cytotoxic therapy for solid tumours are at risk of severe influenza. However, few data are available regarding the immunogenical efficacy of influenza vaccine in these patients. METHODS: In this prospective study, 25 patients with breast (n=13) or prostate (n=12) cancer received a trivalent inactivated influenza vaccine along with docetaxel (Taxotere) administration. The influenza virus type A and B antibody titres were measured using haemagglutinin inhibition (Garten et al, 2009) before and 21 days after the vaccination. Seroconversion rate was defined as the percentage of patients with an increase in the serum titres ≥ 4 after vaccination. RESULTS: Median age was 65 years (range: 33-87 years); 52% were females. Seroconversion rates were low: 28% (95% CI: 23.1-33.3) for H1N1, 8% (95% CI: 7.7-8.3) for H3N2 and 16% (95% CI: 7.7-25) for the B strain. The geometric mean titres ratios were 2.16 (H1N1), 1.3 (H3N2) and 1.58 (B). No serious adverse event (AE) related to the vaccine was reported. All the reported AE were from mild-to-moderate intensity. CONCLUSION: In the patients receiving docetaxel for solid tumours, influenza vaccine triggers an immune response in only one third. Strategies using more immunogenic influenza vaccines must be evaluated in such patients.

[Anti-hepatitis A virus seropositivity in children of immigrant parents living in France and vaccination recommendations]. / Séroprévalence de l'hépatite A chez les enfants issus de familles immigrées vivant en France et conséquences pour la vaccination.

The hepatitis A-seropositivity rate for children born in France is very low: 0 of 81 born to two French-born parents and 5 of 126 (4 %) infants for whom at least one parent was born in an endemic area. In contrast, the rate was high (28.8 %, 17/59) for children born in an endemic area. Hence, recommendations to vaccinate children who could be exposed during overseas trips to visit family or by visiting family members coming from endemic areas are fully justified.

Epidemiology and clinical features of gastroenteritis in hospitalised children: prospective survey during a 2-year period in a Parisian hospital, France.

Rotavirus is recognised as the most important agent of severe acute gastroenteritis (AGE) in young children. In a 2-year prospective survey, we investigated the epidemiology and clinical features of the viral and bacterial pathogens in children hospitalised for AGE. The study was performed in a Parisian teaching hospital from November 2001 to May 2004. Clinical data were prospectively collected to assess the gastroenteritis severity (20-point Vesikari severity score, the need for intravenous rehydration, duration of hospitalisation). Stools were systematically tested for group A rotavirus, norovirus, astrovirus and adenovirus 40/41, sapovirus and Aichi virus and enteropathogenic bacteria. A total of 457 children (mean age 15.9 months) were enrolled. Viruses were detected in 305 cases (66.7%) and bacteria in 31 cases (6.8%). Rotaviruses were the most frequent pathogen (48.8%), followed by noroviruses (8.3%) and adenoviruses, astroviruses, Aichi viruses and sapoviruses in 3.5%, 1.5%, 0.9% and 0.4%, respectively. Cases of rotavirus gastroenteritis were significantly more severe than those of norovirus with respect to the Vesikari score, duration of hospitalisation and the need for intravenous rehydration. Rotaviruses were the most frequent and most severe cause in children hospitalised for AGE, and noroviruses also account for a large number of cases in this population.

[Lymphocytic choriomeningitis virus and fetal anomalies]. / Infection par le virus de la chorioméningite lymphocytaire et fœtopathies.

OBJECTIVE: Lymphocytic choriomeningitis virus (LCMV), a rodent-borne arenavirus, is an uncommonly recognized cause of severe congenital viral infection. The incidence of this infection during pregnancy is still unknown. Our study aimed to evaluate LCMV infection frequency in pregnancy with fetal neurological abnormalities of unknown etiology. MATERIAL AND METHODS: Samples obtained during three years from 160 pregnant women were retrospectively analysed: 155 maternal sera, 150 amniotic fluids (AF) and 12 fetal sera (FS). Congenital neurological anomalies were diagnosed but TORCH and culture investigations were negatives. Serological analysis was performed with L929 cells infected with the Armstrong strain of LCMV. IgG and IgM antibodies against CMLV were researched by immunofluorescence assay using these infected cells. Interferon alpha was also assayed for AF and FS. RESULTS: No positive serology was found in any of the 317 samples investigated even when interferon alpha was detected. CONCLUSION: This result confirms the rarity of LCMV infection in France. Nevertheless, at the light of the recent literature, this teratogenic pathogen should be considered in pregnancy with unexplained congenital malformation, especially after rodent exposure.

[Epidemics of gastroenteritis caused by norovirus in Parisian children]. / Épidémies parisiennes de gastro-entérites à norovirus.

During the months of October and November 2006-2008, norovirus was detected in the stools of 14 children hospitalized with acute diarrhea (no sapovirus). Nine of these noroviruses belonged to a unique GGII4 strain, which produced severe clinical symptoms, present only in 2007 and 2008 and absent in 2006. This strain, identified in Europe mainly in the elderly, seems to be on the rise in children in the Paris area over the past few years.

Chilblains as a diagnostic sign of aicardi-goutières syndrome.

Aicardi-Goutières syndrome (AGS) is a genetically heterogeneous disorder showing variability in age of onset and clinical features. Chilblain lesions have been described in AGS patients and recent papers have discussed the clinical, molecular and cutaneous histopathological overlap with chilblain lupus. Here we report on 2 unrelated children with AGS and chilblain lesions, whose clinical histories and examination findings well illustrate the wide phenotypic variability that can be seen in this pleiotropic disorder. Although both patients show remarkable similarity in the histopathology of their associated skin lesions, with thrombi formation, fat necrosis and hyalinization of the subcutaneous tissue, we note that the histopathology reported in other AGS cases with chilblains does not necessarily demonstrate this same uniformity. Our findings highlight the significant role of the characteristic chilblain skin lesions in the diagnosis of AGS, and variability in the associated histopathology which may relate to the stage and severity of the disease.

Humoral and cellular immune responses after influenza vaccination in kidney transplant recipients.

It has been speculated that influenza vaccination of renal allograft recipients could be associated with de novo production and/or increased titers of anti-HLA antibodies (HLA-Ab). To directly address this issue, we recruited 66 stable renal transplant recipients and 19 healthy volunteers during the 2005-2006 vaccination campaign. At day 0 and day 30 following vaccination, HLA-Ab were screened and in parallel influenza-specific antibody and T-cell responses were assessed. Humoral postvaccinal responses to A/H1N1 and A/H3N2 strains, but not B strain, were less frequent in transplanted patients than in control subjects. Significant expansion of influenza-specific IFN-gamma-producing T cells was observed at similar frequencies in patients and controls. There was no correlation between cellular and humoral postvaccinal responses. No impact of sex, age or immunosuppressive regimen could be evidenced. Vaccination was not associated with any significant change in preexisting or de novo anti-HLA sensitization. No episode of allograft rejection was recorded in any of the patients. Our results suggest that flu vaccination is safe in stable renal transplanted patients. Larger studies are needed for definitive statistical proof of the safety and effectiveness, with regard to the quality of the immune response, of yearly influenza vaccination in immunosuppressed patients.

[Polyomavirus newly discovered]. / Virus Polyoma nouvellement découverts.

Three new polyoma viruses have been recently identified; two of them, the KI et WU viruses are present in nasopharyngeal aspirates during the course of acute respiratory infections. The incidence of these viruses is low compared to other respiratory viruses and the disease has not shown a high severity of clinical signs. The physiopathology of the diseases and the mode of cultivation of these viruses remain unknown. The third virus was discovered from cutaneous biopsies of Merkel tumours with a higher incidence than in tissue from healthy patients. Its mode of transmission and its role in the cancerogenesis need more studies. However, as the virus can integrate into the cellular DNA, it signifies that the virus may have a role in various human tumors.

[Human bocavirus infections]. / Infections à Bocavirus humain.

Human Bocavirus (HboV) was recently cloned by a systematic screening of nasopharyngeal samples from children hospitalized for respiratory tract infections. This virus, genus Bocavirus, family Parvoviridae, was identified by screening for its DNA in 5% of nasopharyngeal aspirates, as reported in several studies. It may be responsible for upper and lower respiratory tract infections of young children under five years with a peak rate in winter. Because of a high rate of viral co-infections, its pathogenic role in these infections should be documented. Further studies are required to determine the role of this possibly systemic virus in other affections.

Unexpected substitution of dominant rotavirus G genotypes in French hospitalized children over five consecutive seasons.

The study was designed to evaluate the circulation of group A rotaviruses in French hospitalized children, and to detect unusual strains. This prospective study was conducted from 2001 to 2006 in children consulting for acute diarrhea at the pediatric emergency department in three French University Hospitals. The rotaviruses were detected by rapid test and genotyped by RT-PCR on the basis of their outer capsid proteins VP4 (P-type) and VP7 (G-type). The stools from 757 children were analyzed. G1P[8] strains were predominant (44.0%), followed by G9P[8] (17.7%), G3P[8] 13.1%, G4P[8] (9.5%), and G2P[4] (1.8%); mixed rotavirus infections occurred in 2.3%. G9 rotaviruses emerged during the 2004-2005 season (73.4%) and remained the second most prevalent strains. Few unusual strains, G6, G8, G12 and P[6]-types, were detected. The monitoring of rotavirus infections should be maintained to document strain distribution and to assess the emergence of new reassortants that may not respond to current rotavirus vaccines.

Two further cases of spondyloenchondrodysplasia (SPENCD) with immune dysregulation.

Although the diagnosis of spondyloenchondrodysplasia (SPENCD) can only be made in the presence of characteristic metaphyseal and vertebral lesions, a recent report has highlighted the pleiotropic manifestations of this disorder which include significant neurological involvement and variable immune dysfunction. Here we present two patients, one of whom was born to consanguineous parents, further illustrating the remarkable clinical spectrum of this disease. Although both patients demonstrated intracranial calcification, they were discordant for the presence of mental retardation, spasticity and white matter abnormalities. And whilst one patient had features consistent with diagnoses of Sjögren syndrome, polymyositis, hypothyroidism and severe scleroderma, the other patient had clinical manifestations and an autoantibody profile of systemic lupus erythematosus. These cases further illustrate the association of SPENCD with immune dysregulation and highlight the differential diagnosis with Aicardi-Goutières syndrome and other disorders associated with the presence of intracranial calcification. Undoubtedly, identification of the underlying molecular and pathological basis of SPENCD will provide important insights into immune and skeletal regulation.

Quantification of neutralizing antibodies to human type I interferons using division-arrested frozen cells carrying an interferon-regulated reporter-gene.

Development of neutralizing antibodies (NAbs) to interferons (IFNs) can reduce the clinical response to IFN therapy. As current cell-based assays for quantifying NAbs have limitations, a highly sensitive and reproducible assay was developed, using division-arrested frozen human U937 cells transfected with the luciferase reportergene controlled by an IFN-responsive chimeric promoter, which allows IFN activity to be determined with precision within hours. Assay-ready PIL5 cells can be stored frozen for >3 years without loss of IFN sensitivity or the need for cell propagation. The assay is highly IFN sensitive (detecting <1.0 IU/mL), reproducible (SE +/- 15%) over concentrations from <1.0 to 100 IU/mL and able to measure different IFN subtypes and their pegylated variants. The use of this assay has shown that NAbs from patients treated with IFN-alpha2 exhibited markedly lower titers against 10 LU/mL of low specific activity IFNs, namely, IFN-alpha1, PEG-Intron(TM) (Schering-Plough, Levallois-Perret,France), or Pegasys(TM) (Hoffmann-La Roche, Neuilly-sur-Seine, France, than against 10 LU/mL IFN-alpha2. Similarly, NAbs from patients treated with IFN-beta1a exhibit lower titers against 10 LU/mL of low specific activity IFN-beta1b than against IFN-beta1a. The combination of the use of division-arrested, IFN-responsive human cells transfected with the luciferase reporter-gene makes the rapid PIL5 assay for NAbs highly advantageous.

Prevalence and genetic diversity of Aichi virus strains in stool samples from community and hospitalized patients.

Aichi virus has been proposed as a causative agent of gastroenteritis. A total of 457 stool specimens from children hospitalized with acute diarrhea and 566 stool specimens from adults and children involved in 110 gastroenteritis outbreaks were screened for the presence of Aichi virus by reverse transcription-PCR (RT-PCR) amplification of the genomic region of the 3C and 3D (3CD) nonstructural proteins. Our results show a low incidence of Aichi virus in pediatric samples and the existence of mixed infections with other microbiological agents in some cases. From the outbreak survey, it appears that the presence of Aichi virus is an indicator of mixed infections causing gastroenteritis outbreaks and that it could be involved in half of the oyster-associated outbreaks. A second RT-PCR was developed to amplify a part of the VP1 gene. The phylogenetic analysis showed a good correlation between the two classifications based on 3CD and VP1 gene sequences and revealed the prevalence of genotype A in France. It also allowed us to partially describe an Aichi virus strain that could represent a new genotype, thus suggesting the existence of a certain diversity.