Patients with primary immunodeficiencies are a reservoir of poliovirus and a risk to polio eradication

ABSTARCT: Immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) have been isolated from primary immunodeficiency (PID) patients exposed to oral poliovirus vaccine (OPV). Patients may excrete poliovirus strains for months or years; the excreted viruses are frequently highly divergent from the parental OPV and have been shown to be as neurovirulent as wild virus. Thus, these patients represent a potential reservoir for transmission of neurovirulent polioviruses in the post-eradication era. In support of WHO recommendations to better estimate the prevalence of poliovirus excreters among PIDs and characterize genetic evolution of these strains, 635 patients including 570 with primary antibody deficiencies and 65 combined immunodeficiencies were studied from 13 OPV-using countries. Two stool samples were collected over 4 days, tested for enterovirus, and the poliovirus positive samples were sequenced. Thirteen patients (2%) excreted polioviruses, most for less than 2 months following identification of infection. Five (0.8%) were classified as iVDPVs (only in combined immunodeficiencies and mostly poliovirus serotype 2). Non-polio enteroviruses were detected in 30 patients (4.7%). Patients with combined immunodeficiencies had increased risk of delayed poliovirus clearance compared to primary antibody deficiencies. Usually, iVDPV was detected in subjects with combined immunodeficiencies in a short period of time after OPV exposure, most for less than 6 months. Surveillance for poliovirus excretion among PID patients should be reinforced until polio eradication is certified and the use of OPV is stopped. Survival rates among PID patients are improving in lower and middle income countries, and iVDPV excreters are identified more frequently. Antivirals or enhanced immunotherapies presently in development represent the only potential means to manage the treatment of prolonged excreters and the risk they present to the polio endgame. Keywords: Poliovirus eradication, Immunodeficiency-associated vaccine-derived polioviruses, Oral poliovirus vaccine, Humoral immunodeficiency, Combined immunodeficiency, Primary immunodeficienc

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Tissus cibles et caractéristiques phylogénétiques du virus de la tumeur nasale enzootique (ENTV) chez la brebis sahélienne

International audienceWe analyzed the nucleotide sequence and tissue distribution of the Enzootic Nasal Tumour Virus (ENTV) circulating in Sahelian breeds of sheep in West Africa. New ENTV specific primers were designed in the variable region spanning from the end of the viral transmembrane (TM) gene to the U3 region of the long terminal repeat (LTR). These primers selectively amplified a fragment of the ENTV genome from the tumour tissues of sheep affected with enzootic nasal adenocarcinoma (ENA). ENTV nucleotides sequences obtained from two separate sheep were 99.5% homolog. The sequence analysis revealed a genome clustering more closely with ENTV-1 (94% homology) than with ENTV-2 (84% homology). An internal primer was designed for enhanced detection after hemi-nested PCR (hn-PCR). Tissues exploration using hn-PCR revealed the presence of provirus in the retropharyngeal lymph node draining the nasal region and in the healthy lung tissue from ENA-sheep. Despite this improved detection assay, the ENTV genome remained undetectable from the peripheral blood leukocytes of ENA sheep. The observed tissue distribution is consistent with the ENTV-1 dissemination pattern. These data are relevant to the preclinical and antemortem diagnosis of sheep ENA.Nous avons analysé la séquence nucléotidique et la distribution tissulaire du virus de la tumeur nasale enzootique (ENTV) qui sévit chez les souches sahéliennes de mouton d’Afrique de l’Ouest. Des oligonucléotides spécifiques du ENTV ont été conçus dans la région variable qui s’étend de la fin du gène codant la protéine virale trans-membranaire (TM) à la région U3 du LTR. Ces amorces permettent d’amplifier sélectivement un fragment du génome viral à partir du tissu tumoral d’ovin atteint d’Adénocarcinome Nasal Enzootique (ENA). Les séquences virales obtenues de deux animaux sont à 99,5 % homologues. Leur analyse a révélé un génome plus proche du ENTV-1 (homologie 94 %) que du ENTV-2 (homologie 84 %). Un «primer» interne a été conçu pour accroître le pouvoir de détection après PCR nichée (hn-PCR). L’exploration des tissus par cette méthode a révélé la présence de pro-virus dans le ganglion rétropharyngé qui draine la région nasale, ainsi que dans le poumon sain de mouton atteint. Malgré cette capacité accrue de détection, le génome du ENTV est resté indétectable depuis les leucocytes circulants de mouton atteint. La distribution tissulaire observée est en accord avec la dissémination du ENTV-1. Ces résultats ont des implications pour le diagnostic pré-clinique et ante-mortem de la tumeur nasale enzootique du mouton

Tissus cibles et caractéristiques phylogénétiques du virus de la tumeur nasale enzootique (ENTV) chez la brebis sahélienne

International audienceWe analyzed the nucleotide sequence and tissue distribution of the Enzootic Nasal Tumour Virus (ENTV) circulating in Sahelian breeds of sheep in West Africa. New ENTV specific primers were designed in the variable region spanning from the end of the viral transmembrane (TM) gene to the U3 region of the long terminal repeat (LTR). These primers selectively amplified a fragment of the ENTV genome from the tumour tissues of sheep affected with enzootic nasal adenocarcinoma (ENA). ENTV nucleotides sequences obtained from two separate sheep were 99.5% homolog. The sequence analysis revealed a genome clustering more closely with ENTV-1 (94% homology) than with ENTV-2 (84% homology). An internal primer was designed for enhanced detection after hemi-nested PCR (hn-PCR). Tissues exploration using hn-PCR revealed the presence of provirus in the retropharyngeal lymph node draining the nasal region and in the healthy lung tissue from ENA-sheep. Despite this improved detection assay, the ENTV genome remained undetectable from the peripheral blood leukocytes of ENA sheep. The observed tissue distribution is consistent with the ENTV-1 dissemination pattern. These data are relevant to the preclinical and antemortem diagnosis of sheep ENA.Nous avons analysé la séquence nucléotidique et la distribution tissulaire du virus de la tumeur nasale enzootique (ENTV) qui sévit chez les souches sahéliennes de mouton d’Afrique de l’Ouest. Des oligonucléotides spécifiques du ENTV ont été conçus dans la région variable qui s’étend de la fin du gène codant la protéine virale trans-membranaire (TM) à la région U3 du LTR. Ces amorces permettent d’amplifier sélectivement un fragment du génome viral à partir du tissu tumoral d’ovin atteint d’Adénocarcinome Nasal Enzootique (ENA). Les séquences virales obtenues de deux animaux sont à 99,5 % homologues. Leur analyse a révélé un génome plus proche du ENTV-1 (homologie 94 %) que du ENTV-2 (homologie 84 %). Un «primer» interne a été conçu pour accroître le pouvoir de détection après PCR nichée (hn-PCR). L’exploration des tissus par cette méthode a révélé la présence de pro-virus dans le ganglion rétropharyngé qui draine la région nasale, ainsi que dans le poumon sain de mouton atteint. Malgré cette capacité accrue de détection, le génome du ENTV est resté indétectable depuis les leucocytes circulants de mouton atteint. La distribution tissulaire observée est en accord avec la dissémination du ENTV-1. Ces résultats ont des implications pour le diagnostic pré-clinique et ante-mortem de la tumeur nasale enzootique du mouton