Recent data on hantaviruses and perspectives for research

The members of the genus Hantavirus are the only representatives of the family Bunyaviridae not transmitted by arthropod vectors but by small mammals. Hantaviruses transmitted by rodents (Order Rodentia) have been discovered at first because of their pathogenicity for humans. The first phylogenetic studies suggested a co-evolution between each hantavirus and its rodent reservoir species. However, further exploration of more animal reservoirs has evidenced that hantaviruses also circulate among insectivores (Order Soricomorpha) and bats (Order Chiroptera), without associated human pathology or even transmission demonstrated up to now. Documented co-circulation of the same hantavirus among sympatric rodent species and new phylogenetic data outlining host-switching events between closely related hantaviruses are currently weakening the concept of strict co-speciation. In addition, the closer analysis of clinical cases invites to moderate the dogma of a clearly distinct pathology in humans between Old World (Europe-Asia) hantaviruses that would provoke Haemorrhagic Fevers with Renal Syndrome (HFRS) and New World (Americas) hantaviruses that would result in a Cardio- Pulmonary Syndrome (HCPS). These topics are discussed because they open interesting perspectives for trans-disciplinary research, from compared immunology between mammals up to modelling of reservoir dynamics in natural environment and sociology of human populations at risk. The most recent data concerning the circulation and pathogenicity of hantaviruses in Europe and in the world are also presented as well as the new technologies for the serological and genetic investigations to discover without a priori new viruses « sleeping » in animal reservoirs and to evaluate their potential for future emergence(s) in manLes virus du genre Hantavirus sont les seuls représentants de la famille des Bunyaviridae qui ne sont pas transmis par des vecteurs arthropodes mais par des petits mammifères. Les hantavirus transmis par les rongeurs (Ordre Rodentia) ont été les premiers découverts en raison de leur pouvoir pathogène chez l’homme. Les premières études phylogénétiques ont suggéré une coévolution entre chaque hantavirus et son espèce de rongeur réservoir. Toutefois, l’exploration d’autres réservoirs animaux a montré que des hantavirus circulent aussi chez les insectivores (Ordre Soricomorpha) et les chauvessouris (Ordre Chiroptera), sans qu’aucune transmission pathogène à l’homme n’ait pu être mise en évidence jusqu’à aujourd’hui. Des observations naturelles de cocirculation d’un même hantavirus au sein de plusieurs espèces de rongeurs sympatriques, ainsi que de nouvelles données phylogénétiques qui soulignent des changements d’hôte (host-switching) entre hantavirus très proches, remettent actuellement en cause la cospéciation stricte. De même, l’observation plus fine de cas cliniques suggère de modérer le dogme d’une maladie distincte chez l’homme, les hantavirus de l’Ancien Monde (Europe- Asie) provoquant une fièvre hémorragique à syndrome rénal (FHRS) et ceux du Nouveau Monde (Amériques) conduisant à une hantavirose à syndrome cardio-pulmonaire (HSCP). Ces points sont discutés car ils ouvrent d’importantes perspectives en matière de recherche transdisciplinaire, depuis l’immunologie comparée chez les mammifères jusqu’à la modélisation de la dynamique des réservoirs dans leur milieu naturel, en passant par la sociologie des populations à risque. Les données récentes sur la circulation et le pouvoir pathogène des hantavirus en Europe et dans le monde sont aussi présentées, ainsi que les nouveaux outils d’investigation sérologique et génétique permettant la découverte sans a priori de nouveaux virus « dormants » dans des réservoirs et l’évaluation de leur potentiel d’émergence chez l’homm

Epidemiological determinants and PCR results in Central African inhabitants with a new and frequent HTLV indeterminate Western Blot pattern exhibiting mostly p28, p32, p36, and a shifted GD21

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Geographical distribution and relative risk of Anjozorobe virus (Thailand orthohantavirus) infection in black rats (Rattus rattus) in Madagascar

Acknowledgements We thank those who facilitated the survey: householders, heads of fokontany, local administration and health authorities from Ministry of Health. We would like to express our gratitude to the staff of the Plague Central Laboratory Unit, Institut Pasteur de Madagascar: Dr. Minoarisoa Rajerison who facilitated this study; Corinne Rahaingosoamamitiana and Soanandrasana Rahelinirina for helping to conduct and organize the field work. We would also like to thank Dr. Fanjasoa Rakotomanana and Dr. Lalaina Arivony Nomenjanahary assistance in the field trips and technical and field support. Funding This work was supported by the Institut Pasteur de Madagascar (Internal Project through ZORA: Zoonoses, Rodent and Arboviruses) and Wellcome Trust Fellowships to ST (#081705, #095171). VR was also supported though Girard’s fellowship undergraduate program from the Institut Pasteur de Madagascar. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Erythroid Progenitor Cells Expanded from Peripheral Blood without Mobilization or Preselection: Molecular Characteristics and Functional Competence

Peer reviewe

HTLV-2 in Central Africa: HTLV-2 subtype B strains similar to those found in Amerindian tribes are endemic in Bakola Pygmies from south Cameroon but not in surrounding Bantus and Baka Pygmies

International audienceBackground:Presence and origin of endemic foci of HTLV-2 infection in Africa remain a matter of debate.Material and methods:To better appreciate the epidemiological and molecular determinants of HTLV-2 infection in Central Africa, we performed a survey in 3903 inhabitants of a South Cameroon forest area, including 1051 Bakola Pygmies, 815 Baka Pygmies and 2037 Bantus living in their neighboring. HTLV-1 and HTLV-2 infection was determined by both specific serological (IFA and WB) and molecular (different generic and specific PCR) methods.Results:HTLV-1/2 prevalence was of 3% (117/3903) with 90 HTLV-1 (2.3%) and 27 HTLV-2 (0.7%). Surprisingly, HTLV-2 infection was restricted to Bakola Pygmies (27/1051 2.5%) with no HTLV-2 infection in any of the 2852 Baka or Bantus individuals. In Bakola Pygmies, HTLV-2 seroprevalence increased with age, reaching 6.5% in the elder persons. Ongoing intrafamilial HTLV-2 transmission was evidenced. Lymphoid T cell lines (CD8+ or CD4+, CD25 +) producing HTLV-2 antigens, were established from PBMCs cultures of HTLV-2 infected individuals. Sequences of a 672 nucleotide LTR fragment, obtained from 7 HTLV-2 samples, showed a very high degree of homologies among samples (< 1% nucleotide divergence) but also surprisingly with Amerindian HTLV-2 B strains. Complete sequence (8954 bp) of one isolate confirmed a typical HTLV-2 B strain.Conclusion:This study demonstrates clearly a HTLV-2 endemic population, with ongoing transmission, in Central Africa. Furthermore, it gives insights into several central questions regarding the origin and evolution rate of HTLV-2 and the migrations of infected populations

Fast, sensitive and specific detection of Thailand orthohantavirus and its variants using one-step real-time reverse-transcription polymerase chain reaction assay

Funding: This study was supported by the Programme Transversal de Recherche (PTR 505) funded by the Institut Pasteur International Network. V.R. was also supported though Girard’s fellowship undergraduate program from the Institut Pasteur de Madagascar and traineeship grants Calmette and Yersin program from the Institut Pasteur International Network. Acknowledgements: We would like to express our gratitude to the staff of the Plague Central Laboratory Unit, Institut Pasteur de Madagascar: Minoarisoa Rajerison, Fehivola Mandanirina Andriamiarimanana, and Soanandrasana Rahelinirina for conducting the field work and for providing samplesPeer reviewedPublisher PD

Revisiting the genetic diversity of emerging hantaviruses circulating in Europe using a pan-viral resequencing microarray

Hantaviruses are zoonotic agents transmitted from small mammals, mainly rodents, to humans, where they provoke diseases such as Hemorrhagic fever with Renal Syndrome (HFRS) and its mild form, Nephropathia Epidemica (NE), or Hantavirus Cardio-Pulmonary Syndrome (HCPS). Hantaviruses are spread worldwide and monitoring animal reservoirs is of primary importance to control the zoonotic risk. Here, we describe the development of a pan-viral resequencing microarray (PathogeniD v3.0) able to explore the genetic diversity of rodent-borne hantaviruses endemic in Europe. Among about 800 sequences tiled on the microarray, 52 correspond to a tight molecular sieve of hantavirus probes covering a large genetic landscape. RNAs from infected animal tissues or from laboratory strains have been reverse transcribed, amplified, then hybridized to the microarray. A classical BLASTN analysis applied to the sequence delivered through the microarray allows to identify the hantavirus species up to the exact geographical variant present in the tested samples. Geographical variants of the most common European hantaviruses from France, Germany, Slovenia and Finland, such as Puumala virus, Dobrava virus and Tula virus, were genetically discriminated. Furthermore, we precisely characterized geographical variants still unknown when the chip was conceived, such as Seoul virus isolates, recently emerged in France and the United Kingdom

Lung Volume, Breathing Pattern and Ventilation Inhomogeneity in Preterm and Term Infants

BACKGROUND: Morphological changes in preterm infants with bronchopulmonary dysplasia (BPD) have functional consequences on lung volume, ventilation inhomogeneity and respiratory mechanics. Although some studies have shown lower lung volumes and increased ventilation inhomogeneity in BPD infants, conflicting results exist possibly due to differences in sedation and measurement techniques. METHODOLOGY/PRINCIPAL FINDINGS: We studied 127 infants with BPD, 58 preterm infants without BPD and 239 healthy term-born infants, at a matched post-conceptional age of 44 weeks during quiet natural sleep according to ATS/ERS standards. Lung function parameters measured were functional residual capacity (FRC) and ventilation inhomogeneity by multiple breath washout as well as tidal breathing parameters. Preterm infants with BPD had only marginally lower FRC (21.4 mL/kg) than preterm infants without BPD (23.4 mL/kg) and term-born infants (22.6 mL/kg), though there was no trend with disease severity. They also showed higher respiratory rates and lower ratios of time to peak expiratory flow and expiratory time (t(PTEF)/t(E)) than healthy preterm and term controls. These changes were related to disease severity. No differences were found for ventilation inhomogeneity. CONCLUSIONS: Our results suggest that preterm infants with BPD have a high capacity to maintain functional lung volume during natural sleep. The alterations in breathing pattern with disease severity may reflect presence of adaptive mechanisms to cope with the disease process

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P &lt; .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients