Hepatitis A virus vaccine escape variants and potential new serotype emergence.

Six hepatitis A virus antigenic variants that likely escaped the protective effect of available vaccines were isolated, mostly from men who have sex with men. The need to complete the proper vaccination schedules is critical, particularly in the immunocompromised population, to prevent the emergence of vaccine-escaping variants

Hepatitis A Virus Vaccine Escape Variants and Potential New Serotype Emergence

These authors contributed equally to this article. Six hepatitis A virus antigenic variants that likely escaped the protective effect of available vaccines were isolated, mostly from men who have sex with men. The need to complete the proper vaccination schedules is critical, particularly in the immunocompromised population, to prevent the emergence of vaccine-escaping variants. In areas where hepatitis A has low to moderate endemicity, introduction of the virus occurs through consumption of imported foods, traveling, or through immigration flows (1–3). Men who have sex with men (MSM) comprise a high-risk group for hepatitis A, and several outbreaks affecting this group have been reported across Europe (4). To prevent the spread of infection, since 1999, vaccination programs have been implemented among preadolescents in the Catalonia Autonomous Community of Spain. Despite some degree of nucleotide heterogeneity at the capsid region of hepatitis A virus (HAV) (5,6), there is not an equivalent degree of amino acid variation (7). HAV replicates as complex dynamic mutant distributions or quasispecies (8) and thus the high degree of conservation of the capsid amino acid sequences among independent strains must be the result o

Person-to-person transmission of Andes virus in hantavirus pulmonary syndrome, Argentina, 2014

Andes virus is unique among hantaviruses because it can be transmitted from person to person. This mechanism was previously supported by epidemiologic data and genetic evidence based only on partial sequences. We used full-length virus sequencing to confirm person-to-person transmission of this virus in a cluster of 3 cases in Argentina in 2014.Fil: Alonso, Daniel O.. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; ArgentinaFil: PéreZ Sautu, Unai. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio E Instituto de Salud "Dr. C. G. Malbran". Departamento Virus; ArgentinaFil: Bellomo, Carla María. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; ArgentinaFil: Prieto, Karla. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio E Instituto de Salud "Dr. C. G. Malbran". Departamento Virus; ArgentinaFil: Iglesias, Ayelén Aluminé. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; ArgentinaFil: Coelho, Rocío María. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; ArgentinaFil: Periolo, Natalia. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Domenech, Isabel. Hospital Zonal de Bariloche; ArgentinaFil: Talmon, Gabriel. Gobierno de la Provincia de Rio Negro. Ministerio de Salud; ArgentinaFil: Hansen, Romina. Gobierno de la Provincia de Rio Negro. Hospital de Area El Bolson; ArgentinaFil: Palacios, Gustavo. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio E Instituto de Salud "Dr. C. G. Malbran". Departamento Virus; ArgentinaFil: Martinez, Valeria Paula. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; Argentin

Andes Virus Genome Mutations That Are Likely Associated with Animal Model Attenuation and Human Person-to-Person Transmission

ABSTRACT We performed whole-genome sequencing with bait enrichment techniques to analyze Andes virus (ANDV), a cause of human hantavirus pulmonary syndrome. We used cryopreserved lung tissues from a naturally infected long-tailed colilargo, including early, intermediate, and late cell culture, passages of an ANDV isolate from that animal, and lung tissues from golden hamsters experimentally exposed to that ANDV isolate. The resulting complete genome sequences were subjected to detailed comparative genomic analysis against American orthohantaviruses. We identified four amino acid substitutions related to cell culture adaptation that resulted in attenuation of ANDV in the typically lethal golden hamster animal model of hantavirus pulmonary syndrome. Changes in the ANDV nucleocapsid protein, glycoprotein, and small nonstructural protein open reading frames correlated with mutations typical for ANDV strains associated with increased virulence in the small-animal model. Finally, we identified three amino acid substitutions, two in the small nonstructural protein and one in the glycoprotein, that were only present in the clade of viruses associated with efficient person-to-person transmission. Our results indicate that there are single-nucleotide polymorphisms that could be used to predict strain-specific ANDV virulence and/or transmissibility. IMPORTANCE Several orthohantaviruses cause the zoonotic disease hantavirus pulmonary syndrome (HPS) in the Americas. Among them, HPS caused by Andes virus (ANDV) is of great public health concern because it is associated with the highest case fatality rate (up to 50%). ANDV is also the only orthohantavirus associated with relatively robust evidence of person-to-person transmission. This work reveals nucleotide changes in the ANDV genome that are associated with virulence attenuation in an animal model and increased transmissibility in humans. These findings may pave the way to early severity predictions in future ANDV-caused HPS outbreaks

''Super-Spreaders'' and Person-to-Person Transmission of Andes Virus in Argentina

BACKGROUND From November 2018 through February 2019, person-to-person transmission of Andes virus (ANDV) hantavirus pulmonary syndrome occurred in Chubut Province, Argentina, and resulted in 34 confirmed infections and 11 deaths. Understanding the genomic, epidemiologic, and clinical characteristics of person-to-person transmission of ANDV is crucial to designing effective interventions. METHODS Clinical and epidemiologic information was obtained by means of patient report and from public health centers. Serologic testing, contact-tracing, and next-generation sequencing were used to identify ANDV infection as the cause of this outbreak of hantavirus pulmonary syndrome and to reconstruct person-to-person transmission events. RESULTS After a single introduction of ANDV from a rodent reservoir into the human population, transmission was driven by 3 symptomatic persons who attended crowded social events. After 18 cases were confirmed, public health officials enforced isolation of persons with confirmed cases and self-quarantine of possible contacts; these measures most likely curtailed further spread. The median reproductive number (the number of secondary cases caused by an infected person during the infectious period) was 2.12 before the control measures were enforced and decreased to 0.96 after the measures were implemented. Full genome sequencing of the ANDV strain involved in this outbreak was performed with specimens from 27 patients and showed that the strain that was present (Epuyén/18–19) was similar to the causative strain (Epilink/96) in the first known person-to-person transmission of hantavirus pulmonary syndrome caused by ANDV, which occurred in El Bolsón, Argentina, in 1996. Clinical investigations involving patients with ANDV hantavirus pulmonary syndrome in this outbreak revealed that patients with a high viral load and liver injury were more likely than other patients to spread infection. Disease severity, genomic diversity, age, and time spent in the hospital had no clear association with secondary transmission. CONCLUSIONS Among patients with ANDV hantavirus pulmonary syndrome, high viral titers in combination with attendance at massive social gatherings or extensive contact among persons were associated with a higher likelihood of transmission.Fil: Martinez, Valeria Paula. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Di Paola, Nicholas. Centers For Disease Control And Prevention. National Center For Infectious Diseases; Estados UnidosFil: Alonso, Daniel Oscar. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Pérez Sautu, Unai. Centers For Disease Control And Prevention. National Center For Infectious Diseases; Estados UnidosFil: Bellomo, Carla María. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Iglesias, Ayelén Aluminé. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Coelho, Rocío María. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: López, Beatriz. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Periolo, Natalia. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Larson, Peter A.. Centers For Disease Control And Prevention. National Center For Infectious Diseases; Estados UnidosFil: Nagle, Elyse R.. Centers For Disease Control And Prevention. National Center For Infectious Diseases; Estados UnidosFil: Chitty, Joseph A.. Centers For Disease Control And Prevention. National Center For Infectious Diseases; Estados UnidosFil: Pratt, Catherine B.. Centers For Disease Control And Prevention. National Center For Infectious Diseases; Estados Unidos. University of Nebraska; Estados UnidosFil: Díaz, Jorge Daniel. Provincia del Chubut. Ministerio de Salud; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Cisterna, Daniel Marcelo. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Campos, Josefina. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Sharma, Heema. National Institutes of Health; Estados UnidosFil: Dighero Kemp, Bonnie. National Institutes of Health; Estados UnidosFil: Biondo, Emiliano. Provincia del Chubut. Ministerio de Salud; ArgentinaFil: Lewis, Lorena. Provincia del Chubut. Ministerio de Salud; ArgentinaFil: Anselmo, Constanza. Provincia del Chubut. Ministerio de Salud; ArgentinaFil: Olivera, Camila P.. Provincia del Chubut. Ministerio de Salud; ArgentinaFil: Pontoriero, Fernanda. Ministerio de Salud ; Gobierno de la Provincia de Rio Negro;Fil: Lavarra, Enzo. Provincia del Chubut. Ministerio de Salud; ArgentinaFil: Kuhn, Jens H.. National Institutes of Health; Estados UnidosFil: Strella, Teresa. Provincia del Chubut. Ministerio de Salud; ArgentinaFil: Edelstein, Alexis. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; ArgentinaFil: Burgos, Miriam I.. Ministerio de Salud de la Nación; ArgentinaFil: Kaler, Mario. Ministerio de Salud de la Nación; ArgentinaFil: Rubinstein, Adolfo Luis. Ministerio de Salud de la Nación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kugelman, Jeffrey R.. Centers For Disease Control And Prevention. National Center For Infectious Diseases; Estados UnidosFil: Sanchez Lockhart, Mariano. Centers For Disease Control And Prevention. National Center For Infectious Diseases; Estados Unidos. University of Nebraska; Estados UnidosFil: Perandones, Claudia. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Palacios, Gustavo Guido. Centers For Disease Control And Prevention. National Center For Infectious Diseases; Estados Unido