Ana Valeria Bussetti

Streptococcus pneumoniae Coinfection Is Correlated with the Severity of H1N1 Pandemic Influenza

Background Initial reports in May 2009 of the novel influenza strain H1N1pdm estimated a case fatality rate (CFR) of 0.6%, similar to that of seasonal influenza. In July 2009, however, Argentina reported 3056 cases with 137 deaths, representing a CFR of 4.5%. Potential explanations for increased CFR included virus reassortment or genetic drift, or infection of a more vulnerable population. Virus genomic sequencing of 26 Argentinian samples representing both severe and mild disease indicated no evidence of reassortment, mutations associated with resistance to antiviral drugs, or genetic drift that might contribute to virulence. Furthermore, no evidence was found for increased frequency of risk factors for H1N1pdm disease. Methods/Principal Findings We examined nasopharyngeal swab samples (NPS) from 199 cases of H1N1pdm infection from Argentina with MassTag PCR, testing for 33 additional microbial agents. The study population consisted of 199 H1N1pdm-infected subjects sampled between 23 June and 4 July 2009. Thirty-nine had severe disease defined as death (n = 20) or hospitalization (n = 19); 160 had mild disease. At least one additional agent of potential pathogenic importance was identified in 152 samples (76%), including Streptococcus pneumoniae (n = 62); Haemophilus influenzae (n = 104); human respiratory syncytial virus A (n = 11) and B (n = 1); human rhinovirus A (n = 1) and B (n = 4); human coronaviruses 229E (n = 1) and OC43 (n = 2); Klebsiella pneumoniae (n = 2); Acinetobacter baumannii (n = 2); Serratia marcescens (n = 1); and Staphylococcus aureus (n = 35) and methicillin-resistant S. aureus (MRSA, n = 6). The presence of S. pneumoniae was strongly correlated with severe disease. S. pneumoniae was present in 56.4% of severe cases versus 25% of mild cases; more than one-third of H1N1pdm NPS with S. pneumoniae were from subjects with severe disease (22 of 62 S. pneumoniae-positive NPS, p = 0.0004). In subjects 6 to 55 years of age, the adjusted odds ratio (OR) of severe disease in the presence of S. pneumoniae was 125.5 (95% confidence interval [CI], 16.95, 928.72; p<0.0001). Conclusions/Significance The association of S. pneumoniae with morbidity and mortality is established in the current and previous influenza pandemics. However, this study is the first to demonstrate the prognostic significance of non-invasive antemortem diagnosis of S. pneumoniae infection and may provide insights into clinical management.

Heart and skeletal muscle inflammation of farmed salmon is associated with infection with a novel reovirus

Atlantic salmon (Salmo salar L.) mariculture has been associated with epidemics of infectious diseases that threaten not only local production, but also wild fish coming into close proximity to marine pens and fish escaping from them. Heart and skeletal muscle inflammation (HSMI) is a frequently fatal disease of farmed Atlantic salmon. First recognized in one farm in Norway in 1999[1], HSMI was subsequently implicated in outbreaks in other farms in Norway and the United Kingdom[2]. Although pathology and disease transmission studies indicated an infectious basis, efforts to identify an agent were unsuccessful. Here we provide evidence that HSMI is associated with infection with piscine reovirus (PRV). PRV is a novel reovirus identified by unbiased high throughput DNA sequencing and a bioinformatics program focused on nucleotide frequency as well as sequence alignment and motif analyses. Formal implication of PRV in HSMI will require isolation in cell culture and fulfillment of Kochs postulates, or prevention or modification of disease through use of specific drugs or vaccines. Nonetheless, as our data indicate that a causal relationship is plausible, measures must be taken to control PRV not only because it threatens domestic salmon production but also due to the potential for transmission to wild salmon populations.

Human Metapneumovirus Infection in Wild Mountain Gorillas, Rwanda

The genetic relatedness of mountain gorillas and humans has led to concerns about interspecies transmission of infectious agents. Human-to-gorilla transmission may explain human metapneumovirus in 2 wild mountain gorillas that died during a respiratory disease outbreak in Rwanda in 2009. Surveillance is needed to ensure survival of these critically endangered animals.

Characterization of the Sandfly fever Naples species complex and description of a new Karimabad species complex (genus Phlebovirus, family Bunyaviridae).

Genomic and antigenic characterization of members of the Sandfly fever Naples virus (SFNV) complex reveals the presence of five clades that differ in their geographical distribution. Saint Floris and Gordil viruses, both found in Africa, form one clade; Punique, Granada and Massilia viruses, all isolated in the western Mediterranean, constitute a second; Toscana virus, a third; SFNV isolates from Italy, Cyprus, Egypt and India form a fourth; while Tehran virus and a Serbian isolate Yu 8/76, represent a fifth. Interestingly, this last clade appears not to express the second non-structural protein ORF. Karimabad virus, previously classified as a member of the SFNV complex, and Gabek Forest virus are distinct and form a new species complex (named Karimabad) in the Phlebovirus genus. In contrast with the high reassortment frequency observed in some South American phleboviruses, the only virus of the SFNV complex with evidence of reassortment was Granada virus.

Discovery of an orthoreovirus in the aborted fetus of a Steller sea lion (Eumetopias jubatus)

An aborted mid-gestational male Steller sea lion fetus with an attached placenta was recovered on the floor of an open floating capture trap located off Norris Rock near Denman Island, British Columbia. Viral culture of the placenta demonstrated cytopathic effect. Although no specific signal was obtained in microarray experiments using RNA obtained from viral culture, elution and sequence analysis revealed the presence of a reovirus. Complete genome pyrosequencing led to the identification of an orthoreovirus that we have tentatively named Steller sea lion reovirus (SSRV). Phylogenetic analysis revealed similarities between SSRV and orthoreoviruses of birds, bats and other mammals that suggests potential for interspecies transmission.

Rapid Molecular Strategy for Orbivirus Detection and Characterization

ABSTRACT Orbiviruses infect a wide range of hosts, including humans. The ability to detect them has been hampered by their diversity. Here we present a simple consensus reverse transcription (RT)-PCR method targeting the polymerase gene for orbivirus recognition and characterization. Phylogenetic assignment is achieved by automated Web-based sequence analysis of amplification products.

Genomic and antigenic characterization of Jos virus

Jos virus (JOSV), originally isolated in Jos, Nigeria in 1967, has remained unclassified despite cultivation in tissue culture, development of animal models of infection and implementation of seroprevalence surveys for infection. Here, we report genetic, ultrastructural and serological evidence that JOSV is an orthomyxovirus distinct from but phylogenetically related to viruses of the genus Thogotovirus.

Molecular characterization of severe and mild cases of influenza A (H1N1) 2009 strain from Argentina.

While worldwide pandemic influenza A(H1N1) pdm case fatality rate (CFR) was 0.4%, Argentinas was 4.5%. A total of 34 strains from mild and severe cases were analyzed. A full genome sequencing was carried out on 26 of these, and a partial sequencing on the remaining eight. We observed no evidence that the high CFR can be attributed to direct virus changes. No evidence of re-assortment, mutations associated with resistance to antiviral drugs, or genetic drift that might contribute to virulence was observed. Although the mutation D225G associated with severity in the latest reports from the Ukraine and Norway is not observed among the Argentine strains, an amino acid change in the area (S206T) surrounding the HA receptor binding domain was observed, the same previously established worldwide.