Peer-reviewed literature - 06 January 2012 (WHO, edited): H3N2v in USA, Oseltamivir-resistant H1N1pdm09 in Australia

[Giuseppe Michieli]

[Source: World Health Organization, full text: (LINK). Edited.]

Peer-reviewed literature - 06 January 2012


Report of human cases of swine origin influenza viruses in the United States of America

The Centers for Disease Control and Prevention released an update on influenza A(H3N2)v transmission and guidelines in the Morbidity and Mortality Weekly Report on December 23, 2011.

The report outlines the development of 12 confirmed cases of human infection with human influenza A(H3N2)v possessing the matrix (M) gene from the influenza A(H1N1)pdm09 virus.

Cases occurred across five States (Indiana, Iowa, Maine, Pennsylvania, and West Virginia) between August 17 and December 23, 2011.

The focus of the report is on the last three of these cases.

The first is an adult male case in Indiana, who had direct contact with swine. He was hospitalized for a period of 4 days and did not receive antiviral treatment before making a full recovery. The report indicates that this highlights the risk of interspecies transmission and details recommendations for swine workers to avoid infection.

The other two cases are children aged <5 years in West Virginia. Both regularly attend the same day-care facility and neither had had recent contact with swine. The first child was already hospitalized for an unrelated condition and was discharged 2 days after the onset of fever while medical care was not sought for the second child. The ten day gap between the onset of their respective illnesses and their lack of exposure to swine was considered by the authors to be strong evidence of limited human-to-human transmission.

Furthermore, the authors recommend that clinicians should consider influenza A(H3N2)v infections in patients who have not had exposure to swine in states where cases have been reported.

The report also contains details of current influenza surveillance of U.S swine. Of 150 isolates sequenced, 30 were A(H3N2) viruses and of these eight possessed the influenza A(H1N1)pdm09 M gene. Further characterization and analysis are ongoing.


Comment:

Human cases of infection with influenza viruses from swine have been reported on multiple occasions over the last several years. The current series of 12 cases differs from those reported previously in that the genetic material of the virus has recombined with that of the influenza A(H1N1)pdm09 virus, which was responsible for the pandemic of 2009, and acquired the M gene from the pandemic virus.

The M gene has been demonstrated in at least one animal study to be involved in human-to-human transmission and the presence of the M gene from the influenza A(H1N1)pdm09 virus raises this concern.

Indeed, this virus has demonstrated the ability to spread from human-to-human on two occasions and perhaps has had multiple generations of transmission in the current report.

However, so far human-to-human transmission has only occurred with close contact in settings known to facilitate transmission of infectious diseases (i.e. daycare centers and homes) and extensive field investigations have failed to find additional cases in the community.

This virus is similar antigenically and genetically to one circulating in the human population in the mid-1990s implying that individuals born before that time may have partial resistance to infection, which would be consistent with the observation that 11 of the 12 cases have been young children. While three of the 12 cases have been hospitalized, only two were for the acute influenza related illness and all recovered uneventfully.

Notably, all of the 12 viruses tested have been sensitive to oseltamivir.


Reference:

1. Centers for Disease Control and Prevention. Update: Influenza A(H3N2)v Transmission and Guidelines — Five States, 2011. Morbidity and Mortality Weekly Report, Vol 60, December 23 2011.
2. Centers for Disease Control and Prevention. Swine-Origin Influenza A(H3N2) Virus Infection in Two Children — Indiana and Pennsylvania, July–August 2011. Morbidity and Mortality Weekly Report, Vol 60, Sept. 9, 2011.
3. Chou YY, et al. The M segment of the 2009 new pandemic H1N1 influenza virus is critical for its high transmission efficiency in the guinea pig model. J. Virol. doi:10.1128/JVI.05794-11.
4. Lina B, et al. S-OtrH3N2 viruses: use of sequence data for description of the molecular characteristics of the viruses and their relatedness to previously circulating H3N2 human viruses. Euro Surveill. 2011;16(50):pii=20039. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20039.



Report of a large cluster of oseltamivir resistant viruses in Australia

On December 29, 2011, Australian investigators released a summary account of the characterization of an outbreak with sustained community transmission of oseltamivir-resistant influenza A(H1N1)pdm09 viruses in the state of New South Wales.

The report focuses on 29 oseltamivir-resistant cases identified from 182 patients in the Hunter New England region of the state between May and August 2011. Only one of these 29 patients had received oseltamivir before specimen collection.

Hemagglutinin and neuraminidase analysis showed that resistant strains were closely related, which indicates the spread of a single A(H1N1)pdm09 variant.

An epidemiological link was demonstrated between 10 of the 29 cases. The report describes the significantly higher IC50 values of oseltamivir-resistant viruses to oseltamivir and peramivir compared to wild-type strains but also indicates that oseltamivir-resistant viruses were as susceptible to zanamivir as wild-type strains.

The report also states that the resistant strains are antigenically similar to the vaccine strain including in patients who received the vaccine.


Comment:

While this outbreak of oseltamivir-resistant influenza viruses raised great concern when first reported, it is notable that since August 2011 no new cases associated with this outbreak have been detected.

Globally, the proportion of viruses with oseltamivir resistance remains about 1% in untreated patients and transmission has been reported only in close settings. Much higher proportions of resistant viruses are detected in some situations such as prolonged treatment in individuals with immunodeficiency.

For the moment, clinicians should continue to use oseltamivir for treatment of high-risk and severe cases of influenza.

However, this event illustrates the need for continued vigilance so that treatment guidelines can be amended when necessary. WHO continues to recommend that countries who have the means to test for oseltamivir-resistant influenza A(H1N1)pdm09 viruses do so in a sample of cases and that all resistant viruses should be sent to a WHO collaborating center for further characterization.

In addition, cases with resistant virus should be investigated for evidence of onward transmission and any findings to suggest that transmission of resistant virus is occurring should be immediately reported to WHO.


Reference:

Hurt, A.C., et. al. Community Transmission of Oseltamivir-Resistant A(H1N1)pdm09 Influenza. NEJM, 2011:2541-2542;365(26).

-
-------