Tag Archives: influenza

Vaccinate the kids to protect the “herd”

Vaccinating young children and adolescents against influenza protects unvaccinated individuals in the wider community (the herd immunity), show results from a clinical trial conducted in rural communities in Canada and published free in the journal JAMA. “Our findings … support selective influenza immunisation of school aged children with inactivated influenza vaccine to interrupt influenza transmission,” writes Mark Loeb and colleagues.

Influenza is an infectious disease which causes significant morbidity and mortality; in the United States around 36,000 people die, and 200,000 people are hospitalised, each year from influenza. Vaccination against seasonal and pandemic flu is fundamental to prevent the spread of disease. Current immunisation policy targets individuals who have a greater risk of flu complications, but flu vaccines can also be used to interrupt the spread of influenza across an entire population. Previous work has shown that children and adolescents play an important role in the transmission of influenza but it is still unclear whether vaccinating these children benefits the community as a whole and protects those that have not been immunised.

Loeb et al. recruited individuals from 46 Hutterite colonies in western Canada to test the community-wide benefits of flu vaccination programmes in children and young adolescents. Their cluster trial included 947 healthy children and adolescents, ranging from 3 to 15 years old, who they randomly assigned according to community to receive either a trivalent seasonal influenza vaccine or a hepatitis A vaccine as a control. They also recruited 2,326 members from the Hutterite communities who were not vaccinated during the study. All participants in the study were followed up for signs and symptoms of influenza over a six month period.

The investigators observed that the uptake of both vaccines in eligible healthy children was similar; 83% for the influenza vaccine and 79% for the hepatitis A vaccine. 119 unvaccinated individuals had laboratory-confirmed influenza; twice as many people in the communities assigned to the control vaccine had the disease compared to those communities assigned to influenza vaccine. Loeb et al. found that this pattern of disease incidence remained even when taking into account all study participants, including those who did and did not receive a vaccine. The researchers concluded that immunising children aged 3–15 years old against seasonal flu conferred 61% indirect protection in unvaccinated people.

“Our data suggest that a significant herd immunity effect can be achieved when the uptake of vaccine is approximately 80%,” write the investigators. Their study suggests that selectively immunising children during flu epidemics may help to prevent spread of the disease in the rest of the population.

ResearchBlogging.orgLoeb, M., Russell, M., Moss, L., Fonseca, K., Fox, J., Earn, D., Aoki, F., Horsman, G., Van Caeseele, P., Chokani, K., Vooght, M., Babiuk, L., Webby, R., & Walter, S. (2010). Effect of Influenza Vaccination of Children on Infection Rates in Hutterite Communities: A Randomized Trial JAMA: The Journal of the American Medical Association, 303 (10), 943-950 DOI: 10.1001/jama.2010.250

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Filed under Infectious Disease, Medicine, Public Health, Vaccine

Host factors help influenza virus replication

German researchers have identified hundreds of host cell genes that affect influenza A virus replication. The work by Alexander Karlas and colleagues and published online in the journal Nature could help identify new drug targets which could be useful against a broad range of influenza viruses.

Influenza A viruses are a global public health threat that cause seasonal flu epidemics and periodic pandemics, the most recent major outbreak being the infamous swine flu pandemic that originated in Mexico in 2009. The influenza virus has a high mutation rate, which means that drugs and vaccines can become ineffective rapidly during a flu outbreak. The influenza virus can only replicate inside living cells and so novel drugs that target host cell functions required for virus replication are an attractive research area.

Karlas et al. conducted a genome-wide RNA interference screen in conjunction with a luciferase reporter assay to identify host cells factor that are important for influenza virus replication in human cells. First, they transfected human epithelial lung cells with 62,000 siRNAs against ~17,000 annotated and ~6,000 predicted human genes and 48 h later they infected the same cells with influenza A H1N1 virus and used immunofluorescence microscopy to check the virus infection rates. Secondly, they transferred the virus supernatants from the lung cells onto human embryonic kidney cells which contained an influenza-virus-specific luciferase reporter that bioluminesces in the presence of the virus to further quantify the virus infection and replication rates.

The scientists identified 287 human genes which appeared to be important in influenza virus replication, including the nuclear export factor genes NXF1 and XPO1, which have already been shown to be important for flu virus replication, and several genes which are connected with pre-mRNA splicing. They confirmed that siRNAs against ~59% (168 out of 287) of these genes decreased the number of endemic H1N1 and the 2009 pandemic H1N1 influenza viruses in human cells by at least five times. Interestingly, a subset of the same siRNAs also decreased replication of the highly pathogenic avian H5N1 influenza A strain. Furthermore, they found that a small molecule inhibitor of CDC-like kinase 1 reduced influenza virus replication by two orders of magnitude, because of impaired splicing of viral M2 messenger RNA. Finally, in vivo mouse studies confirmed the importance of the cell cycle regulator p27 in virus replication, p27-/- knockout mice were infected with H1N1 virus and 2 days later the researchers observed that the viral load within the lungs of the mice was significantly reduced.

This study “provided new and comprehensive information on host cell determinants of replication, and uncovered potential targets for novel antiviral strategies…against a broad spectrum of influenza viruses” write the authors and presents more information on the interaction between viruses and the human host.

ResearchBlogging.orgKarlas, A., Machuy, N., Shin, Y., Pleissner, K., Artarini, A., Heuer, D., Becker, D., Khalil, H., Ogilvie, L., Hess, S., Mäurer, A., Müller, E., Wolff, T., Rudel, T., & Meyer, T. (2010). Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication Nature DOI: 10.1038/nature08760

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