Therapy Analysis - Influenza
Crossing the species barrier
While many strains of influenza are endemic to a particular species, there are occasions when a strain of the virus is able to cross the species barrier. Cases of zoonotic influenza strains have come to particular attention in recent years. One strain of avian influenza, an H5N1 virus normally endemic to birds, has been found to be readily transmissible to humans. Since the first human case of infection was reported in 1997, birdto- human transmission has been on the increase, and H5N1 has emerged as a potential global health threat. Avian H5N1 virus binds to alpha 2-3 sialic acid receptors, differing from human influenza viral strains, which bind the alpha 2-6 sialic acid receptor. This is thought to underlie the ability of the H5N1 virus to infect humans directly from avian species, while reducing the potential for human-to-human transmission. Also, once inside the human host, this receptor preference is thought to cause the virus to replicate primarily in the lower respiratory tract, potentially causing a fatal viral pneumonia. Consequently, the danger to humans is high, with the World Heath Organization (WHO) estimating a 60% mortality rate in confirmed cases of H5N1 infection. This is due to H5N1 potentially causing symptoms not commonly associated with influenza. For instance, there have been reports of H5N1 infection leading to severe symptoms such as diarrhoea and coma, sometimes in the absence of 'flu-like symptoms. In addition, H5N1 virus appears to have a more profound effect on the immune system than common influenza subtypes. While common influenza infection is known to increase levels of inflammatory cytokines such as TNF-alpha and interleukins, H5N1 causes a higher degree of cytokine induction, and can lead to a potentially fatal immune reaction known as a 'cytokine storm', resulting in nausea, fever and inflammation. Human cases of H5N1 have since declined, with 11 reported cases in 2008, compared to 65 and 55 for 2007 and 2006 respectively. However, given its high virulence and mutation rate, H5N1 remains a significant threat to public health.
Recently, another potentially zoonotic strain of influenza has made headline news. Swine 'flu commonly infects pigs and usually involves influenza A, although it can also be due to an influenza C subtype. Several small outbreaks of swine 'flu have been reported in the last 30 years, and resulted in some human fatalities; however, it was not until early 2009 that swine 'flu made a dramatic resurgence. In March 2009, Mexico experienced an outbreak of 'flu, resulting in 85 deaths, mostly in young, healthy adults. The virus was subsequently identified as a mutated H1N1 variant, which developed from the reassortment of four strains: one endemic to humans, one endemic to birds and two endemic to pigs. Since the initial outbreak, there have been almost 13,000 confirmed cases of H1N1 swine 'flu worldwide, with more than 50 countries affected. As of May 2009, there were over 10,700 reported cases in Mexico and the US, with the WHO declaring a Phase 5 pandemic alert. The antiviral drugs oseltamivir (Tamiflu) and zanamivir (Relenza) have since proven effective in treating H1N1 if given within the first two days of infection.
