The Struggle Against Pandemic Influenza A (H1N1) 2009

In the new millennium, the world has seen the emergence of three novel human respiratory viruses: SARS virus (a novel Corona virus) in 2003, Influenza A H5N1 (‘Avian flu’) in 2004 and in the past six months, a pandemic caused by a new strain: the Influenza A (H1N1) 2009 virus.1 In sharp contrast to the SARS and Avian Influenza A H5N1 viruses which emerged from the Asian continent, the Influenza A (H1N1) 2009 virus emerged from North America and unlike the SARS and Avian Influenza A H5N1 viruses, which were never reported in Oman, the novel Influenza A (H1N1) 2009 virus has already been detected here in more than 2,500 patients.

Influenza viruses by nature are highly unpredictable and unstable.2 They have the unique distinction of having a segmented genome which permits them to re-assort their genetic structure resulting in the evolution of new subtypes. This genetic restructuring occurs regularly in nature and at times provides the virus with the unusual capability to cause widespread disease in immunologically naïve populations and swiftly move across geographical borders to cause pandemics.

The 20^th century saw three such pandemics; the first (Spanish flu) caused by influenza A (H1N1) killing between 20–50 million people.3 The other two pandemics, in 1957 and 1968, were relatively milder, but still killed nearly one million.

There are several key epidemiological features that determine the occurrence of a pandemic influenza. According to Miller et al.4 who recently analysed the “signature features” of the three previous influenza pandemics (A/H1N1 in 1918, A/H2N2 in 1957 and A/H3N2 in 1968) four important factors emerge as key determinants: 1) occurrence of a shift in the virus subtype; 2) shifts of the highest death rates to younger populations; 3) successive pandemic waves, and 4) higher transmissibility than that of seasonal influenza.

While the world was grappling with H5N1 Avian flu “which had caused 442 cases and 262 deaths in 15 countries as of September 24^th 2009”,5 and while the world was preparing for a pandemic that could emerge, another influenza virus made a dramatic appearance in Mexico in March 2009 in the form of a novel H1N1 subtype. Many of us were surprised when, instead of H5N1 acquiring mutations necessary for efficient person-to-person transmission, reports emerged from Mexico about a novel influenza virus that was killing young people. The novel Influenza A (H1N1) virus has the genetic structure resulting from re-assortment of genes from four influenza viruses: North American swine influenza, Asia/Europe swine influenza, human influenza and avian influenza (non H5). The virus has a unique genetic composition that has never been seen earlier. As a result of this, within a short period of six months the virus had spread to 189 countries, caused more than 414,000 confirmed cases (the number of cases reported actually understates the real number of cases) and at least 5,000 deaths.6 In Oman as of the latest update, 2,681 people have been reported as infected with the A (H1N1) virus of which 153 cases required hospitalisation and 24 have died.

Most cases described during the three influenza pandemics of the 20^th century and during seasonal influenza involved transient illness not requiring hospitalisation. Most deaths are described in the very young or the elderly or those with underlying disease. The available information also indicates that, unlike seasonal influenza, the current H1N1 pandemic has primarily affected younger adults. This is in contrast to the fact that complications of seasonal influenza affect primarily the elderly or young children.

The reported clinical presentation of the novel Influenza A (H1N1) infection ranges broadly from mild uncomplicated infection to severe pneumonia that can result in death. The available data show that the clinical features of fever, cough and sore throat are similar to those of seasonal influenza. To date, the case fatality ratios (CFR) attributable to the current H1N1 pandemic has been estimated at around 0.4%, based on surveillance data from Mexico and mathematical modelling.7 This CFR is higher than that of average seasonal influenza, but remains of the same order of magnitude. Whether this will change is unknown. The WHO Regional Office for the Eastern Mediterranean (EMRO) reported that 96 of the 14,739 laboratory-confirmed cases as of October 23, 2009 had been fatal.8 Most of these deaths were related to respiratory failure resulting from severe pneumonia with multi-focal infiltrates and acute respiratory distress syndrome.

Unlike most seasonal influenza strains, this pandemic H1N1 2009 strain seems to invade the lower airway and alveoli, not just the upper airways, resulting in more severe illness.9,10 The world’s experience so far tells us that serious illness associated with this virus often manifests as acute lung injury resulting in overwhelming hypoxaemia. Advanced life-support technologies for prolonged periods are often required to save lives.

There are few data on risk factors, severe cases and deaths associated with the pandemic H1N1 influenza 2009. Analysis of available data suggests that the elderly may to some extent be protected from infection. There was underlying disease in at least half of the fatal cases (574 studied). Two risk factors seem of particular importance: pregnancy and metabolic condition (including obesity which has not been considered as risk factor in previous pandemics or seasonal influenza).11

The transmission is thought to occur in the same way as seasonal influenza which is mainly person-to-person transmission through coughing or sneezing of people infected with this virus. People may be infected by touching something with influenza viruses on it and then touching their mouth or nose.

The recommended procedure for laboratory diagnosis of Influenza A (H1N1) 2009 virus infection is real-time reverse-transcriptase polymerase chain reaction (RT-PCR.12 In Oman, this facility is only, at present, available at the Public Health Laboratory (PHL) Muscat, and at Sultan Qaboos University Hospital (SQUH), Muscat.

Two classes of anti-viral medication are available for the treatment and post-exposure chemoprophylaxis of seasonal human influenza: neuraminidase inhibitors (oseltamivir and zanamivir) and adamantanes (amantadine and rimantadine). However, the novel Influenza A (H1N1) 2009 virus is resistant to amantadine and rimantadine, but is sensitive to oseltamivir (Tamiflu) and zanamivir (Relenza).13 Based on experience with other influenza viruses, treatment would be most effective if given within two days of symptom onset. The data show that the virus continues to remain susceptible to oseltamivir and zanamivir. The access to these drugs and their rational use are critical in mitigating the disease as well as prolonging the utility of the drugs by obviating the emergence of resistance.

Presently, a vigorous development process is underway to develop the pandemic vaccine. It is believed that manufacturers could produce 2.5 billion doses of pandemic vaccine in 12 months following receipt of the production strain and global demand can be met within 2–3 years. However, the supply of vaccine, at least during the first year of the pandemic, will be limited and not easily accessible to the vast majority of people living in developing countries. We must therefore identify vulnerable or at-risk groups as a first step. It is also important to note that no immunisation programme is 100% effective and, if therefore a sufficient number of cases are not prevented, we can expect more young critically ill patients to fill all tertiary-level intensive care beds. It is important to highlight here that fair access to the vaccine against the pandemic novel H1N1 influenza virus is an ethical issue involving justice for all. It is also a prerequisite for the success of the global pandemic strategy to safeguard global health.

Intensive public education for adopting cost-effective non-pharmaceutical interventions can yield substantial results.14 Non-pharmaceutical prevention through repeated hand washing and following cough/sneeze etiquettes can be easily employed at all levels in communities and prevent the spread of the disease. Isolation of cases and proper case management, including infection control, are equally important to cut down on the transmission of the disease.

National leadership is needed in all countries. A visible independent health care leadership, with executive powers across all jurisdictions and ultimately accountable to the highest office in the country, must be in place. Next, local leaders must be identified. All stakeholders should have clear communication with and rapid access to experts. We need leaders at all levels who will work together quickly and collaboratively to solve problems such as moving equipment and personnel from one area of a country to another as required without barriers imposed by licensing and hospital privileges.

Since 2003 when Influenza A (H1N1) 2009 emerged as a potential influenza pandemic, the national authorities in Oman have been engaged in strengthening their response efforts with assistance from World Health Organization. The National Influenza Pandemic Preparedness Plan has provided a valuable framework of action and, with minor modifications, was activated to launch an effective response to the current pandemic. The pandemic, however, is far from over, and deaths will unfortunately continue to occur. We should therefore plan for important increases in pandemic H1N1 2009 cases that manifest at the two ends of the spectrum of disease severity.

We must not underestimate a foe like pandemic H1N1 2009, especially now. This pandemic has already created chaos in communities worldwide. The virus’s place of origin, the speed of its spread and the severity of the illness in otherwise healthy people could not be anticipated before the initial outbreaks, even by experts. In addition, containment, a first step in the control of an outbreak, has failed.

It would be naïve to extrapolate the impact of the 1918 pandemic to the current event because today effective tools are available including drugs, diagnostics and a high level of preparedness in place in many countries including such measures as infection control practices, case management facilities and mass media reach for public awareness and risk communication. Advances in technology are now swiftly translatable into tools.

While we still hope for the best, we need to act now to deal with the worst that pandemic H1N1 2009 may deliver. Doing so will save lives.