The outbreak of the H1N1 influenza, earlier referred to as “swine flu”, has drawn major global attention, owing to its rapid spread and high initial mortality rates. In response to the ongoing community level outbreak in various regions and the emergence of a global pandemic, the World Health Organization (WHO) raised the alert level for H1N1 to phase 6, in June, 2009. 1
Initially identified in March and April 2009 across the United States and Mexico, the H1N1 strain spread across 76 countries through human-to-human transmission. As of July 1st 2009, the grand total of laboratory-confirmed cases was 77,201, including 332 officially reported deaths. As per the updates of WHO, the following are the current global statistics of the virus invasion. 2
The number of laboratory confirmed cases in Mexico and the US are 8,680 (including 116 deaths) and 27,717 (inclusive of 127 deaths), respectively.
Australia has become the worst hit continent in the Asia-Pacific region, with a total of 4,090 cases including 7 deaths. Other significant number of confirmed cases reported in the region include 1,518 in China, 1,414 in Thailand (3 deaths), 1,266 in Japan, 711 in New Zealand, and 202 in Republic of Korea.
Among the total 8,890 cases (4 deaths) confirmed in the European Union and European Free Trade Association countries, the maximum numbers were reported in Spain (717, including 1 death) and United Kingdom (6,538, with 3 deaths). 3 Other countries severely affected with H1N1 flu include Argentina (1,587), Canada (7,983) and Chile (6,211), reporting deaths of 26, 25 and 12, respectively.
The commencement of winter in southern hemisphere countries is expected to substantially increase the number of confirmed cases and death toll of the first influenza pandemic of the 21st century.
The novel influenza virus has a novel constellation of gene segments, proposed to have emerged through the re-assortment of Eurasian swine influenza virus and triple-reassortant swine influenza A (H1) virus genes. The triple-reassortant swine virus, consisting of genetic material derived from humans, pigs and birds, has been found circulating in swine for a decade.
Smith et al conducted an evolutionary analysis to estimate the timescale of its origin, and concluded that the reassortment of genes from swine lineages would have occured early before the occurrence of the disease in humans. The presence of multiple genetic ancestries ruled out the chances of artificial origin of the virus. 4 Researchers have raised concerns regarding the chances of reassortment of the virus with the existing human influenza viral strains to emerge as more virulent and transmissible forms. 5
Symptoms, Precautionary Measures and Treatment
The contagious disease manifests itself with symptoms similar to that of regular human flu: runny nose, sore throat, cough, fever, lethargy, and loss of appetite, with vomiting and diarrhea reported in a significant number of cases.
Despite the presumed association of the disease with the pig influenza virus, there is no evidence of viral transmission through food in the form of pork or its products. However, the Centers for Disease Control and Prevention (CDC) has recommended cooking pork to an internal temperature of 160°F to destroy all the pathogens.
Public health measures recommended by CDC to contain the spread of H1N1 influenza 7
- Hands should be washed often with soap or alcohol-based cleansers, especially after coughing or sneezing
- Touching mouth, nose and eyes should be avoided to prevent the spread of pathogens through these routes
- Close contact with patients suffering from influenza-like illness should be avoided
- Persons with flu-like illness should stay at home and avoid crowds
- Testing and antiviral therapy should be prioritized to individuals prone to complications associated with seasonal influenza and those with severe respiratory illnesses
- Nose and mouth should be covered with tissue while coughing or sneezing
There is a lack of scientific evidence regarding the efficacy of disposable facemasks and respirators in reducing the risk of infection. CDC has published interim recommendations on their use, based on updates on the transmission and severity of the virus, public health judgment, and their historical use in preventing the spread of flu and other respiratory viruses. As per the recommendations, facemasks or respirators should be worn by persons at high risk for severe influenza in crowded settings, and also by their caregivers, in cases of close contact. Also, the use of the respirator is recommended for healthcare workers caring for persons with probable or known infection. 8
Tests conducted on H1N1 infected patients in the US and Mexico showed that the virus is susceptible to neuraminidase inhibitors such as oseltamivir (Tamiflu ®) and zanamivir (Relenza ®), but resistant to adamantanes, such as amantadine (Symmetrel ®) and rimantadine (Flumadine ®). 6 The use of empiric antiviral treatment can be recommended for pregnant subjects, with suspected or confirmed infection. The WHO and concerned authorities are closely monitoring the emergence of antiviral drug-resistant strains. The first case of resistance to Tamiflu was reported in June, in Denmark.
CDC has deployed quarter of supplies of the Strategic National Stockpile (SNS), comprising of personal protective equipment, respiratory protection devices and antiviral medications, at all states in the continental US and territories. 1
Vaccine Development and Future Researches
Currently, there is no vaccine available to protect humans from this specific viral strain. CDC has evaluated the level of cross-reactive antibodies against the novel virus in children and adult cohorts, before and after the administration of the 2005-2009 seasonal influenza vaccines. However, none of these recently developed vaccines have conferred effective protection against the H1N1 virus. 9 The Swiss firm, Novartis has successfully produced the first batch of H1N1 vaccine through cell-based technology. The company is planning on initiating clinical trials by July 2009, raising the hope for rapid production and commercialization of the vaccine against the pandemic viral strain. 10
Recently, Huang and colleagues studied the adverse impact of viral genome reassortment on immune evasion and the strategies for developing a potent vaccine. The study showed that the constant antigenic drift through re-assortment can contribute to the acquisition of novel virion glycoprotein spikes of hemagglutinin (HA) and neuraminidase (NA) from other subtype viruses. Eliciting effective T-cell responses, along with antibody production, has been suggested as an effective vaccine development strategy that confers increased levels of cross-protective immunity and broadened antiviral immune response against the virus that reassort continuously. 11
Though the development of H1N1 influenza vaccine is of high value, the global distribution of the vaccine and other antiviral agents through international process would be tedious and time-consuming. Hence, there is an urgent need for more researches to investigate the effects of inexpensive generic agents in mitigating the impact of the pandemic, which could lead to an unprecedented economic and health crisis in both developed and developing nations. 12
Reference
1. Novel H1N1 Flu Situation Update. Centers for Disease Control and Prevention. Last Accessed July 1, 2009.
2. Epidemic and Pandemic Alert and Response (ERP). World Health Organization. Last Accessed July1, 2009.
3. Outbreak of Influenza A(H1N1) virus. European Centre for Disease Prevention and Control. Last Accessed July1, 2009.
4. Smith GJ, Vijaykrishna D, Bahl J, et al. Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic. Nature. 2009 Jun 25;459(7250):1122-5.
5. Peiris JS, Poon LL, Guan Y. Emergence of a novel swine-origin influenza A virus (S-OIV) H1N1 virus in humans. J Clin Virol. 2009 Jul;45(3):169-73. Epub 2009 Jun 11.
6. Key Facts About Swine Influenza. Centers for Disease Control and Prevention. Last Accessed July 1, 2009.
7. Novel H1N1 Flu (Swine Flu) and You. Centers for Disease Control and Prevention. Last Accessed July1, 2009.
8. Interim Recommendations for Facemask and Respirator Use to Reduce Novel Influenza A (H1N1) Virus Transmission. Centers for Disease Control and Prevention. Last Accessed July 1, 2009.
9. Centers for Disease Control and Prevention (CDC). Serum cross-reactive antibody response to a novel influenza A (H1N1) virus after vaccination with seasonal influenza vaccine. MMWR Morb Mortal Wkly Rep. 2009 May 22;58(19):521-4.
10. Novartis successfully demonstrates capabilities of cell-based technology for production of A(H1N1) vaccine. Press Release. Novartis. Last Accessed July1, 2009.
11. Huang YH. 2009 Novel H1N1 Influenza: The Impact of Viral Genomic Reassortment on Immune Evasion and Vaccine Strategy. J Chin Med Assoc. 2009 Jun;72(6):281-2.
12. Fedson DS. Meeting the challenge of influenza pandemic preparedness in developing countries. Emerg Infect Dis. 2009 Mar;15(3):365-71.
