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GUEST EDITORIAL
Year : 2009  |  Volume : 27  |  Issue : 3  |  Page : 179-181
 

Emergence of novel influenza A/H1N1 virus as a pandemic agent


Department of Neurovirology, National Institute of Mental Health And Neuro Sciences, Bangalore-560 029, India

Date of Submission05-Jun-2009
Date of Acceptance06-Jun-2009
Date of Web Publication4-Jul-2009

Correspondence Address:
V Ravi
Department of Neurovirology, National Institute of Mental Health And Neuro Sciences, Bangalore-560 029
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0255-0857.53197

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How to cite this article:
Ravi V. Emergence of novel influenza A/H1N1 virus as a pandemic agent. Indian J Med Microbiol 2009;27:179-81

How to cite this URL:
Ravi V. Emergence of novel influenza A/H1N1 virus as a pandemic agent. Indian J Med Microbiol [serial online] 2009 [cited 2019 Nov 16];27:179-81. Available from: http://www.ijmm.org/text.asp?2009/27/3/179/53197


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 H5N1 ('Avian flu') in 2004 and in the past six weeks, an international outbreak caused by a new strain of Influenza virus 2009 A/H1N1. [1] This novel Influenza 2009 A/H1N1 virus contains a combination of swine, avian, and human influenza virus genes. In sharp contrast to SARS and Avian Influenza H5N1 viruses which emerged from the Asian continent, Influenza 2009 A/H1N1 virus emerged from North America. In mid-April 2009, the World Health Organization (WHO), [2] Geneva, and Centres for Disease Control (CDC), [3] USA, initially recognized a dramatic increase in the number of influenza cases being reported from Mexico. In less than sixty days the novel Influenza 2009 A/H1N1 virus rapidly spread across 66 countries in the world and caused over 52,000 infections including 231 deaths. [2] Amongst them, three North American countries- USA (21,449 cases), Mexico (7629 cases) and Canada (5710 cases) accounted for 88% of the total number of global cases reported. [2] Unlike the SARS and Avian Influenza H5N1 viruses, which never were reported in human beings from India, the novel Influenza 2009 A/H1N1 virus has already been detected in four patients in India. All of them acquired the infection abroad and were detected to be positive upon arrival in our country. Indeed, one of the notable features of the current strain of Influenza 2009 A/H1N1 virus is the high efficiency of human-to-human transmission. This probably explains the alarming spread of the virus across the globe in a very short time and therefore poses a serious pandemic threat. This article is intended to provide a concise update on the current situation of Influenza 2009 A/H1N1 and is by no means an exhaustive review of available literature.

Influenza virus is an enveloped RNA virus of the Orthomyxoviridae family. It is endowed with an inherent capacity for genetic variation and is based on two important features; (i) the presence of a segmented genome, with eight RNA segments that are genetically independent of each other and (ii) a high rate of mutation, especially in the surface heamgglutinin (H) and neuraminidase (N) proteins. These unique molecular features coupled with the ability of the virus to cause infection in a wide host range of humans, domestic animals and birds render it a potential pandemic agent. Domestic pigs and birds because of their proximity to humans provide a great opportunity for the occurrence of mixed influenza infections. Consequently, these two species (pigs and birds) act as 'melting pots' for the generation of re-assortment of viruses and play a crucial role in evolution of influenza pandemics. The current outbreak of Influenza 2009 A/H1N1 is a rare recombination of gene segments from swine with avian and human influenza strains. Phylogenetic analysis of sequences of all genes of A/California/04/2009, the virus isolated from a patient in the recent outbreak in USA, showed that its genome represents a quadruple re-assortment of two swine strains, one human strain, and one avian strain of influenza. [4] The virus has six gene segments (PB2, PB1, PA, HA, NP, and NS) similar to ones previously found, in triple-reasserting swine influenza viruses, circulating in pigs in North America. [5] The North American triple-reasserting virus is itself a combination of the heamagglutinin ( HA ), nucleoprotein ( NP ), and nonstructural protein ( NS ) genes, originating from classic swine influenza A viruses; the polymerase PB2 ( PB2 ) and polymerase ( PA ) genes from avian influenza viruses from the North American lineage; and the polymerase PB1 ( PB1 ) gene from human influenza A viruses. [5] The genes encoding neuraminidase ( NA ) and M protein ( M ) however were most closely related to those in influenza A viruses circulating in swine populations in Eurasia. [6] The largest proportion of genes in this novel virus comes from swine influenza viruses (30.6 per cent from North American swine influenza strains, 17.5 per cent from Eurasian swine influenza strains), followed by North American avian influenza strains (34.4 per cent) and human influenza strains (17.5 per cent) [6] . This particular genetic combination of influenza virus segments had not been seen before in the US or elsewhere. [1],[4]

There are several key epidemiological features that determine the occurrence of a pandemic influenza. According to Miller et al , [7] who recently analyzed the "signature features" of three previous influenza pandemics (A/H1N1 in 1918, A/H2N2 in1957 and A/H3N2 in1968) four important factors emerge as key determinants- (i) occurrence of a shift in the virus subtype, (ii) shifts of the highest death rates to younger populations, (iii) successive pandemic waves, and (iv) higher transmissibility than that of seasonal influenza. The current outbreak of Influenza 2009 A/H1N1 has fulfilled two of these four conditions viz. occurrence of shift in the virus subtype (Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team) and higher transmissibility than that of seasonal influenza. [8] The next six to eoght months would determine whether the remaining two conditions would also be met. However, based on the initial descriptions of the clinical manifestations reported from cases in USA there is sufficient cause for concern at this stage. The age of the 642 confirmed cases Influenza A 2009/H1N1 reported from USA, ranged from three months to 81 years although a majority (60%) were younger than 18 years suggesting thereby that children and young adults may be more susceptible to this infection than older persons. [1],[4] This not a surprise finding as most older adults probably have substantial immunity to H1 variants that have circulated among humans from 1918 through 1957 and then again from 1977 through the present. It is not clear though; whether cross-reacting antibodies from previous H1N1 infections will provide protection against the novel Influenza A 2009/H1N1 virus but the epidemiologic features of the confirmed cases from USA suggest that there may be partial protection from multiple previous influenza infections. [1] The salient clinical manifestations noted in the laboratory confirmed cases [1] of the current outbreak include a self-limiting, uncomplicated febrile respiratory illness and typical symptoms similar to those of seasonal influenza (cough, sore throat, rhinorrhoea, headache, and myalgia). However, 38% of cases have also reported vomiting or diarrhea, neither of which is typical of seasonal influenza. In Mexico, 97 of 5029 laboratory-confirmed cases have been fatal. [2] Most of these deaths were related to respiratory failure resulting from severe pneumonia with multi-focal infiltrates and acute respiratory distress syndrome. [2] In addition to respiratory failure, renal or multi-organ failure occurred in 24 percent of cases in Mexico. Among 11,054 cases in the United States, there have been 17 deaths. Among 1530 cases in Canada, two patients have died, and among 50 cases in Costa Rica, one patient died. [2]

The recommended procedure for laboratory diagnosis of Influenza 2009 A/ H1N1 virus infection is real-time reverse-transcriptase PCR or culture. [9] In India, these facilities are, at present, available at The National Institute of Virology (NIV), Pune, and The National Institute of Communicable Diseases (NICD), New Delhi. To establish the diagnosis of Influenza 2009 A/ H1N1 in the laboratory, an upper respiratory sample (nasopharyngeal swab, nasal swab, throat swab, combined oropharyngeal/nasopharyngeal swab, or nasal aspirate) should be collected. [9] In intubated patients, an endotracheal aspirate should also be obtained. Swabs with a synthetic tip (e.g., polyester or Dacron) and an aluminium or plastic shaft should be used. Swabs with cotton tips and wooden shafts are not recommended. Swabs made of calcium alginate are not acceptable. The collection vial in which the swab is placed should contain one to three ml of viral transport media. Specimens should be placed in viral transport media and placed on ice (4șC) or refrigerated immediately for transportation to the laboratory. [9] Once the samples arrive in the laboratory, they should be stored either in a refrigerator at 4șC or in a minus 70șC freezer. If a minus 70șC freezer is not available, they should be kept refrigerated, preferably for less than or equal to one week. Specimens should be shipped on dry ice to the designated laboratories in clearly labelled containers and should include all information requested by the state health laboratory. [9]

Two classes of anti-viral medication are available for the treatment and post exposure chemoprophylaxis of seasonal human influenza: neuraminidase inhibitors adamantanes (amantadine and rimantadine) and (oseltamivir and zanamivir). However, the novel Influenza 2009 A/H1/N1virus is resistant to amantadine and rimantadine but is sensitive to oseltamivir (Tamiflu) and zanamivir (Relenza). [10],[11] Based on experience with other flu viruses, treatment would be most effective if given within two days of symptom onset. The CDC has recommended that health care workers who provide direct care for patients with known or suspected novel Influenza 2009 A/H1N1virus infection should observe contact and droplet precautions, including the use of gowns, gloves, eye protection, face masks, and fit-tested, disposable N95 respirators. [12] People should be considered contagious until at least seven days after symptom onset; with children, that time might be as long as 10 to 14 days. In addition, patients with confirmed or suspected novel Influenza 2009 A/H1N1virus infection should be placed in a single-patient room with the door closed, and airborne-infection isolation rooms with negative-pressure handling should be used whenever an aerosol-generating procedure is being performed. Frequent hand washing with soap and water may reduce the risk of infection and transmission. No vaccine is available as yet for the Influenza 2009 A/H1/N1virus. Several experts have expressed doubt that the currently available seasonal influenza vaccine offers much, if any, protection. Although our ability to produce a vaccine in sufficient quantities to cover people who are exposed in a first pandemic wave is very limited with today's technology, an inter-wave period would provide time to increase the production of biomedical tools and to vaccinate populations, thereby mitigating the morbidity and mortality associated with successive and potentially more lethal waves. [13] A strain of Influenza 2009 A/H1/N1virus has been identified as a potential egg-derived candidate strain for vaccine development and has been sent to partner laboratories for evaluation and further development.

In conclusion the recent outbreak caused by the novel Influenza 2009 A/H1N1 virus infection, which is rapidly spreading across the globe, appears to have most of the necessary attributes to evolve into a pandemic - the novel virus is anti-genically distinct to other seasonal flu viruses identified thus far, it has a higher transmissibility as compared to circulating seasonal flu viruses and the there appears to be a lack of herd immunity to this agent in the global population especially the young adults and children. Given the rapidly evolving nature of this outbreak, enhanced surveillance for this infection is the need of the hour. India should seize this opportunity to strengthen its capability to tackle the pandemic. Although, the Government of India has recently identified, equipped and trained staff from 12 laboratories across the country, the network of Influenza laboratories is far from functional at present. It is therefore imperative that this network is galvanized into action at the earliest so that the country could effectively tackle the pandemic. Operationalizing this network would also ease the enormous burden of laboratory diagnosis on the two existing reference laboratories at NIV, Pune and NICD, New Delhi.

 
 ~ References Top

1.Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009;361. DOI: 10.1056/NEJMoa0903810.   Back to cited text no. 1    
2.World Health Organization. Influenza A (H1N1) - update 42, 3 June 2009. Available from: http://www.who.int/csr/don/2009_06_01a/en/index.html. [accessed on 2009 June 22].  Back to cited text no. 2    
3.Outbreak of swine-origin influenza A (H1N1) virus infection - Mexico, March-April 2009. MMWR Morb Mortal Wkly Rep 2009;58:467.  Back to cited text no. 3    
4.Belshe, RB. Implications of the emergence of a novel H1 influenza virus. N Engl J Med 2009;361.DOI: 10.1056/NEJMe0903995 .  Back to cited text no. 4    
5.Shinde V, Bridges CB, Uyeki TM, Shu B, Balish A, Xu X, et al . Triple-reassortant swine influenza A (H1) in humans in the United States, 2005-2009. N Engl J Med 2009;361. DOI: 10.1056/NEJMoa0903812.   Back to cited text no. 5    
6.Garten RJ, Davis CT, Russell CA, Shu B, Lindstrom S, Balish A, et al . Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science 2009 (In Press)  Back to cited text no. 6    
7.Miller MA, Viboud C, Balinska M, Simonsen L. The Signature Features of Influenza Pandemics-Implications for Policy. N Engl J Med 2009;361. DOI: 10.1056/NEJMp0903906.   Back to cited text no. 7    
8.Fraser C, Donnelly CA, Cauchemez S, Shu B, Balish A, Xu X, et al . Pandemic Potential of a Strain of Influenza A (H1N1): Early Findings. Science 2009 (In Press).  Back to cited text no. 8    
9.United States Centers for Disease Control and Prevention. Interim guidance on specimen collection, processing, and testing for patients with suspected swine-origin influenza A (H1N1) virus infection. Available from: http://www.cdc.gov/h1n1flu/specimencollection.htm">http://www.cdc.gov/h1n1flu/specimencollection.htm (Accessed May 12, 2009).  Back to cited text no. 9    
10.Update: drug susceptibility of swine-origin influenza A (H1N1) viruses, April 2009. MMWR Morb Mortal Wkly Rep 2009;58:433-435.  Back to cited text no. 10    
11.United States Centers for Disease Control and Prevention. Interim guidance on antiviral recommendations for patients with novel influenza A (H1N1) virus infection and their close contacts. Available at: http://www.cdc.gov/h1n1flu/recommendations.htm[accessed on 2009 May 7].   Back to cited text no. 11    
12.United States Centers for Disease Control and Prevention. H1N1 flu (swine flu). Available from: http://www.cdc.gov/h1n1flu/. [accessed on 2009 Jun 4].   Back to cited text no. 12    
13.Gallaher WR. Towards a sane and rational approach to the management of Influenza H1N1 2009. Virol J 2009;6:51.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]




 

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