Introduction
The Avian Influenza A virus (H5N1) is highly pathogenic and is part of the Orthomyxoviridae family, which are single-stranded, negative-sense ribonucleic acid (RNA) viruses that have segmented genomes. The natural reservoir of Avian influenza is the global wild-bird population. The virus is carried within the intestines of these birds, but they rarely show signs of illness. However, the virus is highly contagious which sickens and kills domesticated birds. [1] Birds shed the H5N1 virus through feces and respiratory secretions. Highly pathogenic viruses can live for extended periods of time in low temperatures. H5N1 can live in bird feces for 35 days or more in low temperatures (i.e., 4°C) and 6 days at higher temperatures (i.e., 37°C). [2] The virus can also remain viable in water, soil, and contaminated surfaces. [3]
The quick culling of birds that are exposed or infected with this highly pathogenic disease is the first line of defense when attempting to control the virus. Properly discarding the remains, effectively quarantining and sterilizing the farms, and restricting the movement of poultry are also essential virus-control measures. These control measures are easier to implement in larger, commercial farms where the poultry is contained, usually inside. However, these procedures are much more difficult to implement in smaller farms or “backyard flocks” where poultry roams freely in rural or semi-urban areas. The free-ranging poultry also pose risks for human exposure to the virus because they are often exposed to infected wild birds when sharing water sources. In poor areas where poultry is a main source of food and income, the birds are often consumed if ill or found dead. The practice of preparing the dead animal exposes individuals to the virus. Farmers are also not paid for poultry that is destroyed through mass-culling efforts, which motivates some farmers to hide their poultry from officials. Vaccination of the poultry can be effective when culling does not control the virus or is impractical to implement. Vaccination is recommended as a supplementary method in high-risk areas, as long as quality vaccines are used and the World Organization for Animal Health guidelines is followed. If vaccines of poor quality are used, risks for mutations in the virus strains also increase. [2]
There are hundreds of strains of Avian influenza, but only four types have been known to infect humans: H5N1, H7N3, H7N7, and H9N2. The H5N1 virus causes the most concern of all Avian influenza viruses because it has a high fatality rate, the most number of human cases and rapid clinical deterioration. The main source of infection of H5N1 for humans is close contact with infected birds, either sick or dead. Risk factors include activities involving the slaughter and preparation of infected birds. Other potential risk factors may include exposure to the feces of infected birds and swimming in bodies of water that contain the carcasses or feces of infected birds. [2]
In 1996 in Guangdong province, China, the H5N1 virus was detected in geese. In the spring of 1997, the virus was detected in chickens in Hong Kong. Also, in May of 1997, the first evidence that the virus had “jumped the species barrier” appeared when a young boy died in a Hong Kong hospital from respiratory failure. The cause of death was first identified as viral pneumonia, but 3 months later the cause was identified as H5N1 Avian influenza. In 1997, the H5N1 virus infected 18 people in Hong Kong, then killing six. Human infection ceased after Hong Kong public health and agricultural authorities implemented effective measures, including limiting the spread of the virus in wet markets (live-animal markets), communication to the public, and conducting widespread culling of poultry in December of 1997. [2][4][5] Epidemiological field studies began within days of the last human cases in 1997and found that exposure to wet markets (i.e., infected poultry or a contaminated environment) was the main risk factor for contracting the H5N1 virus. In 2003, a father and son from Hong Kong contracted the virus while visiting Fujian Province in southern China. The emergence of the severe acute respiratory syndrome (SARS) in late 2003 and early 2004 overshadowed the concerns about these new human cases of the H5N1 virus. After an unprecedented worldwide effort, led by the World Health Organization, to stop the spread of SARS, human and poultry cases of the H5N1 virus began to emerge in Southeast Asia. There were three waves of cases of the H5N1 virus from December 2003 through 2005 that included 133 cases and 68 deaths in China, Vietnam, Thailand, Cambodia, and Indonesia. These waves were from December 26, 2003 to March 10, 2004; July 19, 2004 to October 8, 2004; and from December 16, 2004 to August 5, 2005. The H5N1 virus continues to be detected in humans and poultry, including regions outside of Southeast Asia.[6] For example, the virus was detected in humans and poultry in Turkey by the end of 2005 and in Nigeria by March 2006. Human cases were reported in Pakistan, Myanmar, and Bangladesh from the end of 2007 through early 2008. [5]
If H5N1 causes the next human influenza pandemic, it is estimated that it will have a mortality rate of more than one hundred million people. This estimation is based on the fact that humans have very little to no immunity to the virus and that the mortality rate so far (of those reported to the WHO) is quite high. Viral pathogens must meet three criteria in order to become a pandemic: the general population must have little or no immunity to the virus, the virus must be able to replicate in humans and cause significant clinical illness; and efficient human-to-human transmission of the virus must exist. Currently H5N1 has only met the first two criteria and lacks efficient human-to-human transmission. [3] However, there have been a small number of reported cases resulting from non-sustained human-to-human transmission. [6][7]
Fifteen countries have reported human cases of H5N1 since 2003, but 90% of these cases have occurred in just five countries: Indonesia, Vietnam, Egypt, China, and Thailand. It is not yet understood why human infections have been concentrated in these particular countries whereas little to no human cases have been reported in countries with numerous reports of poultry infected with the virus. [5]
Even though the World Health Organization’s annual reported human cases have declined (109 in 2006, 88 in 2007, and 44 in 2008), the H5N1 virus is still quite active. The virus’ persistence is indicated by the incidences of the virus in humans in China and Vietnam in 2009 (7 cases and 4 deaths in China and 4 cases and 4 deaths in Vietnam), even though these countries have well-established poultry control programs. [5] In addition to China and Vietnam, Egypt has also reported cases to the WHO in 2009 (38 cases and 4 deaths). [8]
Statistic
- From 2003 until November 27, 2009, the cumulative number of human cases of Avian Influenza A (H5N1) reported by the World Health Organization is total of 444 cases which includes 262 deaths. This number is of laboratory-confirmed cases only. The following lists the breakdown of reported cases by country: Azerbaijan (8 cases, 5 deaths); Bangladesh (1 case, no deaths); Cambodia (8 cases, 7 deaths); China (38 cases, 25 deaths); Djibouti (1case, no deaths); Egypt (89 cases, 27 deaths); Indonesia (141 cases, 115 deaths); Iraq (3 cases, 2 deaths); Lao People’s Democratic Republic (2 cases, 2 deaths); Myanmar (1 case, no deaths); Nigeria (1 case, 1 death); Pakistan (3 cases, 1 death); Thailand (25 cases, 17 deaths); Turkey (12 cases, 4 deaths); Vietnam (111 cases, 56 deaths). [9]
- H5N1 infections in poultry and wild birds have been reported in 61 countries since 2003. [5]
- Since 2003, more than 100 million domesticated birds have died from H5N1 infection or from deliberate culling to stop the spread of the virus; most of these birds were chickens and ducks. [6]
- Since 2003, the total human mortality rate for H5N1 infection has been 63%, with ranges from 42% to 82%. [5]
Signs and Symptoms
The following list does not insure the presence of this health condition. Please see the text and your healthcare professional for more information.
The incubation period for the H5N1 virus ranges from 2 to 8 days, but can be as long as 17 days. [2] In most cases the first symptoms develop within 2 to 4 days after exposure to infected poultry. The initial symptoms are typically traditional flu symptoms and include a high fever (higher than 38°C), cough, shortness of breath, sore throat and aching muscles. [2][10] The majority of patients develop pneumonia. The pneumonia appears to be of primary viral origin with no evidence of bacterial supra-infection. [11] Other than respiratory symptoms, many patients also present with gastrointestinal symptoms, such as abdominal pain, diarrhea, and vomiting. In severe cases of infection with the H5N1 virus, patients experience rapidly progressing bilateral pneumonia that requires ventilation support within the first days of symptom onset. Further complications include acute respiratory distress syndrome, renal dysfunction, and multi-organ failure. Most fatalities result from progressive respiratory failure. [11]
Treatment Options
Conventional
The World Health Organization recommends the use of oseltamivir, a neuraminidase inhibitor, for the treatment of H5N1 virus infections. [2][11] Neuraminidase inhibitors inhibit the viral replication, specifically the release of “newly formed virions from an infected host cell. [7] Therefore, in order to be effective, neuraminidase inhibitors should be administered as early as possible (i.e., within the first 48 hours of symptom onset). The World Health Organization recommends the use of oseltamivir phosphate or zanamivir for prophylaxis. [2][7] The WHO currently has a stockpile of oseltamivir in order to control the first outbreaks of an H5N1 human pandemic at the original source, which would most likely be in a developing country in Southeast Asia. [7] Data is available that suggest oseltamivir does reduce the duration of the viral replication as well as improve chances of recovery. The H5N1 virus is resistant to the common antivirals, amantadine and rimantadine. [2]
As of September 2009, there are vaccines available for specific genetic groups, or clades, of the H5N1 virus, but not for the clades characterized since February 2009. These current H5N1 viruses fall into four different clades. Clade 2.2 viruses were found in chickens in Bangladesh; Clade (a group consisting of an organism and all its descendants) 2.2.1 viruses have been detected in poultry in Egypt with sporadic human infections; Clade 2.3.2 viruses are being continually detected in poultry and wild birds found in China Hong Kong Special Administrative Region (Hong Kong SAR), and were found for the first time in the wild birds of Southwestern Siberia and Mongolia; and Clade 2.3.4 viruses were found in the poultry and wild birds of Hong Kong SAR, in the poultry of Vietnam and Lao People’s Democratic Republic, and in one human case in China. [8]
Nutritional Supplementation
As with SARS, there has been limited research time available to test the efficacy of dietary supplementation in treating Avian Flu and therefore there are no nutritional treatments that have been studied in this regard. However, there may be a case to be made for improved nutritional status and the relative immune status of those who may be at risk of being infected. [12] There is currently dialogue within the scientific community of the role of ascorbic acid and note is taken that ascorbic acid is not being given to those at risk or those infected. [13]
Herbal Supplementation
There are numerous botanicals that demonstrate efficacy in improving immune status. However, to date no specific studies have been reported in using botanical medicine to treat Avian Influenza.
Clinical Notes
Diagnosis of the H5N1 virus can only be confirmed with laboratory tests. Reverse transcriptase polymerase chain reaction (RT-PCR) assays are the preferred methods for “rapid subtype-specific diagnostics.” However, designing reliable RT-PCRs is challenging because the H5N1 virus has many genetic sub lineages and also the “changing nature” of the H5 gene. The most current avian and human H5N1 virus genetic sequence information is crucial in order to develop new assays and to bring current assays up to date. [11] In February 2006, the US Food and Drug Administration approved a rapid test, the Virus Real-Time Reverse Transcription Polymerase Chain Reaction Primer and Probe Set, which was developed by the US Centers for Disease Control and Prevention, to identify the “Asian lineage of the H5 influenza strain.” This test takes nearly 4 hours to complete. [6] It was recently found that the nasopharyngeal aspirate is the preferred method to obtain specimens from patients than the nasal swab. [14]
References
- M. Gauthier-Clerc, C. Lebarbenchon, F. Thomas. Recent expansion of highly pathogenic avian influenza H5N1: a critical review. Ibis 2007; 149: 202-214.
- World Health Organization. Avian influenza (“bird flu”). Available from: http://www.who.int/mediacentre/factsheets/avian_influenza/en/print.html. [Accessed on November 3, 2009]
- D.A. Bradt, C.M. Drummond. Avian influenza pandemic threat and health systems response. Emergency Medicine Australasia 2006; 18: 430-443.
- J. Parry. Ten years of fighting bird flu. Bulletin of the World Health Organization 2007; 85(1): 3-5.
- S. Briand, K. Fukuda. Avian influenza A (H5N1) virus and 2 fundamental questions. [editorial commentary]. JID 2009; 199: 1717-1719.
- J.K. Thomas, J. Noppenberger. Avian influenza: a review. Am J Health-Syst Pharm 2007; 64:149-165.
- C. Sellwood, N. Asgari-Jirhandeh, S. Salimee. Bird flu: if or when? Planning for the next pandemic. Postgrad Med J 2007; 83: 445-450.
- World Health Organization. Antigenic and genetic characteristics of influenza A (H5N1) viruses and candidate vaccine viruses developed for potential use in human vaccines. September, 2009. Available from: http://www.who.int/csr/disease/influenza/200909_H5VaccineVirusupdate.pdf. [Accessed on November 1, 2009]
- World Health Organization. Cumulative number of confirmed human cases of Avian Influenza A/(H5N1) reported to WHO. Available from: http://www.who.int/csr/disease/avian_influenza/country/cases_table_2009_11_27/en. [Accessed on November 30, 2009]
- L. Swain. Bird flu. In: Longe JL, editor. The Gale Encyclopedia of Medicine. Vol.1. 3rd edition. Detroit: Gale Group; 2006.p. 542-46.
- A. Gambotto, S.M. Barratt-Boyes, M.D. de Jong. Human infection with highly pathogenic H5N1 influenza virus. Lancet 2008; 371: 1464-1475.
- M.A. Beck, J. Handy, O.A. Levander. Host nutritional status: the neglected virulence factor. Trends Microbiol. 2004 Sep;12(9):417-423.
- J.T. Ely. Ascorbic acid role in containment of the world avian flu pandemic. Exp Biol Med (Maywood). 2007 Jul;232(7):847-851.
- J.M. Nicholls, J.S.M. Peiris. Avian influenza: update on pathogenesis and laboratory diagnosis. Respirology 2008; 13(Suppl. 1): S14-S18.
