Avian Influenza – A Challenge to Poultry Industry and a Threat to Human Health

Avian Influenza – A Challenge to Poultry Industry and a Threat to Human Health

The highly pathogenic avian influenza (HPAI) H5N1 virus, which is panzootic in poultry, continues to spread and pose a major threat to animal and human health. Since pandemic influenza virus has its origin in avian influenza viruses, HPAI H5N1 virus has to be considered a potentially serious pandemic threat. World Organization for animal Health (OIE) has listed the disease as a notifiable AI (NAI) and it has now a significant impact on animal and human health. H5N1 viruses are taking a huge toll on the poultry industry in many developing countries, and this directly or indirectly impacts both economic and social well being. The potential impact of HPAI H5N1 virus (and human reaction to its spread) on wildlife and ecology has received less attention but is also worthy of consideration. While the H5N1 virus transmits from infected poultry to humans, often with fatal consequences, such transmission remains inefficient. Although the virus replicates efficiently in diseased humans, it has not yet adapted to efficient human-to-human transmission. H5N1 therefore continues to challenge our understanding of interspecies transmission of influenza viruses. In addition, since 1997, the consequential human health implications of AI infections of poultry have been identified, especially as a result of the spread of Asian H5N1 virus. This has dramatically drawn the attention of the scientific communities of both veterinary and medical sciences.

Avian Influenza, commonly known as bird flu, is a viral infection that primarily affects birds. While it has been a long-standing challenge for the poultry industry, avian influenza also poses a potential threat to human health. In this article, we will explore the nature of avian influenza, its impact on the poultry industry, and the concerns it raises for human health.

Understanding Avian Influenza

Avian influenza is caused by influenza A viruses that naturally infect wild birds, particularly waterfowl, which serve as reservoirs for these viruses. The disease is categorized into two main types:

1. Low Pathogenic Avian Influenza (LPAI): LPAI typically causes mild or no clinical signs in infected birds. It is often referred to as a “low-pathogenic” form.
2. Highly Pathogenic Avian Influenza (HPAI): HPAI is the more severe form of avian influenza, characterized by high mortality rates in birds. It can rapidly spread and lead to significant economic losses in the poultry industry.

The concern with avian influenza arises when these viruses have the potential to infect humans. Some subtypes, such as H5N1 and H7N9, have been associated with severe human infections, leading to fatalities in some cases. While human-to-human transmission of avian influenza is limited, the virus’s ability to mutate and adapt raises concerns about its pandemic potential.

Avian Influenza in India

Highly Pathogenic Avian Influenza (HPAI), commonly known as Bird Flu, was first detected in India in the state of Maharashtra in February 2006. Since then, the country has experienced annual outbreaks of HPAI in different regions, leading to substantial economic losses. The disease has been reported in 24 states and union territories, resulting in the culling of over 9 million birds to control its spread.

India’s approach to controlling HPAI follows a “detect and cull” policy as outlined in the National Action Plan for Prevention, Control, and Containment of Avian Influenza (revised – 2021). This comprehensive response includes the humane destruction of infected and exposed animals, eggs, feed, litter, and other contaminated materials. Additionally, measures such as restricting the movement of poultry and poultry products, disinfection and clean-up of infected premises, and a Post-Operative Surveillance Plan (POSP) have been implemented. It’s important to note that vaccination against HPAI is not permitted in India.

GENOME ORGANIZATION

Influenza viruses have eight-segmented, single-stranded (ss), negative-sense RNA genome belonging to the family Orthomyxoviridae. At present, Orthomyxoviridae family consists of five genera out of which only viruses of the Influenza virus A genus are known to infect birds. Influenza virus type A causes recurrent epidemics almost every year, leading to significant human morbidity and mortality. However, only influenza A virus is associated with influenza virus pandemics, where an antigenically novel influenza virus emerges to spread rapidly worldwide in an immunologically naive population. In past pandemics, 20 to 30% of the global population was infected within the first year, and in this regard, influenza A viruses are unique human pathogens. The last century witnessed three such pandemics, in 1918 (“Spanish flu”), 1957 (“Asian flu”) and 1968 (“Hong Kong flu”). The pandemic of 1918 is believed to have claimed over 40 million lives, while those of 1957 and 1968 are each believed to have led to over 4 and 1 million deaths, respectively.

Molecular basis of virulence and replication

The eight gene segments of influenza A virus encode 10 proteins: hemagglutinin (HA), neuraminidase (NA), matrix proteins M2 and M1, nonstructural (NS) proteins NS1 and NS2, the nucleocapsid, and the three polymerases, the PB1 (polymerase basic 1), PB2, and PA (polymerase acidic) proteins. For some influenza viruses, the PB1 gene has recently been discovered to encode an additional protein, the PB1-F2 protein. Influenza type A viruses are subtyped based upon the HA and NA antigens, which are surface proteins found on the viral envelope.

Antigenic drift (endemic influenza) and antigenic shift (pandemic influenza)

Replication of influenza genome requires RNA polymerase activity. This enzyme lacks proof-reading ability and has limited potential to correct mistakes during RNA transcription, resulting in a high frequency of mutations in any newly replicated virus population. These new strains accumulate random point mutations that may result in amino acid substitutions in surface glycoproteins that allow new variants to evade immunity. Viruses that have undergone antigenic changes or “antigenic drift” to evade immunity and are capable of re-infection and inter-pandemic outbreaks. Mutation in these genes is selected for by herd-immune selection pressure in the host, leading to a directional antigenic change over time (“antigenic drift”), thereby explaining the repeated epidemics observed with influenza A or B virus. The segmented genome of influenza viruses also allows for genetic reassortment to occur when two influenza viruses infect the same cell. This provides influenza viruses a powerful option for the generation of genetic diversity for interspecies transmission and to evade host immune responses through a major antigenic change (“antigenic shift”). Pandemics arise at infrequent intervals when an influenza virus with a completely novel HA (and sometimes NA) acquires the ability for efficient and sustained human-to-human transmission in a population that is immunologically naive to the virus surface proteins (HA and NA). The H2N2 influenza virus responsible for the pandemic of 1957 arose through genetic reassortment, where the prevailing human influenza A virus (H1N1) acquired the HA (H2), NA (N2), and PB1 genes from an avian virus. Similarly, the pandemic of 1968 arose through the acquisition of a novel HA (H3) and the PB1 gene from an avian source. In contrast, the pandemic of 1918 is believed to have arisen through the direct adaptation of a purely avian virus to efficient transmission in humans, although the lack of genetic information on relevant avian precursors and on the pre-1918 human viruses precludes a definitive conclusion on this matter. Thus, pandemic influenza virus is a zoonosis, and avian viruses play a critical role in its genesis. Since the pandemics of 1957 and 1968 arose in southern China, this region has been identified as a hypothetical pandemic epicenter. Sixteen subtypes of HA (H1 to H16) and nine subtypes of NA (N1 to N9) are recognized in aquatic birds. While many of these subtypes can be consistently detected in wild aquatic waterfowl, only few subtypes have established themselves in mammalian species such as humans (HA [H1, H2, and H3] and NA [N1 and N2]), pigs (HA [H1 and H3] and NA [N1 and N2]), horses (H3N8 and H7N7), and dogs (H3N8). Indeed, only some of the diverse influenza virus subtypes found in aquatic birds have established themselves as low pathogenicity avian influenza (LPAI) virus in terrestrial poultry such as chicken, turkey, and quail (e.g., subtypes H9 and H6). Both human and avian influenza viruses have established stable virus lineages in pigs, possibly a reflection of the fact that receptors for both avian and human influenza viruses are present on the porcine epithelium. For these reasons, pigs have been regarded as being a possible intermediate host (“mixing vessel”) for the generation of pandemic influenza virus through reassortment. Human influenza viruses that have become established in pigs include classical swine H1N1 and H3N2 viruses and reassortants thereof (H1N2 and H3N1). The 1918 H1N1 virus appears to have entered human and pig populations, although the epidemiological evidence favors the initial host as being humans. Avianlike H1N1 viruses have established themselves in pigs in Europe. In addition, other viruses have been transiently detected in pig populations. These include avian virus subtypes H1N1 (Asia), H4N6 (Canada), H9N2 (China), and H5N1 (Asia). More recently, equine H3N8 viruses have been transmitted to racing dog populations in the United States, possibly facilitated by the practice of feeding horsemeat to racing dogs, another example of a human intervention that promoted interspecies transmission of viruses. Overall, there are strong barriers to interspecies transmission that prevent the adaptation of influenza viruses to new hosts. It is likely that these prevent the more frequent emergence of pandemics from the wide diversity of HA subtypes prevalent in waterfowl.

Highly Pathogenic Avian Influenza Virus (HPAI)

Two subtypes of influenza A virus (H5 and H7) are known to give rise to HPAI virus in terrestrial poultry (chicken and turkeys). The HPAI virus phenotypes of these viruses are largely, though not exclusively, to mutations giving rise to multiple basic amino acids in the connecting peptide between the HA1 and HA2 domains of the HA0 precursor protein. In the viral life cycle, post-translational cleavage of the precursor HA molecule (HA0) into two subunits (HA1 and HA2) by host proteases is essential for productive virus replication, since this generates a fusogenic domain mediating the fusion between the viral envelope and the endosomal membrane. This may occur extracellularly by trypsin-like proteases that are restricted in tissue distribution to the respiratory and gastrointestinal tracts. However, when multiple basic amino acids are introduced into the HA cleavage site, the HA0 precursor becomes cleavable by a wide range of proteases (e.g., furins [PC6-like]) with ubiquitous tissue distribution. This permits productive virus replication in organs outside the respiratory and gastrointestinal tracts, including the brain, resulting in fulminant disseminated disease with high mortality, leading to HPAI virus. The acquisition of a carbohydrate side chain near the cleavage site can modulate the pathogenicity of a virus by masking the accessibility of the proteases to the cleavage site. In the 31 years from 1959 to 1990, there were nine HPAI virus outbreaks recorded in Europe, North America, and Australia, and these outbreaks were contained by the “stamping out” of infected flocks. In the 11 years since 1990, there have been 10 further HPAI virus outbreaks, including in Asia. The current HPAI H5N1 virus outbreak (from 2003 onwards) is, however, unprecedented in scale and geographic distribution. These viruses are now panzootic across three continents, leading to huge economic losses, and have transmitted to humans with lethal consequences. The expansion of intensive poultry husbandry, which is the fastest growing livestock industry globally, with an estimated 16 billion chickens and 1 billion ducks worldwide, is likely facilitating the increasing frequency and scale of HPAI virus outbreaks. Furthermore, the commercialized large-scale poultry industry is now associated with the movement of live poultry and poultry products over long distances, thereby facilitating the transmission of infection. On the basis of the genetic sequence of HA and the biological properties of the virus, it appears that the avian influenza viruses that contributed to the origin of the pandemics of 1957 and 1968 were LPAI viruses of chicken and other terrestrial poultry. Therefore, for pandemic preparedness, surveillance of poultry and other avian species must be directed at healthy as well as diseased birds. On the other hand, reconstruction of the H1N1 virus causing the “Spanish flu” pandemic of 1918 suggests that this virus may have had high pathogenicity for terrestrial poultry even though it did not have the multibasic cleavage site in the HA that characterizes HPAI virus. However, direct proof of high pathogenicity of the 1918 virus for chickens is still awaited.

INFLUENZA H5N1 VIRUS IN HUMANS

Transmission and Epidemiology

The first human disease caused by H5N1 was reported in Hong Kong in 1997, with 18 cases and six deaths. The source of human infection appeared to be live-poultry markets where chickens, ducks, geese, and other species of minor poultry (e.g., quail, pheasant, chukka, pigeon, etc.) were sold for human consumption. In February 2003, as the world was girding itself to confront severe acute respiratory syndrome, H5N1 disease was diagnosed in Hong Kong in a father and son who had just returned from a holiday in Fujian Province, China. In retrospect, another case of H5N1 occurred in Beijing, China, in November 2003. Subsequently, with the increasing spread of H5N1 disease in poultry, further human cases from Vietnam, Thailand, Cambodia, Indonesia, and elsewhere were reported. In a number of instances, the detection of a human case in a region was the first indication of the presence of poultry infection in that locality. Since HPAI H5N1 virus in poultry is associated with the presence of infectious virus in many organs, as well as the excretion of large amounts of virus in the feces and other secretions, sick poultry are a major source of human infection. Most human cases of H5N1 infection were associated with the direct handling of infected poultry, slaughtering or preparing sick poultry for consumption, consumption of uncooked poultry products such as raw blood, or close contact with live poultry. Since H5N1 infection may not always be overtly symptomatic, especially so in ducks, even asymptomatic poultry may pose an infection risk, e.g., at wet markets, in areas of endemicity. Contact with a contaminated environment, such as water and poultry feces used as fertilizer or fish feed, has been suspected to be a source of infection in human H5N1 cases that had no direct exposure to poultry. In bird-to-human transmission, the likely portal of virus entry is via the respiratory tract, the gastrointestinal tract, or the conjunctiva. Cats experimentally infected with H5N1 virus after feeding on infected chickens showed evidence of viral replication in gastrointestinal plexi. However, this is not seen in those infected via the respiratory route. In humans, the possibility of intestinal infection is supported by reports of H5N1-infected patients who presented with diarrhea as the only initial symptom as well as by patients who reported consumption of raw duck blood as the sole exposure to poultry. In addition, the presence of infectious virus in fecal material may indicate virus replication in the human gastrointestinal tract. There are a number of enigmas with regard to human H5N1 infection and disease. In spite of large-scale outbreaks of H5N1 viruses among poultry in densely populated areas and presumably massive exposure of humans to the virus, the number of reported H5N1 patients has so far been relatively small. In Hong Kong in 1997, where there was excellent surveillance for symptomatic influenza virus, there were still only small numbers of cases in spite of the exceedingly heavy virus load in retail poultry markets, where 20% of poultry were infected. Seroepidemiological studies following the 1997 H5N1 outbreak in Hong Kong have shown that mildly symptomatic or asymptomatic infections had occurred in a few individuals exposed to infected patients or poultry. Similar studies of persons at risk for H5N1 exposure during the recent H5N1 outbreaks have shown little or no evidence of humanto-human transmission in unprotected health care workers exposed to H5N1 patients. Similarly, villagers, poultry workers, and poultry cullers in Vietnam, Thailand, Indonesia, and Cambodia who are heavily exposed to infected poultry rarely have clinical or asymptomatic (serological) evidence of infection. In contrast, around 10% of poultry stall holders in Hong Kong in 1997 had serological evidence of H5N1 infection without presenting as overt H5N1 disease, although it is unclear whether the seropositivity represented recent infection with HPAI H5N1 virus or prior infection by LPAI H5-subtype viruses known to be present in ducks.

Pathogenesis of Human Influenza H5N1 Virus

Human H5N1 disease is clinically and pathologically distinct from seasonal human influenza virus caused by H3N2 or H1N1 viruses. An understanding of the pathogenesis of human H5N1 disease may derive from three sources: the clinical findings, virology, and pathology of human H5N1 disease; relevant animal models; and studies of cell-virus interactions in vitro or ex vivo. While viral dissemination may contribute to the unusual disease presentation, the primary pathology that contributes to death in most patients is the rapidly progressing fulminant primary viral pneumonia that often progresses to ARDS. The target cells for H5N1 replication in the respiratory tract are not fully defined, but alveolar pneumocytes and macrophages have been identified by immunohistochemistry in autopsies, virus binding studies, and ex vivo infection of lung fragment cultures. Since both H5N1 and human H1N1 influenza viruses can replicate in the alveolar epithelium as well as the nasopharyngeal epithelium, a differential tropism of H5N1 virus within the respiratory tract is unlikely to be a key explanation for the unusual pathogenicity of H5N1 viruses. Human H5N1 disease differs from that of human influenza virus in terms of the viral load kinetics, virus dissemination beyond the respiratory tract, and induction of hypercytokinemia. The clinical manifestations of influenza H5N1 virus including diarrhea, liver, and renal dysfunction, severe lymphopenia, and reactive hemophagocytosis suggest pathology in multiple organs. This may suggest a wider tissue tropism of the virus or may be the manifestations of multiple-organ dysfunction that is related to the systemic effects of a severe “sepsis like” syndrome. For example, it has been reported that Kupffer cell-dependent hepatitis is not uncommon in “conventional” human influenza virus in the absence of virus infection in the liver. Compared to human influenza virus, patients with H5N1 disease have detectable viral RNA in the respiratory tract for a longer period, presumably because of the lack of prior cross reactive immunity. Higher levels of viral RNA in the nasopharynx and detection of viral RNA in the serum were adverse prognostic factors. Virus has been isolated from the plasma, indicating the potential for systemic dissemination. The demonstration of H5N1 RNA in feces from patients and in limited autopsy studies, together with the prominent diarrheal presentation of some patients with H5N1 disease, suggests that the virus very likely affects the gastrointestinal tract either as part of the initial infection or through subsequent dissemination. While the limited postmortem examinations reported so far revealed no evidence of viral replication or viral pathology in organs other than lungs and intestines, more studies, especially during the acute stage of infection, are essential to confirm or exclude the possibility of infection at sites other than the respiratory and gastrointestinal tracts. While the mechanisms of pathogenesis of HPAI viruses such as H5N1 virus infection in chicken are well defined and are determined largely by the multibasic amino acids in the HA connecting peptide and the consequent broad tissue tropism of the virus, these findings cannot be directly extrapolated to mammals or to human disease. H5N1 viruses infect BALB/c mice without prior adaptation. Virulence of H5N1 viruses in mice, ferrets, felids, and viverrids is associated with virus dissemination beyond the respiratory tract to involve multiple organs including the brain. However, primates experimentally infected with H5N1 virus do not manifest virus dissemination, and pathology is restricted to the respiratory tract. Animal models differ among each other and from humans with regard to the attachment of H5N1 virus to respiratory tissues. Fluorescently labeled H5N1 viruses bound more efficiently to the alveolar epithelium than tracheal epithelium in humans, ferrets, cats, and macaques, but the reverse was true in mice. Furthermore, while H5N1 virus attached to type 2 pneumocytes in human, cat, and ferret lungs, the virus bound predominantly to type 1 pneumocytes in macaques. Therefore, while mice are a convenient animal model for some purposes (e.g., vaccine-induced protection from virus challenge), the pathogenesis of H5N1 disease in mice probably differs from that in humans in important ways.

Laboratory Diagnosis

This section addresses issues pertaining to laboratory diagnosis of human H5N1 disease and does not cover veterinary diagnosis. In view of the non-specific nature of the illness, laboratory confirmation of H5N1 influenza virus is essential. Laboratory confirmation of a diagnosis of H5N1 disease is, however, challenging. It requires a high index of suspicion and the most sensitive detection methods available (e.g., reverse transcriptase PCR [RTPCR]) and may require the testing of multiple specimens. The options for diagnosing influenza virus in clinical specimens include virus culture, antigen detection, detection of viral nucleic acids by RT-PCR, and detection of rising titers of antibodies. In the absence of epidemiological links to areas with H5N1 influenza virus activity, further sub-typing is not essential for routine diagnostics. However, in countries where avian influenza H5N1 virus is known to be active, patients with severe pneumonia of unexplained etiology should be investigated virologically for influenza virus and, if positive, further investigated using H5-subtype-specific assays so that appropriate therapy, infection control measures, and timely epidemiological investigations can be initiated. Therefore, there is a need for rapid diagnostic assays which distinguish influenza virus subtypes.

 Clinical specimens for virus detection

Virus has been isolated and viral RNA has been detected in respiratory specimens obtained from H5N1-infected patients for up to 16 days after the onset of illness, indicating that virus is shed and can be detected for prolonged periods. Nasopharyngeal aspirates (NPA) and nasopharyngeal, throat, and nose swabs have all been used for the detection of H5N1 virus, but it remains unclear which is the diagnostic specimen of choice, because parallel studies comparing different diagnostic specimens are limited. Nasal and pharyngeal swabs have been tested in parallel during recent outbreaks in South East Asia, and this comparison suggests higher virus loads and consequent higher diagnostic yields in throat swabs than in nose swabs. NPA were successfully used for H5N1 diagnosis in Hong Kong during the H5N1 outbreak in 1997, but data directly comparing diagnostic yields from NPA and pharyngeal swabs with other respiratory specimens are lacking. An advantage of NPA is that it provides the ideal specimen for the rapid diagnosis of many other respiratory virus infections (e.g., human influenza A or B virus, adenovirus, and parainfluenza virus), which may help to exclude a diagnosis of H5N1 influenza virus, although dual infections with other respiratory viruses remain a possibility. Limited data suggest that viral load is higher in the lower respiratory tract (e.g., endotracheal aspirates) than in throat or nose swabs. Thus, endotracheal aspirates or bronchoalveolar lavages are likely to represent the optimal diagnostic specimens for the diagnosis of H5N1 disease. H5N1 virus has also been isolated and viral RNA has been detected in feces and sera in some but not all H5N1 patients tested and in the cerebrospinal fluid of one patient. However, for screening purposes, respiratory specimens remain the first choice. In H7N7 infected patients, conjunctival swabs appeared to be the specimen of choice for virus detection. However, there appears to be a significant difference in the tropisms of H7 and H5-subtype viruses for the human conjunctiva, with conjunctivitis being a common manifestation in H7N7 infections but not in H5N1 infection. There is no systematic data on the utility (or lack thereof) of conjunctival swab specimens for the diagnosis of human H5N1 disease. Autopsy specimens are critical for confirming or excluding avian H5N1 influenza virus disease. If a full autopsy is not possible, paramortem biopsies are alternative options. Specimens should be transported on ice and tested fresh upon receipt in the laboratory. For long-term storage of specimens for virus detection or isolation, they should be frozen at 70°C, ideally in multiple aliquots. Respiratory specimens should be placed into virus transport medium. WHO guidelines for specimen collection and laboratory testing for H5N1 diagnosis are available.

 Virus isolation

H5N1 viruses can be isolated by inoculation of embryonated eggs or of MardinDarby Canine Kidney (MDCK) or other permissive cell lines. While culture of seasonal human influenza A viruses requires the addition of exogenous trypsin for growth in MDCK cells, H5N1 virus and other HPAI viruses are not dependent on exogenous trypsin supplements for growth. Virus culture still represents the “gold standard” for diagnosis, and virus isolates are essential for further genetic and antigenic characterization of avian influenza viruses. However, because of the length of time required for virus culture and the need for biosafety level 3 (BSL-3) laboratory facilities for culturing HPAI viruses, RT-PCR rather than virus isolation is usually the first diagnostic test applied to suspected clinical specimens.

Antigen detection

Detection of viral antigens in clinical specimens by direct immunofluorescence (IFA) and enzyme immunoassay (EIA) is widely used for the diagnosis of human influenza virus because of their rapidity. Presently, such testing is directed at conserved viral antigens (e.g., nucleoprotein and matrix protein) and does not differentiate human from avian influenza virus subtypes. The EIA-based methods are simple and convenient to use and could theoretically be applicable as point-of-care tests. Commercially available antigen detection EIA test kits have comparable analytical sensitivities for human and avian influenza viruses, but their overall sensitivity was 1,000-fold lower than that for virus isolation. Thus, currently, viral antigen detection tests, while having acceptable clinical sensitivity for the diagnosis of human influenza viruses, appear to have low clinical sensitivity for the diagnosis of avian influenza H5N1 virus. Aside from this apparently poor clinical sensitivity, a positive antigen test only confirms a diagnosis of influenza A virus. Thus, it would require additional subtype-specific diagnostic methods (e.g., RTPCR or culture) to differentiate avian from human influenza virus. Although H5- subtype-specific antigen detection tests are now becoming available on an experimental basis and are undergoing evaluation for the diagnosis of diseased poultry, the current commercially available antigen detection tests seem to have limited clinical utility for the diagnosis of H5N1 disease in humans.

RT-PCR

RT-PCR assays need to be targeted at genes (e.g., matrix gene) that are relatively conserved in order to detect all influenza A viruses and, separately, at the HA or NA genes to identify specific influenza A virus subtypes. Usually, a panel of such RT-PCR assays, which includes generic influenza A virus detection plus specific detection of H5, H3, and H1 subtypes, is used to investigate suspected human H5N1 disease. This strategy helps overcome potentially false-negative PCR results due to the mutation of the HA gene because a specimen with a positive matrix gene that is negative for H5, H3, and H1 would flag that specimen for more detailed investigation. Including the time needed for viral RNA extraction and analysis of the amplification products, the turnaround time for conventional RT-PCR assays is 6 to 8 h (or typically overnight). The use of real-time PCR shortens the turnaround time to around 4 to 6 h, increases sensitivity and specificity by the use of probes, and enables the quantification of the viral target gene. Even more importantly, because these are closed systems, the risk of PCR cross-contamination is minimized. The existence of several distinct sub lineages and the high mutability of H5N1 viruses pose a challenge for molecular diagnostics and necessitate continued evaluation, and possibly the modification of primers or probes, over time. Alternative molecular detection methods such as loop-mediated isothermal amplification tests have also been used, although they are not in routine use.

Antibody detection

The detection of H5N1-specific antibodies is essential for epidemiological investigations. Because of the delayed sero-conversion and the need for paired sera, serology can provide retrospective confirmation of H5N1 infection. While HI is the preferred method for the detection of subtype-specific antibodies to human seasonal influenza viruses in human sera, conventional HI tests (using avian or human erythrocytes) have limited value for detecting antibodies against avian viruses in humans and other mammals because of low sensitivity. Comparison of HI antibody tests with detection of neutralizing antibodies in H5N1-infected persons from the 1997 Hong Kong outbreak showed the latter to be more sensitive. Based on these observations, neutralization assays have become the methods of choice for the detection of H5- specific antibodies in humans. Using these assays, antibodies against H5N1 virus were generally detected 14 or more days after the onset of symptoms in patients infected during the 1997 Hong Kong outbreak. This is comparable to kinetics of the antibody response during primary infection with human influenza viruses. While neutralization assays seem to be the most reliable methods for the detection of human antibodies to avian viruses, the requirement of BSL-3 laboratory facilities and the labor-intensiveness are important disadvantages. HI assays using horse erythrocytes have shown promising results for detecting antibodies against H5N1 viruses in humans and may provide a convenient alternative to neutralization tests and serve as a confirmatory test of a positive neutralization test result. Lentivirus pseudotyped with H5 HA may provide an alternative option for the sero-diagnosis of H5N1 infection in mammals.

Impact on the Poultry Industry

Avian influenza presents various challenges to the poultry industry:

1. Economic Losses: Outbreaks of HPAI can result in significant economic losses. Infected birds are often culled to prevent the virus from spreading, leading to reduced production and market disruption.
2. Trade Restrictions: When avian influenza is detected in a region, many countries impose trade restrictions on poultry and poultry products from that area. This can affect the international poultry trade and lead to financial losses for the industry.
3. Increased Costs: Implementing biosecurity measures and surveillance to prevent avian influenza can increase production costs for poultry farmers.
4. Consumer Confidence: Outbreaks of avian influenza can erode consumer confidence in poultry products, leading to reduced consumption and demand.

Human Health Concerns

While avian influenza primarily affects birds, it is the potential for zoonotic transmission (from animals to humans) that raises significant human health concerns:

1. Severe Infections: Certain strains of avian influenza, such as H5N1 and H7N9, have caused severe infections in humans, resulting in a high mortality rate.
2. Pandemic Potential: The ability of avian influenza viruses to mutate and adapt is a cause for concern. If a highly pathogenic avian influenza virus were to acquire the ability for sustained human-to-human transmission, it could lead to a global pandemic.
3. Zoonotic Transmission: Most human cases of avian influenza have occurred through direct or indirect contact with infected birds. Preventing such transmission requires strict biosecurity measures.
4. Vaccination and Surveillance: Developing effective vaccines and surveillance programs are essential for mitigating the risk of avian influenza transmission to humans.

Prevention and Control

Preventing and controlling avian influenza requires a multi-faceted approach:

1. Biosecurity: Poultry farms should implement strict biosecurity measures to prevent the introduction of the virus. This includes measures such as controlling access to farms, disinfection, and ensuring that workers and visitors follow hygiene protocols.
2. Vaccination: In regions where avian influenza is endemic, vaccination of poultry may be employed to reduce the risk of infection and transmission.
3. Surveillance: Regular monitoring and surveillance of poultry populations, wild birds, and the environment help in early detection and rapid response to outbreaks.
4. Education: Farmers and those involved in the poultry industry should be educated about the risks of avian influenza and the importance of following biosecurity measures.

Conclusion

Avian influenza is a persistent challenge to the poultry industry, with the potential for severe economic losses and a threat to human health. While the risk of a global avian influenza pandemic remains relatively low, it is essential to remain vigilant and prepared. Effective prevention, surveillance, and control measures are critical to mitigating the impact of avian influenza on both the poultry industry and human health. Additionally, international cooperation and information sharing are vital in addressing this global concern.The rationale for particular concern about an H5N1 pandemic is not its inevitability but possible severe impact on human health. Such a pandemic, especially if it arises by direct adaptation rather than genetic reassortment with a preexisting human virus, could well be unusually virulent in humans. Thus, an H5N1 pandemic is an event of low probability but one of high human health impact. What is certain, however, is that the H5N1 panzootic already impacts human health via its economic and consequent nutritional impacts on rural societies and by occasional zoonotic transmission, leading to severe human disease with its attendant social impact. It is just as bad to die of protein malnutrition (because of the depletion of a major protein source for many people) as it is to die of zoonotic “bird flu.” Given the increasing geographical spread and the endemicity of H5N1 viruses in poultry across the world, and its possible (yet-tobe-proven) foothold within wild bird populations, H5N1 is likely to remain a serious threat to human health for quite some time to come. Clearly, there is every reason to attempt to control the current panzootic in poultry. If not, the attendant pandemic threat from H5N1 will continue to pose a predicament for public health.

Compiled  & Shared by- This paper is a compilation of groupwork provided by the

Team, LITD (Livestock Institute of Training & Development)

 Image-Courtesy-Google

 Reference-On Request.

AVIAN INFLUENZA OR BIRD FLU  – A MAJOR ECONOMIC THREAT TO INDIAN POULTRY INDUSTRY

Please follow and like us: