Akshit Tyagi1, Aditi Singh Nimi2, Shivang Madhyan3
1M.V.Sc. Scholar, Department of Veterinary Pathology
C.V.Sc. & A.H., A.N.D.U.A.T., Kumarganj, Ayodhya, U.P. – 224229
2M.V.Sc. Scholar, Division of Parasitology,
Indian Veterinary Research Institute, Izatnagar, Bareilly-243122
3M.V.Sc. Scholar, Department of Veterinary Medicine
COVAS, S.V.P.U.A.T., Meerut – 250110
Outbreaks of Bird Flu in 2025 in different countries of the world including India onceagainchallenge the global public health systems due to their widespread circulation and considerable mortality rates. AI, commonly referred to as bird flu, is caused by viruses belonging to the genus Influenza viruses, which are members of the Orthomyxoviridae family. The AI virus has two subtypes based on glycoproteins, namely, Neuraminidase (NA) and Hemagglutinin (HA) on its surface, which, in addition to its infectivity, are the primary factors influencing the AI virus’ pathogenicity, transmission, and host adaptation. AIVs are categorized into two groups based on their pathogenicity to chickens as determined by the intravenous pathogenicity index (IVPI) test: highly pathogenic avian influenza viruses (HPAIV) and low pathogenic avian influenza viruses (LPAIV). In recent years, the transmission of HPAIV strains such as H5N1, H5N8, and H7N9 has presented substantial threats to public health. Among the various HPAIV strains, the H5N1 virus is regarded as the most pathogenic, with a high mortality rate in chickens and humans.
Although this virus primarily affects poultry, it can also infect humans, pets, livestock, and wild animals. The harmful effects of AI illness can affect both human and animal health and cause financial losses. In humans, AI is classified as a highly contagious respiratory illness that is usually self-limiting but has a significant global impact on morbidity and mortality. In poultry, severe pathogenicity can result in death, but it often has low pathogenicity, causing subclinical infections, respiratory conditions, or decreased egg production.
Poultry, particularly chickens and ducks, was the source of the AI outbreak, ultimately connected to human transmission. AI illness is difficult to control because people regularly come into contact with chickens, ducks, birds, turkeys, and other poultry in daily life, like at farms, marketplaces, and slaughter houses. Since there is currently no effective treatment for AI virus infections in commercial poultry and no widely available vaccine for human AI, treatment options for human infections are limited to supportive therapy and antiviral medication. Resistance to anti-virals is becoming a more significant issue.
Etiology
The RNA virus, termed the AI virus, is a member of the Orthomyxoviridae family. This virus has a single-stranded nucleic acid composed of eight gene segments that encode approximately 11 proteins. The influenza virus envelope comprises a combination of proteins and carbohydrates. The virus uses its spikes to cling to particular receptors in host cells. There are two types of spikes, namely, those containing NA and HA, which are situated outside the virion. The four types of antigens found in influenza viruses are nucleocapsid protein (NP), HA, matrix protein (MP), and NA. Based on the types of NP and MP antigens, influenza viruses are classified as influenza A, B, and C viruses. Influenza A virus infection is highly harmful to both humans and animals, resulting in high rates of morbidity and mortality worldwide and making it a crucial component of the health sector. Because this type of virus is easily mutable and can produce new, more virulent forms through antigenic drift or shift, it can spread globally. There are nine NA and 15 HA subtypes. Epidemiological seroprevalence investigations have demonstrated that a number of influenza A virus subtypes, including H2N2 (1889), H3N8 (1900), H1N1 (1918), H2N2 (1957), H3N2 (1968), H7N7 (1977), and H5N1 (2005), are linked to pandemic outbreaks. Although influenza C virus is infrequently encountered despite its ability to infect both humans and animals, influenza B virus exclusively targets humans. Types B and C influenza viruses infrequently or never produce pandemic outbreaks.
Transmission
The avian influenza virus spreads through direct contact with infected birds, whether wild or domesticated. It can be transmitted via bird droppings, saliva, nasal secretions, and contaminated water or feed. Migratory birds often act as carriers, spreading the H5N1 virus across regions and increasing the risk of outbreaks in poultry farms. Although human-to-human transmission is rare, people can get infected through direct contact with infected birds, their droppings, or contaminated surfaces.
Pathogenesis
AI viruses can infect and kill various bird species. Their virulence divides them into two categories. First, an HPAI virus termed HPAI has been identified as a lethal virus-producing bird plague. This group was restricted to H5 and H7 rats, and the mortality rate was approximately 100%. Second, another virus known as low pathogenic AI (LPAI) causes mild respiratory sickness. There is uncertainty regarding the factors leading to the virus’s transformation from LPAI to HPAI. Under certain conditions, mutations occur quickly once wild birds are introduced. In other instances, the LPAI virus was present in chickens for months before mutation. The pathogenicity of AI viruses is polygenic and heavily dependent on a group of genes that affect immune evasion mechanisms, replication efficiency, and host and tissue tropism. Furthermore, after interspecies transmission, variables specific to the host and species affect the course of infection. There are several ways in which the LPAI virus can infect flocks of chickens. The inhalation or consumption of infectious LPAI or HPAI virions triggers pathogenesis because trypsin-like enzymes in intestinal and respiratory epithelial cells cleave surface HA. This leads to multiple replication cycles in the intestines and respiratory tract, which release infectious virions. Second, HPAI viruses infiltrate the submucosa and enter the capillaries following their initial replication in the respiratory epithelium. This virus reproduces in endothelial cells and then travels through lymphatic and vascular networks to infect and multi ply in different cell types in the skin, brain, and visceral organs. Alternatively, the virus could spread throughout the body before multiplying extensively in vascular endothelial cells. This virus is present in red, white, and plasma blood cells. Macrophages appear to be involved in viral dissemination throughout the body. This pantropic replication is caused by HA proteolytic cleavage sites, which are cleaved by the ubiquitous cellular enzyme furin. Multiple organ failures lead to clinical symptoms and mortality. Third, the intestine or respiratory tract is typically the only place where LPAI viruses can replicate. Most frequently, respiratory injury results in the onset of disease or death, particularly when coupled with subsequent bacterial infection. The LPAI virus replicates and damages renal tubules, pancreatic acinar epithelium, fallopian tubes, and other organs containing epithelial cells that occasionally have trypsin-like enzymes in several animals.
Global Scenario
Between 2003 and February 2025, the World Health Organization has recorded 972 cases of confirmed H5N1 influenza, leading to 468 deaths (1). The true fatality rate may be lower because some cases with mild symptoms may not have been identified as H5N1.
Tens of millions of birds have died of H5N1 influenza and hundreds of millions of birds have been slaughtered and disposed of, to limit the spread of H5N1. Countries that have reported one or more major highly pathogenic H5N1 outbreaks in birds (causing at least thousands but in some cases millions of dead birds) are South Korea, Vietnam, Japan, Thailand, Cambodia, Laos, Indonesia, China, Malaysia, Russia, Kazakhstan, Mongolia, Turkey, Romania, Croatia, Ukraine, Cyprus, Iraq, Nigeria, Egypt, India, France, Niger, Bosnia, Azerbaijan, Albania, Cameroon, Myanmar, Afghanistan, Israel, Pakistan, Jordan, Burkina Faso, Germany, Sudan, Ivory Coast, Djibouti, Hungary, United Kingdom, Kuwait, Bangladesh, Saudi Arabia, Ghana, Czech Republic, Togo, Nepal, Bhutan, the Philippines, and Chile (2).
Indian scenario
On 22 May 2024, the International Health Regulations (IHR) National Focal Point (NFP) for India reported to WHO a case of human infection with avian influenza A (H9N2) virus detected in a child resident of West Bengal state in India. This is the second human infection of avian influenza A(H9N2) notified to WHO from India, with the first in 2019.
According to data of Ministry of Fisheries, Animal Husbandry & Dairying posted on 05 APR 2025 states affected since January in India are Maharashtra, Chhattisgarh, Jharkhand, Andhra Pradesh, Madhya Pradesh, Telangana, Karnataka, Bihar. Total number of Epicenters in 2025 is 34, whereas Active Epicenters are 6 (3 States – Jharkhand (Bokaro and Pakur), Telangana (Ranga Reddy, Nalagonda and Yadadri Bhuvanagiri & Chhattisgarh (Baikunthpur, Korea).
Clinical Symptoms
The type of AI virus and host species determines the clinical manifestations, severity, and fatality rates of AI. Most AI viruses are LPAI viruses (subtypes H1–H16). An infection with the LPAI virus typically results in respiratory symptoms in birds, including sneezing, coughing, nasal and eye discharge, and swelling of the infraorbital sinuses. Sinusitis is common in ducks, quails, and domestic turkey. Respiratory tract lesions typically involve inflammation and blockage of the lungs and trachea. AI symptoms in laying and broiler hens include mucosal edema and inflammatory exudate in the oviduct lumen, decreased egg production, infertility, and egg rupture or involution. Symptoms that are rarely observed in laying hens and broilers include acute renal failure and deposition of visceral uric acid (visceral gout). Clinical symptoms or severe AI-related lesions may not be visible in acute cases before death. However, in severe cases, the lesions could be as follows: Cyanosis and edema of the head, comb, wattles, and snood (in turkey); ischemic necrosis of the comb, wattle, or hair net; edema and red discoloration of the calves and feet as a result of subcutaneous ecchymotic bleeding; petechial hemorrhages in the muscles and visceral organs; and blood staining. Greenish diarrhea is common in severely sick birds. Acute AI infection-surviving birds may develop central nervous system (CNS) involvement, which manifests as torticollis, in coordination, opisthotonos, paralysis, and drooping wings. The location and severity of microscopic lesions vary widely; examples include edema, bleeding, and necrosis in the parenchymal cells of the skin, CNS, and various visceral organs. The symptoms of AI virus infection can range from moderate to severe, especially in those infected with the H5N1 or H7N9 subtypes. These symptoms, which include sore throat, stuffy nose, fever, cough, body aches, headache, exhaustion, and conjunctivitis, are comparable to seasonal flu. Types A and B influenza viruses cause asymptomatic respiratory infections in young and healthy people, but in certain cases, especially in older patients and those with co morbidities or immunosuppressed illnesses, they can be fatal. Symptoms include cough, malaise, fever, chills, sore throat, headache, coryza, anorexia, and myalgia.
Treatment
AI, which affects poultry, has no known cure. However, secondary illnesses can be prevented using broad-spectrum antibiotics, sound husbandry practices, and a healthy diet. Treatment for AI in humans varies among individuals based on the severity of the disorder. The illness may involve a range of drugs in addition to symptomatic care, such as antivirals and antibiotics, to treat or prevent subsequent bacterial pneumonia. Certain AI viruses can be effectively treated with two classes of antiviral medications: adamantane (rimantadine and amantadine) and NA inhibitors (zanamivir, peramivir, laninamivir, and oseltamivir). However, some of these medications (laninamivir and peramivir) are not licensed in all countries.
Diagnosis
AI viruses cannot be identified based only on clinical signs and symptoms because the lesions and symptoms of this illness are diverse and may be mistaken for those of other illnesses. Therefore, serological and virological testing is required, and confirmation must be per formed at a qualified laboratory. Oropharyngeal, cloacal, and tracheal swabs from live birds can be used to detect the AI virus. Several factors, including the virus and bird species, affect the accuracy of this detection. Moreover, droppings and feathers from young birds can be used as helpful samples. All species can benefit from virus characterization through virus isolation, which involves inoculating samples into chicken embryos to identify the characteristics of red blood cell deposition. Despite being time-consuming, this method is the “gold standard” for detecting AI viruses and is mostly utilized for the diagnosis of initial clinical cases as well as the isolation of the virus for additional laboratory investigations. The AI virus can also be diagnosed in a laboratory setting using molecular tests such as real-time polymerase chain reaction (RT-PCR) or serological tests such as the HA inhibition test, anti gen detection enzyme-linked immunosorbent assay (ELISA), agar gel immunodiffusion (AGID), and other immunoassays.
Vaccination
Vaccinating poultry against AI disease using live recombinant vaccine (Fowl pox H5) and inactivated vaccine can limit virus transmission when vaccinated birds become sick, protect birds from clinical disease, and increase resistance to infection. Therefore, by reducing the number of circulating viruses, carefully controlled poultry vaccination can reduce rates of mortality and morbidity, as well as human danger. The best public health measure to prevent influenza in people is annual influenza vaccination, which comes in two trivalent formulations: live attenuated and inactivated formulations containing AI A virus strains (H1N1 and H3N2) and AI B virus. No vaccine for AI is commercially available and has undergone experimental testing that satisfies all the necessary criteria. Most vaccinations achieve the intended outcome, which is protection against clinical illness caused by AI viruses.
Public Health Importance
AI disease outbreaks in domestic and wild birds are uncommon; however, an infection can significantly threaten public, veterinary, and medical health. Following the 1997 epidemic of AI H5N1 in people and poultry in Hong Kong and the 2003 outbreak of AI H7N7 in the Netherlands, there have been concerns that the AI virus may continue to exist in some chicken populations and, through multiple mutations or reassortment, become a pandemic virus for humans. The viruses that emerged in the 20th century were novel HA subtypes against which the human population failed to develop immunity. The reintroduction of H1N1, which over time modified and re-sequenced the AI A genes of multiple AI, human, and swine viruses, resulted in the 2009 H1N1 pandemic. The current strains of AI viruses that pose a threat to global health are many subtypes, namely H5, H7, and H9, which have repeatedly infected humans and caused occasional diseases. One health approach to mitigating the AI virus is vaccinating humans and susceptible farmed and pet animals.
Control
Once the occurrence of HPAI is confirmed through the laboratory tests; all contingency procedures for the containment and eradication of HPAI should be implemented with the following-
- Cross-sectoral notification to health and health related sectors, industry and farmers.
- Restricted access to infected premises and alert zone.
- Restrictions on movement and trade of poultry and its products.
- Depopulation procedures for infected birds.
- Strict compliance to biosafety and biosecurity protocols.
- Vaccination of at-risk human populations.