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In 2003, the Chinese population was infected with a virus causing Severe Acute Respiratory Syndrome (SARS) in Guangdong province. The virus was confirmed as a member of the Beta-coronavirus subgroup and was named SARS-CoV,. The infected patients exhibited pneumonia symptoms with a diffused alveolar injury which lead to acute respiratory distress syndrome (ARDS). SARS initially emerged in Guangdong, China and then spread rapidly around the globe with more than 8000 infected persons and 776 deceases. A decade later in 2012, a couple of Saudi Arabian nationals were diagnosed to be infected with another coronavirus. The detected virus was confirmed as a member of coronaviruses and named as the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The World health organization reported that MERS-coronavirus infected more than 2428 individuals and 838 deaths. MERS-CoV is a member beta-coronavirus subgroup and phylogenetically diverse from other human-CoV. The infection of MERS-CoV initiates from a mild upper respiratory injury while progression leads to severe respiratory disease. Similar to SARS-coronavirus, patients infected with MERS-coronavirus suffer pneumonia, followed by ARDS and renal failure.
Recently, by the end of 2019, WHO was informed by the Chinese government about several cases of pneumonia with unfamiliar etiology. The outbreak was initiated from the Hunan seafood market in Wuhan city of China and rapidly infected more than 50 peoples. The live animals are frequently sold at the Hunan seafood market such as bats, frogs, snakes, birds, marmots and rabbits. On 12 January 2020, the National Health Commission of China released further details about the epidemic, suggested viral pneumonia. From the sequence-based analysis of isolates from the patients, the virus was identified as a novel coronavirus. Moreover, the genetic sequence was also provided for the diagnosis of viral infection. Initially, it was suggested that the patients infected with Wuhan coronavirus induced pneumonia in China may have visited the seafood market where live animals were sold or may have used infected animals or birds as a source of food. However, further investigations revealed that some individuals contracted the infection even with no record of visiting the seafood market. These observations indicated a human to the human spreading capability of this virus, which was subsequently reported in more than 100 countries in the world. The human to the human spreading of the virus occurs due to close contact with an infected person, exposed to coughing, sneezing, respiratory droplets or aerosols. These aerosols can penetrate the human body (lungs) via inhalation through the nose or mouth (Fig. 2),,,.
Since the highly pathogenic H5N1 avian influenza virus (AIV) was first transmitted from birds to humans in Hong Kong in 1997, other pathogenic AIVs, including H7N2, H7N3, H7N7, and H9N2 have been reported in China and other parts of the world.1,2,3,4 However, no human infections with the novel H7N9 virus have been reported until now from China. Here we report a fatal case caused by H7N9 AIV in the very early stage of this endemic.
A 52-year-old retired female resident in Shanghai was admitted to Fudan University affiliated Huashan Hospital due to 7-day history of pyrexia, accompanied by cough, chest stuffiness and dyspnea for the past two days. The patient had a sudden onset on March 27th, 2013 with rigors, and the highest temperature reached 40.6 °C but with no obvious symptoms of cough, pharyngalgia, stuffiness, dyspnea, nausea, vomiting, abdominal pain or diarrhea, and did not receive medication. The next day the patient visited emergency room and chest auscultation demonstrated rough breath sounds, absence of rales. Laboratory tests showed a leukocyte count of 5300/mm3, with 72% of neutrophils, and C reactive protein (CRP) of 26.8 mg/L. The patient was given antibiotics. On the third day, the patient took chest radiography and showed small patchy shadows in lower lobe of the right lung. The patient was given antibiotics intravenously for three consecutive days, still without cough, expectoration or shortness of breath, although her temperature was not resolved. On day 7 after onset of fever, due to quick progression of the symptoms, including cough, chest stuffiness and shortness of breath, the patient visited the emergency department of Fudan University affiliated Huashan Hospital again. Unfortunately, the arterial blood gas analysis showed severe hypoxemia, pH 7.54, PaCO2 4.33 kPa, PaO2 3.66 kPa, and saturation of oxygen 61.3% on room air. In the meantime, chest computed tomography (CT) demonstrated diffuse bilateral consolidation with right pleural effusion (Figure 1). Laboratory findings indicated a leukocyte count of 3290/mm3, with 92% of neutrophils and 5.5% of lymphocytes; platelets of 155 000/mm3; increased myocardial enzymes, prolonged prothrombin time and abnormal serum electrolytes. The patient was suspected severe flu with acute respiratory distress syndrome and thereafter was given endotracheal intubation and placed on a mechanical ventilator. Intravenous injection of methylprednisolone 40 mg was administered to inhibit inflammation and alleviate edema in the lung. On April 3rd (day 8), antimicrobial regimen as well as immune globulin therapy and the methylprednisolone were maintained. However, the patient's condition worsened and died of acute respiratory distress syndrome.
On April 4th, the throat swab was sent to the laboratory of Chinese Center for Disease Control and Prevention and the result revealed the presence of H7N9 avian influenza A virus. Meanwhile laboratory tests for pathogens, including respiratory syncytial virus, influenza B virus, human metapneumovirus, cytomegalovirus, herpes simplex virus 2, human immunodeficiency virus, and severe acute respiratory syndrome coronavirus (SARS-CoV), were all negative. This is one of the six laboratory confirmed fatal cases of H7N9 infection reported to World Health Organization.
To date (April 7th, 2013), a total of 21 cases have been laboratory confirmed with influenza A (H7N9) virus in China, including 6 deaths, 12 severe cases and 3 mild cases.5 An inter-government task force has been formally established, the animal health sector has intensified investigations into the possible sources and reservoirs of the virus. However no definite history of contact with livestock was found in this case. The patient also did not feed or eat poultry at households. Some other confirmed cases had close contact with poultry or with associated environment. It is interesting to note that the virus has also been found in a pigeon in a market in Shanghai. It is unclear how this case was infected by H7N9 AIV, similar to some other cases without known recent close contact with birds or poultry. However, influenza A H7 viruses are a group of influenza viruses that normally circulate among birds and the influenza A (H7N9) virus is one subgroup among the larger group of H7 viruses.6 Although the patient denied close contact with poultry, H7N9 virus was detected among poultry at local market. The most likely source of the virus in this case seems to be from the environment or food contaminated with this novel virus. The emergence of H7N9 AIV infections in humans suggests the avian influenza virus evolves to achieve adaptations including the ability to bind to mammalian cells and to break the species barrier. Fortunately, among close contacts of this case, the patient's husband was pyretic with a temperature of 38 °C, but negative for H7N9 AIV detection and recovered soon, indicating no evidence of human-to-human transmission up to this point. At this time there is no evidence of ongoing human-to-human transmission. The possibility of animal-to-human transmission is being investigated, as is the possibility of person-to-person transmission.
To date, the overall proportion of fatal cases among those reported 21 cases was 28.6% (6/21), lower than that in H5N1 AIV infection in humans (average 59%).7 According to the experience from H5N1 AIV treatment, cases with a fatal outcome were admitted to hospital later (median, 5 days) than those who survived (median, 1 day).7 All fatal cases in Shanghai including this patient were admitted to hospital very late until the symptom of shortness of breath developed. Meanwhile, due to unclear cause of the disease, fatal cases, including this patient, had not been given the anti-influenza drugs such as neuraminidase inhibitors (oseltamivir) as soon as possible and within 2∼4 days of disease onset, leading to loss of valuable salvage time for the severe cases. Since the laboratory testing conducted in China has shown that the influenza A (H7N9) viruses are sensitive to oseltamivir and zanamivir, and if these drugs are given early in the course of illness and the patients are hospitalized earlier, the survival rate of this new emerging infectious disease might be significantly improved. Future strategies to prevent fatal cases should include prompt laboratory diagnosis and early antiviral and steroid treatment, and good supportive care.
LPAIV H7N9 was identified as a newly emerging zoonotic pathogen in early 2013. It has caused since then a total of 680 cases of zoonotic infection, with a case-fatality rate of about 20%, principally in adult and elderly individuals. With an incubation time of 2–8 days, H7N9 virus infection can progress from initial symptoms of high fever and other influenza-like signs to more severe lower respiratory tract infection, respiratory distress and associated complications. Exposure to infected poultry is considered the primary risk factor for human infection. A total of 556 outbreaks have been reported in domestic poultry, including chickens, ducks, geese, pigeons and pheasants, largely concurrently to zoonotic cases of infection (Table 1). A few cases were reported in wild bird species. Because of their low pathogenic nature, H7N9 viruses typically cause asymptomatic or mild infections in birds.
Most animal outbreaks and zoonotic cases of low pathogenic avian influenza H7N9 virus infection occurred in mainland China, while imported zoonotic cases were identified in Canada and Malaysia (Fig. 1). The first epidemic of H7N9 virus infection in poultry peaked in April 2013 soon after the first identification of the virus as a cause of a zoonotic case of infection. Epidemics subsequently re-occurred in winter 2014 and 2015, with the highest reported numbers of animal outbreaks and zoonotic cases of infection during the months of January–February of each year.
LPAIV H7N9, in contrast to most other avian influenza viruses, can bind to the cellular receptors used by seasonal influenza viruses,. This ability is associated with one or two specific amino-acids in the hemagglutinin glycoprotein. Because seasonal influenza viruses and LPAIV H7N9 peak coincidentally during the winter months, they may co-infect an individual and subsequently reassort. This may give rise to a transmissible variant, against which the human population has little pre-existing immunity, and may be at the origin of a new influenza pandemic. Strict monitoring and isolation measures are therefore essential to limit the risk of seasonal influenza and reassortment in individuals with zoonotic H7N9 virus infection.
Coronaviruses belong to the Coronaviridae family in the Nidovirales order. Corona represents crown-like spikes on the outer surface of the virus; thus, it was named as a coronavirus. Coronaviruses are minute in size (65–125 nm in diameter) and contain a single-stranded RNA as a nucleic material, size ranging from 26 to 32kbs in length (Fig. 1). The subgroups of coronaviruses family are alpha (α), beta (β), gamma (γ) and delta (δ) coronavirus. The severe acute respiratory syndrome coronavirus (SARS-CoV), H5N1 influenza A, H1N1 2009 and Middle East respiratory syndrome coronavirus (MERS-CoV) cause acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) which leads to pulmonary failure and result in fatality. These viruses were thought to infect only animals until the world witnessed a severe acute respiratory syndrome (SARS) outbreak caused by SARS-CoV, 2002 in Guangdong, China. Only a decade later, another pathogenic coronavirus, known as Middle East respiratory syndrome coronavirus (MERS-CoV) caused an endemic in Middle Eastern countries.
Recently at the end of 2019, Wuhan an emerging business hub of China experienced an outbreak of a novel coronavirus that killed more than eighteen hundred and infected over seventy thousand individuals within the first fifty days of the epidemic. This virus was reported to be a member of the β group of coronaviruses. The novel virus was named as Wuhan coronavirus or 2019 novel coronavirus (2019-nCov) by the Chinese researchers. The International Committee on Taxonomy of Viruses (ICTV) named the virus as SARS-CoV-2 and the disease as COVID-19,,. In the history, SRAS-CoV (2003) infected 8098 individuals with mortality rate of 9%, across 26 contries in the world, on the other hand, novel corona virus (2019) infected 120,000 induviduals with mortality rate of 2.9%, across 109 countries, till date of this writing. It shows that the transmission rate of SARS-CoV-2 is higher than SRAS-CoV and the reason could be genetic recombination event at S protein in the RBD region of SARS-CoV-2 may have enhanced its transmission ability. In this review article, we discuss the origination of human coronaviruses briefly. We further discuss the associated infectiousness and biological features of SARS and MERS with a special focus on COVID-19.
Frequent human-animal contact is the major cause for viral cross-species transmission. Next-generation sequencing is a highly efficient method for rapid identification of microorganisms and for surveillance of pathogens for infectious diseases. Animal models and other laboratory tests would be needed to pinpoint the causative agents. The novel coronaviruses in Wuhan likely had a bat origin, but how the human-infecting viruses evolved from bats requires further study. The human-infecting virus may become more infectious but less virulent as it continues to (co-)evolve and adapt to human hosts. Since Wuhan is one of the largest inland transportation hubs in China and the city has been closed off, it is urgently necessary to step up molecular surveillance and restrict the movement of people in and out of the affected areas promptly, in addition to closing the seafood markets. To prevent human-to-human transmission events, close monitoring of at-risk humans, including medical professionals in contact with infected patients, should also be enforced. Finally, virome projects should be encouraged to help identify animal viral threats before viral spillover or becoming pandemics.
Since the identification of the first coronavirus – infectious bronchitis virus (IBV) isolated from birds – many coronaviruses have been discovered from such animals as bats, camels, cats, dogs, pigs, and whales. They may cause respiratory, enteric, hepatic, or neurologic diseases with different levels of severity in a variety of hosts, including humans. Coronaviruses have positive-sense single-stranded RNAs, their genomic size are 26 to 32 kilobases, the largest for an RNA virus. And the viruses themselves appear crown-shaped under electron microscopy. Coronaviruses belong to the subfamily Coronavirinae in the family Coronaviridae in the order Nidovirales. Coronavirinae is further divided into four genera, Alpha-, Beta-, Gamma-, and Deltacoronavirus, based on their phylogenetic relationships and genomic structures.
Coronaviruses occasionally jump across host barriers, often with lethal consequences. The alpha- and betacoronaviruses only infect mammals and usually cause respiratory illness in humans and gastroenteritis in animals. Gamma- and deltacoronaviruses mainly infect birds, and no human infection has been reported. Six coronaviruses known to infect humans are 229E, NL63 (genus Alpha-), OC43, HKU1, SARS-CoV, and MERS-CoV (Beta-), whereas only SARS- and MERS-CoV have caused large worldwide outbreaks with fatality, others usually cause mild upper-respiratory tract illnesses. A novel coronavirus was identified in a pneumonia patient in Wuhan on January 9 of this year represents the seventh human-infecting coronaviruses.
Severe acute respiratory syndrome (SARS, induced by SARS-CoV) first emerged in Guangdong province, China in 2002 and quickly spread around the world, with more than 8000 people infected and nearly 800 died. The MERS-CoV is a new member of Betacoronavirus and caused the first confirmed case of Middle East Respiratory Syndrome (MERS) in Saudi Arabia in 2012. Over 2000 MERS-related infections have been reported as of 2019 with a ∼34% fatality rate (https://www.who.int/).
Infectious bronchitis virus (IBV) is, by definition, the coronavirus of the domestic fowl. Although it does indeed cause respiratory disease, it also replicates at many nonrespiratory epithelial surfaces, where it may cause pathology, for example, kidney and gonads [1, 2]. Strains of the virus vary in the extent to which they cause pathology in nonrespiratory organs. Replication at enteric surfaces is considered to not normally result in clinical disease, although it does result in faecal excretion of the virus. Infectious bronchitis (IB) is one of the most important diseases of chickens and continues to cause substantial economic losses to the industry. Infectious bronchitis is caused by IB virus (IBV), which is one of the primary agents of respiratory disease in chickens worldwide. All chickens are susceptible to IBV infection, and the respiratory signs include gasping, coughing, rales, and nasal discharge. Sick chicks usually huddle together and appear depressed. The severity of the symptoms in chickens is related to their age and immune status. Other signs of IB, such as wet droppings, are due to increased water consumption. The type of virus strain infecting a flock determines the pathogenesis of the disease, in other words, the degree and duration of lesions in different organs. The upper respiratory tract is the primary site of infection, but the virus can also replicate in the reproductive, renal, and digestive systems. The conventional diagnosis of the IBV is based on virus isolation in embryonated eggs, followed by immunological identification of isolates. Since two or three blind passages are often required for successful primary isolation of IBV, this procedure could be tedious and time consuming. Alternatively, IBV may be isolated by inoculation in chicken tracheal organ cultures. Furthermore, IBV may be detected directly in tissues of infected birds by means of immunohistochemistry [6, 7] or in situ hybridization. The reverse transcription-polymerase chain reaction (RT-PCR) has proved useful in the detection of several RNA viruses [9, 10]. Outbreaks of the disease can occur even in vaccinated flocks because there is little or no cross-protection between serotypes [2, 11]. The necessity of IB prevention in chicken regarding the nature of the virus with a high mutation rate in the S1 gene dictates the necessity to develop effective vaccines. The first step is to study the virus strains distributed in the geographical region and determine their antigenicity and pathogenicity in order to choose a suitable virus strain for vaccination. This virus was isolated from a flock suspected of IB suffering from severe respiratory distress and experiencing high mortality. The objective of the present study was to clarify some aspects of pathogenesis of the disease caused by IRFIBV32 (793/B serotype) in experimentally infected broilers. RT-PCR test was performed to detect the presence of the virus in body tissues and samples. The clinical signs, gross lesions, and antibody response of the affected chicks were also monitored.
A case was defined as a staff member working at the NTNAMC who was hospitalized for respiratory tract infection between November 1 and November 30, 2012, and confirmed to have C. psittaci infection by polymerase chain reaction (PCR) and/or a four-fold rise in serum microimmunofluorescent antibody titer against C. psittaci (Focus Diagnostics, Cypress, California, USA).
About 70% of microbial agents causing outbreaks of emerging infectious diseases in humans originate directly from animals. Among respiratory virus infections, the influenza A viruses H5N1 and H7N9 from avian species, and the severe acute respiratory syndrome coronavirus from bats have caused large epidemics–. Atypical bacterial pathogens causing community-acquired pneumonia include Chlamydophila psittaci from psittacine birds and Coxiella burnetti from livestock and other animals. However, human outbreaks due to zoonotic bacteria associated with the emergence of a novel animal virus in the animal host were not previously documented.
In November 2012, an outbreak of human psittacosis affecting six staff members occurred at the New Territories North Animal Management Centre (NTNAMC) in Hong Kong. The human outbreak was preceded by an outbreak of avian chlamydiosis among the detained Mealy Parrots (Amazona farinose). Although birds in the tropical and sub-tropical areas are commonly infected with C. psittaci, most infected birds are asymptomatic,. Large human outbreaks are rare even among bird handlers. Although co-infection of C. psittaci and viruses has been reported in outbreaks of avian species–, no virus-bacterium co-infection of implicated avian species has ever been reported in outbreaks of human psittacosis. In this study, we sought to investigate viruses that cause avian co-infection, which may have led to this outbreak of psittacosis.
Avian coronavirus is the main representative of genus Gammacoronavirus, family Coronaviridae, and order Nidovirales. Within the avian coronavirus group, the infectious bronchitis virus (IBV) is among the most researched. This virus is known to cause an important disease that incurs a high economic loss in the poultry industry despite an ongoing vaccination program. It causes respiratory disease while also affecting the kidneys and reproductive tract through viremia with a severity that differs depending on serotypes. Mutations and recombination have produced a high genetic diversity of the virus. In addition, vaccinations performed in the farm setting can influence the evolution of the virus. Many serotypes of IBV are often not cross-protective. Mismatching between the circulating strain and the administered vaccine may contribute to vaccination failure. Ubiquitous IBV and IBV-like viruses have also been found in species other than chicken, such as in peafowl, guinea fowl, partridge, waterfowl, and teal. This finding strengthens the possibility that IBV may have a wider range of hosts than previously thought. Despite this, data relating to IBV in Indonesia is still limited to poultry. Studies of diseases on endemic species are valuable for the conservation effort, yet are rarely conducted.
The Eclectus parrot (Eclectus roratus) is a sexually dichromatic parrot native to a part of Eastern Indonesia and Northern Australia. It is classified as protected in Indonesia according to Government Decree Number 7, Year 1999 and Constitution Number 5, Year 1990. Visually captivating, with both male and female showing radically different plumage, the Eclectus parrot is naturally talkative and popular as a pet. However, there has been limited information about viral diseases among Eclectus parrots. The latest finding on coronavirus in parrots was in 2006 when a virus distinct from IBV was found in the green-cheeked Amazon parrot. Understanding viral diseases in Eclectus parrots may be beneficial for the conservation effort and may provide additional information about viral diseases in birds.
There is limited information as to whether avian coronaviruses cause diseases in Psittacine birds; therefore, information about the presence of this virus among parrots might be valuable for the conservation effort of endemic birds and the poultry industry, which is robust in Indonesia. This study aimed to determine the presence of and to characterize avian coronavirus isolated from Eclectus parrots reared by an Indonesian local bird breeder.
Chickens of all ages and breed types are susceptible to IBV infection, but the extent and severity of the disease is pronounced in young chicks, compared to adults. Similarly, resistance to infection was suggested to increase with increasing age. Experimental evidence suggests that line C white leghorn chickens are more resistant to M41 IBV challenge, compared to line 151, although both lines had similar virus shedding rate [22, 23], perhaps influenced by genetic polymorphism in the chicken major histocompatibility complex (MHC), as observed between B∗15, B∗13, or B∗21 chicken haplotypes.
Anti-viral drugs are thought to be backbone of a management plan of an avian flu pandemic. Only two anti-viral drugs have shown promise in treating avian influenza: oseltamivir (Tamiflu®) and zanamivir (Relenza®). A treatment of Tamiflu® includes 10 pills taken over five days while Relenza® is administered by oral inhalation. The US Food and Drug Administration has approved both anti-viral drugs for treating influenza but only Tamiflu® has been approved to prevent influenza infection. Because antivirals can be stored without refrigeration and for longer periods than vaccines, developing a stockpile of antivirals has advantages as part of an overall strategy to control a flu epidemic. However, there are limitations to the use of antivirals: Tamiflu® needs to be taken within 2 days of initial flu symptoms for it to be effective, but many people may not be aware that they have the flu early in the disease. Some research in animals and recent experience in the use of the drug to treat human cases have also found that Tamiflu may be less effective against the recent strains for the current H5N1 virus than the 1997 strain. Improper compliance to antivirals by irresponsible individuals during an outbreak may results in the emergence of a drug-resistant strain. Lastly, there are current concerns about the safety of Tamiflu® which has been associated with increased psychiatric symptoms among Japanese adolescents.
Only one isolate, defined as parrot/Indonesia/BX9/16, was sequenced for the partial S1 gene of IBV using XCE2+/XCE2− primers (Table-1). Nucleotide sequencing of 323 nucleotides from the partial S1 gene showed that there was no difference in the nucleotide sequence of the parrot/Indonesia/BX9/16 gene when compared with IBV 4/91 Israel variant 1 (AF093794.1) and the 4/91 vaccine strain (KF377577.1) (Figure-1). The nucleotide and amino acid pairwise distance also showed 100% homology with the IBV 4/91 Israel variant 1 (AF093794.1) and the 4/91 vaccine strain (KF377577.1). However, differences were observed between the sequenced gene, the H120 (FJ888351) positive control, and the non-chicken IBV-like peafowl/GD/KQ6/2003 virus (AY641576) (Table-4). A phylogenetic tree (Figure-2) of the aligned nucleotide sequence of the partial S1 gene was constructed using the maximum likelihood method with Mega 7 software with 1000 bootstrap value. The tree showed a close relatedness of viral isolate, parrot/Indonesia/BX9/16, to the IBV strain 4/91 variant 1 Israel (AF093794.1), the 4/91 vaccine strain (KF377577.1), CK/CH/YN/SL 1301-1 (KX107779.1), chicken/Attock/NARC-786/2013 (KU145467.1), and gammaCoV/Ck/Poland/G193/2015 (MK576138.1), whereas there were differences observed when compared with the H120 vaccine (FJ888351.1) positive control.
Although domestic fowl (Gallus gallus) and pheasant (Phasianus spp.) are considered to be natural hosts for IBV, other IBV-like coronaviruses have been identified in nondomestic avian species including pheasant, peafowl, turkey, teal, geese, pigeon, penguins quail, duck, and Amazon parrot [15–18]. Antigenic similarities between turkey coronavirus (TCoV) and avian infectious bronchitis virus (AIBV) have also been demonstrated. Antibodies to IBV have been demonstrated in humans with close contact to poultry, but the virus has not been reported to cause human clinical disease.
The virus isolate used in this study was IRFIBV32 (GenBank: HQ123359.1). It was obtained from Shiraz Veterinary University and was propagated two times in 9- to 11-day-old embryonated chicken eggs. The embryo lethal dose (ELD50) was calculated according to the Reed and Muench formula.
HPAIV H5N1 emerged in Hong Kong in 1997, causing 18 cases of zoonotic infection, including 6 fatalities. After containment of the outbreak in Hong Kong, the virus re-emerged in mainland China in 2003. It infected an unmatched diversity of wild and domestic avian and mammalian species, and subsequently spread over much of Asia, Europe and Africa, evolving into many co-circulating antigenically-distinct clades and lineages. The severity of the disease is highly variable across animal species, ranging from asymptomatic infections, e.g., in dabbling ducks, to severe systemic disease with high mortality rates in other avian species as well as in most mammalian species found infected.
Since 2003, HPAIV H5N1 has caused a total of 834 cases of zoonotic infection in 18 countries, with a case-fatality rate of about 55% (Table 2). As for LPAIV H7N9, exposure to infected poultry is considered the primary risk factor for human infection. However, in contrast to LPAIV H7N9 infection, more than half of the cases were identified in children,. Unusually pathogenic, HPAIV H5N1 can present a long incubation time, ranging between 2 and 17 days. Severe signs of lower respiratory tract infection and extra-respiratory symptoms, such as gastro-intestinal signs, typically rapidly supersede high fever and other influenza-like signs and symptoms.
Since 2014, a wide diversity of reassortants containing the highly pathogenic H5 gene emerged and caused massive outbreaks in poultry and wild birds worldwide. Of these reassortants, only HPAIV H5N6 is reported to have caused zoonotic infections (Table 3). Epidemics of the novel HPAIVs of the H5 subtype typically peaked during the winter and early spring months of December–March. A major exception is the H5N2 virus that emerged and spread in poultry in North America in 2015. Although it emerged during winter, the epidemic peaked in spring during the months of April–May (Fig. 2).
Outbreaks of HPAIVs of the H5 subtype were reported in poultry globally, whereas cases in wild birds were more often detected and reported in North America and Europe. Interestingly, the new reassortant viruses, which are highly pathogenic in poultry, appear to cause asymptomatic or mild infections in most wild birds found infected to date.
Currently, zoonotic cases of H5 virus infection chiefly occur in Egypt, which experienced last winter the largest H5N1 virus outbreak since its emergence in Africa. Zoonotic cases of H5N1 virus infection are also occasionally (and possibly under-) reported in South-East Asia (Fig. 3).
The expanding diversity of HPAIVs of the H5 subtype is worrisome as it may increase opportunities for evolution towards a pandemic variant. The presence of a diverse array of reassortants in wild bird populations worldwide also indicates a major change in the epidemiology of avian influenza viruses in their bird reservoirs. Before the emergence of HPAIV H5N1, HPAIVs were thought to only evolve and spread in poultry populations, where containment and stamping-out measures contributed to their eradication. The reassortant HPAIVs of the H5 subtype represent unprecedented threats to the poultry industry. As did HPAIV H5N1, they have the potential to widely spread, if not establish, in poultry populations. Wild bird populations may represent a direct source of infection for poultry, calling for strict biosecurity measures.
Results related to IBV distribution was checked in all tissues samples collected at 5dpi of all infected chicks. The virus was found in the trachea, lung of all strains, but in the kidney of one strain (IBV/MN) with low viral load. The effect of the virus after one passage in SPF 10 old embryonated eggs showed dwarfism and hemorrhagic spots in all over the body of the embryo, which are considered pathognomonic signs of IBV (Fig. 4).
The virus was re-isolated from all the sampled tissues with a high viral load in the trachea and lungs. No IB virus was re-isolated from the control group. Real time RT-PCR results obtained from the tissues of infected chicks at 5 dpi was closely correlating with those obtains from allantoic liquid of inoculated eggs (Table 6).
Chickens and pheasants are susceptible to infection from this disease. The disease is caused by a virus belonging to the genus Coronavirus. Initially, it was thought that the chicken disease is caused by a pathogenic, homogeneous antigenic strain, which is represented by the Massachusetts strain 41. However, the ability to create multiple variants differing from the original strain of the abovementioned led to the isolation of more than 30 serotypes and antigen variants, with the number steadily growing. Between birds, the infection spreads by the aerogenic route. The pathogen also moves between the henhouse and the farm. The incubation period is from 18 to 72 h (Cavanagh and Naqi 2003). In chickens, Infectious Bronchitis (IB) causes severe inflammatory lesions in the respiratory tract. It leads to the inflammation of the bronchial mucous membranes and the bronchial obstruction occurs as a result. As the disease progresses, the serious secretions obstruct the fork of the trachea leading to dyspnea and “breathing pumping”. In adult birds, the egg-laying capacity is rapidly reduced (within 5–7 days), and the quality of the crust is crispy and discoloured with characteristic deformities. Secondary bacterial complications should be treated with antibiotics (Cavanagh and Naqi 2003). The only effective way to avoid IB losses is through systematic and preventive vaccination. Attenuated and inactivated vaccines are used in this case. Presently, serotypes of members 4/91 are recommended in Europe to provide prototype protection and protect birds against most other antigenic IB strains (Cavanagh and Naqi 2003).
Avian infectious bronchitis (IB) is an acute, highly contagious respiratory disease of chickens, causes major economic losses in poultry industry worldwide. The IB virus (IBV) is a member of Gammacoronavirus genus, previously Group 3, within the Coronaviridae and it is the type species of the avian Coronavirus of the domestic chicken (Gallus Gallus)).
It is generally accepted that chickens are the most important natural host of IBV and epithelial cells of the upper respiratory tract are the primary target, and intensive virus replication, predominantly in the trachea, results in respiratory signs, which are the most frequent clinical manifestation of this disease.
Chickens of all ages are susceptible, but the severity is great in younger ages, and the clinical signs include depression, coughing, dyspnea, sneezing, nasal discharge, and death. However, some strains of IBV can also replicates in the ciliated epithelial cells of organs, such as the kidney, reproductive and enteric tracts, producing severe nephritis, reproductive disorders in males and females, a drop in egg production and quality in laying flocks and deep pectoral myopathy in broiler breeder may occure.
The transmission of IBV is mainly horizontal by direct contact via the respiratory tract from infected chickens. Infection takes place via inhalation of droplets containing the air born virus. Or indirect by contaminated feed and drinking water, including human beings, probably contribute to more local spread. In addition, it has been demonstrate that certain strains of IBV may persist in small amounts in the cecal tonsils of the intestinal tract by asymptomatic way during long time.
IBV is an enveloped, non segmented, positive sense, single stranded RNA virus. Its genome consists of about 27.6 kb and codes for four structural proteins: the membrane (M), small membrane (E), nucleoprotein (N) and spike (S). The multimeric coiled-coil S protein is post-translationally cleaved into smaller proteins namely S1 and S2. The S1 gene contains the hypervariable regions that are responsible for the induction of neutralizing, serotype specific antibodies and protective immunity. Many IBV genotypes and serotypes have been identified and have complicated efforts at control through vaccination, due to the frequent point mutations in S1 gene that can be partially or poorly neutralised by existing vaccine serotypes. For this reason, the sequencing of this gene is the most useful strategy for the molecular characterization of virus isolates existing in the field and the selection of appropriate vaccines.
In Morocco, IBV was identified for the first time in 1983 by El Houadfi & Jones. Subsequently, several reports confirmed the IBV strains related to the Massachusetts and to 4/91 genotypes [13, 14].
Recently, between 2010-2014, an epidemiological survey showed the emergence of a novel strain of Italy02 serotype with a prevalence of 32 %, co-circulating with two serotypes; Massachusetts and 4/91, with a prevalence of 66 % and 2 % respectively, that are isolated from vaccinated and unvaccinated chicken flocks.
Mass vaccination in Morocco is conducted using a vaccine against Massachusetts, which is the most dominant serotype, however no information about pathogenesis and tissue distribution of Italy 02 serotype, hence the objective of this present study which is reported for the first time in Morocco, aims to evaluate the pathogenicity and the tissue distribution of the three isolated Moroccan strains of IBV Italy 02 genotype in one day old experimentally infected SPF chickens. The clinical signs, tracheal ciliary activity, gross and microscopic lesions were evaluated. Serological response by the detection of IBV antibodies of the affected chicks was also checked. Re-isolation of the virus from the affected organs and RT-PCR test was used to detect virus in several tissues of infected birds.
As shown in Table 3, for all the swabs collected from the larynxes of the unvaccinated chickens at 5 and 7 dpc in the control-GD group, the virus-positive rate was 100%. In contrast, the positive rate for all the JS-GD group samples was 0, while in the control group no viruses were detected in the laryngeal swabs.
The HACCP framework enables the identification of risks within a system and the design of control methods. It does not contain the scope for monitoring or ensuring compliance of the control points identified; such control should be applied via other means. Given that EIDs are appearing with increasing frequency, often in countries where they place additional strain on already over-burdened public health and healthcare systems, being able to rapidly identify and design strategies for control has valuable application in responding to emerging health threats such as the Middle East Respiratory Syndrome (MERS) virus which first appeared in Saudi Arabia in late 2012 or the rapidly spreading outbreak of a novel avian influenza A H7H9 in China since March 2013. Conducting detailed, timely and comprehensive field investigations into HPAI H5N1 outbreaks is hampered by the majority of cases occurring in developing countries. Advantages to such a framework are that it requires minimal resources and can be implemented by local health officials and international expertise, if required, can be provided remotely. It also complements recently developed diagnostic statistical models for known pathogens. Subsequent detailed and time-consuming experimental analyses can then be conducted if required. Whereas in-depth epidemiological studies can take weeks or months to produce results and recommendations the HACCP framework may provide a means of producing a response within days of an outbreak occurring.
The influenza virus has been in existence for centuries and has been constantly infecting both humans and animals (including birds). The avian influenza (AI) virus (also called avian flu or bird flu virus) is a subtype that causes contagious respiratory disease mainly in birds. Wild waterfowls, especially ducks, are natural reservoirs and can carry the virus without manifesting symptoms of the disease and spread the virus over great distances. Domesticated poultry are also susceptible to avian flu and can cause varying symptoms ranging from reduced egg production to rapid death. The severe form of the disease is called "highly pathogenic avian influenza" (sometimes abbreviated as HPAI) and is associated with near 100% mortality rates among domesticated birds. AI has become endemic in several parts of Asia and it is believed that this is a result of unregulated poultry rearing practices in rural areas of developing countries. This is of concern because such birds often live in close proximity to humans and this increases the chance of genetic re-assortment between avian and human influenza viruses which may produce a mutant strain that is easily transmitted between humans.
In the past, avian influenza viruses have rarely caused severe disease in humans. However, in Hong Kong during 1997, a highly pathogenic strain of avian influenza of H5N1 subtype crossed from birds to humans who were in direct contact with diseased birds during an avian influenza outbreak among poultry. The cross-infection was confirmed by molecular studies which showed that the genetic makeup of the virus in humans were identical to those found in poultry. The H5N1 virus caused severe illness and high mortality among humans: among 18 persons who were infected, 6 died. The outbreak ended after authorities slaughtered Hong Kong's entire stock of 1.5 million poultry. Since then, AI among birds has been reported all over the world and one of the factors responsible for the spread is the trans-oceanic and trans-continental migration of wild birds. Most deaths from AI have occurred in Indonesia to date and nearly all of the human cases resulted from close contact with infected birds. However, there has been a reported cluster of plausible human-to-human transmission of the H5N1 virus within an extended family in the village of Kubu Sembelang in north Sumatra, Indonesia, in May 2006.
Strains of influenza virus are classified into subtypes by their protein coat antigens, namely haemagglutin (HA) and neuramidase (NA). Of the 15 HA subtypes known, H1, H2 and H3 are known to have circulated among humans in the past century and hence, most people have gained immunity to interrupt the transmission of the virus. However, the H5N1 strain is unfamiliar to most humans and our low herd immunity to it poses a pandemic threat. There are thought to be three pre-requisites for a viral pandemic to occur: (1) the infectious strain is a new virus subtype which the population has little or no herd immunity; (2) the virus is able to replicate and cause serious illness and (3) the virus has the ability to be transmitted efficiently from human to human. The H5N1 virus satisfies the first two pre-requisites of a pandemic but has not developed the ability to be transmitted easily from human to human, yet.
Infection mainly affects young chickens. The disease causes a highly resistant virus classified as Circovirus and designated as CAV (Chicken Anaemia Virus) or CIA (Chicken Infectious Anaemia Virus). The main way of spreading the virus of infectious anaemia is vertically transmitted infection. In this case, the infected pullets transmit the infection to their offspring. It is also possible to spread the infection, especially in young birds, by direct contact with a patient with clinical signs and an inoculated environment (e.g., equipment and clothing) (Miller et al. 2005; Schat 2009; Quinn et al. 2015).
Vaccination against respiratory viral disease is standard practice in commercial poultry operations. Both live and killed vaccines are administered to poultry, and live vaccines are commonly used for a variety of pathogens because they are effective when mass applied and are relatively economical. In general, live vaccines induce local and cell-mediated immunity and provide a broader protective response than killed vaccines, whereas killed vaccines primarily induce humoral immunity and tend to be antigen-specific. The duration of immunity achieved following live vaccine administration depends on the age and type of bird, levels of maternal immunity, disease targeted by the vaccine, immunogenicity of the vaccine, method of vaccine application, number of and interval between boosters, virulence and similarity of the field challenge virus, interval between vaccination and challenge, and immunocompetency of the host.
Avian coronavirus infectious bronchitis virus (IBV) is an upper respiratory tract viral pathogen of poultry and leads to reduced weight gain and feed efficiency, drops in egg production and egg quality, stunted growth, and secondary bacterial infection resulting in airsacculitis. The virus initially replicates in the upper respiratory tract, followed by systemic replication in the reproductive tract and some strains can cause lesions in the kidney. Infected birds may exhibit nasal discharge, coughing, sneezing, and tracheal rales. The disease is prevented by vaccination, and live vaccines are commonly used to induce local immunity and protection. Live vaccines are generally administered to young birds to achieve early protection, and layers and breeders are also boosted with either live or inactivated vaccines, which vary based on their similarity to the circulating field viruses.
Newcastle disease (ND) is caused by virulent strains of avian paramyxovirus type 1, which has recently been reclassified as avian avulavirus 1 (AAvV-1). Depending on the strain of the virus, clinical signs of ND infection may be absent or may involve depression, inappetence, respiratory signs (nasal discharge, sneezing, coughing), reduced egg production and egg quality, and neurological signs (torticollis, circling, paralysis). Strains of Newcastle disease virus (NDV) are characterized as lentogenic, mesogenic, and velogenic, according to their mean death time in embryos. Lentogenic strains are of low pathogenicity causing mild respiratory or enteric infections, followed by mesogenic strains, while velogenic isolates are highly pathogenic often causing neurological signs and mortality. Vaccination regimes against NDV vary and may utilize a combination of live, inactivated, and virus-vectored vaccines. In the United States, the most widely used traditional vaccine strains comprise lentogenic B1 (or virus clones of the B1 strain) and LaSota strains.
Infectious laryngotracheitis (ILT) is a respiratory disease of poultry caused by gallid alphaherpesvirus I, and is economically important worldwide. Clinical manifestations of ILT include increased mortality, reduced egg production, decreased body weight gain, conjunctivitis, tracheitis with expectoration of bloody mucus in severe cases, depression, severe dyspnea and susceptibility to other respiratory pathogens. Live vaccines against ILT virus (ILTV) may be of chicken embryo origin (CEO) or tissue culture origin (TCO), in which they are passaged multiple times in eggs or tissue culture, respectively. Although recombinant vaccines for ILT are commercially available, the CEO vaccine is the most widely used vaccine against ILTV worldwide.
Because of the need to protect chickens against different viral pathogens from an early age, vaccination programs typically include multiple vaccines against a variety of pathogens. Sample vaccination regimes in different poultry sectors are reviewed in the Merck Veterinary Manual (www.merckvetmanual.com), in which the interval between vaccinations is often only a matter of weeks. However, there is little information showing that the intervals between vaccinations are sufficient for the birds to develop adequate immune protection against challenge for each virus. The literature shows that sequential viral infections may result in viral interference, in which one virus blocks the subsequent infection and/or replication of another virus in the host, but until now it is unknown whether this phenomenon results in reduced protection from serially administered attenuated live vaccines in chickens. Interestingly, it has been reported that simultaneous administration of viruses to chickens or turkeys does not result in viral interference. In this study, we investigate how a typical commercial vaccination schedule consisting of a combination of serially administered, live attenuated viral respiratory disease vaccines affects the development and longevity of immunity and protection against homologous challenge.
Avian infectious bronchitis virus (IBV) is a highly contagious pathogen of chickens that replicates primarily in the respiratory tract and also in some epithelial cells of the gut, kidney and oviduct. IBV is a virus member of genus Coronavirus, family Coronaviridae, order Nidovirales. The virus possesses a positive stranded RNA genome that encodes phosphorylated nucleocapsid protein (N), membrane glycoprotein (M), spike glycoprotein (S) and small membrane protein (E). The spike glycoprotein is post-translationally cleaved into two subunits, S1 and S2. The S1 protein forms the N-terminal portion of the peplomer and contains antigenic epitopes mainly within three HVRs. Neutralizing and serotype specific epitopes are associated within the defined HVRs.
Variation in S1 sequences, has been recently used for distinguishing between different IBV serotypes. Diversity in S1 probably results from mutation, recombination and strong positive selection in vivo. Antigenically different serotypes and newly emerged variants from field chicken flocks sometimes cause vaccine breaks. The generation of genetic variants is thought to be resulted from few amino acid changes in the spike (S) glycoprotein of IBV.
In Egypt, isolates related to Massachusetts, D3128, D274, D-08880, 4/91 and the novel genotype; Egypt/Beni-Suef/01 were isolated from different poultry farms. The commonly used IBV attenuated vaccine is H120 while the Mass 41 (M41) strain is commonly used in inactivated vaccines.
In the present study, Egypt/F/03 was isolated from 25-day-old broiler chickens in Fayoum Governorate, identified by Dot-ELISA, RT-PCR and sequenced to determine its serotype. Pathogenicity test to 1-day-old chickens and protection afforded by the commonly used H120 live attenuated vaccine were also performed.