Clinical Profiles

Infectious bronchitis virus (IBV) is a highly contagious avian Gammacoronavirus that affects mainly chickens (Gallus gallus) but can circulate in other avian species. IBV constitutes a significant threat to the poultry industry, causing reduced egg yield, growth and mortality levels that can vary in impact. The virus can be transmitted horizontally by inhalation or direct/indirect contact with infected birds or contaminated fomites, vehicles, farm personnel and litter (Figure 1). The error-prone viral polymerase and recombination mechanisms mean diverse viral population results, with multiple genotypes, serotypes, pathotypes and protectotypes. This significantly complicates control and mitigation strategies based on vigilance in biosecurity and the deployment of vaccination.

Rift Valley fever (RVF) is caused by infection with Rift Valley fever virus (RVFV), a mosquito-borne RNA virus that affects both humans and livestock species. Humans can also acquire infection from contact with infected animals and contaminated bodily fluid. Veterinary vaccines are available for use in livestock, but no vaccines have been approved for humans to date. The virus is currently endemic in most sub-Saharan regions of Africa but numerous incursions into Middle Eastern countries and islands in the Indian Ocean, such as Mayotte (an overseas Department of France), have occurred in the past decade. The risk of further geographical expansion is high and therefore additional investigation is warranted to better understand disease transmission and pathogenic mechanisms to develop threat mitigation strategies.

Avian reoviruses (ARVs) have a significant economic impact on the poultry industry, affecting commercial and backyard flocks. Spread feco-orally, or vertically, many do not cause morbidity, but pathogenic strains can contribute to several diseases, including tenosynovitis/arthritis, which is clinically the most significant. The last decade has seen a surge in cases in the US, and due to ongoing evolution, seven genotypic clusters have now been identified. Control efforts include strict biosecurity and vaccination with commercial and autogenous vaccines. Research priorities include improving understanding of pathogenesis and developing new vaccines guided by ongoing molecular and serologic surveillance.

West Nile virus (WNV) is a positive-sense single-stranded RNA virus belonging to the Flaviviridae family and is maintained in an enzootic cycle between avian hosts and mosquito vectors. Humans, horses and other mammals are susceptible to infection but are dead-end hosts due to a low viraemia. The disease can manifest itself in a variety of clinical signs and symptoms in people and horses from mild fever to severe encephalitis and morbidity. There are no vaccines licensed for human protection, but parts of Europe, North America, Africa and Australia have vaccines commercially available for horses.

Usutu virus (USUV) is an emerging arbovirus belonging to the family Flaviviridae, genus Flavivirus. It is maintained in an enzootic cycle, with mosquitos as the vector and birds as the main amplifying host. Humans, and other mammals such as horses, are dead-end hosts. The virus was originally detected in sub-Saharan Africa, but in the past two decades has spread across Europe. In certain bird species, such as the Eurasian blackbird (Turdus merula), USUV is extremely virulent and can be fatal. Human infection is rare and often asymptomatic, but multiple short-term neurological diseases have been reported, highlighting its public-health risk.

Swine influenza is an acute respiratory disease of swine caused by swine influenza A virus (SwIAV). The ability of SwIAV to spread bidirectionally from animals to humans (zoonotic), and from humans to animals (reverse zoonotic), drives coinfection that can result in gene segment exchange and elevates the risk of generating viruses with pandemic potential. Compared to human-origin influenza A viruses, current data indicate a greater diversity amongst circulating SwIAVs, with three major subtypes (classified by haemagglutinin and neuraminidase) circulating globally in swine (H1N1, H1N2 and H3N2). The lack of protection afforded by human seasonal influenza vaccines against SwIAVs exacerbates the risk associated with reassortment of human, swine and potentially avian viruses. As such, global monitoring of SwIAVs is important for both human and animal health as they represent a true ‘One Health’ challenge with pandemic potential.

Japanese encephalitis (JE) is an infection that occurs predominantly in Asia and the Pacific Islands. It is transmitted by mosquito bites, with the main vector being Culex tritaeniorhynchus, and is maintained in enzootic cycles involving pigs, wild birds and mosquitoes. JE is caused by infection with Japanese encephalitis virus (JEV), a zoonotic pathogen that also causes disease in mammals such as pigs and horses. In humans, most symptoms are mild or flu-like but can progress to encephalitis. Pigs are considered amplification hosts, and sows may have gestational complications. Horses may exhibit neurological signs. Detection of the virus can be confirmed by serological or molecular laboratory tests. Vaccination offers protection against JEV infection in humans, pigs and horses. Whilst there is no effective treatment of JE, human cases may require hospitalization for supportive therapy, which may include administration of fluids, oxygen and medication to treat symptoms.

Staphylococcus epidermidis is the most abundant commensal bacterium of human skin. Despite protecting us from foreign invaders, S. epidermidis itself exploits human vulnerability when given the opportunity. Such opportunities arise when patients are immunocompromised or when biomedical implants present an opportunity to colonize the surface and form biofilms. S. epidermidis is one of the most frequently isolated organisms from implanted devices and from bloodstream infections. However, S. epidermidis infections are often recalcitrant to antibiotics because of biofilm-associated antibiotic tolerance. Furthermore, the emergence and spread of nearly pan-resistant strains is a considerable health concern. Symptoms can be subclinical, making diagnosis challenging, and treatment with antibiotics is inefficient. For now, infection prevention remains the best strategy available.

Newcastle disease (ND) is a highly contagious disease of poultry caused by virulent avian paramyxovirus-1 (APMV-1) (previously termed avian avulavirus-1 and avian orthoavulavirus-1). APMV-1 is endemic in poultry in many developing countries, whilst outbreaks still occur in developed countries, affecting both commercial and backyard flocks. ND outbreaks can have substantial economic consequences due to high mortality rates and the imposition of trade restrictions. APMV-1 nucleic acid can be detected from swabs or tissues of suspected cases by PCR. Evidence of infection or vaccination may be demonstrated by the presence of specific antibodies against HN in serum samples. No anti-viral treatments exist, but vaccines are available, although there are currently concerns over their efficacy.

Rifampicin (also known as rifampin) inhibits RNA synthesis, and is used to treat tuberculosis, leprosy, staphylococcal infections and legionnaires’ disease. It can also protect at-risk populations from   Haemophilus influenzae   type b and   Neisseria meningitidis  . It is a polyketide antibiotic and is on the World Health Organization (WHO) list of essential medicines due to its critical importance to human medicine. The adverse effect of liver toxicity is controlled by testing during prolonged treatment regimes. Rifampicin’s red–orange colour can result in the colouration of sweat, tears and urine. Resistance to rifampicin arises from mutation of the target RNA polymerase or ADP ribosylation of the antibiotic or efflux. Mycobacteria may become singularly resistant to rifampicin or as part of multidrug or extensive drug resistance.

Avian influenza viruses (AIVs) are classified as either low pathogenicity (LP; generally causing sub-clinical to mild infections) or high pathogenicity (HP; capable of causing significant mortality events in birds). To date, HPAIVs appear o be restricted to the haemagglutinin (HA) glycoprotein H5 and H7 AIV subtypes. Both LPAIV and HPAIV H5 and H7 AIV subtypes are classified as the causative agents of notifiable disease in poultry. A broad range of non-H5/non-H7 LPAIVs also exist that have been associated with more severe disease outcomes in avian species. As a result, the constant threat from AIVs causes significant economic damage in poultry production systems worldwide. The close proximity between mammalian and susceptible avian species in some environments provides the opportunity for both inter-host transmission and mammalian adaptation, potentially resulting in novel AIV strains capable of infecting humans.

Tick-borne encephalitis (TBE) is caused by a neurotropic flavivirus, transmitted by the bite of Ixodes species tick vectors, and is increasing in incidence and expanding its geographical range throughout Eurasia and the Far East. Most infections are asymptomatic. However, between 2 and 30 % of cases may develop into severe neurological disease, long-term neurological sequelae or death. Diagnosis is based upon clinical signs of neurological disease and demonstration of virus-specific IgM and IgG antibodies. There is no specific antiviral treatment and supportive care is required for the various manifestations of disease. Vaccination is an effective way of preventing disease.

The Gram-negative bacterium   Actinobacillus pleuropneumoniae   is the causative agent of pleuropneumonia in pigs, its only known natural host. Typical symptoms of peracute disease include fever, apathy and anorexia, and time from infection to death may only be 6 h. Severe lung lesions result from presence of one or two of the ApxI-III toxins. Control is through good husbandry practice, vaccines and antibiotic use. Culture and presence of the species-specific apxIV gene by PCR confirms diagnosis, and identification of serovar, of which 19 are known, informs on appropriate vaccine use and epidemiology.

Carbapenems are potent members of the β-lactam family that inhibit bacterial cell-wall biosynthesis inhibitors . They are highly effective against Gram-negative and Gram-positive drug-resistant infections . As such, carbapenems are typically reserved as an antibiotic of last resort. The WHO lists meropenem as an essential medicine. Nausea and vomiting are reported in ≤20% of carbapenem recipients, with 1.5% suffering seizures. Enzymatic hydrolysis of the β-lactam ring is the main driver of clinical resistance. These enzymes can be classified as Class A, B and D. Classes A and D are serine β-lactamases, whereas Class B rely on metal-mediated hydrolysis, typically through zinc.

Whooping cough (pertussis) is a highly contagious respiratory bacterial infection caused by   Bordetella pertussis   and is an important cause of morbidity and mortality worldwide, particularly in infants.   Bordetella parapertussis   can cause a similar, but usually less severe pertussis-like disease.   Bordetella pertussis   has a number of virulence factors including adhesins and toxins which allow the organism to bind to ciliated epithelial cells in the upper respiratory tract and interfere with host clearance mechanisms. Typical symptoms of pertussis include paroxysmal cough with characteristic whoop and vomiting. Severe complications and deaths occur mostly in infants. Laboratory confirmation can be performed by isolation, detection of genomic DNA or specific antibodies. Childhood vaccination is safe, effective and remains the best control method available. Many countries have replaced whole-cell pertussis vaccines (wP) with acellular pertussis vaccines (aP). Waning protection following immunisation with aP is considered to be more rapid than that from wP. Deployed by resource-rich countries to date, maternal immunisation programmes have also demonstrated high efficacy in preventing hospitalisation and death in infants by passive immunisation through transplacental transfer of maternal antibodies.