Low Pathogenic Avian Influenza (LPAI)

Overview
Earlier this year, a human case of H10N3, a low pathogenic strain of bird flu in China drew
concerns worldwide. The World Health Organization has stated, “as long as avian influenza
viruses circulate in poultry, sporadic infection of avian influenza in humans is not surprising”.
This particular statement corroborates a vivid reminder that the threat of an influenza pandemic
is persistent.

Low Pathogenic Avian Influenza (LPAI) has been detected periodically in live bird markets.
Additionally, poultry farms also have exposure risk to LPAI resulting in a mortality up to 50%,
leading to devastating economic consequence for poultry farmers. The significance of LPAI is
underscored by the fact that subtypes H5 and H7 have a potential to mutate into Highly
Pathogenic Avian Influenza (HPAI) variants that can cause severe progressive disease and high
mortality in birds.

LPAI of subtypes H5 and H7 detected in poultry is a notifiable disease listed by the OIE. As
detailed by the OIE Terrestrial Animal Health Code, unusual mortality among wild birds should
also be reported.

Introduction

Avian influenza A viruses have been isolated from more than 100 different species of wild birds
although aquatic birds are the primordial source of LPAI virus, interplaying in the evolution,
maintenance and spread. Anseriformes (waterfowl), Charadriiformes, Strigiformes,
Pelecaniformes (shorebirds), Passeriformes (passerine birds), Accipitriformes (raptors),
Galliformes (poultry), Columbiformes (doves, pigeons) and Psittaciformes (parrots) have been
well known reservoirs. A wide range of mammalian species like swine, mink, domestic horses
and donkeys, domestic cats and domestic dogs are susceptible to LPAI infection.

The incidence of infection appears to be seasonal, with the highest isolation rate being in juvenile
birds in the fall of the year.
Influenza viruses present two surface-protein antigens: haemagglutinin (HA) and neuraminidase
(NA), of which there are 15 and 9 types respectively. Viruses are classified by the particular HA
and NA combination they express. They are identified by AGID test. The virus can be
inactivated by heat (56-60°C) for 60 minutes and is sensitive to pH extremes (1-3 and 10-14).
They can evolve into a number of host-specific and geographic lineages through extensive
genetic reassortment.

Etiology:

Avian influenza (AI) is caused by members of the genus Influenza virus A under the
Orthomyxoviridae family. It is an enveloped, segmented, negative-sense, single-stranded RNA
virus. Avian Influenza is divided into Low-Pathogenic Avian Influenza (LPAI) and High-
Pathogenic Avian Influenza (HPAI), among which LPAI is the most common.

Zoonotic Potential:

The zoonotic potential of LPAI is outlined by the fact that all of the influenza A viruses of
mammalian sources originated from the avian gene pool. Since 2013, out of the total 1,568 LPAI
accumulated human cases in China, 616 were fatal. Most cases had exposure risk to live-poultry
markets. Conjunctivitis and respiratory illness was the most frequent symptom in human cases of
H7N7 LPAI virus infection in the Netherlands during 2003, with 89 confirmed cases and 1
fatality.

Symptoms:
Infection of poultry with LPAI viruses present mildness ranging from ruffled feathers, a drop in
egg production/infertility, sneezing, coughing, ocular and nasal discharge, swollen infraorbital
sinuses, sinusitis, ova rupture (yolk in the abdominal cavity), involution, mucosal edema,
inflammatory exudates in the lumen of oviduct, visceral gout to undetectable clinical signs. LPAI
viruses can spread rapidly through poultry flocks. The morbidity and mortality is usually low
unless accompanied by infections or aggravated by stress.
Transmission

Virus is shed in faeces (faecal-oral transmission) and respiratory secretions of birds. The possible
sources of transmission are contaminated surfaces and environments, mechanical vectors (flies),
broken infectious eggs and contaminated fomites.

The virus is transmitted by feco-oral contamination, ocular secretions, mucous membranes and
consumption of raw poultry/blood from infected birds. Concurrently, they can be spread through
contaminated feed and water. Their ability to survive for longer period in low temperatures foster
the rapid spread from one farm to another.

Migratory birds carry the virus through long distances along their seasonal migratory flights
from one country to another.

Epidemiology:

Migration routes play an imperative role in viral epidemiology. This allows viral subtypes to
differ according to intermix at stopover sites and nesting sites during migration, which creates
the threat of viral recombination and spillover effects.

It is likely for an H5 or H7 strain of LPAI to incite evolution into HPAI in poultry.

Swine serve as an exemplary medium for viral recombination of LPAI subtypes. LPAI infection
in mammalian hosts emulate conjunctivitis and respiratory disease of variable pathogenicity.

Sporadic natural have occurred in dogs with H5 Eurasian HPAI viruses, H3N8, H3N2 and in cat
with H7N2 infection. Such experimental infections occurred after aerosol or respiratory
exposure, ingestion of infected chickens, or contact exposure. There is evidence that most new
human pandemic strains and variants have originated in southern China, as exemplified by
Webster et al. and pigs serving as the intermediate host in genetic exchange between influenza
viruses in avian and humans. Sporadic infections by any subtype of LPAI viruses can occur, but
H9N2 LPAI is common in commercial and live bird market poultry in Asia, the Middle East, and
North Africa.
During a 10-year surveillance period in the Netherlands, LPAI viruses of subtypes H3N8 and
H4N6 were predominantly detected in wild ducks, in particular mallards, but rarely detected in
poultry. In contrast, LPAI viruses of subtypes H8N4 and H9N2 were most frequently detected in
Dutch poultry but only sporadically detected in wild birds. These findings suggest that
transmission to poultry is selective and is likely influenced by viral factors that determine host
range.

Differential diagnoses:

Infectious bronchitis, Infectious laryngotracheitis, Lentogenic strain of Ranikhet Disease,

mycoplasmosis, Fowl cholera, aspergillosis, and heat exhaustion.

Required samples during a LPAI outbreak:

● Oropharyngeal, tracheal, and/or cloacal swabs from live birds

● Feces can be substituted in place for cloacal swabs

● Postmortem samples: trachea, lungs, air sacs, intestine, spleen, kidney, brain, liver, and heart

● Whole blood or serum for serological test

Prevention and Control measures:

1. Quarantine birds for 21 days before mixing them in the flock, in accordance with OIE’s
Terrestrial Animal Code
2. Biosecurity and disinfection protocol is quintessential to control outbreaks. Disinfecting
with bleach, ethanol, quaternary ammonium compounds, aldehydes, phenols, acids,
povidone iodine, or ionising radiation is suggested. Tools, equipment should be properly
disinfected. Changing of shoes and use of protective equipment and footbath should be
mandatory in a poultry facility.
 3. Efforts should be made to limit interaction between wild birds and pigs since LPAI can
interact with swine and form a new viral subtype
4. Proper carcass, manure and litter disposal of dead birds.
5. Reduction of the risk of introduction of virus from wild bird/live markets to a poultry
farm
6. LPAI vaccines are available for domestic poultry although concerns on the efficacy is
disputable (long-term circulation of the virus in a vaccinated population may result in
both antigenic and genetic changes in the virus). However, vaccination strategies can be
effective as an emergency measure in an outbreak or as a routine measure in an endemic
area.
7. Bird proofing and pest control to shield interactions of domestic birds with wild birds
through confinement rearing
8. Properly cooking poultry meat to inactivate the virus: 70 °C for 3.5 seconds.
9. Regulatory measures such as surveillance, tracing and reporting to the Veterinary
authorities in case of an outbreak
10. Financial compensation scheme/ insurance policies to the poultry farmers for the losses
incurred as a result of culling during outbreaks.

Data Analysis of LPAI viruses worldwide:

Note: All graphs are original works by the author

Why is LPAI of a concern?

LPAI outbreaks are of concern in poultry of the following reasons:

1. Potential of LPAI H5 and H7 to evolve into highly pathogenic viruses who progresses
into rapid spread and death
2. Unproductivity and infertility of flocks progressively leading to overwhelming economic
losses for the poultry farmer
3. Trade restrictions and culling/“stamping out” following a H5 or H7 outbreak
4. Possibility of spillover effect/intermixing of the avian influenza A viruses to transmit to
humans and other mammalian hosts.

References:

Alexander D.J., Brown I.H. (2009). History of highly pathogenic avian influenza. Revue
Scientifique et Technique (International Office of Epizootics), 28(1), 19-38.
 Bergervoet, S. A., Germeraad, E. A., Alders, M., Roose, M. M., Engelsma, M. Y.,
Heutink, R., Bouwstra, R., Fouchier, R., & Beerens, N. (2019). Susceptibility of Chickens to
Low Pathogenic Avian Influenza (LPAI) Viruses of Wild Bird- and Poultry-Associated
Subtypes. Viruses, 11(11), 1010.

Centers for Disease Control and Prevention. (2021). Avian Influenza. Accessed June 19.
Retrieved from: https://www.cdc.gov/flu/avianflu/index.html

Edwards S. (2006). OIE laboratory standards for avian influenza. Developments in

Biologicals, 124, 159-162

Mittal, N., & Medhi, B. (2007). The bird flu: a new emerging pandemic threat and its
pharmacological intervention. International journal of health sciences, 1(2), 277–283.

MSD Veterinary Manual. (2021). Avian Influenza. Accessed June 20. Retrieved from:
https://www.msdvetmanual.com/

Webster, R. G., Bean, W. J., Gorman, O. T., Chambers, T. M., & Kawaoka, Y. (1992).
Evolution and ecology of influenza A viruses. Microbiological reviews, 56(1), 152–179.

World Animal Health Information System - Wild (WAHIS-Wild) Interface. Accessed

June 20. Retrived from: http://www.oie.int/wahis_2/public/wahidwild.php/Index

World Organization for Animal Health. Accessed June 20. Retrieved from:
https://www.oie.int/en/disease/avian-influenza/