April 01, 2014
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Understanding the current status of avian influenza 2014

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As of early March, there were three circulating strains of avian influenza causing severe disease in humans.

First, influenza A(H5N1) has been causing human disease since 2003 and has caused disease in about 656 people in Asia, Africa and the Middle East, with nearly 390 deaths. The virus has been found in poultry in Europe without recorded human infection. Second, influenza A(H7N9) has infected more than 375 people in China since 2013, with more than 110 deaths. Third, influenza A(H10N8) has caused deaths in two people in China since late 2013.

Donald Kaye

In 13 months, A(H7N9) has caused more than half the number of cases in humans that A(H5N1) has caused during the past 10 years.

Excluding the three current circulating strains, avian influenza infection humans has been documented previously in people with exposure to poultry but generally caused only mild disease. From 1996 to 2007, there were multiple small self-limited outbreaks and one relatively large one caused by avian influenza. The small outbreaks occurred in China, the United Kingdom, Canada and the United States and were caused by A(H7N7), A(H9N2), A(H7N2) or A(H7N3). Most of the patients involved had conjunctivitis, but some had mild influenza-like illnesses. The large outbreak, also self-limited, occurred in the Netherlands in 2003 and involved about 90 workers exposed to diseased poultry infected with influenza A(H7N7). In this outbreak, a veterinarian died and the others developed conjunctivitis. The country most often involved in these outbreaks was China.

Fowl serve as primary reservoir

The ultimate reservoir for influenza A viruses is found in wild aquatic birds such as ducks, geese and swans. The influenza viruses multiply to large concentrations in the intestines of the birds and are shed in their droppings. Poultry (in particular chickens and turkeys) are infected from the wild birds mainly by exposure to their droppings, either directly or by indirect means such as contamination of feed and water.

After introduction into poultry, the virus will readily spread by direct or indirect contact between poultry flocks. Currently, 16 distinct hemagglutinin and at least nine distinct neuraminidase antigenic subtypes are recognized to occur in waterfowl in virtually all combinations. Extensive re-assortment of genes occurs so that all combinations of hemagglutinin and neuraminidase antigens (one of each in each viral strain) can be found over time. This results in a possible 144 distinct hemagglutinin and neuraminidase combinations. With the multiple virus clades or sub-lineages for at least some of the hemagglutinin and neuraminidase subtypes, the actual number of possible viral strains in waterfowl is huge. The avian influenza viruses causing infection in domestic poultry have been predominantly viruses with H5 or H7 antigens.

The water birds generally do not get sick. The influenza A viruses that infect poultry are labeled low pathogenicity (LPAI) or high pathogenicity avian influenza viruses (HPAI) depending on the type of disease produced — little or no disease vs. severe disease. Influenza A(H5N1) is a HPAI and A(H7N9) is a LPAI for poultry, yet both cause severe disease in humans. Thus, the high- or low-pathogenicity property for poultry obviously does not translate to pathogenicity in humans because both of these viruses are quite pathogenic in humans.

Low-pathogenicity virus cause for concern

The recent appearance of LPAI viruses pathogenic to humans (H7N9, H10N8) is of particular concern from control aspects because their circulation in domestic poultry, the main source for human infection, is not clinically detectable. Therefore, farmers have no incentive to look for them or seek veterinary assistance in the absence of economic losses. Humans become the sentinels for disease.

The pandemics and subsequent yearly epidemics of influenza A in humans have been caused by H1, H2 and H3 subtypes combined with N1 or N2 subtypes. However, the pandemic of 1901 was caused by influenza A(H3N8) virus.

Prior avian flu outbreaks

Logic tells us that avian influenza outbreaks in humans must have occurred before 1996 that were undetected. Similarly, there probably were some severe outbreaks before A(H5N1) and A(H7N9). The conditions that exist in China and some neighboring countries that seem to predispose to human acquisition of avian influenza include a high human population density with constant exposure to live poultry in backyard flocks — influenza A(H5N1) or in wet markets influenza A(H7N9) — plus large numbers of water birds that come in contact with the poultry. These conditions have been present for many years. If such outbreaks occurred and went undetected, they must have been self-limited, which begs the question as to whether A(H5N1) and A(H7N9) will be self-limited. Considering the human population size, the H7N9 and H5N1 outbreaks constitute very minor events.

Currently, the epidemiologic surveillance to detect unusual outbreaks of influenza-like illnesses and the laboratory ability to prove the presence of influenza is far more advanced in China and some other countries than it was 20 years ago. It also seems likely that besides improvement with time and modernization, the experience with the severe acute respiratory syndrome, or SARS, epidemic greatly stimulated surveillance systems and diagnostic capabilities worldwide, making it more likely that outbreaks of avian influenza, and for that matter Middle East respiratory syndrome, or MERS, would be detected.

For more information:

Donald Kaye, MD, is a professor of medicine at Drexel University College of Medicine, associate editor of the International Society for Infectious Diseases’ ProMED-mail, section editor of news for Clinical Infectious Diseases and is an Infectious Disease News Editorial Board member.

Disclosure: Kaye reports no relevant financial disclosures.