This article is more than 5 years old. Information may no longer be current.

Avian influenza H5N1 and H7N9: The simmering epidemics

Issue: June 2015

ByDonald Kaye, MD, MACP

Add topic to email alerts

Receive an email when new articles are posted on

Please provide your email address to receive an email when new articles are posted on .

Subscribe

Added to email alerts

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

Back to Healio

We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com.

Back to Healio

The world has now had more than 10 years of experience with human infection with avian influenza A(H5N1), and a little more than 2 years of experience with avian influenza A(H7N9). While the H5N1 outbreak appears to have generated more news headlines and scientific interest than the H7N9 outbreak, H7N9 would seem to be a much greater potential threat in terms of human disease.

Human infection

Disease associated with H5N1 infection in humans was first recognized in Hong Kong in 1997, and then reappeared in Vietnam in December 2003. It subsequently spread with yearly outbreaks involving humans in many countries in Asia, Africa and the Middle East (including Azerbaijan, Bangladesh, Cambodia, China, Djibouti, Egypt, Indonesia, Iraq, Laos, Myanmar, Nigeria, Pakistan, Thailand and Turkey). Sporadic outbreaks, affecting birds only, occurred in these areas as well as in Europe. Over the duration of the outbreak, most human cases have occurred in Indonesia, Vietnam and Egypt. In 2014 and 2015, most of the H5N1 cases were in Egypt. As of mid-April, since the onset of the epidemic, there have been more than 820 human cases and 440 deaths (53% mortality) worldwide, but the mortality rate has been only 33% in Egypt, compared with 67% in the rest of the world. Since 2003, there has been an average of 68 cases worldwide per year (45-115 cases annually). However, in just the first 3 months of 2015, 125 cases have been reported by WHO — the highest number of yearly cases ever. The previous peak of 115 cases worldwide occurred in 2006. Further data indicate that as of mid-April, there have been more than 140 cases in Egypt alone this year. This situation clearly needs to be monitored diligently.

Donald Kaye

The H7N9 outbreak in humans started in February 2013, and as of May 1, 2015, there have been 659 human cases. All of these have been acquired in mainland China. Twenty cases, although acquired in China, occurred in Hong Kong (13 cases) and in other countries (seven cases). The mortality rate is difficult to determine because of the presence of mildly ill or asymptomatic cases, but is reported to be about 30%.

Both viruses cause most of their human infections in colder weather. Thus, the H7N9 outbreak has been very active in early 2015, and the H5N1 outbreak, which seemed to be relatively stable, has picked up its pace compared with previous years. With warmer weather, cases will decrease with both viruses.

Pathogenicity

The two avian influenza strains are very different from each other. H5N1 has high pathogenicity for poultry, meaning that many of the infected birds become ill and die. Therefore, an outbreak in the flock becomes apparent, and is likely to be reported. On the other hand, H7N9 is of low pathogenicity in poultry (or rather subclinical); in the absence of clinical disease and of economic significance, it is less likely to be reported. Historically, human infection with H5N1 usually has occurred after contact with sick or dead poultry, typically in backyard flocks, while most human infections with H7N9 have occurred after exposure to poultry in “wet” animal markets.

H5N1 has mainly infected healthy people aged younger than 50 years, with a median age of 18 years. Females are more commonly infected than males. Clusters of cases have occurred among blood-related family members (ie, parent and child or brother and sister, rather than husband and wife), especially those living in the same household. Most of these have resulted from exposure to the same infected poultry. Some clusters have apparently occurred from limited person-to-person transmission. It is unknown if the blood relationship is due to genetic or other factors.

In contrast, infection with H7N9 has occurred primarily in older male adults (aged older than 55 years) with underlying diseases. When it does occasionally infect children, they tend to have milder or asymptomatic disease. Small clusters of cases have occurred with H7N9, usually in families. While there has been no evidence of human-to-human transmission of H7N9, it cannot be excluded.

The mortality rate in documented cases is high for both strains of avian influenza — more than 50% for H5N1 and about 30% to 37% for H7N9. However, these mortality figures for H7N9 are probably too high. Unlike H5N1, asymptomatic as well as mildly symptomatic cases of H7N9 have been observed with some frequency. Therefore, cases of H7N9 are underreported. Although previous studies have found little evidence of frequent asymptomatic or mild H5N1 disease, a very recent seroprevalence study from Egypt suggested asymptomatic or mild infections with H5N1 are common. The authors reported a 2% seropositivity for H5N1 among Egyptians exposed to poultry. The titers were generally low, and the authors pointed out that their results cannot be extrapolated to other countries where H5N1 occurs. However, there have been similar reports from Thailand and Nigeria.

Disease prevention

Control of the spread of influenza in poultry has depended mainly on destruction of infected flocks. Vaccines have been used preventively but are expensive and difficult to maintain. Identification of infected flocks is easy with H5N1 but difficult with H7N9, as there is no overt illness in the H7N9-infected birds, requiring active surveillance. Thus, humans become the sentinel for H7N9. Public health measures, such as warning people not to come in contact with sick poultry in the case of H5N1, and the closing of live poultry markets in the case of H7N9, are important. There is a clear-cut seasonal relationship with both strains. Most cases of H7N9 have occurred in the early months of 2013, 2014 and 2015.

Pandemic potential

Neither virus is easily transmitted from poultry to humans, nor are they easily transmitted from person to person. However, both H5N1 and H7N9 have pandemic potential. They can become more easily transmissible either through mutation or recombination with a human influenza virus. H5N1 has been circulating in wild water birds and poultry for many years over a large land mass, infecting huge numbers of poultry and people across Asia, the Middle East and Africa, yet it has not caused a pandemic. It probably never will. H7N9 is potentially more dangerous because it circulates asymptomatically in poultry and is therefore not obvious when it infects a flock. In the United States and other highly industrialized countries, there are relatively few backyard flocks, and H5N1 would be rapidly identified and contained in a commercial poultry farm as well as a backyard flock. H7N9 would be more difficult to suspect or identify in a flock.

A recent development was the appearance of H5N2 and other H5 (hemagglutinin)-containing viruses in poultry in many states in the U.S. and in Canada. These strains were found first in wild birds and then in poultry starting in late 2014 and early 2015; phylogenetic analysis revealed that they were widely distributed, apparently circulating in Asia, Europe and now also North America. This calls for further epidemiological investigations into their mode of intercontinental spread. At present, the North American strains do not seem to constitute a significant risk to humans as they do not contain genetic markers, which have been linked to transmission to humans. However, they are an economic hardship to poultry growers and because of the nature of influenza genome, pose a risk, albeit low, for humans.

References:

FluTrackers.com. Egypt – 2015 WHO/MoH/Provincial Health Depts H5N1 Confirmed Case List. https://flutrackers.com/forum/forum/egypt/h5n1-tracking-egypt/720309-egypt-2015-who-moh-provincial-health-depts-h5n1-confirmed-case-list. Accessed May 7, 2015.
FluTrackers.com. FluTrackers 2013-15 Human Case List of Provincial/Ministry of Health/Government Confirmed Influenza A(H7N9) Cases with Links. https://flutrackers.com/forum/forum/china-h7n9-outbreak-tracking/143874-flutrackers-2013-15-human-case-list-of-provincial-ministry-of-health-government-confirmed-influenza-a-h7n9-cases-with-links. Accessed May 7, 2015.
Gomaa MR, et al. J Infect Dis. 2015;doi:10.1093/infdis/jiu529.
WHO. Influenza. Cumulative number of confirmed human cases of avian influenza A(H5N1) reported to WHO. http://www.who.int/influenza/human_animal_interface/H5N1_cumulative_table_archives/en/. Accessed May 7, 2015.

For more information:

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