22 March 2018
Will Egypt unleash another flu pandemic?
Published online 12 March 2015
Avian flu cases have soared in Egypt, and now experts say bad practices, lack of information and lax policies could lead to an H5N1 pandemic.
Hardly a week has passed in 2015 without new cases of human H5N1 influenza infection occuring in Egypt. With at least 46 cases and 13 fatalities in just two months, the number is higher than those reported in the whole of 2014.
So, what is the status of avian flu in Egypt?
The story of H5N1 influenza in Egypt dates back to early 2006, when the first human case was detected in Qalyubia governorate shortly after the first outbreak that affected domestic poultry.
Generally, influenza viruses are a large group of pathogens that peacefully inhabit the guts of wild migratory waterfowl. These viruses are continuously evolving and occasionally acquire certain genetic changes that enable them to switch hosts and gain a foothold in domestic birds and mammals. Some are endowed with the right key combinations for decoding human cells, causing infections that can vary from isolated and mild disease to devastating pandemics.
In case of Egypt’s first outbreak, it is believed that this H5N1 virus was a passenger on-board of a wild migratory duck1 visiting Damietta, most likely from Eurasia. Once in Egypt, the newly-arrived H5N1 virus found a hospitable host that allowed it to spread and evolve into a genetically distinct group of “naturalised” viruses. The disease was declared endemic in 2008, and after this recent surge of human cases, Egypt now has the highest number of confirmed human H5N1 cases worldwide.
Fortunately, so far, transmission of H5N1 viruses from chickens to humans was very inefficient and no sustained human-to-human transmission has been detected. If these H5N1 viruses becoming human-adapted, and with the current volume of air passengers, an isolated outbreak could turn into a pandemic in no time.
Pandemics don’t just cause deaths, which we know through modeling studies will be highest in developing countries, but have hefty economic tolls. A recent PNAS study4 has estimated the cost of an influenza pandemic to be somewhere between $374 billion to $7.3 trillion depending on its severity.
In an attempt to uncover mutations that could confer H5N1 human transmissibility, two Nature5 and Science6 studies forced some engineered forms of this virus to adapt to ferrets, a popular animal model for human influenza. Such studies give deep insights into the biological barriers that are keeping H5N1 viruses locked up in their avian hosts. An important finding of these experiments was that most H5N1 strains circulating in Egypt are 2-3 mutations away from those ferret transmissible viruses. So now Egypt is considered as an epicenter7, where the spark of an H5N1 pandemic could ignite.
Vague and volatile situation
The WHO says the current global influenza situation is volatile, especially in Egypt.
According to the WHO, the current global influenza situation is volatile, particularly H5N1 in Egypt. The recent sudden surge is raising questions, and not just among the scientific community.
The preliminary findings released by scientists affiliated with the Food and Agriculture Organization (FAO) identified mutations, in a glycoprotein carried on the virus’ outer surface called hemagglutin (HA), known to enhance adaptation to humans, in the genomes of 52 contemporary poultry isolates. Also, scientists from the US Naval Medical Research Unit 3 (NAMRU-3), Egyptian Ministry of Health and the National Research Center have also studied sequences from four recent human isolates and found no evidence of changes known to be associated with enhanced pathogenicity.
The significance of these observations remains unclear, and we desperately need to learn more about these H5N1 viruses. There is also a need to investigate whether there is a role for co-circulating H9N2 strains in the current surge of human influenza cases.
So, why is H5N1 rampant in Egypt?
The H5N1's place in Egypt is complex and multifaceted, but the continued rise in flu-related economic and human losses in Egypt can be traced back to three main factors.
First is the influenza biology, which we have absolutely no control on. Influenza viruses will continue to evolve as long as their transmission cycle remains unbroken – which translates into an emergence of novel flu variants. Egypt is also considered a hotspot8 for influenza reassortment, and the current co-circulation of H5N1 and H9N2 strains provides a gene pool that is continuously being shuffled around; it could spit out a whole new beast any time. Our only chance in outpacing this virus relies on continuously monitoring its genetic changes by boosting our surveillance efforts. Scientists can make educated guesses and advise policymakers to adopt timely counteractive measures, but they need information.
Another contributing factor is environmental. The majority of Egyptians are tightly packed in rural villages along the River Nile. Raising poultry in the backyards and trading them in live bird markets is a staple in this largely rural culture, which exposes humans to a greater risk of H5N1 transmission from sick birds.
The latest FAO report says 87% of H5N1 outbreaks reported over the last few months occurred in household poultry, and the majority of human H5N1 cases had previously been exposed to poultry.
Public awareness campaigns, which penetrate all layers of society, could significantly help in promoting healthier behaviour.
Finally, if properly applied, the method of choice for controlling H5N1 outbreaks is via testing and culling of all infected birds. But this approach failed to contain the disease when it was firstly reported in Egypt back in 2006.
Mass vaccinations as a strategy also failed for many reasons. Vaccination can help in reducing H5N1 transmission only if it is combined with other disease control measures, such as active surveillance, enhanced biosecurity measures and sound outbreak management.
Vaccinating household poultry can be very challenging, as it relies on a door-to-door approach and the mixture of bird species reared in the backyards may not respond uniformly to the vaccine. For a long time, vaccinating commercial poultry relied on imported vaccines1 that did not offer adequate cross-protection against locally circulating strains. Eventually, a vaccine based on a local Egyptian strain was made, but not mass-produced to satisfy the market needs.
As well, commercial producers don’t receive enough compensation for their bird losses, so they tend not to report flu outbreaks to their local government agencies. They already receive very limited veterinary supervision; they are left on their own to choose between various vaccine types and protocols, which results in varying degrees of coverage among poultry flocks across the country.
Some farmers feed antivirals to their healthy chickens, a practice known to increase the risk of generating drug-resistant flu strains.
Laws to regulate live poultry trade have been drafted, but never implemented. For any national influenza control plan to be effective, all of the above need to be revisited.
Influenza is as unpredictable as ever. Scientists can never pinpoint when or where a pandemic may arise, or even which strain will be the culprit. However, several scientific findings confirm that the Egyptian H5N1 situation is a bubbling volcano. Until universal vaccines, a current active area of research, become available, it is imperative to ensure that human H5N1 vaccines are at arm’s length. We know that influenza vaccines take about six months to manufacture. Our experience with the most recent 2009 H1N1 pandemic tells us that the rush production of billions of pandemic vaccine doses will not guarantee a timely delivery, particularly to developing countries. We need to have a system in place to ensure smooth supply in the event of a pandemic. Vaccinating Egyptians who are at high risk of H5N1 infection is also an approach worth considering.
It is in the best interest of the administration to forge a pandemic preparedness plan that brings everybody to the table, including government agencies and private industries, locally and internationally. We need to get prepared for the worst case scenario.
Islam Hussein is a researcher and virologist at MIT, Massachusetts. He is currently involved in several projects focused on identifying, tracking and investigating any genetic changes that might lead to the generation of potentially pandemic influenza strains.
- Kayali, G. et al. Do commercial avian influenza H5 vaccines induce cross-reactive antibodies against contemporary H5N1 viruses in Egypt. Poultry Science http://dx.doi.org/10.3382/ps.2012-02637 (2012)
- Kayali, G. et al. Active Surveillance for Avian Influenza virus, Egypt, 2010-2012 Emerging Infectious Diseases http://dx.doi.org/10.3201/eid2004.131295 (2014)
- Mokhtar, R.G. et al. Avian Influenza A(H5N1) and A(H9N2) Seroprevalence and risk factors for infection among Egyptians: A prospective, controlled seroepidemiological study. The Journal of Infectious Diseases http://dx.doi.org/10.1093/infdis/jiu529 (2014)
- Pike, J. et al. Economic optimization of a global strategy to address the pandemic threat. PNAS http://dx.doi.org/10.1073/pnas.1412661112 (2014)
- Imai, M. et al. Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature http://dx.doi.org/10.1038/nature10831 (2012)
- Herfst, S. et al. Airborne transmission of Influenza A/H5N1 virus between ferrets. Science http://dx.doi.org/10.1126/science.1213362 (2012)
- Neumann, G. et al. Egyptian H5N1 Influenza viruses - cause for concern? PLOS Pathogens http://dx.doi.org/10.1371/journal.ppat.1002932 (2012)
- Fuller, L.T. et al. Predicting hotspots for Influenza virus reassortment. Emerging Infectious Diseases. http://dx.doi.org/10.3201/eid1904.120903 (2013)