Is the Ebola epidemic really coming to an end?

The initial announcement of the latest outbreak of Ebola was on 25 March, in Guinea – part of West Africa, where the virus has never been known in the population, meaning that they would have been totally unprepared for such an epidemic to occur. As of 14 April, a total of 202 clinical cases of Ebola virus disease (EVD) – which includes confirmed and suspected cases – have been reported in Guinea, Liberia, Mali and Sierra Leone, including 128 deaths. Researchers have also determined that it is genetically similar to Ebola Zaire, but it is a brand new strain. This is significant because it shows that this Ebola epidemic has arisen separately from the previous epidemics in Central Africa. The Ministry of Health of Guinea has announced that with the decrease in the number of new cases, this latest epidemic of EBV is coming to an end; however, the fact that the latest wave of cases involved people in Conakry, Guinea’s capital with an airport, is slightly worrying.

Ebola is a fairly lethal virus, which is actually part of the reason why it hasn’t turned into a pandemic yet; it kills its hosts too quickly – up to 90% of the infected will be dead in a couple of weeks after manifesting symptoms – for them to pass on the virus very far. The other reason is because it is spread via contact with an infected victim’s fluids, unlike the flu, which can spread via air. And that is the next fear – that the virus will mutate such that it can be transmitted through the air, which was suspected to have happened with another species of Ebolavirus known as Reston virus, of the book The Hot Zone fame. On the bright side, it seems that the more people the Ebola virus infects, and the more it adapts to humans, the less lethal it gets.


This is why I bring sanitizing wipes on cruise ships

News broke recently where more than 600 people on a cruise ship fell ill with gastrointestinal symptoms such as vomiting and diarrhea. Unfortunately, the only unusual thing about this is that such a large percentage of the passengers became sick – from 2008 to 2013, there were 83 cruise ships that the CDC reported as having gastrointestinal illness outbreaks. Cruise ships from other countries also reported similar outbreaks.

Going by the symptoms presented, the pathogen in question is most likely to be norovirus (Norwalk virus). This virus is able to spread from person-to-person, and by contact with surfaces contaminated by the virus, such as door handles, elevator buttons, and cutlery. Norovirus spreads even faster in where large groups of people are kept close together in enclosed spaces such as cruise ships and schools. The best way to counteract the spread of norovirus is to sanitize high contact surfaces and minimize item exchange between people as much as possible with chlorine and chlorine-based cleaners; alcohol-based cleaners have less of an effect on noroviruses because they do not have a lipid envelope which could be disrupted by alcohol. People should avoid touching their faces, particularly around the mouth, nose or eyes, and wash their hands prior to eating.

Most sanitizing wipes, unfortunately, are not chlorine-based; nevertheless, they act as a reminder to myself to wash my hands; I also use them to wipe my cutlery and door handles, and throw them away once used. Call me a germaphobe, but I do like to stay healthy as much as I can, and I really don’t fancy spending my days on a cruise ship vomiting or running to the toilet to vacate my bowels every hour.

(Although there were about 20,000 U.S. cruises from 2008 to 2013, not all of the outbreaks occurring may have been reported; only cruises of 3-21 days length, with more than 100 passengers and more than 3% of the passengers ill, coming from an international port to a U.S. port, are required to be reported by the CDC. As the average number of passengers on a cruise ship tends to hover around 100, this means that about half of the 20,000 cruises are not reported upon; if we take into account the other conditions mentioned, it is likely that the number of cruises within the purview of the outbreak updates by the CDC falls even further.)


U.S. Department of Transportation Maritime Administration, North American Cruise Statistical Snapshot, 2011

Coronas are not (just) beers.

Severe acute respiratory syndrome (SARS), as its name suggests, is a respiratory illness Coronaviridaewhich largely targets the upper respiratory tract, with its defining symptom being a fever with a temperature of 38°C (100.4°F) or higher. Other symptoms include flu-like symptoms such as chills, muscle aches, headaches, fatigue and sore throat. As the illness progresses, patients may then develop a dry cough and/or shortness of breath, followed by pneumonia, respiratory failure, and acute respiratory distress, potentially leading to death. The incubation period of the virus is about 2-13 days, with a mean of 5 days.

SARS is caused by the virus SARS-coronavirus (SARS-CoV). This virus was responsible for the SARS epidemic of November 2002 to July 2003. At the end of epidemic, there were a total of 8273 cases, and 775 deaths. The case fatality rate – that is, the number of deaths as a ratio of the number of cases – has been stated as being somewhere between 9.6%-11%, depending on the definition of case fatality rate used. Although the case fatality rate was somewhat high (the case fatality rate for the recent 2009 influenza pandemic was about 0.03%), the number of deaths was likely mitigated by the fact that many of the people infected by SARS-CoV had access to very good supportive/palliative healthcare, helping their immune systems to fight off the virus.

An electron micrograph of a SARS-CoV virion. Image by CDC/ C. D. Humphrey and T. G. Ksiazek.

An electron micrograph of a SARS-CoV virion. Note the distinctive “corona”, which gives the family Coronaviridae its name. Image by CDC/ C. D. Humphrey and T. G. Ksiazek.

SARS-CoV is a coronavirus, so named for the protein spikes that surround this spherical virus, which looks like a corona. Although SARS-CoV was initially suspected to have originated in masked palm civets – which were commonly sold in markets in China, where some of the first cases of SARS was reported – it was finally traced back via phylogenetics to the Chinese horseshoe bat. Both the human and civet cat SARS-CoV were found to have descended from bat coronaviruses.

Although there are no cures or vaccines currently available for SARS-CoV, there is a vaccine in development by MassBiologics, cooperating with researchers at NIH and the CDC. The 2002-2003 epidemic was successfully controlled by quarantining those infected, and suspected to be infected by the virus, and is a viable alternative solution in countries where such measures can be effectively implemented. The determination of the incubation period of the virus was a vital part of this counter-measure, as it enabled health officials to determine how long had to elapse before people who had come into contact with SARS patients could be declared free from SARS.

A similar coronavirus surfaced in Saudi Arabia in April 2012. Known as Middle East respiratory syndrome coronavirus (MERS-CoV), there have been 94 confirmed cases, 16 probable cases and 47 dead, with a case fatality rate of approximately 50%, as of August 2013. Like SARS, this is a viral respiratory illness; its symptoms include fever, cough and shortness of breath, which may be followed by kidney failure and respiratory distress, potentially leading to death. People who have weaker immune systems are more likely to die from Middle East respiratory syndrome (MERS). Thus far, all cases have been linked to the Middle Eastern area.

A negatively-stained electron micrograph of MERS-CoV,  revealing its ultrastructural morphology. Image by CDC/ Cynthia Goldsmith; Azaibi Tamin, Ph.D.

A negatively-stained electron micrograph of MERS-CoV, revealing its ultrastructural morphology. Image by CDC/ Cynthia Goldsmith; Azaibi Tamin, Ph.D.

MERS-CoV can be transmitted from person to person if there has been close contact without protective equipment e.g. gloves and masks, but in general, it appears that there has not been a sustained spread of MERS in people. There are three main epidemiological patterns to the transmission of MERS-CoV – 1) sporadic cases, probably after coming into contact with an animal carrying MERS-CoV. 2) Family clusters and 3) healthcare workers are similar, as they are both sets of people who would have come into close contact with an infected person while the person is contagious. The incubation period of MERS-CoV seems to be from 2-14 days; thus, isolation protocols similar to those as carried out in the SARS 2002-2003 epidemic can be applied to people who are suspected to be infected with MERS-CoV. There is also no known cure or vaccine for MERS-CoV. The only treatment available is supportive/palliative care, ensuring that the patient manages to live while their immune system fights off the virus.

Not much is known about MERS-CoV; it seems to be a genetic match to a coronavirus found in Egyptian tomb bats, but recently there has been a report that camels may be the actual animal reservoir for this strain of coronavirus. It also appears that a large amount of virus is actually needed to cause an infection, as only about 20% of our respiratory epithelial cells – that is to say, about 20% of our lungs and airways – are carrying the protein receptor DPP4, which allows MERS-CoV to enter, and hence infect, them.

On an slightly more unsettling note, it seems that there has been at least one case of asymptomatic MERS – that is to say, a person was infected, and then produced anti-MERS-CoV antibodies, without ever showing signs of MERS. If asymptomatic MERS can be confirmed, and people with asymptomatic MERS can transmit the virus to other people, this could potentially explain the sporadic cases of MERS that seem to pop up out of nowhere. Of course, this would also lower the case fatality rate of MERS-CoV. There are also further concerns about the potential for a serious epidemic as there will be an increase in the number of people going to Mecca in Saudi Arabia for the Muslim Haj. While a vaccine could potentially be developed, it might be that the MERS epidemic would burn itself out the same way the SARS epidemic did, thus rendering the development of the vaccine unnecessary and unprofitable.



Summary of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003

Tracking SARS back to its source

S. K. P. Lau, P. C. Y. Woo, K. S. M. Li, Y. Huang, H-W. Tsoi, B. H. L Wong, S. S. Y. Wong, S-Y. Leung, K-H. Chan and K-Y. Yuen. Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats PNAS Vol. 102 No. 39 14040–14045, doi: 10.1073/pnas.0506735102

Special Online Edition: The SARS Epidemic


A. Rambaut MERS-Coronavirus Molecular Epidemiology and Genetic Analysis – Origin and Evolution

C. BEM Reusken, B. L. Haagmans, M. A. Müller, C. Gutierrez, G-J. Godeke, B. Meyer, D. Muth, V. S. Raj, L. Smits-De Vries, V. M. Corman, J-F. Drexler, S. L. Smits, Y. E. El Tahir, R. De Sousa, J. van Beek, N. Nowotny, K. van Maanen, E. Hidalgo-Hermoso, B-J. Bosch, P. Rottier, A. Osterhaus, C. Gortázar-Schmidt, C. Drosten, M. PG Koopmans Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study The Lancet Infectious Diseases, Volume 13, Issue 10, 859 – 866 doi:10.1016/S1473-3099(13)70164-6

R. Roos Saudis, WHO Report 8 Silent MERS Cases

D. Butler Receptor for new coronavirus found

Virology 100x: Round and round we go; where we stop, nobody knows

Viruses are so varied because each virus has evolved to specifically infect one particular host. There are so many different types of viruses that it’s difficult to describe them with a generality; what they have in common is merely as I wrote in an earlier post – that they’re obligate intracellular parasites comprising of nucleoprotein complexes with a protective protein coat (and possibly a lipid envelope). However, with classification, we are able to make generalisations within a particular subset of viruses – particularly with respect to how they infect and replicate, then bust out of our cells. If we are able to figure out how viruses replicate and infect our cells, we are then in a better position to prevent them from replicating in, or even better, from entering and infecting our cells in the first place.

Viruses are primarily classified according to their genetic material; that is to say, whether they have DNA or RNA. After splitting into these two groups, there are further subsets, such as whether the genetic material is single- or double-stranded; if the viral genome is whole or segmented – amongst others.

Baltimore classification

See text for explanation on Baltimore classification

This method of classification is called the Baltimore classification, after its developer David Baltimore. The genetic nature of a virus is important because it determines where and how the replication of the DNA or RNA takes place (either the nucleus or the cytoplasm), which in turn partially determines what steps the virus must take to get its genome there. Thus, it is possible for us to predict certain features of a virus’s replication cycle based purely on its genetic nature.

The stages in viral replication are so closely linked that it is difficult to separate them sometimes, and the number of stages range from seven to eight, or even nine, depending on who you are talking to. Nevertheless, they can be grouped into three main areas dealing with Entry into, Replication in, and Exit from host cells. Adsorption & Attachment, Entry, and Uncoating are stages in how the viruses enter cells; Transcription, Expression/Synthesis, and Replication are stages in viral replication; Assembly, Maturation, and Release are stages in how viruses exit cells.

As viruses don’t have any means of moving around, they depend on collisions with other things moving around in our bodies to push them along, causing random movement (also known as Brownian motion). Viruses are adsorbed onto the surface of the cells they are trying to infect, where they attach to the host cell by inserting their protein key into the host protein/sugar-chain lock, and thus gain entry into the cell.

The virus then enters the host cell via one of three methods. First, the translocation of the entire virus particle across the cell membrane; not much is known about this process, unfortunately. The second and third methods both involve endocytosis, which is the process by which our cells engulf particles such as nutrients (and in this case, viruses) from outside the cell. Endocytosis causes the formation of little pockets called vesicles, which go on to merge with larger pockets (containing fairly hostile environments) called lysosomes, which break down the particles that are brought into the cell for use throughout the cell. Triggered by the change in environment in lysosomes, viruses undergo uncoating, where the viral genome is exposed to the cellular environment. In the second method of entry, no further direct virus-host interactions are required, whereas in the third method, often employed by enveloped viruses, the viral lipid envelope and the cell membrane fuse to allow entry of the viral genome into the cell.

Upon entry, the virus then takes over the cell machinery and uses the cells’ enzymes to start transcribing and replicating its genome, and synthesizing the protein components of more viral particles. The precise order and manner of these stages is dependent on the nature of the viral genetic material¹.

Finally, the assembly of the newly-synthesized viral proteins and newly-replicated genetic material forms new viral particles, which is followed by protein cleavage where necessary for the maturation of the new viral progeny, and the release of the new viruses into the world again, usually by budding from the cell, or causing the cell to burst.

By deciphering how the various steps of any particular virus’s replication cycle happens, we are better able to prevent and/or treat a viral infection; for instance, the various drugs available in HIV therapy are based around the steps HIV takes to replicate itself. HIV is a class VI virus, meaning that it requires reverse transcriptase to replicate; one of the first HIV treatments was zidovudine (commonly known as AZT), which was aimed at inhibiting reverse transcriptase. Many other HIV drugs have continued to be developed in the same vein, and research has gone into finding drugs that can inhibit virus entry, maturation and exit as well.




1. Viruses are classed using the Baltimore Classification scheme according to how they replicate.

Class I and Class II have DNA for their genetic material. Class I viruses are able to express their genes upon entry as the genes are made of double-stranded DNA; replication of the genome and expression/synthesis of proteins are then carried on concurrently. Replication is almost exclusively nuclear in Class I viruses, with the exception of poxviruses, which are able to replicate their DNA in the cytoplasm. Class II viruses, with single-stranded DNA, typically have to undergo genome replication in the cell nucleus first before protein expression can be carried out.

Class III, IV and V have RNA for their genetic material. Class III viruses have segmented double-stranded RNA genomes, which are transcribed separately to produce mRNA and synthesize proteins in the cell cytoplasm. Class IV viruses’ (+)sense RNA are able to synthesize viral proteins immediately after infection in the cell cytoplasm, as they use their genomes like mRNAs; Class V viruses, on the other hand, have to make a (+)sense RNA from their (-)sense RNA genome first.

Class VI and VII viruses both use reverse transcription in their replication, although the point in the viral replication cycle at which reverse transcription is carried out is different for both classes. Class VI has diploid single-stranded (+)sense RNA, but this genetic material does not serve as mRNA immediately after infection. Instead, they use viral reverse transcriptase to create a DNA intermediate for replication and protein synthesis after infection. Class VII has double-stranded DNA, much like our own cells, which can be transcribed into mRNA, and the resulting mRNA read to make viral proteins. Reverse transcriptase comes in near the end of the replication cycle, to re-create the virus DNA from its mRNA.

Virology 100x: Let’s start from the very beginning

Tobacco Mosaic Virus

The tobacco mosaic virus; the first virus discovered and studied.

Let me get one thing straight first – viruses are NOT the same thing as bacteria. They’re just not. Okay? Great.

What are viruses, then? Well, I could tell you that they’re nucleoprotein complexes that make use of cells to replicate; I could tell you that they are obligate intracellular parasites – that is to say, they’re obliged to be parasites inside our cells; I could even tell you that they do not undergo cell division. But I won’t.

Oh. I already did.

Never mind then.

The point is, viruses are all that and more. One of the most interesting things in the world, we still can’t decide if viruses are living organisms or not. They carry genetic material, and are able to replicate themselves (but only after they’ve infected a host cell). However, outside of cells, they become metabolically inert – they can’t make their own proteins or copy their own DNA (or in the cases of some cells, their own RNA). Yet they can ‘die’ – if they’re outside of their host cell for long enough, or are otherwise exposed to adverse conditions, they can no longer successfully infect cells. This straddling of the line between life and non-life is very likely to be a clue to how life originated; most viral genes are so unlike the genes of the rest of the planet that they may well have come from a common ancestor before cell-based life existed.

The core of any virus is its genetic material – either DNA or RNA; this may be wrapped up with viral proteins to form a nucleoprotein complex (from combining “nucle”ic acid + “protein”). Viral proteins are also incorporated into the protective coat surrounding the nucleoprotein complex to give rise to the basic viral particle (or the virion). Some viruses, particularly those that infect mammals, may also have an additional lipid envelope over its protective coat.

You may think that all viruses are harmful to us, but this is not true. Because of the proteins embedded in their protein coat (or lipid envelope), viruses are very specific about which species they will infect, much like how only one specific key can open one specific lock. In fact, there are viruses, known as bacteriophages, which are beneficial to us because they are able to infect, and thus cause the death of bacteria that are harmful to us. It has been suspected that some “healing waters” may have been effective due to the presence of viruses that infect pathogenic bacteria. Viruses also infect amoeba, fungi, plants, and of course, other animals. In fact, every species on Earth has a whole host of viruses that is specifically only able to infect that species.

lock and key

In this case, the pink object refers to a viral surface protein, while the orange object refers to a host cell surface protein/glycoprotein. Only when viral protein keys are able to fit into host protein/glycoprotein locks can the infection of a cell start to happen, so viruses are VERY specific about who they are able to infect.

The gold standard for determining a new virus is by cultivating and isolating the virus, and viewing it under an electron microscope. Unfortunately, this species specificity means that it is very difficult to cultivate human viruses in order to study them, because they won’t infect non-human cells. The best way to go about studying human viruses would of course be by infecting humans, but this is ethically problematic, to say the least. One partial solution would be to culture human cells in a dish, and throw some human viruses on top to infect the human cells. This helps with studying how viruses infect cells in the first place, and what effects they have on cells in isolation. However, viruses are very finicky, and it first takes a lot of trial and error, and later, precision and time, to properly grow them. This still doesn’t answer how viruses act in the whole body, though – especially in the presence of our immune system, which has been implicated in a large amount of the cellular damage it causes as it tries to rip the virus from our bodies. Scientists thus have to use genetically near-identical species such as monkeys, or modify mice and other model organisms such that they carry human proteins, and are then able to be infected by our human viruses.

Because viruses are basically protein coats around genetic material, they are therefore also ideal as a mechanism for transferring genes to our own genomes. These engineered viruses are known as viral vectors, and have been modified such that they no longer cause disease. Viral vectors have a wide range of applications, including gene therapy, cancer treatmentvaccine development, and even in basic neuroscience research. Virus-like particles, which are viruses emptied of their genetic material, are also being investigated for use in nanotechnology applications like drug delivery and diagnosis.

Ebola: From monkeys to us

Ebola is caused by a virus that causes viral hemorrhagic fever – that is to say, it results in fever and bleeding disorders, shock, and eventually, death. Other symptoms include edema, migraine, fatigue, vomiting, and diarrhea. Occurring most often in the African continent, ebolavirus outbreaks happen when the virus jumps from its animal reservoir to a human, thus spreading through the human population; however, it is still unknown which animal harbours ebolavirus, although a strong suspect is bats. Ebola

The first ebolavirus (EBOV) was isolated in 1976, in what was then known as Zaire (now called the Democratic Republic of the Congo), when it caused an outbreak in the local population, and was thus named the Zaire ebolavirus, or the Zaire virus. Almost simultaneously, a second species of ebola virus was isolated in Sudan, and thus was called Sudan ebolavirus (SUDV); at first it was thought to be of the same species as EBOV, but later studies proved it to be of a different species. Later, animal laboratory workers in Reston, Virginia, got a scare, when ebolavirus was identified in the sick primates that they had been handling. Luckily for them, this turned out to be an Asian species of ebolavirus that did not cause disease in humans. All in all, five genetically and immunologically distinct species of ebolavirus have been isolated, with each species having several different strains. The most virulent species is EBOV, or Zaire virus, with an average case fatality rate of approximately 83%, and there have been more outbreaks of EBOV than any other ebolavirus.

EBOV and its kin are RNA viruses that are unusually genetically stable, allowing researchers to determine that most outbreaks were caused by different strains of different species of ebolavirus, indicating that these outbreaks were probably from different viral reservoirs. Ebolaviruses are unusual in that they are one of the only species of filamentous animal viruses in the world; filamentous viruses are more usually found in plants, so it has been posited that ebolaviruses may have evolved from plant viruses. Ebolaviruses have an outer lipid envelope, which technically means that the virus can be disrupted via alcohol-based agents; however, very low levels of virions are needed for infection to occur in humans (in the range of 1-10 virions). As transmission from humans to humans is via contact with an infected person’s blood or other body fluids, practicing the barrier nursing (or these days, the standard precautions) method, involving the use of protective equipment such as gloves, masks, gowns and so on, is more effective and useful in preventing transmission.

An electron micrograph of an Ebola virus

An electron micrograph of an Ebola virus

It has been problematic to elucidate the mechanism of ebolavirus infection because of a lack of samples and the difficulty of culturing the virus in the laboratory. However, researchers finally figured out the structure of the EBOV glycoprotein (GP) as derived from a human survivor of an outbreak. EBOV GP is the only virally expressed protein on the surface of the virion; it is important in the replication cycle of EBOV because it is responsible for the attachment of the EBOV virion to host cells, as well as virion-cell membrane fusion. Hence, it is a vital target of vaccines against EBOV. Various types of vaccines, including live attenuated and DNA subunit vaccines, have been developed against EBOV, and thus far they have had some promising success in animal models such as mice, guinea pigs, and macaques.

EBOV and its kin primarily attack endothelial cells, white blood cells and red blood cells, and overwhelms the protein synthesis mechanism in these cells. It is also able to interfere with our adaptive immune system by inhibiting the activation of neutrophils, a type of white blood cell. After entering these cells, these viruses replicate in the cytoplasm, then cause the host cell to burst, spreading their virions even further throughout the body. When enough cells burst, this causes the patient’s organs to break down, and their blood to stop clotting, leading to death, if the virus is not expelled from the body by the immune system in time.

Unfortunately, there is no curative treatment available for ebolaviruses; there is only supportive treatment that helps to mitigate the symptoms. Although there is a promising drug target called Niemann–Pick C1(NPC) present in the cell membrane, which is important in helping EBOV bind to our cells, a drug that can successfully target NPC is still under development. Thus the best way to avoid being infected would be to avoid contact with bats or non-human primates, and to wear protective equipment when taking care of people who have been infected with ebolaviruses. Frighteningly, it seems that EBOV can be transmitted between species through the air via large droplets, although the range of such transmission is limited.



Ebola Virus

The Ebola Virus poster (Science Infographics 2011 Honorable Mention)

CDC | Ebola

J E Lee and E O Saphire Ebolavirus glycoprotein structure and mechanism of entry Future Virol. 2009; 4(6): 621–635. doi: 10.2217/fvl.09.56

Structure of the Ebola Virus Glycoprotein Bound to an Antibody from a Human Survivor

N Sullivan, Z-Y Yang, and G J Nabel Ebola Virus Pathogenesis: Implications for Vaccines and Therapies J. Virol Sept 2003 vol. 77 no. 18 9733-9737 doi: 10.1128/JVI.77.18.9733-9737.2003

J. B. McCormick, S. P. Bauer, L. H. Elliott, P. A. Webb and K. M. Johnson Biologic Differences Between Strains of Ebola Virus from Zaire and Sudan J Infect Dis. 1983 vol 147 no. 2 264-267 doi: 10.1093/infdis/147.2.264
M McGrath Growing concerns over ‘in the air’ transmission of Ebola

Gesundheit! Now go wash your hands before you spread that flu to everyone else

I had a little bird, And its name was Enza. I opened the window And in-flew-enza.

A skipping rhyme about the 1918 H1N1 flu pandemic, the most lethal influenza pandemic that killed more people than all the casualties from the then-recent World War I put together (estimates range from 20 to 100 million people). This virus was a result of an avian flu virus making the jump successfully into humans.

Influenza is a viral infection that generally affects the upper respiratory tract; that is to say, the mouth, nose and throat. Symptoms often last a week or so, and range from a sudden high fever, coughing, headache, muscle and joint pain, severe fatigue, to sore throat and runny nose. Although the virus can be transmitted at all times, it is typically a seasonal infection that peaks during winter in temperate countries, presumably because more people are packed closer together in winter; the influenza virus is also able to survive for longer outside the body in cold weather. Influenza is passed from person to person via aerosolized droplets i.e. by sneezing and coughing, and contact with contaminated surfaces. It is also able to infect people of all ages; however, the most vulnerable are the very young, the very old, and those with suppressed immune systems. Special care should be taken in these cases, as severe illness or death may result. ImageIn the United States, seasonal influenza epidemics have caused the deaths of more than 30,000 people yearly, and the hospitalization of more than 100,000. More virulent strains may claim the lives of 10,000 – 15,000 more people each year. Influenza pandemics are caused by strains that are so virulent that in the 1918 flu pandemic, more than 2.5% of those that fell ill died, compared to a case fatality rate of less than 0.05% for the more typical virus strain; these pandemic strains are also able to spread rapidly even in the summer, during what is supposedly their “off” season.

There are three types of influenza virus (A, B & C), but the one that we are most concerned about is the influenza A virus. When we’re talking about H1N1, H2N3, and H7N9, we are talking about the influenza A virus – an RNA virus of the orthomyxoviridae (influenza virus) family that is able to infect birds, pigs, and humans, amongst other animals. Variants of the virus that are endemic in birds are called avian influenza; variants that are endemic in pigs are called swine influenza.

In the naming of the subtypes of influenza A virus, ‘H’ stands for hemagglutinin, and ‘N’ for neuraminidase, both of which are antigens embedded on the lipid envelope surface of influenza A virus particles. HA is a protein that mediates binding of the virion to, and entry of the viral genome into, the host cell, while NA is involved in the release of new influenza virions from infected cells. There are 17a different known hemagglutinin (HA) antigens, and 11 different known neuraminidase (NA) antigens; therefore, there are 187 possible different combinations of HA and NA antigens that can theoretically be expressed on the surface of an influenza A virus particle. The genome of the influenza A virus is segmented; that is to say, the genome is broken up into different segments, and each segment codes for different parts of the viral particle.

Influenza A virus schematic

Influenza A virus schematic; M2 Ion channel is important for viral replication by controlling pH; RNP stands for ribonucleic protein and holds the RNA genome. Illustration by CDC.

Several small details are all that differentiate avian flu from human flu; for example, avian flu HA binds to alpha 2–3 sialic acid receptors on the avian cell surface, while human flu HA binds to alpha 2–6 sialic acid receptors on the human cell surface. Unfortunately, swine flu viruses have the ability to bind both types of sialic acid receptors on swine cell surfaces – this makes them dangerous because virulent avian flu viruses could jump into pigs, undergo reassortment and gain the ability to bind to alpha 2-6 sialic acid receptors, then jump into humans and consequently cause a pandemic. This sudden change in the genetic makeup of the influenza virus is known as antigenic shift.

The best way to prevent being infected by the influenza virus is, of course, by getting the flu vaccine. Typically available as a seasonal trivalent vaccine (that means that it is protective against three viruses, usually two influenza A viruses and one influenza B virus), the seasonal flu vaccine is recommended for people at high risk of getting flu, particularly during its peak season in the winter months. It is also only provides protection for one season (one year) because the surface protein antigens on the influenza viruses mutate over time such that the antibodies put out by our immune system against one year’s vaccine will no longer recognize next year’s viral antigens. In fact, the genes for an influenza virus evolve at a rate which is approximately a million times faster than that of animal (including human) genes. This gradual mutation of antigens is known as antigenic drift.

To decide which influenza viruses to include in each year’s trivalent vaccine, scientists study influenza viruses in the wild to determine which are the most predominant, or most likely to become predominant, in the following year; these viruses are then cultivated, then inactivated or attenuated, and included in the following year’s influenza vaccine. There are three types of inactivated vaccines (with decreasing risk of the virus regaining virulence if the inactivation is carried out improperly): whole virus vaccines, split virus vaccines, and subunit vaccines. Whole and split virus vaccines have names that are mostly self-explanatory, while subunit vaccines make use of only certain antigens from the influenza virus; in this case, primarily HA and NA. Live, attenuated influenza vaccines, on the other hand, are weaker and avirulent strains of the live influenza virus. Live, attenuated vaccines are the most effective, but they are also the ones that are most likely to revert to the virulent strain of influenza.

Influenza viruses that are suspected to be able to cause pandemics are used to create monovalent influenza vaccines; this is primarily to allow for control of manufacture, transport, and administration of the vaccine, so as to reduce the risk of the virus regaining its virulence and spreading throughout the population.

Deaths from pandemics were caused by both the virus (and the immune system’s reaction to the virus) as well as secondary infections that turned lethal when the infected person’s immune system was too busy fighting off the virus. When antibiotics were discovered, the mortality rate of pandemic influenza viruses fell as secondary bacterial pneumonia could now be treated effectively. Antivirals such as Tamiflu, a neuraminidase inhibitor, are a recent development, but they have been shown to be effective against influenza in the most recent 2009 H1N1 influenza pandemic, causing the case fatality rate to fall further to 0.03% – very close to the case fatality rate for seasonal influenza.


J. K. Taubenberger and D. M. Morens 1918 Influenza: the Mother of All Pandemics

Note a: An 18th hemagglutinin antigen was found recently in bats