Influenza: Encyclopedia - Influenza

Influenza

Influenza (or as it is commonly known, the flu or the grippe) is a contagious disease of the upper airways and the lungs, caused by an RNA virus of the orthomyxoviridae family. It rapidly spreads around the world in seasonal epidemics, imposing considerable economic burden, in the form of health care costs and lost productivity. Three influenza pandemics in the 20^th century, each following a major genetic change in the virus, killed millions of people.

The term influenza has its origins in 15th century Italy, where the cause of the disease was ascribed to unfavorable astrological influences. Evolution in medical thought led to its modification to "influenza di freddo" (meaning "influence of the cold"), which by the 18th century became the prevalent terminology in the English-speaking world as well. The latter term underlies the persistent, though unsubstantiated, popular belief that influenza is influenced or caused by exposure to the cold.

Influenza - Types

There are three genera of the virus, identified by antigenic differences in their nucleoprotein and matrix protein:

• Influenza A viruses are known to infect humans, other mammals and birds (see also avian influenza)
• Influenza B viruses are known to infect humans and seals
• Influenza C viruses are known to infect humans and pigs [1].

The A type of influenza virus is the type most likely to cause epidemics and pandemics. This is because the influenza A virus can undergo antigenic shift and present a new, immune target to susceptible people. Populations tend to have more resistance to influenza B and C, because they only undergo antigenic drift, and have more similarity with previous strains.

Influenza A viruses can be further classified, based on the viral surface proteins hemagglutinin (HA or H) and neuraminidase (NA or N) that are essential to the virus' life cycle. Sixteen H subtypes and nine N subtypes have been identified for influenza A virus. Only one H subtype and one N subtype have been identified for influenza B virus. At present, the most common antigenic variants of influenza A virus are H1N1 and H3N2. (Yohannes et al., 2004)

Yet further variation exists; thus, specific influenza strain isolates are identified by a standard nomenclature specifying virus type, geographical location where first isolated, year of isolation, sequential number of isolation, and HA and NA subtype (Yohannes et al 2004) Examples of the nomenclature are A/Moscow/10/99 (H3N2) and B/Hong Kong/330/2001.

The term superflu is used to refer to a strain of flu that spreads unusually quickly, is unusually virulent, or for which the host is uncommonly unresponsive to treatment— the kinds of strains which cause epidemics or pandemics. There is no exact scientific definition of a superflu.

Influenza - Genetics

Influenza A viruses contain their genome in eight separate linear segments of negative-sense RNA, which code for ten proteins (eleven for type A if including the novel PB1-F1 protein) [2]. Each segment contains a single gene, but some can be read twice at different starting points to create two distinct proteins. The segmented nature of the genome also allows for the exchange of entire genes between different viral strains when they cohabitate the same cell. The 8 genes are:

• HA gene encoding hemagglutinin which produces about 500 copies
• NA gene encoding neuraminidase which produces about 100 copies
• NP gene encoding nucleoprotein. Influenza A, B, and C are distinguished by their nucleoproteins
• M gene encoding two matrix proteins (the M1 and the M2) by using different reading frames from the same RNA segment
• NS gene encoding two distinct non-structural proteins by using different reading frames from the same RNA segment
• PA gene encoding an RNA polymerase
• PB1 gene encoding an RNA polymerase and PB1-F2 protein (induces apoptosis) by using different reading frames from the same RNA segment
• PB2 gene encoding an RNA polymerase

The genome segments have common terminal sequences, and the ends of the RNA strands are partially complementary, allowing them to bond to each other by hydrogen bonds. After transcription from negative-sense to positive-sense RNA the +RNA strands get the cellular 5' cap added, allowing its processing as messenger RNA by ribosomes. The +RNA strands also serve for synthesis of -RNA strands for new virions.

The RNA synthesis and its assembly with the nucleoprotein takes place in the cell nucleus, the synthesis of proteins takes place in the cytoplasm. The assembled virion cores leave the nucleus and migrate towards the cell membrane, with patches of viral transmembrane proteins (hemagglutinin, neuraminidase and M2 proteins) and an underlying layer of the M1 protein, and bud through these patches, releasing finished enveloped viruses into the extracellular fluid.

Influenza - History

There were several serious outbreaks of influenza in the 20th century. The most famous (and the most lethal) was the so-called Spanish Flu pandemic (type A influenza, H1N1 strain), which lasted from 1918 to 1919, and is believed to have killed more people in total than World War I. While the war casualties accumulated over several years, the pandemic took most of its toll over a period of weeks. Lesser flu epidemics included the 1957 Asian Flu (type A, H2N2 strain) and the 1968 Hong Kong Flu (type A, H3N2 strain).

Influenza - Known epidemics and pandemics - overview

In our times, some half a million people die of flu each year.

• 1889-90 - Asiatic Flu, mortality rate said to be 0.75-1 death per 1000 (pandemic)
• 1918–20 – Spanish Flu, 500 million ill, 20 to 25 million died (pandemic)
• 1957–58 – Asian Flu, 1 to 1.5 million died (epidemic)
• 1969–69 – Hong Kong Flu, 3/4 to 1 million died (epidemic)

Although there were scares in New Jersey in 1976 (the Swine Flu), worldwide in 1977 (the Russian Flu), and in Hong Kong (as well as in other Asian countries, namely continental China, as became known later) in 1997 (Avian influenza), there have been no major pandemics subsequent to the 1968 infection. Increased immunity from antibodies, and the development of flu vaccines have limited the spread of the virus, and so far prevented any further pandemics.

Influenza - Symptoms

The virus attacks the respiratory tract, is transmitted from person to person by saliva droplets expelled by coughing, and causes the following symptoms:

• Fever
• Headache
• Fatigue/Sore joints (can be extreme)
• Dry cough
• Sore throat
• Nasal congestion
• Sneezing
• Irritated eyes
• Body aches
• Extreme coldness

Influenza's effects are much more severe, and last longer than those of the "cold". Recovery takes about one to two weeks. Influenza can be deadly, especially for the weak, old or chronically ill. Some flu pandemics have killed millions of people.

Most people who get influenza will recover in one to two weeks, but others will develop life-threatening complications (such as pneumonia). Millions of people in the United States (about 10% to 20% of U.S. residents) are infected with influenza each year. An average of about 36,000 people per year in the United States die from influenza, and 114,000 per year are admitted to a hospital as a result of influenza. It has been reported that 2 million people die from influenza complications in the world each year. Even healthy people can be affected, and serious problems from influenza can happen at any age. People age 65 years and older, people of any age with chronic medical conditions, and very young children are more likely to get complications from influenza. Pneumonia, bronchitis, sinus, and ear infections are four examples of such complications.

The flu can make chronic health problems worse. For example, people with asthma may experience asthma attacks while they have the flu, and people with chronic congestive heart failure may have a worsening of this condition, that is triggered by the flu.

Influenza - Variability

Influenza is an extremely variable disease; similar viruses are found in pigs and domestic fowl. In areas where there are high concentrations of humans, pigs and birds in close proximity, such as parts of Asia, simultaneous infections across species enable genetic material to be exchanged between the various strains of flu. This appears to be the principal method by which new infectious strains arise. It is believed that sooner or later, a recombination may occur to produce a strain as lethal as the 1918 virus. In late 1997, a new strain of avian influenza (also known as bird flu) called H5N1 originating from chickens infected 18 people in Hong Kong, of whom 6 died. (Though many milder cases would have gone unreported. [3]) This strain did not appear to be readily transmissible from human to human, but the relatively high mortality rate, and the possibility of a further recombination to make it more infectious, meant that the risk was considered so great that all domestic poultry in Hong Kong was slaughtered. Avian influenza transmissible to humans resurfaced in January 2004 in Cambodia, Vietnam, and Thailand.

Influenza - Flu season

Influenza reaches peak prevalence in winter, and because the Northern and Southern Hemisphere have winter at different times of the year, there are actually two flu seasons each year. Therefore, the World Health Organization makes two vaccine formulations every year; one for the Northern, and one for the Southern Hemisphere.

While most influenza outbreaks in the Northern Hemisphere tend to peak in January or February, not all do. For example, the influenza pandemic of 1918 and 1919 reached peak virulence during late spring and summer worldwide, and not until October in the US. It remains unclear why outbreaks of the flu occur seasonally rather than uniformly throughout the year.

One possible explanation is that, because people are indoors more often during the winter, they are in close contact more often, and this promotes transmission from person to person. Another is that cold temperatures lead to drier air, which may dehydrate mucus, preventing the body from effectively expelling virus particles. The virus may also linger longer on exposed surfaces (doorknobs, countertops, etc.) in colder temperatures. Increased travel and visitation due to the holiday season may also play a role. [4]

Another explanation is that cold weakens the immune system; however, the virus is contracted in a warm indoor environment in which it can thrive.

Influenza - Prevention

It is possible and in many cases recommended to get vaccinated against influenza with a flu vaccine. However, due to the high mutability of the virus, a particular flu vaccine formulation usually only works for about a year. The World Health Organization co-ordinates the contents of the vaccine each year, to contain the most likely strains of the virus which probably will attack the next year. The flu vaccine is usually recommended for anyone in a high-risk group, who would be likely to suffer complications from influenza. Flu vaccine is available as nasal spray vaccine (recommended for all healthy people ages 5 to 49) and as injectable vaccine.

Influenza - Treatment

Antiviral treatments that have proven effective in influenza are amantadine, rimantadine, zanamivir, oseltamivir and ribavirin. As most of these substances are expensive, various healthcare organisations and insurers only support their use where this would make a significant difference, e.g. in the elderly.

Worryingly, investigators at the CDC in Atlanta found high rates of resistance to adamantane derivatives (amantadine, rimantadine) in the H3N2 strain of influenza A: China 74%, Hong Kong (70%), Taiwan (23%), South Korea (15%) (Bright et al 2005). The overall resistance rate in North America was 4%. The enormous rate of resistance in China is believed to be due to the ready availability of amantadine in over-the-counter cold remedies.

A trademarked elderberry extract may aid in shortening the duration of an episode of influenza once contracted, though it has no notable preventive effects (Zakay-Rones et al 1995).

Influenza - Avian influenza

Genetic reassortment ("mixing") of a human flu virus with the current H5N1 avian influenza has been identified as the most likely source of the next pandemic.

The natural host for influenza virus is aquatic birds. Pandemic influenza often occurs when an avian-adapted virus infects a porcine host, which can be infected by human and avian varieties of influenza A virus. The virus may then recombine within the pig, to form a genetically new virus which is able to infect humans and be transmitted from person to person.

The current avian flu threat (2005) is due to the H5N1 virus. This virus is currently still avian-adapted and cannot be transmitted from person to person, though it seems to be able to infect humans and cause mortality. It is thought likely, however, that the virus will eventually become adapted and able to spread from person to person by recombining with a human-adapted form either in a human or pig host. If this happens, a pandemic may be unavoidable, since there will be very little immunity to this genetically new virus, and international travel coupled with densely populated cities will spread the virus rapidly.

Currently, governments are stockpiling anti-viral drugs such as Tamiflu, which can reduce the effects of the virus. It is difficult to design a vaccine for the virus until it has recombined into a human adapted form, but if a pandemic does occur a vaccine will be required urgently.

Although the threat is very real, it is impossible to say when or if the virus will become human-adapted.

Influenza - Sources

• Some of this article was originally from the public domain CDC publication http://www.cdc.gov/
• CDC info on influenza
• NHS Direct Health encyclopedia entry
• Both overview and technical details on influenza viruses with emphasis on the potential H5N1 pandemic Includes details of various nonhuman influenza viruses. Extensive and well done.

Categories: Wikipedia references cleanup | Influenza

Adapted from the Wikipedia article "Influenza", under the G.N U Free Docmentation License. Please also see http://en.wikipedia.org/wiki