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Literature Discussion - Lit-Talk.com
Notes on the Latest Strain of Influenza A Virus, H1 N1
By David Lomuyu (Sudan)
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Definition and Overview
The swine influenza or swine flu, also known as H1 N1, is a new strain of influenza A virus, of the subtype H1 N1, which has never before circulated among humans. Note that the pandemic of 1918 that killed more than 20 million people worldwide was caused by Influenza A virus, subtype H1 N1, but a different and an unusually virulent and deadly strain. (Strain simply means organisms of the same species but with distinctive characteristics.) Also bear in mind that some strains of H1N1 are endemic (or occur regularly at low frequency) in humans and cause a large fraction of all seasonal (or winter) influenza.
Influenza A virus strains are assigned an H (or haemaglutinin) number and an N (or neuraminidase) number based on which forms of these two proteins the strain contains on its surface. The structure of these proteins differs from strain to strain due to rapid genetic mutation in the viral genome.
This H1 N1 virus strain was originally described as swine influenza because genetic testing showed it to share many similarities with influenza viruses which normally infect pigs. But further study has shown that this virus is in fact very different from the influenza virus that normally infects pigs in North America. Rather it contains a mixture of genetic information from viruses that normally infect pigs in Europe and Asia as well as from viruses which normally affect avian (bird) and human hosts.
There are 3 types of influenza viruses recognized: A, B and C. Influenza A is generally responsible for epidemics and pandemics. Influenza B often causes smaller and milder outbreaks, such as in schools or camps. Influenza C rarely produces disease in humans. All these viruses belong to a group known as orthomyxoviruses.
An epidemic simply refers to the occurrence of more cases of a disease than would be expected in a community or region during a given time period; the occurrence may be sudden with the disease spreading rapidly and widely. Pandemic, on the other hand, refers to the extent of an epidemic; that is, over a wide geographic area and affecting a large proportion of the population.
The World Health Organization (WHO) declared this influenza a pandemic, just last month.
Influenza should not be confused with ‘common cold’ or what we commonly (wrongly) call ‘flu’ here in the tropics, which is caused by a different virus known as rhinovirus, belonging to a different group.
It is a fact that seasonal influenza occurs every year (in winter) and the viruses change each year, but many people have some immunity to the circulating virus which helps control infections. Some countries also use seasonal influenza vaccines to reduce illness and deaths. But the current influenza A, described as H1 N1, is a new virus strain and one to which most people have no or little immunity and, therefore, this virus could cause more infections than are seen with seasonal influenza.
But the good news is that it has been noticed that severity of this influenza strain seems to be less than what was observed in the pandemic of 1918.
Immunology and vaccination
Human immunity develops against the haemagglutinin (H) antigen and the neuraminidase (N) antigen, which are the proteins, on the influenza A viral surface, but the virus, as mentioned earlier, through the process of mutation, has the capacity to develop new antigenic variants at regular interval. That is, the structure of these proteins (N and H) on the viral surface keeps changing each year. This means that the body has to develop new immunity each year. Also, this renders vaccines developed for previous strains of the influenza A virus useless on new strains such as the current H1 N1. A major antigenic change (or antigenic shift) gives rise to pandemics; whereas a minor antigenic change (or antigenic drift) results into less severe epidemics, since there is still some immunity in the population.
A minor antigenic change (or antigenic drift), as referred to influenza A virus, involves point mutation resulting into amino acid changes in the two surface proteins. A major antigenic change (or antigenic shift) within an influenza A subtype results from genetic recombination of the RNA (genetic material) of the virus that infects humans with that of influenza A virus that infect animals (e.g. swine). J ?!!
Just to illustrate, one of my favourite quotations is from Albert Einstein, a German-born Jew, who was a famous theoretical physicist. According to Einstein, imagination is more important than knowledge, and I agree with him; absolutely. Try to imagine, just imagine, a key and a padlock and a healthy body together, in relation to influenza A virus, and other similar viruses, to try to understand all this jargon of antigen and immunity (or antibody) and vaccines and mutation and minor changes and marked changes … Let the key and the padlock be very very tiny; that is, to emphasize the fact that they cannot be seen with the naked eyes, just like viruses. Keep imagining, just imagining, that our padlock (antigen) here represents and comes from a particular factory (virus), that manufactures uniform padlocks, and the padlock enters your body during one cold winter. Never mind how; or just imagine it entered through your nose. Now, imagine that to remove that padlock, which is a harmful foreign material, from your body, a key is required to open it, and by being opened, BOOM, it is eliminated; it disappears! Don’t hang up on the imagination, yet. Since you’re healthy your body has the capacity and therefore makes the key (immunity/ antibody) to open and as a result eliminate the padlock. Next year, during winter, when a padlock from the same factory comes and enters you, your body already has the key to the padlock and will produce more copies of the key, if need be, to destroy the same kind of padlock. But what if the factory, all of a sudden, decides to change their padlock, in relation to the key? That’s where the process known as mutation comes in. The new padlock product that enters you won’t be opened with the same old key that your body already has or can produce at a quick notice. Right? Yes. When the change the factory makes to the padlock is little (minor antigenic drift), the old key may be tried, since it can still enter the padlock, and there is a chance that it may open after some fidgeting. But when the change from the factory is marked (major shift), the old key will not even enter the padlock. The padlock is then beyond control. Still within our imagination, if the padlock, as a representative of the factory, has the ability to multiply within us (viruses do) and to spread to people around us, what will happen with this sudden change of events, when the old key from the body will no longer destroy the new strain of padlock? The padlock (or virus) will be unstoppable and spread widely, becoming a pandemic!
To understand the vaccine, let’s still keep in the same imagination and start from the beginning, before the sudden major change decided by the factory executives. I hope we are on the same track again. Now, let’s have it like this: you’re a healthy individual and there’s a padlock (antigen), from a particular factory (virus), which has entered you for the first time; your body produces the key (immunity/ Antibody) to get rid of the padlock, and BOOM, the padlock is eliminated. If another padlock from the same factory that makes uniform padlocks enters you, the same key will be used by your body to open, and therefore, destroy it. To protect people around you who never knew about the virus, say in your neighbourhood, from padlocks coming from the infamous factory, an agency (scientists) decided to make harmless counterfeit copies (vaccines) of the padlock and inject into people in your neighbourhood, including your healthy neighbour. Note that, in this case, it is just a counterfeit copy of the padlock (antigen) and not a counterfeit copy of the factory itself (virus). As a result of the counterfeit padlock now in your neighbour’s body, his body, let’s just assume he’s a man, will produce a copy of the same key , as yours, ready in his blood, and will have the capacity to produce more, in case the same type of real padlock that entered you happens to enter him. This is the basics of immunization or vaccination. What if it happens that the factory changes its padlock configuration (with respect to the key), abruptly? The key that your body has been able to produce, as well as the key that your neighbour’s body has been able to produce, which is the same copy as yours, and even the counterfeit padlocks used to generate copies of the same key in the people being protected, become useless! As simple as that!
Now, enough with padlocks and keys; they don’t exist in virology; just some wild imaginations! Based on the lock-and-key hypothesis I remember from my biology of ages ago. But I do hope that it did make some sense, that is, if you have been able to follow keenly. Have you?
Anyway, at the moment (early July 2009), the World Health Organization (WHO) is working closely with manufacturers to come up with a safe and effective vaccine, but it will be some months (5 to 6) before it is available.
Transmission
Transmission is from person-to-person through:
1) Exposure to infected droplets expelled by coughing or sneezing which is then inhaled or
2) Exposure to infected droplets that have contaminated hands and surfaces and then transferred to the nose or mouth by touching.
Consuming pork or pork products does not result into an infection. The H1N1 viruses are not transmitted by food and hence eating properly handled and cooked pork is safe.
The place of origin of the virus is unknown.
Signs and Symptoms of Infections
The incubation period is usually 1 to 4 days, but can go up to 7 days; that is, the period from acquiring infection to the development of signs and symptoms.
The signs and symptoms are flu-like, that is:
Fever
Cough
Headache
Muscle and joint pain
Sore throat
Running nose
Malaise
Vomiting and diarrhea, sometimes
Chills
Arthralgia
Atypical (unusual) presentation occurs in infants, elderly, and the immunocompromised.
The severity of the disease ranges from very mild symptoms to severe illnesses that can result in death.
Case definitions are changing as we learn more about this virus and the syndromes it causes. Influenza-like illness (ILI) is defined as fever (temperature of 100ºF [or 37.8ºC] and above) with cough or sore throat in the absence of a known cause other than influenza. In other words, consider as a typical case if a patient meets this criteria, as long as an outbreak is confirmed in an area.
Diagnosis
Not all individuals with suspected H1N1 influenza A need to have the diagnosis confirmed, particularly if the illness is mild or the person resides in an area with confirmed cases. Priority for diagnostic tests should be for
1) Those who require hospitalization and
2) Those that are at high risk for severe complications (e.g. chronic lung, cardiac disease, etc.; see complications below).
To establish a diagnosis:
Specimen: upper respiratory sample (nasopharyngeal swab, nasal swab, throat swab) collected and shipped to a central public health laboratory, if available; kept in a refrigerator at a temperature of 4 degrees Celsius (for not more than a week) or, preferably, -70 degrees Celsius freezer.
The following tests can then be carried out using the specimen.
Reverse transcriptase (RT)-PCR is used to confirm the diagnosis of influenza A, B, H1 and N3. However, RT-PCR is performed only when the results will substantially benefit clinical management or when there is a recognized public health benefit. For example, if the first case is suspected in a country, the test should be done to confirm that indeed the problem is now available in the country.
Culture is another way to confirm the diagnosis, but it is too slow for clinical management. In other words, there is no time to wait for results that take days before a decision is made on how to manage the patient. Also, a negative culture does not rule out the virus.
Rapid antigen tests can distinguish between influenza A and B. A positive rapid test for influenza A will suggest H1 N1 if the case detection definition criteria (mentioned earlier) are met, during an outbreak. But sensitivity and specificity for H1 N1 unknown; there is already poor sensitivity demonstrated for seasonal influenza. A negative test does not exclude infection.
Immunofluorescent antibody testing can also distinguish between influenza A and B. A positive test for influenza A will suggest H1 N1 if the case detection definition criteria is met, when there is an outbreak. A negative test does not exclude the virus, since sensitivity is unclear.
Management/ Treatment
The majority of people who contract the virus experience the milder disease and recover without antiviral treatment or medical care. Of the more serious cases, more than half of hospitalized people had underlying health conditions or weak immune systems. This is good news.
For most cases, supportive care at home is all that is needed:
Resting
Plenty of oral fluids
Pain reliever for aches (non aspirin for children and young adults due to the risk of a condition called Reye’s syndrome).
When to seek medical care:
Shortness of breath or difficulty in breathing
Fever > 3 days
Antiviral Drug
Antiviral drugs may reduce the symptoms and duration of illness, just as they do for seasonal influenza. They also may contribute to preventing severe disease or complications and death. Only a small number of people infected with this new influenza strain (H1 N1) have been treated for it with antiviral drugs, however.
There are two classes of antiviral drugs for influenza: inhibitors of neuraminidase such as oseltamivir and zanamivir; and adamantanes, such as amantadine and rimantadine. Tests on viruses obtained from patients in Mexico and the United States have indicated that current new H1N1 viruses are sensitive to neuraminidase inhibitors, but that the viruses are resistant to the other class, the adamantanes.
Antiviral drugs are to be used according to national pandemic influenza preparedness plans. Public health authorities in some countries have decided to treat patients likely to have this disease as a part of public health measures.
Clinicians should make decisions based on assessment of the individual patient's risk, where drugs are available for treatment. Risks versus benefits should also be evaluated on a case by case basis.
The drugs should be used on hospitalized patients or people with high risk for influenza-related complications (see complications below).
Individuals should not buy medicines to prevent this new influenza without a prescription.
Complications
Exacerbation of underlying chronic medical conditions
Upper respiratory tract disease (sinusitis, otitis media, croup)
Lower respiratory tract disease (pneumonia, bronchiolitis, status asthmaticus)
Acute respiratory distress syndrome
Respiratory failure
Cardiac (myocarditis, pericarditis)
Neurologic (Acute and post-infectious encephalopathy, encephalitis, febrile seizures, status epilepticus)
Toxic shock syndrome
Secondary bacterial pneumonia with or without sepsis
High risk factors for complications: chronic lung disease (such as asthma or chronic obstructive pulmonary disease), immunosuppressive conditions (e.g. HIV), cardiac disease, diabetes mellitus, and obesity.
Prevention
1) Infected people should:
Cover their mouth and nose when coughing or sneezing,
Stay home when they are unwell,
Clean their hands regularly, and
Keep some distance from healthy people, as much as possible.
2) Work is already under way to develop a vaccine (update, early July 2nd, 2009). Making a completely new influenza vaccine can take 5 to 6 months.
3) Influenza antiviral drugs. But these should be given only to a person who has been or may be near a person with swine influenza. When used to prevent the flu, antiviral drugs are about 70-90% effective, and the number of days they are used vary, depending on the situation.
Travel
The WHO is not recommending travel restrictions related to the outbreak of this influenza A (H1N1) virus, because limiting travel and imposing travel restrictions would have very little effect on stopping the virus from spreading, as scientific research based on mathematical modeling showed. People need to travel for business and pleasure, etc; restrictions to that will have serious consequences to people’s lives.
References
1) Kumar and Clark; WB Saunders 2002, Clinical Medicine, 5th edition
2) World Health Organization (WHO); online
3) UpToDate (online)
4) MedicineNet.com
5) Wikipedia (online)
6) Italicized illustration (my own creation)
7) Other (online)
Compiled by Dr David L. Lukudu
Assistant Project Health Manager/ Medical Officer
Malteser International
Rumbek, Lakes State, South Sudan
3rd to 5th July 2009
All rights reserved. J
