Monday, October 26, 2009

Pestilence

New Disease: "Swine Flu" a Primer

Over the past several months the increasing incidence of "Swine Flu" in humans has become apparent. In the United States, the Obama administration has declared the 2009 Swine Flu a pandemic and formally instituted a state of Federal Emergency by which to deal with it more effectively.

"Swine Flu" is an influenza which was originally thought to have originated in pigs that for some unknown reason managed to cross the trans-species barrier to humans. However, according to the CDC:

"This virus was originally referred to as 'swine flu' because laboratory testing showed that many of the genes in this new virus were very similar to influenza viruses that normally occur in pigs (swine) in North America. But further study has shown that this new virus is very different from what normally circulates in North American pigs. It has two genes from flu viruses that normally circulate in pigs in Europe and Asia and bird (avian) genes and human genes. Scientists call this a 'quadruple reassortmant' virus."

"The virion is pleomorphic, the envelope can occur in spherical and filamentous forms. In general the virus's morphology is spherical with particles 50 to 120 nm in diameter, or filamentous virions 20 nm in diameter and 200 to 300 (-3000) nm long. There are some 500 distinct spike-like surface projections of the envelope each projecting 10 to 14 nm from the surface with some types (i.e. hemagglutinin esterase (HEF)) densely dispersed over the surface, and with others (i.e. hemagglutinin (HA)) spaced widely apart. The major glycoprotein (HA) is interposed irregularly by clusters of neuraminidase (NA), with a ratio of HA to NA of about 4-5 to 1.

Influenza viruses contain 7 to 8 segments of linear negative-sense single stranded RNA. The total genome length is 12000-15000 nucleotides which encode for 11 proteins (HA, NA, NP, M1, M2, NS1, NEP, PA, PB1, PB1-F2, PB2). The best-characterised of these viral proteins are hemagglutinin and neuraminidase, two large glycoproteins found on the outside of the viral particles. Neuraminidase is an enzyme involved in the release of progeny virus from infected cells, by cleaving sugars that bind the mature viral particles. By contrast, hemagglutinin is a lectin that mediates binding of the virus to target cells and entry of the viral genome into the target cell. The hemagglutinin (H) and neuraminidase (N) proteins are targets for antiviral drugs. These proteins are also recognised by antibodies, i.e. they are antigens. The responses of antibodies to these proteins are used to classify the different serotypes of influenza A viruses, hence the H and N in H5N1."
For more see THIS...

"Swine Flu" now known as 2009 H1N1 Influenza, causes disease in human beings. It is spread through person to person contact--primarily as a result of contamination from the oral/nasal secretions of infected individuals. The most common symptoms include: fever, cough, sore throat, runny or stuffy nose, body aches, headache, chills, fatigue and sometimes, diarrhea and vomiting.

"Swine Flu" or 2009 H1N1 Influenza (also referred to as Novel H1N1 Influenza) is a subtype of Type A influenza as is type-ordinaire seasonal flu. To date 2009 H1N1 Flu appears to be slightly more virulent than seasonal flu but can usually be treated successfully with antiviral medications in patients who become extremely ill. A definitive health statement on the ultimate severity/significance of this new type of flu would be premature at this time due to lack of intermediate and long-range follow-up data.

A vaccine which is purportedly specific for this virus has been developed in an "accelerated fashion" given the sudden appearance of this "quadruple reassortmant" virus in humans. While it is said by federal health officials to be safe, there is very little clinical follow-up data so far in patients to whom it has been administered. At present (October 26, 2009) there is a limited supply (less than 30 million doses) of this vaccine nation-wide and the CDC has instituted a recommended protocol for initial administration until additional doses become available. For more information on flu vaccines see THIS...

It is possible to test for the presence of "Swine Flu" (2009 H1N1 Flu) utilizing laboratory investigation. A number of rapid diagnostic tests (RDT's) [rapid antigen testing] with variable degrees of sensitivity and specificity are currently available (at present they are unable to differentiate between subtypes of influenza and are associated with a significant false negative rate) as well as more sophisticated tests involving viral cultures, immunofluorescence assays, and polymerase chain reaction analysis based on nucleic acid sequencing. Sophisticated laboratory tests for influenza allow characterization by viral subtype but require several days to complete. The RDT's generally are available within the hour.

Currently, questions remain with respect to the ratio of the prevalence of 2009 H1N1 flu vs seasonal flu in the US population. According to the CDC however:

"As of September 2009, more than 99% of circulating influenza viruses in the United States are 2009 H1N1. Therefore, at this time, if your health care provider determines that you have the flu, you most likely have 2009 H1N1." (Editor's note: This assumes that there has been no pre-selection of patients subjected to detailed laboratory testing. In one instance some 60% of those tested have been found to have no flu at all. It is possible that due to CDC recommendations, only the higher-risk patients have been tested utilizing sophisticated assays capable of differentiating between the sub-types of influenza. The effect would be to artificially raise the incidence of “swine flu.” This issue needs to be more carefully detailed in the literature and the results widely circulated.)

Previous vaccination(s) for seasonal flu are not likely to be effective against Swine flu due to the different RNA sequences involved. The antibody production after vaccination for seasonal flu is different from that which is produced in response to vaccination for "Swine Flu."

To date (October 17, 2009) 411 patients with laboratory confirmed cases of "Swine Flu" have died in the United States. In the absence of pre-selection of the higher risk patients for sophisticated laboratory testing, this would seem to represent a higher mortality rate for documented cases of 2009 H1N1 Influenza as compared with seasonal flu. It is unclear however whether this represents an artificially elevated rate due to pre-selection of higher-risk patients for detailed laboratory testing. In other words, we simply do not know the value of the denominator (the total number of patients who have contracted 2009 H1N1 Flu).

According to the CDC:

“The proportion of deaths attributed to pneumonia and influenza (P&I) based on the 122 Cities Report has increased and has been higher than what is expected at this time of year for two weeks. In addition, 11 flu-related pediatric deaths were reported this week; 9 of these deaths were confirmed 2009 H1N1, and two were influenza A viruses, but were not sub-typed. Since April 2009, CDC has received reports of 95 laboratory-confirmed pediatric 2009 H1N1 deaths and another 7 pediatric deaths that were laboratory confirmed as influenza, but where the flu virus subtype was not determined.” For more see THIS…

The US Center for Disease Control (CDC) currently recommends vaccination against Swine Flu for high-risk patients including pregnant women, children up to 18, the debilitated, immunocompromised, those with other serious systemic illness(s) and health care professionals only. For more information see THIS...It should be noted however that response to vaccination in general is quite variable and dependent upon multiple factors enumerated in the appendix below. At this early stage of the pandemic the efficacy of the new "Swine Flu" vaccine is unknown. The CDC has indicated that no serious complications/side-effects have arisen in patients who have received the new vaccine thus far.

Anyone strongly suspected of having Swine Flu and who is a member of any of the high-risk groups of patients delineated above should be considered for the early administration of antiviral medication such as Zanamivir which to date lacks any evidence of viral resistance. The CDC generally recommends treatment with Oseltamivir (Tamiflu) although some minimal resistance to it has developed. Unfortunately, 2009 H1N1 Flu is resistant to Amantadine and Rimantadine. The CDC has also indicated that antiviral treatment regimens may change in the future according to new antiviral resistance or viral surveillance information.

Due to the unavoidable delay in obtaining sophisticated laboratory confirmation of "Swine Flu" it is unnecessary to confirm the diagnosis prior to instituting anti-viral drug therapy but it would be wise for all such patients to have viral cultures, immunofluorescence assays, or polymerase chain reaction analysis done in order to successfully document that the patient has "Swine Flu" rather than seasonal flu. This will assist health care professionals in determining the prevalence, severity and therapeutic response in patients with 2009 H1N1 Flu. For the latest Flu update from the CDC see THIS...

Suggestions:

1.) Minimize unnecessary close personal contact particularly in large groups.

2.) Always practice good hygiene including frequent washing of hands with antiseptic soap and water. Avoid touching the mouth and nose with hands. Do not drink or eat from articles used by others. Do not share food or drink with others once it has been dispensed. Always cover the mouth and nose when coughing or sneezing preferably with a disposable tissue.

3.) Anyone who is ill with symptoms and signs suggesting influenza should remain at home until at least 24 hours after the cessation of fever.

4.) Individuals at high risk (especially children) for developing complications from 2009 H1N1 Flu or otherwise concerned persons should seek medical attention as early as possible to allow their physician the option of initiating antiviral therapy at a time when it is most likely to be effective.

5.) Consider being vaccinated against type-ordinaire seasonal flu as the benefit/risk ratio favors being vaccinated.

6.) Carefully monitor further developments with regard to the prevalence and severity of 2009 H1N1 Flu including the potential toxicity and efficacy of vaccines (incompletely known at this time). As further data and the national supply of vaccines become more widely available, consider being vaccinated if the benefit/risk ratio is acceptably established, especially in the Pediatric age-group which at present is at greater risk of severe "Swine-Flu" related illness and death.

*Appendix: How effective is the inactivated influenza vaccine?

"Overall, in years when the vaccine and circulating viruses are well-matched, influenza vaccines can be expected to reduce laboratory-confirmed influenza by approximately 70% to 90% in healthy adults <65 years of age. Several studies have also found reductions in febrile illness, influenza-related work absenteeism, antibiotic use, and doctor visits.

In years when the vaccine strains are not well matched to circulating strains, vaccine effectiveness can be variably reduced. For example, in a study among persons 50-64 years during the 2003-04 season, when the vaccine strains were not optimally matched, inactivated influenza vaccine effectiveness against laboratory-confirmed influenza was 60% among persons without high-risk conditions, and 48% among those with high risk conditions, but it was 90% against laboratory-confirmed influenza hospitalization (Herrera, et al Vaccine 2006). A study in children during the same year found vaccine effectiveness of about 50% against medically diagnosed influenza and pneumonia without laboratory confirmation (Ritzwoller, Pediatrics 2005). However, in some years when vaccine and circulating strains were not well-matched, no vaccine effectiveness can be demonstrated in some studies, even in healthy adults (Bridges, JAMA 2000). It is not possible in advance of the influenza season to predict how well the vaccine and circulating strains will be matched, and how that match may affect the degree of vaccine effectiveness."
For more from the CDC on this issue see THIS...

Incompletely Answered Questions:

1. How widespread will the pandemic become (prevalence)?
2. How ill (virulence) will patients with “Swine Flu” become?
3. How effective (efficacy) will the new “Swine Flu” vaccine be?
4. What if any side-effects/complications will occur after mass “Swine Flu” vaccine administration and how frequently (vaccine complication rate) will they occur?
(Preliminary data available only)
5. What percentage of patients who have laboratory documented “Swine Flu” experience serious illness or death (Morbidity/Mortality) and is their a predilection for certain age groups? (Preliminary data strongly suggest an increased incidence and severity in small children under age 2.

--Dr. J. P. Hubert

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