Under Siege
Perennially attacked by various mutations of the flu virus, the medical community builds up its arsenal of vaccines and antivirals
By Lucio Victor Jr.
Three pandemics after and scores dead from it in the past century, man it seems has yet to learn from the murderous rage of the flu virus. This invisible assassin can exacerbate some preexisting pulmonary, cardiovascular, renal, and endocrine diseases, take advantage of the immunocompromised and immunosuppressed, and cause significant morbidity while pushing the severely ill populace closer to their graves.
"Anybody-from the very young to the very old, the rich to the poor-is equally susceptible to the flu virus," says Dr. Benilda Galvez, chair of the Council on Tuberculosis and Lung Infection of the Philippine College of Chest Physicians (PCCP). She adds that the propensity of the virus to cause infection is very high since it is very contagious, spreading through respiratory droplets released by the infected person when he talks, coughs, or sneezes.
Killer Profile
An acute viral illness of the respiratory tract, cough, and rhinorrhea are not the only symptoms associated with it. Dr. Galvez adds that it can cause a bad case of myalgia, headache, and fever that are often the reasons why affected persons have to stay home sometimes up to two weeks.
According to her, the flu's impact is felt not only at an individual level but on a wider scale as well. She explains: "[Getting sick] translates into absence from work that results in loss of productivity. For students, absence from school will cause them to double time [on lessons missed]. And of course the ill feeling you get when you are sick-being bedridden and all."
Being incapacitated with flu is not new to everyone. People in fact just dismiss it as a set of symptoms that should eventually go away after a week or so.
But what makes it so stealthy?
Dr. Veronica Chan head of the WHO National Collaboration Center for Influenza, reveals the three types of flu viruses-simply tagged A, B, or C-launch an attack on healthy cells particularly those lining the respiratory tract.
This siege is made possible by two structures on the viral surface. The rod-like hemaglutinin (HA) enables the virus to attach to the cell while the knobby projection neuraminidase (NA) facilitates the release of viral genetic material to the infected cell. As this happens the viral genetic material incorporates itself into the cellular genome making the cell a factory that produces innumerable viral cells. Once the cell is exhausted of its resources, it dies out and the viral cells it has produced will continue to infect other healthy cells.
Influenza A, B, and C are basically similar except for differences in the internal matrix and nucleoprotein. Of the three, Influenza C causes no disease or in especially susceptible individuals, mild illness. Influenza A, on the other hand, is responsible for most epidemics and all pandemics while Influenza B has no capacity for pandemics but on occasion can incite serious epidemics.
Such was the case last year when several grade-school children in Metro Manila were downed by a mysterious illness. Dr. Chan revealed that the epidemic was due to Influenza B and Influenza A (H1N1) circulating at the time.
On Guard
New strains of Influenza A and B-against which humans do not have immunity-appear periodically with minor changes on the surface antigens (antigenic drift) and occasionally leading to seasonal epidemics. Dr. Chan notes that antigenic drift is commonly caused by point mutations that may be as small as a single change in the amino acid sequence but significant enough to cause a remarkable change in any of the surface antigens of the virus.
In the case of Influenza A, major changes in the antigenic glycoproteins take shape (antigenic shift) inducing widespread pandemics. This may be attributed to genetic reassortment, a state wherein large sections of the viral genome rearrange to cause a very marked change in the virus itself.
Dr. Galvez believes that because of the nature of variations in the flu virus and their notoriety in causing illness and exacerbating preexisiting medical conditions, persons at high risk should at least have an annual flu vaccine.
Dr. Chan cites three kinds of flu vaccines in the market. Though all of these are inactivated, the original vaccine that contained whole viral cells has since been pulled out of the market because of adverse effects.
"Virologists took a look and tried to see what was causing the adverse effects in vaccinated individuals and they saw that some components of the whole virus vaccine were responsible for the adverse events…despite ensuring good immunity by enhancing good production of antibodies," said Dr. Galvez.
She adds that these adverse events are mainly due to egg proteins incorporated in the viruses that used for the vaccines. Egg proteins easily incorporate into viral cells since these are cultures on embryonated eggs.
Another type, the purified viral vaccine contained only viral parts or subunits. This vaccine reduced the possibility of adverse reaction by eliminating the allergenic proteins. However, it induced a lower rate of seroconversion among vaccine recipients and thus does not confer as much immunity as the whole virus vaccine.
After exhaustive research was done, virologists split the viral cells open and ensured that only the needed antigens would be included in the vaccine. Removing the component responsible for the adverse reactions gave birth to the split type viral vaccine.
Aside from significantly reducing the occurrence of adverse events, Dr. Chan notes that the split virus vaccine induced remarkable seroconversion. "The purified vaccine suffers in comparison with the split virus vaccine and gives lower antibody production," she adds.
Recently, trials on yet another vaccine began. Composed of live attenuated influenza virus (LAIV), these types of vaccines are now in use in Russia and have been in development in the US since the 1960s. These vaccines are delivered via nasal spray and can induce a broad mucosal and systemic immune response mimicking an actual infection with flu.
A 1996-97 study of children 15 to 71 months showed it was 93-percent effective in preventing culture positive influenza A (H3N2) and B infections. Otitis media in vaccinated children was reduced by 30 percent while otitis media with concurrent antibiotic use was reduced to 35 percent compared with unvaccinated populations. In adults, there was a nine to 24 percent reduction in febrile respiratory illnesses and a 13 to 28 percent reduction in lost work days.
Going for the Cure
Aside from vaccines, antivirals for flu are also available. Dr Chan notes that so far the most effective antiviral available in the Philippines is oseltamivir. A neuraminidase inhibitor, oseltamivir is capable of blocking the action of NA, which is to release viral genetic material into the infected cell. Thus, although the virus may attach to a normal healthy cell, it cannot convert that cell into a virtual virus factory.
Dosage for adults is 75 mg twice a day for five days; two mg per kilogram per day for five days for children. Dr. Chan says this drug is very patient-friendly such that "after consuming the first two capsules within 36 to 48 hours from the onset of fever, you will already feel very normal and be back on your feet." However, she adds: "The advice is to continue the medicine and finish the five-day course to fully eliminate the virus from the system."
Dr. Chan feels oseltamivir is the most effective among the available antivirals because it can be used in the treatment and prevention of both Influenza A and B with no note of viral resistance.
The earlier antivirals like rimantadine and amantadine, which were used for the treatment and prevention of influenza A only, have shown viral resistance. Between the two, amantadine gave very good and high values in the blood while rimantadine showed good availability in the mucosal surface of the respiratory tract.
Another neuraminidase inhibitor, zanamivir can be used to treat both influenza A and B but is not preventive and cannot be used for children younger than seven years of age. Of the antivirals, amantadine and oseltamivir have good coverage throughout pediatric and adult age groups.
Dr. Chan notes that since it takes a minimum of two weeks for any individual with a competent immune system to seroconvert there is a window of opportunity for the flu virus to still infect and cause illness in the individual.
Because of this, it may be actually prudent to use an antiviral that can prevent infection against influenza A and B while waiting for the antibodies to take effect. Also, it is very helpful in persons who may have been vaccinated but still contract the disease because of poor seroconversion. Chemoprophylaxis with antiviral use has shown a 70 to 90 percent prevention from influenza A infection.
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