To Catch a Virus
Constant and systematic surveillance needed to identify particular strains
By Mike Gomez
Under the influence of the stars," said the Italian physicians who first gave a name to an illness that mysteriously seemed to befall just about everyone at the same time. Even after the notion of astrological effects was dismissed and the mechanism of pathogen transmission was established, this age-old disease still goes by its archaic name of "influenza" or "the flu."
Highly communicable, the influenza virus has wreaked havoc on exceedingly large numbers of people long before medical science quite understood how it spread and made people sick. Ironically, the infamy it has earned has caused many people to malign this virus, often blaming it for so many other conditions or syndromes with different etiologies. Many other illnesses are mistaken for influenza, most especially during an outbreak or during the annual "flu season." It is extremely widespread, but it is also widely misdiagnosed.
In most cases though, misdiagnosis hardly matters since influenza management is usually similar to that for most of the other implicated diseases. The efficacy of specific medications for influenza diminishes with time, as they are best administered a day or two after exposure, or when the symptoms of acute respiratory infection are manifest. The best they can do is, in fact, merely reduce the duration of the illness by about a day.
But even if the speed of its progress makes laboratory work unnecessary in case management, it is of great importance to health managers in medium to large scale health systems, and of utmost importance to the global health system. Filipinos came to appreciate this only after being tweaked by a relatively innocuous incident initially thought to be a bioterrorist attack.
WHO and Flu
While the concept of influenza surveillance seemed novel to most people who heard Health Secretary Manuel Dayrit's pronouncements during the "school flu crisis" last year, the global effort has been underway for over half a century. It is, in fact, the longest running laboratory-based disease surveillance in the world, according to Dr. Hitoshi Oshitani, WHO Western Pacific Regional Adviser in Communicable Disease Surveillance and Response.
Thorough vigilance is necessary for influenza because it is not simply one pathogen being looked out for, but a spectrum of related organisms that pose serious threats to public health in entire countries and regions. For all intents and purposes, influenza epidemics are like attacks of completely new pathogens since the susceptible population usually has had no exposure to the specific strains or varieties of the virus involved.
Dr. Oshitani recounted that about 20 million people died of a global outbreak of what is now referred to as the "Spanish flu" of 1918. Since then, he noted, there had been a number of other widespread epidemics involving other varieties of influenza. In each case, the pathogen was completely new to humans.
A significant factor in the emergence of extremely virulent flu variants is the involvement of animals as recombining vessels for previously benign viruses that were unable to pass from human to human. The 1997 Hong Kong avian flu incident remains fresh in the minds of many Filipinos who still harbor images of hundreds of thousands of chickens destroyed and burned.
Bug Watch
The influenza surveillance being conducted globally through the WHO is not aimed at direct intervention for people suffering from the disease. It is more interested in those who are still at risk of infection. The program entails collection of culture specimens from people found by clinical definition to be suffering from influenza, and doing extensive laboratory work on these samples to determine what specific influenza virus variant is responsible.
While this may very well seem like closing the barn door after the cattle have escaped and strayed, health managers are concerned with future epidemics. They are certain that there will be subsequent outbreaks until a permanent solution is effected.
That permanent solution, sad to say, is not forthcoming. Unlike the smallpox and polio viruses, which were subject to highly successful eradication efforts, the influenza viruses are a hardy lot that can mutate much quicker than what the world's health scientists with all their digital technology can keep up with. There is no magic bullet to demolish influenza; neither is there any idea on how a final solution can be implemented. The best the global health community can do is maintain vigilance so that the health system may be aware of the status of the influenza pandemic at a specific time.
The main value is in determining which specific pathogens may have arisen and spread in one part of the world so that vaccine manufacturers would produce only the proper vaccine for the specific variant of influenza that is causing a prevailing epidemic.
This is a global system that works. The different pharmaceutical companies that manufacture influenza vaccines have agreed to take their cue from the WHO. With all the trouble involved just to come out with instructions on a vaccine formulation, it would seem like building the proverbial nuclear reactor just to boil water. That is, unfortunately, what the world needs to unceasingly do.
WHO monitors the global pandemic through a network involving 110 National Influenza Centers in 83 countries. Backstopping these laboratories are the four WHO Collaborating Centers for Virus and Research in the US, Australia, Japan, and the United Kingdom. A geographical information system called "FluNet" was recently established to facilitate monitoring through the Internet.
Home Front Vigilance
The Philippines has long been involved in this worldwide scheme, with a National Influenza Center located at the Department of Medical Microbiology at the University of the Philippines- College of Public Health. Actual surveillance, however, has been limited to minuscule efforts conducted by the staff of the Research Institute for Tropical Medicine (RITM).
As a catchment hospital in the Muntinlupa area, RITM receives its share of influenza cases and many other influenza-like cases. Since late 1998, pharyngeal swabs taken from these patients have been brought to the virology section of the research center where expert laboratory personnel headed by Dr. Fems Paladin grew cultures and proceeded to identify the specific pathogen implicated. Upon determining a positive case of influenza and identifying the virus strain, the sample is dispatched to the Collaborating Center in Australia where further laboratory analysis identifies the particular virus variant.
Such valuable data have provided RITM with at least a rudimentary picture of the flu epidemic in the area, knowing which pathogen was circulating among the target population at any given time. "When we can determine what is circulating, we can predict what may be an epidemic or pandemic strain," Dr. Paladin told MEDICAL OBSERVER.
On the day of the school flu incident late last year, Dr. Paladin's laboratory and the National Epidemiology Center were tasked to conduct disease surveillance of the affected population and flu patients at some cooperative institutions. Specimens were sourced from school clinics, Camp Emilio Aguinaldo, Fort Bonifacio General Hospital, the PSG Hospital, and other sites. Virology work on the samples established that the predominant strain causing the epidemic was Haemophilus influenza B, and not the A strain as earlier feared. In fact, Influenza A was only found in one of the soldiers examined.
Samples sent to Australia indicated that the particular variant of the Influenza B involved was Shandong, a pathogen that had not been present in the Philippines for many years. Dr. Paladin explained that the high incidence of flu at the time might have been due to the lack of immunity among the affected population since the school children would have been injected with a vaccine against the Sichuan variant. B-Sichuan was previously tagged by global surveillance as the predominant flu pathogen in the area. Unfortunately, B-Shandong is antigenically different from B-Sichuan, Dr. Paladin explained.
While RITM responded superbly to the perceived crisis, the influenza surveillance and virology work it had been engaged in for three years was little more than experimental. Not quite institutionalized yet, Dr. Paladin's project relied on funding from alternative sources, including the pharmaceutical industry. Manufacturers of vaccines do, after all, hold a large stake in the effort to accurately identify circulating pathogens so they can tailor-make the succeeding batches of influenza vaccines.
Devious Disease Agent
Even with the WHO generating recommendations twice a year, the war against this disease rages unceasingly without any prospect of final victory in sight. Due to the nature of the virus, influenza cannot be totally eliminated. The most humanity can do is hold the epidemic at bay with the best systems and technology, granted ample funding is available. Unfortunately, vaccination against this disease is not among the priorities of a government that is still addressing vaccine-preventable killer diseases. Flu immunization offers only short-term protection against the specific pathogens the vaccine is meant to combat.
While the flu vaccine's immunological efficacy is believed to be as high as 90 percent, this rate drops to 70 to 80 percent in practical application due to the compromised health condition of many vaccine recipients particularly the young and sickly and the elderly. It is, therefore, not very useful in controlling an ongoing outbreak. Neither is it deemed very effective in terms of disease prevention, Dr. Oshitani indicated, pointing out, however, that it is more useful in preventing severe complications like pneumonia.
Managing influenza is not as simple either as administering the prescribed drug. The current flu antivirals might not be justly regarded as "cures" since they only alleviate the flu's symptoms or its sequelae and shorten its duration. Dr. Oshitani pointed out, however, that many of the fatalities attributed to influenza are caused by secondary infections, often bacterial, which should be treated with antibiotics.
When enough people acquire some immunity after exposure or through vaccination, the disease could execute a flanking maneuver and strike with a different virus variant that the population is not prepared to combat. Monitoring of the pandemic over several decades yielded a good amount of information on the annual epidemic patterns-indicating the expected peaks in flu cases.
During these peak seasons, correct diagnosis becomes much easier because most cases showing up at emergency rooms or outpatient departments actually are influenza. The same cannot be said for the Philippines, Dr.
Oshitani observed, since the expected peaks are never clearly pronounced. The cold months are considered influenza season because people typically tend to crowd close together-seeking each other's warmth and company. In a tropical milieu such as the Philippines, there is never really any cold season that cause people to overcrowd and transmit whatever viruses they may be harboring.
Dr. Oshitani believes the slight peaks detected in the Philippines that coincide with the sharp peaks in temperate countries in the Northern Hemisphere are not due to any human behavior pattern, but to the effects of regional epidemics on the Philippine population. With the increased frequency in international travel, the flu can easily spread throughout a region or a continent. Dr. Oshitani believes the virus can spread across a country as large as the US in just a few days.
It is, after all, the highly contagious nature of influenza that gives it its name and merits global concern. Dr. Mark Edward White of the US Centers for Disease Control and Prevention vividly describes this process: "When someone with flu coughs or talks, billions of infectious particles of little gobbets of saliva and slime are blasted out into the air where they float into the lungs of nearby people."
It is for this reason that many other illnesses that seem to affect a large number of adjacent people at the same time are loosely referred to as flu. Dr. White notes that the disease many Filipinos refer to as "intestinal flu" is a euphemism for an uncomplicated gastrointestinal tract infection that will usually just go away by itself. It is not caused by influenza virus, and is therefore not really flu.
The mode of transmission of this disease is not the same as that of influenza, which is airborne through droplets or aerosolized fluids; or even through hand-to-hand contact. "Ever wonder what happens when you don't have flu?" Dr. White poses. "You are still sharing fluids with the people in your environment."
Getting a Grip on La Grippe
When Dr. Dayrit announced initiatives to establish influenza surveillance, he was not referring to the existing work of RITM, but to a widely expanded project of the National Center for Disease Prevention and Control. After a recent workshop to frame up the new project, it was decided to expand the present surveillance effort to a larger pilot area that would include City Health Offices in a few other areas apart from the existing sentinel site in Muntinlupa. A pilot project, it precedes the establishment of influenza surveillance in every province and city in the country.
National Epidemiology Center's Dr. Agnes Benegas, who heads the field surveillance component of this new project, noted that the expansion has to be done in phases because there remain lessons to be learned before going full blast. On the ground level, there is still some degree of discord on the clinical diagnosis of influenza. Although influenza is among the "reportable" diseases of the National Epidemic Sentinel Surveillance System, what are actually being reported are "influenza-like" cases, Dr. Benegas admits. For the new expanded surveillance effort, an updated case definition is being considered.
Actual surveillance will be carried out similarly to the nationwide Acute Flaccid Paralysis surveillance. Some of the existing infrastructure of the poliomyelitis surveillance system will be mobilized for the flu effort.
The system will involve stockpiling the select sentinel sites with the necessary materials for collecting viral samples. The transport media needed for containing the virus and the ice packs required to keep temperature low during transit have to be provided to the sentinel sites in sufficient quantity. Throat swabs taken from influenza-suspect patients at these sites will be sent quickly to RITM for initial laboratory analysis. Since the virus is rather sensitive, the transport media with the virus sample should be handled within a cold chain system similar to that of the Expanded Program on Immunization.
Dr. Benegas also hopes to explore the possibility of tapping the services of a private delivery service to take care of dispatching influenza virus samples. The DoH presently engages the services of DHL in transporting specimens taken from patients exhibiting acute flaccid paralysis for analysis in Metro Manila.
While this scheme will involve health workers at government facilities, the participation of private practitioners will be an indispensable element of the future system.
Dr. Paladin communicated the same concern with pediatric infectious disease expert Dr. Salvacion Gatchalian, stressing the need for specialists in the private sector to get involved in such widespread efforts.
"Slowly we establish the pilot effort, know our limitations, understand operational issues, then move on to expand to supplemental surveillance among private medical practitioners," Dr. Paladin said. She admitted, though, that the program proponents might need to offer something in exchange when inviting private physicians to join the global surveillance effort. "We have to validate their interests and commitments."
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