Who Will Stand Up for the H1N1 Vaccine?

To raise vaccination rates and also to ease citizens' minds, the Department of Health announced that beginning on January 9 citizens could choose between the vaccine produced by the domestic pharmaceutical manufacturer Adimmune and the imported vaccine made by Novartis. But are vaccines really a case where "imported goods are better"? What are the relative risks of getting these shots versus forsaking them? And if you do decide to roll up your sleeve, what concerns should you have?

According to World Health Organization statistics released on January 10, 2010, the H1N1 flu virus had resulted in the deaths of over 13,000 people during the previous six months. At 7016, North America suffered the largest number of deaths. It was followed by Europe (2788) and the western Pacific (1447). Taiwan had 38 deaths caused by the virus.

The H1N1 virus is similar to the extremely deadly 1918 influenza A strain that is known as the Spanish or swine flu. To meet this enemy head on, the WHO early on called for every country to use vaccines to prevent its spread. Drug manufacturers around the world mobilized for production, but because they were only accustomed to collectively producing about 9 million doses of the seasonal flu vaccine each year, their capacity was insufficient to meet the needs of the world's 6.8 billion people.

Adverse effects:

Executive Yuan personnel getting H1N1 flu vaccine shots. Each year in Taiwan about 2 million doses of seasonal flu vaccine are administered. Another 200,000 doses of three-in-one vaccines for diphtheria, tetanus, and whooping cough are given to newborns. The 5.56 million doses of H1N1 flu vaccine administered this fall and winter have helped to limit the outbreak.

Under these conditions of scarcity both in Taiwan and abroad, the ROC's Department of Health twice solicited bids for production of the vaccine, but it couldn't find suitable bidders. Consequently, responsibility for producing the vaccine in Taiwan fell to the sole domestic manufacturer of seasonal flu vaccines: Adimmune. To cope with the four to five months that Adimmune needed to move from human trials to production, the DOH also purchased 5 million doses from the Swiss company Novartis at 7.95 per dose (about NT$380, or twice what it paid to Adimmune).

At the end of December 2009, after the media exposed several cases of people allegedly dying from adverse reactions to the vaccine, the number of people getting inoculated dropped precipitously. It sparked a debate about whether Adimmune's vaccine was safe.

When you peruse the figures announced by the ROC's Central Epidemic Command Center, you see that to January 18, 2010, 1051 apparent adverse reactions had been reported. Of these, 892 were associated with the Adimmune vaccine, giving a rate of occurrence of 17.5 cases per 100,000 doses, as against 89 cases or 18.1 per 100,000 for Novartis. Of the 298 apparent serious adverse reaction (such as death, life-threatening illness, permanent disability, and birth defects), 277 (5.4 per 100,000) were associated with the Adimmune vaccine, and 16 (3.2 per 100,000) with the Novartis vaccine. The difference between these rates of occurrence is quite large. Of the deaths allegedly associated with the vaccines, 28 occurred after Adimmune shots, as against two after receiving the Novartis vaccine.

When you look at how infectious diseases have affected mankind over the course of history, the development of vaccines has proven to be extremely effective at saving lives and preventing epidemics.

The way vaccines work is by exposing people's immune systems to small, less toxic amounts of a pathogen, letting the body produce antibodies to it so that it will be better able to repel the enemy when it next encounters it. Yet vaccines aren't a silver bullet, and they don't work for everyone. For instance, the immune systems of the elderly may be so weak that they can't muster a sufficient reaction. And some pathogens are particularly adept at mutating and avoiding the defense system created by the vaccine. Take, for instance, malaria, tuberculosis, and HIV-all have eluded attempts to create effective vaccines.

H1N1 had seemingly disappeared for over 30 years, but this outbreak hit hard, so the government would have been remiss in its duties by not taking strong counter measures.

But there are risks to any strategic decision. The human body, after all, is a subtle structure. The same vaccine can elicit different reactions in different people. In extreme cases, vaccination can cause an adverse reaction and even kill someone. Suffice it to say that the last wave of swine flu created a worldwide public health disaster.

In January of 1976, 18-year-old army recruit David Lewis came down with various symptoms of the flu including a fever, a runny nose, and full body shakes. A few hours after entering the hospital, he died of pneumonia. The army also had another 300 cases with similar symptoms. A clinical specimen from Lewis' body was sent to the US Centers for Disease Control and Prevention, where H1N1 was found in it. The discovery greatly alarmed disease prevention officials, because the 1918 flu outbreak that had killed 40 million people was H1N1. They were concerned that Lewis' death was a harbinger of an epidemic to come.

The CDC immediately found itself with a dilemma: Although the afflicted were few and scattered, under the belief that preventing disease is like going to war and that you hit the enemy with all that you've got, the US government announced plans to vaccinate all citizens. With a US population of about 200 million back then, Congress specially allocated US$135 million, and in 10 days 1 million people had been vaccinated.

Yet at about the same time, scattered reports began to come in about people dying after getting vaccinated, and there was a steady stream of doubts about the wisdom of the vaccination policy. By the time US public health agencies woke up to the severity of the situation in the middle of December, there had already been 40 million people vaccinated, and there had been 67 reported cases of patients dying due to adverse reactions. Many people also found that the vaccine had bad effects on their nervous systems: Some felt sapped of energy and others found it difficult to swallow. And to top it off, it turned out that this whole national mobilization was for naught: No outbreak of swine flu ensued!

Some 33 years later, there has likewise been alarm about H1N1 and calls to get everyone inoculated. But one thing is certain: research and development have brought advances in vaccination techniques from three decades previous. Admittedly there have been some blemishes. (Not long ago, for instance, the United States announced it was calling back 800,000 vaccine doses for children under the age of three from Sanofi Pasteur-the vaccine division of the French Sanofi-Aventis Group-because its potency fell 12% below US government standards.) Yet the epidemic has been moderating throughout the world, which bears witness to the value of disease prevention efforts this time.

Yet questions nag about side effects caused by the H1N1 flu vaccine and about deaths allegedly caused by it.

As of January 18, there had been 298 cases of alleged serious adverse reactions to the H1N1 vaccine in Taiwan, including 30 deaths. There were 47 people still being treated at hospitals, and most of the remaining had already returned to health. Problems included convulsions (27 cases), Bell's palsy (35 cases), immune thrombocytopenia (10 cases), and vasculitis (seven cases). Most of these problems were connected with the medical histories of the individuals afflicted.

On January 7 the Department of Health announced its findings about the first group of six deaths: all of them, it found, died of reasons unrelated to the vaccine. The seven-year-old son of Taichung obstetrician Liu Jincheng, who had a red rash spread from his feet and a fever that wouldn't subside, experienced complications and died from bleeding in the brain stem. The boy's father wondered if some component of the vaccine caused his son's immune system to weaken, leading to his death.

In their findings based on an autopsy and pathology tests, coroners with the Institute of Forensic Medicine at the Ministry of Justice stated that they believed an infection of parvovirus B19 had invaded the cells in the boy's bone marrow that produce red blood cells, leading to hemophagocytic syndrome. This in turn caused enlargement of the liver and spleen, tissue necrosis in multiple organs, and disseminated intravascular coagulation, finally resulting in death due to bleeding in the brain stem. The causes of the child's death had been complex, but death due to infection with such a common virus was indeed a rare event.

Su Ih-jen, former director of the ROC's Centers for Disease Control and a professor of pathology at National Cheng Kung University's medical school, looks at the issue from a different angle: Whether or not people get the vaccines, every week in Taiwan there are 389 new cases of people afflicted with Bell's palsy, 842 of people suffering convulsions, 1532 cerebral strokes, and 745 myocardial infarctions, he notes. Now that 5 million Taiwanese have been given the H1N1 vaccine, when one of them becomes afflicted with those other conditions, people are likely to erroneously connect it to the vaccine.

Su explains that babies in Taiwan are inoculated with a three-in-one vaccine for diphtheria, tetanus, and whooping cough. The inoculations of the 200,000 newborns are spread throughout all 12 months of the year, and although there are scattered cases of adverse effects, people have little sense of them. Moreover, the 2 million doses of seasonal flu vaccine that are administered in Taiwan each year, which are spread over five months from the end of September through January, have resulted in adverse side effects and, allegedly, even some deaths. Yet people don't regard the problem as serious. Now, however, with such a large number of H1N1 vaccines administered in so short a time, the cases of subsequent medical conditions have attracted a lot of scrutiny. When the Department of Health didn't immediately provide this context, it resulted in a collapse of confidence in the nation's vaccination policy. And at this point comments from health experts have less impact than the tears of much-pitied parents who have lost their son.

According to World Health Organization estimates, the death rate from the current wave of H1N1 is 0.45%-much higher than the rate of 0.1% for most flu strains. On average 4500 people in Taiwan die each year from the flu or resulting complications, placing it ninth among all causes of death. From these statistics, it can be estimated that if no one in Taiwan was given the H1N1 vaccine, and if the antiviral drug Tamiflu was never prescribed to fight it, then the number of deaths would surpass 10,000.

Seasonal flu typically hits the elderly hardest (with 80% of total deaths seen in those over the age of 65), but H1N1 on the other hand, can result in overstimulation of a young person's immune system in response to the virus, which can damage the lungs and kidneys and even potentially cause organ failure and death.

Su observes that there hasn't been a severe outbreak of seasonal flu this fall and winter, and it seems as if the flu strains are interfering with each other. The more virulent H1N1 has seemed to suppress seasonal flu. But if the historical patterns of the H1N1 outbreak in 1918 and the H2N2 outbreak in Asia in 1957 bear out, although the virus may start to weaken as spring approaches, a second wave of cases is likely to hit six months later, perhaps as a result of strains mutating and combining. Consequently, Taiwan will have to be more vigilant this fall, and the public will still have to confront the question of whether to get vaccinated or not.

Some people compare refusing a vaccination to being a "freeloader" in game theory: So long as others get vaccinated, you're also safe. It's like having your cake and eating it too. Yet if no one else were to get vaccinated, the situation would become one where you've got to protect yourself and "whoever gets vaccinated first is safest." And since there's no better way of protecting yourself from the swine flu than getting vaccinated, it would be best to let the controversy over H1N1 return to the scientific realm where it belongs. Only then will we be able to defeat this invisible enemy.