The Novel H1N1 Flu Pandemic: Are we prepared?
The Novel H1N1 Flu Pandemic: Are we prepared?
Robert C. A. Yang, PhD
Abstract Key words: Swine flu, novel influenza A (H1N1) virus, The 2009 swine flu pandemic is caused 2009 flu pandemic, gene reassortment, by a novel influenza A (H1N1) virus. seasonal flu epidemic, flu pandemic Phylogenetic study reveals that this timeline virus possesses genes derived from viruses of swine, avian and human Initial outbreaks origins through several reassortments. Towards mid-April this year (2009) This virus is capable of spreading from the swine flu that broke out in Mexico person to person readily resulting in a causing numerous cases of infection worldwide pandemic flu as of June 11, and claiming many lives has caught 2009. The flu pandemic timeline for the the international health authorities by past century demonstrates that all the surprise. Why not the HN1 avian flu causative viruses for the pandemics or the SARS-like epidemic? The whole as well as the seasonal epidemics are world has been geared to face any attributed to the type A influenza. The challenges from the two for many years, novel H1N1 virus has established itself since the major outbreaks of the HN1 rapidly as a dominant influenza A strain avian flu with human casualties as of in most parts of the world. So far, most, if late December 200 and ongoing to not all, of the pandemic patients suffers date. It is noted that after HN1 emerged a mild illness. The majority (90%) of the widely in Asia in 200, killing about world's population lives in the northern 0-0 percent of the humans infected hemisphere who is as yet to experience by the virus, many countries took steps the first fall and winter seasons, when it to prevent a similar crisis. SARS was is most prone for flu outbreaks due to the rampant for approximately six months cold and dry weather. A second wave of between February and July 200 with a the pandemic attacks seems inevitable. case fatality rate or CFR of approximately
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10%. It even spread from Asia to the North America in a cluster. The current swine flu epidemic spread quickly across the borders to the immediate neighbor, the U.S.A. and even further north to Canada. The panic was understandably Fig. 1. Pandemic Influenza Phases reflected by the sharp world wide plummeting of the stock market during Phase criteria: In addition to the one week in late April. The rest of the criteria defined in Phase , the same world has not been left unscathed. As virus has caused sustained community- level outbreaks in at least one other the time goes by the H1N1 virus has country in another WHO region 1 invaded other continents beyond the (Courtesy of the WHO). North America, such as South America, T h e W H O h a s s u b s e q u e n t l y Europe, Asia, Australia and Africa. admitted on July 1 that the pandemic The number of countries affected has is unstoppable. As of this date, the increased rapidly. By July 21, the WHO WHO will give up all reports on lab- (World Health Organization) reported confirmed total cases, whilst fatal cases 1,1 laboratory-confirmed cases and due to the novel H1N1 should be lab- 1 deaths (CFR at 0. %) worldwide confirmed. The argument is that it is from 1 affected countries. A month either wasteful or pointless to carry out prior, all 0 states in the United States, costly diagnosis, as the new flu has the District of Columbia, Puerto Rico, become so rampant in most, if not all, and the U.S. Virgin Islands had reported communities and countries. Because it novel H1N1 infection. is a mild flu, most people have chosen to stay home until self-recovery. So, the WHO declares: 2009 Flu pandemic reporting of totals has become much too On June 11th, the WHO announced that inaccurate and actually meaningless. its alert level for H1N1 influenza should In mid-July, experts believe that in the be raised to phase - see the following USA alone there might have been more chart. A global pandemic is officially than a million cases. However, the WHO under way. This is just to signal the and the CDC (Centers for Disease beginning of the so-called first summer Control and Prevention, USA) stress on wave of the pandemic (see Fig. 1. the significance of reports for unusual Pandemic Influenza Phases ). clusters of the new H1N1 virus and the
The Novel H1N1 Flu Pandemic: Are we prepared? related severe cases by the national Viral origins health authorities. In particular, any drug- P h y l o g e n e t i c a n a l y s i s t h r o u g h resistant cases should be reported and international collaboration has produced the strains involved should be shared insights in the origins of the novel 2009 among the international flu scientists. As flu. Obviously it is a human flu in that from now both the WHO and the CDC it is spreading from person to person. consider that to estimate the spread But unambiguously this virus has its of the “unstoppable” virus through immediate origins in pigs. Specifically computer-modeling is more sensible it is the product of reassortment events than counting the total cases.1,2 between at least two swine flu variants. Moreover, one of the variants has some Clinical symptoms genes linked to an avian virus and A recent study carried out by the CDC human HN2 virus (one of the circulating has shown that sufferers of the new seasonal flu agents to date). In short, the H1N1 tend to come down with fever novel 2009 swine flu virus is an influenza (9%) and cough (%). Besides the two type-A virus consisting of genes derived most common symptoms, the following from viruses of swine, avian and human signs are also seen: as shortness origins through several reassortments,. of breath (%), fatigue/weakness Evidence from multiple outbreak sites (0%), chills (%), myalgias (%), demonstrates that the H1N1 pandemic rhinorrhea or running nose (%), sore 2009 virus has rapidly established itself throat (1%), headache (1%), vomiting and is now the dominant influenza strain (29%), wheezing (2%), diarrhea (2%). in most parts of the world. The pandemic The manifestations and the mode of will persist in the coming months as transmission are very similar to those of the virus continues to move through susceptible populations. the seasonal influenza. Patients with at least two signs of the acute respiratory Seasonal flu epidemics illness should call their care providers Influenza epidemics recur annually promptly. The duration of illness is mostly in the cold dry winter seasons. typically - days. The infectious period A n n u a l i n f l u e n z a e p i d e m i c s a r e for a confirmed case is defined as 1 day estimated to affect -1% of the global prior to the onset of symptoms to days population. Most cases are mild, but may after onset. The CDC has noted that cause severe illness in - million people most infections continue to be mild and and around 20,000-00,000 deaths recovery is extremely quick. worldwide. In industrialized countries
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severe illness and deaths occur mainly to 100 million people were killed worldwide. in the high-risk populations of infants, the An estimated 00 million people, one third - elderly, and chronically ill patients. of the world's population (approximately Pandemic timeline 1. billion at the time), became infected. In the past century, Influenza A virus The estimated numbers are definitely very strains caused three major global imprecise given the fact that the influenza epidemics: the Spanish flu in 191 virus was only formally discovered in 19 (caused by influenza A virus subtype by Smith and colleagues.9 By the same H1N1), Asian flu in 19(caused by token, since no laboratory techniques influenza A virus subtype H2N2) and were available at that time for confirmation Hong Kong flu in 19-9 (caused by other than clinical manifestations, the influenza A virus subtype HN2). These gross estimated figures include both the pandemics were all caused by various pandemic and the seasonal flu sufferers. subtypes of Influenza A virus that had t was no doubt that a dreadful pandemic undergone major genetic reassortments I and for which the population did not took place globally that killed more people possess significant immunity. The overall than those (1 million, 1% of the 1. effects of these pandemics and epidemics billion of the world's population) killed in are summarized in the table below., the World War I including both military It is estimated that anywhere from 20 personnel and civilians (Table 1.).
Table. 1. 20th century flu pandemics Influenza A virus People infected Deaths Case fatality Pandemic Year subtype (approx) (est.) rate (CFR) 191 flu 0. to 1 billion 191-19 H1N1 20 to 100 million >2.% pandemic (near 0%) Asian flu 19- H2N2 2 million <0.1% Hong Kong flu 19-9 HN2 1 million <0.1% mainly A/HN2, –1% 20,000-00,000 Seasonal flu* Every year <0.0% A/H1N1, and B (0 million - 1 billion) per year * Seasonal flu is not a pandemic, but is listed to compare the several flu strains endemic in humans which produce seasonal flu with the rare new strain that results in a flu pandemic.
Comparison: 191 and 2009 pandemics transportations, scientific knowledge and others, comparative studies can be Notwithstanding the fact that there are substantial differences between the living carried out for predicting the outcomes of environments of now and 90 years ago, the current pandemic. Although the two in terms of demography, public health pandemics are both caused by H1N1 system, medications, technologies, viruses, the two causative influenza type
The Novel H1N1 Flu Pandemic: Are we prepared?
A variants do not share exact biology/ among people 2 to 9 years of age virulence. There might be subtle and yet (1%), followed by people 0 to year different genetic makeup between the of age (2%) and people to 2 year of two flu viruses. So far we have not got age (1%) (Fig. ). This is a very different enough information as to the molecular pattern from what is seen in seasonal pathogenesis and the epidemiology of influenza, where an estimated 90% of the 2009 novel H1N1 flu. The majority influenza-related deaths occur in people of the world's population resides in the years of age and older (see Fig. 2). northern hemisphere and has not yet experienced the flu-prone winter season since the advent of the novel swine flu in April in Mexico. It remains to be seen whether this flu will be as powerful/ devastating as the 191 flu. Historical and epidemiological data are inadequate Fig. . Novel H1N1 U.S. Deaths, By Age Group to identify the geographic origin of the In Fig. , the pattern appears like 191 pandemic flu. Most of its victims an “A” shape rather than a “W” were healthy young adults aged between as seen in the 191 pandemic (see 2 and (see Fig. 2 for the solid curve), Fig. 2 for the solid curve). However, in contrast to most seasonal influenza the two letters share a common middle outbreaks which predominantly affect protruding point in that all points to the juvenile, elderly, or otherwise weakened vulnerability of the 2-9 age group. The patients (see Fig. 2 for the dotted curve). 0- and the ≧ age groups as well as the people with chronic diseases do not appear to be stricken badly at present. When the pandemic advances to its maturity the “A” shape may become subject to transformation with significant statistical data due to be collected globally. In the seasonal flu epidemics, a Fig. 2. Death-age group relationship - the 191 flu typical “U” curve is observed with the pandemic versus seasonal flu epidemics. 0- and the ≧ age groups sticking out CDC studied the hospital records at the both ends of the U letter (see Fig. of 2 patients hospitalized with novel 2 for the dotted curve). H1N1 flu early on during the outbreak. In Fig. 2, the 2- age group The number of deaths was highest stands out as a single peak in the middle
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of the W-shaped curve for the pandemic December of 191, a relatively calm flu, whilst the same age group remains period took over for nearly nine months flat in the annual U-shaped curve until mid October of 1919 when cases observed for the seasonal flu epidemics of flu started to rise. The pandemic flu prior to 191. Why the 191 H1N1 virus resumed as of December and lasted had its surprising effect on younger and until the end of February 1920 and then healthier people, particularly those aged began to die out. In this wave, another between 2 and . Kobasa and co- 1, people were infected, and workers reported that monkeys (Macaca among them19,2 people succumbed fascicularis) infected with the recreated (CFR at 12.9%). The high CFR could be 1 9 1 p a n d e m i c s t r a i n e x h i b i t e d due to sudden emergence of a mutated classic symptoms of the pandemic, an H1N1 with augmented virulence. By the overreaction of the immune system, same token, the abrupt disappearance of cytokine storm.10 the pandemic flu could likely be attributed to a weakened virus and possession of 191 pandemic in Taiwan immunity by the general population. In The Spanish flu occurred in Taiwan three total, the pandemic flu infected 92,0 months later than the United States / people and caused , deaths (CFR Europe, and coincided with most of other at .%). Asian countries. There were three waves It is unambiguous to note that the of the 191 flu pandemic recurrences in geographic origin of the pandemic flu Taiwan: wave I (June to mid-September, in Taiwan was Japan where 2, 191), wave II (late October to the deaths were attributed to influenza by end of December, 191), and wave III July 1919, giving an estimated 0.2% (December, 1919 to February, 1920). mortality rate (or 2 per 100,000 Within wave I, although more than usual people). The initial entry point was the numbers of people got flu-like symptoms Keelung harbor. The feverish Japanese in the hot summer days, little official soldiers of two shiploads disembarked at record by the local health authorities this international seaport shortly before could be discovered retrospectively. A June 191 and the pandemic flu started dramatic surge of cases erupted in the to spread in the military battalions, then second wave. In this period, it caused the Japanese civilians and finally the more than 9,2 cases of infection vast Taiwanese population.11 (1,9 males and ,9 females) The total population of Taiwan was and 2,9 deaths (CFR at .%). ,9, at that time according to the The wave II subsided after the end of census kept prior to the pandemic. This
The Novel H1N1 Flu Pandemic: Are we prepared? means that the infection rate of the are other antiviral agents, such as pandemic against the population stands at amantadine, rimantadine which are approximately 2.%, the gross mortality M2 Protein inhibitors. M2 protein (an rate at 1.2 % (or 1,200 per 100,000 ion channel), which is required for the people). It was noted that a “U” curve viral particle to become "uncoated" instead of a “W” curve was observed in once taken inside a cell by endocytosis. the mortality profile for the 191 pandemic Amantadine was approved by the Food in Taiwan (data not shown). A plausible and Drug Administration (FDA) on explanation for this is that throughout the October 19 as a prophylactic agent flu pandemic period of two years (191 against Asian influenza and eventually June-1920 June), Taiwan enjoyed a received approval for the treatment of rather peaceful and stable social status. Influenzavirus A. However they are not Inversely, in March of 191, most of recommended because of the drug the West European cities were quite resistance problem to many influenza devastated and war-torn after four years strains (e.g. HN1, HN2) documented of World War I. The exhausted young over the past several years. soldiers were crowded in military camps Suggested regimes of Tamiflu and and in trains by hundreds or thousands Relenza for both adult dose and pediatric 1 to be sent home when the pandemic flu dose can be found in. The more we use erupted. Although they were not killed by the antivirals against the flu, the more we a bullet earlier in the battle field, many of find the drug resistant viruses. A score them didn't survive the attack by the virus. of Tamiflu resistant H1N1 viruses have The official tally of the death toll of the been reported due to point mutations at 191 pandemic is about 21. million, the the NA gene. Fortunately, so far, all the most conservative number12 and that of Tamiflu-resistant viruses have remained World War I is 1 million. sensitive to Relenza. On the other hand, cases of Relenza resistant H1N1 have Medications 1 been isolated in Australia. Australian The H1N1 influenza A (swine flu) virus researchers have reported the first is susceptible to the antiviral drugs evidence of resistance to Relenza in oseltamivir [Tamiflu] and zanamivir seasonal influenza A (H1N1) strains. [Relenza] which are neuraminidase In 191 the salts of quinine and [NA] inhibitors, and the CDC has issued aspirin have been most generally used interim guidance for the use of these during the pandemic. Nowadays, in drugs to treat and prevent infection addition to the antivirals as mentioned, with swine influenza viruses. There we are able to apply other basic
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supportive medications (i.e., hydration, may enter our body readily to cause analgesics, cough suppressants) for infections. As the season advances relieving symptoms. Treatment of into the dry and cold winter, the above hospitalized patients and patients at phenomenon becomes more serious. higher risk for influenza complications Also, viral particles in aerosols will should be prioritized. Face masks for remain active longer in the cold weather various purposes are available, such as than in summer. All of these will provide healthcare professionals and patients and the ideal opportunities for the H1N1 people working at customs and so on. to spread rapidly in the fall and winter The usual vaccine for seasonal seasons. influenza administered prior to the flu So far the clinical picture of season is not effective for this viral pandemic influenza is largely consistent strain. Effective vaccines against the across all countries. The overwhelming 2009 novel H1N1 virus are being made m a j o r i t y o f p a t i e n t s c o n t i n u e t o by some major drug manufacturers. experience mild illness. However, Whether an effective vaccine will be increased risks for some vulnerable available in time for preventing the groups are well documented, such as pandemic will be a real challenge. women during pregnancy and people with predisposing conditions (asthma, Prospect of 2009 H1N1 pandemic diabetes, immunosuppression, and The majority of the world's population obesity).1 Studies have detected no -about 90% lives in the northern signs that the virus has mutated to a hemisphere while the remaining 10% more virulent or lethal form. But there lives in the southern hemisphere. As is no absolute guarantee that the novel northern hemisphere residents, we H1N1 will remain dormant without abrupt are about to enter the fall season as of genetic mutation throughout the coming September, when all students will return fall and winter seasons in the northern to school and crowd the classrooms hemisphere. and vacationers come back to their References: offices. The autumn is the season when the air in the atmosphere begins to get 1. World Health Organization. Influenza-like illness in the United States and Mexico. drier and the temperature gets lower WHO Epidemic and Pandemic Alert and than the summer. The mucosal surface Response. Available at 10 The Novel H1N1 Flu Pandemic: Are we prepared? ncbi.nlm.nih.gov/genomes/FLU/SwineFlu. V2009 #0. html>. Accessed May , 2009. 摘要 . CDC USA. Novel H1N1 flu: facts and fig- ures. 藥學雜誌 100期 11