Introduction
  Influenza is a disease that has existed since early times. However it is in 1933, when the influenza virus type A was discovered for the first time, that its true form was understood. Epidemiological studies performed later on led, as might be expected, to rapid progress in research regarding diagnosis and prevention. Nevertheless there have been influenza outbreaks every year resulting in a high number of patients and fatalities. Actually a radical solution to this issue was still far away at that time.
  However the situation regarding influenza has remarkably changed in less than a decade. In particular, the re-evaluation of influenza vaccine and the emergence of anti-flu agents and rapid diagnostic kits have radically modified the conventional concept regarding influenza control measures. I think that their efficacy and the issues will progressively become clear. However I feel uneasy about the future tendencies.
Epidemiology of influenza
  "Pandemic" is one of the terms specific to influenza. Pandemics are large-scale epidemics spanning all over the world, and they occur right after the emergence of new types of virus. Four pandemics have occurred since the beginning of the 20th century. One of them, the "Spanish flu" has caused extremely severe damages. It occurred from 1918 to 1919 and claimed at least 20 million fatalities in the whole world. In Japan, nearly 400,000 people succumbed to the disease. The three other pandemics that followed are the Asian flu (H2N2) from 1957 to 1967, the Hong Kong flu (H3N2) from 1968, and the Russian flu from 1977. All of these pandemics were caused by the influenza virus type A. Type B causes only localized epidemics. Incidentally H (HA: hemagglutinin) and N (NA: neurominidase) express the surface proteins of the virus, and the digits mean the type of immunogenicity. This is a coding method peculiar to type A for which subtypes exist.
  From 1977 onward, three types, namely Russian type A, Hong Kong type A and type B have been causing epidemics (a single type prevailing during certain years, several types during other years). Amid these types, the Hong Kong type has been circulating almost every year. From 1990 up to now (2002/2003 season), this type has not been prevalent during one season only. Hong Kong type A has a strong infectivity and pathogenicity. Excess mortality increases in case of large epidemics caused by this type, with a high incidence of encephalitis and encephalopathy amongst children. Type B circulates practically every other year, and it tends to follow Hong Kong type A.
Influenza vaccine
  The current influenza vaccines are inactivated vaccines. They are made by inoculating the vaccine strains to embryonated hen's eggs. This operation is followed by purification and concentration. These vaccines have an extremely high purity. Vaccines for Russian type A, Hong Kong type A and type B are respectively prepared and mixed. Then they are filled into vials and released on the market.
  One of the characteristics of the influenza virus is the frequency of HA and NA antigenic changes. Therefore the vaccine strains must be changed each time the antigenicity of the circulating virus varies considerably. The strains of Hong Kong type A change frequently. However the same strain has been in use for a long time for the Russian type A. This reflects the fact that the major type that has been circulating in recent years is Hong Kong type A. In case of type B, the vaccine contains two kinds of strains depending upon the season, since two lines of virus with a different antigenicity are circulating.
  The vaccination rate for the influenza vaccine fell excessively in the wake of the revision of the Vaccination Law in 1994. However the efficacy of the vaccine has been reassessed in late years, and the coverage has practically recovered to the level of the 1980s. However the major difference is that the target for vaccination has been switched from elementary and junior high school students to high-risk groups, primarily senior citizens. In Western countries, the vaccination of high-risk groups began many years ago, and the effectiveness of the vaccine has been demonstrated. Vaccination cuts by 50%~80% the risk of symptom aggravation, resulting in hospitalization, pneumonia, death, etc. It will be interesting to note that the recommendation made by the US Vaccination Advisory Committee in 2002 encourages the immunization of infants and young children with the influenza vaccine.
Anti-flu drugs
  Amantadine was cleared for marketing in the US in 1966 as an effective drug against influenza type A. This product used in Japan as an anti-parkinsonian agent was approved for the treatment for influenza in 1998. Its administration requires several precautions. Since the drug is effective only for type A, it should be used after confirming that the patient is infected with this type or if this infection is anticipated. Efficacy cannot be expected unless the drug is administered within 48 hours after onset. One should avoid using Amantadine for long periods, since resistant viruses emerge quite frequently. Since this product is also a psychotropic drug, adverse reactions should be monitored carefully. Amantadine is used extensively in the United States as preventative medication, in order to check the propagation of outbreaks in institutional settings.
  A recent epoch-making discovery is neuraminidase inhibitors. Two types of products are on the market. One is Zanamivir (Relenza), launched in December 2000, and the other one is Oseltamivir (Tamiflu) capsules, available since February 2001. Oseltamivir Dry Syrup has been put on the market in July 2002. This product is convenient for administration to young children. All of these drugs exert a high efficacy if they are given within 48 hours after disease onset. Their major advantages are efficacy for both types A and B, a low incidence of adverse reactions and practically no emergence of resistant strains.
Rapid diagnostic kits
  Rapid diagnostic kits for influenza have been put on the market practically at the same time new anti-influenza drugs were launched. These kits have become rapidly popular. They have revolutionized the medical practice, since they allow to know the results very rapidly (10~20 minutes) and to determine the treatment strategy during consultation.
  The measurement principle of the majority of kits initially marketed was based on the enzyme immunoassay technique (EIA), and they had an outstanding detection capability. However this technique involves numerous reaction steps, and its usage during influenza outbreaks when a great number of patients have to be examined was a major burden. Easy-to-use kits based upon immunochromatography have been developed in recent years. Many manufacturers are selling these kits. Numerous reports indicate that the sensitivity and specificity of the kits are fully consistent with the results of virus isolation. However the positiveness rate of these kits varies with the medical institutes and it is not always high. Therefore the manufacturers will have to improve their kits and the physicians will have to upgrade their sample collection technique.