Prevention and Treatment by Drugs of the Influenza Virus

Amantidine hydrochloride and its analog rimantadine are antiviral drugs for systemic use in the prevention of influenza A if protection is to result. Amantidine is relatively nontoxic but may produce central nervous system stimulation with dizziness and insomnia, particularly in the elderly. It should be considered for persons with chronic obstructive respiratory diseases, cardiac insufficiency, or renal disease, particularly if they have not been vaccinated yearly or if a new influenza A strain is epidemic. Amantidine may also modify the severity of influenza A if started within 24-48 hours after onset of illness.


Influenza occurs in successive waves of infection, with peak incidence during the winter, influenza A infections may vary from a few isolated cases to extensive outbreaks that within a few weeks involve 10% or more of the population, with rates of 50-75% in children of school age. The period between epidemic waves of influenza A is 2-3 years. All known pandemics were caused by influenza A strains. During the pandemic of 1918-1919 more than 20 million persons died, mainly from complicating bacterial pneumonia. Recent pandemics occurred in 1957-1958 owing to A influenza (H2N2) and in 1968 owing to A influenza (H3N2). In 1976 in New Jersey, a new type of influenza arose that resembled swine influenza (Hsw1H1), but it failed to spread in spite of a lack of immunity in most people under age 50 years. An enormous government-sponsored vaccination campaign was stopped because Guillain-Barre syndrome appeared in some vaccinated individuals. The predominant influenza A in the USA in 1978-1979 was an H1H1 variant of the strains prevalent in the 1950s.

Influenza B tends not to spread through communities as quickly as influenza A. Its inter epidemic period is from 3 to 6 years. Small outbreaks of influenza B were frequent in the USA in 1979-1980. The main reason for the periodic occurrence of epidemic influenza is the accumulations of a sufficient number of susceptibles in a population that harbors the virus in a few sub-clinical or minor infections throughout the year. Epidemics may be started when the virus mutates to a new antigenic type that has survival advantages and when antibodies in the population are low to this new type. A much more drastic change in the segmented RNA genome occurs when antigenic shift occurs. This involves the recombination of different segments of the RNA, each of which functions as an individual gene.

Surveillance for influenza outbreaks is more extensive than for any other disease in order to identify the early appearance of new strains, with the aim of preparing vaccines against them before an epidemic occurs. Surveillance also extends into animal populations, especially birds, pigs, and horse. Some believe that pandemic strains arise from recombinants of human and animal strains. Since the virus causing fowl plague was identified as human influenza A type in 1955, many influenza viruses have been isolated from a wide variety of domestic and wild bird species. Some of these include the major H and N antigens related to human strains.

Avian influenza ranges from highly lethal infections in chickens and turkeys to in-apparent infections in these and other avian species that harbor the same strains, Domestic ducks and quail often manifest influenza by coughing, sneezing and swelling around the beak, with variable mortality rates. Wildlife species and most domestic fowl show little or no signs of disease. The possibility that influenza viruses are transmitted between birds and mammals including humans may seem unlikely, particularly if the transfer were to be only by the respiratory route. However, influenza viruses of ducks multiply in the cells lining the intestinal tract and are shed in high concentrations into water. These viruses remain viable for days or weeks in water. It is possible that influenza among birds is a water-borne infection, moving from wild to domestic birds and even to humans.

Current research approaches to better influenza vaccines

  1. A neuraminidase-specific vaccine, which antibodies only to the neuraminidase antigen of the prevailing influenza virus. Antibody to neuraminidase reduces the amount of virus replicating in the respiratory tract and he ability to transmit virus to contacts. It reduces clinical symptoms in the infected person but permits sub-clinical infection that may give rise to more lasting immunity.
  2. A live vaccine using temperature-sensitive (ts) mutants. Such ts mutants grow well at the cooler (33 degree Celsius) temperature of the upper respiratory tract but fail to grow at the higher (37 degrees Celsius) temperature of the lung. Mutants selected for this ts property appear to be attenuated or avirulent. Thus, they might be given as a live vaccine into the respiratory tract, stimulating local as well as systemic immunity. By recombination of the ts gene with the gene for the current major antigen, potent live vaccines could theoretically be produced and rapidly administered to cope with an influenza epidemic. Attenuated live influenza virus vaccine has been in the USSR with reported success. The attenuated virus was selected by serial transfer through embryonated eggs rather by genetic manipulation.
  3. Combined yearly vaccination of persons at high risk, using the best mix of important antigens, and administration of Amantadine or other anti-influenza drugs at times of particular stress, eg surgery, hospitalization.