Over the course of six days, a case report of two novel H1N1 influenza (swine flu) infections in California¹ transformed into a phase 5 influenza pandemic “characterized by human-to-human spread of the virus into at least two countries in one [World Health Organization] region.”^2,3 At this convergence of an early pandemic of H1N1 influenza, rapid emergence of antiviral resistance, expanding coverage of seasonal influenza vaccines, and the ease of transglobal travel, it has become difficult to be an accurate prognosticator of the reach and effects of influenza. However, as in all biological systems, the final realized outcome of an influenza outbreak is constrained within a finite set of possibilities. Consideration of 12 basic rules of influenza can help shape public policy and clinical responses.

1. Human influenza viruses are transmitted person-to-person; if this chain is broken, no additional cases can occur. Corollary: Social distancing—maintaining distance between susceptible persons and cases—is a uniformly effective measure that will prevent transmission.⁴ Clinical application: Information provided to our patients can be an effective early intervention to prevent H1N1 influenza.

2. Influenza viruses are primarily transmitted by respiratory droplets; droplets are governed by basic rules of gravity and physics. Droplets are formed from respiratory secretions and propelled forth by a cough or sneeze. Corollary: Deflecting or containing respiratory droplets will prevent transmission. Face masks, used by infected or susceptible persons, can be effective in preventing transmission.⁵ Clinical application: Health care facilities should have adequate supplies of masks for patient care staff and patients, along with educational posters.

3. Influenza viruses prefer cool, dry air. Influenza is a highly seasonal virus with most transmission limited to late fall and winter across temperate latitudes. Corollary: Transmission can occur at other times, but is far less efficient. Significant transmission can also occur under other circumstances, depending on the nature of the virus and the population.⁶ Clinical application: When novel viruses (such as H1N1 influenza) emerge, transmission can occur at unusual times because of the absence of immunity.

4. Influenza viruses target respiratory mucosa. The potentially “exposed” respiratory mucosa covers the nasal passages, nasopharynx, conjunctiva, pharynx, larynx, trachea, bronchi, bronchioles, and alveoli. Corollary: Protection of respiratory mucosa from droplets and/or direct contact will prevent transmission. Contaminated hands can provide direct contact. Handwashing reduces direct contact.⁷ Clinical application: Frequent handwashing and the use of masks can protect respiratory mucosa from exposure to H1N1 influenza.

5. Once exposed, there is a fairly predictable incubation period for influenza viruses. Clinical illness will appear within 24 to 72 hours following infection. Corollary: The lack of clinical illness following exposure signifies no infection, adequate immunity, or subclinical infection.⁸ Clinical application: A history of exposure to a confirmed case of H1N1 influenza one to three days before symptom onset is an excellent clinical clue.

6. Once infected, there is a fairly predictable period of virus shedding and transmissibility. Peak shedding of the virus occurs during day two to three of clinical illness, generally corresponding to the period of peak symptoms. Corollary: Sick persons are less likely to move through the community. Medical systems, however, often require sick persons to present to the community (see rule 1). After five to six days of illness, an individual is unlikely to transmit influenza.⁹ Clinical application: Understanding the period of viral shedding will help patients understand the value of staying home during their illness.

7. Once infected, a pathway leading to immunity is triggered within the influenza host. The immune response leads to some of influenza's symptoms. Corollary: Infection and recovery produce lasting immunity to that particular strain of influenza, provided that the host's immune system is intact.¹⁰ Clinical application: Patients who avoid H1N1 influenza will be susceptible in the future and should be vaccinated once a vaccine is available and recommended.

8. Infection leads to recovery and immunity, or death. Corollary: The propensity towards host death depends on strain and host factors. In general, influenza mortality is highest in very young and very old, and in the most immunocompromised persons.¹¹ Clinical application: Physicians should be aware of the changing spectrum of H1N1 influenza and which patients have the highest morbidity and/or mortality.

9. Immunity may be acquired via infection or via immunization. Corollary: Previous infection with other strains and/or immunization does not guarantee immunity. Host factors and poor vaccine match can significantly reduce immunity.¹² Clinical application: When an H1N1 influenza vaccine becomes available, physicians will need to immunize patients according to recommendations.

10. Influenza epidemics follow predictable patterns over time. This general behavior can be modeled using estimates of immunity, transmissibility, and generation time. Corollary: Many of the parameters needed to model epidemics are difficult to obtain; models work best in retrospect.¹³ Clinical application: Many excellent regional and national surveillance systems exist. Surveillance information can help guide appropriate practice.

11. There is a delicate interplay between the infectivity of a virus and the population's level of pre-existing immunity. For transmission to occur, susceptible persons in the exposed population are needed. Reducing the likelihood of contact with a susceptible person reduces the infectivity of a virus. Corollary: Novel influenza viruses are unconstrained by factors of immunity and achieve high infectivity potential.¹⁴ Clinical application: H1N1 influenza is emerging at an unusual time. As late fall and winter return, H1N1 influenza may become significantly worse.

12. “All living things contain a measure of madness that moves them in strange, sometimes inexplicable ways.”¹⁵ Any of these rules may be broken at any time; influenza viruses have a high potential for mutation, genomes may be recombined, and population patterns are not fixed. Corollary: Whereas basic rules can set the conversation for planning activities, ongoing surveillance and modification of response are necessary for influenza prevention and control efforts. Clinical application: Family physicians are at the front line of influenza care in the United States. They need to keep abreast of changing information to best care for their patients and communities.

H1N1 influenza is characterized by a fever of 100°F (37.8°C) coupled with a cough, sore throat, or coryza. Suspected cases have an epidemiologic link to a confirmed case or to a community in which H1N1 influenza has been confirmed. The Centers for Disease Control and Prevention (CDC) provides excellent guidance to case identification, laboratory testing, and treatment. Influenza prevention and control depends on the appropriate interaction between public health practice and clinical interventions. Attention to reducing transmission through social distancing, use of face masks, and frequent handwashing are important initial steps in outbreak mediation as surveillance activities are undertaken, vaccines are developed, and antiviral options are formulated. These public health measures should help combat H1N1 influenza. In addition, the CDC recommends the use of the neuraminidase inhibitors oseltamivir (Tamiflu) or zanamivir (Relenza) for the primary treatment of H1N1 influenza.¹⁶ Further information about H1N1 influenza is available from the CDC Web site (http://www.cdc.gov/h1n1flu/guidance/ and http://www.cdc.gov/swineflu/guidance_homecare.htm).