H1N1 (Swine Flu): Antiviral Ring Prophylaxis for Containment of Influenza Outbreaks

There has been a lot of discussion about the use of antiviral medications to reduce the impact and spread of influenza.  A just released study in the New England Journal of Medicine (NEJM) researches the use of Oseltamivir ring chemoprophylaxis, together with prompt identification and isolation of infected personnel.  This study concludes that the ring therapy was effective in reducing the impact of outbreaks of 2009 H1N1 influenza in semiclosed settings.

Although antiviral “ring chemoprophylaxis” strategies (aimed at geographically targeted containment by means of prophylaxis) were predicted to be effective in mathematical models, data was needed to document the actual effectiveness during a pandemic. The research team studied the effectiveness of the therapy in response to four outbreaks of the 2009 pandemic influenza A (H1N1) virus in military camps (including one in a health care setting).

The research was conducted in Singapore, which is a city–state of 4.84 million people. All Singaporean men perform 2 years of military service after high school, at 18 to 19 years of age. Most military personnel live in barracks-style accommodations on weekdays and return home on weekends, resulting in an interaction between the military community and the Singapore population.

Singapore identified its first imported case of infection with the 2009 pandemic H1N1 virus on May 27, 2009, and the first transmission to the local community was reported on June 18, 2009. In line with WHO recommendations, Singapore began the transition to mitigation on July 1, 2009. The Singapore Armed Forces (SAF) identified its first imported case of infection on June 15, 2009, and its first four outbreak clusters (outbreaks I, II, III, and IV) involving local transmission from June 22 to 25, 2009.

Performing its function as a critical national resource, the SAF implemented additional interventions to contain the spread of the H1N1 virus. Primarily, “ring prophylaxis” with oseltamivir (Tamiflu), at a dose of 75 mg daily, was administered to coworkers of the patient with confirmed infection for a period of 10 days after exposure. The oseltamivir had been purchased and stockpiled several years previously as part of the SAF influenza-pandemic preparedness plan. A coworker was defined as a member of the same military unit, where contact opportunities were substantial even if they did not fulfill the Singapore Ministry of Health criteria for close contact. This wider definition was prompted by difficulties in identifying actual contacts and the practicalities of rapidly administering prophylaxis. Larger prophylaxis rings were instituted if cases were present in multiple units. In addition, interactions between affected units and other units were reduced within the camp, by allocating to each unit different times of arrival, departure, and meal delivery.

The four outbreaks occurred in different locations: one in each of three military units and one at a camp medical center. All personnel with suspected infection were tested and isolated in the hospital if the test was positive. In addition, all asymptomatic personnel in the same unit were screened through the collection of nasopharyngeal swabs, three times a week, to detect subclinical infections. A written questionnaire was administered at each screening visit, as well as after the completion of prophylaxis, to collect data on demographic characteristics, medical history, activity patterns, and clinical symptoms. Screening was performed until no additional cases were identified for 3 days after the last previously identified case or after the end of the 10-day prophylaxis period, whichever was later. After the prophylaxis period, a telephone questionnaire was administered to personnel who had left camp before the screening was completed.

Timing of Events and Cases during Outbreak 1, According to Date of Onset of Influenza. Generations 1 and 2 are the first and second generations, respectively, of 2009 H1N1 influenza spread from the three presumed index cases.

Many essential services are provided by persons who work in semiclosed or closed environments where influenza outbreaks can be rapid and severe.

• In an influenza outbreak among Taiwanese military recruits, the rate of infection was 57.7%
• An influenza A (H3N2) outbreak on a U.S. Navy ship had an infection rate of 42%.
• High rates of infection are also reported at schools, which are similarly enclosed.
  • One boarding school had 56 cases (in 6.5% of the population) a week after the index case occurred, and another had an overall rate of infection of 71%.
  • During a New York City school outbreak of the 2009 pandemic influenza A (H1N1) virus, 35% of students reported symptoms of influenza-like illness.
  • In this study, during outbreak #4, 59 cases occurred within 4 days after the first contact with the index patient.

Researches concluded that their experience provides evidence that early case detection and the use of antiviral ring prophylaxis effectively truncate the spread of infection during an epidemic, giving empirical support to theoretical mathematical models. Aggressive prophylaxis may be justifiable to provide protection from an influenza strain that causes severe disease or to protect vulnerable populations such as frail or elderly residents of long-term care facilities or persons in closed or semiclosed environments such as schools, prisons, and military camps. Finally, containing the pandemic’s spread may postpone the onset of substantial illness and distribute temporally the burden on the health care system until other control measures, such as vaccine, become available.

http://content.nejm.org/cgi/content/full/362/23/2166