In 2009, governments found themselves racing to stay on top of the influenza A (H1N1) pandemic, and Singapore was among the nations confronted with the challenge of tracking and containment efforts to effectively thwart the spread of this virus.
The risk of viral transmission is especially severe within ‘closed’ environments such as schools or workplaces, but some models suggest that a strategy known as ‘ring prophylaxis’ could prove effective at outflanking influenza in such settings. “Essentially, you treat all the people that are likely to be in contact with people affected with the disease,” explains Martin Hibberd of the A*STAR Genome Institute of Singapore. “The treated people should be resistant to the disease, if the models are correct, and thus the virus cannot be transmitted to unaffected people.”
Hibberd helped put this strategy to the test last summer, when his group partnered with clinicians and scientists associated with the Singaporean government in efforts to contain H1N1 transmission at four different military installations. At each site, medical staff promptly isolated confirmed cases and treated co-workers in contact with the affected individuals with oseltamivir (Tamiflu), an effective treatment for H1N1. Regular screening of asymptomatic personnel ensured that additional positive cases would be quickly identified.
Because of influenza’s high mutation rate, analysis of genomic variations can help researchers to reconstruct infection patterns; Hibberd and his co-workers used whole-genome sequencing to characterize viral samples whenever possible. This enabled them to chart viral spread at each site and confirm the internal transmission of the virus—as opposed to multiple, independent infection events—at each military installation.
The ring prophylaxis strategy proved highly effective at limiting viral spread at each site: the investigators determined that the average number of secondary cases arising by transmission from a given infected individual switched from a level representing a rapid expansion, pre-intervention, to a halt of the outbreak, post-intervention.
Further analysis demonstrated that this reduction was significantly greater than if confirmed cases were simply isolated. “Clearly, this approach could be used as an effective method to prevent disease spread, perhaps in places like hospitals,” says Hibberd.
Individuals at each of the outbreak sites were generally compliant with prophylaxis—overall, 95.4% of personnel completed treatment—but a handful of new H1N1 cases nevertheless emerged post-intervention, and the investigators are now trying to understand why. “We are currently looking at whether the very few failures were due to evolution leading to drug-resistant viruses or late delivery of prophylaxis,” says Hibberd.
The A*STAR-affiliated researchers mentioned in this highlight are from the Genome Institute of Singapore.