Nonpharmaceutical Interventions
As has been demonstrated in recent events such as Ebola and 2009 H1N1 pandemic, national governments and responding agencies may seek to employ nonpharmaceutical interventions (NPIs) in disease outbreaks, either in coordination with available medical countermeasures or, in the absence of developed vaccines and therapeutics, as the primary measure to prevent or slow down disease spread. NPIs principally aim to limit the degree to which exposure to ongoing infectious disease threats can occur, both at the individual and community levels.
The degree to which NPI measures will be effective at preventing or limiting transmission of high-impact respiratory pathogens is uncertain and will largely depend on the context, timing, and epidemiology of the outbreak. In addition, the range of NPIs that might be called for in response to a high-impact respiratory pandemic (see Box 8 for the most commonly considered) all differ considerably in terms of objectives, feasibility, costs, downside consequence, and evidence. In determining whether and how to implement NPIs, countries must assess each proposed measure on the following dimensions:121
1. Epidemiologic assessment: Do available data or experience suggest a specific NPI will work to prevent or slow transmission in a meaningful way?
2. Logistical assessment: Is the particular NPI measure feasible given available resources?
3. Social, economic, and political assessment: What are the possible unintended adverse societal consequences of a particular NPI?

Box 8: Definitions of NPI
While NPIs cover a variety of measures, those that might be most likely to be considered or called for in the setting of a pandemic caused by a high-impact respiratory pathogen include: travel restrictions, movement restrictions, quarantine, and social distancing.
Travel restrictions refer to enforceable limitations on travel but should not be confused with travel alerts or notices, which provide information for travelers on ongoing health events.
Movement restrictions are measures implemented to prevent or limit contact between infectious individuals and susceptible populations, ranging from limits on how or where an individual can travel to full quarantine.
Quarantine is a separation of potentially infectious individuals from susceptible populations. It is often confused with isolation, which refers to separating individuals known to be transmissible (typically implemented in a health facility). Though isolation is routinely used in healthcare and public health practice, the use of quarantine is rare and has been controversial.
Social distancing covers an array of measures aimed at reducing contact between members of the community that could potentially result in disease transmission, including closing schools, canceling mass gatherings, facilitating remote- or tele-working, and suspending mass transit operations.

In the context of a high-impact respiratory pathogen, quarantine may be the least likely NPI to be effective in controlling the spread due to high transmissibility. To implement effective quarantine measures, it would need to be possible to accurately evaluate an indi- vidual’s exposure, which would be difficult to do for a respiratory pathogen because of the ease of widespread transmission from infected individuals. Quarantine measures will be least effective for pathogens that are highly transmissible, have short incubation periods, and spread through true airborne mechanisms, as opposed to droplets. As with travel restrictions, quarantine appears to delay the introduction of highly transmissible diseases but not prevent their spread entirely. Quarantine measures also appear more effective with pathogens that had a longer incubation period, such as measles, compared to those with shorter incubation periods, such as influenza.123 Experiences with quarantine during the West Africa Ebola epidemic highlight the added difficulty of implementing such measures on a large scale, which would only be more difficult in the case of a highly trans- missible respiratory disease.129

NPIs often require addressing additional considerations or challenges to implement. For example, quarantine requires strict adherence to be effective, so it works best when government has a trusting relationship with the public. Quarantine and other movement restrictions also involve legal and ethical considerations and should be supported by available evidence to prevent undue burden on affected individuals. The government must have both the legal authority to quarantine individuals and the operational ability to enforce quarantine orders. Other considerations when quarantine is being considered include the responsibility for ensuring the safety of affected individuals that are quarantined and providing medical, communication, and legal services as well as food, shelter, and other necessary supplies.

Monitoring and enforcing some of these NPI measures would be quite difficult if not impossible, due to the inability to fully monitor large communities and address noncom- pliance issues. In pandemic conditions when leaders are under great pressure to act, NPIs could be employed in inappropriate circumstances or have serious secondary or tertiary consequences that could themselves hinder outbreak response efforts. For example, travel restrictions could potentially hinder response efforts, as they could slow or prevent the transportation of personnel or materials. They would place additional economic burdens on the affected country, as the restrictions could hamper or stop their ability to trade. The disruption of normal activities such as schools closing may result in children congregating elsewhere, thus making social distancing efforts irrelevant. Quar- antine efforts could be highly disruptive to societies and economies if they are imple- mented for prolonged periods.121 In the response to government efforts to quarantine apartment complexes in Hong Kong during the SARS response, inhabitants of those buildings fled before authorities arrived, increasing risk of spread and driving the disease underground.130

NPIs would be highly likely to be considered or used by countries during a high-impact disease outbreak for a number of reasons. If there are no available medical countermeasures, NPIs may be viewed as the primary intervention to contain and control the event. NPIs such as travel restrictions have also been employed by countries as a political or social measure to abate fear rather than a necessary public health measure. While national public health guidelines generally recommend NPIs during an outbreak to limit contact frequency between individuals and to decrease the potential risk of spread of respiratory pathogens, there is a broad lack of evidence of efficacy and a lack of understanding about secondary adverse impacts. It is necessary to further study the effectiveness of NPIs in a variety of contexts to ensure that they are employed properly with a strong evidence base, and that the value of taking any specific NPI intervention in a particular pandemic setting is not outweighed by the potential harm. It is important to communicate to political leaders the absence of evidence surrounding many NPI interventions and the adverse consequences that may follow them.