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respiratory pathogens, and it provides conclusions to strengthen that preparedness. Box 1: Viral Groups Most Likely to Be a Source of Pandemic-Initiating Pathogens Of the multiple ways in which a microorganism can be transmitted between humans (eg, body fluids, vectorborne, fecal-oral, foodborne, respiratory), the respiratory route poses greatest concern in terms of pandemic risk. As noted in a recent report titled Characteristics of Pandemic Pathogens, several features of respiratory transmission are important determinants of pathogen risk.15 The primary reason respiratory transmission (which includes pathogens spread by both airborne and respiratory droplet transmission) is the transmission route posing the greatest pandemic risk is that standard public health measures may not easily interrupt transmission. By contrast, each of the other major forms of disease transmission can be interrupted with sanitation, hand-washing, or other forms of intervention. Respiratory transmission can occur with coughing or simply breathing (in aerosol transmission), making containment much more challenging. Recent high-impact outbreaks of respiratory viruses make this case. In 2009, for example, a novel pandemic influenza virus emerged in Mexico and achieved prolific spread across the planet, causing disruption and widespread illness. Similarly, the 2003 emergence of SARS, caused by a zoonotic coronavirus, was characterized by billions of dollars of economic losses, worldwide circulation fostered by superspreading respiratory events, and severe disruptions. MERS, also caused by a coronavirus of animal origin, bears many of the hallmarks of SARS, including superspreading respiratory events, though it has thus far spread less widely than SARS. These respiratory-borne viruses are testament to the challenges of containment of respiratory pathogens.22,23 20 Another important aspect of pathogen transmission is the timing of transmission. While this is a factor in all modes of transmission, it takes on a heightened role in respiratory transmission because of the relative ease with which respiratory transmission takes place. If an infection is contagious in its incubation period—that is, prior to symptom onset—spread will likely have taken place before awareness of the risk of the infection. This phenomenon is exemplified by diseases like influenza, in which contagiousness precedes symptoms.24 Coupled with contagiousness during incubation period is the ability of a microbe to cause a spectrum of illness or have a time course of severity. If a pathogen is capable of causing asymptomatic or mildly symptomatic infections that either do not or only minimally interrupt activities of daily living, many individuals may be exposed. Viruses that cause the common cold, including coronaviruses, have this attribute and are important factors in the widespread nature of the common cold. This mild illness phenotype was also seen in 2 US importations of MERS . Modeling studies have identified this factor as being decisive in outbreak control.25 Many respiratory viruses possess RNA (as opposed to DNA) genomes, which may also confer special status on this group in terms of pandemic potential. An RNA genome is often characterized by high degrees of mutability, some of which may confer vaccine escape, antiviral resistance, heightened viral shedding, or increased pathogenicity. RNA viruses also tend to replicate in the cytoplasm of host cells and not the nucleus, a feature that may tie them less to one species and allow more promiscuity of host type (exceptions exist).26 Salient features of several classes of respiratory-borne viruses are summarized in the table below. While only a subset of these have caused documented pandemics, these groups all have viruses that have characteristics consistent with increased pandemic potential. Other than influenza and enterovirus, no systematic surveillance occurs for these viruses and there are no vaccines or unequivocally effective antivirals.15 Table 1: Viral Groups with Characteristics Most Consistent with Pandemic Pathogens Viral Group Important Members Special Features Orthomyxovirus Influenza Contagious during incubation period, demonstrated pandemic capacity, airborne and droplet transmission, high mutability Respirovirus* Human parainfluenza viruses 1 and 3 Highly contagious, spectrum of illness, capacity to cause severe infection, no countermeasures Henipavirus* Nipah Zoonotic origin, limited human-to-human spread, very high mortality, no countermeasures Rubulavirus* Human parainfluenza viruses 2 and 4 Highly contagious, spectrum of illness, capacity to cause severe infection Coronavirus MERS, SARS Zoonotic origin, human-to-human spread, high mortality, no countermeasures Enterovirus** EV-D68, EV-D71 Highly contagious, spectrum of illness, capacity to cause severe infection, no countermeasures Rhinovirus** Human rhinovirus C Highly contagious, ubiquitous, spectrum of illness, capacity to cause severe infection, no countermeasures *These 3 are paramyxovirus genera. **These 2 are picornavirus genera. 21 Box 2: Measles Is Bad Enough. What if It Were Worse? Measles is a highly contagious viral disease that causes serious and sometimes fatal clinical syndromes in children and adults worldwide.27 Measles is characterized by high fever, runny nose, cough, and a red blotchy rash, among other symptoms.28 It is spread via droplets, either airborne or through direct contact, when an infected person coughs or sneezes.29 Deaths due to measles usually occur following complications such as pneumonia or acute encephalitis.30 These complications are seen more often in children under 5, pregnant women, and people who are immunocompromised.31 The measles vaccine is safe for most people over 12 months of age and is 93% effective after 1 dose; it is 97% after 2 doses.27 With easily identifiable clinical symptoms, lack of carrier state, lack of an animal reservoir, a safe vaccine, and relatively low mortality, measles would be expected to be easily controlled compared to other viruses that commonly cause disease in humans.30 But while measles was declared eliminated from the United States in 2000, it has since seen a resurgence due to a combination of factors, including the lack of access to