Emerging and Re-emerging Infectious Diseases
At least yearly, it seems, an outbreak of a new or old infectious disease makes the news, accompanied by reports of severe illness and even death. While no one consensus definition exists, the CDC defines emerging infectious diseases as those that have arisen or increased in the human population in the past 2 decades. Examples include news-makers like SARS and Zika virus, as well as some that fly under the radar, such as the recently identified Candida auris yeast (discussed shortly). Emerging infectious disease (EID) outbreaks may seem to come from nowhere (e.g., Zika virus) and in some cases this represents significant geographic spread of known human pathogens.
On the other hand, re-emerging pathogens are those that were formerly rare, viewed as largely under control or exhibiting reduced infection rates, but that have recently begun to resurge. This can be due to the development of drug resistance (e.g., tuberculosis), acquisition of new virulence factors (e.g., MRSA), or environmental changes that enhance transmission rates or geographic range (e.g., Ebola and dengue virus). Figure 17-7 illustrates the global regions where infectious disease emerged or re-emerged in the past 75 years, highlighting the expanding geography of this issue.
FIGURE 17-7 Emerging and re-emerging infectious disease origin points over the past 75 years. Global map with a blue-to-yellow transition showing the point of origin of newly emerged infectious diseases in 5-year increments from 1940 to 2010. [Data from EcoHealth alliance data and NPR; https://eidr.ecohealthalliance.org/event-map.]
Some Noteworthy New Infectious Diseases Have Appeared Recently
New infectious diseases come in all categories, infecting the young and old, the well and unwell. For example, Zika virus is spread via mosquitoes and sexual contact, but has minimal impact in adult hosts. However, significantly compromised neurological development has been seen in the fetuses and newborns of some women who become infected while pregnant. In Brazil alone, Zika is now estimated to have generated billions in lost income, added significantly to entrenched systems of economic inequality, and increased the burden on an already stressed health care system (see Clinical Focus Box 17-1).
Contaminated surfaces are likely to blame for a recent outbreak of a new and highly virulent strain of yeast, Candida auris. This fungal pathogen has so far remained isolated to health care facilities, taking advantage of those who are elderly, ill, and often immune compromised. This newly emerging infectious disease is particularly troubling because it is difficult to identify and has acquired resistance to many of the common antifungal drugs in use.
In November 2002, an unexplained atypical pneumonia was seen in the Guangdong Province of China, proving resistant to any treatment. A physician who had cared for some of these patients traveled to Hong Kong and infected guests in his hotel, who then seeded a multinational outbreak that lasted until May 2003. By the time the disease, called severe acute respiratory syndrome (SARS), was contained, 8096 cases had been reported, with 774 deaths. A rapid response by the biomedical community identified the etiologic agent as a coronavirus, so named because the spike proteins emanating from these viruses give them a crown-like appearance (Figure 17-8). This virus was soon traced to several marketplace animals (especially exotic cats) and ultimately to its likely animal reservoir in nature—bats. SARS is a member of the coronaviruses family, known for many years, primarily as the cause of a mild form of the common cold. This newly emerged variant, likely due to a mutation that allowed spread from marketplace animals to vendors, had not been seen previously. Animal models for SARS showed that antibodies to the viral spike protein could thwart replication of the virus, leading to the rapid development of an intranasal vaccine that could induce protective immunity. This was an example of rapid and efficient global detection, containment, and characterization of a new infectious disease, with a very short vaccine pipeline.
FIGURE 17-8 The coronavirus that caused the outbreak of severe acute respiratory syndrome, or SARS. The virus is studded with spikes that in cross-section give it the appearance of a crown, hence the name coronavirus.
West Nile virus (WNV), first identified in Uganda in 1937, was not seen outside Africa or western Asia until 1999, when it suddenly appeared in the New York City area. By 2016 it had been reported in all 50 states with the exception of Alaska. WNV is a flavivirus that replicates very well in certain species of birds and is carried by mosquitoes from infected birds to so-called dead-end hosts such as horses and humans. Transmission between humans via mosquitoes is inefficient because the titer of virus in human blood is low and the amount of blood transferred by the insect bite is small. WNV may, however, be transferred from human to human by blood transfusion and may be passed from infected pregnant mothers to their newborns. Its major impact appears to be in individuals with compromised immune function, in whom it can cross the blood-brain barrier and cause life-threatening encephalitis and meningitis. The primary public health control measure to combat WNV remains education of the public concerning mosquito control.
Are emerging infectious diseases actually occurring with increased frequency? Heightened awareness and increased spread of EIDs do appear to be the new normal and may not be surprising if we consider three important recent factors: increased access to international travel, climate change, and greater human contact with wild animals (due mostly to deforestation and encroachment). For instance, international travel is what helped Ebola virus spread from one African nation to another and finally across U.S. borders. Tropical diseases are no longer isolated to the tropics. Thanks to rapid travel between countries and spreading habitats for vectors and intermediate hosts, much of the southern United States can now also lay claim to some tropical fever. We know from both current changes taking place and historical data, including recorded El Niño/La Niña patterns, that microbes responsible for malaria, dengue fever, and Lyme disease are likely to spread to new regions if we remain on the current climate trajectory. Finally, the plague of our time, HIV, likely made its leap to humans thanks to the increased association between man and nonhuman primates around the middle of the twentieth century. Alas, none of these factors are likely to recede any time soon, leading to an anticipated increase in EIDs in the future.
Diseases May Re-emerge for Various Reasons
Tuberculosis is a re-emerging disease now receiving considerable attention. Twenty years ago, public health officials were convinced that tuberculosis would soon disappear as a major health consideration in the United States. A series of events conspired to interrupt that trend, including the AIDS epidemic and other immunosuppressive conditions, allowing Mycobacterium strains to regain a foothold and even evolve resistance to the conventional battery of antibiotics. Infected individuals then passed on newly emerged, antibiotic-resistant strains of M. tuberculosis to others. Despite the disappointment of not eradicating this disease in the United States, rates of tuberculosis have been declining annually by about 1.5% per year since 2000. Still, worldwide, tuberculosis remains one of the top 10 leading causes of death and is the culprit for more than one-third of all fatalities associated with AIDS.
The first recorded case of Ebola, one of the most deadly infectious agents, occurred after an outbreak in Africa in 1976, although it likely predates this documented incident. By 1977, the causative virus had been isolated and classified as a filovirus, a type of RNA virus that includes the similarly deadly Marburg virus, a close relative of Ebola. The most pathogenic strain, Ebola-Zaire, causes a particularly severe hemorrhagic fever, killing between 50% and 90% of those infected, often within days of the onset of symptoms. Ironically, the short incubation, debilitating illness, and high death rate normally blunt human-to-human spread of this virus—a factor that may have contained the early episodes of its outbreak. Ebola is an example of a zoonotic pathogen with the fruit bat as its likely primary host. Infected bats appear to be largely unharmed, but they do create a local “reservoir” for spread of the virus. Encroachment of humans into bat habitats and contact with infected monkeys is credited with almost all of the initial outbreaks of Ebola. One such naturally acquired infection that began in Guinea in late 2013 was transmitted through human contact to other African countries and ultimately to the United States. The 2014–2016 cross-continent West African outbreak was the largest in history, and the associated international focus brought much-needed attention and money to the study of this disease. Thanks in part to this, previously stalled vaccine efforts have now yielded two promising vaccine candidates, generating memory responses lasting at least 1 year (see Recombinant Vector Vaccines, in the next section). There is speculation that the first Ebola vaccine may be on the near horizon.
Laxity in adherence to established vaccination programs can also lead to re-emergence of diseases that were nearly eradicated. For example, diphtheria began to re-emerge in parts of the former Soviet Union in 1994, where it had almost vanished thanks to European vaccination programs. By 1995, over 50,000 cases were reported and thousands died. The social upheaval and instability that came with the breakup of the Soviet Union, leading to lapses in vaccination and public health programs, was almost certainly a major factor in the re-emergence of this disease. Likewise, poliomyelitis has been on the verge of worldwide eradication for decades. Social unrest and war have delayed progress, although today we are closer than ever to meeting this goal. The only remaining countries still reporting wild polio (cases not associated with vaccination; see below) are Afghanistan and Pakistan, with only 22 cases of naturally acquired polio reported for 2017. However, this kind of progress can sometimes lead to less urgency in vaccination routines. Even in the United States, an increasing trend in some regions to delay or opt out of childhood vaccination has led to sporadic local outbreaks in previously rare childhood diseases such as measles and whooping cough. In some states there has been a backlash to this laxity, resulting in greater enforcement and even legislative mandates, leading to interesting ethical debates.