Symposium on Infectious Diseases — February 2017
Tex Med. 2017;113(2):31-36.
By Herbert L. DuPont, MD
Emerging and reemerging infections have become prevalent in the United States since the 1970s, causing illness, death, and fear among the public. The published literature was reviewed to offer a perspective on risk factors for disease acquisition and to allow a prediction of the next microbial assault after Ebola and Zika. Four well-integrated factors likely will contribute simultaneously: animals colonized or infected by pathogens capable of human transmission, microbes recurrently changing their virulence, a growing number of susceptible people, and climatic and environmental factors encouraging disease transmission. The next pathogen likely to emerge in an important way in the United States is a new mutant virus arising from a well-established RNA virus family. Standard public health principles, including monitoring general populations for disease, developing new reagents as pathogens arise, implementing control efforts such as effective antibiotic stewardship programs, and vaccine development and administration will minimize damage from the emerging organisms.
Infectious diseases have been important causes of suffering and death throughout history, with intermittent pandemics that produced millions of deaths. In recent years in Western countries, we continue to see emerging infectious diseases with origins in tropical and semitropical regions with less dramatic health impact for general populations. In this review, we will look at the factors important in emergence and reemergence and consider the role played by animals in human infections. Prediction of the next disease epidemics will be made along with thoughts about critical public health efforts needed to control future infectious disease threats.
Infectious Diseases in Evolution
An important concept in the history of infectious diseases is that first societal exposure to a virulent microbe may have greater health implications than disease from endemic microorganisms. The indigenous populations of Aztecs in Mexico and Incas in Peru lived isolated from other groups. In the early 1500s, Hernando Cortes and Francisco Pizarro and their men and other European colonialists coming from complex integrated societies brought with them smallpox, measles, and other infectious agents to the susceptible Native American populations, resulting in high rates of disease and devastation.1
Measles virus arrived in the Hawaiian Islands for the first time in 1848, killing 10 percent to 33 percent of the native population.2 During 1918–19, a new pandemic strain of H1N1 influenza virus of avian origin killed 20 million people worldwide. When the Apollo flights of 1963–72 returned to Earth from the moon, the astronauts were trapped and observed in NASA trailers for three weeks to prevent importation of lunar microbes to susceptible populations on earth. The mobile unit used is on display in the Smithsonian Institute in Washington, D.C.3
In the early 20th century, advances in water quality, sanitation, vaccines, antibiotics, and reduced fertility rate in the western world were associated with an apparent reduction in serious infections, leading to an era of optimism about the future burden of infectious diseases. Things began to change when the American Legion held its three-day annual meeting at the Bellevue-Stratford Hotel in Philadelphia in 1976. The same year, an outbreak of Ebola virus infection occurred in the Democratic Republic of Congo, followed by the first cases of AIDS in 1981 followed a global increase in multidrug-resistant tuberculosis. Group A Streptococcus pyogenes invasive disease emerged in the mid-1980s.
The myriad subsequent microbial threats seen in rapid succession led the Institutes of Medicine to establish committees to address the problem and prepare for future microbial threats by producing two publications.4,5 The books described the evolutionary potential of infectious microbes and the complacency of our country with reduced public health awareness, and warned the United States that as we enter the 21st century we must focus on three elements in the war against microbes: emergence, detection, and response.
The Trust for America's Health estimated in 2008 that at least 170,000 people in the United States died that year from emerging or reemerging infectious diseases.6 Some of the more important causes of fatalities in the United States are influenza, with an estimated 36,000 deaths,7 health care-associated infections with 99,000 deaths,8 Clostridium difficile infection with up to 29,000 associated deaths,9 and foodborne infections with 3,000 deaths per year.10
Emerging and Reemerging Infections
Emerging infections are those species that have appeared in human populations for the first time or, if reported before, are occurring in greater frequency than before or in new populations not previously involved in disease transmission. Reemerging infections are those seen before but that now appear in new locations, in resistant forms, or are found again after elimination.11 Reemergence may relate to change in host range of an infectious agent (e.g. monkey poxvirus and Coronaviruses) or because the organism has undergone alteration, allowing it to be human adaptive as seen in influenza virus. The burden caused by infectious diseases is greatest in low-income countries and regions with reduced socioeconomic level with greater contact with wild animals, making these emerging disease hotspots.12
Many of the infectious agents considered emerging produce chronic syndromes13 such as stomach and cervical cancer, leukemia, Guillain-Barré syndrome, chronic liver diseases, paralytic disease, post-infectious functional bowel disease, and renal disease. Persistent or chronic disease after infections should be sought by careful follow-up and undoubtedly will be seen more commonly than appreciated. Cancers, autoimmune, end organ failure, and gastrointestinal and neurodevelopmental disorders are candidates for explorative studies focusing on basic and epidemiologic research.
In understanding emerging infectious disease outbreaks, it is not possible to focus only on the human host. Four integrated factors simultaneously contribute to infectious disease outbreaks: animals and zoonotic pathogens, microbes in transition, an increasingly susceptible human population, and climate and environment. (See Figure 1.)
Animals and Zoonoses
Zoonoses are diseases and infections transmitted between vertebrate animals and humans. More than 1 billion cases, or two-thirds of all infections of humans, originate in animals14 and are referred to as zoonoses.15 Zoonotic infectious agents are twice as likely to spread to humans as are non-zoonotic pathogens.
Three bacterial organisms of animal origin are currently threatening our food supply ― Shiga toxin-producing Escherichia coli, Campylobacter jejuni, and Salmonella spp.16
The animal reservoirs of human viruses that have the greatest potential for emergence include rodents and ungulates (horses, deer, camels, etc.), primates, carnivores, and bats and birds. Typically, the pathogens do not cause disease in the infected or colonized animals. An important step in emergence for viruses is jumping between one host animal species and humans.14,17 More than 60 percent of the newly identified viruses have been discovered in North America and Europe, not the regions of origin, because of better diagnostic capability.12 As examples of animal transmission of viruses, the 1998 Hendra virus outbreak in Australia was traced to infected horses seeking shelter under trees in which naturally infected bats roosted.18 Nipah virus caused viral encephalitis in Bangladesh, and Malaysia was similarly associated with fruit bats infecting people picking fruit.19
Animal pathogens can be spread by direct contact via wounds, sexual contact, vertical routes from a mother to fetus, or the respiratory tract; indirectly through ingestion of contaminated food or from environmental surfaces; and by a biting insect.20 Zoonotic infectious organisms show highest risk of transmission when acquired directly and indirectly compared with exposure though the vector-borne route.
The Microbe in Evolution
The list of emerging and reemerging infectious diseases is long and includes bacteria, viruses and prions, and parasites. They have been categorized into groups A, B, and C depending upon their risk as agents of bioterrorism.21
Bacterial pathogens are becoming more resistant in the face of widespread use of antibiotics, complicating therapy. During antimicrobial therapy of an infection, the gut microbiota develops resistance to the drug and can lead to later endogenous infection. These are especially seen in the hospital setting where the Centers for Disease Control and Prevention (CDC) estimated for 2002 that 1.7 million health care infections occurred in the United States with a health care cost of $20 billion.8
Microbial mutation allows pathogens to better survive but may facilitate disease occurrence. Mutating RNA viruses explain one-third of all emerging and reemerging infections,19 and mutation of M proteins in strains of Streptococcus pyogenes in the 1980s led to outbreaks of invasive Group A Streptococcus infections in Europe and the United States.22
The Human Host in Promoting Infectious Diseases
The fastest growing U.S. populations are the elderly and infirm23 who are more susceptible to infectious diseases with their reduced efficiency of the immune system. The behavior of people also contributes to transmission of infectious microorganisms through urbanization and increased international travel and by purchasing imported foods in increasing amounts. In our megacities, health conditions may be reduced due to crowding and more efficient spread of communicable infectious agents.24 Urban centers where 3.9 billion people live are the likely settings for new infectious disease epidemics.25
About 1.1 billion people crossed international boundaries in 2014,26 efficiently carrying their personal microbes with them and picking up new ones. International air travel is an important facilitator of pandemic influenza by transporting infected people who will enter susceptible populations.27 The most graphic example of the efficiency of global spread of a microbial pathogen was in 2003 when the SARS coronavirus spread from China within weeks to 25 countries across five continents.28 In 2014, Ebola virus travel from West Africa to the United States by air, during which time intra-airplane transmission was documented.29 Zika virus appears to have arrived in the Americas, probably Brazil, from French Polynesia between May and December 2013, following the pathway of chikungunya and dengue viruses.30-32 West Nile virus was shown to move across country borders by air travel of infected mosquitoes.33
We have seen an important growth in food importation in the United States with a growing cost from $40 billion in 1998 to more than $70 billion in 2007.34 On average, each person in the United States consumes 390 pounds of food (19 percent of the total) imported from another country.35 CDC estimated that one in six people in the United States (48 million cases per year) develop foodborne disease,36 with produce now being associated with nearly half of the cases.37 This is compounded by the emphasis on eating fresh vegetables for health purposes.38 Because of good crop growth, proximity, and the North American Free Trade Agreement, Mexico now provides almost half of the imported vegetables and vegetable products brought into the United States.34
The Climate and the Environment
The global warming being experienced presents challenges to humans and wildlife through a series of changing interactions with insects and microbes.39 With warmer temperatures and increased rainfall, mosquito-transmitted infections may be enhanced (e.g., Zika virus, dengue, and malaria). With the El Niño Southern Oscillation, we are seeing important weather changes; elevation in sea surface temperatures, especially associated with water-related infections (cholera and non-cholera Vibrios); drought linked in some areas with the emergence of hantavirus pulmonary syndrome; and crop failure and famine in areas, leading to migration along with undernutrition and decreased hydration,40 all of which contribute to a greater impact of infectious disease.
Deforestation and Reforestation
Deforestation in the Amazonian basin and other areas of the world has changed local ecosystems and vector communities, exposing humans and livestock to new arthropod-borne etiologic agents such as Crimean-Congo hemorrhagic fever. Deforestation may bring together infected bird populations into areas where humans live. Deforestation of tropical forests increases contact between hunters and wildlife. Clear-cut logging is likely to be less associated with human infectious disease transmission than selective extraction involving greater human activity and exposure during the construction of roads and transportation of workers. The emergence of Lyme disease in Europe and the United States appears to be related to reforestation resulting in increasing populations of deer and the vector of disease, the deer tick.41
Predicting the Next Important Pandemic
While endemic rates of important infectious diseases will continue in the United States, the past and future pathogens of greatest concern for outbreaks are new RNA viruses falling within well-recognized families of Filoviridae, Bunyaviridae, Orthomyxoviridae, and Flaviviridae. (See Table 1.)
While viral infections in Western civilizations have been tracked since the 1930s, beginning in the early 1950s until the present time we have seen between three and four new viral species emerge each year.42 RNA viruses undergo mutational variations because of the high rate of error of the viral polymerase enzymes responsible for genome replication compared with DNA viruses.19 The list of recently emerging RNA viral infections includes Hantavirus pulmonary syndrome, SARS, dengue, chikungunya fever, Ebola, H1N1 influenza, and Zika.
Segmented RNA viruses undergo gene reassortment important in pandemic influenza strains43 where new strains are reassortments of animal and human viruses.44 This gene swapping characteristically occurs in a permissive host such as a pig infected with avian and human influenza viruses facilitating a new strain with a unique hemagglutinin surface protein45 to which humans lack immunity from previous exposure.20 In 1997, a new recombinant Rift Valley bunyavirus outbreak was seen in Kenya and Somalia after a period of abnormal rainfall.46 Genetic recombination also explains the emergence of new coronaviruses such as SARS.47 Reassortment is an evolutionary mechanism for the viruses48 with humans paying the price.
Protecting the Public From Infections
Because of the slow development of effective antiviral drugs, health authorities have focused on attempting to control epidemics by employing traditional public health measures. The backbone of public health control is etiologic diagnosis and epidemiological surveillance. Because of the importance of animals as reservoirs of new pathogens, public health leaders and clinicians need to communicate with veterinary science leaders to help identify public health opportunities. Speed is important in defining the epidemiology of emerging or reemerging infectious diseases so that control measures can be implicated before the disease reaches high rates of endemicity. Because the most communicable viruses contain RNA, they are subject to diagnosis with nucleic acid detection methods. Genomic approaches to discovery of new pathogens, including polymerase chain reaction, microarrays, and next-generation sequencing methods, are vital to keep ahead of viral pathogen discovery.49
Improved methods of global surveillance are necessary, and syndromic monitoring of diseases must be established in U.S. communities. We need early detection methods that deliver real-time data through ongoing programs of active surveillance. Because of the importance of antibiotic resistance and the knowledge that a high percentage of antibiotics are used inappropriately, effective antibiotic stewardship programs must be established. Sensitive and practical methods for inspecting food for microbial safety are necessary to assure public health. New diagnostic methods for infections are needed to help monitor for emerging infections. Public health officials need to have the resources to quickly respond to outbreaks, and industry must be nimble in the efficient development of viral vaccines for control.
Emerging viral infectious agents are currently threatening human health. We will continue to see emergence of new RNA viruses as a result of mutation of viruses from established virus families, causing public fear and requiring new public health approaches to investigation and control. Emergence and reemergence by a virulent microbe cannot be predicted with accuracy with the myriad of moving targets influencing host pathogen interaction through microbial adaptation, increasing susceptibility of humans, the climate, and the environmental changes and exposure to infected wildlife.
Surveillance of diseases and disorders in human populations is critical and will require medical and veterinary clinicians and laboratory diagnosticians to work jointly and to communicate with public health officials.
Herbert L. DuPont, MD, is director of the Center for Infectious Diseases at The University of Texas Health Science Center at Houston School of Public Health, clinical professor at Baylor College of Medicine in Houston, and president of the Kelsey Research Foundation.
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- Nearly half a million Americans suffered from Clostridium difficile infections in a single year. Atlanta, GA: Centers for Disease Control and Prevention; February 25, 2015.
- Estimates of Foodborne Illness in the United States. Atlanta, GA: Centers for Disease Control and Prevention; 2014.
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