Emerging and Re-emerging Viral Diseases

Emerging and re-emerging infectious diseases (EIDs) have surfaced in recent decades. An “emerging infection” is either a new infection that has never appeared before or a known infection that has a recent increase in prevalence. 

The immunodeficiency virus and (SARS-CoV-2 virus that causes COVID-19 are prototypical examples of the emerging infectious diseases that the public did not face prior to the 1980s and 2019, respectively. A “re-emerging infection” is a familiar infection that recurs. Influenza A virus pandemics of 1918, 1957, and 1968 are prototypical examples of re-emerging infections.

Many factors contribute to the appearance of EIDs. These factors are complex but can be classified into three different categories: virus factors, human factors, and ecological factors.

Viral Factors

Most of the viral agents in EID are RNA viruses that have high mutation rates. This leads to their rapid evolution and environmental adaptability, so that RNA viruses can reach adaptive equilibrium within their host species very rapidly. There are three fundamental mechanisms in the genetic variation of the viral genome: (1) point mutation, (2) recombination, and (3) reassortment.

Point Mutation

Point mutation is a change in a single base pair of DNA by substitution, deletion, or insertion of a single nitrogenous base. Usually, viral proteins differing by as little as 1 or 2 amino acid residues confer striking differences in phenotype. For example, certain mutations in HIV-1 viral proteins or enzymes can lead to virus resistance to antiviral drugs.

A receptor-binding domain (RBD) is a key part of a virus located on its ‘spike’ domain that allows it to dock to body receptors to gain entry into cells and lead to infection. These are also the primary targets in the prevention and treatment of viral infections, including SARS-CoV-2. The spread of SARS-CoV-2 variants in the population depends on their ability to anchor the ACE2 receptor in the host cells. Differences in the electrostatic potentials of the spike protein RBD (electropositive/basic) and ACE2 receptor (electronegative/acidic) play a key role in both the rapprochement and the recognition of the coronavirus by the cell receptors. Accordingly, point mutations that result in an increase in electropositively charged residues, could contribute to their spreading capacity by favoring their recognition by the electronegatively charged ACE2 receptors. All SARS-CoV-2 variants that have been recognized as being highly transmissible, such as the kappa (κ), delta (δ) and omicron (o) variants, which display an enhanced electropositive character in their RBDs associated with point mutations.

Recombination

The second viral mutation strategy for adaptation is recombination. Recombination allows two copies of genetic materials to exchange, producing a new “mixed” or “hybrid” genome molecule. A high recombination rate occurs in coronavirus. SARS-CoV represents a typical case of recombination. When two CoVs infect the same cell, there is the potential for two RNA molecules to cross over.

Reassortment

The third viral adaptation mechanism is gene reassortment. Gene reassortment occurs when segmented viruses, which are viruses with multiple segmented genomes, co-infect the same cell and eventually lead to the progeny virus containing a genome set derived from the multiple parent viruses. Coinfection of the same cell in the host animal by different virus strains allows for widely divergent sequences to occur by recombination or reassortment.

Omicron Subvariants are Masters of Immune Evasion

Coronaviruses have evolved multiple strategies to evade host antiviral immunity. SARS-CoV-2 can evade the host immune response by inducing a delayed interferon (IFN) response, which provides a window for uncontrolled viral replication. Inhibition and further dysregulation of type I and III IFN responses lead to hyperinflammation in coronavirus disease 2019 (COVID-19) patients. Moreover, it has been hypothesized that a delayed but exaggerated type I IFN response contributes to the severe progression of COVID-19.

Human Factors

Surprisingly, the genetic evolution of viruses does not seem to be the major cause of virus emergence. In fact, a microbe introduced into a new region may have a greater or lesser impact, depending on the susceptibility of a host population. Human factors are actually the most potent factors driving disease emergence.

In Africa, many Ebola virus outbreaks were linked to funeral practices. It is common for the women to prepare (i.e. wash and clean) the body of their deceased relatives for the ceremony.

Keeping dangerous viral pathogens (such as smallpox) in research laboratories raises concern for lapses in biosafety. The increased threat of the use of viruses as biological weapons by bioterrorists is a great concern.

Injudicious use or misuse of antibiotics and anti-viral drugs often occur in poor countries and can hasten the evolution of resistant strains. Transfusions can be a very efficient way of transmitting blood-borne viruses. Poor hospital practices inadvertently help the spread of disease.

The use of immunosuppressive drugs and chronic corticosteroid treatment decreases the capacities of the immune system and encourages opportunistic infections including human cytomegalovirus and respiratory syncytial virus. The use of animal organs as a source of transplantation, xenotransplantation, increases the possibility of directly introducing animal viruses into human beings.

Public health measures, including basic sanitation and disease control activities, are not well-maintained during war, civil strife, or natural disaster. War is accompanied by economic collapse, famine, and homelessness as well as water-borne and rodent-related diseases. STDs are associated with refugee campuses.

In some developing countries, wild animal species (such as beavers, civet cats, domestic cats, hares, raccoon dogs, snakes, pangolin) are commonly sold in live-animal markets (also called “wet markets”). Direct contact of humans with animal blood, bodily fluids, or excreta during food handling appears to be the simplest and most plausible explanation for the cross-species transmission of viruses. The extension of agricultural cultivation into forests may alter the existing zoonotic transmission cycles. Expanding human habitation in a region may put people in direct contact with new animal species and thus their viruses. Monkeypox is most often transmitted to humans through contact with the animal's blood or through a rodent bite.

Population Growth

Since the pathogen of a disease needs to be introduced into the human population and then subsequently spread and maintain itself in the population, a large human population size favors the spread and perpetuation of diseases. The dramatic increase in the human population means that more space for living is needed. Therefore, the expansion of the human population into virgin forests could disturb the virus reservoirs and increase the opportunities for viral transmission from animals to humans, ultimately causing EIDs.

Urbanization

Urbanization brings with it the problems of housing, sanitation, pollution, drinking water, and health care facilities. Increasing population densities and urban poverty encourage the spread of viruses; under poor sanitary conditions, people are more susceptible to pulmonary and gastrointestinal infections.

Human Population Movements and Migration

Due to intense human traffic, the spread of infectious diseases can be led to new areas at any time. Viruses present in rural areas of the world, such as rural areas of Africa or Asia, may show up in more developed parts of the world, such as in Europe or the United States. As more people migrate and reproduce, the strained infrastructure of public health faces increased pressure, and can ultimately break down.

Global travel enables viremic travelers to reach any part of the world in less than 24 hours, possibly initiating a global pandemic. Viruses can be spread around the world by international air travelers. Unplanned migration due to war or natural disasters has played a large part in introducing infectious diseases into humans.

Global Food Production Chain

Today, mass food processing combines large amounts of raw materials for worldwide distribution. Unfortunately, global trade expanded the markets for imported foods, which occasionally contain microbial contaminants due to uneven sanitary practices during manufacture and processing of food in different parts of the world. Food-borne viral infections are also increasingly recognized as an additional cause of illness in humans.

Animal Trade

Imported experimental monkeys, such as vervet monkeys used in biomedical research, from tropical countries into Western countries, were responsible for an outbreak of Marburg virus in Marburg (Germany) and Ebola virus in Virginia (US) in 1969 and 1989, respectively.

Sexual Behavior

Having multiple sex partners increases the risk of sexually transmitted diseases (STDs). Long-term sex-relationships in populations dramatically increased the size, speed, and variability of the HIV epidemic. In the current monkeypox outbreak, the virus is spreading primarily through sexual contact.

Ecological Factors

Many EID outbreaks have occurred after extreme climatic conditions such as floods and droughts, demonstrating a clear relationship between environmental characteristics and virus emergence. A slight rise in global temperature could trigger explosions of the earth's insect population. Mosquito-borne infections (including dengue fever and yellow fever) are being reported at high elevations in South and Central America, Asia, and East and Central Africa since the expansion of mosquito populations. The rise in industrialization-related human activities might even have imposed conditions for the emergence of future coronavirus cycles.