Chapter 5: Emerging and Reemerging Infectious Diseases: Emergence and Global Spread of Infection

Emerging infectious diseases

An emerging disease is an infectious disease whose incidence has increased in the past two decades and/or that threatens to increase soon. Emerging infectious diseases reflect the arrival of a new pathogen or an old pathogen that is increasing in incidence, clinical or laboratory characteristics, or geographic range. The appearance of the severe acute respiratory syndrome (SARS) coronavirus is an example of a new pathogen, multidrug-resistant Mycobacterium tuberculosis represents an old pathogen with new characteristics, and cholera in the Americas is an example of an old pathogen with a new geographic range (Asia to South America). New methods of detection (eg, molecular) and surveillance (eg, global) have greatly improved our ability to detect and characterize emerging and reemerging infectious diseases. The fundamental methodologies of molecular epidemiology are described in Chapter 4, and their specific applications are discussed in many other chapters throughout this book.

Some factors that increase emergence or reemergence of infectious pathogens include:

• Human and animal demographics and population movement with intrusion into new habitats (particularly tropical forests)

• Irrigation, especially primitive irrigation systems, which fail to control arthropods and enteric organisms

• Uncontrolled urbanization, with vector populations breeding in stagnant water

• Increased international commerce and travel with contact or transport of arthropod vectors and pathogens

• Breakdown in public health measures, including sanitation, vector control, immunization programs related to social unrest, civil wars, and major natural disasters

• Ecological changes, including global climate change, deforestation with farmers and their animals exposed to new arthropods, flood/drought

• Microbial evolution, related to indiscriminate use of antiinfective agents, leading to natural selection of multidrug-resistant agents (eg, methicillin-resistant staphylococci; highly virulent strains of influenza A)

Zoonotic infections are disproportionately common emerging pathogens. New, often unexpected, infectious diseases continue to emerge or reemerge despite public health efforts. Although mortality rates declined dramatically during much of the 20th century in the United States (Figure 5–1), the mortality rate from infectious diseases increased dramatically in the early 1980s with the introduction of HIV. The global distribution of some emerging and reemerging infectious diseases is illustrated in Figure 5–2.

Infectious diseases of humans may be caused by exclusively human pathogens such as Shigella; by environmental organisms such as Legionella pneumophila; or by organisms that have their primary reservoir in animals such as Salmonella.

Noncommunicable infections are those that are not transmitted from human to human and include: (1) infections related to the patient’s microbiota gaining access to a previously sterile site, such as peritonitis after rupture of the appendix; (2) infections caused by the ingestion of preformed toxins, such as botulism; and (3) infections caused by organisms found in the environment, such as clostridial gas gangrene. Some diseases transmitted from animals to humans (zoonotic infections), such as rabies and brucellosis, are not transmitted between humans, but others such as plague may be. Noncommunicable infections may still occur as common-source outbreaks, such as food poisoning from an enterotoxin-producing Staphylococcus aureus–contaminated chicken salad or multiple cases of pneumonia from extensive dissemination of Legionella through an air-conditioning system. Because these diseases are not transmissible to others, they do not lead to secondary spread.

Communicable infections require an organism to leave the body in a form that is either directly infectious or able to become so after development in a suitable environment. The respiratory spread of influenza virus is an example of direct communicability. In contrast, the malarial parasite requires a developmental cycle in a biting mosquito before it can infect another human. Communicable infections can be endemic, present in the population at a low and constant level, or epidemic, present at a level of infection higher than that usually found in the community or population. With some infections, such as influenza, the infection can be endemic and persist at a fairly low level from season to season; however, introduction of a new strain may result in epidemics, as illustrated in Figure 5–3. Communicable infections that are both widespread, for example, worldwide, and have high attack rates are termed pandemic.

An important consideration in the study of the epidemiology of communicable organisms is the distinction between infection and disease. Infection involves multiplication of the organism in or on the host and may be clinically inapparent, such as during the incubation period or latency (when little or no replication is occurring, eg, with herpesviruses). Disease occurs when the infection becomes clinically apparent, that is, there is evidence of injury to the host as a result of the infection. With many communicable organisms, infection is much more common than disease, and apparently healthy infected individuals are important for propagation of the infectious agent. Inapparent infections are termed subclinical, and the individual is sometimes referred to as a carrier. The latter term is also applied to situations in which an infectious agent establishes itself as part of a patient’s microbiota or causes low-grade chronic disease after an acute infection. For example, the clinically inapparent presence of S aureus in the anterior nares is termed carriage, as is chronic gallbladder infection with Salmonella serotype Typhi that can follow an attack of typhoid fever and result in fecal excretion of the organism for years.

With some infectious diseases such as measles, infection is almost invariably accompanied by clinical manifestations of the disease itself. These manifestations facilitate epidemiologic detection and control, because the existence and extent of infection in a community are readily apparent. Organisms associated with long incubation periods or high frequencies of subclinical infection, such as human immunodeficiency virus (HIV) or hepatitis B virus, may propagate and spread in a population for long periods before the extent of the problem is recognized. This makes epidemiologic control more difficult.

The severity of infection reflects biologic characteristics of the organism as well as the host’s response. Infectivity reflects the secondary attack rate, or the number ill per number exposed. Pathogenicity reflects the ability of the agent to induce disease. Virulence is the severity of the disease after infection occurs. The expected severity of infection reflects pathogen factors (including infectivity, pathogenicity, and virulence) and host factors (eg, immune status). Immunogenicity is the ability of a pathogen to produce a durable immune response to protect against reinfection with the same or a related organism. Some pathogens induce lifelong immunity while others are weakly immunogenic, so reinfections commonly occur.

The incubation period is the time between the exposure to the organism/infection and the appearance of the first clinical manifestations of the disease. Organisms that multiply rapidly and produce local infections, such as gonorrhea and influenza, are associated with short incubation periods (eg, 2-4 days). Diseases such as typhoid fever, which depend on hematogenous spread and multiplication of the organism in distant target organs to produce symptoms, often have longer incubation periods (eg, 10 days to 3 weeks). Some diseases have even more prolonged incubation periods because of slow passage of the infecting organism to the target organ, as in rabies, or with slow growth of the organism, as in tuberculosis or leprosy. Incubation periods for one agent may also vary widely depending on route of acquisition and infecting dose; for example, the incubation period of hepatitis B virus infection may vary from a few weeks to several months.

Communicability of a disease in which the organism is shed in secretions may occur primarily during the incubation period. In other infections, the disease course is short but the organisms can be excreted from the host for extended periods. In yet other cases, the symptoms are related to host immune response rather than the organism’s action and, thus, the disease process may extend far beyond the period in which the etiologic agent can be isolated or spread. Some viruses can integrate into the host genome or survive by replicating very slowly in the presence of an immune response. Such dormancy or latency is exemplified by the herpesviruses, and the organism may emerge long after the original infection and potentially infect others.

The inherent infectivity and virulence of an agent are also important determinants of attack rates of disease in a community. In general, organisms of high infectivity spread more easily, and those of greater virulence are more likely to cause disease than subclinical infection. The infecting dose of an organism also varies with different organisms and, thus, influences the chance of infection and development of disease.

Various transmissible infections may be acquired from others by direct contact, indirectly through contaminated inanimate objects or materials, or by aerosol transmission of infectious secretions. Some infections, such as malaria, involve an animate insect vector. These routes of spread are often referred to as horizontal transmission, in contrast to vertical or perinatal transmission—from mother to fetus or infant.

Vertical or Perinatal Transmission

Some infections can spread from mother to fetus through the placenta, during childbirth, or during breastfeeding. For example, rubella virus may cause birth defects when transmitted from the mother’s bloodstream across the placenta during the first trimester of pregnancy. Neonatal infections with group B streptococci, Chlamydia trachomatis, and Neisseria gonorrhoeae can occur following passage through the birth canal. Cytomegalovirus (CMV) can be acquired prenatally (across the placenta) or perinatally (from passage through an infected cervix, contact with blood, or through breast milk).

Important effects of perinatal infection include prematurity, intrauterine growth retardation (IUGR) and low birth weight, developmental abnormalities, congenital disease, and persistent perinatal infection. Historically, common causes of IUGR and developmental abnormalities associated with congenital infection during the first trimester include toxoplasmosis, rubella, CMV, herpes simplex, and syphilis. Zika virus, transmitted by Aedes mosquitos, was recognized recently to cause similar abnormalities when acquired in the first trimester of gestation.

The major routes of horizontal transmission of infectious diseases are summarized in Table 5–1 and discussed in the following text.

Respiratory Spread: Airborne or Contact with Respiratory Secretions

Many infections are transmitted by the respiratory route, often by aerosolization of respiratory secretions with subsequent inhalation by other persons. The efficiency of this process depends, in part, on the extent and method of propulsion of discharges from the mouth and nose, the size of the aerosol droplets, and the resistance of the infectious agent to desiccation and inactivation by ultraviolet light. In still air, a particle 100 μm in diameter requires only seconds to fall the height of a room; a 10 m particle remains airborne for about 20 minutes, smaller particles even longer. When inhaled, particles with a diameter of 6 μm or more are usually trapped by the mucosa of the nasal turbinates, whereas particles of 0.6 to 5.0 μm attach to mucous sites at various levels along the upper and lower respiratory tract and may initiate infection. These “droplet nuclei” are most important in transmitting many respiratory pathogens (eg, M tuberculosis).

Respiratory secretions are often transferred on hands or inanimate objects (fomites) and may reach the respiratory tract of others in this way. For example, spread of the common cold may involve transfer of infectious secretions from nose to hand by the infected individual, with transfer to others by hand-to-hand contact and then from hand to nose. Transmission of infectious secretions by direct contact with the nasal mucosa or conjunctiva often accounts for the rapid dissemination of agents, such as respiratory syncytial virus and adenovirus. The risk of spread in these instances can be reduced by simple hygienic measures such as handwashing.

Salivary Spread: Kissing or Bite

Some infections, such as herpes simplex and infectious mononucleosis, can be transferred directly by contact with infectious saliva by drooling small children or through kissing. Saliva containing rabies virus can transmit rabies when the rabid animal bites.

Eye-to-Eye Transmission

Infections of the conjunctiva may occur in epidemic or endemic form. Epidemics of adenovirus and Haemophilus conjunctivitis may occur, and are highly contagious. The major endemic disease is trachoma, caused by Chlamydia, which remains a common cause of blindness in developing countries. These diseases may be spread by direct contact via ophthalmologic equipment or by secretions passed manually or through fomites such as towels.

Skin-to-Skin Transfer

Skin-to-skin transfer occurs with a variety of infections in which the skin is the portal of entry such as the spirochete of syphilis (Treponema pallidum), strains of group A streptococci that cause impetigo, and the dermatophyte fungi that cause ringworm and athlete’s foot. In most cases, an unapparent break in the epithelium is involved in infection. Other diseases may be spread indirectly from skin-to-skin through fomites such as shared towels and inadequately cleansed shower and bath floors. Skin-to-skin transfer usually occurs through abrasions of the epidermis, which may be unnoticed.

Genital Transmission

Disease transmission through the genital tract has been and remains one of the most common infections worldwide. Spread can occur between sexual partners or from the mother to the infant at birth. Major factors related to the persistence of these infections are high rates of asymptomatic carriage and the frequency of recurrence of organisms such as C trachomatis, CMV, herpes simplex virus, and Neisseria gonorrhoeae.

Foodborne or Waterborne Transmission: Fecal–Oral Spread

Fecal–oral spread involves direct or finger-to-mouth spread, the use of human feces as a fertilizer, or fecal contamination of food or water. Food handlers who are infected with an organism transmissible by this route constitute a special hazard, especially when they fail to wash their hands. Some viruses disseminated by the fecal–oral route infect and multiply in cells of the oropharynx and then disseminate to other body sites to cause infection. However, organisms that are spread in this way commonly multiply in the intestinal tract and may cause intestinal infections. They must, therefore, be able to resist the acid in the stomach, the bile, and the gastric and small intestinal enzymes. Many bacteria and enveloped viruses are rapidly killed by these conditions, but members of the Enterobacteriaceae and unenveloped viral intestinal pathogens (eg, enteroviruses) are more likely to survive. Even with these organisms, the infecting dose in patients with reduced or absent gastric hydrochloric acid is often much smaller than in those with normal stomach acidity.

Blood or Transfusion-Borne

Bloodborne transmission of infection through insect vectors requires a period of multiplication or alteration within an insect vector before the organism can infect another human host, as occurs with the female Anopheles mosquito and the malarial parasite. Direct transmission from human to human through blood has become increasingly important because of the use of blood transfusions and blood products and the increased self-administration of illicit drugs by intravenous or subcutaneous routes using shared nonsterile equipment. Hepatitis B and C viruses, as well as HIV, were frequently transmitted in this way before the institution of universal screening of blood.

Vector-borne and Zoonotic

Zoonotic infections are spread from animals, where they have their natural reservoir, to humans. Some zoonotic infections such as rabies are directly contracted from the bite of the infected animal, whereas others are transmitted by vectors, especially arthropods (eg, ticks, mosquitoes). Many infections contracted by humans from animals are dead-ended in humans, whereas others may be transferred between humans once the disease is established in a population. Plague, for example, has a natural reservoir in rodents. Human infections contracted from the bites of rodent fleas may produce pneumonia, which may then spread to other humans by the respiratory droplet route.

Classically the term vector was restricted to arthropods like ticks and mosquitoes; however, it is often used to refer to any animal that can transmit a pathogen to a human host. The probability of vector-borne transmission depends on the biology of the vector (mosquito, tick, snail, etc) and the infectivity of organism.

Epidemic Propensity

The likelihood and characterization of epidemics and their recognition in a community involve several quantitative measures and some specific epidemiologic definitions. Infectivity, in epidemiologic terms, equates to attack rate and is measured as the frequency with which an infection is transmitted when there is contact between the agent and a susceptible individual. The disease index of an infection can be expressed as the number of persons who develop the disease divided by the total number infected. The virulence of an agent can be estimated as the number of fatal or severe cases per total number of cases. Incidence, the number of new cases of a disease within a specified period, is described as a rate in which the number of cases is the numerator and the number of people in the population under surveillance is the denominator. This is usually normalized to reflect a percentage of the population that is affected. Prevalence, which can also be described as a rate, is primarily used to indicate the total number of cases existing in a population at risk at a point in time. Diseases are more prevalent if they are especially common or less common but persist for a long time.

The prerequisites for propagation of an epidemic from person to person are: (1) a sufficient degree of infectivity to allow the organism to spread; (2) sufficient virulence for an increased incidence of disease to become apparent; and (3) sufficient level of susceptibility in the host population to permit transmission and amplification of the infecting organism. Thus, the extent of an epidemic and its degree of severity are determined by complex interactions between infectious agent and host. Host factors such as age, genetic predisposition, and immune status can dramatically influence the manifestations of an infectious disease. Together with differences in infecting dose, these factors are largely responsible for the wide spectrum of disease manifestations that may be seen during an epidemic.

The effect of age can be dramatic. For example, in an epidemic of measles in an isolated population in 1846, the attack rate for all ages averaged 75%; however, mortality rate was 90 times higher in children less than 1 year of age (28%) than in those 1 to 40 years of age (0.3%). Conversely, in one outbreak of poliomyelitis, the attack rate of paralytic polio was 4% in children 0 to 4 years of age, and 20% to 40% in those 5 to 50 years of age. Sex may be a factor in disease manifestations; for example, the likelihood of becoming a chronic carrier of hepatitis B is twice as high for males as for females.

Prior exposure of a population to an organism may alter immune status and the frequency of acquisition, severity of clinical disease, and duration of an epidemic. For example, measles is highly infectious and attacks most susceptible members of an exposed population. However, infection gives solid lifelong immunity. Thus, in unimmunized populations in which the disease is maintained in endemic form, epidemics occur at approximately 3-year intervals when a sufficient number of nonimmune hosts has been born to permit rapid transmission between them. When a sufficient immune population is reestablished, epidemic spread is blocked and the disease again becomes endemic. When immunity is short-lived or incomplete, epidemics can continue for decades if the mode of transmission is unchecked, which accounts for the present epidemic of gonorrhea.

Prolonged and extensive exposure to a pathogen during previous generations selects for a higher degree of innate genetic immunity in a population. For example, extensive exposure of Western urbanized populations to tuberculosis during the 18th and 19th centuries conferred a degree of resistance greater than that among the progeny of rural or geographically isolated populations. The disease spread rapidly and in severe form, for example, when it was first encountered by Native Americans. An even more dramatic example concerns the resistance to the most serious form of malaria that is conferred on people of West African descent by the sickle cell trait. These instances are clear cases of natural selection—a process that accounts for many differences in immunity in different races and populations.

Occasionally, an epidemic arises from an agent against which immunity is essentially absent in a population and that is either of enhanced virulence or appears to be of enhanced virulence because of the lack of immunity. When such an organism is highly infectious, the disease it causes may become pandemic and worldwide. An example is the appearance of a new major antigenic variant of influenza A virus against which there is little, if any, cross-immunity from recent epidemics with other strains. The 1918 to 1919 pandemic of influenza was responsible for more deaths than World War I (>20 million). Subsequent but less serious pandemics have occurred at intervals because of the development of strains of influenza virus with major antigenic shifts (see Chapter 9). Another example, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), illustrates the same principles but also reflects changes in human ecologic and social behavior.

A major feature of serious epidemic diseases is their frequent association with poverty, malnutrition, disaster, and war. The association is multifactorial and includes overcrowding, contaminated food and water, an increase in arthropods that parasitize humans, and the reduced immunity that can accompany severe malnutrition or certain types of chronic stress. Overcrowding and understaffing in day-care centers or institutions for the mentally impaired can similarly be associated with epidemics of infections.

In recent years, increasing attention has been given to health-care associated infections. Important health-care associated infections include central-line associated bloodstream infections, catheter-associated urinary tract infections, and ventilator-associated pneumonia. Previously these were called hospital (nosocomial) infections; however, the change in nomenclature to health-care associated infections reflects the variety of locations in which individuals now receive care, including long-term care facilities. Hospitals and other health-care facilities are not immune to the epidemic diseases that occur in the community; and outbreaks result from the association of infected patients or persons with those who are unusually susceptible because of chronic disease, immunosuppressive therapy, or the use of bladder, intratracheal, or intravascular catheters and tubes. Control depends on sterile technique with procedures and good infection control practices, including handwashing by medical personnel, hospital hygiene, and effective surveillance.

Control of Epidemics

The first principle of control is recognition of the existence of an epidemic. This recognition is sometimes immediate because of the high incidence of disease but, often, the evidence is obtained from ongoing surveillance activities, such as routine disease reports to health departments and records of school and work absenteeism. The causative agent must be identified, and studies to determine route of transmission (eg, food poisoning) must be initiated.

Measures must then be adopted to control the spread and development of further infection. These methods include: (1) blocking the route of transmission, if possible (eg, improved food hygiene or arthropod control); (2) identifying, treating, and, if necessary, isolating infected individuals and carriers; (3) raising the level of immunity in the uninfected population by immunization; (4) making selective use of chemoprophylaxis for subjects or populations at particular risk of infection, as in epidemics of meningococcal infection; and (5) correcting conditions such as overcrowding or contaminated water supplies that have led to the epidemic or facilitated transfer.

Epidemiologic study is essential to identify, characterize, and control infectious diseases. Combating emerging infections requires recognizing new agents and patterns of disease, understanding their nature and spread, and then instituting control measures. The latter may involve prompt treatment of cases, prevention through selective chemoprophylaxis or immunization, implementation of environmental controls, and public education, depending on the specific agent. However, application of epidemiologic principles is essential for the health of both individuals and communities.