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onset of an epidemic

Pandemic

A worldwide epidemic

Portal of entry

Surface or orifice through which a disease-causing agent enters the body

Portal of exit

Surface or orifice from which a disease-causing agent exits and disseminates

Prevalence

The total number of cases in a given population at risk at a point in time

Reservoir

The natural habitat of a disease-causing organism

Asymptomatic Carriers A person can harbor a pathogen with no ill effects whatsoever, acting as a carrier of the disease agent. These people may shed the organism intermittently or constantly for months, years, or even a lifetime.

Some carriers have an asymptomatic infection; their immune system is actively responding to the invading microorganism, but they have no obvious clinical symptoms. Because these people often have no reason to consider that they are a reservoir, they move freely about, spreading the pathogen. People with asymptomatic infections are a significant complicating factor in the control of sexually transmitted diseases such as gonorrhea. Up to 50% of women infected with Neisseria gonorrhoeae have no obvious symptoms, which means they often unknowingly transmit the disease to their sexual partners. In contrast, most infected men are symptomatic and therefore seek medical treatment. Gonorrhea infections can be treated with antibacterial drugs, but tracking down sexual contacts of infected people is difficult and costly. As another example, people who recover from typhoid fever without benefit of antibiotic treatment may harbor the causative strain of Salmonella in their gallbladder, shedding it in their feces. Even after typhoid fever has been controlled in a population, the presence of chronic carriers poses a threat of disease recurrence for many years. ■ Neisseria gonorrhoeae, p. 644 ■ typhoid fever, p. 616

Some pathogens can colonize the skin or mucosal surfaces, establishing themselves as part of a person's microbial flora. For example, at least 60% of the population carry Staphylococcus aureus as a part of their nasal or skin flora during some period of their life. At least 20% of these are chronic carriers who harbor the organism for a year or more. Staphylococcus aureus carriers may never have any illness or disease as a result of the organism, but they remain a potential source of infection to themselves and others. Likewise, some people are carriers of the pathogen Streptococcus pyogenes. Health care workers who carry this bacterium have been linked to outbreaks in hospitals. Ridding a colonized carrier of the infectious organism is often difficult, even with the use of antimicrobial drugs. ■ Staphylococcus aureus, p. 537 ■ Streptococcus pyogenes, p. 565

Non-Human Animal Reservoirs

Non-human animal reservoirs are the source of some pathogens. For example, poultry are a reservoir of gastrointestinal pathogens such as species of Campylobacter and Salmonella. In the United States, raccoons, skunks, and bats are the reservoir of the rabies virus. Recall that rodents are the reservoir of Yersinia pestis, the causative agent of plague. Occasional transmission of plague to humans is still reported in the southwestern states where Y. pestis is endemic in prairie dogs and other rodents, but rodent control has helped prevent epidemics of the disease. Rodents, particularly the deer mouse, are also the reservoir for hantavirus. ■ Campylobacter, p. 617 ■ Salmonella, p. 616

Diseases such as plague and rabies that can be transmitted to humans but primarily exist in other animals are called zoonotic diseases or zoonoses. Zoonotic diseases are often more severe in humans than in the normal animal host because the infection in humans is accidental; there has been no evolution toward the balanced pathogenicity that normally exists between a host and parasite. ■ balanced pathogenicity, p. 465

20.1 Principles of Epidemiology 489

Environmental Reservoirs

Some pathogens have environmental reservoirs. For example, Clostridium botulinum, which causes botulism, and Clostridium tetani, which causes tetanus, are both widespread in soils. Legionella pneumophila is found in water in association with amebas. Unfortunately, pathogens that have environmental reservoirs are probably impossible to eliminate.■ Clostridium botulinum, p. 672 ■ Clostridium tetani, p. 699 ■ Legionella pneumophila, p. 584

Portals of Exit

Microorganisms must leave one host in order to be transmitted to another. Those that inhabit the intestinal tract are routinely shed in the feces. Pathogens such as Vibrio cholerae that cause massive volumes of watery diarrhea may have an evolutionary advantage because the large volumes discharged may enhance their dispersal. Respiratory organisms are expelled in droplets of saliva when people talk, laugh, sing, sneeze, or cough (see figure 20.1b). Pathogens such as Mycobacterium tuberculosis and various respiratory viruses exit the body via this route. Meanwhile, organisms that inhabit the skin are constantly shed on skin cells. Even as you read this text you are shedding skin cells, some of which may have Staphylococcus aureus on their surface. Genital pathogens such as Neisseria gonorrhoeae can be carried in semen and vaginal secretions. Some pathogens, such as the eggs of the helminth Schistosoma hematobium, can exit in urine. Hantavirus is found in the saliva, urine, and droppings of the deer mouse. ■ Vibrio cholerae, p. 611 ■ Neisseria gonorrhoeae, p. 644 ■ Mycobacterium tuberculosis, p. 582 ■ Staphylococcus aureus, p. 537

Transmission

A successful pathogen must somehow be passed from its reservoir to the next susceptible host. Transmission of a disease-causing organism from one person to another through contact, ingestion of food or water, or via a living agent such as an insect is called horizontal transmission. This contrasts with vertical transmission, which is the transfer of a pathogen from a pregnant woman to the fetus, or from a mother to her infant during childbirth. Certain microbes can cross the placenta and damage a developing fetus, causing diseases such as congenital syphilis. Others, such as group B streptococci, can infect the newborn as it passes through the birth canal. ■ syphilis, p. 648 ■ group B streptococci, p. 666

Contact

Transmission of a pathogen from one person to another often involves some form of contact. This can be through direct touch, inhalation of droplets of respiratory secretions or saliva, or indirect contact by way of a non-living object.

Direct Contact Direct contact occurs when one person physically touches another. It can be through an act as simple as a handshake, or a more intimate contact such as sexual intercourse. In some cases, direct contact is the primary way in which an organism is transmitted. This is particularly true if the transfer of even very low numbers of an organism can initiate an infection. For example, the infectious dose of Shigella species, which are intestinal pathogens, is approximately 10 to 100 organisms, a

490 Chapter 20 Epidemiology number easily passed when shaking hands. Once on the hands, the organisms can inadvertently be ingested. This is just one example of how fecal-oral transmission, the inadvertent consumption of organisms that originate from the intestine, can occur. Handwashing, a fairly simple routine that physically removes organisms, is important in preventing this type of spread of disease. Even washing in plain water reduces the numbers of potential pathogens on the hands, which in turn decreases the possibility of transferring or ingesting sufficient numbers of an organism to establish an infection. In fact, routine handwashing is considered to be the single most important measure for preventing the spread of infectious disease. ■ Shigella sp., p. 613

Pathogens that cannot survive for extended periods in the environment must generally, because of their fragile nature, be transmitted through direct contact. For example, Treponema pallidum, which causes syphilis, and Neisseria gonorrhoeae, which causes gonorrhea, both die quickly when exposed to a relatively cold dry environment and thus require intimate sexual contact for their transmission. ■ Treponema pallidum, p. 648 ■ Neisseria gonorrhoeae, p. 644

Indirect Contact Indirect transmission involves transfer of pathogens via inanimate objects, or fomites, such as clothing, table-tops, doorknobs, and drinking glasses. For example, carriers of Staphylococcus aureus may inoculate their hands with the organism when touching a skin lesion or colonized nostril. Organisms on the hands can then easily be transferred to a fomite. Another person can readily acquire the microbes when handling that object. Again, handwashing is an important control measure.

Droplet Transmission Large microbe-laden respiratory droplets generally fall to the ground no farther than a meter (approximately 3 feet) from release. People in close proximity can inhale those droplets, however, resulting in the spread of respiratory disease via droplet transmission. Although physical contact is not necessary, droplet transmission is considered direct transmission because of the close range involved. Droplet transmission is particularly important as a source of contamination in densely populated buildings such as schools and military barracks. Desks or beds in such locations ideally should be spaced more than 4 feet and preferably 8 to 10 feet apart to minimize the transfer of infectious agents. Another way to minimize the spread of respiratory diseases is to educate people about the importance of covering their mouths with a tissue when they cough or sneeze.

Food and Water

Pathogens, particularly those that infect the gastrointestinal tract, can be transmitted through contaminated food or water. Foods can become contaminated in a number of different ways. Animal products such as meat and eggs may harbor pathogens that originated from the animal itself. This is the case with poultry that is contaminated with species of Salmonella or Campylobacter and hamburger that is contaminated with E. coli O157:H7. Pathogens can also be inadver tently added during food preparations. For example, typhoid carriers who do not wash their hands thoroughly after defecating and prior to preparing food can easily contaminate the food. This is yet another example of how fecal-oral transmission can occur. Cross-contamination results when pathogens from one food are transferred to another. A cutting board used first to carve raw chicken and then to cut cooked potatoes can serve as a fomite, transferring Salmonella species from the chicken onto the potatoes. Because many foods are a rich nutrient source, microorganisms can multiply to high numbers if the contaminated food is improperly stored. Sound food-handling methods, including sanitary preparation as well as thorough cooking and proper storage, can prevent foodborne diseases. ■ food storage, p. 123

Waterborne disease outbreaks can involve large numbers of people because municipal water systems distribute water to large areas. For example, the 1993 waterborne outbreak of Cryptosporidium parvum, an intestinal parasite, in Milwaukee, Wisconsin, was estimated to have involved approximately 400,000 people. Prevention of waterborne diseases requires chlorination and filtration of drinking water and proper disposal and treatment of sewage. ■ Cryptosporidium parvum, p. 626 ■ drinking water treatment, p. 791 ■ sewage treatment, p. 786

Respiratory diseases can also be transmitted through the air. When particles larger than 10 mm are inhaled, they are usually trapped in the mucus lining of the nose and throat and eventually swallowed. Smaller particles, however, can enter the lungs, where any pathogens they carry can potentially cause disease.

As mentioned earlier, when people talk, laugh, or sneeze they continually discharge microorganisms in liquid droplets. While large droplets quickly fall to the ground, the smaller droplets dry, leaving one or two organisms attached to a thin coat of the dried material, creating droplet nuclei. The droplet nuclei can remain suspended indefinitely in the presence of even slight air currents. Other airborne particles, including dead skin cells, household dust, and soil disturbed by the wind, may also carry respiratory pathogens. An air conditioning system may be a source of infectious agents, because it can distribute air contaminated by people or with organisms growing within the system.

The number of viable organisms in air can be estimated by using a machine that pumps a measured volume of air, including any suspended dust and particles, against the surface of a nutrient-rich medium in a Petri dish. This technique has shown that the number of bacterial colonies in the air sampled rises in proportion to the number of people in a room (figure 20.3). The survival of organisms in air varies greatly with the type of organism and with air conditions such as humidity, temperature, and degree of light. In general, Gram-positive organisms survive longer in air than do Gram-negative organisms, and survival in dim light is greater than that in bright light.

Understandably, airborne transmission of pathogens is very difficult to control. To prevent the buildup of airborne pathogens, modern public buildings have ventilation systems that

Figure 20.3 Air Sample Cultures (a) Air from a clean, empty hospital room. (b) Air from a small room containing 12 people. In both situations, 5 cubic feet of air was sampled.

Figure 20.3 Air Sample Cultures (a) Air from a clean, empty hospital room. (b) Air from a small room containing 12 people. In both situations, 5 cubic feet of air was sampled.

constantly change the air. Hospital microbiology laboratories can be kept under a slight vacuum so that air flows in from the corridors, preventing microorganisms and viruses from being swept out of the lab to other parts of the building. Air in some laboratories, specialized hospital rooms, and jetliners is circulated through high-efficiency particulate (HEPA) filters to remove airborne organisms that may be present. ■ HEPA filters, p. 122

Vectors

A vector such as a mosquito or flea can transmit some diseases. The term vector applies to any living organism that can carry a disease-causing microbe, but most commonly these are arthropods such as mosquitoes, fleas, lice, and ticks. A vector may carry a pathogen externally or internally.

Flies that land on feces can pick up intestinal pathogens such as Escherichia coli O157:H7 and Shigella species on their legs. If the fly then moves to a food, it transfers the microorganisms to a source that could be consumed. In this case, the fly serves as a mechanical vector, carrying the microbe on its body from one place to another.

Diseases such as such as malaria, plague, and Lyme disease are transmitted via arthropods that harbor the pathogen internally. The vector either injects the infectious agent while taking a blood meal or defecates, depositing the pathogen onto a person's skin where it can then be inadvertently inoculated when the individual scratches the bite. For example, fleas inject Yersinia pestis while attempting to take a blood meal. In the case of malaria, caused by species of the eukaryotic pathogen Plasmodium, the mosquito is not only the transmitter of the parasite but also serves as an essential part of its reproductive life cycle. A vector that is required as a part of a parasite's life cycle is called a biological vector. An important significance of a biological vector is that the pathogen can multiply to high numbers within the vector.

Prevention of vector-borne disease relies on control of mosquitoes, ticks, and other arthropods. The success of such controls was demonstrated when malaria, once endemic in the continental United States, was successfully eliminated from the nation. This was accomplished through a combination of mos-

20.1 Principles of Epidemiology 491

quito elimination and prompt treatment of infected patients. Unfortunately, worldwide eradication efforts that initially showed great promise ultimately failed, in part due to the decreased vigilance that accompanied the dramatic but short lived decline of the disease.

Portals of Entry

To cause disease, not only must a pathogen be transmitted from its reservoir to a new host, it must also enter or colonize a surface of that new host. Colonization is generally a prerequisite for causing disease. For example, cells of a Shigella species may be transferred via a handshake, but they will only cause disease if the person then transfers them to his or her mouth or to food and inadvertently ingests them. This allows the pathogen the opportunity to establish itself in the intestinal tract. Respiratory pathogens that are released into the air during a cough generally cause disease only when someone inhales them. Many organisms that cause disease if they enter one body site are harmless if they enter another. For example, Enterococcus fae-calis may cause a bladder infection if it enters the normally sterile urinary tract, but it is harmless in the intestine where it frequently resides as a member of the normal flora.

The importance of the route of entry in disease development is illustrated in the case of plague transmission. When a flea that normally resides on the rodent reservoir becomes infected and then bites a person, Yersinia pestis is injected and the form of plague called bubonic plague develops. The bacteria multiply rapidly inside lymph nodes, resulting in a disease that is not contagious but has a mortality rate of 50% to 75% if not treated promptly. In a small percentage of people with bubonic plague, however, the organism spreads to the lungs, resulting in a different manifestation of the disease, pneumonic plague. Pneumonic plague presents a much more severe situation, because it is nearly always fatal and is readily transmitted from person to person through respiratory droplets. ■ Yersinia pestis, p. 724

Factors that Influence the Epidemiology of Disease

An infectious agent that is successfully transmitted from a reservoir to a new host can potentially cause disease. The outcome of such transmission events, however, is affected by many different factors including the dose, the incubation period, and characteristics of the host population.

The Dose

The probability of infection and disease is generally lower when an individual is exposed to small numbers of a pathogen. This is because there must be a certain minimum number of cells of the pathogen in the body to produce enough damage to cause disease symptoms. For example, if 30 Salmonella typhi cells are ingested in contaminated drinking water yet 1,000,000 are required to produce typhoid fever symptoms, then it will take some time for the bacterial population to increase to that number. Because host defenses are being mobilized at the same time and are racing to eliminate the bacteria, small doses often result in a higher percentage of asymptomatic infections. The immune

492 Chapter 20 Epidemiology system sometimes eliminates the organism before symptoms appear. On the other hand, there are few if any infections for which immunity is absolute. An unusually large exposure to a pathogen, such as can occur in a laboratory accident, may produce serious disease in a person who has immunity to ordinary doses of the pathogen. Therefore, even immunized persons should take precautions to minimize exposure to infectious agents. This principle is especially important for medical workers who attend patients with infectious diseases.

The Incubation Period

The extent of the spread of an infectious agent is influenced by the incubation period. Diseases with typically long incubation periods such as AIDS can spread extensively before the first cases appear. An excellent example of the importance of this factor was the spread of typhoid fever from a ski resort in Switzerland in 1963. As many as 10,000 people had been exposed to drinking water containing small numbers of Salmonella Typhi, the causative agent of the disease. The long incubation period of the disease, 10 to 14 days, allowed widespread dissemination of the organisms by the skiers, since they flew home to various parts of the world before they became ill. As a result, there were more than 430 cases of typhoid fever in at least six countries. ■ incubation period, p. 463

Population Characteristics

Certain population groups are more likely to be affected by a given disease-causing agent. Population characteristics that influence the occurrence of disease include:

■ Immunity to the pathogen. Previous exposure or immunization of the population to a disease agent or antigenically related agents influences the number of people who become ill from a disease. A disease is unlikely to spread very widely in a population in which 90% of the people are immune to the disease agent. If humans are the only reservoir, then a continuous source of susceptible people is required or the disease will disappear from the population. Recall that the requirement for a susceptible host allowed smallpox to be eradicated. When an infectious agent cannot spread in a population because it lacks a critical concentration of non-immune hosts, a phenomenon called herd immunity results. The non-immune individuals are essentially protected by the lack of a reservoir of infection. Unfortunately, some infectious agents are able to undergo antigenic variation so that they can continue to propagate even in a previously exposed population. ■ antigenic variation, pp. 187, 472

■ General health. Malnutrition, overcrowding, and fatigue increase the susceptibility of people to infectious diseases and enhance the diseases' spread. Infectious diseases have generally been more of a problem in poor areas of the world where individuals are crowded together without proper food or sanitation. Factors that promote good general health result in increased resistance to diseases such as tuberculosis. When infection does occur in a healthy individual, it is more likely to be asymptomatic or to result in mild disease.

■ Age. The very young and the elderly are generally more susceptible to infectious agents. The immune system of young children is not fully developed, and consequently, they are predisposed to certain diseases. For example, young children are particularly susceptible to meningitis caused by Haemophilus influenzae. The elderly are more prone to disease because the immune system wanes over time. Influenza outbreaks in nursing homes can have fatal consequences. ■ meningitis, p. 664

■ Gender. In some cases, gender influences disease distribution. For example, women are more likely to develop urinary tract infections because their urethra, the tube that connects the bladder to the external environment, is relatively short. Microbes can ascend the urethra into the bladder. Women who are pregnant are more susceptible to listeriosis, caused by Listeria monocytogenes. ■ Listeria monocytogenes, p. 668

■ Religious and cultural practices. The distribution of disease is also influenced by religious and cultural practices. For example, infants who are breast-fed are less likely to have diarrhea caused by infectious agents because of the protective effects of antibodies in the mother's milk. Groups who eat traditional dishes made from raw freshwater fish are more likely to acquire tapeworm, a parasite normally killed by cooking.

■ Genetic background. Natural immunity can vary with genetic background, but it is usually difficult to determine the relative importance of genetic, cultural, and environmental factors. In a few instances, however, the genetic basis for resistance to infectious disease is known. For example, many people of black African ancestry are not susceptible to malaria caused by Plasmodium vivax because they lack a specific red blood cell receptor used by the organism. Some populations of Northern European ancestry are less susceptible to HIV infection because they lack a certain receptor on their white blood cells. Studies of the incidence of tuberculosis in identical twins suggest that genetic factors play a role in the disease process, and there is also evidence of a genetic influence in the development of paralytic poliomyelitis.

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