1. The Epidemiology of Infectious Disease Concepts 1. The science of epidemiology deals with the occurrence and distribution of disease within a given population. Infectious disease epidemiology is concerned with organisms or agents responsible for the spread of infectious diseases in human and other animal populations. 2.Because numbers and time are major epidemiological parameters, statistics is an important working tool in this discipline. Statistics are used to determine morbidity, frequency, and mortality rates. 3.To trace the origin and manner of spread of an infectious disease outbreak, it is necessary to learn what pathogen is responsible. 4.Epidemiologists investigate five links in the infectious disease cycle: (1) Characteristics of the pathogen, (2) Source and/or reservoir of the pathogen, (3) Mode of transmission, (4) Susceptibility of the host, and (5) Exit mechanisms. 5.Emerging and reemerging diseases and pathogens are a major global concern, as is the potential threat of bioterrorism. 6.Global travel requires global health considerations. 7.The control of nosocomial (hospital acquired) infections has received increasing attention in recent years because of the number of individuals involved, increasing costs, and the length of hospital stays.

2. Epidemiological Terminology When a disease occurs occasionally, and at irregular intervals in a human population, it is a sporadic disease (e.g., typhoid fever). When it maintains a steady, low-level frequency at a moderately regular interval, it is an endemic disease (e.g., the common cold). Hyperendemic diseases gradually increase in occurrence frequency beyond the endemic level but not to the epidemic level (e.g., the common cold during winter months). An epidemic is a sudden increase in the occurrence of a disease above the expected level. Influenza is an example of a disease that often achieves epidemic status. The first case in an epidemic is called the index case. An outbreak, on the other hand, is the sudden, unexpected occurrence of a disease, usually focally or in a limited segment of a population (e.g., Legionnaires’ disease). A pandemic is an increase in disease occurrence within a large population over a very wide region (usually the world). Usually, pandemic diseases spread among continents. The influenza outbreak of the 1960s and AIDS in the 1980s are good examples.

3. Figure 1.2: A graph illustrating three epidemics. The solid blue line indicates the expected number of endemic cases. The connected red dots indicate the actual number of cases. Epidemics (marked by brackets) are sharp increases in the number of cases of a disease above that which is normally expected (solid line).

4. Disease Prevalence and Disease Incidence As an example, let us use a classroom of 50 students exposed to a new strain of influenza. Before exposure, the prevalence and incidence in this population are both zero (0/50). If in one week, 5 out of the 50 people contract the disease, the prevalence is 5/50 = 10%, and the incidence is 1 in 9 (5 cases compared with 45 healthy persons). If after 2 weeks, 5 more students contract the flu, the prevalence becomes 5 + 5 = 10/50 = 20%, and the incidence becomes 1 in 8 (5/40). When dealing with large populations, the incidence is usually given in numbers of cases per 1,000 or 100,000 population.

5. Morbidity Rate and Mortality Rate For example, if there were 15,000 deaths due to AIDS in a year, and the total number of people infected was 30,000, the mortality rate would be 15,000 per 30,000 or 1 per 2 or 50%.

6. Infectious Disease Epidemiology Recognition of an Infectious Disease in a Population Surveillance Epidemiologists can recognize an infectious disease in a population by using various surveillance methods. Some combination of the following surveillance methods is used most often: 1.Generation of morbidity data from case reports. 2.Collection of mortality data from death certificates. 3.Investigation of actual cases. 4.Collection of data from reported epidemics. 5.Field investigation of epidemics. 6.Review of laboratory results: surveys of a population for antibodies against the agent and specific microbial serotypes, skin tests, cultures, stool analyses, etc.

7. 7.Population surveys using valid statistical sampling to determine who has the disease. 8.Use of animal and vector disease data. 9.Collection of information on the use of specific biologics—antibiotics, antitoxins, vaccines, and other prophylactic measures. 10.Use of demographic data on population characteristics such as human movements during a specific time of the year. 11.Use of remote sensing and geographic information systems.

8. Remote Sensing and Geographic Information Systems: Charting Infectious Diseases Remote sensing and geographic information systems are map-based tools that can be used to study the distribution, dynamics, and environmental correlates of microbial diseases. Remote sensing (RS) is the gathering of digital images of the Earth’s surface from satellites and transforming the data into maps. Correlation with a Single Causative Agent After an infectious disease has been recognized in a population, epidemiologists correlate the disease outbreak with a specific organism—its exact cause must be discovered.

9. Monitoring the Frequency of a Disease in a Population The changes in incidence and prevalence are usually followed over a seasonal, yearly, and long-term basis and are helpful in predicting trends

10. Recognition of an Epidemic Types of Epidemics A common-source epidemic is characterized as having reached a peak level within a short period of time (1 to 2 weeks) followed by a moderately rapid decline in the number of infected patients. A propagated epidemic is characterized by a relatively slow and prolonged rise and then a gradual decline in the number of individuals infected

11. Figure 1.5: Epidemic curves. (a) In a common-source epidemic, there is a rapid increase up to a peak in the number of individuals infected and then a rapid but more gradual decline. Cases usually are reported for a period that equals approximately one incubation period of the disease. (b) In a propagated epidemic the curve has a gradual rise and then a gradual decline. Cases usually are reported over a time interval equivalent to several incubation periods of the disease.

12. Antigenic Shift and Antigenic Drift An antigenic shift can be so extensive that the pathogen is no longer recognized by the host’s immune system. For example, influenza viruses frequently change by recombination from one antigenic type to another. Smaller antigenic changes also can take place by a mutation in pathogen strains and help the pathogen avoid host immune responses. These smaller changes are called antigenic drift. Whenever antigenic shift or drift occurs, the population of susceptibles increases because the immune system has not been exposed to the new mutant strain. For example, the morbidity rates of diphtheria and measles among school children may reach epidemic levels if the number of susceptibles rises above 30% for the whole population. As a result the goal of public health agencies is to make sure that at least 70% of the population is immunized against these diseases to provide the herd immunity necessary for protection of those who are not immunized.

13. The Infectious Disease Cycle: Story of a Disease Figure 1.8: Infectious disease cycle or chain of infection. See text for further details.

14. Emerging and Reemerging Infectious Diseases and Pathogens Antibiotics, vaccines, and aggressive public health campaigns had yielded a string of victories over old enemies like whooping cough, pneumonia, polio, and smallpox. In developed countries, people were lulled into believing that microbial threats were a thing of the past. However, this downward trend ended in 1982 and the death rate has risen in the past 20 years. In these 20 years, the world has seen the global spread of AIDS, the resurgence of tuberculosis, and the appearance of new enemies like hantavirus pulmonary syndrome, hepatitis C and E, Ebola virus, Lyme disease, cryptosporidiosis, and the deadly E. coli O157:H7. In addition, during this same time period: A “bird flu” virus that had never before attacked humans began to kill people in Hong Kong.

15. A new variant of a fatal brain disease, Creutzfeldt-Jakob disease (see section 38.5 and table 38.6), was identified in the United Kingdom, apparently transmitted by beef from animals with “mad cow disease.” Staphylococcus bacteria with increased resistance to vancomycin, long the antibiotic of first choice, were seen for the first time. The United States was hit with several major multistate foodborne outbreaks, including those caused by parasites on raspberries, viruses on strawberries, and bacteria in produce, ground beef, cold cuts, and breakfast cereal. A new strain of tuberculosis that is resistant to many drugs, and occurs most often in people infected with HIV, arose in the city of New York and other large cities.

16. Many factors characteristic of the modern world undoubtedly favor the development and spread of these microorganisms and their diseases. Examples include: 1.Unprecedented worldwide population growth, population shifts (demographics), and urbanization 2.Increased international travel 3.Increased worldwide transport (commerce), migration, and relocation of animals and food products 4.Changes in food processing, handling, and agricultural practices 5.Changes in human behavior, technology, and industry 6.Human encroachment on wilderness habitats that are reservoirs for insects and animals that harbor infectious agents 7.Microbial evolution (e.g., selection pressure) and the development of resistance to antibiotics and other antimicrobial drugs (e.g., penicillin- resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant enterococci) 8.Changes in ecology and climate 9.Modern medicine (e.g., immunosuppression) 10.Inadequacy of public infrastructure and vaccination programs 11.Social unrest and civil wars 12. The possibility of bioterrorism 13.Virulence-enhancing mechanisms of pathogens (e.g., the mobile genetic elements—bacteriophages, plasmids, transposons)

17. Control of Epidemics The Types of Control Measures There are three types of control measures. The first type is directed toward reducing or eliminating the source or reservoir of infection: 1.Quarantine and isolation of cases and/or carriers. 2.Destruction of an animal reservoir of infection. 3.Treatment of sewage to reduce water contamination. 4.Therapy that reduces or eliminates infectivity of the individual.

18. The second type of control measure is designed to break the connection between the source of the infection and susceptible individuals. Examples include general sanitation measures: 1.Chlorination of water supplies. 2.Pasteurization of milk. 3.Supervision and inspection of food and food handlers. 4.Destruction of vectors by spraying with insecticides.

19. The third type of control measure reduces the number of susceptible individuals and raises the general level of herd immunity by immunization. Examples include the following: 1.Passive immunization to give a temporary immunity following exposure to a pathogen or when a disease threatens to take an epidemic form. 2.Active immunization to protect the individual from the pathogen and the host population from the epidemic.