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Microbiology

16.1 The Language of Epidemiologists

Microbiology 16.1 The Language of Epidemiologists
  1. Preface
  2. 1 An Invisible World
    1. Introduction
    2. 1.1 What Our Ancestors Knew
    3. 1.2 A Systematic Approach
    4. 1.3 Types of Microorganisms
    5. Summary
    6. Review Questions
      1. Multiple Choice
      2. Fill in the Blank
      3. Short Answer
      4. Critical Thinking
  3. 2 How We See the Invisible World
    1. Introduction
    2. 2.1 The Properties of Light
    3. 2.2 Peering Into the Invisible World
    4. 2.3 Instruments of Microscopy
    5. 2.4 Staining Microscopic Specimens
    6. Summary
    7. Review Questions
      1. Multiple Choice
      2. Fill in the Blank
      3. Short Answer
      4. Critical Thinking
  4. 3 The Cell
    1. Introduction
    2. 3.1 Spontaneous Generation
    3. 3.2 Foundations of Modern Cell Theory
    4. 3.3 Unique Characteristics of Prokaryotic Cells
    5. 3.4 Unique Characteristics of Eukaryotic Cells
    6. Summary
    7. Review Questions
      1. Multiple Choice
      2. True/False
      3. Fill in the Blank
      4. Short Answer
      5. Critical Thinking
  5. 4 Prokaryotic Diversity
    1. Introduction
    2. 4.1 Prokaryote Habitats, Relationships, and Microbiomes
    3. 4.2 Proteobacteria
    4. 4.3 Nonproteobacteria Gram-Negative Bacteria and Phototrophic Bacteria
    5. 4.4 Gram-Positive Bacteria
    6. 4.5 Deeply Branching Bacteria
    7. 4.6 Archaea
    8. Summary
    9. Review Questions
      1. Multiple Choice
      2. True/False
      3. Fill in the Blank
      4. Short Answer
      5. Critical Thinking
  6. 5 The Eukaryotes of Microbiology
    1. Introduction
    2. 5.1 Unicellular Eukaryotic Parasites
    3. 5.2 Parasitic Helminths
    4. 5.3 Fungi
    5. 5.4 Algae
    6. 5.5 Lichens
    7. Summary
    8. Review Questions
      1. Multiple Choice
      2. Fill in the Blank
      3. Short Answer
      4. Critical Thinking
  7. 6 Acellular Pathogens
    1. Introduction
    2. 6.1 Viruses
    3. 6.2 The Viral Life Cycle
    4. 6.3 Isolation, Culture, and Identification of Viruses
    5. 6.4 Viroids, Virusoids, and Prions
    6. Summary
    7. Review Questions
      1. Multiple Choice
      2. True/False
      3. Fill in the Blank
      4. Short Answer
      5. Critical Thinking
  8. 7 Microbial Biochemistry
    1. Introduction
    2. 7.1 Organic Molecules
    3. 7.2 Carbohydrates
    4. 7.3 Lipids
    5. 7.4 Proteins
    6. 7.5 Using Biochemistry to Identify Microorganisms
    7. Summary
    8. Review Questions
      1. Multiple Choice
      2. True/False
      3. Matching
      4. Fill in the Blank
      5. Short Answer
      6. Critical Thinking
  9. 8 Microbial Metabolism
    1. Introduction
    2. 8.1 Energy, Matter, and Enzymes
    3. 8.2 Catabolism of Carbohydrates
    4. 8.3 Cellular Respiration
    5. 8.4 Fermentation
    6. 8.5 Catabolism of Lipids and Proteins
    7. 8.6 Photosynthesis
    8. 8.7 Biogeochemical Cycles
    9. Summary
    10. Review Questions
      1. Multiple Choice
      2. True/False
      3. Matching
      4. Fill in the Blank
      5. Short Answer
      6. Critical Thinking
  10. 9 Microbial Growth
    1. Introduction
    2. 9.1 How Microbes Grow
    3. 9.2 Oxygen Requirements for Microbial Growth
    4. 9.3 The Effects of pH on Microbial Growth
    5. 9.4 Temperature and Microbial Growth
    6. 9.5 Other Environmental Conditions that Affect Growth
    7. 9.6 Media Used for Bacterial Growth
    8. Summary
    9. Review Questions
      1. Multiple Choice
      2. Matching
      3. Fill in the Blank
      4. Short Answer
      5. Critical Thinking
  11. 10 Biochemistry of the Genome
    1. Introduction
    2. 10.1 Using Microbiology to Discover the Secrets of Life
    3. 10.2 Structure and Function of DNA
    4. 10.3 Structure and Function of RNA
    5. 10.4 Structure and Function of Cellular Genomes
    6. Summary
    7. Review Questions
      1. Multiple Choice
      2. True/False
      3. Matching
      4. Fill in the Blank
      5. Short Answer
      6. Critical Thinking
  12. 11 Mechanisms of Microbial Genetics
    1. Introduction
    2. 11.1 The Functions of Genetic Material
    3. 11.2 DNA Replication
    4. 11.3 RNA Transcription
    5. 11.4 Protein Synthesis (Translation)
    6. 11.5 Mutations
    7. 11.6 How Asexual Prokaryotes Achieve Genetic Diversity
    8. 11.7 Gene Regulation: Operon Theory
    9. Summary
    10. Review Questions
      1. Multiple Choice
      2. True/False
      3. Fill in the Blank
      4. Short Answer
      5. Critical Thinking
  13. 12 Modern Applications of Microbial Genetics
    1. Introduction
    2. 12.1 Microbes and the Tools of Genetic Engineering
    3. 12.2 Visualizing and Characterizing DNA, RNA, and Protein
    4. 12.3 Whole Genome Methods and Pharmaceutical Applications of Genetic Engineering
    5. 12.4 Gene Therapy
    6. Summary
    7. Review Questions
      1. Multiple Choice
      2. True/False
      3. Fill in the Blank
      4. Short Answer
      5. Critical Thinking
  14. 13 Control of Microbial Growth
    1. Introduction
    2. 13.1 Controlling Microbial Growth
    3. 13.2 Using Physical Methods to Control Microorganisms
    4. 13.3 Using Chemicals to Control Microorganisms
    5. 13.4 Testing the Effectiveness of Antiseptics and Disinfectants
    6. Summary
    7. Review Questions
      1. Multiple Choice
      2. True/False
      3. Fill in the Blank
      4. Short Answer
      5. Critical Thinking
  15. 14 Antimicrobial Drugs
    1. Introduction
    2. 14.1 History of Chemotherapy and Antimicrobial Discovery
    3. 14.2 Fundamentals of Antimicrobial Chemotherapy
    4. 14.3 Mechanisms of Antibacterial Drugs
    5. 14.4 Mechanisms of Other Antimicrobial Drugs
    6. 14.5 Drug Resistance
    7. 14.6 Testing the Effectiveness of Antimicrobials
    8. 14.7 Current Strategies for Antimicrobial Discovery
    9. Summary
    10. Review Questions
      1. Multiple Choice
      2. True/False
      3. Fill in the Blank
      4. Short Answer
      5. Critical Thinking
  16. 15 Microbial Mechanisms of Pathogenicity
    1. Introduction
    2. 15.1 Characteristics of Infectious Disease
    3. 15.2 How Pathogens Cause Disease
    4. 15.3 Virulence Factors of Bacterial and Viral Pathogens
    5. 15.4 Virulence Factors of Eukaryotic Pathogens
    6. Summary
    7. Review Questions
      1. Multiple Choice
      2. Fill in the Blank
      3. Short Answer
      4. Critical Thinking
  17. 16 Disease and Epidemiology
    1. Introduction
    2. 16.1 The Language of Epidemiologists
    3. 16.2 Tracking Infectious Diseases
    4. 16.3 Modes of Disease Transmission
    5. 16.4 Global Public Health
    6. Summary
    7. Review Questions
      1. Multiple Choice
      2. Matching
      3. Fill in the Blank
      4. Short Answer
      5. Critical Thinking
  18. 17 Innate Nonspecific Host Defenses
    1. Introduction
    2. 17.1 Physical Defenses
    3. 17.2 Chemical Defenses
    4. 17.3 Cellular Defenses
    5. 17.4 Pathogen Recognition and Phagocytosis
    6. 17.5 Inflammation and Fever
    7. Summary
    8. Review Questions
      1. Multiple Choice
      2. Matching
      3. Fill in the Blank
      4. Short Answer
      5. Critical Thinking
  19. 18 Adaptive Specific Host Defenses
    1. Introduction
    2. 18.1 Overview of Specific Adaptive Immunity
    3. 18.2 Major Histocompatibility Complexes and Antigen-Presenting Cells
    4. 18.3 T Lymphocytes and Cellular Immunity
    5. 18.4 B Lymphocytes and Humoral Immunity
    6. 18.5 Vaccines
    7. Summary
    8. Review Questions
      1. Multiple Choice
      2. Matching
      3. Fill in the Blank
      4. Short Answer
      5. Critical Thinking
  20. 19 Diseases of the Immune System
    1. Introduction
    2. 19.1 Hypersensitivities
    3. 19.2 Autoimmune Disorders
    4. 19.3 Organ Transplantation and Rejection
    5. 19.4 Immunodeficiency
    6. 19.5 Cancer Immunobiology and Immunotherapy
    7. Summary
    8. Review Questions
      1. Multiple Choice
      2. Matching
      3. Fill in the Blank
      4. Short Answer
      5. Critical Thinking
  21. 20 Laboratory Analysis of the Immune Response
    1. Introduction
    2. 20.1 Polyclonal and Monoclonal Antibody Production
    3. 20.2 Detecting Antigen-Antibody Complexes
    4. 20.3 Agglutination Assays
    5. 20.4 EIAs and ELISAs
    6. 20.5 Fluorescent Antibody Techniques
    7. Summary
    8. Review Questions
      1. Multiple Choice
      2. Fill in the Blank
      3. Short Answer
      4. Critical Thinking
  22. 21 Skin and Eye Infections
    1. Introduction
    2. 21.1 Anatomy and Normal Microbiota of the Skin and Eyes
    3. 21.2 Bacterial Infections of the Skin and Eyes
    4. 21.3 Viral Infections of the Skin and Eyes
    5. 21.4 Mycoses of the Skin
    6. 21.5 Protozoan and Helminthic Infections of the Skin and Eyes
    7. Summary
    8. Review Questions
      1. Multiple Choice
      2. Fill in the Blank
      3. Short Answer
      4. Critical Thinking
  23. 22 Respiratory System Infections
    1. Introduction
    2. 22.1 Anatomy and Normal Microbiota of the Respiratory Tract
    3. 22.2 Bacterial Infections of the Respiratory Tract
    4. 22.3 Viral Infections of the Respiratory Tract
    5. 22.4 Respiratory Mycoses
    6. Summary
    7. Review Questions
      1. Multiple Choice
      2. Fill in the Blank
      3. Short Answer
      4. Critical Thinking
  24. 23 Urogenital System Infections
    1. Introduction
    2. 23.1 Anatomy and Normal Microbiota of the Urogenital Tract
    3. 23.2 Bacterial Infections of the Urinary System
    4. 23.3 Bacterial Infections of the Reproductive System
    5. 23.4 Viral Infections of the Reproductive System
    6. 23.5 Fungal Infections of the Reproductive System
    7. 23.6 Protozoan Infections of the Urogenital System
    8. Summary
    9. Review Questions
      1. Multiple Choice
      2. Fill in the Blank
      3. Short Answer
      4. Critical Thinking
  25. 24 Digestive System Infections
    1. Introduction
    2. 24.1 Anatomy and Normal Microbiota of the Digestive System
    3. 24.2 Microbial Diseases of the Mouth and Oral Cavity
    4. 24.3 Bacterial Infections of the Gastrointestinal Tract
    5. 24.4 Viral Infections of the Gastrointestinal Tract
    6. 24.5 Protozoan Infections of the Gastrointestinal Tract
    7. 24.6 Helminthic Infections of the Gastrointestinal Tract
    8. Summary
    9. Review Questions
      1. Multiple Choice
      2. Fill in the Blank
      3. Short Answer
      4. Critical Thinking
  26. 25 Circulatory and Lymphatic System Infections
    1. Introduction
    2. 25.1 Anatomy of the Circulatory and Lymphatic Systems
    3. 25.2 Bacterial Infections of the Circulatory and Lymphatic Systems
    4. 25.3 Viral Infections of the Circulatory and Lymphatic Systems
    5. 25.4 Parasitic Infections of the Circulatory and Lymphatic Systems
    6. Summary
    7. Review Questions
      1. Multiple Choice
      2. Fill in the Blank
      3. Short Answer
      4. Critical Thinking
  27. 26 Nervous System Infections
    1. Introduction
    2. 26.1 Anatomy of the Nervous System
    3. 26.2 Bacterial Diseases of the Nervous System
    4. 26.3 Acellular Diseases of the Nervous System
    5. 26.4 Fungal and Parasitic Diseases of the Nervous System
    6. Summary
    7. Review Questions
      1. Multiple Choice
      2. Matching
      3. Fill in the Blank
      4. Short Answer
      5. Critical Thinking
  28. A | Fundamentals of Physics and Chemistry Important to Microbiology
  29. B | Mathematical Basics
  30. C | Metabolic Pathways
  31. D | Taxonomy of Clinically Relevant Microorganisms
  32. E | Glossary
  33. Answer Key
    1. Chapter 1
    2. Chapter 2
    3. Chapter 3
    4. Chapter 4
    5. Chapter 5
    6. Chapter 6
    7. Chapter 7
    8. Chapter 8
    9. Chapter 9
    10. Chapter 10
    11. Chapter 11
    12. Chapter 12
    13. Chapter 13
    14. Chapter 14
    15. Chapter 15
    16. Chapter 16
    17. Chapter 17
    18. Chapter 18
    19. Chapter 19
    20. Chapter 20
    21. Chapter 21
    22. Chapter 22
    23. Chapter 23
    24. Chapter 24
    25. Chapter 25
    26. Chapter 26
  34. Index

Learning Objectives

  • Explain the difference between prevalence and incidence of disease
  • Distinguish the characteristics of sporadic, endemic, epidemic, and pandemic diseases
  • Explain the use of Koch’s postulates and their modifications to determine the etiology of disease
  • Explain the relationship between epidemiology and public health

Clinical Focus

Part 1

In late November and early December, a hospital in western Florida started to see a spike in the number of cases of acute gastroenteritis-like symptoms. Patients began arriving at the emergency department complaining of excessive bouts of emesis (vomiting) and diarrhea (with no blood in the stool). They also complained of abdominal pain and cramping, and most were severely dehydrated. Alarmed by the number of cases, hospital staff made some calls and learned that other regional hospitals were also seeing 10 to 20 similar cases per day.

  • What are some possible causes of this outbreak?
  • In what ways could these cases be linked, and how could any suspected links be confirmed?

Jump to the next Clinical Focus box.

The field of epidemiology concerns the geographical distribution and timing of infectious disease occurrences and how they are transmitted and maintained in nature, with the goal of recognizing and controlling outbreaks. The science of epidemiology includes etiology (the study of the causes of disease) and investigation of disease transmission (mechanisms by which a disease is spread).

Analyzing Disease in a Population

Epidemiological analyses are always carried out with reference to a population, which is the group of individuals that are at risk for the disease or condition. The population can be defined geographically, but if only a portion of the individuals in that area are susceptible, additional criteria may be required. Susceptible individuals may be defined by particular behaviors, such as intravenous drug use, owning particular pets, or membership in an institution, such as a college. Being able to define the population is important because most measures of interest in epidemiology are made with reference to the size of the population.

The state of being diseased is called morbidity. Morbidity in a population can be expressed in a few different ways. Morbidity or total morbidity is expressed in numbers of individuals without reference to the size of the population. The morbidity rate can be expressed as the number of diseased individuals out of a standard number of individuals in the population, such as 100,000, or as a percent of the population.

There are two aspects of morbidity that are relevant to an epidemiologist: a disease’s prevalence and its incidence. Prevalence is the number, or proportion, of individuals with a particular illness in a given population at a point in time. For example, the Centers for Disease Control and Prevention (CDC) estimated that in 2012, there were about 1.2 million people 13 years and older with an active human immunodeficiency virus (HIV) infection. Expressed as a proportion, or rate, this is a prevalence of 467 infected persons per 100,000 in the population.1 On the other hand, incidence is the number or proportion of new cases in a period of time. For the same year and population, the CDC estimates that there were 43,165 newly diagnosed cases of HIV infection, which is an incidence of 13.7 new cases per 100,000 in the population.2 The relationship between incidence and prevalence can be seen in Figure 16.2. For a chronic disease like HIV infection, prevalence will generally be higher than incidence because it represents the cumulative number of new cases over many years minus the number of cases that are no longer active (e.g., because the patient died or was cured).

In addition to morbidity rates, the incidence and prevalence of mortality (death) may also be reported. A mortality rate can be expressed as the percentage of the population that has died from a disease or as the number of deaths per 100,000 persons (or other suitable standard number).

Graph of HIV prevalence and incidence in the US 1980-2010. The number o people living with HIV/AIDS was near 0 in 1980 and has increased steadily to over 1 million. There as a short plateau from 1990 to 1995. The number of new infections increased to nearly 200,000 in 1985 and dropped until 1990. It remains steady at somewhere near 50,000.
Figure 16.2 This graph compares the incidence of HIV (the number of new cases reported each year) with the prevalence (the total number of cases each year). Prevalence and incidence can also be expressed as a rate or proportion for a given population.

Check Your Understanding

  • Explain the difference between incidence and prevalence.
  • Describe how morbidity and mortality rates are expressed.

Patterns of Incidence

Diseases that are seen only occasionally, and usually without geographic concentration, are called sporadic diseases. Examples of sporadic diseases include tetanus, rabies, and plague. In the United States, Clostridium tetani, the bacterium that causes tetanus, is ubiquitous in the soil environment, but incidences of infection occur only rarely and in scattered locations because most individuals are vaccinated, clean wounds appropriately, or are only rarely in a situation that would cause infection.3 Likewise in the United States there are a few scattered cases of plague each year, usually contracted from rodents in rural areas in the western states.4

Diseases that are constantly present (often at a low level) in a population within a particular geographic region are called endemic diseases. For example, malaria is endemic to some regions of Brazil, but is not endemic to the United States.

Diseases for which a larger than expected number of cases occurs in a short time within a geographic region are called epidemic diseases. Influenza is a good example of a commonly epidemic disease. Incidence patterns of influenza tend to rise each winter in the northern hemisphere. These seasonal increases are expected, so it would not be accurate to say that influenza is epidemic every winter; however, some winters have an usually large number of seasonal influenza cases in particular regions, and such situations would qualify as epidemics (Figure 16.3 and Figure 16.4).

An epidemic disease signals the breakdown of an equilibrium in disease frequency, often resulting from some change in environmental conditions or in the population. In the case of influenza, the disruption can be due to antigenic shift or drift (see Virulence Factors of Bacterial and Viral Pathogens), which allows influenza virus strains to circumvent the acquired immunity of their human hosts.

An epidemic that occurs on a worldwide scale is called a pandemic disease. For example, HIV/AIDS is a pandemic disease and novel influenza virus strains often become pandemic.

A graph of the percentage of emergency department visits for influenza-like illness. The X axis is times of the year and the Y axis is percent. The national baseline is near 2.5%. All yeas have a small peak in January and a larger peak February to April. 2007-2008 had the largest peak in February to April. 2008 – 2009 had an additional peak from May to September.
Figure 16.3 The 2007–2008 influenza season in the United States saw much higher than normal numbers of visits to emergency departments for influenza-like symptoms as compared to the previous and the following years. (credit: modification of work by Centers for Disease Control and Prevention)
A graph of the percentage of all deaths due to influenza an pneumonia. The X axis is years and the Y axis is percent. The seasonal baseline fluctuates to a high in winter. The epidemic threshold is just a half percent higher than the baseline. The actual mortality fluctuates above and below both of these lines.
Figure 16.4 The seasonal epidemic threshold (blue curve) is set by the CDC-based data from the previous five years. When actual mortality rates exceed this threshold, a disease is considered to be epidemic. As this graph shows, pneumonia- and influenza-related mortality saw pronounced epidemics during the winters of 2003–2004, 2005, and 2008. (credit: modification of work by Centers for Disease Control and Prevention)

Check Your Understanding

  • Explain the difference between sporadic and endemic disease.
  • Explain the difference between endemic and epidemic disease.

Clinical Focus

Part 2

Hospital physicians suspected that some type of food poisoning was to blame for the sudden post-Thanksgiving outbreak of gastroenteritis in western Florida. Over a two-week period, 254 cases were observed, but by the end of the first week of December, the epidemic ceased just as quickly as it had started. Suspecting a link between the cases based on the localized nature of the outbreak, hospitals handed over their medical records to the regional public health office for study.

Laboratory testing of stool samples had indicated that the infections were caused by Salmonella bacteria. Patients ranged from children as young as three to seniors in their late eighties. Cases were nearly evenly split between males and females. Across the region, there had been three confirmed deaths in the outbreak, all due to severe dehydration. In each of the fatal cases, the patients had not sought medical care until their symptoms were severe; also, all of the deceased had preexisting medical conditions such as congestive heart failure, diabetes, or high blood pressure.

After reviewing the medical records, epidemiologists with the public health office decided to conduct interviews with a randomly selected sample of patients.

  • What conclusions, if any, can be drawn from the medical records?
  • What would epidemiologists hope to learn by interviewing patients? What kinds of questions might they ask?

Jump to the next Clinical Focus box. Go back to the previous Clinical Focus box.

Etiology

When studying an epidemic, an epidemiologist’s first task is to determinate the cause of the disease, called the etiologic agent or causative agent. Connecting a disease to a specific pathogen can be challenging because of the extra effort typically required to demonstrate direct causation as opposed to a simple association. It is not enough to observe an association between a disease and a suspected pathogen; controlled experiments are needed to eliminate other possible causes. In addition, pathogens are typically difficult to detect when there is no immediate clue as to what is causing the outbreak. Signs and symptoms of disease are also commonly nonspecific, meaning that many different agents can give rise to the same set of signs and symptoms. This complicates diagnosis even when a causative agent is familiar to scientists.

Robert Koch was the first scientist to specifically demonstrate the causative agent of a disease (anthrax) in the late 1800s. Koch developed four criteria, now known as Koch’s postulates, which had to be met in order to positively link a disease with a pathogenic microbe. Without Koch’s postulates, the Golden Age of Microbiology would not have occurred. Between 1876 and 1905, many common diseases were linked with their etiologic agents, including cholera, diphtheria, gonorrhea, meningitis, plague, syphilis, tetanus, and tuberculosis. Today, we use the molecular Koch’s postulates, a variation of Koch’s original postulates that can be used to establish a link between the disease state and virulence traits unique to a pathogenic strain of a microbe. Koch’s original postulates and molecular Koch’s postulates were described in more detail in How Pathogens Cause Disease.

Check Your Understanding

  • List some challenges to determining the causative agent of a disease outbreak.

The Role of Public Health Organizations

The main national public health agency in the United States is the Centers for Disease Control and Prevention (CDC), an agency of the Department of Health and Human Services. The CDC is charged with protecting the public from disease and injury. One way that the CDC carries out this mission is by overseeing the National Notifiable Disease Surveillance System (NNDSS) in cooperation with regional, state, and territorial public health departments. The NNDSS monitors diseases considered to be of public health importance on a national scale. Such diseases are called notifiable diseases or reportable diseases because all cases must be reported to the CDC. A physician treating a patient with a notifiable disease is legally required to submit a report on the case. Notifiable diseases include HIV infection, measles, West Nile virus infections, and many others. Some states have their own lists of notifiable diseases that include diseases beyond those on the CDC’s list.

Notifiable diseases are tracked by epidemiological studies and the data is used to inform health-care providers and the public about possible risks. The CDC publishes the Morbidity and Mortality Weekly Report (MMWR), which provides physicians and health-care workers with updates on public health issues and the latest data pertaining to notifiable diseases. Table 16.1 is an example of the kind of data contained in the MMWR.

Incidence of Four Notifiable Diseases in the United States, Week Ending January 2, 2016
Disease Current Week (Jan 2, 2016) Median of Previous 52 Weeks Maximum of Previous 52 Weeks Cumulative Cases 2015
Campylobacteriosis 406 869 1,385 46,618
Chlamydia trachomatis infection 11,024 28,562 31,089 1,425,303
Giardiasis 115 230 335 11,870
Gonorrhea 3,207 7,155 8,283 369,926
Table 16.1

Check Your Understanding

  • Describe how health agencies obtain data about the incidence of diseases of public health importance.

Footnotes

  • 1 H. Irene Hall, Qian An, Tian Tang, Ruiguang Song, Mi Chen, Timothy Green, and Jian Kang. “Prevalence of Diagnosed and Undiagnosed HIV Infection—United States, 2008–2012.” Morbidity and Mortality Weekly Report 64, no. 24 (2015): 657–662.
  • 2 Centers for Disease Control and Prevention. “Diagnoses of HIV Infection in the United States and Dependent Areas, 2014.” HIV Surveillance Report 26 (2015).
  • 3 Centers for Disease Control and Prevention. “Tetanus Surveillance—United States, 2001–2008.” Morbidity and Mortality Weekly Report 60, no. 12 (2011): 365.
  • 4 Centers for Disease Control and Prevention. “Plague in the United States.” 2015. http://www.cdc.gov/plague/maps. Accessed June 1, 2016.
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