Disease – Epidemiology and Control Introduction to Microbiology Chapters 14 and 20

Epidemiology The study of where and when diseases occur Centers for Disease Control and Prevention (CDC) – Collects and analyzes epidemiological information in the United States – Publishes Morbidity and Mortality Weekly Report (MMWR) –

John Snow1848–1849Mapped the occurrence of cholera in London Ignaz Semmelweis1846–1848Showed that handwashing decreased the incidence of puerperal fever Florence Nightingale 1858Showed that improved sanitation decreased the incidence of epidemic typhus Epidemiology

Descriptive: Collection and analysis of data – Snow Analytical: Comparison of a diseased group and a healthy group – Nightingale Experimental: Controlled experiments – Semmelweis

Case reporting: Health care workers report specified disease to local, state, and national offices Nationally notifiable diseases: Physicians are required to report occurrence Epidemiology

The CDC Morbidity: Incidence of a specific notifiable disease Mortality: Deaths from notifiable diseases Morbidity rate: Number of people affected in relation to the total population in a given time period Mortality rate: Number of deaths from a disease in relation to the population in a given time

Pathology, Infection, and Disease Pathology: The study of disease Etiology: The study of the cause of a disease Pathogenesis: The development of disease Infection: Colonization of the body by pathogens Disease: An abnormal state in which the body is not functioning normally

Normal Microbiota and the Host Transient microbiota may be present for days, weeks, or months Normal microbiota permanently colonize the host Symbiosis is the relationship between normal microbiota and the host

Representative Normal Microbiota Figure 14.1

Symbiosis In commensalism, one organism benefits, and the other is unaffected In mutualism, both organisms benefit In parasitism, one organism benefits at the expense of the other Some normal microbiota are opportunistic pathogens

Normal Microbiota and the Host Microbial antagonism is a competition between microbes. Normal microbiota protect the host by – Occupying niches that pathogens might occupy – Producing acids – Producing bacteriocins Probiotics: Live microbes applied to or ingested into the body, intended to exert a beneficial effect

Classifying Infectious Diseases Symptom: A change in body function that is felt by a patient as a result of disease Sign: A change in a body that can be measured or observed as a result of disease Syndrome: A specific group of signs and symptoms that accompany a disease

Classifying Infectious Diseases Communicable disease: A disease that is spread from one host to another Contagious disease: A disease that is easily spread from one host to another Noncommunicable disease: A disease that is not transmitted from one host to another

Occurrence of a Disease Incidence: Fraction of a population that contracts a disease during a specific time Prevalence: Fraction of a population having a specific disease at a given time Sporadic disease: Disease that occurs occasionally in a population

Occurrence of a Disease Endemic disease: Disease constantly present in a population Epidemic disease: Disease acquired by many hosts in a given area in a short time Pandemic disease: Worldwide epidemic Herd immunity: Immunity in most of a population

Severity or Duration of a Disease Acute disease: Symptoms develop rapidly Chronic disease: Disease develops slowly Subacute disease: Symptoms between acute and chronic Latent disease: Disease with a period of no symptoms when the causative agent is inactive

Extent of Host Involvement Local infection: Pathogens are limited to a small area of the body Systemic infection: An infection throughout the body Focal infection: Systemic infection that began as a local infection Superinfection: occurs when a pathogen develops resistance to the drug being used for treatment or when normally resistant microbiota multiply excessively, adding to infection.

Extent of Host Involvement Sepsis: Toxic inflammatory condition arising from the spread of microbes, especially bacteria or their toxins, from a focus of infection Bacteremia: Bacteria in the blood Septicemia: Growth of bacteria in the blood

Extent of Host Involvement Toxemia: Toxins in the blood Viremia: Viruses in the blood Primary infection: Acute infection that causes the initial illness Secondary infection: Opportunistic infection after a primary (predisposing) infection Subclinical disease: No noticeable signs or symptoms (inapparent infection)

Predisposing Factors Make the body more susceptible to disease – Short urethra in females – Inherited traits, such as the sickle cell gene – Climate and weather – Fatigue – Age – Lifestyle – Chemotherapy

The Stages of a Disease Figure 14.5

The Spread of Infection Reservoirs of Infection – Continual sources of infection Human: AIDS, gonorrhea – Carriers may have inapparent infections or latent diseases Animal: Rabies, Lyme disease – Some zoonoses may be transmitted to humans Nonliving: Botulism, tetanus – Soil

The Spread of Infection – Transmission Types Contact Vehicle Vector

Transmission of Disease Contact – Direct: Requires close association between infected and susceptible host – Indirect: Spread by fomites Fomite – inanimate object that can spread disease. – Example: toys, clothing, utensils, etc. – Droplet: Transmission via airborne droplets

Transmission of Disease Vehicle – Contact with food, water, other liquids These are constantly taken into the body, so they serve as “vehicles” into the body.

Transmission of Disease Vector – Transmission from an animal (insect)

Transmission of Disease Figure 14.6a, d

Vehicle Transmission Transmission by an inanimate reservoir (food, water, air) Figure 14.7b

Nosocomial Infections Are acquired as a result of a hospital stay Affect 5–15% of all hospital patients Figure 14.6b

Nosocomial Infections Figure 14.9

Nosocomial Infections Table 14.5

Percentage of Total Infections Percentage Resistant to Antibiotics Coagulase-negative staphylococci 25%89% S. aureus16%80% Enterococcus10%29% Gram-negative rods23%5-32% C. difficile13%None Common Causes of Nosocomial Infections

MRSA USA100: 92% of health care strains USA300: 89% of community-acquired strains Clinical Focus, p. 422

Which Procedure Increases the Likelihood of Infection Most? Clinical Focus, p. 422

Emerging Infectious Diseases Diseases that are new, increasing in incidence, or showing a potential to increase in the near future

Emerging Infectious Diseases Contributing factors – Genetic recombination E. coli O157, avian influenza (H5N1) – Evolution of new strains V. cholerae O139 – Inappropriate use of antibiotics and pesticides Antibiotic-resistant strains – Changes in weather patterns Hantavirus

Emerging Infectious Diseases Modern transportation – West Nile virus Ecological disaster, war, and expanding human settlement – Coccidioidomycosis Animal control measures – Lyme disease Public health failure – Diphtheria

Crossing the Species Barrier Clinical Focus, p. 371

Treatment – Antibiotics/Antimicrobials Chemotherapy: The use of drugs to treat a disease Antimicrobial drugs: Interfere with the growth of microbes within a host Antibiotic: A substance produced by a microbe that, in small amounts, inhibits another microbe Selective toxicity: A drug that kills harmful microbes without damaging the host

1928: Fleming discovered penicillin, produced by Penicillium 1940: Howard Florey and Ernst Chain performed first clinical trials of penicillin Antimicrobial Drugs Figure 1.5

Most Antibiotics come from other Microorganisms

The Spectrum of Antimicrobial Activity

Broad spectrum – Treats a variety of microbes Narrow spectrum – Treats few microbes

Bactericidal – Kill microbes directly Bacteriostatic – Prevent microbes from growing Ideally, an antimicrobial should target the pathogen only and not disrupt normal microbiota – Risk vs. Benefit Analysis The Action of Antimicrobial Drugs

Commonly used Antimicrobials – Modes of Action -Inhibitors of Cell Wall Synthesis -Antimycobacterial Antibiotics -Inhibitors of Protein Synthesis -Injury to the Plasma Membrane -Inhibitors of Nucleic Acid (DNA/RNA) Synthesis -Competitive Inhibitors of the Synthesis of Essential Metabolites

Commonly Used Antimicrobials Antibacterial Antibiotics: Inhibitors of Cell Wall Synthesis – All penicillins (natural and semisynthetic) – Carbapenems – Cephalosporins – Bacitracin – Vancomycin

Commonly Used Antimicrobials Antimycobacterial Antibiotics – Isoniazid (INH) and ethambutol inhibit cell wall synthesis in mycobacteria.

Commonly Used Antimicrobials Inhibitors of Protein Synthesis – Chloramphenicol, aminoglycosides, tetracyclines, macrolides, and streptogramins inhibit protein synthesis at 70S ribosomes. – Oxazolidinones prevent formation of 70S ribosomes.

Commonly Used Antimicrobials Injury to the Plasma Membrane – A new class of antibiotics inhibits fatty-acid synthesis, essential for plasma membranes. Polymyxin B and bacitracin cause damage to plasma membranes.

Commonly Used Antimicrobials Inhibitors of Nucleic Acid (DNA/RNA) Synthesis Rifamycin inhibits mRNA synthesis; it is used to treat tuberculosis. Quinolones and fluoroquinolones inhibit DNA gyrase for treating urinary tract infections.

Commonly Used Antimicrobials Competitive Inhibitors of the Synthesis of Essential Metabolites – Sulfonamides competitively inhibit folic acid synthesis.

Antiviral Drugs Protease inhibitors – Indinavir: HIV Integrase inhibitors – HIV Inhibit attachment – Zanamivir: Influenza – Block CCR5: HIV Inhibit uncoating – Amantadine: Influenza Nucleoside and Nucleotide Analogs – Inhibit DNA/RNA synthesis Enzyme inhibitors – Inhibit fusion, Inhibit attachment, Inhibit uncoating Interferons – Prevent spread of viruses to new cells

Metronidazole – Damages DNA –Entamoeba, Trichomonas Nitazoxanide – Interferes with metabolism of anaerobes Antiprotozoan Drugs

Antihelminthic Drugs Niclosamide – Prevents ATP generation Tapeworms Praziquantel – Alters membrane permeability Flatworms Figure 12.26

Antihelminthic Drugs Figure 12.28a Mebendazole – Inhibits nutrient absorption Intestinal roundworms Ivermectin – Paralyzes worm Intestinal roundworms

Testing Effectiveness of Treatment Disk Diffusion Test (Kirby Bauer) Broth Dilution Test MIC (minimal inhibitory concentration) Test – The E-test – Microtitre plates

The Disk-Diffusion Method Figure 20.17

The E Test Figure 20.18

Microtitre Plate Figure 20.19

Antibiotic Resistance A variety of mutations can lead to antibiotic resistance Mechanisms of antibiotic resistance 1.Enzymatic destruction of drug 2.Prevention of penetration of drug 3.Alteration of drug's target site 4.Rapid ejection of the drug Resistance genes are often on plasmids or transposons that can be transferred between bacteria

Antibiotic Resistance Misuse of antibiotics selects for resistance mutants. Misuse includes – Using outdated or weakened antibiotics – Using antibiotics for the common cold and other inappropriate conditions – Using antibiotics in animal feed – Failing complete the prescribed regimen – Using someone else's leftover prescription

Effects of Combinations of Drugs Synergism occurs when the effect of two drugs together is greater than the effect of either alone Antagonism occurs when the effect of two drugs together is less than the effect of either alone

Synergism between Two Different Antibiotics Figure 20.23

Antagonism Between Antimicrobials – The D-test

The Future of Antimicrobial Treatment and Development Chemicals produced by plants and animals are providing new antimicrobial agents called antimicrobial peptides. Phage therapy is also something that is being investigated for new treatment