Introduction to Infectious Diseases Flashcards
Overview of Infectious Diseases and Learning Objectives
Goal of the Chapter: To provide a comprehensive understanding of how infectious diseases manifest within susceptible populations, including modes of transmission, common epidemiological terminology, and the emergence of new pathogens.
Learning Objectives: * Defining and describing pathogenic microbes. * Understanding microbial virulence strategies. * Identifying how infectious diseases are transmitted. * Proving that specific microbes cause specific infections. * Analyzing how pathogens evolve.
Historical Impact of Disease on Human Populations
Historical Timeline of Major Events: * 1300s: The Bubonic plague ravages global populations. * 1500s‒1600s: Exploration of the Americas brings European diseases to indigenous human populations. * Early 1900s: The Spanish flu pandemic occurs. * 2019–Present: The Covid-19 pandemic.
Case Study: Napoleon’s Army (1812 Russia Campaign): * Initial Force: Napoleon took soldiers to Russia. * Survival Rate: Fewer than soldiers returned. * Original Diagnosis: Deaths were attributed to Typhus and trench fever (characterized by diarrhea and lice). * 2002 Investigation: Samples from a mass grave in Lithuania were analyzed using Nested PCR, identifying multiple pathogens. * 2025 Identification: Further analysis using Shotgun Sequencing identified: * Paratyphoid (Salmonella): Caused fever, diarrhea, and dehydration. * Relapsing Fever (Borrelia): Caused recurring fevers and weakness, spread via lice. * Context: Both thrived due to the unsanitary conditions inherent in military operations.
Current Global Status: Despite advances in vaccinations, antibiotics, sanitation, and medical care, the burden remains high, particularly in developing countries. * Trends (1998–2008): Deaths from measles decreased significantly, while deaths from respiratory diseases and tuberculosis remained fairly constant.
Pathogenic Microbes: Definitions and Concepts
Disease: A disturbance in the normal functioning of an organism.
Infectious Disease: A disease caused by a microbe that can be transmitted from host to host (e.g., Influenza, HIV, Hepatitis B).
Zoonotic Diseases: Infectious diseases originating in animals that can cause disease when transmitted to humans (e.g., Rabies, West Nile fever).
Pathogenesis: The specific mechanism a microbe uses to cause a disease state.
Infection: The replication of a pathogen in or on its host.
Pathogen Types: * Primary Pathogens: Produce disease readily in healthy hosts. * Opportunistic Pathogens: Generally only cause disease when displaced to an unusual site or when the host immune system is weakened.
Virulence and Clinical Manifestations
Virulence: A measure of the severity of the disease a pathogen can induce.
Case-to-Infection (CI) Ratio: The proportion of infected individuals who develop the clinical disease.
Virulence Levels: * Attenuated Strains: Show decreased virulence; these are often useful for vaccine development. * Avirulent Strains: Strains that can no longer cause disease.
Carriers: Individuals infected with a pathogenic microbe who never exhibit overt signs or symptoms (asymptomatic) but can still transmit the microbe (e.g., Mary Mallon, known as ‘Typhoid Mary’).
Microbial Virulence Strategies
General Requirements for Infection: 1. Gain entry to the host. 2. Attach to and invade specific cells or tissues. 3. Evade host defenses. 4. Obtain nutrients from the host. 5. Exit the host.
Attachment, Invasion, and Replication: * Protein-Protein Interactions: Viruses often utilize specific host cell receptors for attachment. * Generalized Interactions: Example: Rice blast fungus spores adhere to most hydrophobic surfaces, including cells.
Host Range: The group of organisms a pathogen can infect, determined by its ability to attach, invade, and replicate. * Host Range Expansion Example: Feline panleukopenia virus (FPLV) in cats mutated to become canine parvovirus (CPV) in dogs. DNA/protein analysis suggests evolution from FPV or mink enteritis virus (MEV), possibly through an intermediate in foxes. A mutation in the capsid protein permitted replication in canine cells.
Methods of Evasion: * Antigenic Variation: Shifting surface protein structures so the immune system must "play catch-up" (e.g., T. brucei, N. gonorrhoeae). * Latency: The virus inserts its genome into host cells and stops replication (e.g., Herpes simplex virus). Reactivation occurs due to host stress, leading to lytic replication (e.g., cold sores). * Capsules: Bacterial capsules make them difficult for phagocytes to engulf. * Intracellular Replication: Some microbes replicate inside phagocytes.
Bacterial Defenses vs. Phages: * Restriction Endonucleases: Enzymes that digest invading phage DNA. * Methylation: Bacteria protect their own DNA by adding a methyl group () to bases within restriction enzyme recognition sites.
Pathogenesis Mechanisms: * Exotoxins: Proteins produced and secreted that negatively affect host cells. * Endotoxins: Toxins that are part of the microbial structure itself. * Viral Strategies: Viruses typically do not produce toxins; they cause disease via cell death or apoptosis triggered by the immune system.
Transmission and Epidemiology
Transmission: Spread of an agent from one host to another or from a natural reservoir to a host.
Routes of Transmission: * Contact: Direct (physical) or Indirect (via an object called a fomite). * Fecal–Oral Route * Respiratory (‘Aerosol’) * Vectorborne: Transmitted via another species (e.g., mosquitoes carrying malaria). * Sexual Transmission
Directional Transmission: * Horizontal: Between members of a species other than parent to offspring. * Vertical: From parent to child (e.g., HIV via birth or in utero).
Zoonotic Transfers: Humans are often ‘dead-end’ hosts where the pathogen is not efficiently transferred person-to-person.
Epidemiological Measures
Terminology: * Morbidity Rate: Rate of disease in a population. * Mortality Rate: Death rate of a disease. * Case: Carefully defined group including symptomatic and sometimes asymptomatic/subclinical individuals.
Incidence vs. Prevalence: * Incidence: Number of new cases in a population during a specific time. * Incidence Rate Formula: * Prevalence: Total number of cases in a population at a particular time.
Epidemiological Patterns: * Endemic Disease: Habitually present in a population, often cyclical (e.g., Rabies in North American wildlife; West Nile encephalitis peaking in August in the Northern US due to mosquito vectors). * Epidemic: Incidence rises significantly above expected values. * Outbreak: Unexpected cluster of cases in a short time in a localized population. * Pandemic: A global epidemic (e.g., 1918 Spanish flu, Plague, Smallpox, Cholera, AIDS, SARS-CoV-2).
Epidemic Patterns: * Common-source Epidemics: Single source of infection; rapid increase and decrease in incidence (e.g., food poisoning). Cases cluster spatially near the source (e.g., John Snow and the 1854 Broad Street pump cholera outbreak). * Propagated Epidemics: Passed host-to-host; gradual increase over time with multiple small peaks corresponding to several incubation periods (e.g., measles, influenza, Covid-19).
Proving Cause and Effect: Koch’s Postulates
Classic Postulates: 1. The suspected microbe must be identified in every person with the disease, but not in healthy individuals. 2. A pure culture of the microbe must be obtained. 3. Experimental inoculation into a healthy host must cause the same illness. 4. The microbe must be recovered from the experimentally inoculated host.
Limitations: * Some microbes (e.g., Streptococcus pyogenes) are found in healthy people. * Genetic differences in hosts (e.g., SJL/J mice are resistant to MHV-A59 because they produce a variant receptor protein the virus cannot bind to). * Ethical issues with human inoculation.
Molecular Koch’s Postulates (Modern): 1. The virulence factor should be present in the pathogen. 2. Inactivation of the virulence gene should decrease virulence. 3. Reversion of the change should restore virulence. 4. The gene must be expressed during infection. 5. Immunity to the pathogen must provide protection.
Pathogenicity Islands: Clusters of virulence factor genes (adhesion, invasion, toxins) often passed via horizontal gene transfer.
Pathogen Evolution and Emerging Diseases
HIV Evolution: * SIV (Simian Immunodeficiency Virus) transferred into humans as HIV. * HIV-1: Divided into four groups: M, N, O, and P. of infections are HIV-1 group M. * Group M has 9 distinct clades and Circulating Recombinant Forms (CRFs).
Lyme Disease: * Caused by Borrelia burgdorferi; reservoir in deer and mice; vector is the black-legged tick (Ixodes scapularis). * Symptoms: Bull’s-eye rash. Incidence increased since the 1970s due to human habitation spreading into wooded areas.
Increasing Virulence Examples: * E. coli O157:H7: Acquired a toxin from Shigella via horizontal gene transfer that shuts down host protein production. * MRSA (Methicillin-resistant Staphylococcus aureus): Selective pressure from antibiotic overuse led to resistance traits.
Emerging Pathogen Case: Chikungunya Virus: * Enveloped ssRNA virus ( diameter) in the Togaviridae family. * Name means ‘contorted’ in Kimakonde (Tanzania/Mozambique). * Spread to Western Hemisphere in 2013; suspected cases by 2015.
Surveillance and Public Health
Surveillance Organizations: CDC (Centers for Disease Control and Prevention), WHO (World Health Organization), PAHO (Pan American Health Organization), BIDS (Border Infectious Disease Surveillance Project).
Reporting: CDC Morbidity and Mortality Weekly Report (MMWR) tracks notifiable diseases (e.g., Anthrax, Cholera, Lead poisoning, HIV, Malaria, SARS).
Polio Eradication Case Study: * 1952: cases in the US. * 1964: cases post-immunization. * 1979: Last wild case in the US. * Current Status: Endemic only in Pakistan and Afghanistan.