McCance 10 - M 10.1 - Infection Overview

Infection Overview

• Infection has been a primary cause of human mortality.
• Public health, vaccinations, and antibiotics greatly improved disease prevention and treatment.
• Smallpox eradicated worldwide (last case in 1975), measles nearly eradicated in Western Hemisphere.
• Tuberculosis and polio are on the decline.
• In the United States in 2014, influenza/pneumonia was the eighth and septicemia was the eleventh ranked cause of death in adults.
• Bacterial sepsis was the seventh leading cause of neonatal deaths.
• Infectious diseases remain a threat, with infections being a top ten cause of death in low income countries: lower respiratory infections (#1), HIV/AIDS (#2), diarrheal diseases (#3), malaria (#6), and tuberculosis (#8).
• Morbidity and mortality exist due to emerging infections, reemerging old infections and antibiotic resistance.
• Factors driving these include urbanization causing public health breakdown and rapid infection spread, poverty and social inequality, war and famine, global travel spreading disease rapidly, wilderness encroachment increasing human contact with infectious agents, antibiotic overuse, government denial of problems, insecticide decline, and increased global warming expanding insect vector ranges.

Emerging Infections

• The rate of previously unknown infections is unprecedented; over 40 have arisen in one generation.
• Some infections jumped from animals to humans (zoonotic), for example, SARS-coronavirus from bats, Middle East respiratory syndrome (MERS) from dromedary camels.
• Zika virus is another recently emerged infection that has spread globally.
• Some infections have extremely high mortality rates (>50%), like SARS (older than 65), Ebola, Marburg, "mad cow" disease, Nipah virus (up to 75%), and acquired immunodeficiency syndrome (AIDS) (almost 100% in untreated persons).
• Most spread slowly or appear in isolated areas that are effectively controlled by quarantine.
• Some infections were previously controlled by antibiotics or vaccination but reemerged due to antibiotic resistance or decreased compliance with recommended vaccinations such as Streptococcus pneumoniae, Staphylococcus aureus, tuberculosis, diarrheal diseases, malaria, meningitis, respiratory tract infections, STIs, and HIV.
• Noncompliance with vaccinations has led to outbreaks of diseases that were once under control (e.g., measles and pertussis).
• Agents such as smallpox, anthrax, and plague are microbes that present an intentional threat to public health and safety.

Microorganisms and Humans: A Dynamic Relationship

• The human body is a hospitable site for growth for microorganisms.
• Symbiotic relationship: benefits only the human, with no harm to the microorganism.
• Mutualism: benefits both human and microorganism.
• Commensalism: benefits only the microorganism with no harm to human.
• Pathogenicity: benefits the microorganism; harms the human.
• Opportunism: benign microorganisms become pathogenic because of decreased human host resistance.
• Microorganisms comprise the normal microbiome found in the skin, mouth, gastrointestinal tract, respiratory tract, and genital tract.
• Bacteria in gut receive nutrients from ingested food and produce digestive enzymes, antibacterial factors and usable metabolites e.g., vitamin K, B vitamins).
• Homeostasis is maintained through the gut's physical integrity and mechanisms that sequester microorganisms on the mucosal surface.

Microorganisms and Infections

• Microorganisms are classified by morphology and life cycle, but disease-causing microorganisms share properties of clinical disease, infection processes, and protective system evasion.
• Clinical infection occurs in stages:
  • Incubation period is from initial exposure to symptom onset.
  • Prodromal stage includes initial mild symptoms of discomfort and tiredness.
  • Invasion period is rapid pathogen multiplication, tissue invasion, triggering of immune and inflammatory responses.
  • Convalescence sees successful removal of the infectious agent or the disease may be fatal or enter latency.
• Clinical manifestations vary depending on the pathogen, affected organ system, and intensity of inflammatory response.
• Disease may be clinical i.e., measurable or subclinical i.e., no apparent symptoms.
• Initial symptoms include fatigue, malaise, weakness, and loss of concentration.
• Fever shows body temperature regulated to a higher-than-normal level because pyrogens are outside the host derived.
• Cytokines raise the thermoregulatory set point through stimulation of prostaglandin synthesis in thermoregulatory (brain) and non-thermoregulatory (peripheral) tissue.
• Fever is a beneficial adaptive host-defense response in killing of temperature-sensitive microorganisms.
• Several factors that influence severity of disease include:
  • Communicability: ability to spread.
  • Immunogenicity: ability to induce immune response.
  • Infectivity: ability to invade and multiply.
  • Mechanism of action: how tissue damage occurs.
  • Pathogenicity: ability to produce disease, depending on communicability, infectivity, tissue damage, and virulence.
  • Portal of entry: how infection occurs.
  • Toxigenicity: ability to produce toxins.
  • Virulence: capacity to cause severe disease.
• Infectious diseases are also classified by prevalence and spread:
  • Endemic: relatively high, constant rates.
  • Epidemic: new infections greatly exceed normal.
  • Pandemic: epidemic spreads over a large area/worldwide.
• Some infections are relatively minor inconveniences, while others have a major impact because of severe morbidity and mortality.
• An evolving list of notifiable infectious diseases helps monitor, control, and prevent the spread of disease.
• STIs are among the most common reportable diseases in 2015: Chlamydia (>1.5 million cases), gonorrhea (about 400,000 cases), HIV (>33,000 cases), and syphilis (>23,000 cases).
• Process includes colonization, invasion, multiplication, and dissemination. The symbiotic relationship with the normal flora is maintained by physical barriers, microbiome complexity, and inflammatory/immune systems.

Process of Infection

• Opportunistic microorganisms cause infection when protective barriers are weakened.
• Physical damage to intestinal tract during trauma or surgery releases intestinal bacteria, potentially leading to sepsis, shock, and death.
• Cuts in the skin may allow normally contained bacteria such as Staphylococcus aureus, to cause local infections and invade various organs.
• Alterations in microbiome by antibiotics can allow local overgrowth of opportunistic microorganisms such as Clostridium difficile and Candida albicans causing infection.
• Immune deficiencies may allow invasive systemic infections, e.g., systemic fungal infections.
• True pathogens circumvent defenses and cause infection due to adequate numbers rather than host compromise.
• Minimum infective dose varies.
• Pathogenic microorganisms usually exist in reservoirs that include:
  • the environment e.g., contaminated water, soil
  • vertebrate animals
  • or infected humans.
• Direct transmission may occur through direct contact with infections of another individual.
• Vertical transmission is the spread of microorganisms from mother to child across the placenta, ascending birth canal, or through breast milk.
• Horizontal transmission is also present.
• Indirect transmission occurs through contact with contaminated materials or vectors.
• Respiratory transmission may occur:
  • by inhaling mist created from coughing or sneezing - or via larger droplets infecting surfaces.
• Some agents are airborne by circulating air that carries microorganisms picked up elsewhere.
• Many ingested substances like food and water can be contaminated by minuscule amounts of human feces.
• Zoonotic infections may be directly transmitted from animals (e.g., rabies).
• Most zoonotic infections are transmitted indirectly by vector-borne transmission (primarily insects) that feed off the blood of infected individuals.
• Vector transmission may be mechanical e.g., passively transferring microorganisms on the outside of the body, or biological including arthropods, where the agent multiplies inside the organism.
• In transmission, successful pathogens undergo adherence to tissue and colonization beginning when adherence is stabilized through specific surface receptors, localized to particular sites (tissue tropism).
• Biofilms consist of mixed species of microorganisms, including bacteria and fungi, immersed in a highly organized extracellular matrix that protect and exchange genetic information for antibiotic resistance.
• Invasion follows colonization and extracellular pathogens invade via direct extension using adhesion molecules and toxins, and intracellular pathogens spread directly from cell to cell.