10.1 Recorded Lecture - Infection Stages, Transmission, and Fever

• Historically, infection was a primary cause of death but has been mitigated by modern public health initiatives like vaccines and antibiotics.
• The emergence of new infections, re-emergence of old ones, and antibiotic resistance keep infection a significant cause of morbidity and mortality.

Stages of Infection

• Incubation period: Time from initial exposure to symptom onset, lasting hours to years.
• Prodromal stage: Initial symptoms appear.
• Invasion: Pathogen multiplies rapidly, triggering inflammatory and immune responses, causing tissue damage.
• Convalescence: Immune and inflammatory systems successfully remove the infectious agent.
• Fever, marked by raised thermal regulatory set point in the brain and peripheral tissues, is a hallmark of infectious disease, mediated by cytokines like interleukins 1 and 6, interferon, and tissue necrosis factor.

Transmission

• Infection can occur with opportunistic organisms exploiting broken barriers or weakened defenses.
• True pathogens circumvent defenses, with infection dependent on the number of microorganisms.
• Direct transmission occurs through contact with infectious individuals, like fungal skin infections or STIs.
• Indirect transmission involves contact with contaminated materials, such as food or surfaces.
• Respiratory transmission is common for viral diseases like colds, influenza, and measles.

Microorganisms

• Infectious microorganisms differ in invasion mechanisms, reproduction, and size.
• Classes include bacteria, fungi, parasites, protozoa, and viruses.

Bacteria

• Bacterial pathogens produce toxins that can kill cells, damage tissue, or evade host defenses.
• Excess toxins released during microbial growth can have specific or broad effects.
• Endotoxins, when released in sufficient amounts, can lead to fatal septic shock.
• Gram-positive bacteria have thick, layered cell walls, while gram-negative have a thin peptidoglycan layer, aiding in antibiotic sensitivity determination.
• Tissue damage from infections is secondary to the host's inflammatory and immune responses.
• Bacteria exploit this damage to further infect the host.
• Rapid bacterial progression can overwhelm the immune system.
• Some bacteria have evolved mechanisms for intracellular survival, like preventing lysosome-phagosome fusion or neutralizing lysosomal enzymes.

Fungi

• Fungal cells contain organelles similar to human cells like mitochondria, Golgi apparatus etc.
• Many fungi are toxic to their hosts.
• Fungal invasion involves adherence to epithelial cell walls or silicone.
• Fungi cause tissue damage through secreted enzymes and inflammatory responses.
• Pulmonary exposure to spores can cause excessive granulation of mast cells, leading to shock.
• Fungi protect themselves against phagocytosis.

Parasites and Protozoans

• Parasites establish symbiosis, benefiting at the expense of the host.
• Parasites range from unicellular protozoa to large intestinal worms.
• Toxoplasma gondii is the most common parasitic infection in the US.
• Invasion involves adherence to and breakdown of connective tissue and basement membranes.
• Toxins are not prevalent, and tissue damage is caused by invasion enzymes or parasitic accumulation.
• Parasites use mechanisms to block protective immune responses; malaria is very successful.

Infectious Viruses

• Viruses are simple microorganisms lacking metabolic organelles.
• Many RNA viruses alter DNA, becoming part of the host cell's DNA.
• Viruses adhere to cells invade the reproductive cycle, typically without producing toxins.
• Viruses hide and proliferate within cells, evading immune responses.
• Some viruses can infect and kill immune cells, leading to immunosuppression.
• Some viruses have an envelope that needs to be removed for invasion.
• The viral life cycle includes attachment, binding, endocytosis, replication, and release by exocytosis.

HIV

• HIV is a retrovirus that infects and depletes the immune system.
• Early diagnosis was a death sentence, but treatment has made it a chronic illness.
• In Africa, HIV is predominantly heterosexual; in the US, it initially affected gay males, then spread to IV drug users and heterosexuals.
• HIV is a blood-borne pathogen transmitted through blood, sexual activity, and maternal transmission.
• Lymphoid areas are the primary initial infection sites.
• The HIV life cycle involves attachment, fusion, viral DNA insertion, dormancy or replication.
• Early identification and treatment are essential, using highly active antiretroviral therapy (HAART).

HIV Treatments

• Antiretroviral agents include reverse transcriptase inhibitors, entry inhibitors, protease inhibitors, and viral integration inhibitors.
• Therapy goals are reducing viral loads, morbidity, prolonging survival, and preventing transmission.
• Treated individuals may survive decades but face shortened life expectancy due to immune activation, inflammation, and drug toxicity.
• Pediatric HIV transmission has been reduced to 1% with prenatal anti-viral therapy and neonatal prophylaxis.
• Without intervention, 20% of children with HIV develop opportunistic infections within the first year and face reduced life expectancy.

Safeguarding

• Sewage removal and high-quality food and water are essential.
• Lack of implementation has led to re-emergence of some diseases.

Antibiotics

• Antibiotics, derived from microorganisms, kill or inhibit growth of other microorganisms.
• Bactericidal antibiotics kill, while bacteriostatic antibiotics inhibit growth.
• Mechanisms of action include inhibiting cell wall function, preventing protein synthesis, blocking DNA replication, or interfering with folic acid metabolism.

Vaccines

• Surviving infection is the most effective means of developing lifelong immunity.
• Vaccination induces active immunologic protection before exposure, with boosters needed.
• Mass vaccination programs eradicated measles in US by 2000, smallpox in 1979, and polio in 1994.
• Complacency or resistance to immunisation can cause resurgence of disease, such as measles.

Immunotherapy

• Passive immunotherapy involves giving pre-formed antibodies to an individual.