Session 22 Infectious Pathology

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Lecture Notes

Session 22: Infectious Pathology

Felician Sikujua (MD)

Learning tasks

At the end of this session, students are expected to be able to:

Explain pathogenesis of infectious agents.

Categorize infectious agents.

Explain bacterial infectious diseases.

Explain fungal infectious diseases.

Explain viral infectious diseases.

Explain protozoans infectious diseases.

Explain helminthes infectious diseases.

Introduction

Infectious diseases remain an important health worldwide despite the availability and use of effective vaccines and antibiotics.

Infectious diseases are important causes of death to

Elderly.

People with the acquired immunodeficiency syndrome (AIDS).

Persons with chronic diseases.

Patients receiving immunosuppressive drugs.

Introduction cont…

In developing countries, unsanitary living conditions and malnutrition contribute to a massive burden of infectious diseases.

The most common victims are children with respiratory and diarrheal infections.

A pathogen can establish infection if it possesses virulence factors that overcome normal host defenses or if the host defenses are compromised.

Components of infectious diseases transmission

An agent capable of infecting man.

A source (an infected host or reservoir).

A portal of exit from the source.

A suitable means of transmission.

A portal of entry into a new host.

A susceptible host.

Characteristics of infectious agents

Resistance

Ability of an agent to survive under adverse condition.

Infectivity

Capacity of a microorganism to enter a susceptible host.

Pathogenicity

Capacity of an agent to cause an overt disease.

Antigenicity

Ability of an agent to induce antibody production.

Toxigenicity

Ability to produce a toxin that cause pathologic effects.

Virulence

It is the degree of pathogenicity of an infectious agent.

Refers to the severity of the disease

Host factors

The host’s susceptibility to infection depends on

Age.

Sex.

Nutritional status.

Co-morbid disease.

Body immunity.

Host defenses against infection

Skin

Tough keratinized barrier, low pH, fatty acids.

Respiratory system

Alveolar macrophages and mucociliary clearance by bronchial epithelium, IgA.

Gastrointestinal system

Acidic gastric pH, viscous mucus, pancreatic enzymes and bile, defensins, IgA, and normal flora.

Urogenital tract

Repeated flushing and acidic environment created by commensal vaginal flora

Modes of transmission of infectious agents

Transmission of infections can occur by

Contact (direct and indirect).

Respiratory droplets (Inhalation).

Fecal-oral route.

Sexual transmission.

Vertical transmission from mother to fetus or newborn (during pregnancy, giving birth and breastfeeding).

Insect/arthropod vectors.

Transmission of infectious agents to the host

The ability of a microbe to infect an individual as well as the nature and extent of the disease also depends on how it is transmitted to the host.

This is determined by

Virulence of infectious agent.

Portal of entry.

Vector medium (if any).

Predisposing or protective environmental factors.

Infective dose is the minimum number of microorganisms or infective agents required to cause overt/clinical disease.

How microorganisms cause disease

Infectious agents establish infection and damage tissues by any of three (3) mechanisms:

They can contact or enter host cells and directly cause cell death.

They may release toxins that kill cells at a distance, release enzymes that degrade tissue components, or damage blood vessels and cause ischemic necrosis.

They can induce host immune responses that, although directed against the invader, cause additional tissue damage.

Categories of infectious agents

Prions.

Viruses.

Bacteria (including intracellular bacteria like Chlamydia & Rickettsia).

Fungi.

Protozoans.

Helminthes.

Prions

Prions are composed of abnormal forms of a host protein termed prion protein (PrP).

Prions are not microorganisms.

These agents cause transmissible spongiform encephalopathies, including Kuru (associated with human cannibalism), Creutzfeldt-Jakob Disease (CJD).

PrP is found normally in neurons.

Prions cont…

Diseases occur when the PrP undergoes a conformational change that confers resistance to proteases.

The protease-resistant PrP promotes conversion of the normal protease-sensitive PrP to the abnormal form, explaining the infectious nature of these diseases.

Accumulation of abnormal PrP leads to neuronal damage and distinctive spongiform pathologic changes in the brain.

Viruses

Viruses are obligate intracellular parasites that depend on the host cell’s metabolic machinery for their replication.

They consist of a nucleic acid genome surrounded by a protein coat (called a capsid) that is sometimes encased in a lipid membrane.

Some viral components and particles aggregate within infected cells and form characteristic inclusion bodies.

For example: Cytomegalovirus (CMV), Herpesviruses, smallpox virus, rabies virus.

Viruses cont…

Viruses are classified by

Their nucleic acid genome (DNA or RNA but not both).

The shape of the capsid (icosahedral or helical).

The presence or absence of lipid envelope.

Their mode of replication.

The preferred cell type for replication (called tropism).

The type of pathology they cause.

Viruses cont…

Viruses can cause illnesses in several ways.

Many viruses cause transient illnesses (e.g., colds, influenza).

Other viruses are not eliminated from the body and persist within cells of the host for years:

Continuing to multiply (e.g., chronic infection with hepatitis B virus [HBV]).

Surviving in some nonreplicating form (termed latent infection) with the potential to be reactivated later (e.g. herpes zoster virus, the cause of chickenpox establish latency, later on reactivated and causing shingle).

Viruses cont…

Some viruses are involved in transformation of a host cell into a benign or malignant tumor (e.g., human papillomavirus [HPV]-induced benign warts and cervical carcinoma).

Different species of viruses can produce the same clinical picture (e.g., upper respiratory infection)

Conversely, a single virus can cause different clinical manifestations depending on host age or immune status (e.g., CMV).

Mechanisms of viral injury

Viruses can directly damage host cells by entering them and replicating at the host’s expense.

The manifestations of viral infection are largely determined by the tropism of the virus for specific tissues and cell types.

A major determinant of tissue tropism is the presence of viral receptors on host cells.

Mechanisms of viral injury cont…

In some cases, host proteases are needed to enable binding of virus to host cells.

The ability of the virus to replicate inside some cells but not in others depends on the presence of cell type–specific transcription factors that recognize viral enhancer and promoter elements.

Physical circumstances, such as chemicals and temperature, contribute to tissue tropism.

Mechanisms of viral injury cont…

Once viruses are inside host cells, they can damage or kill the cells by a number of mechanisms:

Lysis of host cells.

Immune cell-mediated killing.

Alteration of apoptosis pathways.

Induction of cell proliferation and transformation, resulting in cancer.

Inhibition of host cell DNA, RNA, or protein synthesis.

Damage to plasma membranes.

Damage to cells involved in antimicrobial defense, leading to secondary infections.

Bacteria

Bacterial infections are common causes of disease.

Bacteria are prokaryotes, meaning that they have a cell membrane but lack membrane-bound nuclei and other membrane-enclosed organelles.

Most bacteria are bound by a cell wall consisting of peptidoglycan, a polymer of long sugar chains linked by peptide bridges surrounding the cell membrane.

Bacteria cont…

There are two common forms of cell wall structure

Thick wall that retains crystal-violet stain (Gram-positive bacteria).

Thin cell wall surrounded by an outer membrane (Gram-negative bacteria).

Bacteria are classified by

Gram staining (positive or negative).

Shapes (spherical ones are cocci; rod-shaped ones are bacilli).

Need for oxygen (aerobic or anaerobic).

Bacteria cont…

Motile bacteria have flagella that rotate and move the bacteria.

Some bacteria possess pili that can attach bacteria to host cells or extracellular matrix.

Bacteria synthesize their own DNA, RNA, and proteins,

But they depend on the host for favorable growth conditions.

Most bacteria remain extracellular.

Some can grow only within host cells (obligate intracellular bacteria e.g. Chlamydia, Rickettsia).

Others can survive and replicate either outside or inside of host cells (facultative intracellular bacteria).

Bacteria cont…

Normal healthy people can be colonized by as many as 1012 bacteria on the skin, 1010 bacteria in the mouth, and 1014 bacteria in the gastrointestinal tract.

Bacteria colonizing the skin include Staphylococcus epidermidis and Propionibacterium acnes, the cause of acne.

Aerobic and anaerobic bacteria in the mouth, particularly Streptococcus mutans, contribute to dental plaque, a major cause of tooth decay.

Most of normal intestinal flora of an individual human are anaerobes.

Chlamydia

Chlamydia is an obligate intracellular bacteria which replicate inside membrane-bound vacuoles in epithelial cells.

Chlamydia gets most or all of their energy source (ATP) from the host cell.

Chlamydia trachomatis is the most frequent infectious cause of

Female sterility (by scarring and narrowing of the fallopian tubes).

Blindness (by chronic inflammation of the conjunctiva that eventually causes scarring and opacification of the cornea).

Rickettsia

Rickettsiae is an obligate intracellular bacteria which replicate inside membrane-bound vacuoles in endothelial cells.

Rickettsia gets most or all of their energy source (ATP) from the host cell.

Causes hemorrhagic vasculitis, injure CNS (as in Rocky Mountain spotted fever and epidemic typhus).

Transmitted by arthropod vectors, including

Lice (in Epidemic typhus).

Ticks (in Rocky mountain spotted fever and ehrlichiosis).

Mites (in Scrub typhus).

Mechanisms of bacterial injury

Bacterial damage to host tissues depends on the ability of the bacteria to:

Adhere to host cells.

Invade cells and tissues.

Deliver toxins.

Fungi

Eukaryotes that possess thick, chitin-containing cell walls and ergosterol-containing cell membranes.

Fungi can grow either as rounded yeast cells, slender, filamentous hyphae or dimorphic.

Hyphae may be septate or aseptate.

Some of pathogenic fungi exhibit thermal dimorphism.

Grow as hyphal forms at room temperature but as yeast forms at body temperature.

Fungi may produce sexual spores or, more commonly, asexual spores called conidia.

Fungi cont…

Fungi may cause superficial or deep infections.

Superficial infections involve the skin, hair, and nails.

Fungal species that cause superficial infections are called dermatophytes (‘skin lovers’) or Tinea infections.

Certain fungi invade the subcutaneous tissue, causing abscesses or granulomas sometimes called mycetomas.

Deep fungal infections can spread systemically and invade tissues, destroying vital organs in immunocompromised hosts.

Usually resolve or remain latent in otherwise normal hosts.

Fungi cont…

Fungi are also divided into endemic and opportunistic species.

Endemic fungi are invasive species that are limited to particular geographic regions.

Opportunistic fungi (e.g., Candida, Aspergillus, Mucor, Cryptococcus) in immunodeficient individuals, give rise to life-threatening invasive infections with little or no inflammatory response.

Fungi cont…

Patients with HIV/AIDS often are infected by the opportunistic fungi

Candida albicans causing oral, esophageal candidiasis.

Cryptococcus neoformans causing meningitis.

Pneumocystis jiroveci (previously called Pneumocystis carinii) causing Pneumonia.

Protozoa

Protozoa are single-celled eukaryotes.

Protozoa can replicate

Intracellularly within a variety of cells (e.g., Plasmodium in red cells, Leishmania in macrophages)

Extracellularly in the urogenital system, intestine or blood.

Trichomonas vaginalis is sexually transmitted flagellated protozoal parasite that often colonize the vagina and male urethra.

Protozoa cont…

The most prevalent intestinal protozoans are Entamoeba histolytica and Giardia lamblia.

Ingested as nonmotile cysts in contaminated food or water and become motile trophozoites that attach to intestinal epithelial cells.

Blood borne protozoa (e.g., Plasmodium, Trypanosoma, Leishmania) are transmitted by insect vectors, in which they replicate before being passed to new human hosts.

Toxoplasma gondii is acquired either through contact with oocyst-shedding kittens or by eating cyst-ridden, undercooked meat.

Helminthes

They are highly differentiated multicellular organisms.

They have complex life cycles.

Most alternate between sexual reproduction in the definitive host and asexual multiplication in an intermediate host or vector in their life cycles

Humans may harbor adult worms (e.g., Ascaris lumbricoides), immature stages (e.g., Toxocara canis), or asexual larval forms (e.g., Echinococcus spp.).

Groups of Helminthes

Roundworms (Nematodes)

Circular in cross-section and nonsegmented.

E.g. Ascaris lumbricoides and hookworms.

Tapeworms (Cestodes)

Have head (scolex) and a ribbon of multiple flat segments (proglottids).

E.g. Fish, beef, and pork tapeworms.

Flukes (Trematodes)

Leaf-shaped flatworms with prominent suckers that are used to attach to the host.

E.g. Blood, liver and lung flukes.

Strategies (mechanisms) in which microbes evade immune system

Remaining inaccessible to host defences.

Constantly changing antigenic repertoires.

Inactivating antibodies or complement.

Resisting phagocytosis.

Growing within phagocytes after ingestion.

Suppressing the host adaptive immune response.

Key points

Infectious diseases are due to organisms ranging in size from viruses to parasitic worms.

Pathogenicity is the capacity of a particular microbe to cause disease.

Spread of microbes to other sites depend on microbial tissue tropisms.

Prions are not microorganism; they are abnormal host proteins commonly seen in neurons.

Most of intestinal bacteria are anaerobes.

Tinea infections are caused by superficial fungi.

Any stage of helminthes can cause inflammation.

Review questions

Explain pathogenesis of infectious agents.

Explain five (5) mode of transmission of infectious diseases.

Explain five (5) mechanisms on how viruses damage or kill the cells once they are inside host cells.

Explain three (3) mechanisms on how bacteria cause diseases.

List five (5) strategies used by microbes to evade immune system.

References

Kumar V. ; Abbas A. K. ; Aster J. C.;(2013): Robbins and Contran Pathologic Basis of Disease (9th Ed.) Elsevier Saunders, USA. Pg. 309-322.

Xiu P.;(2012): Crash Course Pathology (4th Ed.) Elsevier Saunders, USA. Pg. 25-35.

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Session 22 Infectious Pathology

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