Pathogenesis and Diagnosis of Parasitic Infections​-72

What does Disability-Adjusted Life Years (DALYs) measure?

A composite measure of disease burden that captures both premature mortality and prevalence and severity of ill health; quantifies the health loss due to a specific disease or injury

Why is thorough diagnosis important in parasitic infections?

• Parasites usually affect one organ system, but may migrate, causing more severe damage

• Different parasites can produce similar symptoms

• Accurate (differential) diagnosis is critical to select the appropriate treatment, especially since some antiparasitic agents are quite toxic

What challenges do parasites present for diagnosis and treatment?

• Usually affect one organ system, but can migrate, leading to more severe damage

• Different parasites can cause similar symptoms

• Accurate (differential) diagnosis is essential because some antiparasitic treatments are highly toxic

What cell does Plasmodium vivax infect and how does it attach?

• Causes malaria

• Infects red blood cells

• Attachment via merozoite (non–complement-mediated)

• Requires Duffy antigen

What does Giardia duodenalis cause, where does it attach, and how?

• Causes diarrhea

• Attaches to duodenal and jejunal epithelium

• Attachment via mechanical suction, microtubules, and lectin-mediated mechanisms

What does Entamoeba histolytica cause, where does it attach, and how?

• Causes dysentery

• Attaches to colonic epithelium

• Attachment via lectin and N-acetylglucosamine conjugates

What does Trypanosoma cruzi cause, what cell does it target, and how?

• Causes Chagas disease

• Targets fibroblasts

• Attachment via penetrin, fibronectin, and fibronectin receptor

What does Leishmania major cause, what cell does it infect, and how?

• Causes leishmaniasis

• Infects macrophages

• Uses adsorbed C3bi and CR3 receptor for attachment

What does Leishmania mexicana cause, what cell does it infect, and how?

ack:

• Causes leishmaniasis

• Infects macrophages

• Uses surface glycoprotein gp63 and CR2 receptor

What parasitic organisms are associated with pressure atrophy?

• Echinococcus spp.

• Cysticercus spp.

What are the key immune responses to parasitic infections?

• Helminths: TH2 response; activation of complement, IgE, mast cells, and eosinophils

• Th2:

  • IgG and IgA block parasite binding and entry into cells

  • IgE binds mast cells and eosinophils → triggers histamine and toxic substance release to promote parasite expulsion

  • Stimulates mucus secretion in colon

• Th1:

  • Critical for intracellular infections (e.g., Leishmania)

  • Promotes inflammation and granuloma formation (e.g., Schistosoma)

• Th17:

  • Enhances epithelial and neutrophil responses for extracellular parasites

What is Type 1 hypersensitivity in parasitic infections?

• Anaphylactic

• Antigen + IgE on mast cells → histamine release

• Leads to anaphylactic shock, bronchospasm, local inflammation

• Seen in helminth infection, African trypanosomiasis

What is Type 2 hypersensitivity in parasitic infections?

• Cytotoxic

• Antibody + antigen on cell surface → complement activation or antibody-dependent cellular cytotoxicity

• Causes lysis of antigen-bearing cells

• Seen in Trypanosoma cruzi infection

What is Type 3 hypersensitivity in parasitic infections?

• Immune complex

• Antibody + extracellular antigen forms complexes

• Complex deposition → inflammation, tissue damage, glomerulonephritis, vasculitis

• Seen in malaria, schistosomiasis, trypanosomiasis

What is Type 4 hypersensitivity in parasitic infections?

• Cell-mediated (delayed)

• Sensitized T-cells react with antigen → lymphokine release, cytotoxicity

• Causes inflammation, macrophage activation, mononuclear accumulation, tissue damage

• Seen in leishmaniasis, schistosomiasis, trypanosomiasis

What is antigenic variation and which parasites use it?

• Variation of surface antigens within the host

• Used by: African trypanosomes, Plasmodium spp., Babesia spp., Giardia spp.

What is molecular mimicry and which parasites use it?

• Microbial antigens mimic host antigens, leading to a poor antibody response

• Seen in: Plasmodium spp., trypanosomes, schistosomes

What is antigenic masking and which parasites use it?

• Concealment of antigenic sites by acquiring a host molecule coating

• Seen in: hydatid cyst, filaria, schistosomes, trypanosomes

How does intracellular location help parasites evade immunity?

• Parasites fail to display antigens on the host cell surface

• Used by: Plasmodium spp. (RBCs), trypanosomes, Leishmania spp., Toxoplasma spp.

Which parasite inhibits phagolysosomal fusion?

Toxoplasma spp.

Which parasites escape the phagosome to replicate in the cytoplasm?

• Leishmania spp.

• Trypanosoma cruzi

How do parasites use immunosuppression?

• Suppress parasite-specific B-cell and T-cell responses

• Seen in: trypanosomes, Plasmodium spp.

Which parasite degrades immunoglobulins?

Schistosomes

What enables antigenic variation in trypanosomes?

• VSG: Variant Surface Glycoproteins

• VSG silent archive is transferred to VSG expression sites to change surface antigens

What factors are crucial for laboratory diagnosis of parasitic diseases?

• hysician’s knowledge/alertness – “Think parasite”

• Patient’s exposure history (some worms live for decades)

• Traveler vs. semi-immune resident

• Use of prophylaxis

• Host immune status

• Parasitic life cycle and pathogenesis

• Innate virulence of the parasite

• Infectious dose / organism burden

• Note: Chloroquine resistance impacts malaria treatment

What is required for proper diagnosis of a parasitic disease?

• hysician must consider the possibility of parasitic disease

• Appropriate specimens must be obtained and transported

• Correct procedures for recovery and ID of the agent must be used

• Lab results must be effectively communicated to the physician

• Results must be correctly interpreted and applied to care

• Understanding the parasite’s life cycle and pathogenesis is crucial

What are common diagnostic techniques in parasitology?

• Macroscopic examination

• Microscopic examination (wet mounts, stained stool, concentrates, blood, tissue)

• Immunodiagnostics (antigen detection, antibody response)

• Molecular diagnostics (nucleic acid hybridization/amplification)

• Culture

• Animal inoculation

• Xenodiagnosis

What are key considerations for diagnosing intestinal and urogenital parasitic infections?

• Microscopic stool exam (O&P) may miss some parasites

• Wet mounts/stained smears often inadequate

• May require repeated specimens, concentration, or duodenal aspiration/small bowel biopsy

• Proctoscopic/sigmoidoscopic exam in some cases

• Immunoassays can be very effective

• Fecal collection: 3 specimens recommended, handled properly (fast delivery, preservatives, no interfering meds)

• Sputum for certain parasites

• Urine/urogenital specimens (e.g., Trichomonas vaginalis)

How are parasitic infections of blood and tissue diagnosed?

• Blood films (thin and thick, stained)

• Cerebrospinal fluid

• Tissue specimens, biopsies, sputum

• Immunodiagnostics: agglutination, complement fixation, immunofluorescence, EIA

• Antibody and antigen detection

• Molecular diagnostics: nucleic acid hybridization, amplification, sequencing

• Culture (e.g., Trichomonas, Entamoeba)

• Animal inoculation (Trypanosomes)

• Xenodiagnosis (Chagas disease)