Pathogenesis of Parasitic Diseases - 13 Aug 2023

Lecture 1
Introduction to Medical Microbiology

- Pathogenesis of Parasitic diseases
SCI 8007SEF Medical Microbiology & Virology
By Dr. Andy YY CHEUNG

cheungyy@hkmu.edu.hk
Book references
• Murray, P. R., Rosenthal, K. S., & Pfaller, M. A. (2016). Medical
microbiology.
• Brooks, G. F., Carroll, K. C., Butel, J. S., Morse, S. A., &

Mietzner, T. A. (2013). Jawetz, Melnick & Adelberg’s Medical
Microbiology 26th Ed., by The McGraw-Hill Companies.
• Mahon, C. R., & Lehman, D. C., (2019). Textbook of diagnostic

microbiology. Elsevier.
Pathogenesis of Parasitic Diseases
• Given the wide diversity that exists among human parasites, it is not surprising
that the pathogenesis of protozoan and helminthic disease is highly variable
• Although the various human parasites exhibit a wide range of direct pathogenic
mechanisms, in most instances, the organisms themselves are not highly virulent,
are unable to replicate within the host, or have both characteristics
• Thus the severity of illness caused by many parasites is related to the infecting
dose and the number of organisms acquired over time
• Unlike many bacterial and viral infections, parasitic infections are often chronic,
lasting months to years
• Repeated exposures result in an ever-increasing parasite burden
• When infection with a particular organism is associated with a strong immune
response, there is undoubtedly a considerable immunopathologic contribution to
the disease manifestations attributed to the infection
Murray, P. R., Rosenthal, K. S., & Pfaller, M. A. (2016). Medical microbiology 8th edition.
correct parasite with correct route —> cause diseases
• Parasites are almost always exogenous to the human host and thus must enter
the body through ingestion or direct penetration of anatomic barriers
• Inoculum size and duration of exposure greatly influence the disease-causing
potential of an organism
• Likewise, the route of exposure is critical for most organisms
• For example, pathogenic strains of Entamoeba histolytica are unlikely to cause
disease on exposure to intact skin but may cause severe dysentery after oral
ingestion
• Many parasites have active self-directed means of invading the human host
• Once they have invaded, parasites attach to specific host cells or organs, avoid
immune detection, replicate (most protozoa and some helminths), produce toxic
substances that destroy tissue, and cause disease secondary to the host’s own
immunologic
• In addition, some parasites physically obstruct and damage organs and tissues
because of their size alone
Factors Associated with Parasite Pathogenicity
• Infective dose and exposure
• Penetration of anatomic barriers
• Attachment
• Replication
• Cell and tissue damage
• Disruption, evasion, and inactivation of host defenses
Exposure and Entry
• Although many infectious diseases are caused by endogenous organisms that are part of the
normal flora of the human host, this is not the case with most diseases caused by protozoan and
helminthic parasites
• These organisms are virtually always acquired from an exogenous source and as such have
evolved numerous ways to enter the body of the human host
• The most common modes of entry are oral ingestion or direct penetration through the skin or
other surfaces
• Transmission of parasitic diseases is frequently facilitated by environmental contamination with
human and animal wastes
• This is most applicable to diseases transmitted by the fecal-oral route but also applies to
helminthic infections such as hookworm disease and strongyloidiasis, which rely on larval
penetration of the skin
Exposure and Entry
節肢動物
• Many parasitic diseases are acquired via the bites of arthropod vectors
• Transmission of disease in this manner is extraordinarily effective, as evidenced by the
widespread distribution of diseases such as malaria, trypanosomiasis, and filariasis
• Additional factors that determine the outcome of the interaction between parasite and host are
route of exposure and inoculum size
• Most human parasites have a limited range of organs or tissues in which they can replicate or
survive
• For example, simple skin contact with most intestinal protozoa does not result in disease; rather,
the organisms must be ingested for the disease process to be initiated
Exposure and Entry
• Likewise, a minimum number of organisms is required to establish infection
• Although some parasitic diseases may be acquired by ingestion or inoculation of only a few
organisms, a sizable inoculum is usually required.
• Whereas an individual may acquire malaria by a single bite of an infected female mosquito, large
inocula are usually necessary to produce diseases such as amebiasis in humans
Parasite Ports of Entry
Route Examples
Ingestion Giardia spp.,
Entamoeba histolytica,
Cryptosporidium spp.,
cestodes,
nematodes
Direct penetration
➢ Arthropod bite Malaria,
Babesia spp.,
filaria,
Leishmania spp.,
trypanosomes
➢ Transplacental penetration Toxoplasma gondii
➢ Organism-directed penetration Hookworm, Strongyloides spp.,

schistosomes
Adherence and Replication
• Most infections are initiated by the attachment of the organism to host tissues, followed by
replication to establish colonization
• The life cycle of a parasite is based on species and tissue tropisms, which determine the organs or
tissues of the host in which a parasite can survive
• Attachment of the parasite to host cells or tissue can be relatively nonspecific, can be mediated
by mechanical or biting mouthparts, or can result from the interaction between structures on the
parasite surface known as adhesins and specific glycoprotein or glycolipid receptors found on
some cell types but not on others
• Specific surface structures that facilitate parasite adhesion include surface glycoproteins (e.g.,
glycophorin A and B), complement receptors, adsorbed components of the complement cascade,
fibronectin, and N-acetylglucosamine conjugates
Parasitic Adherence Mechanisms
• E. histolytica is a good model for the importance of adhesins in virulence
• The pathogenesis of invasive amebiasis requires adherence of amebae to the colonic mucosal
layer, parasite attachment to and lysis of colonic epithelium and acute inflammatory cells, and
resistance of the amebic trophozoites to host humoral and cell-mediated immune defense
mechanisms
• Amebic adherence to colonic mucins, epithelial cells, and leukocytes is mediated by a surface
lectin inhibitable by galactose or N-acetyl-d-galactosamine
• Binding of the galactose-inhibitable adherence lectin to carbohydrates on the host cell surface is
required for E. histolytica trophozoites to exert their cytolytic activity
• The presence of the galactose-inhibitable adherence lectin is one feature that distinguishes
pathogenic from nonpathogenic strains of E. histolytica
• Various attachment mechanisms have been associated with specific infections
• For example, the Duffy blood group antigen acts as an attachment site for Plasmodium vivax
• Red blood cells from most West Africans, in contrast to those from Europeans, lack the Duffy
antigen
• Accordingly, malaria resulting from P. vivax is almost unknown in West Africa
• The physical structures of parasites may act with adhesion molecules to promote attachment to
host cells
• Giardia duodenalis (formerly intestinalis/lamblia) is a protozoan parasite that uses a ventral disk
to attach to the intestinal epithelium by a clasping or suction-like mechanism
• Two recently identified adhesins, trypsin-activated G. lamblia lectin (taglin) and G. lamblia
adherence molecule-1 (GLAM-1), may also be important in attachment to enterocytes
• It is believed that initial contact of the parasite with the intestinal surface is facilitated by taglin,
which is distributed over the surface of the parasite, and that the disk-specific GLAM-1 is
responsible for avid attachment of the disk to the enterocyte surface
• After attachment to the specific cell or tissue type, the parasite may undergo replication as the
next step in establishing infection
• Most protozoan parasites replicate intracellularly or extracellularly in the human host, whereas
replication is generally not observed with the helminths capable of establishing human infection
• Temperature may also play an important role in the ability of parasites to infect a host and cause
disease
• For example, Leishmania donovani replicates well at 37°C and causes visceral leishmaniasis
involving the bone marrow, liver, and spleen
• In contrast, Leishmania tropica grows well at 25°C to 30°C but poorly at 37°C and causes an
infection of the skin without involvement of deeper organs
Cell and Tissue Damage
• Although some microorganisms may cause disease by localized multiplication and elaboration of
potent microbial toxins, most organisms initiate the disease process by invading normally sterile
tissue, with subsequent replication and destruction
• Parasitic protozoa and helminths are generally not known to produce toxins with potencies
comparable to those of classic bacterial toxins such as anthrax toxin and botulinum toxin;
however, parasitic disease can be established by elaboration of toxic products, mechanical tissue
damage, and immunopathologic reactions
Pathologic Mechanisms in Parasitic Diseases
Toxic Parasite Products
• Hydrolytic enzymes, proteinases, collagenase, elastase [Schistosomes
(cercariae), Strongyloides spp., hookworm, Entamoeba histolytica,
African trypanosomes, Plasmodium falciparum]
• Amebic ionophore [Entamoeba histolytica]
• Endotoxins [African trypanosomes, Plasmodium falciparum]
• Indole catabolites [Trypanosomes]
Mechanical Tissue Damage
• Blockage of internal organs [Ascaris spp., tapeworms, schistosomes,
filaria]
• Pressure atrophy [Echinococcus spp., Cysticercus spp.]
• Migration through tissue [Helminthic larvae]
Pathologic Mechanisms in Parasitic Diseases
Immunopathology
• Hypersensitivity
• Autoimmunity
• Protein-losing enteropathies [Hookworm, tapeworm, Giardia spp.,
Strongyloides spp.]
• Metaplastic changes [Opisthorchis spp. (liver flukes), schistosomes]
Toxic enzymes

• Numerous authors have suggested that toxic products elaborated by parasitic
protozoa are responsible for at least some aspects of pathology
• Proteases and phospholipases may be secreted and are released upon destruction of the
parasites
• These enzymes can cause host cell destruction, inflammatory responses, and gross tissue
pathology
Toxic enzymes

• For example, the intestinal parasite E. histolytica produces proteinases that can degrade epithelial
basement membrane and cell-anchoring proteins, disrupting epithelial cell layers
• Furthermore, the amebae produce phospholipases and an ionophore-like protein that lyse the
responding host neutrophils, resulting in release of neutrophil constituents that are toxic to host
tissues
• The expression of certain proteinases increases relative to the virulence of the strain of E.
histolytica
Mechanical tissue damage - blockage

• In contrast to the protozoan parasites, many of the pathogenic consequences of helminthic
infections are related to the size, movement, and longevity of the parasites
• The host is exposed to long-term damage and immune stimulation, as well as the sheer physical
consequences of being inhabited by large foreign bodies
• The most obvious forms of direct damage from helminthic parasites are those resulting from
mechanical blockage of internal organs or from the effects of pressure exerted by growing
parasites
Mechanical tissue damage - blockage

• Large adult Ascaris organisms can physically block the intestine and bile ducts
• Likewise, blockage of lymph flow, leading to elephantiasis, is associated with the presence of
adult Wuchereria organisms in the lymphatic system
• Some neurologic manifestations of cysticercosis are due to the pressure exerted by the slowly
expanding larval cysts of Taenia solium on the central nervous system (CNS) and eyes
• Migration of helminths (usually larval forms) through body tissues such as the skin, lungs, liver,
intestines, eyes, and CNS can damage tissues directly and initiate hypersensitivity reactions
Immunopathology - hypersensitive

• As with many infectious agents, the manifestations of parasitic disease are due not only to the
mechanical or chemical tissue damage produced by the parasite but also to host responses to the
presence of the parasite
• Cellular hypersensitivity is observed in protozoan and helminthic disease
• During a parasitic infection, host cell products such as cytokines and lymphokines are released
from activated cells
• Immunopathologic reactions range from acute anaphylactic reactions to cell-mediated delayed
hypersensitivity reactions
Immunopathologic Reactions to Parasitic Disease
Immunopathology - metaplastic change

• The fact that many parasites are long-lived means that many inflammatory changes
become irreversible, producing functional changes in tissues
• Examples include hyperplasia of the bile ducts secondary to the presence of liver flukes
and extensive fibrosis leading to genitourinary and hepatic dysfunction in chronic
schistosomiasis
• Migration of larval helminths through tissues such as skin, lungs, liver, intestine, CNS, and
eyes produces immune-mediated inflammatory changes in these structures
• Finally, chronic inflammatory changes around parasites such as Clonorchis sinensis and
Schistosoma haematobium have been linked to the induction of carcinomatous changes
in the bile ducts and bladder, respectively
How parasite escape from host defenses
Disruption, Evasion, and Inactivation of Host

Defenses
• Although the processes of cell and tissue destruction are often sufficient to initiate clinical
disease, the parasite must be able to evade the host’s immune defense system for the disease
process to be maintained. Like other organisms, parasites elicit humoral and cell-mediated
immune responses; however, parasites are particularly adept at interfering with or avoiding these
defense mechanisms
• Organisms can shift antigenic expression, such as that observed with the African trypanosomes
• Rapid variation of expression of antigens in the glycocalyces of these organisms occurs each time
the host exhibits a new humoral response
• Similar changes have been observed with Plasmodium, Babesia, and Giardia species
• Some organisms may produce antigens that mimic host antigens (mimicry) or
acquire host molecules that conceal the antigenic site (masking), thus preventing
immune recognition by the host
Microbial Interference with or Avoidance of
Immune Defenses
Disruption, Evasion, and Inactivation of Host
Defenses
• Many protozoan parasites evade the immune response by assuming an
intracellular location in the host
• The organisms that reside in macrophages have developed a variety of mechanisms to avoid
intracellular killing
• These include prevention of phagolysosome fusion, resistance to killing after exposure to
lysosomal enzymes, and escape of phagocytosed cells from the phagosome into the cytoplasm,
with subsequent replication of the organism
• Immunosuppression of the host is often observed during the course of parasitic infections
• The immunosuppression may be parasite specific or generalized, involving a response to various
nonparasite and parasite antigens
• Proposed mechanisms include antigen overload, antigenic competition, induction of suppressor
cells, and production of lymphocyte-specific suppressor factors
• Certain helminths, such as Schistosoma mansoni, may also produce proteinases that can degrade
immunoglobulins

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Lecture 1

Introduction to Medical Microbiology

SCI 8007SEF Medical Microbiology & Virology

By Dr. Andy YY CHEUNG

• Brooks, G. F., Carroll, K. C., Butel, J. S., Morse, S. A., &

• Mahon, C. R., & Lehman, D. C., (2019). Textbook of diagnostic

➢ Transplacental penetration Toxoplasma gondii

➢ Organism-directed penetration Hookworm, Strongyloides spp.,

Cell and Tissue Damage

Cell and Tissue Damage

Cell and Tissue Damage

Cell and Tissue Damage

Cell and Tissue Damage

Cell and Tissue Damage

Disruption, Evasion, and Inactivation of Host

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