Reading material for Basic Mechanisms of Diseases/S.

Wahyuni/Department of Parasitology/ Medical

Faculty, Hasanuddin University/2009

HELMINTH:
Pathogenesis and Defenses
Introduction
Helminth is a general term for a parasitic worm. The helminths include the Platyhelminthes or
flatworms (flukes and tapeworms) and the Nematoda or roundworms.
All helminths are relatively large (> 1 mm long); some are very large (> 1 m long). All have welldeveloped organ systems and most are active feeders. The body is either flattened and covered with
plasma membrane (flatworms) or cylindrical and covered with cuticle (roundworms). Some helminths are
hermaphrodites; others have separate sexes.
Helminths are worldwide in distribution; infection is most common and most serious in poor
countries. The distribution of these diseases is determined by climate, hygiene, diet, and exposure to
vectors.
The mode of transmission varies with the type of worm; it may involve ingestion of eggs or larvae,
penetration by larvae, bite of vectors, or ingestion of stages in the meat of intermediate hosts. Worms are
often long-lived.
Many infections are asymptomatic; pathologic manifestations depend on the size, activity, and
metabolism of the worms. Immune and inflammatory responses also cause pathology.
Nonspecific defense mechanisms limit susceptibility. Antibody- and cell-mediated responses are
important, as is inflammation. Parasites survive defenses through many evasion strategies.
Helminths - worms - are some of the world's commonest parasites. They belong to two major
groups of animals, the flatworms or Platyhelminthes (flukes and tapeworms) and the roundworms or
Nematoda. All are relatively large and some are very large, exceeding one meter in length.
Their bodies have well-developed organ systems, especially reproductive organs, and most
helminths are active feeders. The bodies of flatworms are flattened and covered by a plasma membrane,
whereas roundworms are cylindrical and covered by a tough cuticle. Flatworms are usually
hermaphroditic whereas roundworms have separate sexes; both have an immense reproductive capacity.
The most serious helminth infections are acquired in poor tropical and subtropical areas, but
some also occur in the developed world; other, less serious, infections are worldwide in distribution.
Exposure to infection is influenced by climate, hygiene, food preferences, and contact with vectors. Many
potential infections are eliminated by host defenses; others become established and may persist for
prolonged periods, even years. Although infections are often asymptomatic, severe pathology can occur.
Because worms are large and often migrate through the body, they can damage the host's tissues directly
by their activity or metabolism. Damage also occurs indirectly as a result of host defense mechanisms.
Almost all organ systems can be affected.
Host defense can act through nonspecific mechanisms of resistance and through specific immune
responses. Antibody-mediated, cellular, and inflammatory mechanisms all contribute to resistance.
However, many worms successfully avoid host defenses in a variety of ways, and can survive in the face
of otherwise effective host responses.
Transmission of Infection
Helminths are transmitted to humans in many different ways fig 1

Reading material for Basic Mechanisms of Diseases/S. Wahyuni/Department of Parasitology/ Medical

Faculty, Hasanuddin University/2009

Figure 1. Entry and localization of pathogenic helminthes

The simplest is by accidental ingestion of infective eggs (Ascaris, Echinococcus, Enterobius, Trichuris) or
larvae (some hookworms). Other worms have larvae that actively penetrate the skin (hookworms,
schistosomes, Strongyloides). In several cases, infection requires an intermediate host vector. In some
cases the intermediate vector transmits infective stages when it bites the host to take a blood meal (the
arthropod vectors of filarial worms); in other cases, the larvae are contained in the tissues of the
intermediate host and are taken in when a human eats that host (Clonorchis in fish, tapeworms in meat
and fish, Trichinella in meat). The levels of infection in humans therefore depend on standards of hygiene
(as eggs and larvae are often passed in urine or feces), on the climate (which may favor survival of
infective stages), on the ways in which food is prepared, and on the degree of exposure to insect vectors.
Host Factors Influencing Susceptibility
Human behavior is a major factor influencing susceptibility to infection. If the infective stages of helminths
are present in the environment, then certain ways of behaving, particularly with regard to hygiene and
food, will result in greater exposure. Because helminths, with few exceptions (Strongyloides, Trichinella,
some tapeworm larvae), do not increase their numbers by replication within the same host, the level of
infection is directly related to the number of infective stages encountered. Obviously, not every exposure
results in the development of a mature infection. Many infective organisms are killed by the host's
nonspecific defense mechanisms. Of those that do become established, many are destroyed or
eliminated by specific defenses. The number of worms present at any one time therefore represents a
dynamic balance between the rate of infection and the efficiency of defense. This balance (which reflects
the host's overall susceptibility) is altered by changes in the host's behavior and ability to express forms of
defense. Children are more susceptible to many helminths than are adults, and frequently are the most
heavily infected members of a community. The waning of immune competence with age may also result

Reading material for Basic Mechanisms of Diseases/S. Wahyuni/Department of Parasitology/ Medical

Faculty, Hasanuddin University/2009
in increased levels of infection. Individuals differ genetically in their ability to resist infection, and it is well
known that in infected populations, some individuals are predisposed to heavier infections than others.
Changes in diet may affect susceptibility, as do the hormonal-immune changes accompanying pregnancy
and lactation. An important cause of increased susceptibility is the immune suppression that
accompanies concurrent infections with some other pathogens and the development of certain tumors.
Similarly, immunosuppressive therapies (irradiation, immunosuppressant drugs) may enhance
susceptibility to helminth infection. A particular hazard in immunocompromised patients is the
development of disseminated strongyloidiasis, in which large numbers of larvae develop in the body by
autoinfection from relatively small numbers of adult Strongyloides stercoralis. It is interesting that the
human immunodeficiency virus does not result in an overall increase in susceptibility to helminth infection.
Pathogenesis
1. Direct Damage from Worm Activity: The most obvious forms of direct damage are those
resulting from the blockage of internal organs or from the effects of pressure exerted by growing
parasites fig 2.

Figure 2. Pathogenesis: direct damage caused by large helminthes

Large Ascaris or tapeworms can physically block the intestine, and this may occur after some forms of
chemotherapy; migrating Ascaris may also block the bile duct. Granulomas that form around schistosome
eggs may block the flow of blood through the liver, and this may lead to pathological changes in that
organ and elsewhere. Blockage of lymph flow, leading to elephantiasis, is associated with the presence of
adult Wuchereria in lymphatics. Pressure atrophy is characteristic of larval tapeworm infections (hydatid
cyst, the larva of Echinococcus granulosus) where the parasite grows as a large fluid-filled cyst in the
liver, brain, lungs, or body cavity. The multilocular hydatid cysts caused by Echinococcus multilocularis
have a different growth form, metastasizing within organs and causing necrosis. The larvae of Taenia

Reading material for Basic Mechanisms of Diseases/S. Wahyuni/Department of Parasitology/ Medical

Faculty, Hasanuddin University/2009
solium, the pork tapeworm, frequently develop in the central nervous system (CNS) and eyes. Some of
the neurological symptoms of the resulting condition, called cysticercosis, are caused by the pressure
exerted by the cysts.
Intestinal worms cause a variety of pathologic changes in the mucosa, some reflecting physical and
chemical damage to the tissues, others resulting from immunopathologic responses. Hookworms
(Ancylostoma and Necator) actively suck blood from mucosal capillaries. The anticoagulants secreted by
the worms cause the wounds to bleed for prolonged periods, resulting in considerable blood loss. Heavy
infections in malnourished hosts are associated with anemia and protein loss. Protein-losing
enteropathies may also result from the inflammatory changes induced by other intestinal worms.
Diversion of host nutrients by competition from worms is probably unimportant, but interference with
normal digestion and absorption may well aggravate undernutrition. The tapeworm Diphyllobothrium
latum can cause vitamin B12 deficiency through direct absorption of this factor.
Many helminths undertake extensive migrations through body tissues, which both damage tissues directly
and initiate hypersensitivity reactions. The skin, lungs, liver, and intestines are the organs most affected.
Petechial hemorrhages, pneumonitis, eosinophilia, urticaria and pruritus, organomegaly, and
granulomatous lesions are among the signs and symptoms produced during these migratory phases.
Feeding by worms upon host tissues is an important cause of pathology, particularly when it induces
hyperplastic and metaplastic changes in epithelia. For example, liver fluke infections lead to hyperplasia
of the bile duct epithelium. Chronic inflammatory changes around parasites (for example, the granulomas
around schistosome eggs in the bladder wall) have been linked with neoplasia, but the nature of the link
is not known. The continuous release by living worms of excretory-secretory materials, many of which are
known to have direct effects upon host cells and tissues, may also contribute to pathology.
2. Indirect Damage from Host Response
As with all infectious organisms, it is impossible to separate the pathogenic effects caused strictly by
mechanical or chemical tissue damage from those caused by the immune response to the parasite. All
helminths are foreign bodies not only in the sense of being large and invasive but also in the
immunologic sense: they are antigenic and therefore stimulate immunity. An excellent illustration of this
interrelation between direct and indirect damage is seen in the pathology associated with schistosome
infections, especially with Schistosoma mansoni (Fig. 3)

Reading material for Basic Mechanisms of Diseases/S. Wahyuni/Department of Parasitology/ Medical

Faculty, Hasanuddin University/2009

Fig 3. Figure 87-3. Pathogenesis: indirect damage caused by immunopathologic responses (for
example, in Schistosomiasis)
Hypersensitivity-based, granulomatous responses to eggs trapped in the liver cause a physical
obstruction to blood flow, which leads to liver pathology. Hypersensitivity-based inflammatory changes
probably also contribute to the lymphatic blockage associated with filarial infections (Brugia, Wuchereria).
Immune-mediated inflammatory changes occur in the skin, lungs, liver, intestine, CNS, and eyes as
worms migrate through these structures. Systemic changes such as eosinophilia, edema, and joint pain
reflect local allergic responses to parasites. The pathologic consequences of immune-mediated
inflammation are seen clearly in intestinal infections (especially Strongyloides and Trichinella infections).
Structural changes, such as villous atrophy, develop. The permeability of the mucosa changes, fluid
accumulates in the gut lumen, and intestinal transit time is reduced. Prolonged changes of this type may
lead to a protein-losing enteropathy. The inflammatory changes that accompany the passage of
schistosome eggs through the intestinal wall also cause severe intestinal pathology. Heavy infections with
the whipworm Trichuris in the large bowel can lead to inflammatory changes, resulting in blood loss and
rectal prolapse.
The severity of these indirect changes is a result of the chronic nature of the infection. The fact that many
worms are extremely long-lived means that many inflammatory changes become irreversible, producing
functional changes in tissues. Three examples are the hyperplasia of bile ducts in long-term liver fluke
infections, the extensive fibrosis associated with chronic schistosomiasis, and the skin atrophy associated
with onchocerciasis. Severe pathology may also result when worms stray into abnormal body sites.
Defenses Against Infection
1. Nonspecific Resistance
Infective stages attempting to enter via the mouth or through the skin are opposed by the same nonspecific defenses that protect humans from invasion of other pathogens. Following oral ingestion,
parasites must survive passage through the acid stomach to reach the small bowel. The natural parasites
of humans are adapted to do this, but opportunistic parasites may be killed. Similarly, natural parasites

Reading material for Basic Mechanisms of Diseases/S. Wahyuni/Department of Parasitology/ Medical

Faculty, Hasanuddin University/2009
are adapted to the environmental conditions of the bowel (and in many cases require them as cues for
development), but accidental parasites may find them inappropriate. Penetration into the intestinal wall
may trigger inflammatory responses that immobilize and kill the worm. This may itself lead to serious
pathology (as in Anisakis infection). Worms entering through the skin must survive the skin secretions,
penetrate the epidermal layers, and avoid inflammatory trapping in the dermis. Invasion of humans by the
larvae of dog and cat hookworms (Ancylostoma spp.) results in dermatitis and creeping eruption as the
worms become the focus of inflammatory reactions that form trails in the skin.
Once in the tissues, worms need the correct sequence of environmental signals to mature. Absent or
incomplete signals constitute a form of nonspecific resistance that may partially or completely prevent
further development. The parasite may not die, however; indeed, prolonged survival at a larval stage may
result in pathology from the continuing inflammatory response (e.g. Toxocara infection).
2. Specific Acquired Immunity
There is no doubt that specific immunity is responsible for the most effective forms of host defense,
although the dividing line between nonspecific and specific mechanisms is difficult to draw with precision
(Fig. 4)

Figure 4. Host defense and parasite escape

A schematic diagram of the development and expression of acquired immunity to helminths and of the
ways in which parasites escape the immune response.
All helminths stimulate strong immune responses, which can easily be detected by measuring specific
antibody or cellular immunity. Although these responses are useful for diagnosing infection, they
frequently appear not to be protective. The high prevalence of helminth infection in endemic areas
(sometimes approaching 100 per cent), and the fact that individuals may remain infected for many years
and can easily be reinfected after they are cured by chemotherapy, suggest that protective immunity
against helminths is weak or absent in humans. However, some degree of immunity does appear to
operate, because the intensity of infection often declines with age, and many individuals in endemic areas

Reading material for Basic Mechanisms of Diseases/S. Wahyuni/Department of Parasitology/ Medical

Faculty, Hasanuddin University/2009
remain parasitologically negative and/or clinically normal. Evidence from laboratory studies provides
some clues as to the mechanisms involved. Antibodies that bind to surface antigens may focus
complement- or cell-mediated effectors that can damage the worm. Macrophages and eosinophils are the
prime cytotoxic effector cells, and IgM, IgG and IgE are the important immunoglobulins. Antibodies may
also block enzymes released by the worm, thus interfering with its ability to penetrate tissues or to feed.
Inflammatory changes may concentrate effector cells around worms, and the release of cellular mediators
may then disable and kill the worm. Encapsulation of trapped worms by inflammatory cells may also result
in the death of the worm, although this is not always the case. Intestinal worms can be dislodged by the
structural and physiologic changes that occur in the intestine during acute inflammation. It has long been
suspected that IgE-mediated hypersensitivity reactions, involving mast cells and basophils, contribute to
this process, but the evidence is still circumstantial. Despite the abundance of IgA in the intestinal lumen,
there is no conclusive evidence that it is involved in protective immunity in humans, although some field
and laboratory data suggest it is.
Avoidance of Host Defenses
Despite their immunogenicity, many helminths survive for extended periods in the bodies of their hosts.
Some of the reasons have already been mentioned (size, motility), but we now know that worms employ
many sophisticated devices to render host defenses ineffective (fig. 4)
Some worms (schistosomes) disguise their outer surface by acquiring host molecules which reduce their
antigenicity; intrinsic membrane changes also make these worms resistant to immune attack. Filarial
nematodes acquire serum albumin on their cuticle, which may act as a disguise. Many worms release
substances that depress lymphocyte function, inactivate macrophages, or digest antibodies. Larval
cestodes appear to prolong their survival by producing anticomplement factors which protect their outer
layers from lytic attack. Antigenic variation in the strict sense is not known to occur, but many species
show a stage-specific change of antigens as they develop, and this phenomenon may delay the
development of effective immune mechanisms. All helminths release relatively large amounts of antigenic
materials, and this voluminous production may divert immune responses or even locally exhaust immune
potential. Irrelevant antibodies produced by the host may block the activity of potentially protective
antibodies, as has been shown to be the case in schistosome infections.
It is striking that many helminth infections are associated with a degree of immune suppression, which
may affect specific or general responsiveness. Many explanations have been proposed for this immune
suppression, including antigen overload, antigenic competition, induction of suppressor cells, and
production of lymphocyte-specific suppressor factors. Reduced immune responsiveness may not only
prolong the survival of the original infecting worm species but increase the host's susceptibility to other
pathogens. Epidemiologic evidence also raises the possibility that infections acquired early in lifebefore
or shortly after birthmay induce a form of immune tolerance, allowing heavy worm burdens to
accumulate in the body.
The subtlety with which parasitic worms manipulate the host's immune system not only increases their
importance as pathogens but also creates formidable problems for their control and eradication.
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4. Despommier DD, Gwadz RW, Hotez PJ: Parasitic Diseases. 3rd Ed. Springer-Verlag, New York,
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Reading material for Basic Mechanisms of Diseases/S. Wahyuni/Department of Parasitology/ Medical

Faculty, Hasanuddin University/2009
5. Manson-Bahr PEC, Bell DR: Manson's Tropical Diseases. 19th Ed. Balliere Tindall, London, 1987
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