Chapter 48: Parasites—Basic Concepts

The discipline of Medical Parasitology encompasses a broad spectrum of organisms belonging to the kingdoms Protista and Animalia that include diverse phylogenetic groupings such as the subkingdoms Protozoa and Metazoa, respectively. The latter include the trematodes, cestodes (Platyhelminthes), and nematodes (Nemathelminthes). Although often quite dissimilar, many parasites do share some important traits. They are opportunists by nature and exploit environmental niches and lifestyles within their hosts that suit their individual needs. Many have high prevalence rates, given the right set of circumstances, and may cause significant morbidity and mortality. All have exceedingly complex life cycles. The purpose of this chapter, and Chapters 49 and 50 that follow, is to lay a foundation of basic definitions and concepts that hopefully will aid the student in better understanding the specific diseases that will be described in succeeding chapters.

Within the context of this section of the book, the term parasite refers to organisms that are physiologically dependent upon their host for survival and belong to the major taxonomic groupings mentioned earlier: Protozoa, Platyhelminthes, and Nemathelminthes. Parasitism, however, denotes a relationship in which one organism, the parasite, usually benefits at the expense of the other, the host. Protozoa are microscopic, single-celled eukaryotes with a membrane-bound nucleus and organelles. Helminths, comprising both Platyhelminthes and Nemathelminthes, in contrast, are macroscopic, multicellular worms possessing differentiated tissues and complex organ systems; they vary in length from more than 1 m to less than 1 mm. The majority of both Protozoa and helminths are free living, play a significant role in the ecology of the planet, and seldom inconvenience the human race. The less common disease-producing species are typically obligate parasites, dependent on vertebrate hosts, arthropod hosts, or both for their survival. Most parasites are perfectly happy living in a commensalistic relationship with their host, producing little or no injury. Of importance to us are those that disturb this relationship, leading to pathogenesis and, occasionally, to death of both the host and parasite.

The relative infrequency of parasitic infections in the temperate societies of the industrialized world with strict sanitation has sometimes led to the parochial view that knowledge of parasitology has little relevance for physicians practicing in these areas. In spite of this view, parasites such as Toxoplasma gondii, Cryptosporidium spp., Giardia, Trichomonas vaginalis, and Enterobius vermicularis thrive in our midst. Many others pose risks as imported agents and our medical communities are continuously challenged to both identify and treat them. In addition, the continuing presence of parasitic disease among the impoverished, immunocompromised, sexually active, and peripatetic segments of industrialized populations means that most physicians throughout the world regularly encounter those pathogens. Parasitic diseases remain among the major causes of human misery and death in the world today and, as such, are important obstacles to the development of economically less favored nation (Table 48–1). Moreover, political, socioeconomic, and medical instabilities in several parts of the world have combined to produce a dramatic recrudescence of several parasitic diseases with important consequences to both the United States and the developing world.

Currently, about half of the world’s population lives in areas where malaria transmission could or does occur; of these, approximately 200 to 300 million experience new cases annually, with many individuals being infected more than once during any given year. About 700 000 people, predominantly children living in Sub-Saharan Africa, die of malaria each year. Plasmodium falciparum, the deadliest of the malarial organisms and responsible for cerebral malaria, has developed resistance to several categories of antimalarial agents, and resistant strains are now found throughout Southeast Asia, parts of the Indian subcontinent, Southeast China, large areas of tropical America, and tropical Africa. Disturbingly, this parasite is developing increased resistance to artemisinin, the current frontline drug in the treatment of malaria. Although several new drugs are in development, it could take years before they reach the public that needs them the most. Growing resistance of the anopheline mosquito vectors of malaria to the less toxic and less expensive insecticides has resulted in a cutback of many malaria control programs. On top of that, many mosquito vectors of malaria are changing their habits, perhaps in response to our efforts to control them. In countries such as India, Pakistan, and Sri Lanka, where eradication efforts had previously interrupted parasite transmission, the disease incidence has increased 100-fold in recent years. In tropical Africa, the intensity of transmission has been greatly reduced largely due to the compliant use of insecticide impregnated bed nets. Presently, approximately 2000 cases of imported malaria are reported to the Centers for Disease Control and Prevention. Most of these are the result of individuals travelling to malarious areas and not being compliant in taking prophylactic medicines.

Entamoeba spp., many of which are strictly commensalistic, are intestinal Protozoa that infect about 50% of the world’s population, with rates varying substantially depending on sanitary conditions. The pathogenic Entamoeba has historically been thought of as Entamoeba histolytica and it is estimated that up to 10% of the world’s population harbor this parasite. A noninvasive species, Entamoeba dispar, which is morphologically similar to E histolytica has been recognized and probably accounts for 90% of all reported E histolytica-like infections. The invasive E histolytica, which is morphologically identical to E dispar, produces amebiasis, a disease characterized by intestinal ulcers and liver abscesses. Rates up to 4% are seen in the United States. It is more commonly seen in areas of the world with poor sanitation, but occurs in the United States as well, particularly in institutions for the mentally retarded and among migrant workers and some male homosexuals.

In the poor, rural areas of Latin America, Trypanosoma cruzi infects an estimated 12 million individuals, leaving many with the characteristic heart and gastrointestinal lesions of Chagas disease that characterize the chronic phase of this disease. This parasite has a large reservoir host population, including many animals that live in peridomestic situations. This disease is transmitted by triatomine bugs that have also been found to be infected with T cruzi in the United States. In Africa, from the Sahara Desert in the north to the Kalahari in the south, related organisms, belonging to subspecies of the ancestral Trypanosoma brucei, cause one of the most lethal of human infections, sleeping sickness. Animal strains of this same organism limit food supplies by making the raising of cattle economically unfeasible over vast areas of the African continent. A large part of this latter problem is influenced by the activity of the vectors, members of the tsetse fly genus Glossina.

Leishmaniasis, a disease produced by an intracellular protozoan and transmitted by sandflies of the genus Phlebotomus, is found in parts of Europe, Asia, Africa, and Latin America. Clinical manifestations range from a self-limiting skin ulcer, known as oriental sore, through the mutilating mucocutaneous infection of espundia, to a highly lethal infection of the reticuloendothelial system (kala azar).

In 1947, in an article entitled “This Wormy World,” Stoll estimated that between the Tropic of Cancer and the Tropic of Capricorn, there were many more intestinal worm infections than people. The prevalence was judged to be far lower in temperate climates. The most serious of the helminthic diseases, schistosomiasis, affects an estimated 200 million individuals in Africa, Asia, and the Americas. These infections tend to be very chronic and persons with heavy worm burdens develop bladder, intestinal, and liver disease, which may ultimately result in death. The pathology accompanying schistosomiasis is largely the result of immune responses directed against eggs that get trapped in various tissues. Unfortunately, the disease is frequently spread because of rural development schemes involving irrigation projects. Egypt, Sudan, Ghana, and Nigeria have seen significant increases in the incidence of the disease in these areas due to extension of the snail vectors into new areas, often mitigating the economic gains of the development program itself.

The parasitic nematodes Ascaris lumbricoides, hookworms, and Trichuris infect more than 1.5 billion people. Collectively they account for tremendous morbidity that is manifest as reduced growth rates among children, iron deficiency, and anemia. Ascaris females can produce up to 250 000 extremely environmentally resistant eggs per day!

Larval tapeworm infections are a far more serious threat to human health than infections with adult tapeworms. This is exemplified by infection with the cysticercus of Taenia solium, which frequently results in neurocysticercosis. Another larval tapeworm infection caused by Echinococcus granulosus, results in hydatid cyst disease in humans. An endemic pocket of this disease exists in the four corners area of the United States.

Larval and adult nematode infections cause serious illness. Two closely related filarial worms, Wuchereria bancrofti and Brugia malayi, which are endemic in Asia and Africa and transmitted by many species of mosquitoes, interfere with the flow of lymph and can produce grotesque swellings of the legs, arms, and genitals. Another filarid, transmitted by black flies, produces onchocerciasis (river blindness) in millions of Africans and Americans, leaving thousands blind.

Toxoplasmosis, giardiasis, trichomoniasis, cryptosporidiosis, and pinworm (enterobiasis) infections are five cosmopolitan parasitic infections well known to American physicians. Toxoplasmosis, a protozoan infection of cats, infects possibly one-half of the world’s human population. Although it is usually asymptomatic, infection acquired in utero may result in abortion, stillbirth, prematurity, or severe neurologic defects in the newborn. Asymptomatic infection acquired either before or after birth may subsequently produce visual impairment. Immune suppression, such as caused by HIV infection and immunosuppressive therapy may reactivate latent infections, producing severe encephalitis.

Protozoa

Classification

The classification schemes for the Protozoa seem to be evolving even quicker than the organisms themselves. Within the context of this book a classification scheme used by classical parasitologists in textbooks has been adopted. It is based largely on light and electron microscopy and modes of locomotion, but considers current evolutionary thinking based on comparative genetics. Within the context of this scheme, the Protozoa are considered a subkingdom within the kingdom Protista.

The subkingdom Protozoa, includes the following phyla: Sarcomastigophora, including the flagellates and amebas; Apicomplexa, including malaria parasites, Cryptosporidium and Toxoplasma; Microsporidia, including the microsporidia; and Ciliophora, including the ciliates (Table 48–2).

The Sarcomastigophora are an extremely diverse group including true flagellates of the subphylum Mastigophora and parasites such as those belonging to the genera Leishmania, Trypanosoma, Giardia, Trichomonas, and Dientamoeba. Mastigophorans include those that are obligate intracellular parasites (Leishmania), parasites of the blood vascular system (Trypanosoma), intestinal track (Giardia), or genital–urinary track (Trichomonas). The subphylum Sarcodina can also be found within this phylum and include the important genera Entamoeba, Acanthamoeba, and the ameba–flagellate Naegleria.

The Apicomplexa also represent a diverse group of organisms that have been placed together phylogenetically because of the presence of complex apical organelles in life cycle stages responsible for cellular invasion. All are obligate intracellular parasites for most of their life cycles. Parasites in this taxonomic grouping include members of the genera Plasmodium, Toxoplasma, Cryptosporidium, Cyclospora, Isospora, Sarcocystis, and Babesia.

The Microsporidia include an opportunistically important group of parasites called the microsporidia. Many infections in this group are seen in immunocompromised patients with the more important genera being Enterocytozoon and Encephalitozoon. The Ciliophora include a single genus, Balantidium, which is only occasionally encountered in humans.

Form and Function

Protozoa range in size from slightly more than 1 to more than 100 μm. They are single-celled organism and have a true membrane-bound nucleus. The nucleus contains clumped or dispersed chromatin and a central nucleolus or karyosome. The shape, size, and distribution of the nucleus can be useful in distinguishing protozoan species from one another.

The cytoplasm is frequently divided into an inner endoplasm and a thin outer ectoplasm. The granular endoplasm is concerned with nutrition and often contains food reserves, contractile vacuoles, and undigested particulate matter. The ectoplasm may be organized into specialized organelles of locomotion. In some species, these organelles appear as blunt, dynamic extrusions known as pseudopods. In others, highly structured thread-like cilia or flagella arise from intracytoplasmic basal bodies. Flagella are longer and less numerous than cilia and possess a structure and a mode of action distinct from those seen in prokaryotic organisms.

Most parasitic Protozoa are heterotrophic and must assimilate organic nutrients. This assimilation is accomplished by engulfing soluble or particulate matter in digestive vacuoles, processes termed pinocytosis and phagocytosis, respectively. In some species, food is ingested at a definite site, the peristome or cytostome. Food may be retained in special intracellular reserves, or vacuoles. Undigested particles and wastes are extruded at the cell surface by mechanisms that are the reverse of those used in ingestion. The intracellular location of many of these parasites means that host cells may have to be modified to accommodate for transport and assimilation of nutrients. This is especially true among the apicomplexans and parasites like Leishmania. Many parasitic protozoans are facultative anaerobes in their definitive host (E histolytica and Giardia are excellent examples). The African trypanosomes must switch from an inefficient anaerobic to a more efficient mode of aerobic respiration when they take up residence in their vector. This is accomplished by profound changes that take place within the kinetoplast–mitochondrial complex of these organisms. The malaria parasite P falciparum has been found to complete its development within the microaerophilic environment of post capillary venules. This discovery now allows investigators to extensively cultivate this parasite in vitro. Some parasitic Protozoa are amitochondriate and utilize specialized organelles such as mitosomes (Giardia) or hydrogenosomes (T vaginalis) where terminal events of electron transfer in anaerobic respiration occur.

Survival is ensured by fastidious reproductive and protective techniques. Reproduction in many parasitic protozoans is accomplished primarily by simple binary fission. In one phylum of Protozoa, the Apicomplexa, a cycle of multiple fission (schizogony) alternates with a period of sexual reproduction (sporogony). A similar mode of reproduction is seen in the microsporidia although somewhat modified. Many Protozoa, when exposed to an unfavorable milieu, become less active metabolically and secrete a cyst wall capable of protecting the organism from physical and chemical conditions that would otherwise be lethal. In this form, the parasite is better equipped to survive passage from host to host in the external environment. Giardia, Entamoeba, Naegleria, Cryptosporidium, Cyclospora, and others are all capable of forming environmentally protective cysts or oocysts. The microsporidia produce spores. Immunoevasive mechanisms described in later chapters also contribute to survival of these parasites within the host.

Helminths

Classification

As for the Protozoa, the classification of helminth parasites is ever changing. The scheme used in this book is a more classical one and readily accepted and understood by most parasitologists. Accordingly, the various helminth groups discussed are placed into distinct phyla within the subkingdom Metazoa of the kingdom Animalia, which includes all multicellular organisms. These phyla include the Platyhelminthes with the important classes Trematoda (flat worms) and Cestoidea (tapeworm) the Nemathelminthes, or roundworms, and the Acanthocephala, or thorny-headed worms (Table 48–3).

The class Trematoda includes important parasites belonging to the genera Schistosoma, Fasciola, Fasciolopsis, Clonorchis, and Paragonimus. Cestoidea includes the tapeworm parasitic genera Diphyllobothrium, Taenia, Echinococcus, and Hymenolepis.

The Nemathelminthes include important parasites belonging to the genera Trichuris, Trichinella, Capillaria, Strongyloides, Necator, Ancylostoma, Ascaris, Toxocara, Wuchereria, Brugia, and Onchocerca.

The Acanthocephala contains only one genus, Macracanthorhynchus, considered to be of occasional importance to humans.

Form and Function

All helminths are multicellular organisms. The Trematoda vary in size from a few millimeters to several inches and are usually flat in shape. They all are invested in a tegument that is organized as a multicellular syncytium. Absorption of nutrients and excretion of wastes occur across the tegument. They are acoelomate with a body filled with parenchymal tissue. Embedded within this tissue are an incomplete digestive tract composed of ceca and the reproductive organs of both sexes. The schistosomes are an exception to this, have separate sexes, and are tubular in shape. Trematodes usually possess two suckers which help them to locomote and anchor to host tissue. Most trematodes have complex life cycles involving snails as a required first intermediate host in which asexual multiplication of larval stages takes place. Larval stages called cercaria emerge from snail and may either directly penetrate the final definitive host (the schistosomes), or encyst openly in the environment or within a second intermediate host (all other parasitic trematodes).

The Cestoidea, or tapeworms, have a flattened, ribbon-like body, or strobila, composed of segments called proglottids. Like the trematodes, they are invested in a tegument and are acoelomate with proglottids filled with parenchymal tissue. Each proglottid serves as an individual reproductive unit harboring both sets of male and female reproductive organs and are classified as being immature, mature, or gravid (egg filled). At the anterior end of the worm is a scolex (head region) that may or may not be armed with hooks. This body region is anchored to host tissue. Tapeworms continuously produce proglottids, which may be shed individually (apolysis) or as a chain once the eggs are released (anapolysis). They also possess a primitive nervous system that links the scolex to the proglottids. Tapeworms have complex life cycles that vary tremendously and will be discussed in chapters that follow. Infections by larval tapeworms usually result in greater pathogenesis to the host than infection by adult tapeworms. This is true of infections caused by Diphyllobothrium latum, T solium, E granulosus, and Echinococcus multilocularis.

The Nemathelminthes, or nematodes, have a cylindrical fusiform body and a tubular alimentary tract that extends from the mouth at the anterior end to the anus at the posterior end. They are invested in a tough cuticle that must be shed as they go through molts to become adults. They are considered as pseudocoelomate organisms with a body cavity filled with fluid. These worms possess only longitudinal muscles that allow them to flex and put pressure on internal organs so they can function. The sexes are separate, and the male worm is typically smaller than the female. An unusual feature in males is that sperms are ameboid and not flagellated. A variety of reproductive modes are used by these worms including oviparity (egg laying), ovoviviparity (egg followed by larval birth in utero), and parthenogenesis. First larval stages are considered as L₁ upon hatching and molt four times to become adults. Life cycles vary tremendously within this group from being direct (Trichuris), indirect, and complex (Strongyloides), to those requiring an intermediate host (all filarial parasites). These life cycles will be discussed in chapters to follow. Helminth parasites are nourished by ingestion (nematodes) or absorption (trematodes and cestodes) of the body fluids, lysed tissue, or intestinal contents of their hosts. Carbohydrates are rapidly metabolized, and the glycogen concentration of the worms is high. Respiration is primarily anaerobic, although larval offspring frequently require oxygen. A large part of the energy requirement is devoted to reproductive needs. The daily output of offspring can be as high as 200 000 for some worms.

Protection from the host’s digestive and body fluids is afforded by the tegument or cuticle and the secretion of enzymes. Some worms, such as the schistosomes, can protect themselves from immunologic attack by the incorporation of host antigens into their tegument. The life span of the adult helminth is often measured in weeks or months, but some, such as the hookworms, filariae, and flukes, can survive within their hosts for decades, producing chronic infections with attendant morbidity or mortality.

Parasites usually encounter one or more hosts during their life cycles, but the one host they must visit is the definitive host. This is the host in which the parasite reaches sexual maturity. Many protozoa do not have a sexual stage of the life cycle, in which case, if there is more than one host type in the life cycle, the more evolved host is usually considered the definitive host. Purists would argue that the mosquito is the definitive host for malaria because the sexual union of gametes occurs in that host, yet for this book, the definitive host is considered to be man. If some development of a parasite occurs in another host, then that host is considered an intermediate host. Snails are intermediate hosts for schistosome parasites and tsetse flies for most African trypanosomes. For one parasite, Trichinella, the same host is both a definitive and intermediate host, because adult sexually active worms reside in the intestinal tract and the first-stage larvae are nurtured within muscle cells of the same host. Snail and tsetse fly intermediate hosts may also be considered vectors. However, there can be vectors in which no development takes place. Such a vector is then considered a mechanical vector. Such a host can also be referred to as a paratenic or transport host. Flies are considered transport hosts for Giardia, Cryptosporidium, and E histolytica. For many parasites there are also reservoir hosts. Such a host is a reservoir of infection from which other hosts can be infected. The East African trypanosomes have many ungulate species as reservoir hosts. These animals are considered as definitive hosts as well.

Some parasites, such as Cryptosporidium hominis and Cyclospora cayetanensis are highly host specific. In these cases, humans are the only hosts. Cryptosporidium parvum, on the other hand is a zoonotic species with many animals serving as reservoirs from which man can become infected. Trichinella, mentioned earlier, is an example of a parasite that has loose host specificity. Any carnivorous animal can serve as a host for this parasite.

Parasitic infections that are transmissible from animals to humans are considered zoonotic. Many parasitic infections considered in the following chapters fall into this category. Those transmissible from humans to humans or back to animals are considered anthroponotic. Cryptosporidium hominis is readily transmissible from humans to humans, and some of the primate malarias encountered in South America are thought to have arisen from human malarias brought to the new world after colonization. Transmission patterns that only involve animals are considered enzootic. If a transmission pattern occurs in association with man, it is considered synanthropic. Many parasitic infections fall into this pattern of transmission. Transmission patterns may also involve life cycles occurring away from man and these usually involve animal hosts and are considered sylvatic. Echinococcus granulosus has a synanthropic cycle involving dogs, sheep, and man, and a sylvatic cycle involving deer and coyotes or moose and wolves.

Single-Host Parasite Life Cycle Examples

As is evident from the previous discussion, many parasites require but a single host species for the completion of their life cycles. The method by which the parasite is transmitted from individual to individual within that species is determined in large part by its viability in the external environment and, in the case of helminths, by the conditions required for the maturation of eggs or offspring. The mode of transmission, in turn, determines the social, economic, and geographic distribution of the parasite. A few examples are described in Table 48–4.

The protozoan T vaginalis does not produce a protective cyst form. Although its active or trophozoite form is relatively hardy, it can survive only a few hours outside of its normal habitat, the human genital tract. Thus, for all practical purposes, transmission requires the direct genital contact of sexual intercourse. Thus, trichomoniasis is cosmopolitan, occurring wherever human hosts engage in sexual activity with multiple partners.

Another protozoan, E histolytica, inhabits the human gut and produces hardy cysts that are passed in the stool. Transmission occurs when another individual ingests these cysts. Like T vaginalis, the organism can be passed by direct physical contact, in this case by oral–anal sexual activity. This mode of transmission, in fact, accounts for the high incidence of amebic infections in male homosexuals. Unlike T vaginalis, however, the cysts can survive for prolonged periods in the external environment, where they may eventually contaminate food or drinking water. Thus, in environments such as mental institutions, where the level of personal hygiene is low, or in populations in which methods for the sanitary disposal of human wastes are not available, amebiasis is common.

The intestinal helminth A lumbricoides illustrates still another transmission pattern. In this infection, highly resistant eggs are passed in the human stool. Unlike the situation with E histolytica described previously, the eggs are not immediately infective but must incubate in soil under certain conditions of temperature and humidity before they are fully embryonated and infectious. Thus, this parasite cannot be transmitted directly from host to host. The organism spreads only when indiscriminate human defecation results in deposition of eggs on soil and subsequent exposure of that soil to the climatic conditions required for embryonation of the eggs. For this reason, Ascaris infections are most prevalent in areas of the tropics and subtropics and are associated with poor sanitation.

Multiple-Host Parasite Life Cycle Examples

A few Protozoa and many helminths require two or more host species in their life cycle. As stated previously, to avoid confusion, it is customary to refer to the species in which the parasite reproduces sexually as the definitive host and that in which asexual reproduction or larval development takes place as the intermediate host. When there is more than one intermediate host, they are known simply as the first and second intermediate hosts. In some cases, such as that of Taenia saginata, the beef tapeworm, both host species are vertebrates; humans serve as the definitive host and cattle as the intermediate host. Among parasites that inhabit the blood and tissues of humans, it is more common for a blood-feeding arthropod to serve as a second host and as the transmitting vector. An example is malaria, in which the causative Plasmodium is transmitted from person-to-person by the bite of an infected female mosquito of the genus Anopheles. As mentioned previously, people argue whether mosquito or man is the definitive host as the sexual union of gametes occurs in the mosquito.