Introduction to Helminth Infections

James H. Maguire *

Keywords

anthelmintics; cestodes; disease elimination or eradication; eosinophilia; helminths; mass drug administration; nematodes; parasitism; trematodes

The helminthiases are among the most prevalent infections in the world and a leading cause of morbidity, particularly in low-income and resource-constrained regions. More than one billion persons harbor at least one species of parasitic worm.¹^,² The helminths that parasitize humans include the nematodes (roundworms) and platyhelminths (flatworms); the latter group consists of cestodes (tapeworms) and trematodes (schistosomes and other flukes). Leeches, ectoparasites belonging to the phylum Annelida (segmented worms), are not discussed here (see Chapter 293). Some helminths are exclusively or primarily human parasites, whereas others parasitize both humans and various other mammals, and others are parasites of lower mammals and infect human beings incidentally.

Biology of Helminths

Helminths are multicellular organisms that range from less than 1 cm to more than 10 m in length. They are covered by a cuticle or tegument that protects them from digestion and environmental stresses. Reproductive organs take up a large part of the body regardless of whether the sexes are separate or the species is hermaphroditic, as is the case with cestodes and nonschistosomal trematodes. Neuromuscular, digestive, excretory, and secretory systems typically are smaller and less complex, in keeping with the parasitic state.

The life cycle of all worms includes an egg, one or more larval stages, and the adult. Transmission to humans occurs by ingestion of helminth eggs or larvae, penetration of intact skin by larvae, or inoculation of larvae by biting insects. Depending on the species, humans are the only host; the intermediate host, in which asexual reproduction takes place; or, when there are one or two intermediate hosts, the definitive host in which sexual reproduction occurs. Most helminths are unable to complete their life cycle within the human host, and development of eggs or larvae on soil, in water, within a plant, arthropod, or other animal intermediate host is necessary. Hence, the geographic distribution of these parasites reflects the environmental conditions necessary for development of eggs or larvae or for survival of intermediate hosts and vectors. The only way for the intensity of infection in a person to increase is by further exposure to the infective stage; in the absence of continued exposure, the infection lasts only as long as the life span of the adult worm. In contrast, a few species, most notably Strongyloides stercoralis, are able to reproduce and multiply in numbers within the definitive human host. In the case of Strongyloides, infectious larvae can be passed directly from one person to another, and transmission is possible in all geographic areas. Infection can persist for the life span of the host, and in the setting of immunosuppression, accelerated autoinfection can lead to overwhelming numbers of organisms even after a distant and light exposure.

Epidemiology

The prevalence of helminth disease is highest in warm, developing areas, where climate, environment, and an abundance of vectors favor completion of the life cycle and where poverty leads to increased exposure to parasites because of poor sanitation, lack of clean water, and inadequate housing. Human activity can facilitate transmission, as seen in the huge numbers of new cases of schistosomiasis and foodborne trematode infections resulting from water resource development projects for hydroelectric power, irrigation, and aquaculture.³^,⁴ Conversely, in some endemic areas, large-scale control programs have led to interruption or dramatically decreased transmission of dracunculiasis (guinea worm disease), filariasis, onchocerciasis, and other parasitic worms.⁵ Helminth infections are less common in temperate and industrialized areas, where they have been imported after travel or residence in tropical areas or acquired locally from domestic or wild animals, via improperly prepared meat, fish, or vegetables, or from close personal contact, as in the case of pinworm infections.

Helminths produce large numbers of eggs or larvae and have a high reproductive capacity, which can lead to an extremely high prevalence of human infection when conditions are conducive to transmission, such as in rural areas in the tropics. Helminths are not uniformly distributed in human populations but are overdispersed, with most infected individuals harboring low worm burdens and only a small number harboring heavy infections.⁶ The basis for aggregation of helminths in human populations may be related to the intrinsic biology of the parasites and density-dependent constraints on parasites, such as competition for nutrients, parasite-induced pathology, and host factors, including genetic susceptibility to infection, immunity, nutrition, and behavioral factors.

Pathogenesis and Host-Parasite Relationship

Most infected persons harbor few worms and have few or no signs or symptoms of disease, whereas a small proportion of persons with large numbers of worms are at risk of severe disease. Children with even moderate numbers of worms may be at risk of malnutrition, impaired growth, and impaired intellectual development.⁷^,⁸ Polyparasitism is widespread throughout the tropics and subtropics, and infection with multiple species of helminths seems to have an additive or multiplicative effect on nutrition and pathology.⁹ Although mortality rates attributable to helminth infections are low, rates of chronic morbidity and debilitation are substantial.

Helminths produce disease by a variety of mechanisms, including mechanical effects such as intestinal obstruction (e.g., ascariasis), invasion of host cells or tissues with damage or loss of function (e.g., trichinellosis), or competition for nutrients (e.g., vitamin B₁₂ deficiency from fish tapeworm infection). The host responses may lead to immunopathologic lesions, such as schistosome egg granulomas, which contribute significantly to disease. Interactions with other pathogens or potential carcinogens may contribute to chronic sequelae, such as advanced liver disease associated with coinfection of hepatitis B or C with Schistosoma mansoni or bladder cancer associated with Schistosoma haematobium.¹⁰

Basic to understanding the pathogenesis of helminthiasis is an appreciation of the size of the organisms, the multiplicity of their antigens, and the chronicity of the infection. Host responses are composed of myriad immunologic and nonimmunologic factors, some of which contribute to disease. Sterilizing immunity to helminth infections does not develop, and the extent to which previous infections with helminths lead to resistance to subsequent reinfection is not well defined. A degree of acquired immunity has been shown in infected individuals who were cured chemotherapeutically and then continued to live under the same conditions of exposure to infection.¹¹ These findings suggest that induction of resistance by vaccines may be a viable control strategy.

Eosinophilia is a characteristic of many helminth infections. Peripheral blood, bone marrow, and tissue eosinophilia is associated with the migration or presence of worms in tissues. Eosinophilia is not observed in infections with helminths that reside in the lumen of the human gut (e.g., tapeworms) or are contained in cystic structures (e.g., echinococcal cysts). Eosinophils seem to play a significant role in the killing of helminths and host resistance to helminth infections and are responsible for a considerable amount of inflammatory pathology.¹² Chronic infection with worms typically leads to a constant state of immune activation characterized by a dominant Th2 type of cytokine profile and high immunoglobulin E levels, as well as proliferation and activation of eosinophils.¹³ It is hypothesized that such an immune profile may have an adverse impact on the efficacy of vaccines against other classes of organisms¹⁴ and progression of other infections, such as malaria and human immunodeficiency virus/acquired immunodeficiency syndrome.¹⁵^,¹⁶ Helminth infections may affect the expression of allergic disease and, in some studies, were associated with decreased risk of asthma and other atopic conditions, although other studies showed increased or no risk.¹⁷^,¹⁸

Worms have successfully developed multiple strategies to evade host protective responses. Mechanisms include encapsulation within a host fibrous reaction (hydatid cyst), intraluminal location (e.g., Ascaris), inhibition and modulation of the immune response (filariae, cysticerci), and acquisition of host antigens (schistosomes).

Diagnosis and Treatment of Helminth Infections

Recognition of helminth infections requires knowledge of their clinical presentation, geographic distribution, and epidemiologic risk factors. Persons with light infections may be asymptomatic, and the only clues to diagnosis may be a history of travel and potential exposure to the parasite as well as peripheral blood eosinophilia. It should be kept in mind, however, that eosinophilia may be absent, even in persons with invasive infections. The diagnosis of helminth infections rests heavily on microscopic examination of stool, urine, blood, other body fluids, and tissue (Table 287-1).¹⁹^,²⁰ When eggs or larvae are produced in abundance, microscopy can be extremely sensitive, but multiple examinations or concentration procedures may be necessary to detect light infections or infections with organisms such as Strongyloides, which often shed low numbers of larvae in the stool. Serologic tests may offer greater sensitivity than microscopic examination and may be the only way to avoid invasive diagnostic procedures for infections with tissue-invading helminths. Some serologic tests for helminths are available only from reference laboratories, and they may lack sensitivity or specificity and not distinguish between past and present infections. Assays to detect helminth antigens and molecular diagnostic techniques, used mostly for research purposes and monitoring and evaluating control programs, are expected to play a greater role in future diagnosis and management of individual patients.²¹ Detailed information on laboratory procedures for diagnosis of parasitic infections, an image library, and instructions for obtaining prompt assistance in diagnosis is available on DPDx, the parasitology diagnostic website of the Centers for Disease Control and Prevention (http://dpd.cdc.gov/dpdx).

Table 287-1

Diagnosis of Major Helminth Infections

	MICROSCOPIC DIAGNOSIS
PARASITE	Stage	Specimen	OTHER METHODS
Roundworms (Nematodes)
Intestinal Roundworms
Ascaris lumbricoides (large intestinal roundworm)	Eggs	Feces	Identification of passed worm
Trichuris trichiura (whipworm)	Eggs	Feces
Ancylostoma duodenale, Necator americanus (hookworm)	Eggs, larvae	Feces
Strongyloides stercoralis (threadworm)	Larvae	Feces, duodenal fluid, sputum	Serology*
Enterobius vermicularis (pinworm)	Eggs	Swab of perianal skin; occasionally in feces	Cellophane tape test; identification of adult worms on skin
Tissue Roundworms
Trichinella spiralis (trichinellosis)	Larvae	Muscle biopsy	Serology*
Dracunculus medinensis (guinea worm)			Identification of emergent adult worm
Wuchereria bancrofti, Brugia malayi (lymphatic filariasis)	Microfilariae	Blood, urine (in setting of chyluria)	Serology,* antigen test (blood)
Loa loa (African eye worm)	Microfilariae	Blood	Identification of adult worm in eye, serology
Onchocerca volvulus (river blindness)	Microfilariae	Skin snip	Identification of adult worm in resected nodules
Ancylostoma braziliense, other species (cutaneous larva migrans, creeping eruption)			Inspection of rash
Toxocara canis, Toxocara cati (visceral larva migrans), Baylisascaris procyonis	Larvae	Biopsy of liver, other tissues (usually not necessary)	Serology* (preferred)
Flukes (Trematodes)
Schistosoma mansoni, Schistosoma haematobium, Schistosoma japonicum, Schistosoma mekongi	Eggs	Feces, rectal snips, urine (S. haematobium)	Serology,* antigen test (serum and urine)
Fasciolopsis buski (intestinal fluke)	Eggs	Feces
Heterophyes heterophyes (intestinal fluke)	Eggs	Feces
Metagonimus yokogawai (intestinal fluke)	Eggs	Feces
Clonorchis sinensis, Opisthorchis spp. (liver fluke)	Eggs	Feces, bile	Serology
Fasciola hepatica (liver fluke)	Eggs	Feces, bile	Serology
Paragonimus spp. (lung fluke)	Eggs	Sputum, feces	Serology*
Tapeworms (Cestodes)
Intestinal Tapeworms
Taenia saginata (beef tapeworm)	Eggs	Stool	Identification of passed proglottid (segment)
Hymenolepis nana (dwarf tapeworm)	Eggs	Stool
Diphyllobothrium latum (fish tapeworm)	Eggs	Stool	Identification of passed proglottid
Taenia solium (pork tapeworm)	Eggs	Stool	Identification of passed proglottid; stool antigen test; serology
Larval Tapeworms
Echinococcus granulosus (cystic hydatid disease)	Protoscolices, hooklets	Fluid from cyst	Serology,* CT, MRI, or ultrasonography can be diagnostic
Echinococcus multilocularis (alveolar hydatid disease)	Larvae	Liver biopsy	Serology
Cysticercus (larval Taenia solium)	Larvae	Brain biopsy	Serology,* CT, or MRI of head can be diagnostic