eMedicine Specialties > Pediatrics: General Medicine > Parasitology
Ancylostoma Infection
Updated: May 1, 2008
Introduction
Background
Hookworm is the common name for blood-sucking nematodes of the Ancylostomatidae family. The 2 species that most commonly infect humans are Ancylostoma duodenale and Necator americanus.
Members of the Ancylostoma genus cause the following 3 clinical entities in humans:
- Classic hookworm disease is a GI infection with chronic blood loss that leads to iron deficiency anemia and protein malnutrition. The disease is caused by A duodenale, the major anthropophilic hookworm, and, less commonly, by the zoonotic species Ancylostoma ceylanicum.
- Cutaneous larva migrans is an infection caused most commonly by larvae of Ancylostoma braziliense, whose definitive hosts include dogs and cats. The manifestations of cutaneous larva migrans are limited to the skin.
- Eosinophilic enteritis is a GI infection caused by the dog hookworm Ancylostoma caninum.1 The disease is characterized by abdominal pain but no blood loss.
N americanus causes only classic hookworm disease, as defined above.
In 1880, an epidemic called miners' anemia occurred among Italian laborers building the Saint Gotthard railway tunnel in the Swiss Alps. A duodenale was responsible for the epidemic.
Pathophysiology
Eggs deposited on warm, moist soil develop into infective larvae over 5-7 days. Infective larvae are developmentally arrested and nonfeeding. If unable to infect a new host, the larvae die when their metabolic reserves are exhausted, usually in about 6 weeks. Humans are the major reservoir, and infection is maintained by continual contamination of soil by human feces.
Classic hookworm infection
The life cycle of hookworms is depicted in Media file 1. Humans acquire infection either by exposing skin to soil contaminated with A duodenale larvae or N americanus larvae or by ingesting soil contaminated with A duodenale larvae.
Eggs are passed in the stool undefined, and the larvae hatch in 1-2 days under favorable conditions (see Media file 2). The released rhabditiform larvae grow in the feces and/or soil undefined (see Media file 3). After 5-10 days, they become filariform larvae that are infective (see Media file 4). These infective larvae can survive for 3-4 weeks in favorable environmental conditions.
Upon contact with the human host, the larvae penetrate the skin. The larvae elaborate a protease that helps the organisms bore through the skin. The larvae are carried through the veins to the heart and then to the lungs. They penetrate the pulmonary alveoli, ascend the bronchial tree to the pharynx, and are swallowed. During the migratory phase, larvae evoke an eosinophilic inflammatory response.
After passively reaching the proximal small intestine, larvae develop into adult, sexually mature male and female worms. The adult worm attaches with its mouth to the mucosa of the small intestine and begins to feed. The hookworm digests the tissue within its buccal capsule, using its teeth or cutting plates, powerful esophageal muscles, and hydrolytic enzymes. At the same time, the worm releases a potent anticoagulant, which causes profound bleeding from eroded capillaries in the lamina propria.
Larvae require about 6-8 weeks from the time of skin penetration to develop into adults. Worms mate in the small intestine, and the females deposit fertilized eggs into the lumen. Eggs begin to appear in feces about 8-12 weeks after infection. Worms change location every 4-8 hours, producing minute, bleeding, mucosal ulcerations. Adult worms are eliminated in 1-2 years, but longevity records can reach several years.
Following penetration of the host skin, some A duodenale larvae can become dormant (in the intestine or muscle). In addition, infection by A duodenale may also occur by the oral and transmammary route. However, N americanus requires a transpulmonary migration phase.
Larva migrans
The infective larvae of zoonotic species such as A braziliense do not elaborate sufficient concentrations of hydrolytic enzymes to penetrate the junction of the dermis and epidermis. These larvae remain trapped superficial to this layer, where they migrate laterally at a rate of 1-2 cm/d and create the pathognomonic serpiginous tunnels of cutaneous larva migrans. Larvae can survive in the skin for about 10 days before dying (even in untreated persons).
Eosinophilic enteritis
Larvae of A caninum typically enter a human host by skin penetration, although infection by oral ingestion is possible. These larvae probably remain dormant in skeletal muscles and create no symptoms.
In some individuals, larvae may reach the gut and mature into adult worms. Why some individuals sustain A caninum development and then respond with a severe localized allergic reaction is unknown.
Adult worms secrete various potential allergens into the intestinal mucosa. Some patients have been reported to have increasingly severe recurrent abdominal pain, which may be analogous to a response to repeated insect stings.
Frequency
United States
Classic hookworm infection is most common among travelers, immigrants, and adoptees from developing countries. A low prevalence of the infection, mainly due to N americanus, is still found in pockets of the southeastern United States.
Cutaneous larva migrans is endemic in the southeastern states and Puerto Rico. The dog hookworm, A caninum, has reportedly caused eosinophilic enteritis in Australia and the United States; increased human infections are anticipated because of the global distribution of dogs.
International
Human infection with A duodenale and N americanus is estimated to affect approximately one fourth of the world's population. These parasites drain the equivalent of all the blood from approximately 1.5 million people every day. Infection is most prevalent in tropical and subtropical zones, roughly between the latitudes of 45°N and 30°S. Hookworm infection occurs only in isolated temperate areas.
Infection is endemic in most developing countries. However, even in endemic regions, infection is usually confined to rural areas, especially where human feces are used as fertilizer or where sanitation is inadequate. In developed countries, infection is most commonly encountered in travelers, immigrants, and adoptees from developing countries.
A duodenale is the predominant species in the Mediterranean region, in northern regions of India and China, and in North Africa. A ceylanicum is found in focally endemic areas in southern Asia. N americanus is the predominant species in southern China, Southeast Asia, the Americas, most of Africa, and parts of Australia. This differential distribution is not absolute, and mixed infections with both species are common in individual patients.
Mortality/Morbidity
- As is true with most helminthic infections in endemic areas, relatively few persons carry heavy parasite burdens, although hookworm disease may be fatal, especially in infants.
- A single adult A duodenale causes about 0.2 mL of blood loss per day, and each adult N americanus causes about 0.02 mL blood loss per day.
- The extent of infection may be categorized as light (ie, <100 worms), moderate (ie, 100-500 worms), or heavy (ie, 500-1000 worms). People who develop an initial heavy infection seem to reacquire heavy infection, and individuals who are lightly infected reacquire light infections, which suggests an underlying genetic susceptibility.
- Individuals with light infection have minimal blood loss and may have infection but not disease, especially if iron intake or reserves are adequate to compensate for the blood loss.
- Moderate-to-heavy infections cause iron deficiency anemia.
- Hookworm anemia may be noted.
- Hookworms are the leading cause of iron deficiency anemia in developing countries.
- In one study involving 492 children, in children with N americanus, the prevalence of anemia and the prevalence of ferritin levels of less than 12 μ g/L were 60.5% and 33.1%, respectively; in children with A duodenale, the respective prevalences were 80.6% and 58.9%.2
- The timing of anemia onset depends on the patient's preexisting iron stores.
- Because iron is also required for the biosynthesis of neurotransmitters, anemia may affect cognitive development.
- Significant anemia can cause growth and developmental delay.
- Malabsorption may occur.
- Heavy infections can cause significant protein loss as the host loses RBCs and plasma.
- Adult hookworms also secrete a potent inhibitor of digestive enzymes, which may contribute to malabsorption.
- Malabsorption leads to hypoproteinemia, which aggravates malnutrition.
- Malabsorption is more common in children than in adults.
- Anemia and protein malnutrition occur together in as many as 25% of infected individuals.
Sex
- Both sexes are equally susceptible.
Age
- In endemic areas, the highest prevalence is among school-aged children and adolescents, which may be because of age-related changes in exposure and the acquisition of immunity.
- Once infected, children are more vulnerable to developing morbidity because dietary intake often fails to compensate for intestinal losses of iron and protein, especially in developing countries.
- A fulminant form of acute GI hemorrhage associated with acute ancylostoma infection has been described in newborns.
Clinical
History
- Acute stage of classic hookworm disease
- Pruritus at the site of larval penetration (also called ground itch or dew itch) is proportionate to the number of infecting larvae. Infection with zoonotic hookworms, especially A braziliense, can progress with a lateral migration of larvae that results in cutaneous tracts of larva migrans.
- Cough and wheezing can occur about one week after exposure and is due to larval migration through the lungs. Unlike that in ascariasis, pulmonary symptoms are uncommon and usually mild, except in severe infections.
- An acute intestinal phase occurs in heavy infections and is characterized by abdominal pain, nausea, anorexia, and diarrhea that usually develops around one month after infection.
- Wakana disease is characterized by nausea, vomiting, dyspnea, and eosinophilia and occurs after the oral ingestion of a large number of infective A duodenale larvae. This may represent a severe immediate hypersensitivitylike reaction to A duodenale antigens.
- Chronic stage of classic hookworm disease
- Moderate-to-heavy infections cause significant blood loss, which may manifest as melena. Once iron reserves are exhausted, anemia develops and causes symptoms such as fatigue and dyspnea upon exertion.
- Deficits in physical and intellectual growth can occur, which may be irreversible when they occur during infancy.
- Eosinophilic enteritis: This is characterized by repeated episodes of abdominal pain in approximately 97% of affected individuals. These episodes typically occur with increasing severity and are associated with peripheral eosinophilia in almost 100% of patients and with leukocytosis in approximately 75% of patients. Extreme cases may mimic appendicitis or intestinal perforation.
Physical
- Acute stage of classic hookworm disease
- Erythema with small papules or vesicles develops at the site of larval entry, typically on the feet, and usually persists for 1-2 weeks.
- Intense scratching may lead to a secondary bacterial infection, which is quite common.
- Scattered wheezing may be heard during larval migration through the pulmonary system.
- Chronic stage of classic hookworm disease
- Pallor, chlorosis (greenish yellow skin discoloration), tachycardia, and other signs of high-output cardiac failure are caused by anemia.
- Edema is caused by hypoproteinemia.
- Signs of malnutrition are evident.
- Cutaneous larva migrans: This manifests as pathognomonic, raised serpiginous tracts ("creeping eruptions") with surrounding erythema that may last one month if untreated. Lesions are most commonly seen on lower extremities but may be limited to the trunk or upper extremities based on the site of entry of infective larvae.
Causes
- Several Ancylostoma species cause disease in humans, such as the following:
- A duodenale primarily infects humans and is responsible for classic hookworm disease.
- A ceylanicum primarily infects animals but can cause milder classic hookworm disease in humans.
- A braziliense and A caninum also primarily infect animals (eg, cats, dogs); humans are accidental hosts. Both species can cause cutaneous larva migrans, although most cases are caused by A braziliense. A caninum causes eosinophilic enteritis.
- Hookworm microbiology includes the following:
- Each adult A duodenale is about 1 cm in length. The buccal capsule of an adult worm has teeth to facilitate attachment to mucosa. A muscular esophagus creates suction in the buccal capsule.
- Adult worms release hyaluronidase, which degrades intestinal mucosa and erodes blood vessels, resulting in blood extravasation. Worms also ingest some blood. An anticoagulant facilitates blood flow by blocking the activity of blood coagulation factors Xa and VIIa.
- Adult worms also elaborate factors (eg, neutrophil inhibitory factor), which protect them from host defenses.
- Each mature A duodenale female produces about 10,000-30,000 eggs daily; a female N americanus produces 5000-10,000 eggs daily. Under appropriate conditions, eggs develop into infective larvae.
- Infective larvae are barely visible to the naked eye (ie, about 500-700 µm in length).
- The natural life span is about one year for an adult A duodenale and 3-5 years for an adult N americanus.
- The larvae's ability to enter a dormant state in the human host may be an adaptive response to increase the chances of propagation. If all larvae were to mature promptly during dry seasons of the year, females would release eggs onto inhospitable soil. Eggs produced and released during the wet season have a much greater chance of encountering optimal soil conditions for further development.
- Environmental conditions include the following:
- The optimal conditions for egg development in soil are ambient temperatures of 20-30°C and warm, moist, well-aerated soil that is shielded from sunlight. These conditions occur during cultivation of numerous agricultural products (eg, tea in India, mulberry leaves in China, coffee in Central and South America, rubber in Africa). Hence, hookworm infections occur primarily in rural areas.
- Larvae fail to develop in temperatures below 13°C and are destroyed by temperatures below 0°C and above 45°C. Drying and direct sunlight also kill larvae.
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Further Reading
Keywords
hookworm infection, hookworm, hookworm disease, Ancylostomatidae, Ancylostoma duodenale, Necator americanus, Ancylostoma caninum, Ancylostoma ceylanicum, Ancylostoma braziliense, cutaneous larva migrans, eosinophilic enteritis, iron deficiency anemia, protein malnutrition, iron deficiency anemia, protein malnutrition, helminthic infections, hookworm anemia, malabsorption, hypoproteinemia, malnutrition, GI hemorrhage, ancylostoma infection, ground itch, dew itch, Wakana disease, melena, leukocytosis, erythema
Overview: Ancylostoma Infection