Hookworms

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Hookworms

AUTHOR AND EDITOR INFORMATION

 

Author: David R Haburchak, MD, Program Director, Professor, Department of

Internal Medicine, Division of Infectious Disease, Medical College of

Georgia

 

David R Haburchak is a member of the following medical societies: Infectious

Diseases Society of America

 

Editors: Pranatharthi Haran Chandrasekar, MD, Director of Infectious Disease

Fellowship, Professor, Department of Internal Medicine, Harper Hospital,

Wayne State University School of Medicine; Francisco Talavera, PharmD, PhD,

Senior Pharmacy Editor, eMedicine; Ronald A Greenfield, MD, Professor,

Department of Internal Medicine, Section of Infectious Diseases, University

of Oklahoma College of Medicine; Eleftherios Mylonakis, MD, Clinical and

Research Fellow, Department of Internal Medicine, Division of Infectious

Diseases, Massachusetts General Hospital; Burke A Cunha, MD, Professor of

Medicine, State University of New York School of Medicine at Stony Brook;

Chief, Infectious Disease Division, Winthrop-University Hospital

 

Author and Editor Disclosure

 

Synonyms and related keywords: hookworms, hookworm, nematodes, nematode

infection, Ancylostoma duodenale, A duodenale, Necator americanus, N

americanus, Ascaris species, helminthiasis, Trichuris species, Strongyloides

species, hookworm infection, hookworm infestation, ground itch

 

 

[image: Healthverve] <http://www.healthverve.blogspot.com>

 

 

[image: Healthverve] <http://www.healthverve.blogspot.com>

 

 

 

INTRODUCTION

 

Background

 

Hookworms represent a widespread and clinically important human nematode

infection. Prevalence figures indicate that the roundworms Ancylostoma

duodenale and Necator americanus infect 576-740 million people and that they

cause anemia in approximately 10% of those infected. Hookworms may persist

for many years in the host and impair the physical and intellectual

development of children and the economic development of communities.

 

Hookworm infection is acquired through skin exposure to larvae in soil

contaminated by human feces. Adults, especially agricultural workers, are at

equal or higher risk of exposure than children. Soil becomes infectious

about 9 days after contamination and remains so for about 2 weeks.

Individual hookworm treatment consists of iron replacement and anthelmintic

therapy. Community eradication has proven difficult, even with intensive,

yearly, school-based programs. Despite this, successful control and

eradication of hookworms is a worthy goal for new methods that would offer

huge economic and social benefits to much of Africa and Asia.

Pathophysiology

 

Necator and Ancylostoma adults are roundworms that range in length from 5-13

mm. Females release thousands of eggs into stool daily. In sandy moist soil,

eggs hatch and must molt twice before developing into third-stage larvae.

 

Third-stage larvae are 500-700 µm long and are capable of rapid penetration

into normal skin, most commonly of the feet. Transmission occurs after 5 or

more minutes of skin contact with soil that contains viable larvae. They

puncture and feed on mucosal capillaries in the jejunum. Ground itch at the

site of penetration is more common with Ancylostoma species than with

Necator.

 

The larvae burrow into venules and embolize the lungs, where they break into

alveoli. A mild and usually asymptomatic alveolitis with eosinophilia

ensues. (Hookworm is one of the causes of the pulmonary infiltrates and

eosinophilia [PIE] syndrome, along with Ascaris and Strongyloides species.)

Coughing brings the larvae to the mouth, where swallowing transports them to

the intestine. Approximately 5 weeks after skin penetration, adult females

begin to produce eggs.

 

Ancylostoma larvae may also infect via ingestion, but they do not migrate

into the body in this instance. This worm may lie dormant in tissues and

later be transmitted through breast milk. Neither worm multiplies within the

host. If the host is not reexposed, the infection disappears after the worm

dies. Necator has a 5-year lifespan; Ancylostoma has a 1-year lifespan.

 

Each Necator worm ingests 0.03 mL of blood per day; each Ancylostoma worm

ingests 0.2 mL of blood per day. Subsequent host anemia is proportional to

diet, iron reserves, and worm burden. Threshold worm loads for anemia differ

nationally, with as few as 40 worms producing anemia in countries with low

iron consumption. Severe anemia affects intellectual and physical

development in children and the cardiovascular performance in adults.

 

In the 19th century, an autopsy of an Italian tunnel worker who died of

anemia revealed 1500 worms. Before worker sanitation was enforced, epidemic

hookworm infection was common in mines and tunnels in Europe.

 

Recent work has suggested that malnutrition and immunocompromise,

independent of anemia, can occur in children and adults with significant

infection. This is the result of a protein-losing enteropathy, with

immunoglobulins among the proteins lost, as a result of worm digestion. This

results in stunted growth, as well as an increased susceptibility to

infections such as malaria and gastrointestinal disease. This protein-losing

enteropathy can also contribute to a more rapid progression of an HIV

infection.

 

Apparently, the risk of atopy and dust-mite sensitization is inversely

related to the burden of hookworm infestation in endemic areas. Whether this

relationship is causative in either direction remains undetermined. The

production of interleukin (IL)–5 during primary hookworm infection appears

to enhance eosinophil function in limiting second-episode infection by

invading larvae. Worms, however, also seem to provoke IL-10, IL-4, IL-5, and

IL-13, which shift the cytokine response toward T helper 2 cells rather than

toward T helper 1 cells. Hookworms also appear to secrete an inhibitor or

natural killer cells, thereby suppressing production of gamma-interferon and

the T helper 2 response that would be expected to clear the parasite. The

increased prevalence of atopy, asthma, and food allergy in areas free of

worm infestation has been cited as supportive of the hygiene hypothesis and

even prompted investigation of worms as therapy for such diseases.

 

In the search for possible vaccine targets, investigators have ascertained

the existence of hookworm molecular inhibitors of coagulation factors Xa and

VIIa-tissue factor and metalloproteases that degrade hemoglobin and

intestinal mucosal cells. ASP-2, a protein isolated from larval N

americanus, appears necessary for chemokine receptor binding and invasion

and has shown some promise in animal vaccine trials.

Frequency

United States

 

Although hookworm infection is now thought to be rare in the United States,

hookworm played an important role in the impoverishment of the South until

the 1930s. Studies performed in the early 1970s indicated prevalence as high

as 14.8% among schoolchildren from rural Kentucky and as high as 12% among

schoolchildren from rural coastal Georgia. Infection and disease are now

most likely to be found in immigrants and refugees from tropical countries.

Occasionally, persons returning from travel abroad present with acute watery

diarrhea with eosinophilia upon return to the United States.

International

 

Infection is widely distributed throughout tropical and subtropical areas,

with prevalence in some communities as high as 90%. The disease flourishes

in rural communities with moist shaded soil and inadequate latrines.

Agricultural laborers have traditionally been at high risk of hookworm

infection. Improper disposal of human feces and the common habit of walking

barefoot are important epidemiologic features. However, the use of footwear

has not been shown to affect hookworm prevalence, as the larvae can invade

through any skin surface.

 

In 2005, The World Health Organization (WHO) estimated that 198 million

individuals in sub-Saharan Africa were infected with hookworms, 149 million

in East Asia/Pacific, 71 million in India, 59 million in other parts of

South Asia, 50 million in Latin America and the Caribbean, 39 million in

China, and 10 million in the Middle East and North Africa. Both Necator and

Ancylostoma species have worldwide distribution, but Necator is more

prevalent in Africa. Co-infection with Ascaris and Trichuris species is

common in many parts of the world.

 

Infection is closely associated with poverty; inadequate sanitation, poor

housing construction, and lack of access to essential medications are major

factors in this relationship. As countries develop, these factors improve,

and hookworm infestation decreases.1

Mortality/Morbidity

 

- Adults carry larger worm burdens than children and are generally more

subject to disease. However, the relationship is nonlinear and depends on

diet and activity thresholds. The increasing prevalence of hookworm disease

and higher worm burden among adults in many infected communities, especially

China, suggests that hookworm is immunosuppressive.

- Young women, especially those who are pregnant, and laborers are most

susceptible to symptomatic anemia. Adolescent girls and women of

child-bearing age are particularly at risk for poor outcomes such as

increased maternal mortality, prematurity, low birth weight, and impaired

lactation. Up to 30-54% of moderate to severe anemia among Africa and Asian

women is attributed to hookworm.

- Severe anemia retards childhood development and intellectual

performance. Vigorous labor is possible only with hemoglobin levels of more

than 7 g/dL.

 

Age

 

- Because infection is usually acquired by walking, handling, or lying in

contaminated soil, hookworm infection is uncommon in young children. Studies

performed in Brazil indicate that the prevalence and intensity of infection

is higher among poorer households. Similar studies in Uganda indicate that,

compared with the spotty geographic prevalence of ascariasis and

trichuriasis, hookworm is more homogeneously distributed.2

- Recent studies from China and Brazil indicate consistently increasing

prevalence of disease, from 15% at age 10 years to 60% at age 70 years and

older. Egg counts in stool also increase in a similar pattern. These data

suggest the need for a larger control target than infected schoolchildren

and the need to overcome what appears to be an immunocompromised state with

respect to the parasite.

 

 

CLINICAL

 

History

 

Most individuals who develop hookworm infection are from known endemic

areas.

 

 

- Early symptoms of hookworm infection are proportional to the intensity

of exposure.

- Necator produces a local irritation, termed ground itch, at the site of

skin invasion. An intensely pruritic, erythematous, or vesicular rash

usually appears on the feet or hands. This should be distinguished from a

creeping eruption due to skin migration of the cat or dog hookworm

Ancylostoma braziliense.

- Severe infection with either A duodenale or N americanus may produce

pneumonitis (Loefflerlike syndrome) that manifests as cough, fever, and

malaise.

- As worms mature in the jejunum, patients may experience diarrhea, vague

abdominal pain, colic, and/or nausea. These symptoms are more common with

initial exposures than with subsequent exposures.

- Patients with severe iron deficiency anemia may present with lassitude,

headache, palpitations, dyspnea, and edema.

 

Physical

 

- Skin and pulmonary findings are minimal.

- Signs of iron deficiency anemia are often insensitive. In severe cases,

patients may exhibit pallor, spooning nails, tachycardia, and peripheral

edema. Poor skin texture, edema, and susceptibility to cutaneous infection

suggest possible malnutrition.

 

 

DIFFERENTIALS

 

Eosinophilia

Gastroenteritis, Bacterial

Hemolytic Anemia

Hypersensitivity Pneumonitis

Iron Deficiency Anemia

Plummer-Vinson Syndrome

Pneumonia, Bacterial

 

WORKUP

 

Lab Studies

 

- Direct microscopic stool examination for ova and parasites usually

reveals oval, 60-µm X 40-µm eggs with thin colorless shells that can be seen

2 months after exposure. Concentration techniques may be helpful for

diagnosis of minimal infections expected during control programs. Because

the intensity and prevalence of hookworm infection decrease with public

health intervention, newer stool-concentration techniques such as FLOTAC

have some merit over older methods such as ether concentration or the

Kato-Katz thick smear.3

- Anemia is confirmed by CBC count and peripheral blood smear results

that demonstrate signs typical of iron deficiency anemia. Upon initial

infection, eosinophilia is usually present during the migratory phase before

stool findings are positive. Eosinophilia is surprisingly persistent and may

be due to attachment of the adult worms to the intestinal mucosa. Peak

eosinophil counts are 1,350-3,828 cells/µL at 5-9 weeks after experimental

human exposure to 45-50 infective larvae. Eosinophilia can be a clue to

hookworm, as well as Strongyloides infestation, in chronically infected

patients.

 

Imaging Studies

 

- Chest radiography may show diffuse alveolar infiltrates during the

migration of the worms through the lung in severe infection.

 

 

TREATMENT

 

Medical Care

 

- Albendazole or mebendazole is the drug of choice for hookworm

infection. These drugs provide a short-term cure in 90-95% of children, with

up to a 99% reduction in egg counts. Quarterly retreatment of Zanzibari

preschool children resulted in improved anemia and malnutrition after one

year.4 Concomitant iron supplementation in a recent study in Kenya did not

improve final hemoglobin concentrations in children or adults.5

- Rapid hookworm reinfection is common in endemic areas and is made

particularly problematic by the high prevalence and worm burden in adults

who are untreated and who continue to contaminate soil.

- Repeated community treatment may result in an emerging drug resistance.

In a Zanzibari population of children treated repeatedly over 5 years, cure

and egg elimination rates both decreased significantly with time.4 This

suggests the need for a renewed emphasis on community-wide sanitation,

education, and, possibly, vaccine development.

- Iron replacement and nutritional supplementation (protein and vitamins)

should be part of the management strategy and may have greater efficacy than

anthelmintics in reducing morbidity in selected populations, such as

pregnant women and patients who are not infected with HIV. Such combined

therapy has been successful in Peru and Brazil, but less so in Kenya.6, 5

 

 

 

MEDICATION

 

Imidazoles are the most convenient and effective drugs to treat hookworm.

Other older agents are also effective but may have lower clearance rates.

Pyrantel pamoate has been effectively used in hookworm infections. Newer

drugs are being sought because of developing resistance in areas with

frequent periodic deworming, such as Java. Unfortunately, the market for new

antiparasitic drugs is small. A promising alternative to albendazole is

tribendimidine, a synthetic drug developed in China.7

 

Drug Category: Benzimidazoles

 

These agents are poorly absorbed, relatively nontoxic broad-spectrum

anthelmintics that act by inhibiting tubulin polymerization. They have shown

high clearance rates.

Drug NameAlbendazole (Albenza) DescriptionA single dose of albendazole is

the treatment of choice for hookworm. It has a high eradication rate and is

easy to administer. Adult Dose400 mg PO as single dose Pediatric Dose<24

months: Balance potential risk of toxicity

>24 months: Administer as in adults ContraindicationsDocumented

hypersensitivity InteractionsCoadministration with carbamazepine may

decrease efficacy; dexamethasone, cimetidine, and praziquantel may increase

toxicity PregnancyC - Fetal risk revealed in studies in animals but not

established or not studied in humans; may use if benefits outweigh risk to

fetus

PrecautionsDiscontinue use if LFTs increase significantly (resume when

levels decrease to pretest values); abdominal pain, nausea, vomiting,

diarrhea, dizziness, vertigo, fever, increased intracranial pressure, and

alopecia may occur

 

Drug NameMebendazole (Vermox) DescriptionA 3-day course of mebendazole has

a reported cure rate of 95% and egg reduction rate of 99.9%. Single-dose

therapy is often advocated but may not be as effective as a single dose of

albendazole. Adult Dose100 mg PO bid for 3 d; alternatively 500 mg PO as

single dose Pediatric DoseAdminister as in adults ContraindicationsDocumented

hypersensitivity InteractionsCarbamazepine and phenytoin may decrease

effects; cimetidine may increase levels PregnancyC - Fetal risk revealed in

studies in animals but not established or not studied in humans; may use if

benefits outweigh risk to fetus

PrecautionsAdjust dose in hepatic impairment

 

 

FOLLOW-UP

 

Deterrence/Prevention

 

- Community control of hookworm infection is challenging.

- Successful programs have included economic, sanitary, and

mass-treatment components.

- Cost studies comparing various management strategies favor

community-wide, single-dose albendazole chemotherapy at intervals of 18

months. Some programs have been more intensive, with dosing frequency up to

quarterly in school children.

-

- Community control is difficult unless socioeconomic conditions,

sanitation, education, and the availability of proper footwear

significantly

improve.

- Current WHO recommendations for hookworm infection include periodic

mass therapy to lower the overall worm burden until conditions permit a

multicomponent physical and educational program. Community

leaders should be

trained about WHO recommendations.

- Major efforts are underway to develop an effective vaccine against both

hookworm species.8 These are based on various candidate antigens such as

antithrombotics, proteases, protease inhibitors, and secretory proteins

necessary for larval and adult worms. A hamster model using the Na-ASP-2

hookworm vaccine has suggested encouraging results in lowering worm burdens

and inhibiting growth delay. The necessity to express worm proteins in

eukaryotic cell systems and the inherent immunosuppressive nature of

hookworm infection make progress challenging.8

- The combined use of periodic deworming, improved sanitation, and an

at-least partially effective hookworm vaccine is hoped to decrease the

medical, social, and economic burden of anemia due to hookworm in developing

countries. The emergence of benzimidazole resistance is a concern, and new

drugs are being sought. A promising agent is tribendimidine, which was first

synthesized in China in the 1980s; tribendimidine seems equal or superior to

single-dose albendazole in initial trials.7

- Integrated control of hookworm with control of other helminth

infections can be provided with a package of medicines at a cost of $0.50

per patient per year.1 Such dual therapy has been shown effective in various

geographic contexts.9 Major partnerships of organizations are coordinating

integrated management through the Global Network for Neglected Tropical

Disease Control.10 Such efforts provide hope to improve the health and

economic development of millions worldwide.

 

Prognosis

 

- Most patients become reinfected within months unless they are relocated

to an area of significantly improved sanitation.

 

 

MISCELLANEOUS

 

Medical/Legal Pitfalls

 

- Failure to recognize, diagnosis, and properly treat the hookworm

infection

 

 

 

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