Hookworm Disease

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Human hookworm disease is a common helminth infection that is predominantly caused by the nematode parasites Necator americanus and Ancylostoma duodenale; organisms that play a lesser role include Ancylostoma ceylonicum, Ancylostoma braziliense, and Ancylostoma caninum. Hookworm infection is acquired through skin exposure to larvae in soil contaminated by human feces (see the image below). Soil becomes infectious about 9 days after contamination and remains so for weeks, depending on conditions.

Worldwide, hookworms infect an estimated 472 million people. Although most of those affected are asymptomatic, ^{[1, 2]} approximately 10% experience anemia. Hookworms may persist for many years in the host and impair the physical and intellectual development of children and the economic development of communities.

Historically, hookworm infection has disproportionately affected the poorest among the least-developed nations, largely as a consequence of inadequate access to clean water, sanitation, and health education. The frequent absence of symptoms notwithstanding, hookworm disease substantially contributes to the incidence of anemia and malnutrition in developing nations. ^[3] It occurs most commonly in the rural tropical and subtropical areas of Asia, sub-Saharan Africa, and Latin America. ^[1]

Individual hookworm treatment consists of iron replacement and anthelmintic therapy. Community eradication has proven difficult, even with intensive, yearly, school-based programs. Part of the difficulty may be failure to clear infection from adults with high worm burden. Despite this, successful control and eradication of hookworms is a worthy goal for new methods that could offer huge economic and social benefits to much of Africa and Asia.

See Common Intestinal Parasites, a Critical Images slideshow, to help make an accurate diagnosis.

The life cycle of hookworms (see the image below) begins with the passing of hookworm eggs in human feces and their deposition into the soil. ^{[4, 5]}

Each day in the intestine, a mature female A duodenale worm produces about 10,000-30,000 eggs, and a mature female N americanus worm produces 5000-10,000 eggs (see the image below). After deposition onto soil and under appropriate conditions, each egg develops into an infective larva. These larvae are developmentally arrested and nonfeeding. If they are unable to infect a new host, they die when their metabolic reserves are exhausted, usually in about 6 weeks.

Larval growth is most proliferative in favorable soil that is sandy and moist, with an optimal temperature of 20-30°C. Under these conditions, the larvae hatch in 1 or 2 days to become rhabditiform larvae, also known as L1 (see the image below).

The rhabditiform larvae feed on the feces and undergo 2 successive molts; after 5-10 days, they become infective filariform larvae, or L3 (see the image below). These L3 go through developmental arrest and can survive in damp soil for as long as 2 years. However, they quickly become desiccated if exposed to direct sunlight, drying, or salt water. L3 live in the top 2.5 cm of soil and move vertically toward moisture and oxygen.

The L3 larvae are 500-700 µm long (barely visible to the naked eye) and are capable of rapid penetration into normal skin, most commonly on the hands or feet. Transmission occurs after 5 or more minutes of skin contact with soil that contains viable larvae. The skin penetration may cause a local pruritic dermatitis, also known as ground itch. Ground itch at the site of penetration is more common with Ancylostoma than with Necator.

The larvae migrate through the dermis, entering the bloodstream and moving to the lungs within 10 days. Once in the lungs, they break into alveoli, causing a mild and usually asymptomatic alveolitis with eosinophilia. (Hookworms are among the causes of the pulmonary infiltrates and eosinophilia [PIE] syndrome, along with Ascaris and Strongyloides species.)

Having penetrated the alveoli, the larvae are carried to the glottis by means of the ciliary action of the respiratory tract. During pulmonary migration, the host may develop a mild reactive cough, sore throat, and fever that resolve after the worm migrates into the intestines. At the glottis, the larvae are swallowed and carried to their final destination, the small intestine.

During this part of the migration, the larvae undergo 2 further molts, developing a buccal capsule and attaining their adult form. The buccal capsule of an adult A duodenale has teeth to facilitate attachment to mucosa, whereas an adult N americanus has cutting plates instead. A muscular esophagus creates suction in the buccal capsule.

Using their buccal capsule, the adult worms attach themselves to the mucosal layer of the proximal small intestine, including the lower part of the duodenum, jejunum, and proximal ileum (see the image below). In so doing, they rupture the arterioles and venules along the luminal surface of the intestine.

The adult worms release hyaluronidase, which degrades intestinal mucosa and erodes blood vessels, resulting in blood extravasation. They also ingest some blood. An anticoagulant facilitates blood flow by blocking the activity of factors Xa and VIIa. Adult worms also elaborate factors (eg, neutrophil inhibitory factor) that protect them from host defenses.

In 3-5 weeks, the adults become sexually mature, and the female worms begin to produce eggs that appear in the feces of the host.

Although N americanus infects only percutaneously, A duodenale can also infect by means of ingestion; however, in su Ancylostoma may also lie dormant in tissues and later be transmitted through breast milk. This ability to enter dormancy in the human host may be an adaptive response evolved 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.

Neither Necator nor Ancylostoma multiplies within the host. If the host is not reexposed, the infection disappears after the worm dies. The natural life span for an adult A duodenale is about 1 year, and that for an adult N americanus is 3-5 years.

Hookworm infection gives rise to the following 3 clinical entities in humans:

Classic hookworm disease – This is a gastrointestinal (GI) infection characterized by chronic blood loss that leads to iron-deficiency anemia and protein malnutrition; it is caused primarily by N americanus and A duodenale and less commonly by the zoonotic species A ceylonicum

Cutaneous larva migrans – This is an infection whose manifestations are limited to the skin; it is most commonly caused by A braziliense, whose definitive hosts include dogs and cats

Eosinophilic enteritis – This is a GI infection characterized by abdominal pain but no blood loss; it is caused by the dog hookworm A caninum

In cutaneous 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. The larvae thus remain trapped superficial to this layer, where they migrate laterally at a rate of 1-2 cm/day and create the pathognomonic serpiginous tunnels associated with this condition. Larvae can survive in the skin for about 10 days before dying.

In eosinophilic enteritis, A caninum larvae typically enter a human host by penetrating the skin, though infection by oral ingestion is also 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 experience increasingly severe recurrent abdominal pain, which may be analogous to a response to repeated insect stings.

Intestinal blood loss secondary is the major clinical manifestation of hookworm infection. ^[6] In fact, hookworm disease historically refers to the childhood syndrome of iron deficiency anemia, protein malnutrition, growth and mental retardation with lethargy resulting from chronic intestinal blood loss secondary to hookworm infection in the face of an iron deficient diet.

Hookworms ingest and digested some of the blood from the injured mucosa by means of a multienzyme cascade of metallohemoglobinases. Each Necator worm ingests 0.03 mL of blood daily, whereas each Ancylostoma worm ingests 0.15-0.2 mL of blood daily. Inhibited host coagulation due to a series of anticoagulants directed against factor Xa and the factor VIIa–tissue factor (TF) complex, as well as against platelet aggregation, further exacerbates blood loss.

The amount of blood loss and the degree of anemia are positively correlated with the worm burden, whereas hemoglobin, serum ferritin, protoporphyrin levels are significantly and negatively correlated with the number of worms. ^[4] Threshold worm loads for anemia differ nationally, with as few as 40 worms producing anemia in countries with low iron consumption.

Generally, the extent of hookworm infection may be categorized as follows:

Light (< 100 worms)

Moderate (100-500 worms)

Heavy (500-1000 worms)

People who develop an initial heavy infection seem to reacquire heavy infection, and individuals who are lightly infected reacquire light infections. Since each adult worm is the molt of a single infective larva, this suggests continuing exposure to highly contaminated environments with little amnestic immunity in the host. 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.

In addition, because A duodenale consumes more blood per worm than N americanus does, the severity of anemia may differ as a factor of the hookworm species that is causing the infection. Severe anemia affects intellectual and physical development in children and cardiovascular performance in adults.

Because of the clinically significant blood loss and the worm’s ingestion of serum proteins, hypoproteinemia may also develop, which is clinically manifested as weight-loss, anasarca, and edema.

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 infections with enteric bacteria, viruses, and protozoa. This protein-losing enteropathy can also contribute to a more rapid progression of an HIV infection. In patients with high enough iron intake, enteropathy may occur independent of anemia.

Hookworms appear to evade or inhibit effective human immune responses. The persistence of hookworm infection supports the theory that the worms have evolved adaptive molecular mechanisms to achieve a homeostatic balance with the host immune response. ^{[6, 7, 8, 9]}

Little is known about the innate immune response to metazoan in general and hookworms in particular. ^[10] Hookworm-derived pathogen-associated molecular patterns (PAMPS) of molecules are thought to react with receptors on dentritic cells or basophiles to stimulate interleukin (IL)–4 and initiate an immunological cascade resulting in a type 2 regulatory response from Th2 helper cells. This may be augmented by “alarmins” such as thymic stromal lymphopoietin (TSLP), IL-33, and IL-25 released from epithelial cells damaged by worms. These activate newly described innate lymphoid type-2 cells (ILC2) that provide early rise in protective TH2 cytokines IL-5 and IL-13.

Meanwhile, worm products inhibit IL-12 and TSLP induces basophil production of IL-4, both promoting differentiation of Th2 cells. The antiparasite Th2 cells produce more IL-4, IL-5, and IL-13, which cause B cell immunoglobulin G type 1 (IgG1) and immunoglobulin E (IgE) class switching. Antiworm IgE binds the parasite and actives mast cells, which release inflammatory molecules, while IL-5 promotes eosinophil expansion and activation and M2 macrophage differentiation, which damage and produce granulomas, respectively. Other effector molecules include transforming growth factor-beta (TGF-b), resistinlike molecule (RELM)–alpha, chitinases, and matrix metalloproteases, all of which damage or limit the parasite.

At the same time, this intense Th2 immune response must be regulated by the host to avoid immunopathology, and by the parasite to allow survival. Helminths enhance expression of T cell co-inhibitory molecules that include PD-1 and CTLA-4, and promote differentiation of tolerogenic dentric cells and T regulatory cells. T regulatory cells produce anti-inflammatory cytokines IL-10 and TGF-b. Hookworms also appear to secrete an inhibitor of natural killer cells, thereby suppressing production of interferon gamma and the Th2 response that would be expected to clear the parasite.

Since 1989 with David Strachan’s observation of a correlation between incidence of hay fever in children and low family size, the hygiene hypothesis has excited investigators as to a possible inverse relationship between helminth infections and allergic and autoimmune disease.

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 has even prompted investigation of worms or worm products as therapy for such diseases. Similarly, areas of high hookworm endemicity have low rates of reaction to dust mite antigens. It is thought that worm-activated regulatory and counter-regulatory processes involving Th2 and T regulatory cells and cell products may paradoxically inhibit Th2 responses that in the absence of worms, cause reactions to potential allergens.

In the search for possible vaccine targets, investigators have focused on hookworm molecular inhibitors of coagulation factors Xa and VIIa-TF and metalloproteases that degrade hemoglobin and intestinal mucosal cells. The Sabin Vaccine Institute has developed a 2 antigen human hookworm vaccine comprising recombinant Necator antigens Na- GST-1 and Na- APR-1, each of which is required for hookworm use of host blood. ^[11] Another antigen, Ancylostoma -secreted protein 2 (ASP-2), appears necessary for chemokine receptor binding and invasion and has shown some promise in animal vaccine trials. The 3-dimensional structure of Na-ASP-2 has recently been reported and identified as a conserved tandem histidine motif necessary for catalytic or proteolytic activity. ^[12] Unfortunately, this vaccine produced urticarial reactions among previously infected recipients, and its development was halted. ^[13]

Organisms that have been shown to cause hookworm disease include the following:

N americanus

A duodenale

A ceylonicum

A caninum

A braziliense

N americanus is the globally predominant human hookworm and is the only member of its genus known to infect humans. ^[14] It is a small, cylindrical, off-white worm; adult males measure 7-9 mm, and adult females measure 9-11 mm. ^[4]

A duodenale is more geographically restricted than N americanus and is one of several anthropophilic members of the genus Ancylostoma. It primarily infects humans and is responsible for classic hookworm disease. A duodenale resembles N americanus in appearance but is somewhat larger, with adult males measuring 8-11 mm and adult females measuring 10-13 mm.

On microscopy, N americanus can be differentiated from A duodenale on the basis of the cutting plates that it possesses in place of teeth (see the images below). ^[15]

A ceylonicum primarily infects canines and felines but can cause milder classic hookworm disease in humans. A braziliense is a canine and feline hookworm that, in humans, causes cutaneous larva migrans, or creeping eruption, a self-limiting condition characterized by serpiginous burrows formed as the larvae migrate through the epidermis. A caninum is a canine hookworm that mainly causes eosinophilic enteritis in humans (though it also causes cutaneous larva migrans in a minority of cases).

Poor sanitation, limited access to clean water, and low income are well-documented risk factors for hookworm infection. High-risk populations include international travelers, refugees, international adoptees, and recent immigrants. ^[16]

Favorable environmental conditions conduce to the development of hookworm disease. Optimal conditions for eggs include 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; 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. They are also killed by drying and direct sunlight.

Although hookworm infection is now thought to be rare in the United States, hookworm played an important role in the impoverishment of the southeastern region of the country until the 1930s. Studies performed in the early 1970s indicated prevalences as high as 14.8% among schoolchildren from rural Kentucky and as high as 12% among schoolchildren from rural coastal Georgia. A low prevalence of classic hookworm infection, mainly due to N americanus, is still found in pockets of the southeastern United States. A 2017 report demonstrated 39% prevalence of N americanus among 24 rural households in Lowndes County, Alabama, who depended on poorly functioning septic tank systems, suggesting continued vulnerability of rural poor populations, even today. ^[17]

Hookworm infection and disease are now most likely to be found in immigrants, refugees, and adoptees from tropical countries. Occasionally, people returning from travel abroad present with acute watery diarrhea with eosinophilia upon their return to the United States.

Cutaneous larva migrans is endemic in the southeastern states and Puerto Rico. The canine hookworm A caninum has reportedly caused eosinophilic enteritis in Australia and the United States.

Human infection with A duodenale or N americanus is estimated to affect approximately 472 million people worldwide. ^{[18, 19, 20]} 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; in some communities, prevalence may be 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. Improper disposal of human feces and the common habit of walking barefoot are key epidemiologic features. However, the use of footwear has not been shown to affect hookworm prevalence, in that the larvae can invade through any skin surface.

In 2010, it was estimated that 117 million individuals in sub-Saharan Africa were infected with hookworms, as well as 64 million in East Asia, 140 million in South Asia, 77 million in Southeast Asia, 30 million in Latin America and the Caribbean, 10 million in Oceania, and 4.6 million in the Middle East and North Africa. Oceania has the highest prevalence (49%), followed by sub-Saharan Africa (13%), Southeast Asia (12.6%), South Asia (8.6%), East Asia (5%), and Latin America/Caribbean (5%). ^[18] These represent approximately 20% decreases in prevalence from 2005 WHO estimates.

Infection is closely associated with poverty; inadequate sanitation, poor housing construction, and lack of access to essential medications are major factors in this relationship. Studies performed in Brazil indicate that the prevalence and intensity of infection is higher among poorer households. Similar studies in Uganda indicate that in comparison with the spotty geographic prevalence of ascariasis and trichuriasis, hookworm disease is more homogeneously distributed. ^[21] Recycled human sewerage for fertilizer is now being practiced on a large scale and could pose a risk for epidemic infection. ^[22]

As countries develop, the factors conducing to hookworm disease are mitigated, and hookworm infestation decreases. ^[23] In developed countries, infection is most commonly encountered in travelers, immigrants, and adoptees from developing countries.

Both Necator and Ancylostoma species have worldwide distribution. A duodenale predominates in the Mediterranean region, in northern regions of India and China, and in North Africa. A ceylonicum is found in focally endemic areas in southern Asia. N americanus predominates in southern China, Southeast Asia, the Americas, most of Africa, and parts of Australia. This differential distribution is not absolute, and mixed infections may occur in individual patients. Coinfection with Ascaris or Trichuris is common in many parts of the world.

In endemic areas, the highest prevalences are reported among school-aged children and adolescents, possibly because of age-related changes in exposure and the acquisition of immunity. ^[24] 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.

Although children bear a large disease burden, hookworm infection appears to have an atypical age distribution. Unlike other soil-transmitted helminth infections, such as ascariasis and trichuriasis (for which the incidence peaks in childhood), hookworm infection appears to increase throughout childhood until it reaches a plateau in adulthood. ^[25] Studies from China and Brazil indicate a consistently increasing prevalence, from 15% at age 10 years to 60% at age 70 years and older. Egg counts in stool also increase in a similar pattern.

Although adults carry larger worm burdens than children do and are generally more subject to disease, 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 in China, suggests that hookworm is immunosuppressive.

Males and females are equally susceptible to hookworm infection.

With proper treatment, the prognosis is excellent. Mortality is low, though those hookworm-related deaths that do occur are probably underrecognized as a consequence of the insidious nature of the disease.

In classic hookworm disease, appropriate anthelmintic treatment and iron and diet therapy typically result in complete recovery from anemia and malnutrition, though some deficits in intellectual function may persist. In endemic areas, reinfection is very likely: Most patients become reinfected within months unless they are relocated to an area of significantly improved sanitation.

In cutaneous larva migrans, the larvae die even when no treatment is provided, and symptoms resolve within a few weeks to several months. Eosinophilic enteritis promptly responds to mebendazole therapy.

Anemia remains the most significant clinical consequence of hookworm infection. Hookworms are the leading cause of iron-deficiency anemia in developing countries. Severe anemia retards childhood development and intellectual performance and can cause significant disability in heavily infected communities. Vigorous labor is possible only with hemoglobin levels higher than 7 g/dL.

The timing of anemia onset depends on the patient’s preexisting iron stores. In a study involving 492 children, the prevalence of anemia and the prevalence of ferritin levels lower than 12 μg/L were 60.5% and 33.1%, respectively, in those with N americanus infection, compared with 80.6% and 58.9%, respectively, in those with A duodenale infection. ^[26]

Young women, especially those who are pregnant, and laborers are most susceptible to symptomatic anemia. Adolescent girls and women of child-bearing age are at particular risk for poor outcomes such as increased maternal mortality, prematurity, low birth weight, and impaired lactation. As many as 30-54% of cases of moderate-to-severe anemia among African and Asian women are attributable to hookworm.

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.

Patient education focuses on preventive measures. Walking barefoot outdoors in endemic areas should generally be discouraged; however, the effect of wearing proper footwear on hookworm transmission is likely to be overestimated. Inadequate sanitation remains a primary risk factor for hookworm infection. ^{[27, 28]} Public health education about proper hygiene and improved sanitation may considerably reduce the risk of infection.

de Silva NR, Brooker S, Hotez PJ, Montresor A, Engels D, Savioli L. Soil-transmitted helminth infections: updating the global picture. Trends Parasitol. 2003 Dec. 19(12):547-51. [Medline].

Stoltzfus RJ, Dreyfuss ML, Chwaya HM, Albonico M. Hookworm control as a strategy to prevent iron deficiency. Nutr Rev. 1997 Jun. 55(6):223-32. [Medline].

World Health Organization. Parasitic Diseases. Available at http://www.who.int/vaccine_research/diseases/soa_parasitic/en/index2.html. Accessed: April 22, 2012.

Brooker S, Bundy DAP. Soil-transmitted Helminths (Geohelminths). Cook GC, Zumla AI, eds. Manson’s Tropical Diseases. 22nd ed. Philadelphia, PA: WB Saunders; 2009. 1515-48.

Centers for Disease Control and Prevention. Hookworm Infection. Available at http://www.cdc.gov/parasites/hookworm/index.html. Accessed: April 22, 2012.

Hotez PJ, Bethony J, Bottazzi ME, Brooker S, Buss P. Hookworm: “the great infection of mankind”. PLoS Med. 2005 Mar. 2(3):e67. [Medline]. [Full Text].

Quinnell RJ, Pritchard DI, Raiko A, et al. Immune responses in human necatoriasis: association between interleukin-5 responses and resistance to reinfection. J Infect Dis. 2004 Aug 1. 190(3):430-8. [Medline].

Brooker S, Bethony J, Hotez PJ. Human hookworm infection in the 21st century. Adv Parasitol. 2004. 58:197-288. [Medline].

Bungiro R, Cappello M. Hookworm infection: new developments and prospects for control. Curr Opin Infect Dis. 2004 Oct. 17(5):421-6. [Medline].

Finlay CM, Walsh KP, Mills KH. Induction of regulatory cells by helminth parasites: exploitation for the treatment of inflammatory diseases. Immunol Rev. 2014 May. 259(1):206-30. [Medline].

Hotez PJ, Diemert D, Bacon KM, et al. The Human Hookworm Vaccine. Vaccine. 2013 Apr 18. 31 Suppl 2:B227-32. [Medline]. [Full Text].

Mason L, Tribolet L, Simon A, et al. Probing the equatorial groove of the hookworm protein and vaccine candidate antigen, Na-ASP-2. Int J Biochem Cell Biol. 2014 May. 50:146-55. [Medline].

Blair P, Diemert D. Update on prevention and treatment of intestinal helminth infections. Curr Infect Dis Rep. 2015 Mar. 17 (3):465. [Medline].

Capello M, Hotez PJ. Chapter 276: Intestinal Nematodes. SS, ed-in-chief; Pickering LK, Prober CG, eds. Long Principles and Practice of Pediatric Infectious Diseases. 3rd ed. Philadelphia, PA: Churchill Livingstone, an imprint of Elsevier Science; 2008. 1298-1300.

Centers for Disease Control and Prevention. Hookworm. CDC DPDx: Laboratory Identification of Parasites of Public Health Concern. Available at http://www.dpd.cdc.gov/DPDx/HTML/Hookworm.htm.

AAP. Hookworm infections. Red Book 2009: Report of the Committee on Infectious Diseases. 28th ed. American Academy of Pediatrics; 2009. 364(9450): 375-6.

McKenna ML, McAtee S, Bryan PE, Jeun R, Ward T, Kraus J, et al. Human Intestinal Parasite Burden and Poor Sanitation in Rural Alabama. Am J Trop Med Hyg. 2017 Nov. 97 (5):1623-1628. [Medline].

Pullan RL, Smith JL, Jasrasaria R, Brooker SJ. Global numbers of infection and disease burden of soil transmitted helminth infections in 2010. Parasit Vectors. 2014 Jan 21. 7:37. [Medline].

Jourdan PM, Lamberton PHL, Fenwick A, Addiss DG. Soil-transmitted helminth infections. Lancet. 2017 Sep 4. [Medline].

Adu-Gyasi D, Asante KP, Frempong MT, Gyasi DK, Iddrisu LF, Ankrah L, et al. Epidemiology of soil transmitted Helminth infections in the middle-belt of Ghana, Africa. Parasite Epidemiol Control. 2018 Aug. 3 (3):e00071. [Medline].

Kabatereine NB, Tukahebwa EM, Kazibwe F, et al. Soil-transmitted helminthiasis in Uganda: epidemiology and cost of control. Trop Med Int Health. 2005 Nov. 10(11):1187-9. [Medline].

Amoah ID, Adegoke AA, Stenström TA. Soil-transmitted helminth infections associated with wastewater and sludge reuse: a review of current evidence. Trop Med Int Health. 2018 Jul. 23 (7):692-703. [Medline].

Hotez P. Hookworm and poverty. Ann N Y Acad Sci. 2008. 1136:38-44. [Medline].

Bhatia V, Das MK, Kumar P, Arora NK. Infantile hookworm disease. Indian Pediatr. 2010 Feb. 47(2):190-2. [Medline].

Hotez PJ, Brooker S, Bethony JM, et al. Hookworm infection. N Engl J Med. 2004 Aug 19. 351(8):799-807. [Medline].

Albonico M, Stoltzfus RJ, Savioli L, Tielsch JM, Chwaya HM, Ercole E, et al. Epidemiological evidence for a differential effect of hookworm species, Ancylostoma duodenale or Necator americanus, on iron status of children. Int J Epidemiol. 1998 Jun. 27(3):530-7. [Medline].

Ziegelbauer K, Speich B, Mäusezahl D, Bos R, Keiser J, Utzinger J. Effect of sanitation on soil-transmitted helminth infection: systematic review and meta-analysis. PLoS Med. 2012 Jan. 9(1):e1001162. [Medline]. [Full Text].

Gunawardena K, Kumarendran B, Ebenezer R, Gunasingha MS, Pathmeswaran A, de Silva N. Soil-transmitted helminth infections among plantation sector schoolchildren in Sri Lanka: prevalence after ten years of preventive chemotherapy. PLoS Negl Trop Dis. 2011 Sep. 5(9):e1341. [Medline]. [Full Text].

Feldmeier H, Schuster A. Mini review: Hookworm-related cutaneous larva migrans. Eur J Clin Microbiol Infect Dis. 2012 Jun. 31(6):915-8. [Medline].

Stoltzfus RJ, Albonico M, Tielsch JM, Chwaya HM, Savioli L. Linear growth retardation in Zanzibari school children. J Nutr. 1997 Jun. 127(6):1099-105. [Medline].

Heukelbach J, Feldmeier H. Epidemiological and clinical characteristics of hookworm-related cutaneous larva migrans. Lancet Infect Dis. 2008 May. 8(5):302-9. [Medline].

Stoltzfus RJ, Kvalsvig JD, Chwaya HM, Montresor A, Albonico M, Tielsch JM, et al. Effects of iron supplementation and anthelmintic treatment on motor and language development of preschool children in Zanzibar: double blind, placebo controlled study. BMJ. 2001 Dec 15. 323(7326):1389-93. [Medline]. [Full Text].

Stoltzfus RJ, Albonico M, Chwaya HM, Tielsch JM, Schulze KJ, Savioli L. Effects of the Zanzibar school-based deworming program on iron status of children. Am J Clin Nutr. 1998 Jul. 68(1):179-86. [Medline].

Blouin B, Casapía M, Joseph L, Kaufman JS, Larson C, Gyorkos TW. The effect of cumulative soil-transmitted helminth infections over time on child development: a 4-year longitudinal cohort study in preschool children using Bayesian methods to adjust for exposure misclassification. Int J Epidemiol. 2018 Jul 12. [Medline].

Weatherhead JE, Hotez PJ. Worm Infections in Children. Pediatr Rev. 2015 Aug. 36 (8):341-52; quiz 353-4. [Medline].

Hughes RG, Sharp DS, Hughes MC. Environmental influences on helminthiasis and nutritional status among Pacific schoolchildren. Int J Environ Health Res. 2004. 14(3):163-77.

Gasser RB, Cantacessi C, Loukas A. DNA technological progress toward advanced diagnostic tools to support human hookworm control. Biotechnol Adv. 2008 Jan-Feb. 26(1):35-45. [Medline].

Verweij JJ, Brienen EA, Ziem J, Yelifari L, Polderman AM, Van Lieshout L. Simultaneous detection and quantification of Ancylostoma duodenale, Necator americanus, and Oesophagostomum bifurcum in fecal samples using multiplex real-time PCR. Am J Trop Med Hyg. 2007 Oct. 77(4):685-90. [Medline].

Jelinek T, Maiwald H, Nothdurft HD, Löscher T. Cutaneous larva migrans in travelers: synopsis of histories, symptoms, and treatment of 98 patients. Clin Infect Dis. 1994 Dec. 19(6):1062-6. [Medline].

Utzinger J, Rinaldi L, Lohourignon LK, et al. FLOTAC: a new sensitive technique for the diagnosis of hookworm infections in humans. Trans R Soc Trop Med Hyg. 2008 Jan. 102(1):84-90. [Medline].

de Silva N, Guyatt H, Bundy D. Anthelmintics. A comparative review of their clinical pharmacology. Drugs. 1997 May. 53(5):769-88. [Medline].

Keiser J, Utzinger J. The drugs we have and the drugs we need against major helminth infections. Adv Parasitol. 2010. 73:197-230. [Medline].

Horton J. Albendazole: a review of anthelmintic efficacy and safety in humans. Parasitology. 2000. 121 Suppl:S113-32. [Medline].

Humphries D, Simms BT, Davey D, et al. Hookworm infection among school age children in Kintampo north municipality, Ghana: nutritional risk factors and response to albendazole treatment. Am J Trop Med Hyg. 2013 Sep. 89(3):540-8. [Medline]. [Full Text].

Keiser J, Utzinger J. Efficacy of current drugs against soil-transmitted helminth infections: systematic review and meta-analysis. JAMA. 2008 Apr 23. 299(16):1937-48. [Medline].

Steinmann P, Utzinger J, Du ZW, et al. Efficacy of single-dose and triple-dose albendazole and mebendazole against soil-transmitted helminths and Taenia spp.: a randomized controlled trial. PLoS One. 2011. 6(9):e25003. [Medline]. [Full Text].

Soukhathammavong PA, Sayasone S, Phongluxa K, et al. Low efficacy of single-dose albendazole and mebendazole against hookworm and effect on concomitant helminth infection in Lao PDR. PLoS Negl Trop Dis. 2012 Jan. 6(1):e1417. [Medline]. [Full Text].

Moser W, Schindler C, Keiser J. Efficacy of recommended drugs against soil transmitted helminths: systematic review and network meta-analysis. BMJ. 2017 Sep 25. 358:j4307. [Medline].

Bethony J, Brooker S, Albonico M, et al. Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm. Lancet. 2006 May 6. 367(9521):1521-32. [Medline].

Flohr C, Tuyen LN, Lewis S, et al. Poor sanitation and helminth infection protect against skin sensitization in Vietnamese children: A cross-sectional study. J Allergy Clin Immunol. 2006 Dec. 118(6):1305-11. [Medline].

Bennett A, Guyatt H. Reducing intestinal nematode infection: efficacy of albendazole and mebendazole. Parasitol Today. 2000 Feb. 16(2):71-4. [Medline].

Albonico M, Bickle Q, Ramsan M, et al. Efficacy of mebendazole and levamisole alone or in combination against intestinal nematode infections after repeated targeted mebendazole treatment in Zanzibar. Bull World Health Organ. 2003. 81(5):343-52. [Medline].

Schneider B, Jariwala AR, Periago MV, Gazzinelli MF, Bose SN, Hotez PJ, et al. A history of hookworm vaccine development. Hum Vaccin. 2011 Nov 1. 7(11):[Medline].

Xiao SH, Hui-Ming W, Tanner M, et al. Tribendimidine: a promising, safe and broad-spectrum anthelmintic agent from China. Acta Trop. 2005 Apr. 94(1):1-14. [Medline].

Tyagi R, Maddirala AR, Elfawal M, Fischer C, Bulman CA, Rosa BA, et al. Small Molecule Inhibitors of Metabolic Enzymes Repurposed as a New Class of Anthelmintics. ACS Infect Dis. 2018 Jul 13. 4 (7):1130-1145. [Medline].

Hu Y, Nguyen TT, Lee ACY, Urban JF Jr, Miller MM, Zhan B, et al. Bacillus thuringiensis Cry5B protein as a new pan-hookworm cure. Int J Parasitol Drugs Drug Resist. 2018 Aug. 8 (2):287-294. [Medline].

Stoltzfus RJ, Chway HM, Montresor A, Tielsch JM, Jape JK, Albonico M, et al. Low dose daily iron supplementation improves iron status and appetite but not anemia, whereas quarterly anthelminthic treatment improves growth, appetite and anemia in Zanzibari preschool children. J Nutr. 2004 Feb. 134(2):348-56. [Medline].

Le Huong T, Brouwer ID, Nguyen KC, Burema J, Kok FJ. The effect of iron fortification and de-worming on anaemia and iron status of Vietnamese schoolchildren. Br J Nutr. 2007 May. 97(5):955-62. [Medline].

Larocque R, Casapia M, Gotuzzo E, et al. A double-blind randomized controlled trial of antenatal mebendazole to reduce low birthweight in a hookworm-endemic area of Peru. Trop Med Int Health. 2006 Oct. 11(10):1485-95. [Medline].

Friis H, Mwaniki D, Omondi B, et al. Effects on haemoglobin of multi-micronutrient supplementation and multi-helminth chemotherapy: a randomized, controlled trial in Kenyan school children. Eur J Clin Nutr. 2003 Apr. 57(4):573-9. [Medline].

Bhatia V, Das MK, Kumar P, Arora NK. Infantile hookworm disease. Indian Pediatr. 2010 Feb. 47(2):190-2. [Medline].

Vercruysse J, Behnke JM, Albonico M, Ame SM, Angebault C, Bethony JM, et al. Assessment of the anthelmintic efficacy of albendazole in school children in seven countries where soil-transmitted helminths are endemic. PLoS Negl Trop Dis. 2011 Mar 29. 5(3):e948. [Medline]. [Full Text].

Soukhathammavong PA, Sayasone S, Phongluxa K, Xayaseng V, Utzinger J, Vounatsou P, et al. Low efficacy of single-dose albendazole and mebendazole against hookworm and effect on concomitant helminth infection in Lao PDR. PLoS Negl Trop Dis. 2012 Jan. 6(1):e1417. [Medline]. [Full Text].

Lone FW, Qureshi RN, Emanuel F. Maternal anaemia and its impact on perinatal outcome. Trop Med Int Health. 2004 Apr. 9(4):486-90. [Medline].

Brooker S, Hotez PJ, Bundy DA. Hookworm-related anaemia among pregnant women: a systematic review. PLoS Negl Trop Dis. 2008 Sep 17. 2(9):e291. [Medline]. [Full Text].

Imhoff-Kunsch B, Briggs V. Antihelminthics in pregnancy and maternal, newborn and child health. Paediatr Perinat Epidemiol. 2012 Jul. 26 Suppl 1:223-38. [Medline].

Bungiro R, Cappello M. Twenty-first century progress toward the global control of human hookworm infection. Curr Infect Dis Rep. 2011 Jun. 13(3):210-7. [Medline].

Kabatereine NB, Brooker S, Koukounari A, Kazibwe F, Tukahebwa EM, Fleming FM, et al. Impact of a national helminth control programme on infection and morbidity in Ugandan schoolchildren. Bull World Health Organ. 2007 Feb. 85(2):91-9. [Medline]. [Full Text].

Sakti H, Nokes C, Hertanto WS, Hendratno S, Hall A, Bundy DA, et al. Evidence for an association between hookworm infection and cognitive function in Indonesian school children. Trop Med Int Health. 1999 May. 4(5):322-34. [Medline].

Schulz JD, Moser W, Hürlimann E, Keiser J. Preventive Chemotherapy in the Fight against Soil-Transmitted Helminthiasis: Achievements and Limitations. Trends Parasitol. 2018 Jul. 34 (7):590-602. [Medline].

McSorley HJ, Loukas A. The immunology of human hookworm infections. Parasite Immunol. 2010 Aug. 32(8):549-59. [Medline].

Cho Y, Vermeire JJ, Merkel JS, Leng L, Du X, Bucala R, et al. Drug repositioning and pharmacophore identification in the discovery of hookworm MIF inhibitors. Chem Biol. 2011 Sep 23. 18(9):1089-101. [Medline].

Hotez PJ. The global fight to develop antipoverty vaccines in the anti-vaccine era. Hum Vaccin Immunother. 2018 Feb 2. 1-4. [Medline].

Diemert DJ, Bethony JM, Hotez PJ. Hookworm vaccines. Clin Infect Dis. 2008 Jan 15. 46(2):282-8. [Medline].

Hotez PJ, Zhan B, Bethony JM, Loukas A, Williamson A, Goud GN, et al. Progress in the development of a recombinant vaccine for human hookworm disease: the Human Hookworm Vaccine Initiative. Int J Parasitol. 2003 Sep 30. 33(11):1245-58. [Medline].

Loukas A, Bethony J, Brooker S, Hotez P. Hookworm vaccines: past, present, and future. Lancet Infect Dis. 2006 Nov. 6(11):733-41. [Medline].

Bethony JM, Simon G, Diemert DJ, Parenti D, Desrosiers A, Schuck S, et al. Randomized, placebo-controlled, double-blind trial of the Na-ASP-2 hookworm vaccine in unexposed adults. Vaccine. 2008 May 2. 26(19):2408-17. [Medline].

Tang H, Jin X, Li Y, et al. A large-scale screen for coding variants predisposing to psoriasis. Nat Genet. 2014 Jan. 46(1):45-50. [Medline].

Reddy M, Gill SS, Kalkar SR, et al. Oral drug therapy for multiple neglected tropical diseases: a systematic review. JAMA. 2007 Oct 24. 298(16):1911-24. [Medline].

Hotez PJ, Molyneux DH, Fenwick A, et al. Control of neglected tropical diseases. N Engl J Med. 2007 Sep 6. 357(10):1018-27. [Medline].

Easton AV, Oliveira RG, O’Connell EM, Kepha S, Mwandawiro CS, Njenga SM, et al. Multi-parallel qPCR provides increased sensitivity and diagnostic breadth for gastrointestinal parasites of humans: field-based inferences on the impact of mass deworming. Parasit Vectors. 2016 Jan 27. 9 (1):38. [Medline].

Albonico M, Savioli L. Hookworm: a neglected resurgent infection. BMJ. 2017 Oct 24. 359:j4813. [Medline].

Gulland A. Sixty seconds on . . hookworm. BMJ. 2017 Sep 26. 358:j4423. [Medline].

David R Haburchak, MD, FACP Professor Emeritus of Medicine, Department of Medicine, Division of Infectious Diseases, Medical College of Georgia at Augusta University

David R Haburchak, MD, FACP is a member of the following medical societies: American College of Physicians, American Osler Society, American Society for Microbiology, Christian Medical and Dental Associations, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Christopher M Watson, MD, MPH Associate Professor, Department of Pediatrics, Medical College of Georgia at Augusta University

Christopher M Watson, MD, MPH is a member of the following medical societies: American Academy of Pediatrics, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Vinod K Dhawan, MD, FACP, FRCPC, FIDSA Professor, Department of Clinical Medicine, University of California, Los Angeles, David Geffen School of Medicine; Chief, Division of Infectious Diseases, Rancho Los Amigos National Rehabilitation Center

Vinod K Dhawan, MD, FACP, FRCPC, FIDSA is a member of the following medical societies: American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Pranatharthi Haran Chandrasekar, MBBS, MD Professor, Chief of Infectious Disease, Department of Internal Medicine, Wayne State University School of Medicine

Pranatharthi Haran Chandrasekar, MBBS, MD is a member of the following medical societies: American College of Physicians, American Society for Microbiology, International Immunocompromised Host Society, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Jeffrey L Arnold, MD, FACEP Chairman, Department of Emergency Medicine, Santa Clara Valley Medical Center

Jeffrey L Arnold, MD, FACEP is a member of the following medical societies: American Academy of Emergency Medicine and American College of Physicians

Disclosure: Nothing to disclose.

Basim Asmar, MD Director, Department of Pediatrics, Division of Infectious Diseases, Children’s Hospital of Michigan; Professor, Department of Pediatrics, Wayne State University School of Medicine

Basim Asmar, MD is a member of the following medical societies: American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Anika Baxter Tam, MD Staff Physician, Department of Emergency Medicine, New York University / Bellevue Hospital

Disclosure: Nothing to disclose.

Pranatharthi Haran Chandrasekar, MBBS, MD Professor, Department of Internal Medicine, Director of Infectious Disease Fellowship, Harper Hospital, Wayne State University School of Medicine

Pranatharthi Haran Chandrasekar, MBBS, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Swati Garekar, MBBS Staff Physician, Department of Pediatrics, Children’s Hospital of Michigan

Swati Garekar, MBBS is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Aaron Hexdall, MD Assistant Professor, Director of the International Emergency Medicine Initiative, Department of Emergency Medicine, Tufts University School of Medicine, Baystate Medical Center

Disclosure: Nothing to disclose.

Patrick W Hickey, MD, FAAP Assistant Professor of Pediatrics and Preventive Medicine, Uniformed Services University of the Health Sciences; Consulting Staff, Department of Pediatrics, Division of Pediatric Infectious Disease, Walter Reed Army Medical Center

Patrick W Hickey, MD, FAAP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society of Tropical Medicine and Hygiene, and Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Ashir Kumar, MD, MBBS, FAAP Professor Emeritus, Department of Pediatrics and Human Development, Michigan State University College of Human Medicine

Ashir Kumar, MD, MBBS, FAAP is a member of the following medical societies: American Association of Physicians of Indian Origin and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Mark Louden, MD Assistant Professor of Clinical Medicine, Division of Emergency Medicine, Department of Medicine, University of Miami, Leonard M Miller School of Medicine

Mark Louden, MD is a member of the following medical societies: American Academy of Emergency Medicine and American College of Emergency Physicians

Disclosure: Nothing to disclose.

Russell W Steele, MD Head, Division of Pediatric Infectious Diseases, Ochsner Children’s Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Eric L Weiss, MD, DTM&H Medical Director, Office of Service Continuity and Disaster Planning, Fellowship Director, Stanford University Medical Center Disaster Medicine Fellowship, Chairman, SUMC and LPCH Bioterrorism and Emergency Preparedness Task Force, Clinical Associate Progressor, Department of Surgery (Emergency Medicine), Stanford University Medical Center

Eric L Weiss, MD, DTM&H is a member of the following medical societies: American College of Emergency Physicians, American College of Occupational and Environmental Medicine, American Medical Association, American Society of Tropical Medicine and Hygiene, Physicians for Social Responsibility, Southeastern Surgical Congress, Southern Association for Oncology, Southern Clinical Neurological Society, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Hookworm Disease

Research & References of Hookworm Disease|A&C Accounting And Tax Services
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