The hookworm is a parasitic nematode that lives in the small intestine of its host, which may be a mammal such as a dog, cat, or human. Two species of hookworms commonly infect humans, ''Ancylostoma duodenale'' and ''Necator americanus''. ''A. duodenale'' predominates in the Middle East, North Africa, India and (formerly) in southern Europe, while ''N. americanus'' predominates in the Americas, Sub-Saharan Africa, Southeast Asia, China, and Indonesia. Hookworms are thought to infect more than 600 million people worldwide. The ''A. braziliense'' and ''A. tubaeforme'' species infect cats, while ''A. caninum'' infects dogs. ''Uncinaria stenocephala'' infects both dogs and cats.

Hookworms are much smaller than the larger roundworm ''Ascaris lumbricoides'', and the complications of tissue migration and mechanical obstruction so frequently observed with roundworm infestation are less frequent in hookworm infestation. The most significant risk of hookworm infection is anemia, secondary to loss of iron (and protein) in the gut. The worms suck blood voraciously and damage the mucosa. However, the blood loss in the stools is not visibly apparent.

Ancylostomiasis, also known by several other names, is the disease caused when ''A. duodenale'' hookworms, present in large numbers, produce an iron deficiency anemia by sucking blood from the host's intestinal walls.

Hookworm is a leading cause of maternal and child morbidity in the developing countries of the tropics and subtropics. In susceptible children hookworms cause intellectual, cognitive and growth retardation, intrauterine growth retardation, prematurity, and low birth weight among newborns born to infected mothers. In developed countries, hookworm infection is rarely fatal, but anemia can be significant in a heavily infected individual.

Signs and symptoms

There are no specific symptoms or signs of hookworm infection. As mentioned above, they arise from a combination of intestinal inflammation and progressive iron/protein-deficiency anaemia. Larval invasion of the skin might give rise to intense, local itching, usually on the foot or lower leg, which can be followed by lesions that look like insect bites, can blister ("ground itch"), and last for a week or more. Animal hookworm larvae on penetrating humans may produce a creeping eruption called cutaneous larva migrans. The larvae migrate in tortuous tunnels in between stratum germinativum and stratum corneum of the skin, causing serpigenous vesicular lesions. With advancing movement of the larvae, the rear portions of the lesions become dry and crusty. The lesions are typically intensely pruritic. Coughing, chest pain, wheezing, and fever will sometimes be experienced by people who have been exposed to very large numbers of larvae. Epigastric pains, indigestion, nausea, vomiting, constipation, and diarrhea can occur early or in later stages as well, although gastrointestinal symptoms tend to improve with time. Signs of advanced severe infection are those of anemia and protein deficiency, including emaciation, cardiac failure and abdominal distension with ascites.

Pathophysiology

Morphology

''A. duodenale'' worms are grayish white or pinkish with the head slightly bent in relation to the rest of the body. This bend forms a definitive hook shape at the anterior end for which hookworms are named. They possess well developed mouths with two pairs of teeth. While males measure approximately one centimeter by 0.5 millimeter, the females are often longer and stouter. Additionally, males can be distinguished from females based on the presence of a prominent posterior copulatory bursa.

''N. americanus'' is very similar in morphology to ''A. duodenale''. ''N. americanus'' is generally smaller than ''A. duodenale'' with males usually 5 to 9 mm long and females about 1 cm long. Whereas ''A. duodenale'' possess two pairs of teeth, ''N. americanus'' possesses a pair of cutting plates in the buccal capsule. Additionally, the hook shape is much more defined in ''Necator'' than in ''Ancylostoma''.

Pathology

Hookworm infection is generally considered to be asymptomatic, but as Norman Stoll described in 1962, hookworm is an extremely dangerous infection because its damage is “silent and insidious.” There are general symptoms that an individual may experience soon after infection. Ground-itch, which is an allergic reaction at the site of parasitic penetration and entry, is common in patients infected with ''N. americanus''. Additionally, cough and pneumonitis may result as the larvae begin to break into the alveoli and travel up the trachea. Then once the larvae reach the small intestine of the host and begin to mature, the infected individual will suffer from diarrhea and other gastrointestinal discomfort. However, the “silent and insidious” symptoms referred to by Stoll are related to chronic, heavy-intensity hookworm infections. Major morbidity associated with hookworm is caused by intestinal blood loss, iron deficiency anemia, and protein malnutrition. They result mainly from adult hookworms in the small intestine ingesting blood, rupturing erythrocytes, and degrading hemoglobin in the host. This long-term blood loss can manifest itself physically through facial and peripheral edema; eosinophilia and pica caused by iron deficiency anemia are also experienced by some hookworm-infected patients. Recently, more attention has been given to other important outcomes of hookworm infection that play a large role in public health. It is now widely accepted that children who suffer from chronic hookworm infection can suffer from growth retardation as well as intellectual and cognitive impairments. Additionally, recent research has focused on the potential of adverse maternal-fetal outcomes when the mother is infected with hookworm during pregnancy.

The disease was linked to nematode worms (''Ankylostoma duodenalis'') from one-third to half an inch long in the intestine chiefly through the labours of Theodor Bilharz and Griesinger in Egypt (1854).

The symptoms can be linked to inflammation in the gut stimulated by feeding hookworms, such as nausea, abdominal pain and intermittent diarrhea, and to progressive anemia in prolonged disease: capricious appetite, pica (or dirt-eating), obstinate constipation followed by diarrhea, palpitations, thready pulse, coldness of the skin, pallor of the mucous membranes, fatigue and weakness, shortness of breath and in cases running a fatal course, dysentery, hemorrhages and edema.

Blood tests in early infection often show a rise in numbers of eosinophils, a type of white blood cell that is preferentially stimulated by worm infections in tissues (large numbers of eosinophils are also present in the local inflammatory response). Falling blood hemoglobin levels will be seen in cases of prolonged infection with anemia.

In contrast to most intestinal helminthiases, where the heaviest parasitic loads tend to occur in children, hookworm prevalence and intensity can be higher among adult males. The explanation for this is that hookworm infection tends to be occupational, so that plantation workers, coalminers and other groups maintain a high prevalence of infection among themselves by contaminating their work environment. However, in most endemic areas, adult women are the most severely affected by anemia, mainly because they have much higher physiological needs for iron (menstruation, repeated pregnancy), but also because customarily they have access to much poorer food than the men.

An interesting consequence of this in the case of ''Ancylostoma duodenale'' infection is translactational transmission of infection: the skin-invasive larvae of this species do not all immediately pass through the lungs and on into the gut, but spread around the body via the circulation, to become dormant inside muscle fibers. In a pregnant woman, after childbirth some or all of these larvae are stimulated to re-enter the circulation (presumably by sudden hormonal changes), then to pass into the mammary glands, so that the newborn baby can receive a large dose of infective larvae through its mother's milk. This accounts for otherwise inexplicable cases of very heavy, even fatal, hookworm infections in children a month or so of age, in places such as China, India and northern Australia.

An identical phenomenon is much more commonly seen with ''Ancylostoma caninum'' infections in dogs, where the newborn pups can even die of hemorrhaging from their intestines caused by massive numbers of feeding hookworms. This also reflects the close evolutionary link between the human and canine parasites, which probably have a common ancestor dating back to when humans and dogs first started living closely together.

Life cycle

See the image for the biological life cycle of the hookworms where it thrives in warm earth where temperatures are over 18°C. They exist primarily in sandy or loamy soil and cannot live in clay or muck. Rainfall averages must be more than 1000 mm (40 inches) a year. Only if these conditions exist can the eggs hatch. Infective larvae of ''Necator americanus'' can survive at higher temperatures, whereas those of ''Ancylostoma duodenale'' are better adapted to cooler climates. Generally, they live for only a few weeks at most under natural conditions, and die almost immediately on exposure to direct sunlight or desiccation.

Infection of the host is by the larvae, not the eggs. While ''A. duodenale'' can be ingested, the usual method of infection is through the skin; this is commonly caused by walking barefoot through areas contaminated with fecal matter. The larvae are able to penetrate the skin of the foot, and once inside the body, they migrate through the vascular system to the lungs, and from there up the trachea, and are swallowed. They then pass down the esophagus and enter the digestive system, finishing their journey in the intestine, where the larvae mature into adult worms.

Once in the host gut, ''Necator'' tends to cause a prolonged infection, generally 1–5 years (many die within a year or two of infecting), though some adult worms have been recorded to live for 15 years or more. On the other hand, ''Ancylostoma'' adults are short lived, surviving on average for only about 6 months. However, infection can be prolonged because dormant larvae can be "recruited" sequentially from tissue "stores" (see Pathology, above) over many years, to replace expired adult worms. This can give rise to seasonal fluctuations in infection prevalence and intensity (apart from normal seasonal variations in transmission).

They mate inside the host, females laying up to 30,000 eggs per day and some 18 to 54 million eggs during their lifetime, which pass out in feces. Because it takes 5–7 weeks for adult worms to mature, mate and produce eggs, in the early stages of very heavy infection, acute symptoms might occur without any eggs being detected in the patient's feces. This can make diagnosis very difficult.

;Summary of Biological Life Cycle

''N. americanus'' and ''A. duodenale'' eggs can be found in warm, moist soil where they will eventually hatch into first stage larvae, or L1. L1, the feeding non-infective rhabditoform stage, will feed on soil microbes and eventually molt into second stage larvae, L2. L2, which is also in the rhabditoform stage, will feed for approximately 7 days and then molt into the third stage larvae, or L3. L3 is the filariform stage of the parasite, that is, the non-feeding infective form of the larvae. The L3 larvae are extremely motile and will seek higher ground to increase their chances of penetrating the skin of a human host. The L3 larvae can survive up to 2 weeks without finding a host. While ''N. americanus'' larvae only infect through penetration of skin, ''A. duodenale'' can infect both through penetration as well as orally. After the L3 larvae have successfully entered the host, the larvae then travel through the subcutaneous venules and lymphatic vessels of the human host. Eventually, the L3 larvae enter the lungs through the pulmonary capillaries and break out into the alveoli. They will then travel up the trachea to be coughed and swallowed by the host. After being swallowed, the L3 larvae are then found in the small intestine where they molt into the L4, or adult worm stage. The entire process from skin penetration to adult development takes about 5–9 weeks. The female adult worms will release eggs (''N. Americanus'' about 9,000-10,000 eggs/day and ''A. duodenale'' 25,000-30,000 eggs/day) which are passed in the feces of the human host. These eggs will hatch in the environment within several days and the cycle with start anew.

;Incubation Period

The incubation period can vary between a few weeks to many months and is largely dependent on the number of Hookworm parasites an individual is infected with.

Diagnosis

Diagnosis depends on finding characteristic worm eggs on microscopic examination of the stools, although this is not possible in early infection. The eggs are oval or elliptical, measuring 60 µm by 40 µm, colourless, not bile stained and with a thin transparent hyaline shell membrane. When released by the worm in the intestine, the egg contains an unsegmented ovum. During its passage down the intestine, the ovum develops and thus the eggs passed in feces have a segmented ovum, usually with 4 to 8 blastomeres. As the eggs of both ''Ancylostoma'' and ''Necator'' (and most other hookworm species) are indistinguishable, to identify the genus, they must be cultured in the lab to allow larvae to hatch out. If the fecal sample is left for a day or more under tropical conditions, the larvae will have hatched out, so eggs might no longer be evident. In such a case, it is essential to distinguish hookworms from ''Strongyloides'' larvae, as infection with the latter has more serious implications and requires different management. The larvae of the two hookworm species can also be distinguished microscopically, although this would not be done routinely, but usually for research purposes. Adult worms are rarely seen (except via endoscopy, surgery or autopsy), but if found, would allow definitive identification of the species. Classification can be performed based on the length of the buccal cavity, the space between the oral opening and the esophagus: hookworm rhabditoform larvae have long buccal cavities whereas ''Strongyloides'' rhabditoform larvae have short buccal cavities.

Recent research has focused on the development of DNA-based tools for diagnosis of infection, specific identification of hookworm, and analysis of genetic variability within hookworm populations.

Prevention

The infective larvae develop and survive in an environment of damp dirt, particularly sandy and loamy soil. They cannot survive in clay or muck. The main lines of precaution are those dictated by sanitary science:

Do not defecate in places other than latrines, toilets etc.

Do not use human excrement or raw sewage or untreated 'night soil' as manure/fertilizer in agriculture

Do not walk barefoot in known infected areas

Deworm pet dogs — canine and feline hookworms rarely develop to adulthood in humans (''Ancylostoma caninum'', the common dog hookworm, occasionally develops into an adult to cause eosinophilic enteritis in people), but their invasive larvae can cause an itchy rash called cutaneous larva migrans.

Moxidectin has been released in the United States as part of Advantage Multi (imidacloprid + moxidectin) Topical Solution for dogs and cats. It utilizes moxidectin for control and prevention of roundworms, hookworms, heartworms, and whipworms.

With an estimated 740 million individuals infected, hookworm is a major public health concern in our world today. While hookworm infection may not directly lead to mortality, its effects on morbidity demand immediate attention. When considering disability-adjusted-life-years (DALYs), neglected tropical diseases, including hookworm, rank among diarrheal diseases, ischemic heart disease, malaria, and tuberculosis as one of the most important health problems of the developing world.

It has been estimated that as many as 22.1 million DALYs have been lost due to hookworm. Recently, there has been increasing interest to address the public health concerns associated with hookworm. For example, the Bill & Melinda Gates Foundation recently donated US$34 million to fight Neglected Tropical Diseases including hookworm infection. Former US President Clinton also announced a mega-commitment at the Clinton Global Initiative (CGI) 2008 Annual Meeting to de-worm 10 million children.

Most of these public health concerns have focused on children who are infected with hookworm. This focus on children is largely due to the large body of evidence that has demonstrated strong associations between hookworm infection and impaired learning, increased absences from school, and decreased future economic productivity. In 2001, the 54th World Health Assembly passed a resolution demanding member states to attain a minimum target of regular deworming of at least 75% of all at-risk school children by the year 2010. A 2008 World Health Organization publication reported on these efforts to treat at-risk school children. Some of the interesting statistics were as follows: 1) only 9 out of 130 endemic countries were able to reach the 75% target goal; and 2) less than 77 million school-aged children (of the total 878 million at risk) were reached which means that only 8.78% of at-risk children are being treated for hookworm infection. While there is progress being made, these numbers also remind us of how much work is still to be done.

School-based mass deworming programs have been the most popular strategy to address the issue of hookworm infection in children. School-based programs are extremely cost effective as schools already have an available, extensive, and sustained infrastructure with a skilled workforce that has a close relationship with the community. With little training from a local health system, teachers can easily administer the drugs which often cost less than $0.50 per child per year.

Recently, many people have begun to question if the school-based programs are necessarily the most effective approach. An important concern with school-based programs is that they often do not reach children who do not attend school, thus ignoring a large amount of at-risk children. A 2008 study by Massa et al. continued the debate regarding school-based programs. They examined the effects of community-directed treatments versus school-based treatments in the Tanga Region of Tanzania. A major conclusion was that the mean infection intensity of hookworm was significantly lower in the villages employing the community-directed treatment approach than the school-based approach. The community-directed treatment model used in this specific study allowed villagers to take control of the child’s treatment by having villagers select their own community drug distributors to administer the antihelminthic drugs. Additionally, villagers organized and implemented their own methods for distributing the drugs to all children. The positive results associated with this new model highlight the need for large-scale community involvement in deworming campaigns.

Many mass deworming programs also combine their efforts with a public health education. These health education programs often stress important preventative techniques such as: always wearing shoes, washing your hands before eating, and staying away from water/areas contaminated by human feces. But while these may seem like simple tasks, they raise important public health challenges. The fact is that most infected populations are from poverty-stricken areas with very poor sanitation. Thus, it is most likely that at-risk children cannot afford shoes to wear, do not have access to clean water to wash their hands, and live in environments with no proper sanitation infrastructure. Health education, therefore, must address preventive measures in ways that are both feasible and sustainable in the context of resource-limited settings.

Evaluation of numerous public health interventions have generally shown that improvement in each individual component ordinarily attributed to poverty (for example, sanitation, health education, footwear, and underlying nutrition status) often have minimal impact on transmission. For example, one study found that the introduction of latrines into a resource-limited community only reduced the prevalence of hookworm by four percent. Another study in Salvador, Brazil found that improved drainage and sewerage had minimal impact of the prevalence and no impact at all on the intensity of hookworm. This seems to suggest that environmental control alone has minimal effect on the transmission of hookworm. It is imperative, therefore, that more research be performed to understand the efficacy and sustainability of integrated programs that combine numerous preventive methods including education, sanitation, and treatment.

Management

The most common treatment for hookworm are benzimidazoles, specifically albendazole and mebendazole. BZAs kill adult worms by binding to the nematode’s β-tubulin and subsequently inhibiting microtubule polymerization within the parasite. This substantiates prior claims that albendazole is much more effective than mebendazole for Hookworm infections. Also of note is that the World Health Organization does recommend anthelmintic treatment in pregnant women after the first trimester.]] It is estimated that between 576-740 million individuals are infected with hookworm today. The major etiology of hookworm infection is ''N. Americanus'' which is found the Americas, sub-Saharan Africa, and Asia. ''A. duodenale'' is found in more scattered focal environments, namely Europe and the Mediterranean. Most infected individuals are concentrated in sub-Saharan Africa and East Asia/the Pacific Islands with each region having estimates of 198 million and 149 million infected individuals, respectively. Other affected regions include: South Asia (50 million), Latin America and the Caribbean (50 million), South Asia (59 million), Middle East/North Africa (10 million).

• 42.8% infection rate of predominantly ''N. Americanus'' although with some ''A. Duodenale'' infection

• Both hookworm infection load and degree of anemia in the mild range

Xiulongkan Village, Hainan Province, China (Gandhi et al. 2001)

• 60% infection rate of predominantly ''N. Americanus''

• Important trends noted were that prevalence increased with age (plateau of about 41 years) and women had higher prevalence rates than men

Hoa Binh, Northwest Vietnam (Verle et al. 2003)

• 52% of a total of 526 tested households infected

• Could not identify species, but previous studies in North bob reported ''N. Americanus'' in more than 95% of hookworm larvae

Minas Gerais, Brazil (Fleming et al. 2006)

• 62.8% infection rate of predominantly ''N. Americanus''

KwaZulu-Natal, South Africa (Mabaso et al. 2004)

• Inland areas had a prevalence rate of 9.3% of ''N. Americanus''

• Coastal plain areas had a prevalence rate of 62.5% of ''N. Americanus''

There have also been recent technological developments that will hopefully facilitate more accurate mapping of hookworm prevalence. Some researchers have begun to use geographical information systems (GIS) and remote sensing (RS) to examine helminth ecology and epidemiology. Brooker et al. utilized this technology to create helminth distribution maps of sub-Saharan Africa. By relating satellite derived environmental data with prevalence data from school-based surveys, they were able to create detailed prevalence maps. The study focused on a wide range of helminths, but interesting conclusions about hookworm specifically were found. As compared to other helminths, hookworm is able to survive in much hotter conditions and was highly prevalent throughout the upper end of the thermal range. Hopefully this information along with more detailed prevalence maps can lead to more effective public health measures.

Improved molecular diagnostic tools are another technological advancement that could help improve existing prevalence statistics. Recent research has focused on the development of DNA-based tool that can be used for diagnosis of infection, specific identification of hookworm, and analysis of genetic variability in hookworm populations. Again this can serve as a major tool for different public health measures against hookworm infection. Most research regarding diagnostic tools is now focused on the creation of a rapid and cost-effective assay for the specific diagnosis of hookworm infection. Many are hopeful that its development can be achieved within the next 5 years. The hookworm exhibit was a prominent part of the 1910 Mississippi state fair. The program nearly eradicated hookworm and would flourish afterwards with new funding as the Rockefeller Foundation International Health Division.

In the 1920s, hookworm eradication reached the Caribbean and Latin America, where great mortality was reported among Black people in the West Indies towards the end of the 18th century, as well as through descriptions sent from Brazil and various other tropical and sub-tropical regions.

Early treatment relied on the use of Epsom salt to reduce protective mucous, followed by thymol to kill the worms. Later tetrachloroethylene was the leading method. It was not until later in the mid-20th century when new organic drug compounds were developed.

Research

Anemia in pregnancy

It is estimated that a third of all pregnant women in developing countries are infected with hookworm, 56% of all pregnant women in developing countries suffer from anemia, 20% of all maternal deaths are either directly or indirectly related to anemia. Numbers like this have led to an increased interest in the topic of hookworm-related anemia during pregnancy. With the understanding that chronic Hookworm infection can often lead to anemia, many people are now questioning if the treatment of hookworm could effect change in severe anemia rates and thus also on maternal and child health as well. Most evidence suggests that the contribution of hookworm to maternal anemia merits that all women of child-bearing age living in endemic areas be subject to periodic anthelmintic treatment. The World Health Organization even recommends that infected pregnant women be treated after their first trimester.

This lack of deworming of pregnant women is explained by the fact that most individuals still fear that anthelmintic treatment will result in adverse birth outcomes. But a 2006 study by Gyorkos et al. found that when comparing a group of pregnant women treated with mebendazole with a control placebo group, both illustrated rather similar rates in adverse birth outcomes. The treated group demonstrated 5.6% adverse birth outcomes, while the control group had 6.25% adverse birth outcomes. Furthermore, Larocque et al. illustrated that treatment for hookworm infection actually led to positive health results in the infant. This study concluded that treatment with mebendazole plus iron supplements during antenatal care significantly reduced the proportion of very low birth weight infants when compared to a placebo control group. Studies so far have validated recommendations to treat infected pregnant women for hookworm infection during pregnancy.

The intensity of hookworm infection as well as the species of hookworm have yet to be studied as they relate to hookworm-related anemia during pregnancy. Additionally, more research must be done in different regions of the world to see if trends noted in completed studies persist.

Malaria co-infection

Co-infection with hookworm and ''Plasmodium falciparum'' is fairly ubiquitous throughout Africa due to spatial congruence. Although exact numbers are unknown, preliminary analyses estimate that as many as a quarter of African schoolchildren (17.8–32.1 million children aged 5–14 years) may be coincidentally at-risk for both ''P. falciparum'' and hookworm. While original hypotheses stated that co-infection with multiple parasites would impair the host’s immune response to a single parasite and increase susceptibility to clinical disease, studies have yielded contrasting results. For example, one study in Senegal showed that the risk of clinical malaria infection was increased in helminth-infected children in comparison to helminth-free children while other studies have failed to reproduce such results. Some hypotheses and studies even suggest that helminth infections may protect against cerebral malaria due to the possible modulation of pro-inflammatory and anti-inflammatory cytokines responses. Furthermore, the mechanisms underlying this supposed increased susceptibility to disease are unknown. For example, it is known that helminth infections cause potent and highly polarized immune response characterized by increased T-helper cell type 2 (T_h2) cytokine and Immunoglobulin E(IgE) production. However, the effect of such responses on the human immune response is unknown. Additionally, both malaria and helminth infection can cause anemia, but the effect of co-infection and possible enhancement of anemia is poorly understood.

Hygiene hypothesis

The hygiene hypothesis states that infants and children who lack exposure to infectious agents are more susceptible to allergic diseases via modulation of immune system development. As Mary Ruebush writes in her book ''Why Dirt is Good'', “what a child is doing when he puts things in his mouth is allowing his immune response to explore his environment. Not only does this allow for ‘practice’ of immune responses, which will be necessary for protection, but it also plays a critical role in teaching the immature immune response what is best ignored.” The theory was first proposed by David P. Strachan who noted that hay fever and eczema were less common in children who belonged to large families. Since then, studies have noted the effect of gastrointestinal worms on the development of allergies in the developing world. For example, a study in Gambia found that eradication of worms in some villages led to increased skin reactions to allergies among children.

Although the exact mechanism is unknown, scientists hypothesize that the helper T cells are key players. Allergic diseases, which are immunological responses to normally harmless antigens, are driven by a TH2-mediated immune response. Bacteria, viruses, and parasites, on the other hand, elicit a TH1-mediated immune response which inhibits or down-regulates the TH2 response. TH1 also inhibits the activity of TH17 which is heightened in numerous inflammatory diseases including multiple sclerosis and asthma. More research is currently being performed to better understand the possible mechanism for the hygiene hypothesis.

Vaccines

While annual or semi-annual mass antihelminthic administration is a critical aspect of any public health intervention, many have begun to realize how unsustainable it is due to aspects such as poverty, high rates of re-infection, and diminished efficacy of drugs with repeated use. Current research, therefore, has focused on the development of a vaccine that could be integrated into existing control programs. The goal of vaccine development is not necessarily to create a vaccine with sterilizing immunity or complete protection against immunity. A vaccine that reduces the likelihood of vaccinated individuals developing severe infections and thus reduced blood and nutrient levels could still have a significant impact on the high burden of disease throughout the world.

Current research focuses on targeting two stages in the development of the worm: the larval stage and the adult stage. Research on larval antigens has focused on proteins that are members of the pathogenesis-related protein superfamily, ''Ancylostoma'' Secreted Proteins. Although they were first described in ''Anyclostoma'', these proteins have also been successfully isolated from the secreted product of ''N. americanus''. ''N. americanus'' ASP-2 (Na-ASP-2) is currently the leading larval-stage hookworm vaccine candidate. A randomized, double-blind, placebo-controlled study has already been performed; 36 healthy adults without a history of hookworm infection were given three intramuscular injections of three different concentrations of Na-ASP-2 and observed for six months after the final vaccination. The vaccine induced significant anti-Na-ASP-2 IgG and cellular immune responses. In addition, it was safe and produced no debilitating side effects. The vaccine is now in a phase one trial; healthy adult volunteers with documented evidence of previous infection in Brazil are being given the same dose concentration on the same schedule used in the initial study. If this study is successful, the next step would be to conduct a phase two trial to assess the rate and intensity of hookworm infection among vaccinated persons. Because the Na-ASP-2 vaccine only targets the larval stage, it is critical that all subjects enrolled in the study be treated with antihelminthic drugs to eliminate adult worms prior to vaccination.

Adult hookworm antigens have also been identified as potential candidates for vaccines. When adult worms attach to the intestinal mucosa of the human host, erythrocytes are ruptured in the worm’s digestive tract which causes the release of free hemoglobin which is subsequently degraded by a proteolytic cascade. Several of these proteins that are responsible for this proteolytic cascade are also essential for the worm’s nutrition and survival. Therefore, a vaccine that could induce antibodies for these antigens could interfere with the hookworm’s digestive pathway and impair the worm’s survival. Three proteins have been identified: the aspartic protease-hemoglobinase APR-1, the cysteine protease-hemoglobinase CP-2, and a glutathione S-transferase. Vaccination with APR-1 and CP-2 led to reduced host blood loss and fecal egg counts in dogs. With APR-1, vaccination even led to reduced worm burden. Research is currently stymied at the development of at least one of these antigens as a recombinant protein for testing in clinical trials.

Hookworm in therapy

Moderate hookworm infections have been demonstrated to have beneficial effects on hosts suffering from diseases linked to overactive immune systems. This is possibly explained by the hygiene hypothesis. Research at the University of Nottingham conducted in Ethiopia observed a small subset of people with hookworm infections were half as likely to experience asthma or hay fever. Potential benefits have also been hypothesized in cases of multiple sclerosis, Crohn's Disease and diabetes.

Research conducted by the Queensland Institute of Medical Research (QIMR) and the Princess Alexandra Hospital (located in Australia) has shown favourable results in clinical trials using hookworms to treat coeliac disease.

Quick Facts

! Genus and Species	! Necator americanus	! Ancylostoma duodenale
		Adult – IDA Microcytic, Hypochromic Anemia

See also

Hookworm disease

Cutaneous larva migrans (Creeping eruption)

List of parasites (human)

Dr. Lillian H. South

Notes

References

External links

CDC Department of Parasitic Diseases images of the hookworm life cycle

Centers for Disease Control and Prevention

Dog hookworm (''Ancylostoma caninum'') at MetaPathogen: facts, life cycle, references

Human hookworms (''Ancylostoma duodenale'' and ''Necator americanus'') at MetaPathogen: facts, life cycle, references

Category:Nematodes Category:Parasitic animals Category:Neglected diseases Category:Conditions diagnosed by stool test

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Coordinates	12°58′0″N77°34′0″N
name	Blind Blake
background	solo_singer
birth name	Arthur Blake
born	ca. 1893
died	1933?
origin	Jacksonville, Florida, United States (uncertain)
instrument	Guitar, Vocals
genre	Piedmont blues, ragtime, country blues
associated acts	Irene Scruggs
notable instruments	}}

"Blind" Blake (born Arthur Blake, circa 1893, Jacksonville, Florida; died: circa 1933) was an influential blues/ragtime singer and guitarist. He is often called "The King of Ragtime Guitar".

Biography

Blind Blake recorded about 80 tracks for Paramount Records between 1926 and 1932. He was one of the most accomplished guitarists of his genre with a surprisingly diverse range of material. He is best known for his distinct guitar sound that was comparable in sound and style to a ragtime piano.

Little is known about his life. His birthplace was listed as Jacksonville, Florida by Paramount Records but that is not firmly established. On one recording he slipped into a Geechee dialect, prompting speculation that he was from the Georgia coastal region. Nothing is definitely known of his death and even his name is not certain. According to one source, his real name was Arthur Phelps, although concrete evidence for this claim is lacking. The "Phelps" name theory was entirely based on a response given by Blind Willie McTell in an interview conducted in 1955 in Atlanta, where Blake has never been reported; nor did McTell ever reside in Chicago. Recent research has discovered that many of Blind Blake's recordings were copyrighted under the name 'Arthur Blake', and in his two-part recording with Papa Charlie Jackson, "Papa Charlie and Blind Blake Talk About It", the following dialogue is heard:

Jackson: What is your right name?

Blake: My right name is Arthur Blake!

There is only one surviving photograph of him in existence.

His first recordings were made in 1926 and his records sold very well. His first solo record was "Early Morning Blues" with "West Coast Blues" on the B-side. Both are considered excellent examples of his ragtime-based guitar style and are prototypes for the burgeoning Piedmont blues. Blake made his last recordings in 1932, the end of his career aided by Paramount's bankruptcy. It is often said that the later recordings have much less sparkle. Stefan Grossman and Gayle Dean Wardlow think its possible that only one side of Blake's last record is actually by him. "Champagne Charlie Is My Name" does not actually sound like Blake's playing or singing. Allegedly, Blind Blake was drinking heavily in his final years. It is likely that this led to his early death at only 40 years old. The exact circumstances of his death are not known; Reverend Gary Davis said in an interview that he had heard Blake was killed by a streetcar.

His complex and intricate finger picking has inspired Reverend Gary Davis, Jorma Kaukonen, Ry Cooder, Ralph McTell, Leon Redbone and many others. French singer-songwriter Francis Cabrel refers to Blind Blake in the song "Cent Ans de Plus" on the 1999 album ''Hors-Saison.''

Other people that used the same name

On a few records where white jazz guitarist Eddie Lang sat in with African American groups, the record companies listed Lang as "Blind Blake". Most of those recordings, principally with Lonnie Johnson, gave Lang the name "Blind Willy Dunn".

There is also a different artist who recorded multiple LPs under the name "Blind Blake". Alphonso "Blind Blake" Higgs was one of the most popular singers in The Bahamas in the 1950s, leading the house band at the Royal Victoria Hotel. His records were spread all over the U.S. by tourist fans, and several of his songs became folk standards.

References

External links

Illustrated Blind Blake discography

Category:Acoustic blues musicians Category:Piedmont blues musicians Category:Country blues musicians Category:Delta blues musicians Category:Chicago blues musicians Category:Ragtime musicians Category:Songster musicians Category:African American musicians Category:Country blues singers Category:American blues guitarists Category:American male singers Category:Blind musicians Category:King Records artists Category:Blues Hall of Fame inductees Category:People from Jacksonville, Florida Category:1893 births Category:1933 deaths Category:Blind bluesmen

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