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Not to be confused with Pinworm or Ringworm.
Necator americanus and Ancylostoma duodenale
Scientific classification
Kingdom: Animalia
Phylum: Nematoda
Class: Secernentea
Order: Strongiloidae
Family: Ancylostomatidae
Genus: Necator/Ancylostoma
Species
Species N. americanus and A. duodenale
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.
Contents [hide]
1 Signs and symptoms
2 Pathophysiology
2.1 Morphology
2.2 Pathology
2.3 Life cycle
3 Diagnosis
4 Prevention
5 Management
6 Epidemiology
7 History
8 Research
8.1 Anemia in pregnancy
8.2 Malaria co-infection
8.3 Hygiene hypothesis
8.4 Vaccines
8.5 Hookworm in therapy
9 Quick Facts
10 See also
11 Notes
12 References
13 External links
[edit] Signs and symptomsThere 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.
[edit] Pathophysiology[edit] MorphologyA. 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.[1]
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.[1]
[edit] PathologyHookworm 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.”[2] 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.[1] 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.[1] 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.[3] They result mainly from adult hookworms in the small intestine ingesting blood, rupturing erythrocytes, and degrading hemoglobin in the host.[4] 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.[1] 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.[4] 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.
[edit] Life cycle
Hookworm life cycleSee 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.[4][5]
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).
Civilian Public Service workers built and installed 2065 outhouses for hookworm eradication in Mississippi and Florida from 1943 to 1947.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.[3][4][6]
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.[7]
[edit] Diagnosis
Hookworm eggDiagnosis 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.[1]
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.[8] Because hookworm eggs are often indistinguishable from other parasitic eggs, PCR assays could serve as a molecular approach for accurate diagnosis of hookworm in the feces.[8][9]
[edit] PreventionThe 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.[10] Former US President Clinton also announced a mega-commitment at the Clinton Global Initiative (CGI) 2008 Annual Meeting to de-worm 10 million children.[11]
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.[4] 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.[12] 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.[13] 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.[12] 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.[14]
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.[15] 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.[16] 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.[17] 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.
[edit] ManagementThe 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.[3] In certain circumstances, levamisole and pyrantel pamoate may be used.[4] The 2008 study by Keiser and Utzinger, Efficacy of Current Drugs Against Soil-Transmitted Helminth Infections: Systematic Review and Meta-analysis, examined the relative efficacies of different drug treatments. They found that the efficacy of single-dose treatments for Hookworm infections were as follows: 72% for albendazole, 15% for mebendazole, and 31% for pyrantel pamoate.[18] 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.[3] It is also recommended that if the patient also suffers from anemia that ferrous sulfate (200 mg) be administered three times daily at the same time as anthelmintic treatment; this should be continued until hemoglobin values return to normal which could take up to 3 months.[1]
Other important issues related to the treatment of hookworm are reinfection and drug resistance. It has been shown that reinfection after treatment can be extremely high. Some studies even show that 80% of pretreatment hookworm infection rates can be seen in treated communities within 30–36 months.[3] While reinfection may occur, it is still recommended that regular treatments be conducted as it will minimize the occurrence of chronic outcomes. There are also increasing concerns about the issue of drug resistance. Drug resistance has appeared in front-line anthelmintics used for livestock nematodes. Generally human nematodes are less likely to develop resistance due to longer reproducing times, less frequent treatment, and more targeted treatment. Nonetheless, the global community must be careful to maintain the effectiveness of current anthelmintic as no new anthelmintic drugs are in the late-stage development.[3]
The hookworm can be treated with local cryotherapy when it is still in the skin.
Albendazole is effective both in the intestinal stage and during the stage the parasite is still migrating under the skin.
In case of anaemia, iron supplementation can cause relief symptoms of iron deficiency anemia. However, as red blood cell levels are restored, shortage of other essentials such as folic acid or vitamin B12 may develop, so these might also be supplemented.
[edit] Epidemiology
Disability-adjusted life year for hookworm disease per 100,000 inhabitants in 2002.
no data
less than 10
10-15
15-20
20-25
25-30
30-35
35-40
40-45
45-50
50-55
55-60
more than 60It is estimated that between 576-740 million individuals are infected with hookworm today.[3] Of these infected individuals, about 80 million are severely affected.[8] The major etiology of hookworm infection is N. Americanus which is found the Americas, sub-Saharan Africa, and Asia.[4] 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).[3] A majority of these infected individuals live in poverty-stricken areas with poor sanitation. Hookworm infection is most concentrated among the world’s poorest who live on less than $2 a day.[4]
Many of the numbers regarding the prevalence of hookworm infection are estimates as there is no international surveillance mechanism currently in place to determine prevalence and global distribution.[4] Some prevalence rates have been measured through survey data in endemic regions around the world. The following are some of the most recent findings on prevalence rates in regions endemic with hookworm.
Darjeeling, Hooghly District, West Bengal, India (Pal et al. 2007)[19]
• 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)[20]
• 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)[21]
• 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)[22]
• 62.8% infection rate of predominantly N. Americanus
KwaZulu-Natal, South Africa (Mabaso et al. 2004)[23]
• 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.[24]
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.[8]
[edit] History
Not to be confused with Pinworm or Ringworm.
Necator americanus and Ancylostoma duodenale
Scientific classification
Kingdom: Animalia
Phylum: Nematoda
Class: Secernentea
Order: Strongiloidae
Family: Ancylostomatidae
Genus: Necator/Ancylostoma
Species
Species N. americanus and A. duodenale
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.
Contents [hide]
1 Signs and symptoms
2 Pathophysiology
2.1 Morphology
2.2 Pathology
2.3 Life cycle
3 Diagnosis
4 Prevention
5 Management
6 Epidemiology
7 History
8 Research
8.1 Anemia in pregnancy
8.2 Malaria co-infection
8.3 Hygiene hypothesis
8.4 Vaccines
8.5 Hookworm in therapy
9 Quick Facts
10 See also
11 Notes
12 References
13 External links
[edit] Signs and symptomsThere 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.
[edit] Pathophysiology[edit] MorphologyA. 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.[1]
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.[1]
[edit] PathologyHookworm 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.”[2] 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.[1] 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.[1] 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.[3] They result mainly from adult hookworms in the small intestine ingesting blood, rupturing erythrocytes, and degrading hemoglobin in the host.[4] 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.[1] 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.[4] 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.
[edit] Life cycle
Hookworm life cycleSee 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.[4][5]
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).
Civilian Public Service workers built and installed 2065 outhouses for hookworm eradication in Mississippi and Florida from 1943 to 1947.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.[3][4][6]
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.[7]
[edit] Diagnosis
Hookworm eggDiagnosis 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.[1]
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.[8] Because hookworm eggs are often indistinguishable from other parasitic eggs, PCR assays could serve as a molecular approach for accurate diagnosis of hookworm in the feces.[8][9]
[edit] PreventionThe 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.[10] Former US President Clinton also announced a mega-commitment at the Clinton Global Initiative (CGI) 2008 Annual Meeting to de-worm 10 million children.[11]
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.[4] 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.[12] 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.[13] 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.[12] 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.[14]
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.[15] 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.[16] 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.[17] 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.
[edit] ManagementThe 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.[3] In certain circumstances, levamisole and pyrantel pamoate may be used.[4] The 2008 study by Keiser and Utzinger, Efficacy of Current Drugs Against Soil-Transmitted Helminth Infections: Systematic Review and Meta-analysis, examined the relative efficacies of different drug treatments. They found that the efficacy of single-dose treatments for Hookworm infections were as follows: 72% for albendazole, 15% for mebendazole, and 31% for pyrantel pamoate.[18] 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.[3] It is also recommended that if the patient also suffers from anemia that ferrous sulfate (200 mg) be administered three times daily at the same time as anthelmintic treatment; this should be continued until hemoglobin values return to normal which could take up to 3 months.[1]
Other important issues related to the treatment of hookworm are reinfection and drug resistance. It has been shown that reinfection after treatment can be extremely high. Some studies even show that 80% of pretreatment hookworm infection rates can be seen in treated communities within 30–36 months.[3] While reinfection may occur, it is still recommended that regular treatments be conducted as it will minimize the occurrence of chronic outcomes. There are also increasing concerns about the issue of drug resistance. Drug resistance has appeared in front-line anthelmintics used for livestock nematodes. Generally human nematodes are less likely to develop resistance due to longer reproducing times, less frequent treatment, and more targeted treatment. Nonetheless, the global community must be careful to maintain the effectiveness of current anthelmintic as no new anthelmintic drugs are in the late-stage development.[3]
The hookworm can be treated with local cryotherapy when it is still in the skin.
Albendazole is effective both in the intestinal stage and during the stage the parasite is still migrating under the skin.
In case of anaemia, iron supplementation can cause relief symptoms of iron deficiency anemia. However, as red blood cell levels are restored, shortage of other essentials such as folic acid or vitamin B12 may develop, so these might also be supplemented.
[edit] Epidemiology
Disability-adjusted life year for hookworm disease per 100,000 inhabitants in 2002.
no data
less than 10
10-15
15-20
20-25
25-30
30-35
35-40
40-45
45-50
50-55
55-60
more than 60It is estimated that between 576-740 million individuals are infected with hookworm today.[3] Of these infected individuals, about 80 million are severely affected.[8] The major etiology of hookworm infection is N. Americanus which is found the Americas, sub-Saharan Africa, and Asia.[4] 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).[3] A majority of these infected individuals live in poverty-stricken areas with poor sanitation. Hookworm infection is most concentrated among the world’s poorest who live on less than $2 a day.[4]
Many of the numbers regarding the prevalence of hookworm infection are estimates as there is no international surveillance mechanism currently in place to determine prevalence and global distribution.[4] Some prevalence rates have been measured through survey data in endemic regions around the world. The following are some of the most recent findings on prevalence rates in regions endemic with hookworm.
Darjeeling, Hooghly District, West Bengal, India (Pal et al. 2007)[19]
• 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)[20]
• 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)[21]
• 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)[22]
• 62.8% infection rate of predominantly N. Americanus
KwaZulu-Natal, South Africa (Mabaso et al. 2004)[23]
• 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.[24]
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.[8]
[edit] History