Hookworm
Introduction
Hookworm infection is caused by the blood-feeding nematode parasites of the species Ancylostomaduodenale and Necatoramericanus. Together, the hookworms infect an estimated 576-740 million individuals today of which 80 million are severely infected. The morbidity associated with severe infection includes intestinal blood loss, anemia, and protein malnutrition. The burden of infection is concentrated mostly among the world’s poorest who live on less than $2 a day. A particularly vulnerable population is children in low and middle income countries as infection with hookworm can stunt growth and physical fitness and impair and intellectual and cognitive development. The tragic irony of the situation is that there are readily available and cheap resources for treatment which often cost less than 2 cents per pill.[1]
Morphology
Adult 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 (Figure 1). 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 Figure 1. Teeth of Ancylostoma on the right and cutting plates of Necator on the left.[1] 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 (Figure 1). Additionally, the hook shape is much more defined in Necator than inAncylostoma.[1]

Life Cycle | | | Figure 2. Life Cycle of hookworm[9] |
Step 1: Eggs are passed in the stool of an infected person. Hookworm eggs are not infective.

Step 2: Under favorable conditions (moisture, warmth, and shade), larvae hatch in 1 to 2 days.

Step 3: The released first stage (rhabditiform) larvae grow in the feces and/or the soil, and after 5 to 10 days they become third stage (filariform) larvae. These infective larvae can survive 3 to 4 weeks in favorable environmental conditions.

Step 4: Upon contact with the human host (mostly through the skin but larvae can also be ingested) the larvae penetrate the skin and are carried through the veins to the heart and then to the lungs. They penetrate the pulmonary alveoli, ascend the bronchial tree to the pharynx, and are swallowed.

Step 5: The larvae reach the small intestine, where they reside and mature into adults. Adult worms live in the lumen of the small intestine, where they attach to the intestinal wall, with resultant blood loss by the host. The presence of between 40 and 160 adult hookworms in the human intestine results in blood loss sufficient to cause anemia and malnutrition. Most adult worms are eliminated in 1 to 2 years, but they can live for several years.[10]

Biochemical Properties
To infect their hosts, hookworm larvae must exsheath and migrate through connective tissue. A modified in vitro skin chamber was used to show that the human hookworm Ancylostoma duodenale and the zoonotic canine hookworm Ancylostoma caninum penetrate epidermis, basement membrane, and dermis in similar ways. These similarities in tissue invasion properties reflect the observed biochemical similarities in parasite protease composition. The larvae of both species contain protease activity that is inhibited by o-phenanthroline; this identifies the proteases as metalloproteases. The enzyme activities exhibit an alkaline pH optimum between pH 9 and 10. During modified sodium dodecyl sulfate-polyacrylamide gel electrophoresis in which a protein substrate (either casein or gelatin) was used, the protease activities resolved into a major band at an Mr of 68,000 and a minor band at an Mr of 38,000. Proteases were released by living A. caninum larvae in vitro and degraded purified and radiolabeled casein to smaller peptides. Motile hookworm larvae were also incubated with purified and radiolabeled connective tissue macromolecules in vitro. Both Ancylostoma species degraded human fibronectin to a 60,000-Mr polypeptide intermediate, but could not degrade solubilized bovine elastin or human laminin. In contrast, the obligate skin-penetrating nematode Strongyloides stercoralis degraded all three substrates. This biochemical difference may explain some observed differences in invasiveness.[2]
Pathogenesis and Immunity in Hookworm Infection

The species of hookworm that parasitize man can be segregated according to whether or not the adult hookworms induce intestinal haemorrhage. By radioisotope tracer techniques, it has been shown that the 3 hookworms which infect man (Ancylostoma duodenale, Necator americanus and Ancylostoma ceylanicum), are prodigious blood-suckers. The haematophagous appetites of these 4 hookworms constitute the primary pathogenic mechanism of ancylostomiasis. Since it appears that whole blood is lost into the intestine, the strain on protein, particularly albumin, metabolism must not be overlooked. Some aspects of the development of a polyvalent X-irradiated vaccine for hookworm disease of dogs are reviewed, with particular emphasis on the mechanisms by which vaccinated dogs resist the potential pathogenesis of challenge infections.
Circumstantial evidence, which suggests that man also develops immunity to reinfection with hookworms, is discussed in the light of the findings from experiments with vaccinated dogs, and with reference to the hypothetical benefits that might be conferred on children by vaccination.[4]

Diseases
Hookworms (Ancylostoma duodenale and Necator americanus) are the most common intestinal nematodes in the world. Hookworms are a leading cause of Ancylostomiasis and Necatoriasis (Hookworm infection). These cause iron deficiency anemia in children and, if left untreated, can lead to growth retardation and arrested intellectual development. [5]
Infection Acquiring
Infection is acquired by invasion of the infective larval stages through the skin (A. duodenalelarvae are also orally infective). Following host entry, the larvae undergo a journey through the vasculature, then the lungs and other tissues.[6]
Intensity of Infection
Because hookworms do not replicate in humans, the morbidity of hookworm is highest among patients that harbor large numbers of adult parasites. Estimates of the intensity of hookworm infection are typically obtained by using quantitative fecal egg counts as a surrogate marker for worm burden. The World Health Organization defines moderate-intensity infections as those with 2,000–3,999 eggs per gram of feces, and heavy-intensity infections as those with 4,000 or more eggs per gram (p. 26 in ). [7]
Clinical Manifestations
Symptoms
Abdominal discomfort, Cough, Diarrhea, Fatigue, Fever, Gas, Itchy rash, Loss of appetite, Nausea, vomiting and Pale skin. [8]
Complications
Adult hookworms cause morbidity in the host by producing intestinal hemorrhage. The adult hookworms then ingest the blood, rupture the erythrocytes, and degrade the hemoglobin. Therefore, the disease attributed to hookworm is silent blood loss leading to iron deficiency anemia and protein malnutrition. There is a correlation between parasite intensity and host intestinal blood loss. In children, chronic heavy-intensity infections are associated with growth retardation, as well as intellectual and cognitive impairments; in pregnant women, they are associated with adverse maternal–fetal outcomes.[6] Severe protein loss with fluid buildup in the abdomen (ascites) may occur.[8]
Diagnosis
Tests that can help diagnose the infection include: * Complete blood count (CBC) with differential.[8] * Stool ova and parasites exam.[8] * Multiplex PCR.[8] * Hookworm Culture by Agar-plate:
The efficacy of agar-plate culture has been evaluated for the detection of hookworm, compared with direct smear, the formalin-ether sedimentation technique and the filter-paper method. Of 1085 stool samples from the routine laboratory service at King Chulalongkom Memorial Hospital in Bangkok, 241 samples harboured S. 153 hookworm . The recovery rate of hookworm by agar-plate culture is significantly superior to the other methods (P < 0·005). The ratios of positive results from the methods used to the total number of hookworm positive cases were as follows: 1:1·03 by agar-plate culture, 1:1·85 by the filter-paper method, 1:1·98 by the sedimentation technique and 1:10·48 by direct stool smear. The characteristic furrows left by hookworm larvae can be used for preliminary species identification. Daily search for furrows on agar plates for up to 6 consecutive days resulted in an increased sensitivity for diagnosis of hookworm infections.[3]
This infection may also affect the results of a D-xylose absorption test.[8]

References
1-Introduction&morphology:Stanford university article " Hookworm: Ancylostoma duodenale and Necator americanus" https://web.stanford.edu/group/parasites/ParaSites2009/PinedaANDYang_Hookworm/PinedaANDYang_Hookworm.htm 2-Biochemical properties: American society for microbiology http://iai.asm.org/content/58/12/3883.short
3- Oxford Journals, Medicine & Health, Transactions Royal Soc Tropical Med & Hyg, Volume 93, Issue 4, Pp. 398-400. http://trstmh.oxfordjournals.org/content/93/4/398.short. 4-Oxford Journals, Medicine & Health, Transactions Royal Soc Tropical Med & Hyg, Volume 62, Issue 4, Pp. 473-489. http://trstmh.oxfordjournals.org/content/62/4/473.abstract
5- Hookworms/Ancylostoma duodenale and Necator americanus,
James B. Peter, M.D., Ph.D.
6-Hookworm: “The Great Infection of Mankind” Peter J Hotez,* Jeff Bethony, Maria Elena Bottazzi, Simon Brooker, and Paulo Buss. Published online 2005 Mar 29.
7- Montresor A, Crompton DWT, Gyorkos TW, Savioli L. Helminth control in school-age children: A guide for managers of control programmes. Geneva: World Health Organization; 2002.
8-U.S National Library of Medicine; Updated by: Jatin M. Vyas, MD, PhD, Assistant Professor in Medicine, Harvard Medical School; Assistant in Medicine, Division of Infectious Disease, Department of Medicine, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Bethanne Black, and the A.D.A.M. Editorial team.
9-Centers for Disease Control and Prevention 1600 Clifton Rd. Atlanta, GA 30329-4027, USA
800-CDC-INFO (800-232-4636) TTY: (888) 232-634
10-USAID's Neglected tropical disease program: Soil transmitted helminthiasis, hookworm.

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