Strongloidiasis

Disease Type: Parasitic DiseaseCommon Name: StrongloidiasisCausative Agent: Strongyloides stercoralisDisease Discription: Strongloidiasis is an infection caused by the parasitic worm (nematode) Strongyloides stercoralis (strong-e-loyd-eez stare-coral-is) invading the small intestine (gut). Humans are the main home (reservoir) of S. stercoralis, but cats and dogs can also carry the parasite. Strongyloidiasis was first described in 1876, and is not a Nationally Notifiable Disease.

Fig.Respiratory hyperinfection with Strongyloides stercoralis in a patient with renal failure

Causes of Disease:

Infections are initiated when exposed skin contacts contaminated soil. Autoinfection commonly occurs allowing infection to persist decades. The longest documented asymptomatic infection was more than 65 years. Hyperinfection typically is triggered by drug-induced or disease-associated defects in cellular immunity, which allows a massive increase in parasite burden and dissemination to nearly all organ systems.

Causative Agent: Pathogen Name: Strongyloides stercoralisPathogen Description:Strongyloides stercoralis, also known as the threadworm, is the scientific name of a human parasitic roundworm causing the disease of strongyloidiasis.

Strongyloides stercoralis is a nematode that can parasitize humans. The adult parasitic stage lives in tunnels in the mucosa of the small intestine. The genus Strongyloides contains 53 species[1][2] and S. stercoralis is the type species. S. stercoralis has been reported in other mammals, including cats and dogs. However, it seems that the species

in dogs is typically not S. stercoralis, but the related species S. canis. Non-human primates are more commonly infected with S. fuelleborni and S. cebus although S. stercoralis has been reported in captive primates. Other species of Strongyloides naturally parasitic in humans, but with restricted distributions, are S. fuelleborni in central Africa and S. kellyi in Papua New Guinea.

Taxonoimic Classification:

First stage larva (L1) of S. stercoralis

Morphology and toxin production:

Whereas males grow to only about 0.9 mm in length, females can be anywhere from 2.0 to 2.5 mm. Both genders also possess a tiny buccal capsule and cylindrical esophagus without a posterior bulb.[8] In the free-living stage, the esophagi of both sexes are rhabditiform. Males can be distinguished from their female counterparts by two structures: the spicules and gubernaculum.

Kingdom: Animalia

Phylum: Nematoda

Class: Secernentea

Order: Rhabditida

Family: Strongyloididae

Genus: Strongyloides

Species: S. stercoralis

Auto-infection

An unusual feature of S. stercoralis is autoinfection. Only one other species in the Strongyloides genus, S. felis, has the trait of autoinfection. Autoinfection is the development of L1 into small infective larvae in the gut of the host. These autoinfective larvae penetrate the wall of the lower ileum or colon or the skin of the perianal region, enter the circulation again, up to the lungs, and back down to the small intestine thus repeating the cycle. Autoinfection makes strongyloidiasis due to S. stercoralis an infection with several unusual features.

Persistence of infection is the first of these important features. Because of autoinfection, humans have been known to still be infected up to 65 years after they were first exposed to the parasite (e.g. World War II or Vietnam veterans). Once a host is infected with S. stercoralis, infection is life-long unless effective treatment eliminates all adult parasites and migrating autoinfective larvae.

Strongyloidiasis in immunocompetent individuals is usually an indolent disease. However, in immunocompromised individuals strongyloidiasis can cause a hyperinfective syndrome (also called disseminated strongyloidiasis) due to the

reproductive capacity of the parasite inside the host. This hyperinfective syndrome has a mortality rate of close to 90%.[10]

Immunosuppressive drugs, such as those used for tissue transplantation, (especially corticosteroids) can increase the rate of autoinfection to the point where there is an overwhelming number of larvae migrating through the lungs, and in many cases this can prove fatal. Additionally, diseases such as HTLV-1 (Human T-cell Lymphotropic Virus 1), which enhance the Th1 arm of the immune system and lessen the Th2 arm, increase the disease state. Another consequence of autoinfection is that the autoinfective larvae can carry gut bacteria back into the body. About 50% of people with hyperinfection present with bacterial disease due to enteric bacteria. Finally, a unique effect of autoinfective larvae is larva currens due to the larvae migrating rapidly through the skin. Larva currens appears as a red line that appears, moves rapidly (>5 cm/day) and then quickly disappears. It is pathogonomic for autoinfective larvae and can be used as a diagnostic criterion for strongyloidiasis due to S. stercoralis.

History: Strongyloidiasis was first described in the nineteenth century in French soldiers returning home from expeditions in IndoChina. Today, the countries of the old IndoChina (Vietnam, Cambodia and Laos) still have endemic strongyloidiasis.

Epidemiology:

Strongyloides stercoralis may coexist with hookworms; both require similar soil and climatic conditions for development. Warm, moist soils that foster reproduction by the free-living stages may become heavily contaminated with S stercoralis. Because of autoinfection, persons who have contracted this infection in endemic areas may remain infected for years after leaving such areas.

Strongyloidiasis is most common in tropical and subtropical areas, but is much less prevalent than hookworm infection. Recent surveys in the Philippines and Indonesia rarely found the parasite, even with the use of filter paper cultures. Other parts of Southeast Asia, however, have a higher prevalence of infection, and parts of Africa report prevalence as high as 21 percent. In the United States, infections are more common in the South and in institutionalized populations.

Dogs are sometimes infected with S stercoralis. Although dogs are considered a source of human infections, the primary source continues to be humans.

Cases have been reported in which the infection was transferred to a new host along with a kidney transplant. These patients were immunosuppressed.[14]

Disease Host: Human and other animal.

Disease Transmission:Most infections with S stercoralis are asymptomatic except for the ground itch that may occur when infective larvae from the soil penetrate the skin in large numbers. Pneumonitis can result from larval invasion in the lung. Intestinal invasion may lead to epigastric pain and mucous diarrhea. Eosinophilia is common. Dissemination of strongyloidiasis into extraintestinal organs sometimes occurs in persons receiving immunosuppressive drugs. The infection can be perpetuated by an autoinfection cycle, which can lead to massive infection, especially in the immunocompromised host. Linear skin lesions on the lower abdomen and buttocks may also develop in patients with autoinfection due to penetration of the perianal skin by infective larvae. This condition is called larva currens.

Life Cycle

S. Stercoralis have a heterogonic life cycle which consists of a parasitic generation and a free-living generation. The parasitic has a homogenic life cycle, while the free-living has a heterogonic life cycle. The heterogonic life cycle is advantageous to the parasite because it allows for the parasite to reproduce for one or more generations in the absence of a host. First stage larvae pass out in the feces and develop in feces on the ground to infective larvae. This development can occur via two routes: directly from L1 to IL via three molts or indirectly. The indirect route results first in the development of free-living adult females and males which mate, females lay eggs which hatch and then develop to IL. The direct route gives IL faster (3 days) versus the indirect route (7-10 days), However, the indirect route results in an increase in the number of IL produced. Speed of

development of IL is traded off for increased numbers. The free-living males and females of S. stercoralis die after one generation; they do not persist in the soil.

The infectious larvae penetrate the skin when there is contact with the soil. While S. stercoralis is attracted to chemicals such as carbon dioxide or sodium chloride, these chemicals are very non-specific. Larvae have been thought to locate their hosts via chemicals in the skin, predominantly urocanic acid, a histidine metabolite on the uppermost layer of skin that is removed by sweat or the daily skin-shedding cycle. [7] Urocanic acid concentrations can be up to five times greater in the foot than any other part of the human body. Some of them enter the superficial veins and ride the blood vessels to the lungs, where they enter the alveoli. They are then coughed up and swallowed into the gut, where they parasitise the intestinal mucosa (duodenum and jejunum). However, research in dogs has shown that most of the larvae that penetrate the skin migrate randomly through the body until they reach the small intestine. Only females will reach reproductive adulthood in the intestine. Female strongyloides reproduce through parthenogenesis. The eggs hatch in the intestine and young larvae are then excreted in the feces. It takes about two weeks to reach egg development from the initial skin penetration. By this process, S. stercoralis can cause both respiratory and gastrointestinal symptoms. Adult worms can live up to a year in dogs.

Fig.Life Cycle of Strongyloides stercoralis

The Strongyloides life cycle is more complex than that of most nematodes with its alternation between free-living and parasitic cycles, and its potential for autoinfection and multiplication within the host.  Two types of cycles exist:Free-living cycle: The rhabditiform larvae passed in the stool (see "Parasitic cycle" below) can either molt twice and become infective filariform larvae (direct development)

or molt four times and become free living adult males and females that mate and produce eggs from which rhabditiform larvae hatch .  The latter in turn can either develop into a new generation of free-living adults (as represented in ), or into infective filariform larvae .  The filariform larvae penetrate the human host skin to initiate the parasitic cycle (see below) .Parasitic cycle: Filariform larvae in contaminated soil penetrate the human skin , and are transported to the lungs where they penetrate the alveolar spaces; they are carried through the bronchial tree to the pharynx, are swallowed and then reach the small intestine .  In the small intestine they molt twice and become adult female worms .  The females live threaded in the epithelium of the small intestine and by parthenogenesis produce eggs , which yield rhabditiform larvae.  The rhabditiform larvae can either be passed in the stool (see "Free-living cycle" above), or can cause autoinfection .  In autoinfection, the rhabditiform larvae become infective filariform larvae, which can penetrate either the intestinal mucosa (internal autoinfection) or the skin of the perianal area (external autoinfection); in either case, the filariform larvae may follow the previously described route, being carried successively to the lungs, the bronchial tree, the pharynx, and the small intestine where they mature into adults; or they may disseminate widely in the body.  To date, occurrence of autoinfection in humans with helminthic infections is recognized only in Strongyloides stercoralis and Capillaria philippinensis infections.  In the case of Strongyloides, autoinfection may explain the possibility of persistent infections for many years in persons who have not been in an endemic area and of hyperinfections in immunodepressed individuals.

Mechanism:

Light infections elicit only a mild inflammatory response, whereas in heavy infections, damage to the intestines may be severe, with edema, inflammation, ulceration, increased secretion of mucus and sloughing of the mucosa, as well as functional changes of the gut . A malabsorption syndrome has been reported. In disseminated strongyloidiasis the parasite may be found in any part of the body. In pulmonary infections there may be pneumonia and hemorrhage. Meningitis is also reported. Hyper-disseminated infections may be fatal.

Host Defenses

Immunity in strongyloidiasis is not well understood but autoinfection generally occurs in persons with suppressed cell-mediated immunity. Most susceptible are patients who have lymphocytic leukemia, malignancy, malnutrition, leprosy, or systemic lupus

erythematosus and who are receiving immunosuppressive therapy. Serum lgE levels usually are elevated in persons with this parasite. In severe strongyloidiasis, some patients may have significantly decreased IgG levels and low levels of IgA and IgM. It has also been suggested that human lymphotrophic virus type 1 (HTLV-1) has a association with strongyloidiasis and that the mechanism may involve the supression of the IgE response. Eosinophil counts also may be depressed in patients with massive infections. These findings indicate that eosinophils and antibodies may be important in the defense against S stercoralis larvae.[14]

Signs and symptoms of disease: Symptoms include dermatitis: swelling, itching, and mild hemorrhage at the site where the skin has been penetrated. If the parasite reach the lungs, the chest may feel as if it were burning, and wheezing and coughing may result along with pneumonia-like symptoms. Eventually, the intestines could be invaded, leading to burning pain, tissue damage, sepsis, and ulcers. In severe cases, edema may result in obstruction of the intestinal tract as well as loss of peristaltic contractions. [9]

Diagnosis:

Locating juvenile larvae, either rhabditiform or filariform, in recent stool samples will confirm the presence of this parasite.[11] Other techniques used include direct fecal smears, culturing fecal samples on agar plates, serodiagnosis through ELISA, and duodenal fumigation. Still, diagnosis can be difficult because of the varying juvenile parasite load on a daily basis.

Eosinophilia, epigastric pain, and mucous diarrhea suggest S stercoralis infection, but definitive diagnosis requires finding larvae in the stool or, on rare occasions, in sputum or urine. Eggs are not found except in cases of severe dysentery. Direct smear or concentration methods of stool examination usually suffice, but the sample can be cultured in cases where infection is suspected but unconfirmed. Baermanization of charcoal fecal cultures is recommended. (A Baermann apparatus is a funnel with a rubber tube with a pinch-clamp attached to the spout. A sieve is placed in the funnel, gauze is added, and a culture placed on the gauze. Warm water is added to the funnel just above the culture. Larvae will migrate into the water and fall to the bottom. After a few hours, the pinch-clamp is opened and the larvae are flushed out into a flask and examined microscopically.) A newly described culture method using agar plates has been reported to be successful in detecting the parasite. Larval stages of S stercoralis must be distinguished from hookworm larvae. The rhabditiform larvae resemble those of hookworms but can be distinguished by the shorter buccal capsule and larger genital primordium. The filariform larvae also resemble those of hookworms, but the tail is notched and the esophagus is about one-half the length of the body.

Duodenal intubation and examination of aspirates, or a string test (Enterotest) and examination of intestinal mucus, is recommended in suspected cases, even when serial

stool examinations are negative. A number of reliable serology tests are also available to aid in the diagnosis of strongyloidiasis. [14]

Treatment:

The ideal method would be prevention by improved sanitation (proper disposal of feces), practicing good hygiene (washing of hands), etc., before any drug regimen is administered.

Ivermectin is the drug of first choice for treatment because of higher tolerance in patients[12] . Thiabendazole was used previously, but owing to its high prevalence of side effects (dizziness, vomiting, nausea, malaise) and lower efficacy, it has been superseded by ivermectin and as second line, albendazole. However, these drugs have little effect on the majority of these autoinfective larvae during their migration through the body. Hence, repeated treatments with ivermectin have to be administered to kill adults which develop from the autoinfective larvae.

In the UK, Mebendazole and Piperazine are currently (2007) preferred.[13]

Prevention of disease:

Like other soil-transmitted nematode infections, strongyloidiasis can be controlled by improving sanitary conditions and by proper disposal of feces. Patients with this infection should be treated even if they are asymptomatic to preclude possible onset of autoinfection. Immunosuppressants are contraindicated in these patients. Strongyloidiasiasis must be ruled out in persons to be given immuno-suppressants, especially those with eosinophilia.

Thiabendazole, the most effective therapeutic agent, can cause side effects of vertigo, nausea and vomiting. Prolonged or repeated treatment may be required in patients receiving immunosuppressive drugs. Ivermectin and albendazole have recently been reported to also be effective.

Geographical Distribution:

S. stercoralis has a very low prevalence in societies where fecal contamination of soil or water is rare. Hence, it is a very rare infection in developed market economies and is less prevalent in urban areas in developing countries than in rural areas, where sanitation standards are poor. S. stercoralis can be found in areas with tropical and subtropical climates. [3]

Strongyloidiasis was first described in the nineteenth century in French soldiers returning home from expeditions in IndoChina. Today, the countries of the old IndoChina (Vietnam, Cambodia and Laos) still have endemic strongyloidiasis, typical prevalences being 10% or less. Regions of Japan used to have endemic strongyloidiasis, but control

programs have probably reduced prevalences markedly. Strongyloidiasis appears to have a high prevalence in some areas of Brazil and Central America. Strongyloidiasis is endemic in Africa, but the prevalence is typically low (1% or less). Pockets of strongyloidiasis have been reported from rural Italy, but current status is unknown. In the Pacific islands strongyloidiasis is rare although there have been reports of cases from Fiji. In tropical Australia, some rural and remote Australian Aboriginal communities have very high prevalences of strongyloidiasis[4] . In some African countries (e.g., Zaire) S. fuelleborni was more common than S. stercoralis in parasite surveys from the 1970s, but current status is unknown. In Papua New Guinea, S. stercoralis is endemic, but prevalence is low. However, in some areas another species, S. kellyi,[5] is a very common parasite of children in the PNG highlands and Western Province.[6]

Knowledge of the geographic distribution of strongyloidiasis is of significance to travelers who may acquire the parasite during their stay in endemic areas.

Disease Statistics:Today, the countries of the old IndoChina (Vietnam, Cambodia and Laos) still have endemic strongyloidiasis, typical prevalences being 10% or less. Regions of Japan used to have endemic strongyloidiasis, but control programs have probably reduced prevalences markedly. Strongyloidiasis appears to have a high prevalence in some areas of Brazil and Central America. Strongyloidiasis is endemic in Africa, but the prevalence is typically low (1% or less). Pockets of strongyloidiasis have been reported from rural Italy, but current status is unknown. In the Pacific islands strongyloidiasis is rare although there have been reports of cases from Fiji. In tropical Australia, some rural and remote Australian Aboriginal communities have very high prevalences of strongyloidiasis[4] . In some African countries (e.g., Zaire) S. fuelleborni was more common than S. stercoralis in parasite surveys from the 1970s, but current status is

unknown. In Papua New Guinea, S. stercoralis is endemic, but prevalence is low. However, in some areas another species, S. kellyi,[5] is a very common parasite of children in the PNG highlands and Western Province.[6]

Refrence:1. Speare R. Identification of species of Strongyloides. In: Grove DI. (ed)

Strongyloidiasis: a major roundworm infection of man. Taylor & Francis: London. 1989;11-83.

2. Skerratt LF. Strongyloides spearei n. sp. (Nematoda: Strongyloididae) from the common wombat Vombatus ursinus (Marsupialia: Vombatidae). Systematic Parasitology 1995;32:81-89.

3. Segarra-Newnham, M. (2007). Manifestations, diagnosis, and treatment of Strongyloides stercoralis infection. Ann Pharmacother. 41(12): 1992-2001.

4. Johnston FH, Morris PS, Speare R, McCarthy J, Currie B, Ewald D, Page W, Dempsey K. Strongyloidiasis: A review of the evidence for Australian practitioners. Australian Journal of Rural Health 2005;13:247-254.

5. Dorris M, Viney ME, Blaxter ML. Molecular phylogenetic analysis of the genus Strongyloides and related nematodes. Int J Parasitol 2002;32(12):1507-17.

6. King SE, Mascie-Taylor CG. Strongyloides fuelleborni kellyi and other intestinal helminths in children from Papua New Guinea: associations with nutritional status and socioeconomic factors. P N G Med J 2004;47(3-4):181-91.

7. Safer, D., Brenes, M., Dunipace, S., and Schad, G. (2006). Urocanic acid is a major chemoattractant for the skin-penetrating parasitic nematode Strongyloides stercoralis. PNAS 104(5), 1627-1630.

8. Roberts, L., Janovy, Jr., J. Foundations of Parasitology. 2005. 412. 9. Roberts, L., Janovy, Jr., J. Foundations of Parasitology. 2005. 414-415. 10. Igra-Siegman Y, Kapila R, Sen P, Kaminski ZC, Louria DB. Syndrome of

hyperinfection with Strongyloides stercoralis. Rev Infect Dis 1981;3:397-407. 11. Roberts, L., Janovy, Jr., J. Foundations of Parasitology. 2005. 415. 12. Johnston FH, Morris PS, Speare R, McCarthy J, Currie B, Ewald D, Page W,

Dempsey K. Strongyloidiasis: A review of the evidence for Australian practitioners. Australian Journal of Rural Health 2005;13:247-254.

13. NHS Direct Health Encyclopedia by: Dr. Dave Cheever .14. gsbs.utmb.edu15.