Strongyloidiasis

Strongyloidiasis
Other names: Disseminated strongyloidiasis[1], Threadworm infection[2]
Top: Different clinical syndromes of Strongyloides stercoralis, including acute, chronic, disseminated, and hyperinfection syndromes[3] Bottom:Micrograph showing strongyloidiasis; a fragment of a worm is seen in the lower right hand corner. H&E stain.
Specialty	Infectious disease
Symptoms	Abdominal pain, diarrhea, weight loss[4]
Complications	Hyperinfection syndrome[4]
Causes	Strongyloides stercoralis[4]
Risk factors	Immunocompromisation[4]
Diagnostic method	Serology, stool tests[4]
Differential diagnosis	Intestinal obstruction,Loffler syndrome,ARDS,peritonitis[4]
Treatment	Ivermectin[4]

Strongyloidiasis is a human parasitic disease caused by the nematode called Strongyloides stercoralis, or sometimes the closely related S. fülleborni. These helminths belong to a group of nematodes called roundworms. These intestinal worms can cause a number of symptoms in people, principally skin symptoms, abdominal pain, diarrhea and weight loss, but also many other specific and vague symptoms in disseminated disease, and severe life-threatening conditions through hyperinfection. In some people, particularly those who require corticosteroids or other immunosuppressive medication, Strongyloides can cause a hyperinfection syndrome that can lead to death if untreated. The diagnosis is made by blood and stool tests. The medication ivermectin is widely used to treat strongyloidiasis.^[4][5][6][7]

Strongyloidiasis is a type of soil-transmitted helminthiasis. Low estimates postulate it to affect 30–100 million people worldwide,^[8] mainly in tropical and subtropical countries, while higher estimates conservatively extrapolate that infection is upwards to or above 370 million people.^[9] It belongs to the group of neglected tropical diseases, and worldwide efforts are aimed at eradicating the infection.^[10]

Signs and symptoms

Strongyloides infection occurs in several forms. As the infection continues and the larvae matures, there may be respiratory symptoms (Löffler's syndrome). The infection may then become chronic with mainly digestive symptoms. On reinfection from the skin to the lungs and finally to the small intestine, there may be respiratory, skin and digestive symptoms. Finally, the hyperinfection syndrome causes symptoms in many organ systems, including the central nervous system.^[11][12][4]

Uncomplicated

Frequently asymptomatic, gastrointestinal system symptoms include abdominal pain and diarrhea and/or conversely constipation. Pulmonary symptoms can occur during pulmonary migration of the filariform larvae. Pulmonary infiltrate may be present through radiological investigation. Dermatologic manifestations include urticarial rashes in the buttocks and waist areas as well as larva currens. Eosinophilia is generally present. Strongyloidiasis can become chronic and then become completely asymptomatic.^[4][13]

Disseminated

Disseminated strongyloidiasis occurs when patients with chronic strongyloidiasis become immunosuppressed. There is a distinction to be made between dissemination and hyperinfection. It is mainly a semantic distinction. There can be mild dissemination where the worm burden is relatively lower yet causes insidious symptoms, or extreme dissemination that the term hyperinfection is used to describe. Thus hyperinfection of varying levels of severe dissemination may present with abdominal pain, distension, shock, pulmonary and neurologic complications, sepsis, haemorrhage, malabsorption, and depending on the combination, degree, number, and severity of symptoms, is potentially fatal. The worms enter the bloodstream from the bowel wall, simultaneously allowing entry of bowel bacteria such as Escherichia coli. This may cause symptoms such as sepsis,^[14] and the bacteria may spread to other organs where they may cause localized infection such as meningitis.^[15] Dissemination can occur many decades after the initial infection^[16] and has been associated with high dose corticosteroids, organ transplant, any other instances and causes of immunosuppression.^[17][18]

Cause

Strongyloides stercoralis is a soil-transmitted helminth.Contagiousness via textiles, unlike Enterobius vermicularis, is unfounded. It has rarely been transmitted through organ transplantation.^[4][19] Married Vietnam War veterans who were infected, yet never developed significant hyperinfection, lived for multiple decades with non-debilitating disseminated infection, without treatment, with wives who failed to ever contract infection.^[20] Contraction occurs overwhelmingly from skin exposure to any contaminated soil, contaminated potting soil, contaminated waters, lack of sanitation, or environmental factors as potential vectors. Nearly never to extraordinarily very rarely documented is transmission from person to person, other than closeness of contact to the productive coughing of a very ill hyperinfected individual. It has been shown possible to occur in that situation, or potentially other similar scenarios, it is speculated via pulmonary secretions of a direly hyperinfected individual. In which case treatment for others may be indicated, if deemed necessary by proximity, symptoms, precautions, probable exposures to the same vectors, or through screening of serology and stool samples, until infection is eradicated.^[21]

Mechanism

In terms of the mechanism that causes Strongyloidiasis we find that the larvae can develop into free-living adult males and females. These adults reproduce sexually, ready to continue the cycle. They actively penetrate the skin of a human host, often through bare feet.The larvae enter the bloodstream and travel to the lungs.From the lungs, they migrate to the trachea and are swallowed.In the intestine, the larvae mature into adult female worms.The females reproduce through a process called parthenogenesis, laying eggs that hatch into larvae in the intestine.Larvae are then either excreted or larvae develop into a new generation of infective larvae within the host, leading to autoinfection.^[4][22]

Diagnosis

Diagnosis rests on the microscopic identification of larvae (rhabditiform and occasionally filariform) in the stool or duodenal fluid. Examination of many samples may be necessary, and not always sufficient, because direct stool examination is relatively insensitive, with a single sample only able to detect larvae in a small percent of cases. It can take 4 weeks from initial infection to the passage of larvae in the stool.The stool can be examined in wet mounts via a variety of methods^[23][4][24]

Culture techniques are the most sensitive, but are not routinely available in the West. In the UK, culture is available at either of the Schools of Tropical Medicine in Liverpool or London. Direct examination must be done on stool that is freshly collected and not allowed to cool down, because hookworm eggs hatch on cooling and the larvae are very difficult to distinguish from Strongyloides.Finding Strongyloides in the stool is negative in up to 70% of tests. It is important to undergo frequent stool sampling as well as duodenal biopsy if a bad infection is suspected. The duodenal fluid can be examined using techniques such as the Enterotest string or duodenal aspiration. Given the poor ability of stool examination to diagnose Strongyloides, detecting antibodies by ELISA can be useful.^[25][4][26]

Serology can cross-react with other parasites, remain positive for years after successful treatment or be falsely negative in immunocompromised patients.^[23][27] Infected patients will also often have an elevated eosinophil count, with an average of absolute eosinophil count of 1000 in one series.^[28] It would be greatly useful to have significant advances in the sensitivity of the means of diagnosis, as it would also solve the challenging problem of proof of cure. If definitive diagnosis is solved then it stands to reason that proof of cure becomes easily realizable.^[29]

Differential diagnosis

In terms of the DDx in the affected individual we find the following:^[4]

• Intestinal obstruction
• Loffler syndrome
• ARDS
• Peritonitis
• Pneumonia
• Pneumonitis

Screening

It is often recommended that patients being started on immunosuppression be screened for chronic strongyloidiasis; however, in developed countries, the prevalence of chronic strongyloidiasis is very small, so screening is usually not cost-effective, except in endemic areas.^[31][30]

Screening should be performed before administering steroids for infection in even remotely susceptible individuals in order to prevent escalating the infection is advised. As not doing so in certain cohorts can have high mortality rates from inadvertently caused hyperinfection via immunosuppression of application of certain steroids. Thus caution with respect to iatrogenic risks is crucial to avoiding adverse consequences in treatment.^[32][30]

People with high exposure to Strongyloides stercoralis may mitigate the risk of strongyloidiasis hyperinfection associated with corticosteroid treatment, with the presumptive use of ivermectin. Such hyperinfection has been a particular concern during the COVID-19 pandemic because of the use of corticosteroids for treatment of COVID-19 symptoms. The CDC and other international bodies recommend the use of ivermectin for refugees from areas which have a risk of strongyloidiasis.^[33]

Treatment

The consensus drug of choice for the treatment of uncomplicated strongyloidiasis is ivermectin. However, even if it is considered the main drug of choice, recent studies have illustrated the challenges in ivermectin curing strongyloidiasis.^[35] Ivermectin does not kill the Strongyloides larvae, only the adult worms, therefore repeat dosing may be necessary to properly eradicate the infection. There is an auto-infective cycle of roughly two weeks in which ivermectin should be re-administered; however, additional dosing may still be necessary as it will not kill Strongyloides in the blood or larvae deep within the bowels or diverticula.^[36] Other drugs that can be effective are albendazole and thiabendazole (25 mg/kg twice daily for 5 days—400 mg maximum (generally)).^[18] All patients who are at risk of disseminated strongyloidiasis should be treated. The optimal duration of treatment for patients with disseminated infections is not clear.^[17]

Treatment of strongyloidiasis can be difficult and if ceasing treatment before being entirely cleared Strongyloides via the autoinfective cycle has been known to live in individuals for decades;^[37] even after initial or inadequate sustained treatment. Continued treatment, blood and stool monitoring thus may be necessary even if symptoms temporarily resolve. As cited earlier, due to the fact that some infections are insidiously asymptomatic, and relatively expensive bloodwork is often inconclusive via false-positives or false-negatives,^[38] just as stool samples can be unreliable in diagnoses,^[39] there is yet unfortunately no real gold standard for proof of cure, mirroring the lack of an efficient and reliable methodology of diagnosis.^[11][29][40] An objective eradication standard for strongyloidiasis is elusive given the high degree of suspicion needed to even begin treatment, the sometimes difficulty of the only definitive diagnostic criteria of detecting and isolating larvae or adult Strongyloides, the importance of early diagnosis, particularly before steroid treatments,^[41] and the very wide variability and exclusion/inclusion of differing collections of diffuse symptoms. Disregarding mis-ascribing bonafide delusional parasitosis disorders,^[42][43][44] strongyloidiasis should be more well known among medical professionals and have serious consideration for broad educational campaigns in effected geographic locales both within the semi-tropical developed world and otherwise, as well as in the tropical developing world where, among many other neglected tropical diseases, it is endemic.^[7][45]

There are conflicting reports on effective drug treatments. Ivermectin ineffectiveness and rising drug resistance has been documented.^[46] Albendazole is noted by the WHO as being the least effective.^[47] Thiabendazole can have severe side effects and is unavailable in many countries.^[48]

Prognosis

In terms of the prognosis we find that acute and chronic infections is positive, when treatment occurs. But in hyperinfection syndrome and disseminated infection, 70 to 100 percent is the current mortality rate^[4]

It is important to note that there is not necessarily any eosinophilia in the disseminated disease. Absence of eosinophilia in an infection limited to the gastrointestinal tract may indicate poor prognosis.^[49]

Epidemiology

Low estimates postulate it to affect 30–100 million people worldwide,^[8] mainly in tropical and subtropical countries, while higher estimates conservatively extrapolate that infection is upwards to or above 370 million people.^[9]

It belongs to the group of neglected tropical diseases, and worldwide efforts are aimed at eradicating the infection.^[10]

• 
  Pooled prevalence of S. stercoralis in Southeast Asia^[50]
• 
  Prevalence Strongyloides stercoralis^[51]

History

The disease was first recognized in 1876 by the French physician Louis Alexis Normand, working in the naval hospital in Toulon; he identified the adult worms, and sent them to Arthur Réné Jean Baptiste Bavay, chief inspector for health, who observed that these were the adult forms of the larvae found in the stool.^[52]

In 1883 the German parasitologist Rudolf Leuckart made initial observations on the life cycle of the parasite, and Belgian physician Paul Van Durme (building on observations by the German parasitologist Arthur Looss) described the mode of infection through the skin. The German parasitologist Friedrich Fülleborn described autoinfection and the way by which strongyloidiasis involves the intestine. Interest in the condition increased in the 1940s when it was discovered that those who had acquired the infection abroad and then received immunosuppression developed hyperinfestation syndrome.^[52] During the 1940s, the treatment of choice was enteric coated tablets of 60 mg gentian violet, three times daily, for 16 days.^[53]

References

Further reading

• WHO guideline on preventive chemotherapy for public health control of strongyloidiasis. World Health Organization. 2024. ISBN 978-92-4-009402-4. Archived from the original on 2025-02-08. Retrieved 2025-04-23.

External links

• Strongyloidiasis Archived 2010-10-31 at the Wayback Machine. U.S. Centers for Disease Control and Prevention (CDC)