A human infective nematode found in canine carriers for the first time

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A human infective nematode found in remote northern areas of Australia has been identified in canine carriers for the first time.

Flinders University environmental health researchers, with experts in the U.S., have found a form of the soil-borne Strongyloides worm in faeces collected from dogs.

Strongyloidiasis, carried by several kinds of Strongyloides spp., is estimated to infect up to 370 million people around the world, mainly in places with poor sanitation in developing or disadvantaged communities.

The infection in the gut remains hidden, but can cause abdominal pain, diarrhoea and bloating.

Some people may experience nausea, vomiting, weight loss, weakness or constipation but doctors may not check for the condition.

In chronic infections, skin and chest symptoms can persist but the condition often goes unchecked.

The Australian study, involving 273 dog faeces samples compared to four human samples were screened using real-time PCR, of which 47 dog and four human DNA samples were then amplified by conventional PCR with further sequencing.

The complete set of amplified sequence variants (ASVs) was then analysed.

“Ultimately, we were able to confirm for the first time that potentially zoonotic S. stercoralis populations are present in Australia and suggest that dogs might represent a potential reservoir of human strongyloidiasis in remote Australian communities,” says Flinders Ph.D. candidate Mira Beknazarova.

Credit: Flinders University

“Our study was able to independently support previous reports of at least two genetically distinct groups of S. stercoralis; one infecting both dogs and humans and another group that is specific to dogs,” she says.

Flinders University environmental health senior lecturer Dr. Kirstin Ross, who regularly consults with remote Indigenous communities in Australia, says the study does not show direct transmission from dogs to humans, or vice-versa, but builds on the need for further investigations into preventative measures including better sanitation.

“Much needs to be done if you consider the risk to older and younger residents of Indigenous and non-Indigenous communities in northern Australia who are at risk of infection,” says Dr. Ross, who has studied strongyloidiasis for many years.

“The latest results strongly support moves to treat both humans and dogs for the infection,” she says.

The Australian study is similar to a separate study in Cambodia where Strongyloides was found in dog faeces.

The infective form of the worm, the larva, lives in soil which has been contaminated by faeces of an infected person.

If a person comes in contact with this soil, the larvae can burrow through the person’s skin and make its way to the lungs and then the gut where they eventually become adult worms.

Testing and treating for the larvae in human blood or faeces is often delayed by the slow acceleration of symptoms.

The findings, “Detection of classic and cryptic Strongyloides genotypes by deep amplicon sequencing: A preliminary survey of dog and human specimens collected from remote Australian communities” has been published in PLOS Neglected Tropical Diseases (PLOS ONE).

Risultati immagini per Strongyloides worm

Strongyloidiasis is the term used to indicate infection by Strongyloides stercoralis.

It differs from the other helminth infections by its ability to cause overwhelming hyperinfection in immunocompromised individuals.

Even though it can present a severe risk to life, it is one of the most neglected among the so-called neglected tropical diseases[1].

Strongyloides infection can last the host’s lifetime due to its autoinfection life cycle.

Manifestations of infection can range from asymptomatic eosinophilia to severe, life-threatening disease in immunocompromised patients.[2]

Etiology

Strongyloides stercoralis is a soil-transmitted helminth.

It is classified as a roundworm or nematode.

There are more than 50 species of Strongyloides.

Most of them do not infect humans.

HIV infection, human T-lymphotropic virus type 1 (HTLV-1) infection, and alcoholism have been reported as risk factors for Strongyloidiasis.

Risk factors for severe infection are corticosteroid therapy and HTLV-1 infection.

Other less important risk factors include malignancy, alcoholism, and organ transplant. 

Contrary to popular belief, HIV does not seem to be a risk factor for superinfection.

This is likely secondary to HIV CD4 cell immunosuppression predisposing more for bacterial and viral infections than for parasitic infections.[3]

Epidemiology

Worldwide and local prevalence of Strongyloides is seriously underestimated because of the low sensitivity of tests and poor reporting in high incidence countries.

It is more frequently found in warm, moist areas and countries with poor sanitary conditions.

It is present worldwide except in the far north and far south. 

Some studies have reported incidences as high as 91% in Gabon and 75% in Peru, but prevalence varies widely depending on the diagnostic methods used.

Studies identifying the incidence of this disease are non-existent.[4]

In developed countries, Strongyloidiasis is more frequently seen in farmers and miners, as well as immigrant populations, tourists and military returning from high prevalence areas.

In the United States, the highest incidence is in immigrants from Africa and Asia (46% found in one study on Sudanese refugees), followed by Central and Latin America.[5]

It is important to note that refugee populations receive deworming therapy when entering the United States.

Pathophysiology

Infection occurs through skin contact with soil that contains the filariform (infective) larvae.

After penetrating the skin, larvae travel to the lungs where it matures.

It then travels up the trachea. Here, it is swallowed and then invades the mucosa of the small upper intestine, where they mature and lay eggs.

The eggs hatch inside the mucosa and then the rhabditiform (non-infective) larvae travel to the intestinal lumen and is then excreted in the feces.

The larvae that are excreted in the soil may mature into an ineffective filariform larva or complete a free-living cycle where then male and female produce rhabditiform larvae that can later mature into filariform larvae.[4]

Some rhabditiform larvae may mature inside the intestinal lumen into filariform larvae.

They can then penetrate the perianal skin again and complete an autoinfection cycle, perpetuating the infection inside the host.

Hyperinfection syndrome is the most severe manifestation of disease with high mortality rates.

It occurs in chronically infected individuals that become immunosuppressed or in acutely infected immunosuppressed patients[4].

It stems from uncontrolled and accelerated autoinfection resulting in dissemination of the larvae to end organs like liver or brain.

Sepsis is a common complication caused by bacterial translocation from the intestinal wall.

History and Physical

Strongyloidiasis is often asymptomatic in immunocompetent individuals[4].

In this case, the only sign of infection may be peripheral eosinophilia.

Acute infection may show an itchy serpiginous skin rash in the area where the larvae penetrate the skin.

This is known as ground itch and is usually present in feet or hands, but can be perianal, abdominal or virtually anywhere in the body.

Intradermal migration is very fast (5 cm to 15 cm an hour) and the rash it causes is known as larva currens.

Passage of the larvae through the lungs can give a dry cough and cause a Loeffler-like syndrome with dyspnea, wheezing, eosinophilia, and migratory pulmonary infiltrates.

Intestinal symptoms can be diarrhea, vomiting, and epigastric pain.

Hyperinfection syndrome presents with fever, gram-negative bacteremia and sepsis and signs of end-organ damage (hemoptysis, gastrointestinal bleed, ileus, hyponatremia).

Evaluation

Diagnosis of Strongyloidiasis is made by stool examination or via serologic methods.

  • Standard stool examination has a sensitivity of only 21%. Better methods for diagnosis are stool concentration methods (Baermann technique is 72% sensitive or agar plate culture, 89% sensitive) which increase the yield of the stool sample. Nevertheless, consecutive samples can still fail to diagnose disease.[6]
  • Serologic tests (IFAT, ELISA, NIE-LIPS) tend to have a better sensitivity, although not perfect, but they are also more expensive and may not be readily available in resource-poor areas where the infection is more prevalent.[7] Nevertheless, given the low sensitivity of stool tests and our low prevalence setting, they should be strongly considered as the test of choice. The disadvantage of serologic techniques is the lack of specificity because of the cross-reactivity with other helminthic antigens, specially filariasis. The ELISA test has the benefit of being able to detect coproantigen and thus work as a marker of current infection.
  • Gold standard tests for S. Stercoralis infection are yet to be developed. PCR and RT-PCR are currently being tested and show promising results with nearly 100% specificity and very high sensitivity.[8]
  • Hyperinfection can be diagnosed by studying stools, body fluids and tissue which usually contain a high number of ineffective larvae.

Treatment / Management

Treatment of strongyloidiasis is indicated for all patients regardless of the severity of the disease.

  • First-line therapy consists of ivermectin 200 mg daily for two days. This regimen has shown the best efficacy, and side effect profile is similar to albendazole as demonstrated by the latest meta-analysis.
  • Second-line is Albendazole 400 mg bid for 7 days but has lower efficacy than ivermectin.
  • Thiabendazole has fallen out of favor due to increased incidence of adverse events, although it is as effective as ivermectin.[9]

Treatment may be prolonged in immunocompromised individuals.

Treatment of hyper infection includes anthelmintics (ivermectin as the preferred treatment) and broad-spectrum antibiotics with coverage for enteric bacteria.

Stopping or decreasing immunosuppressive treatment should be considered.

Treatment should continue until larvae are undetectable in stool, urine, and sputum for at least 14 days.

Response to treatment should be followed up with serial stool exams or anti-Strongyloides titers for one to two years in all patients.

Screening should be strongly considered before starting immunosuppressive treatments.[10]

Pearls and Other Issues

Prevention of disease, as with other soil-transmitted helminth infections, is undertaken by sanitation, access to clean water, and with hand washing and general hygiene.[11]

On an individual basis, it should be strongly considered to screen for Strongyloidiasis in individuals at risk for developing a hyper infection, for example, patients on immunosuppressants, particularly those on corticosteroids, or patients infected with HTLV-1 in high prevalence areas and in those who have visited those areas.

Enhancing Healthcare Team Outcomes

The diagnosis and management of strongyloidiasis is best done with a multidisciplinary team that includes a gastroenterologist, infectious disease expert, pathologist, laboratory professional, and the internist.

The pharmacist plays a key role in ensuring medication compliance.

While all patients are treated with ivermectin, monitoring is required to ensure that no more larvae are detectable in the body fluids.

Response to treatment should be followed up with serial stool exams or anti-Strongyloides titers for one to two years in all patients. Screening should be strongly considered before starting immunosuppressive treatments.[10]

The infectious disease nurse should educate the patient on maintenance of sanitation, washing hands and maintaining general hygiene.


More information: Meruyert Beknazarova et al. Detection of classic and cryptic Strongyloides genotypesby deep amplicon sequencing: A preliminary survey of dog and human specimens collected from remote Australian communities, PLOS Neglected Tropical Diseases (2019). DOI: 10.1371/journal.pntd.0007241

Journal information: PLoS ONE , PLoS Neglected Tropical Diseases
Provided by Flinders University

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