CATMAT statement on disseminated strongyloidiasis: Prevention, assessment and management guidelines - CCDR: Volume 42-1, January 7, 2016: Emerging infectious diseases

ISSN 1481-8531
(On-line)
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Advisory Committee Statement

CATMAT statement on disseminated strongyloidiasis: Prevention, assessment and management guidelines

Boggild AKFootnote 1,Footnote 2,Footnote 3, Libman MFootnote 4, Greenaway CFootnote 5, McCarthy AEFootnote 6, on behalf of the Committee to Advise on Tropical Medicine and Travel (CATMAT)Footnote *

Abstract

Background: Strongyloides stercoralis is a parasitic nematode found in humans, with a higher prevalence in tropical and sub-tropical regions worldwide. If untreated, the infection can progress to disseminated strongyloidiasis, a critical illness which may be fatal.

Objective: To provide clinical guidance on the prevention, assessment and management of disseminated strongyloidiasis.

Methods: A literature review was conducted to evaluate the current evidence and to identify any systematic reviews, case reports, guidelines and peer reviewed and non-peer reviewed medical literature. The Committee to Advise on Tropical Medicine and Travel (CATMAT) assembled a working group to develop this statement, which was then critically reviewed and approved by all CATMAT members.

Recommendations: CATMAT recommends that screening for strongyloidiasis should be considered for individuals with epidemiologic risk and/or co-morbidities that place them at risk for Strongyloides hyperinfection and dissemination. Those at highest risk of hyperinfection and dissemination are individuals born in a Strongyloides-endemic area who undergo iatrogenic immunosuppression or have intercurrent human T-lymphotropic virus (HTLV-1) infection. Diagnosis of strongyloidiasis is based on serologic testing and/or examination of stools and other clinical specimens for larvae. Referral to a tropical medicine specialist with expertise in the management of strongyloidiasis is recommended for suspected and confirmed cases. A diagnosis and treatment algorithm for strongyloidiasis has been developed as a reference tool.

Conclusion: Strongyloidiasis is relatively widespread in the global migrant population and screening for the disease should be based on an individual risk assessment. A practical tool for the clinician to use in the prevention, assessment and management of disseminated strongyloidiasis in Canada is now available.

Preamble

The Committee to Advise on Tropical Medicine and Travel (CATMAT) provides the Public Health Agency of Canada with ongoing and timely medical, scientific and public health advice relating to tropical infectious disease and health risks associated with international travel. The Agency acknowledges that the advice and recommendations set out in this statement are based upon the best current available scientific knowledge and medical practices and is disseminating this document for information purposes to both travellers and the medical community caring for travellers.

Persons administering or using drugs, vaccines or other products should also be aware of the contents of the product monograph(s) or other similarly approved standards or instructions for use. Recommendations for use and other information set out herein may differ from that set out in the product monograph(s) or other similarly approved standards or instructions for use by the licensed manufacturer(s). Manufacturers have sought approval and provided evidence as to the safety and efficacy of their products only when used in accordance with the product monographs or other similarly approved standards or instructions for use.

Introduction

Strongyloidiasis is a disease caused by a nematode (i.e., a roundworm), which is present mainly in tropical and sub-tropical regions, but also in temperate climates. Precise data on prevalence are unknown in endemic countries; however, it is estimated that 30-100 million people are infected worldwide Footnote 1. Most people who are infected with Strongyloides are asymptomatic and unaware of their infection; however, people who are immunosuppressed are at risk of developing the severe form of disseminated strongyloidiasis which, if untreated, can lead to potentially fatal illness Footnote 2. Although strongyloidiasis has traditionally been considered a tropical disease, increased worldwide travel and immigration have led to an increased number of cases seeking medical care in Canada.

The objectives of this statement are to:

  1. Raise awareness of disseminated strongyloidiasis among clinicians who may encounter these cases (including front-line clinicians such as emergency room physicians, infectious diseases specialists, rheumatologists, dermatologists, gastroenterologists, oncologists, intensivists and transplant teams).
  2. Assist clinicians in the prevention, assessment and management of disseminated strongyloidiasis.

Methods

This statement was created after CATMAT identified a need to inform Canadian clinicians about disseminated strongyloidiasis. A CATMAT working group was assembled and a member was elected to lead the statement development. The available literature was assessed for systematic reviews, guidelines, case reports and peer reviewed and non-peer reviewed medical literature. Based on the evidence compiled as well as expert opinion, a diagnosis and treatment algorithm for strongyloidiasis was designed as a reference tool for clinicians in Canada. The statement was then critically reviewed and approved by all CATMAT members.

Epidemiology

Strongyloides stercoralis is a parasitic nematode of humans, which is found throughout the tropics and sub-tropics worldwide. High prevalence of infection is found focally in the Caribbean, in West and East Africa and particularly Southeast Asia Footnote 3. Data support that anywhere between 10% to 40% of the population in tropical and sub-tropical regions are affected by strongyloidiasis, with rates as high as 60% in countries with ecologies and socioeconomic factors permissive to the transmission of S. stercoralis Footnote 3. A Canadian study of refugees documented a 77% seroprevalence among refugees from Cambodia and a 12% seroprevalence among refugees from Vietnam Footnote 4. Furthermore, strongyloidiasis was the fifth most common diagnosis among 1,321 ill new immigrants presenting for care at a Canadian Travel Medicine Network (CanTravNet) site over a three-year period Footnote 5,Footnote 6. Given that 6.8 million Canadians are foreign-born, with approximately 85% emigrating from regions endemic for strongyloidiasis Footnote 7, a substantial proportion of the immigrant and refugee population of Canada is at risk for strongyloidiasis. Asia continues to be the largest source region for immigrants to Canada, with the Philippines, China and India serving as the top single source countries Footnote 7. Immigrant populations from Africa, the Caribbean, Central and South America are increasing over time as well Footnote 7.

In Canada, approximately 2.5-million individuals are estimated to have simple intestinal strongyloidiasis, assuming a source country prevalence of 40% Footnote 3. This estimate excludes travel-acquired strongyloidiasis, which is expected to account for a minority of cases in Canada. However, it is important to recognize that even short-term travel to highly endemic areas may be associated with acquisition of strongyloidiasis Footnote 8,Footnote 9,Footnote 10.

It is difficult to estimate the proportion of Canadian immigrants and refugees who are at risk of developing disseminated strongyloidiasis, such as individuals who require iatrogenic immunosuppression or have HTLV-1 co-infection.

Pathogenesis

Strongyloidiasis is acquired when infectious larvae, found in sand or soil, penetrate intact human skin and after an obligatory tissue migration phase, mature into adults in the small bowel. Unlike other parasitic helminths, Strongyloides has an indefinite lifespan in the human host and due to an autoinfection cycle whereby infective stage larvae re-penetrate host skin or bowel, clinical disease is a lifelong risk unless treated.

Clinical features

Strongyloides infection may cause a spectrum of illness ranging from asymptomatic eosinophilia to gastrointestinal symptoms to accelerated autoinfection (or "hyperinfection syndrome") to fulminant and fatal disseminated disease. Immune suppression such as that which occurs in the setting of prolonged corticosteroid therapy, HTLV-1 infection, or hematologic malignancy, is a risk factor for disseminated strongyloidiasis Footnote 11,Footnote 12,Footnote 13,Footnote 14, an entity documented to carry a mortality rate in excess of 85% Footnote 15,Footnote 16. The exact mechanisms for immunologic control of this infection are unclear.

Diagnosis and screening

The Canadian Consortium on Refugee and Immigrant Health (CCRIH) has recently recommended Strongyloides screening only for refugees from Southeast Asia and Sub-Saharan Africa Footnote 17. Broader-based screening was not recommended as there are little data on the prevalence of strongyloidiasis in immigrant populations and serologic screening is not easily or rapidly available in many parts of Canada. It has been our collective clinical experience, however, that strongyloidiasis is widespread in the global migrant population and screening should be based on a risk assessment, taking into account the risk of exposure to Strongyloides, the risk of disseminated disease and the presenting clinical syndrome (including asymptomatic persons who are planned to undergo iatrogenic immune suppression). This is supported by a case series in Toronto that documented ten cases of disseminated strongyloidiasis over a seven-month period, all of which occurred in immigrants to Canada, originating from Southeast Asia, the Caribbean, South America or Italy Footnote 11. Collectively, members of CATMAT have contributed to the care of patients with strongyloidiasis arising from travel to or residence in the Mediterranean, all parts of Africa, the Caribbean and Latin America, South Asia including the Indian sub-continent and the very high-risk Southeast Asia. Thus, we recommend careful consideration of epidemiologic risk as outlined below in order to inform screening decisions.

Due to the low sensitivity of stool examination for ova and parasites (O&P) arising from low larval burden and intermittent shedding in the stool, serologic testing is the diagnostic method of choice in the patient suspected to have simple intestinal strongyloidiasis.

It is important to note that sensitivity of serology may be reduced in the patient with immunosuppression, especially due to HTLV-1 infection or hematologic malignancy and associated chemotherapy Footnote 18,Footnote 19. These individuals are also at risk of developing disseminated strongyloidiasis and screening should generally involve both serologic and stool testing as outlined below. A stool O&P sample that is positive for Strongyloides larvae should prompt screening for HTLV-1 infection and referral to a specialist in tropical medicine with expertise in the management of strongyloidiasis. Physician members of the Canadian Malaria Network are available to provide advice in such cases Footnote 20.

Treatment

The drug of choice for treatment of simple intestinal and asymptomatic strongyloidiasis is ivermectin Footnote 15,Footnote 21 given in two doses. Persons born or with prolonged residence in nations of the rainforest area of central Africa (e.g., Cameroon, Equatorial Guinea, Gabon, Central African Republic, Congo and the Democratic Republic of the Congo, as well as southern areas of Nigeria, Chad, South Sudan and northern Angola) should have high microfilaremic loiasis excluded prior to administration of ivermectin. This should be done by daytime blood film examination for microfilaria of Loa loa.

For Strongyloides hyperinfection or dissemination syndrome, CATMAT recommends dual-therapy with ivermectin and albendazole as outlined below, which is based on case report data Footnote 11,Footnote 22,Footnote 23,Footnote 24,Footnote 25, expert opinion and the clinical experience of CATMAT members. Clinical specimens, including sputum and stool, should be rechecked periodically during the course of treatment of Strongyloides hyperinfection or dissemination to ensure clearance of larvae.

In order to prevent the development of disseminated strongyloidiasis, patients at risk for treatment failure or complications, such as those with HTLV-1 or Loa loa co-infection, should be referred to a tropical medicine specialist with expertise in the management of such infections. There is no evidence to support that a "test and treat" strategy is superior or more cost-effective compared to empiric administration of ivermectin to at-risk individuals about to undergo immune suppression Footnote 26. As access to ivermectin is limited in Canada, CATMAT recommends that empiric treatment be reserved for individuals whose planned immune suppression cannot await diagnostic testing, as outlined in Step 3 of the diagnosis and treatment algorithm below.

Any patient with disseminated strongyloidiasis should also receive empiric treatment with broad-spectrum antibiotics to cover polymicrobial sepsis, a common complication of the hyperinfection syndrome. Both albendazole and ivermectin are pregnancy category C agents. In a pregnant person with Strongyloides hyperinfection or dissemination, the benefits of treatment likely outweigh the risks due to the life-threatening nature of disseminated strongyloidiasis. Ivermectin and albendazole are only available in Canada through the Special Access Programme of Health Canada Footnote 27. Applications to the program typically have a one-week turnaround time, although emergency use, same-day requests may be made by telephone.

Infection control issues

Patients with disseminated strongyloidiasis should be managed in contact precautions due to the risk of infectious filariform larvae being shed in effluents such as stool, urine, sputum and endotracheal aspirates. Most of these patients are critically unwell and require intensive nursing and medical care, thus precautions to prevent nosocomial transmission to health care workers is important. However, it must be noted that nosocomial transmission is a theoretical risk that has not been well documented in the literature Footnote 28,Footnote 29.

Contact precautions are also recommended for laboratory workers, due to the potential risk of encountering infectious filariform larvae, particularly in cultures of stool or sputum that have been sent to the laboratory to exclude bacterial infection. Agar plates of specimens from patients with disseminated strongyloidiasis should be handled with gloves and sealed with Parafilm tape. Filariform larvae of other nematode helminths are susceptible to 70% ethanol for 10 minutes, 0.5% Dettol® for 20 minutes and chlorinated hydrocarbons (tetrachloroethylene) Footnote 30. Filariform larvae can also be inactivated by water heated above 80°C Footnote 30. Household contacts of patients with disseminated strongyloidiasis or Strongyloides hyperinfection syndrome should be screened for strongyloidiasis serologically and by stool examination in order to identify person-to-person transmission.

Diagnosis and treatment algorithm for strongyloidiasis - Steps 1-4

Note to reader: All steps are to be completed sequentially, as Step 3 requires input from Steps 1 and 2.

 
Step 1: Define risk category for disseminated strongyloidiasis based on epidemiologic and clinical factors

Epidemiologic risk category
for Strongyloides
exposure/Infection
Clinical risk factor for disseminated Strongyloides
  • No known defects in cell mediated immunity
Birth or residence or long-term travelStep 1 table note 4 in Southeast Asia, Oceania, Sub-Saharan Africa, South America, Caribbean High Moderate
Birth or residence or long-term travelStep 1 table note 4 in Mediterranean countries, Middle East, North Africa, Indian sub-continent, Asia Moderate Low
Birth or residence or long-term travelStep 1 table note 4 in Australia, North AmericaStep 1 table note 5 or Western Europe Very low Very low
 
Step 2: Define suspected clinical syndrome

Suspected clinical syndrome Appropriate diagnostic test Appropriate diagnostic specimen
Asymptomatic ± eosinophilia (This would include asymptomatic individuals undergoing planned immune suppression.)
  • Serology
  • Stool ova and parasites (O&P) examination
(Very low risk)
Simple intestinal strongyloidiasisStep 2 table note 1
  • Serology
  • Stool O&P examination
  • Serum
  • SAF-preserved stool specimen
(Low risk)
Mild hyperinfection syndromeStep 2 table note 2
  • Serology
  • Stool O&P examination
  • Sputum O&P examination
  • Agar plate culture
  • Serum
  • SAF-preserved stool specimen
  • Fresh sputum in sterile container
  • Fresh stool/sputum for agar plate culture
(Moderate risk)
Disseminated strongyloidiasisStep 2 table note 3
  • Serology
  • Stool O&P examination
  • Sputum O&P examination
  • Urine O&P examination
  • CSFStep 2 table note 5 O&P examination
  • Tissue O&P examination
  • Agar plate culture
  • Serum
  • SAF-preserved stool specimen
  • Fresh sputum in sterile container
  • Urine in sterile container
  • CSF in sterile container
  • Tissue, paraffin-embedded or unprocessed
  • Any fresh specimen as above for agar plate culture
(High risk)
 
Step 3: Suggested diagnostic and empiric management approach based on identified risk category (Step 1) and clinical syndrome (Step 2)

Risk category
(as per Step 1)
Suspected clinical syndrome (as per Step 2)
Asymptomatic ±
eosinophiliaStep 3 table note 1
Simple intestinal
strongyloidiasis
Mild hyperinfection
syndrome
Disseminated
strongyloidiasis
High Send appropriate specimens for diagnostic testingStep 3 table note 2

(Moderate risk)
Empiric treatment while awaiting diagnostic testing

(High risk)
Empiric treatment while awaiting diagnostic testing

(High risk)
Empiric treatment while awaiting diagnostic testing

(High risk)
Moderate Send appropriate specimens for diagnostic testing

(Moderate risk)
Send appropriate specimens for diagnostic testing

(Moderate risk)
Empiric treatment while awaiting diagnostic testing

(High risk)
Empiric treatment while awaiting diagnostic testing

(High risk)
Low Send appropriate specimens for diagnostic testing

(Low risk)
Send appropriate specimens for diagnostic testing

(Low risk)
Send appropriate specimens for diagnostic testing

(Low risk)
Send appropriate specimens for diagnostic testing

(Low risk)
Very low Screening not recommended. Consider alternate diagnosis

(Very low risk)
Screening not recommended. Consider alternate diagnosis

(Very low risk)
Send appropriate specimens for diagnostic testing

(Very low risk)
Send appropriate specimens for diagnostic testing

(Very low risk)
 
Step 4: Treat strongyloidiasis according to clinical syndrome and diagnostic results

Clinical syndrome Diagnostic confirmation Adult management Pediatric management
Asymptomatic ± eosinophilia (including asymptomatic individuals undergoing planned immune suppression)
  • Serology
  • Stool ova and parasites (O&P) examination for larvae
Ivermectin 200 µg/kg/day po once daily × 2 doses on day 1 and 2, or 14-days apartStep 4 table note 1 Ivermectin 200 µg/kg/day po once daily × 2 doses on day 1 and 2, or 14-days apartStep 4 table note 1
(Very low risk)
Simple intestinal strongyloidiasisStep 4 table note 2
  • Serology
  • Stool O&P examination for larvae
Ivermectin 200 µg/kg/day po once daily × 2 doses on day 1 and 2, or 14-days apartStep 4 table note 1 Ivermectin 200 µg/kg/day po once daily × 2 doses on day 1 and 2, or 14-days apartStep 4 table note 1
(Low risk)
Mild hyperinfection syndromeStep 4 table note 3
  • Serology
  • Stool O&P
  • Sputum O&P examination for larvae
Ivermectin 200 µg/kg/day po once daily × 2 doses on day 1 and 2, or 14-days apartStep 4 table note 1
PLUS
Albendazole 400 mg po BID × 7 days
OR, Monotherapy:
Ivermectin 200 µg/kg/day po once daily × 7 days
Ivermectin 200 µg/kg/day po once daily × 2 doses on day 1 and 2, or 14-days apartStep 4 table note 1
PLUS
Albendazole 400 mg po BID × 7 days
OR, Monotherapy:
Ivermectin 200 µg/kg/day po once daily × 7 days
(Moderate risk)
Disseminated strongyloidiasis Step 4 table note 4,Step 4 table note 5
  • Serology
  • Stool O&P examination for larvae
  • Sputum O&P examination for larvae
  • Urine, cerebrospinal fluid (CSF) or other body fluid or tissue examination for larvae.
Ivermectin 200 µg/kg/day po or scStep 4 table note 6 once daily
PLUS
Albendazole 400 mg po BID until cessation of larval shedding and clinical improvement
Ivermectin 200 µg/kg/day po or scStep 4 table note 6 once daily
PLUS
Albendazole 400 mg po BID until cessation of larval shedding and clinical improvement
(High risk)

Conclusion

Strongyloidiasis is relatively widespread in the global migrant population. Screening for the disease should be based on an individual risk assessment, taking into account the risk of exposure to Strongyloides, the risk of disseminated disease and the presenting clinical syndrome (which may include asymptomatic persons who are planned to undergo iatrogenic immune suppression). This statement summarizes the available relevant information on strongyloidiasis and provides a practical tool for the clinician to use in the prevention, assessment and management of disseminated strongyloidiasis in Canada.

Key points

  • Screening for strongyloidiasis should be considered for individuals with epidemiologic risk and/or co-morbidities that place them at risk for Strongyloides hyperinfection and dissemination. Those at highest risk of hyperinfection and dissemination are individuals born in a Strongyloides-endemic area who undergo iatrogenic immunosuppression, or have intercurrent HTLV-1 infection.
  • Diagnosis of strongyloidiasis rests on serologic testing and/or examination of stools and other clinical specimens for larvae. Serology is generally highly sensitive, while stool examination is highly specific.
  • Performance characteristics of diagnostic tests may be altered by immune suppression and co-infections such as HTLV-1, in that stool examination sensitivity may improve, while sensitivity of serology may decline.
  • Referral to a tropical medicine specialist with expertise in the management of strongyloidiasis is recommended for any patient with suspected or confirmed disseminated strongyloidiasis and for patients with both Strongyloides and HTLV-1 or Loa loa infections.

Acknowledgements

CATMAT acknowledges and appreciates the contribution of Mihaela Gheorghe.

CATMAT members: McCarthy A (Chair), Boggild A, Brophy J, Bui Y, Crockett M, Greenaway C, Libman M, Teitelbaum P and Vaughan S.

Liaison members: Audcent T (Canadian Paediatric Society), Gershman M (United States Centers for Disease Control and Prevention) and Pernica J (Association of Medical Microbiology and Infectious Disease Canada).

Ex officio members: Marion D (Canadian Forces Health Services Centre, Department of National Defence), McDonald P (Division of Anti-Infective Drugs, Health Canada), Schofield S (Pest Management Entomology, Department of National Defence) and Tepper M (Directorate of Force Health Protection, Department of National Defence).

Conflict of interest

None.

Funding

This work was supported by the Public Health Agency of Canada.

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