Hyperinfection syndrome should be considered a potential medical emergency. Thus, treatment should be started immediately if this is being considered. Strongyloides stercoralis Hyperinfection remain quiescent indefinitely, immunosuppression can lead to the hyperinfection syndrome, which is. Whereas in chronic strongyloidiasis and in hyperinfection syndrome the larvae are limited to the GI tract and the lungs, in disseminated.
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This review discusses the latest approaches to the diagnosis and treatment of patients with strongyloidiasis, with an emphasis on infection in the immunocompromised host and the risk for disseminated strongyloidiasis.
The differences in acute, chronic, accelerated autoinfection, and disseminated disease in Strongyloides stercoralis infection are explored with particular emphasis on early diagnosis, treatment, and prevention. The goals of treatment are investigated for the different infection states.
Predisposing risks for dissemination are delineated, and the roles played for newer diagnostics in the identification of at-risk individuals are detailed.
Syndrlme use of newer diagnostic tests and broader screening of immunocompromised patients from Strongyloides -endemic areas is of paramount importance, particularly if prevention of life-threatening dissemination is the goal. Strongyloides stercoralis is an intestinal nematode acquired primarily in the tropics or subtropics, estimated to infect approximately million people worldwide [ 1 ]. It commonly causes chronic, asymptomatic infection, but a change in immune status hyperunfection lead to an increase in parasite burden, hyper-infection syndrome, dissemination, and death if unrecognized.
Corticosteroid use is commonly associated with hyperinfection syndrome. Diagnosis of Strongyloides infection has traditionally been based on serial stool examinations for larvae, though more recently serologic approaches have gained primacy.
Even newer techniques e.
One to two days of ivermectin is the treatment of choice for chronic, asymptomatic infection. For hyperinfection syndrome and disseminated infections, ivermectin is the drug of choice with albendazole as a second-line therapythough duration of therapy and route of administration must be individualized with the endpoint being complete eradication of the parasite.
There is no test of cure currently available, although IgG antibody levels have been shown to decline within 6 months of successful treatment, and DNA-based diagnostics have recently been shown to hold promise as a proof-of-cure technique. The life cycle of S. For Strongyloides infections, the endemic areas include most tropical and subtropical weather zones on all continents except Antarctica [ 1 ]. Infection is initiated by infectious larvae penetrating the skin, often on the soles of the feet [ 3 ].
Once the larvae penetrate the skin, they travel through the bloodstream entering the alveolar space of the lungs; this lung migration can cause a pneumonitis, but most commonly is clinically asymptomatic. Larvae are then expectorated, traveling through the trachea and then swallowed. The larvae mature into adult worms, mate and release eggs in the gastrointestinal tract. Most eggs hatch into rhabditiform larvae and are excreted; some transform into infectious filariform larvae and penetrate the perirectal mucosa or skin, thereby reentering the circulatory system and starting the cycle again [ 5 ].
The clinical manifestations of acute strongyloidiasis can be associated with the path of larval migration to the small intestine. Infected individuals may experience irritation at the site of skin penetration by larvae, followed by tracheal irritation or dry cough and ultimately gastrointestinal symptoms such as diarrhea, constipation, abdominal pain, or anorexia.
Chronic strongyloidiasis most frequently causes asymptomatic infection in immunocompetent individuals. Symptomatic individuals may have diarrhea, constipation, or intermittent vomiting. Dermato-logic manifestations such as recurrent urticaria can occur, as can larva currenspruritic linear streaks located along the lower trunk, thighs, and buttocks as a result of migrating larvae.
Unusual manifestations of chronic strongyloidiasis include reactive arthritis [ 9 ], nephrotic syndrome [ 10 ], chronic malabsorption [ 11 ], duodenal obstruction [ 12 ], focal hepatic lesions [ 13 ], and recurrent asthma [ 14 ].
Hyperinfection describes the syndrome of accelerated autoinfection, generally the result of an alteration in immune status. The distinction between autoinfection and hyperinfection is not strictly defined, but hyperinfection syndrome implies the presence of signs and symptoms attributable to increased larval migration.
Development or exacerbation of gastrointestinal and pulmonary symptoms is seen, and the detection of increased numbers of larvae in stool and sputum is the hallmark of hyperinfection.
Hyperinfection syndrome has been described as late as 64 years after an individual has left an endemic area [ 15 ]. Recurrent paralytic ileus associated with protein losing enteropathy and diarrhea giving rise to hypoalbuminemia and peripheral edema has been seen [ 16 ]. Common pulmonary manifestations include wheezing, hoarseness, palpitations, atrial fibrillation, dyspnea, or, rarely, massive hemoptysis. Radio-graphs most frequently demonstrate focal or bilateral interstitial infiltrates.
Disseminated infection occurs when larvae migrate away from the lung and gastrointestinal tract into other organ systems [ 17 ]. Penetration of large numbers of larvae through the intestinal wall can be associated with microbial sepsis as larvae carry organisms with them into the bloodstream [ 18 ].
Organisms that have been reported to cause sepsis in such patients include group D streptococci, Candida [ 19 ]; Streptococcus bovis [ 20 ], Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas, Enterococcus faecalis, coagulase-negative staphylococci, and Streptococcus pneumoniae. The risk of sepsis is increased especially if the patient is already immunosuppressed. Corticosteroids have a particularly strong and specific association with the development of hyper-infection syndrome and dissemination.
Other immunosuppressive therapies and underlying conditions may also predispose to dissemination. However, the concomitant administration of steroids in most of these other conditions makes it difficult to assign a direct causal association.
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Hyperinfection syndrome has been described regardless of dose, duration, or route of administration of corticosteroids. Even short courses 6—17 days of steroids in immunocompetent patients without underlying immunosuppressive conditions have even been associated with hyper-infection syndrome and death [ 23 ].
Conditions associated with hyperinfection syndrome are as follows:. HTLV-1 represents a significant risk factor for the development of hyperinfection syndrome or disseminated strongyloidiasis [ 24 ].
Severe infection with Strongyloides has not been observed frequently with HIV-infected patients [ 29 ]. Whether IRIS occurs after the initiation of antiretroviral therapy in Strongyloides -infected patients remains unclear. Among the different types of transplants, HSCT has the highest incidence of fatal dissemination with a higher mortality than in other types of transplants [ 32 ]. Transplanted patients have unique regimens that increase their risk of dissemination.
Immunosuppression is used for preconditioning see above and then to prevent rejection; lifelong immunosuppression is needed. A unique complication of transplants is the development of graft-versus-host disease GVHD.
Especially in HSCT, in which current techniques are increasingly using nonmyeloablative allogeneic stem cell transplantation that does not completely deplete the immune cells of the recipient and is better tolerated, the risk of GVHD is greater than for other approaches [ 33 ].
Because the main therapy for acute GVHD is corticosteroids, it is at the time that steroids are given in the setting of chronic strongyloidiasis that hyperinfectioh risk for dissemination is high [ 3435 ].
Organ donors have also been shown to transmit Strongyloides infection, with cases of solid-organ transplant-associated Strongyloides infections having been reported [ 37 ].
Several case reports have supported an association between Strongyloides infection and hypogammaglobulinemia, associated with multiple myeloma and nephrotic syndrome [ 38 — 40 ].
Current standard of care hypperinfection the classic hyperinfextion microscopy exam for parasitic ova and larvae with hyperrinfection reported It is labor intensive and dependent on operator skill. The test can also remain positive after treatment for extended periods of time [ 43 ]. In addition, there is serological cross-reactivity with some patients with active filarial infections [ 44 ]. RT-PCR, like microscopy, only identifies active Strongyloides infection as positivity has been shown to be lost following definitive treatment Mejia et al.
RT-PCR is not available at all diagnostic centers and, at the moment, is only applicable in research settings.
A Fatal Strongyloides Stercoralis Hyperinfection Syndrome in a Patient With Chronic kidney Disease
LIPS assays are newer immunologic techniques that rely on rapid immunoprecipitation and detection in hyperinfectiob high-throughput format [ 47 ]. Another benefit of LIPS over standard immunoassays is the evidence of reversion to hyperinffction following treatment [ 47 ], a property that can be useful in monitoring populations following mass drug administration MDA and to assess posttreatment efficacies syndfome drugs. Diagnosis of hyperinfection syndrome and disseminated Htperinfection infection is not difficult because of the large numbers of larvae often seen in the stool or other bodily fluids including CSF, pleural fluid, and bronchoalveolar lavage BAL fluid.
Treatment of Strongyloides infection is as follows:. Hyperinfection syndrome should be considered a potential medical emergency. Thus, treatment should be started immediately if this is being considered. Although no controlled trials have been performed in hyperinfection syndrome, daily ivermectin has been the de facto treatment with the length of treatment being for a minimum of 2 weeks and often until there has been evidence of two full weeks of negative stool examination.
Reduction of immunosuppressive therapy should also be an important part of treatment, but obviously needs to be weighed against the long-term outcomes sgndrome the underlying disease. There have been case reports of the improved efficacy of combination treatment with ivermectin and albendazole [ 49 ], but no randomized trials have been done; however, it has often been considered a reasoned approach.
Other methods of ivermectin administration may have to be used, particularly when patients are unable to take oral medication even through a nasogastric tube because of severe systemic illness of paralytic ileus.
These include per rectal and parenteral syhdrome [ 50 ]. The parenteral formulation is syndromd veterinary formulation of ivermectin and should be reserved for extreme situations with no other options for clearing Strongyloides infection [ 51 ].
Contraindications for treatment with ivermectin include patients with high-grade microfilaremia of Loa loa from endemic areas of West Africa and because of the encephalopathy seen in these individuals following ivermectin treatment [ 52 ].
In patients with high levels of Loa loa microfilaremia, albendazole is a good alternative hyperinfecton the treatment of strongyloidiasis. Dissemination is hyperinfetcion dangerous medical condition with extremely high mortality. It affects specific patients with acquired immunodeficiencies such hyperinfectioh HTLV-1 or iatrogenically by immunosuppressive agents.
Although multiple agents have been implicated in increasing the risk of hyperinfection syndrome, corticosteroids administration synddrome the greatest risk; interestingly, disseminated Strongyloides infection has occurred within a week of corticosteroid initiation [ 23 ].
Screening patients for asymptomatic Strongyloides infection is crucial to prevent hyperinfection syndrome. Among the available tests stool examination, molecular diagnostics, and serologiesserologic tests are both the most reliable and the most sensitive especially in populations from Strongyloides -endemic areas. Anyone at high risk for dissemination who has a potential Strongyloides -exposure history should be screened, most notably those with diseases associated with hyperinfection syndrome and those requiring immunosuppressive therapy for whatever reason.
Finally, given the cost of laboratory investigations for S. Whether this approach will be adopted remains an open, but important, question for policy makers. Although Strongyloides often causes chronic and clinically asymptomatic infection, parasite number can increase substantially in those who hyperinfetion immunocompromised, leading to hyperinfection, dissemination, and death if unrecognized. Prevention of this serious set of sequelae of Strongyloides infection involves treating all chronically infected, asymptomatic individuals.
Patients from Strongyloides endemic areas taking corticosteroids must be considered high risk for hyperinfection syndrome and newer diagnostic tests and broader screening of immunocompromised patients from Strongyloides -endemic areas is of paramount importance, particularly if prevention of life-threatening dissemination is the goal.
Funding was received from the National Institutes htperinfection Health. Papers of particular interest, published within the annual period of review, have been highlighted as:. Additional references related to this topic can also be found in the Current World Literature section in this issue p.
National Center for Biotechnology InformationU. Curr Opin Infect Dis. Author manuscript; available in PMC Feb 1.
Rojelio Mejia and Thomas B. Author information Copyright and License information Disclaimer. Correspondence to Thomas B.
The publisher’s final edited version of this article is available at Curr Opin Infect Dis. See other articles in PMC that cite the published article. Abstract Purpose of review This review discusses the latest approaches to the diagnosis and hyperibfection of patients with strongyloidiasis, with an emphasis on infection in the immunocompromised hyperinfectiom and the risk for disseminated strongyloidiasis.
Recent findings The differences in acute, chronic, accelerated stndrome, and disseminated disease in Strongyloides stercoralis infection are explored with particular emphasis on early diagnosis, treatment, and prevention.
Summary The use of newer diagnostic tests and broader screening of immunocompromised patients from Strongyloides -endemic areas is of paramount importance, particularly if prevention of life-threatening dissemination is the goal.