-
BMJ Case Reports Sep 2022Strongyloidiasis is a disease caused by the intestinal helminth When the immune system of infected individuals is compromised, larvae may migrate from the...
Strongyloidiasis is a disease caused by the intestinal helminth When the immune system of infected individuals is compromised, larvae may migrate from the gastrointestinal tract to other tissues, causing hyperinfection syndrome, which has a reported mortality of 71%. In this case, we report a patient with hyperinfection syndrome with central nervous system (CNS) involvement. An elderly South East Asian male tourist presented with pulmonary symptoms, fever and infiltrates on chest X-ray. He later developed symptoms of CNS infection. larvae were found in a stool sample. Microbiological examination of cerebrospinal fluid revealed specific DNA. The patient was treated with oral and rectal ivermectin and albendazole. The condition was complicated by sepsis, bacteraemia and hypereosinophilia. Unfortunately, the patient eventually died from pulmonary oedema and insufficiency. This case highlights the global importance of CNS infection in endemic and non-endemic regions.
Topics: Aged; Albendazole; Animals; Eosinophilia; Humans; Ivermectin; Larva; Male; Strongyloides stercoralis; Strongyloidiasis; Syndrome
PubMed: 36137646
DOI: 10.1136/bcr-2021-247032 -
Proceedings of the National Academy of... Jan 2018hyperinfection causes high mortality rates in humans, and, while hyperinfection can be induced by immunosuppressive glucocorticoids, the pathogenesis remains unknown....
hyperinfection causes high mortality rates in humans, and, while hyperinfection can be induced by immunosuppressive glucocorticoids, the pathogenesis remains unknown. Since immunocompetent mice are resistant to infection with , we hypothesized that NSG mice, which have a reduced innate immune response and lack adaptive immunity, would be susceptible to the infection and develop hyperinfection. Interestingly, despite the presence of large numbers of adult and first-stage larvae in -infected NSG mice, no hyperinfection was observed even when the mice were treated with a monoclonal antibody to eliminate residual granulocyte activity. NSG mice were then infected with third-stage larvae and treated for 6 wk with methylprednisolone acetate (MPA), a synthetic glucocorticoid. MPA treatment of infected mice resulted in 50% mortality and caused a significant >10-fold increase in the number of parasitic female worms compared with infected untreated mice. In addition, autoinfective third-stage larvae, which initiate hyperinfection, were found in high numbers in MPA-treated, but not untreated, mice. Remarkably, treatment with Δ7-dafachronic acid, an agonist of the parasite nuclear receptor -DAF-12, significantly reduced the worm burden in MPA-treated mice undergoing hyperinfection with Overall, this study provides a useful mouse model for autoinfection and suggests a therapeutic strategy for treating lethal hyperinfection.
Topics: Animals; Cholestenes; Female; Methylprednisolone; Methylprednisolone Acetate; Mice; Strongyloides stercoralis; Strongyloidiasis
PubMed: 29203662
DOI: 10.1073/pnas.1712235114 -
Parasitology Jan 2022This study analysed Strongyloides stercoralis genetic variability based on a 404 bp region of the cox1 gene from Latin-American samples in a clinical context including... (Observational Study)
Observational Study
This study analysed Strongyloides stercoralis genetic variability based on a 404 bp region of the cox1 gene from Latin-American samples in a clinical context including epidemiological, diagnosis and follow-up variables. A prospective, descriptive, observational study was conducted to evaluate clinical and parasitological evolution after ivermectin treatment of 41 patients infected with S. stercoralis. Reactivation of the disease was defined both by clinical symptoms appearance and/or direct larvae detection 30 days after treatment or later. We described 10 haplotypes organized in two clusters. Most frequent variants were also described in the Asian continent in human (HP24 and HP93) and canine (HP24) samples. Clinical presentation (intestinal, severe, cutaneous and asymptomatic), immunological status and eosinophil count were not associated with specific haplotypes or clusters. Nevertheless, presence of cluster 1 haplotypes during diagnosis increased the risk of reactivation with an odds ratio (OR) of 7.51 [confidence interval (CI) 95% 1.38–44.29, P = 0.026]. In contrast, reactivation probability was 83 times lower if cluster 2 (I152V mutation) was detected (OR = 0.17, CI 95% 0.02–0.80, P = 0.02). This is the first analysis of S. stercoralis cox1 diversity in the clinical context. Determination of clusters during the diagnosis could facilitate and improve the design of follow-up strategies to prevent severe reactivations of this chronic disease.
Topics: Animals; Dogs; Feces; Humans; Latin America; Molecular Typing; Prospective Studies; Strongyloides stercoralis; Strongyloidiasis
PubMed: 35184784
DOI: 10.1017/S0031182021001517 -
The Lancet. Infectious Diseases Aug 2021Strongyloidiasis represents a major public health issue, particularly in resource-limited countries. Preliminary studies suggest that moxidectin might serve as an... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of ascending doses of moxidectin against Strongyloides stercoralis infections in adults: a randomised, parallel-group, single-blinded, placebo-controlled, dose-ranging, phase 2a trial.
BACKGROUND
Strongyloidiasis represents a major public health issue, particularly in resource-limited countries. Preliminary studies suggest that moxidectin might serve as an alternative to the only available treatment option, ivermectin. We aimed to evaluate the efficacy and safety of ascending doses of moxidectin in Strongyloides stercoralis-infected patients.
METHODS
We did a randomised, parallel-group, single-blinded, placebo-controlled, dose-ranging, phase 2a trial in four villages in northern Laos. Eligible adults (aged 18-65 years) with S stercoralis infection intensities of at least 0·4 larvae per g of stool in at least two stool samples were randomly assigned (1:1:1:1:1:1:1) by use of computerised, stratified, block randomisation into seven treatment groups: 2 mg of moxidectin, 4 mg of moxidectin, 6 mg of moxidectin, 8 mg of moxidectin, 10 mg of moxidectin, 12 mg of moxidectin, or placebo. Participants and primary outcome assessors were masked to treatment allocation, but study site investigators were not. Participants received a single oral dose of their allocated dose of moxidectin in 2 mg tablets, or four placebo tablets. Three stool samples were collected at baseline and two stool samples were collected 28 days after treatment from each participant. A Baermann assay was used to quantify S stercoralis infection and Kato-Katz thick smears were used to qualitatively identify coinfections with additional helminths species. The primary endpoint was cure rate against S stercoralis and was analysed in an available case analysis set, defined as all randomly assigned participants with primary endpoint data. Predicted cure rates and associated CIs were estimated with hyperbolic E models. Safety was evaluated in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04056325, and is complete.
FINDINGS
Between Nov 27, 2019, and March 15, 2020, 785 adults were screened for trial eligibility. Of these, 223 participants were randomly assigned to treatment groups and 209 completed the study and were analysed for the primary outcome. 2 mg of moxidectin had a predicted cure rate of 75% (95% CI 59-87; 22 [73%] of 30 cured) against S stercoralis compared with a predicted cure rate of 14% (5-31; four [14%] of 29 cured) for placebo. With escalating doses, the probability of cure increased from 83% (95% CI 76-88; 26 [90%] of 29 cured) at 4 mg to 86% (79-90; 27 [84%] of 32 cured) at 6 mg, and to 87% (80-92; 24 [83%] of 29 cured) at 8 mg, levelling off at 88% (80-93; 29 [97%] of 30 cured) at 10 mg and 88% (80-93; 26 [87%] of 30 cured) at 12 mg. Moxidectin was well tolerated across all treatment groups, with no serious adverse events being recorded and all reported symptoms being classified as mild.
INTERPRETATION
4-12 mg of moxidectin showed promising tolerability and efficacy profiles in the treatment of S stercoralis infections in adults. Because 8 mg of moxidectin is used for the treatment of onchocerciasis and has been evaluated for other helminth infections, we recommend this dose for phase 2b and phase 3 trials of strongyloidiasis therapy.
FUNDING
Fondazione Adiuvare.
Topics: Adult; Animals; Anthelmintics; Drug-Related Side Effects and Adverse Reactions; Feces; Female; Humans; Laos; Macrolides; Male; Middle Aged; Single-Blind Method; Strongyloides stercoralis; Strongyloidiasis; Treatment Outcome
PubMed: 33798487
DOI: 10.1016/S1473-3099(20)30691-5 -
Epidemiology and Health 2021The objective of this study was to evaluate the prevalence of Strongyloides stercoralis and other intestinal parasites in patients receiving immunosuppressive drugs in...
OBJECTIVES
The objective of this study was to evaluate the prevalence of Strongyloides stercoralis and other intestinal parasites in patients receiving immunosuppressive drugs in northern Iran and to investigate related risk factors.
METHODS
This cross-sectional study was conducted among 494 patients receiving immunosuppressive drugs, including cancer patients undergoing chemotherapy (n=188) and those treated with prolonged corticosteroid administration (n=306). All fresh fecal samples were examined using the direct wet-mount, formalin ethyl acetate concentration, and agar plate culture techniques.
RESULTS
In total, 16.8% of patients were positive for at least 1 intestinal parasite; the helminthic and protozoan infection rates were 5.1% and 12.3%, respectively. The infection rate was significantly higher in corticosteroid-treated individuals (19.6%) than cancer patients (12.2%) (p<0.05). The prevalence rate of S. stercoralis among patients receiving chemotherapy and those treated with corticosteroids were 4.3% and 5.2%, respectively. The prevalence rate of S. stercoralis infection was significantly higher in older patients (p<0.05).
CONCLUSIONS
Strongyloidiasis is one of the most common parasites among patients receiving immunosuppressive drugs in northern Iran. Early diagnosis and proper treatment of these patients are necessary to minimize the complications of severe strongyloidiasis.
Topics: Adult; Animals; Cross-Sectional Studies; Feces; Female; Humans; Immunosuppressive Agents; Intestinal Diseases, Parasitic; Iran; Male; Middle Aged; Prevalence; Risk Factors; Strongyloides stercoralis
PubMed: 33494130
DOI: 10.4178/epih.e2021009 -
Molecular and Biochemical Parasitology Sep 2022The gastrointestinal (GI) nematode Strongyloides stercoralis (S.s.) causes human strongyloidiasis, a potentially life-threatening disease that currently affects over 600...
The gastrointestinal (GI) nematode Strongyloides stercoralis (S.s.) causes human strongyloidiasis, a potentially life-threatening disease that currently affects over 600 million people globally. The uniquely pernicious aspect of S.s. infection, as compared to all other GI nematodes, is its autoinfective larval stage (L3a) that maintains a low-grade chronic infection, allowing undetectable persistence for decades. Infected individuals who are administered glucocorticoid therapy can develop a rapid and often lethal hyperinfection syndrome within days. Hyperinfection patients often present with dramatic increases in first- and second-stage larvae and L3a in their GI tract, with L3a widely disseminating throughout host organs leading to sepsis. How glucocorticoid administration drives hyperinfection remains a critical unanswered question; specifically, it is unknown whether these steroids promote hyperinfection through eliminating essential host protective mechanisms and/or through dysregulating parasite development. This current deficiency in understanding is largely due to the previous absence of a genetically defined mouse model that would support all S.s. life-cycle stages and the lack of successful approaches for S.s. genetic manipulation. However, there are currently new possibilities through the recent demonstration that immunodeficient NOD.Cg-PrkdcIl2rg/SzJ (NSG) mice support sub-clinical infections that can be transformed to lethal hyperinfection syndrome following glucocorticoid administration. This is coupled with advances in transcriptomics, transgenesis, and gene inactivation strategies that now allow rigorous scientific inquiry into S.s. biology. We propose that combining in vivo manipulation of host immunity and deep immunoprofiling strategies with the latest advances in S.s. transcriptomics, piggyBac transposon-mediated transgene insertion, and CRISPR/Cas-9-mediated gene inactivation will facilitate new insights into the mechanisms that could be targeted to block lethality in humans with S.s. hyperinfection.
Topics: Animals; Glucocorticoids; Humans; Larva; Mice; Mice, Inbred NOD; Parasites; Strongyloides stercoralis; Strongyloidiasis
PubMed: 36007683
DOI: 10.1016/j.molbiopara.2022.111511 -
Clinical Microbiology and Infection :... Jun 2015Strongyloides stercoralis differs from the other soil-transmitted helminths because it puts infected subjects at risk of a fatal syndrome (in cases of immunosuppression... (Review)
Review
Strongyloides stercoralis differs from the other soil-transmitted helminths because it puts infected subjects at risk of a fatal syndrome (in cases of immunosuppression for medical conditions, immunosuppressant therapies, or both). Chronic strongyloidiasis is often a non-severe condition, or is sometimes even asymptomatic, but diagnosis and effective therapy are essential in order to eradicate the infection and the life-long risk involved. Therefore, diagnostic methods need to be highly sensitive. Stool microscopy and the Kato-Katz technique are commonly used in prevalence studies, but they are inadequate for S. stercoralis detection. This is probably the main reason why the global prevalence has long been underestimated. Concentration methods, the Baermann technique and Koga agar plate culture have better, but still unsatisfactory, sensitivity. Serological tests have demonstrated higher sensitivity; although some authors have concerns about their specificity, it is possible to define cut-off values over which infection is almost certain. In particular, the luciferase immunoprecipitation system technique combined with a recombinant antigen (NIE) demonstrated a specificity of almost 100%. ELISA coproantigen detection has also shown promising results, but still needs full evaluation. Molecular diagnostic methods are currently available in a few referral centres as in-house techniques. In this review, on the basis of the performance of the different diagnostic methods, we outline diagnostic strategies that could be proposed for different purposes, such as: prevalence studies in endemic areas; individual diagnosis and screening; and monitoring of cure in clinical care and clinical trials.
Topics: Animals; Clinical Laboratory Techniques; Diagnostic Tests, Routine; Humans; Parasitology; Strongyloides stercoralis; Strongyloidiasis
PubMed: 25887711
DOI: 10.1016/j.cmi.2015.04.001 -
Revue Medicale Suisse May 2022Before starting immunosuppressive therapy, it is important to screen for latent tuberculosis and, in case of particular exposures (e.g. travel, origin,…), for...
Before starting immunosuppressive therapy, it is important to screen for latent tuberculosis and, in case of particular exposures (e.g. travel, origin,…), for parasitosis such as amoebiasis, echinococcosis, strongyloidiasis and American trypanosomiasis. The Division of Tropical and Humanitarian Medicine of the Geneva University Hospitals has developed an algorithm to identify which screening is recommended according to exposure. Analysis of this practice shows that the most frequently detected latent disease is tuberculosis, followed by strongyloidiasis. For the latter, as the sensitivity of the serological test is reduced due to immunosuppression, the algorithm combine antibody testing with parasitological (Baermann and culture) and molecular (PCR) stool testing.
Topics: Animals; Feces; Humans; Immunocompromised Host; Mass Screening; Parasites; Serologic Tests; Strongyloides stercoralis; Strongyloidiasis
PubMed: 35510282
DOI: 10.53738/REVMED.2022.18.780.898 -
Clinical Infectious Diseases : An... Dec 2020Strongyloidiasis can cause devastating morbidity and death in immunosuppressed patients. Identification of reliable biomarkers for strongyloidiasis in immunosuppressed...
BACKGROUND
Strongyloidiasis can cause devastating morbidity and death in immunosuppressed patients. Identification of reliable biomarkers for strongyloidiasis in immunosuppressed patients is critical for the prevention of severe disease.
METHODS
In this cross-sectional study of solid organ transplant (SOT) candidates and recipients, we quantified Strongyloides-specific IgG to the recombinant NIE-Strongyloides antigen and/or to a soluble extract of S. stercoralis somatic antigens ("crude antigen") using enzyme-linked immunosorbent assays (ELISAs). We also measured peripheral eosinophilia, 4 different eosinophil granule proteins, and intestinal fatty acid-binding protein (IFABP).
RESULTS
We evaluated serum biomarkers in 149 individuals; 77 (52%) pre-SOT and 72 (48%) post-SOT. Four percent (6/149) tested positive by NIE ELISA and 9.6% (11/114) by crude antigen ELISA (overall seropositivity of 9.4% [14/149]). Seropositive patients had higher absolute eosinophil counts (AECs) than seronegative patients (P = .004). AEC was positively correlated to the levels of eosinophil granule proteins eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO) (P < .05), while IFABP was positively related to the 2 other eosinophil granule proteins (major basic protein [MBP] and eosinophil-derived neurotoxin [EDN]; Spearman's r = 0.3090 and 0.3778, respectively; P < .05; multivariate analyses slopes = 0.70 and 2.83, respectively).
CONCLUSIONS
This study suggests that, in SOT patients, strongyloidiasis triggers both eosinophilia and eosinophil activation, the latter being associated with intestinal inflammation. These data provide insight into the pathogenesis of S. stercoralis infection in the immunocompromised population at high risk of severe strongyloidiasis syndromes.
Topics: Animals; Cross-Sectional Studies; Eosinophils; Humans; Inflammation; Organ Transplantation; Strongyloides stercoralis; Strongyloidiasis
PubMed: 32155244
DOI: 10.1093/cid/ciaa233 -
Parasitology Research Jul 2017Strongyloides stercoralis can cause severe infection both in humans and dogs. Coproparasitological examination has low sensitivity for the diagnosis of this parasite;...
Strongyloides stercoralis can cause severe infection both in humans and dogs. Coproparasitological examination has low sensitivity for the diagnosis of this parasite; hence, different diagnostic techniques have been implemented. However, serology and molecular methods have been assessed almost exclusively in humans. In this study, two serologic assays and a real-time PCR (RT-PCR), routinely used for the diagnosis of strongyloidiasis in humans, have been tested for the diagnosis in dogs. Five dogs living in the same kennel in Bari, southern Italy, were diagnosed with S. stercoralis infection by detection of larvae in fecal samples processed by the Baermann method. Serum, fecal, and tissue (lungs, scraping of intestinal tract) samples from the same dogs were tested with two serologic assays (commercial ELISA, in-house IFAT) and with an in-house RT-PCR, routinely used for diagnosis in humans. IFAT was positive in all serum samples, ELISA in 3/7 (42.8%) samples. RT-PCR was positive in all pre-treatment fecal samples, in all fecal debris, and in intestinal scraping (three samples from the same deceased dog). The results suggest that IFAT and RT-PCR techniques routinely used for S. stercoralis diagnosis in humans could be useful for the diagnosis of the infection in dogs.
Topics: Animals; Dog Diseases; Dogs; Enzyme-Linked Immunosorbent Assay; Feces; Italy; Molecular Diagnostic Techniques; Real-Time Polymerase Chain Reaction; Strongyloides stercoralis; Strongyloidiasis
PubMed: 28493000
DOI: 10.1007/s00436-017-5468-0