Strongyloidiasis-related lung involvement: too much of a bad thing.

PURPOSE OF REVIEW: Strongyloidiasis is a soil-transmitted helminthiasis, a neglected tropical disease that affects 300-900 million individuals globally. Strongyloides stercoralis is associated with cutaneous, respiratory, and gastrointestinal clinical manifestations. Chronicity is due to an autoinfective cycle, and host immunosuppression can lead to severe and fatal disease. Lung involvement is significant in severe strongyloidiasis, and Strongyloides has a complex association with a number of lung diseases, which will be discussed in this review. RECENT FINDINGS: The treatment of chronic lung diseases such as asthma and chronic obstructive pulmonary disease with corticosteroids is an important risk factor for Strongyloides hyperinfection syndrome (SHS)/disseminated strongyloidiasis. The use of corticosteroids in the treatment of coronavirus disease 2019 (COVID-19) and potentially COVID-19-induced eosinopenia are risk factors for severe strongyloidiasis. Recent findings have demonstrated a significant immunomodulatory role of Strongyloides in both latent and active pulmonary tuberculosis associated to an impaired immune response and poor outcomes in active pulmonary tuberculosis. SUMMARY: Strongyloides lung involvement is a common finding in severe infection. Prompt recognition of Strongyloides infection as well as prevention of severe disease by screening or presumptive treatment are important goals in order to improve Strongyloides outcomes in at-risk population.

Strongyloidiasis - diagnostic and therapeutic dilemmas in hyperinfection patients: a case series.

The helminth infection caused by Strongyloides stercoralis is widespread in tropical regions, but rare in European countries. Unfamiliarity with the disease and diagnostic obstacles could contribute to its lethal outcome. Frequent use of corticosteroids during the COVID-19 pandemic could increase its significance. The aim of this retrospective descriptive study was to explore disease patterns and discuss clinical dilemmas in patients with S. stercoralis hyperinfection treated at the University Hospital for Infectious Diseases 'Dr. Fran Mihaljevic' in Zagreb, Croatia, between 2010 and 2021. Five out of 22 (22.7%) immunosuppressed patients treated due to strongyloidiasis developed hyperinfection. All patients were male, median 64 years; four were immunosuppressed by corticosteroids (although ileum resection could have been the trigger in one) and one by rituximab. The diagnosis was established after a median of 1.5 months of symptom duration, accidentally in all patients, by visualizing the parasite in the gastric/duodenal mucosa in four cases, and bronchial aspirate in one. All patients were cachectic, four out of five had severe hypoalbuminemia and all suffered secondary bacterial/fungal infection. Despite combined antibiotic, antifungal and antihelmintic therapy, three out of five of the patients died, after failing to clear living parasites from stool samples. We can conclude that significant delays in diagnosis and lack of clinical suspicion were observed among our patients with the most severe clinical presentations of strongyloidiasis. Although being beyond diagnostic recommendations for strongyloidiasis, an early upper gastrointestinal endoscopy with mucosal sample analysis could expedite diagnosis in severe, immunosuppressed patients. The persistence of viable parasites in the stool despite antihelmintic therapy should be further investigated.

Strongyloides Hyperinfection Syndrome among COVID-19 Patients Treated with Corticosteroids.

Widespread use of corticosteroids for COVID-19 treatment has led to Strongyloides reactivation and severe disease in patients from endemic areas. We describe a US patient with COVID-19 and Strongyloides hyperinfection syndrome and review other reported cases. Our findings highlight the need for Strongyloides screening and treatment in high-risk populations.

Comparison of Trials Using Ivermectin for COVID-19 Between Regions With High and Low Prevalence of Strongyloidiasis: A Meta-analysis.

Importance: A widely cited meta-analysis of randomized clinical trials has claimed ivermectin as an effective treatment for prevention of mortality in COVID-19. However, an unrecognized interaction variable with the relative risk (RR) of mortality may substantially change the appropriate interpretation of this analysis. Objective: To evaluate the association between regional prevalence of strongyloidiasis and ivermectin trial results for the outcome of mortality by testing the hypothesis that strongyloidiasis prevalence interacts with the RR of mortality. Data Sources: Original meta-analysis as well as a manual review of all references in a dedicated ivermectin trial database (c19ivermectin) from January 1, 2019, to November 6, 2021. Study Selection: Randomized clinical trials using ivermectin as a treatment for COVID-19 and reporting the outcome of mortality. Studies were excluded in the event of publications revealing suspected trial fraud and/or randomization failure. Data Extraction and Synthesis: Study characteristics and RR estimates were extracted from each source. Estimates were pooled using random-effects meta-analysis. Differences by strongyloidiasis prevalence were estimated using subgroup meta-analysis and meta-regression. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline was followed. Main Outcomes and Measures: Relative risk of mortality in ivermectin trials in regions of high vs low strongyloidiasis prevalence and correlation coefficient of meta-regression analysis between RR of mortality and regional prevalence of strongyloidiasis. Results: A total of 12 trials comprising 3901 patients were included in the analysis. Four trials (33%) took place in regions of high strongyloidiasis prevalence and 8 (67%) trials took place in regions of low strongyloidiasis prevalence. Ivermectin trials that took place in areas of low regional strongyloidiasis prevalence were not associated with a statistically significant decreased risk of mortality (RR, 0.84 [95% CI, 0.60-1.18]; P = .31). By contrast, ivermectin trials that took place in areas of high regional strongyloidiasis prevalence were associated with a significantly decreased risk of mortality (RR, 0.25 [95% CI, 0.09-0.70]; P = .008). Testing for subgroup differences revealed a significant difference between the results of groups with low and high strongyloidiasis prevalence (χ21 = 4.79; P = .03). The estimate for τ2 (the variance of the study effect sizes) was 0 (95% CI, 0.0000-0.2786), and the estimate for I2 (percentage of variability that is explained by between-study heterogeneity) was 0 (95% CI, 0-43.7%). The meta-regression analysis revealed an RR decrease of 38.83% (95% CI, 0.87%-62.25%) for each 5% increase in strongyloidiasis prevalence. Conclusions and Relevance: In this meta-analysis of 12 trials including 3901 patients, strongyloidiasis prevalence was found to interact with the RR of mortality for ivermectin as a treatment for COVID-19. No evidence was found to suggest ivermectin has any role in preventing mortality among patients with COVID-19 in regions where strongyloidiasis was not endemic.