Sars-CoV-2 and human strongyloidiasis

The Sars-CoV-2, the virus that causes Covid-19 (coronavirus disease 2019), is highly transmissible and of rapid dissemination, and transmitted by respiratory droplets and by direct contact, which can cause respiratory failure and reach multiple organs. Although there is still no effective treatment for the disease, the use of corticosteroids has shown positive results in patients with severe Covid-19, such as dexamethasone, which acts as an immunosuppressant to control cytokine storm syndrome (CSS). In this review, we will abroad the challenge of establishing a balance between risk and benefit in corticosteroid therapy in severe cases of the disease, since corticosteroids can activate the latent infection by Strongyloides stercoralis and develop the critical form of strongyloidiasis, the Strongyloides stercoralis hyperinflation syndrome (SHS). For these circumstances, screening and empirical treatment with ivermectin is recommended for those patients at moderate to high risk of hyperinfection. The keywords used were "Strongyloides" AND "Covid" and the searched databases were PubMed, Scopus, and Web of Science. The selected articles were published from 2020 to 2021 and without language restriction.Copyright © 2022 Sociedade Brasileira de Pneumologia e Tisiologia. All rights reserved.

Strongyloides stercoralis: A Neglected but Fatal Parasite.

Strongyloidiasis is a disease caused by Strongyloides stercoralis and remains a neglected tropical infection despite significant public health concerns. Challenges in the management of strongyloidiasis arise from wide ranging clinical presentations, lack of practical high sensitivity diagnostic tests, and a fatal outcome in immunocompromised hosts. Migration, globalization, and increased administration of immunomodulators, particularly during the COVID-19 era, have amplified the global impact of strongyloidiasis. Here, we comprehensively review the diagnostic tests, clinical manifestations, and treatment of strongyloidiasis. The review additionally focuses on complicated strongyloidiasis in immunocompromised patients and critical screening strategies. Diagnosis of strongyloidiasis is challenging because of non-specific presentations and low parasite load. In contrast, treatment is simple: administration of single dosage ivermectin or moxidectin, a recent anthelmintic drug. Undiagnosed infections result in hyperinfection syndrome and disseminated disease when patients become immunocompromised. Thus, disease manifestation awareness among clinicians is crucial. Furthermore, active surveillance and advanced diagnostic tests are essential for fundamental management.

Diagnostic value of metagenomics next-generation sequencing technology in disseminated strongyloidiasis.

The symptoms of disseminated strongyloidiasis are not typical, and it is difficult for clinicians to identify strongyloidiasis in some non-endemic areas. We report a 70-year-old woman who was diagnosed with Guillain-Barré syndrome due to autonomic disturbance, symmetrical bulbar palsy, and lower-motor-nerve damage in the extremities; her symptoms continued to worsen after hormone and immunoglobulin therapy. Later, parasitic larvae were found in the patient's gastric fluid, and metagenomic next generation sequencing (mNGS) detection of bronchoalveolar-lavage fluid also found a large number of Strongyloides roundworms. The patient was diagnosed with disseminated strongyloidiasis. The patient was given albendazole for anthelmintic treatment, but died two days after being transferred to the intensive care unit due to the excessive strongyloidiasis burden. In recent years, mNGS has been increasingly used in clinical practice, and is becoming the main means of detecting strongyloides stercoralis in non-endemic areas. Especially during the corona virus disease 2019 pandemic, mNGS technology has irreplaceable value in identifying the source of infection.

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.

Hepatic Disorders in Adults Associated with the Use of Ivermectin for SARS-CoV-2 Infection: A Pharmacovigilance Study in VigiBase: An International Journal of Medical Toxicology and Drug Experience

Introduction: In the face of the global health emergency due to SARS-CoV-2, Ivermectin has been, among other drugs, repurposed in some Latin American countries to treat COVID-19 [1]. Studies are needed on the safety of Ivermectin for this new indication. VigiBase is the WHO pharmacovigilance database that registers all Individual Case Safety Reports (ICSRs) from more than 130 countries. Objective: To review in VigiBase the reports of serious hepatic disorders in adults associated with the use of Ivermectin for COVID19. Methods: We extracted, in men or women aged > 18 years between 1 January 2020 and 7 march 2021, all ICSRs registered as serious associated with the use of ivermectin, and established the prevalence of serious hepatic disorders when Ivermectin was indicated for COVID-19 Results: During the study period, there were 1,393 ICSRs in VigiBase associated with Ivermectin, of which 60 (4.3%) were registered as serious;in 25 of those, Ivermectin had been used for COVID-19. Out of those 25, five reported serious cases of hepatic disorders (hepatitis, hepatocellular injury, cholestasis, increased alanine aminotransferase and aspartate aminotransferase, abnormal liver function test). Three patients were male and overall mean age was 59.2 ± 9.7 years. Ivermectin was administered during a mean of 2.5 ± 2.4 days, and the mean daily dose was 14.3 ± 2.9 mg. Two patients simultaneously received other drugs (Remdesivir, Hydroxychloroquine, Azithromycin). Two patients had concurrent conditions (strongyloidiasis, diabetes mellitus). Only in 2 patients liver enzyme data were reported. In all patients the evolution was favorable after stopping the drug (de-challenge), and no patient was re-exposed (rechallenge). Causality analysis was reported in 3 cases, qualifying as possible or probable. Conclusion: The safety of the use of Ivermectin should be studied more exhaustively, especially as regards the probability of hepatic disorders when used for COVID-19

A Rare Presentation of Strongyloides stercoralis Infection from an Immunocompetent Individual in a Tertiary Care Center in South India

Strongyloidiasis is a neglected parasitic disease caused by the intestinal parasite, Strongyloides stercoralis. Most patients with strongyloidiasis are asymptomatic, but few present with varied clinical manifestations such as cutaneous, gastrointestinal, pulmonary, and disseminated disease. It creates a diagnostic dilemma and undue delay in the diagnosis of patients. We report the case of a 79-yearold male who presented with fever and abdominal pain due to strongyloidiasis with no history of immunosuppression. The infection resolved entirely on treatment with ivermectin.

Screening for strongyloidiasis in Spain in the context of the SARS-CoV-2 pandemic: Results of a survey on diagnosis and treatment.

INTRODUCTION: The generalization of treatment with dexamethasone or other immunosuppressants in patients with SARS-CoV-2 infection may increase the risk of occurrence of severe forms of strongyloidiasis. A nationwide survey was conducted to better understand the diagnostic and therapeutic situation of strongyloidiasis in SARS-CoV-2 co-infected patients in Spain. MATERIALS AND METHODS: A survey was designed and sent to all SEIMC members during February and March 2021. Responses were exported for computer processing to Microsoft Excel 2017 and statistically processed with the free software PSPP. RESULTS: 189 responses were received, of which 121 (64%) were selected for further processing. Eighty-four centers (69.5%) had no specific strongyloidiasis screening protocol. Forty-two centers (34.7%) had serological techniques available in their laboratories and the rest were sent to a reference laboratory. Only 22 centers (18%) screened for strongyloidiasis in SARS-CoV-2 infected patients. A total of 227 cases of strongyloidiasis were diagnosed in patients with SARS-CoV-2 infection. In four cases patients developed a massive hyperinfestation syndrome leading to the death of one patient. CONCLUSION: COVID-19 has highlighted the need to unify screening and treatment protocols for imported pathologies such as strongyloidiosis. Efforts to disseminate knowledge are needed to ensure that this potentially fatal disease is adequately treated in patients with the highest risk of complications, such as those with COVID-19.

Atypical pulmonary presentation of Strongyloides stercoralis hyperinfection in a patient with philadelphia chromosome-positive acute lymphoblastic leukemia: Case report.

Strongyloides stercoralis is a soil-transmitted helminth endemic to tropical and subtropical regions and can be acquired due to parasite penetration through the skin. It can remain dormant in the gastrointestinal system for decades after the primary infection. In immunocompromised patients, this parasite can cause autoinfection with progression to hyperinfection syndrome. Here we report a unique case of pulmonary strongyloidiasis in a 32-year-old female, originally from Guatemala, with a significant clinical history of Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia diagnosed in 2019. The patient is status post chemotherapy with tyrosine kinase inhibitor plus hyper-CVAD regimen (Cyclophosphamide, Vincristine sulfate, Doxorubicin hydrochloride (Adriamycin), and Dexamethasone). History of drug-induced hyperglycemia and obesity was also noted. Her current chief complaint included dyspnea, tachycardia, and chest pain. Chest computerized tomography (CT) scan showed diffuse interstitial pulmonary edema with septal thickening, scattered ground-glass opacities, and small pericardial effusion. Due to normal ejection fraction, the differential diagnosis included non-cardiogenic pulmonary edema, pneumonitis secondary to chemotoxicity, and infection. She rapidly progressed to acute hypoxic respiratory failure, and a bronchoalveolar lavage study revealed numerous larvae consistent with Strongyloides hyperinfection. Further workup revealed eosinophilia with negative Strongyloides IgG antibody. Given the rarity of this infection in the United States and the patient's place of birth, acquired latent Strongyloides infection is favored as the initial source of infection. The reactivation of the infection process was most likely secondary to her chemotherapy treatment. Strongyloides hyperinfection diagnosis can be challenging to establish and entails a high level of suspicion. Cytology evaluation is an essential factor for diagnosis.

Mucormycosis, one month after recovery from COVID-19: A case report.

Introduction: and importance: There are increasing case reports of mucormycosis in patient with coronavirus disease 2019 (Covid-19). Herein, we describe the case of mucormycosis after recovery from Covid-19. Case presentation: The patient was a 73 years old woman with a history of chronic kidney disease, diabetes mellitus, hypertension, and dyslipidemia that referred to the emergency department with clinical presentation of Covid-19. On the third day of admission, the Covid-19 PCR test was negative, but the patient presented headache and pain in her upper jaw. Physical examination showed fever, erythema, and tenderness in the right cheek. Emergency biopsy and culture from sinus by subsection to mucormycosis conducted. and the diagnosis of mucormycosis was confirmed by the positive result of biopsy and culture. Despite anti-fungal treatment with Amphotericin B, patient developed severe diarrhea and became hemodynamically unstable. In the stool analysis, Strongyloides stercoralis was reported. Unfortunately, patient was expired on day thirty-two of this admission. Clinical discussion: Mucormycosis is a dangerous infection, and its rapid diagnosis is so important. On the other hand, Covid-19 may associated with many nonspecific sign and symptoms. These finding may overlap with other infections.In patients with prolonged mucormycosis infection, the development of strongyloidiasis should not be neglected. A single dose of ivermectin as strongyloidiasis prophylaxis should be given if the duration of the illness is prolonged. Conclusion: Clinicians should consider mucormycosis and its complications after Covid-19 treatment in diabetic and immunocompromised patients.

Strongyloides stercoralis.

Strongyloidiasis has been estimated to affect over 600 million people worldwide. It is caused by Strongyloides stercoralis, a roundworm endemic to the tropics and subtropics, especially areas where sanitation is suboptimal Autochthonous transmission has been documented in rural areas of the USA and Europe. Humans are infected when larvae penetrate the skin or are ingested. Autoinfection, in which larvae generated in the host go on to re-infect the host, leads to a state of chronic asymptomatic infection often with eosinophilia. Hyperinfection syndrome may develop when patients develop immune suppression, due to medications such as corticosteroids or following solid-organ transplantation. Hyperinfection is characterized by exponential increase in parasitic burden, leading to tissue invasion and life-threatening disease and associated bloodstream infections due to enteric organisms. Cases following use of corticosteroids for COVID-19 pneumonia have been described. Strongyloidiasis can be diagnosed by direct visualization of larvae in stool or other body fluids, or by serology. Ivermectin is highly effective in treating the disease. Patients with exposure to endemic areas and those expected to become immune suppressed should be screened and treated before starting immune suppressive agents. Empiric treatment should be considered when timely testing is not readily available.

Influence of the drugs used in migrant patients with severe acute respiratory syndrome coronavirus 2 and the development of symptomatic strongyloidiasis.

BACKGROUND: The use of dexamethasone in patients infected with Strongyloides stercoralis can cause severe complications. It is necessary to investigate the relationship between coronavirus disease 2019 (COVID-19) and strongyloidiasis infection. METHODS: A retrospective, longitudinal, descriptive study was undertaken to review all patients admitted with a diagnosis of COVID-19 infection at the Complejo Asistencial Universitario de Salamanca, Spain, during 1 March-31 December 2020. RESULTS: A total of 2567 patients received a diagnosis of COVID-19. Eighty-six patients from endemic areas were included. Seven patients had strongyloidiasis. Five patients were female. The mean age (±SD) was 39 (±10.8) y. Six patients were Latin-American and only one patient was from Africa. Six patients had previous symptoms compatible with strongyloidiasis infections. Only three patients received dexamethasone (6 mg once daily) for 10 d. In all cases, the clinical courses of the patients were satisfactory. No patient died or was admitted to the ICU. CONCLUSIONS: Screening programmes using serological techniques should be implemented in COVID-19 patients to prevent strongyloidiasis. Our study suggested that drugs used against COVID-19 in patients with strongyloidiasis did not affect the evolution of the disease. However, more studies are necessary to elucidate the role of dexamethasone in COVID-19 patients infected with Strongyloides.

COVID-19-associated opportunistic infections: a snapshot on the current reports.

Treatment of the novel Coronavirus Disease 2019 (COVID-19) remains a complicated challenge, especially among patients with severe disease. In recent studies, immunosuppressive therapy has shown promising results for control of the cytokine storm syndrome (CSS) in severe cases of COVID-19. However, it is well documented that immunosuppressive agents (e.g., corticosteroids and cytokine blockers) increase the risk of opportunistic infections. On the other hand, several opportunistic infections were reported in COVID-19 patients, including Aspergillus spp., Candida spp., Cryptococcus neoformans, Pneumocystis jiroveci (carinii), mucormycosis, Cytomegalovirus (CMV), Herpes simplex virus (HSV), Strongyloides stercoralis, Mycobacterium tuberculosis, and Toxoplasma gondii. This review is a snapshot about the main opportunistic infections that reported among COVID-19 patients. As such, we summarized information about the main immunosuppressive agents that were used in recent clinical trials for COVID-19 patients and the risk of opportunistic infections following these treatments. We also discussed about the main challenges regarding diagnosis and treatment of COVID-19-associated opportunistic infections (CAOIs).

Ivermectin treatment for Strongyloides infection in patients with COVID-19.

Ivermectin, an antiparasitic agent, is not recommended for prophylaxis or treatment of coronavirus disease 2019 (COVID-19). Inappropriate use of ivermectin for treatment of COVID-19 may make it less available for patients with serious parasitic infections who could benefit from its use and worsen the current shortage of ivermectin in Canada. However, patients with COVID-19 who are candidates to receive immunomodulatory therapies (e.g. corticosteroids and interleukin-6 inhibitors) may be at risk of hyperinfection syndrome and disseminated disease from Strongyloides stercoralis. These complications can be severe and even fatal. It is important to recognize and screen patients who may be at risk of strongyloidiasis, as these patients may require treatment with ivermectin to avoid the potential for a hyperinfection syndrome and disseminated disease, which is frequently deadly. Clinicians should follow evidence-based recommendations to screen and treat for Strongyloides infection in patients with COVID-19 who are under consideration to receive specific COVID-19 therapies that alter immune response and may lead to hyperinfection syndrome or disseminated disease.

Preventing Infectious Complications of Immunomodulation in COVID-19 in Foreign-Born Patients.

Immunomodulating therapies for COVID-19 may carry risks of reactivating latent infections in foreign-born people. We conducted a rapid review of infection-related complications of immunomodulatory therapies for COVID-19. We convened a committee of specialists to formulate a screening and management strategy for latent infections in our setting. Dexamethasone, used in severe COVID-19, is associated with reactivation of latent tuberculosis, hepatitis B, and dissemination/hyperinfection of Strongyloides species and should prompt screening and/ or empiric treatment in appropriate epidemiologic contexts. Other immunomodulators used in COVID-19 may also increase risk, including interleukin-6 receptor antagonist (e.g., tocilizumab) and kinase inhibitors. People with specific risk factors should also be screened for HIV, Chagas disease, and endemic mycoses. Racial and ethnic minorities in North America, including foreign-born persons, who receive immunomodulating agents for COVID-19 may be at risk for reactivation of latent infections. We develop a screening and management pathway for such patients.

Corticosteroids in Covid-19 pandemic have the potential to unearth hidden burden of strongyloidiasis.

COVID-19 pandemic has posed formidable public health and clinical challenges to the entire humanity. A significant proportion of the COVID-19 patients have been provided immunosuppressive agents, particularly corticosteroids, as a part of management of moderate to severe COVID-19 disease. This has the drawback of development of strongyloides hyperinfection to disseminated infection in latent strongyloides infection patients. We are reporting the case of strongyloidiasis hyperinfection in a COVID-19 patient from a developing country, who initially received corticosteroid therapy for management of COVID-19, but later presented to hospital with non-specific, strongyloides related symptoms.