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.

Strongyloides stercoralis infection: an underlying cause of invasive bacterial infections of enteric origin. Results from a prospective cross-sectional study of a northern Italian tertiary hospital.

PURPOSE OF THE STUDY: We assessed the prevalence of S. stercoralis in a cohort of inpatients with invasive bacterial infections of enteric origin to investigate whether the parasite may facilitate these bacterial infections even in the absence of larval hyperproliferation. METHODS: We performed a prospective cross-sectional study in a hospital in northern Italy. Subjects admitted due to invasive bacterial infection of enteric origin and potential previous exposure to S. stercoralis were systematically enrolled over a period of 10 months. S. stercoralis infection was investigated with an in-house PCR on a single stool sample and with at least one serological method (in-house IFAT and/or ELISA Bordier). Univariate, bi-variate and logistic regression analyses were performed. RESULTS: Strongyloidiasis was diagnosed in 14/57 patients (24.6%; 95% confidence interval 14.1-37.8%) of which 10 were Italians (10/49, 20.4%) and 4 were migrants (4/8, 50.0%). Stool PCR was performed in 43/57 patients (75.4%) and no positive results were obtained. Strongyloidiasis was found to be significantly associated (p ≤ 0.05) with male gender, long international travels to areas at higher endemicity, deep extra-intestinal infectious localization and solid tumors. In the logistic regression model, increased risk remained for the variables deep extra-intestinal infectious localization and oncologic malignancy. CONCLUSIONS: Our findings suggest a new role of chronic strongyloidiasis in favoring invasive bacterial infections of enteric origin even in the absence of evident larval dissemination outside the intestinal lumen. Further well-designed studies should be conducted to confirm our results, and possibly establish the underlying mechanisms.

Strongyloides hyperinfection syndrome and cytomegalovirus infection in a patient with type II diabetes mellitus.

Strongyloidiasis is a gastrointestinal parasitic infection caused by percutaneous infection with Strongyloides stercoralis, which is mainly distributed in the tropics and subtropics worldwide. Digestive symptoms like diarrhea and abdominal pain are the main manifestation, but serious infections such as bacterial pneumonia, purulent meningitis and sepsis also occur in immunocompromised individuals. Herein, we present a rare case of a type II diabetes mellitus (T2DM) patient presented with gastrointestinal hemorrhage and sepsis caused by concomitant Strongyloides stercoralis and cytomegalovirus (CMV) infection. This 51-year-old male patient presented to the hospital with vomiting, diarrhea, dyspnea, palpitation and weakness. Examination revealed skin soft-tissue infection with T2DM, and upper endoscopy revealed gastric mucosal erosion and hemorrhage. Radiology revealed bilateral diffuse interstitial infiltrates and thickened walls of the colon. Importantly, stool and vomitus examination showed numerous larvae of Strongyloides stercoralis. Then the diagnosis of Strongyloides hyperinfection syndrome was made. But antibiotics and albendazole treatment did not improve the patient's symptoms of gastrointestinal bleeding and sepsis. Subsequently, other pathogens were screened by sequence and a positive CMV gene was found in the peripheral blood. Thus, antibiotics, albendazole and ganciclovir were all used which ultimately resolved the infection in this patient. Therefore, this case indicated CMV could also by co-infected with Strongyloides stercoralis in the immunocompromised patient, which remind us that an CMV test should also be performed when encountered in severe strongyloidiasis infection, which could improve the prognosis of the patient.

Ulcerative colitis exacerbated by strongyloidiasis.

We herein report a case of ulcerative colitis (UC) exacerbated by strongyloidiasis. Parasites including Strongyloides stercoralis and Entamoeba histolytica can cause chronic gastrointestinal inflammation and long-lasting symptoms resembling UC. On the other hand, it is not well-known that such organisms can trigger the exacerbation of pre-existing UC. We would like to highlight the importance of recognition of strongyloidiasis in the management of UC patients who have lived in or migrated from endemic regions, such as Asia, Africa, and South America.

Strongyloides stercoralis hyperinfection syndrome mimicking pseudomembranous enteritis, complicated by Escherichia coli bacteremia and Pneumocystis jirovecii pneumonia in a patient after immunosuppressive therapy: a case report.

BACKGROUND: Strongyloidiasis, caused by Strongyloides stercoralis (S. stercoralis), is endemic worldwide, especially in countries with warm and humid climates. Strongyloides stercoralis hyperinfection syndrome (SHS) is an extremely serious manifestation of strongyloidiasis, which results from an acute exacerbation of auto-infection and is often fatal. CASE PRESENTATION: We present a case of SHS mimicking pseudomembranous enteritis with a final definitive diagnosis of a triple infection including S. stercoralis, Escherchia coli (E. coli) and Pneumocytis jirovecii (P. jirovecii) that occurred in a microscopic polyangiitis (MPA) patient after immunosuppressive therapy. SHS, together with E. coli bacteremia and Pneumocytis jirovecii pneumonia (PJP) in the same patient, is rare in clinical practice, which is first reported worldwide, to our knowledge. After the diagnosis was confirmed, the treatment protocol was quickly adjusted; however, the patient's life could not be saved. CONCLUSION: This case reminds us of the necessity to consider strongyloidiasis as a differential diagnosis in immunocompromised populations who live in or have visited to S. stercoralis endemic areas, especially patients with suspected pseudomembranous enteritis, even if stool examination, serological tests, and eosinophilia are negative. For this group, it is advisable to complete the relevant endoscopy and/or PCR as soon as possible. The fundamental solution to prevent this catastrophic outcome is to implement effective preventive measures at multiple levels, including physicians, patients, and relevant authorities.

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.

Fatal outcome in a patient under immunosuppressant therapy infected with human T-lymphotropic virus type 1 (HTLV-1), cytomegalovirus (CMV) and Strongyloides stercoralis: a case report.

BACKGROUND: Strongyloidiasis is a gastrointestinal parasitic infection caused by percutaneous infection with Strongyloides stercoralis. Digestive symptoms such as diarrhea and abdominal pain are the main manifestation, but serious infections such as septicemia, purulent meningitis, and bacterial pneumonia may occur in individuals harboring human T-lymphotropic virus type 1 (HTLV-1) or who are immunocompromised. Although coinfection with Strongyloides stercoralis and HTLV-1 can lead to chronic strongyloidiasis and a disseminated form of the disease, there is a high rate of response to the anthelmintic ivermectin. CASE PRESENTATION: We report a case of strongyloidiasis infection syndrome that was difficult to differentiate from immune reconstitution inflammatory syndrome (IRIS) for various reasons. The patient had been treated with the corticosteroids tacrolimus (Tac) and mycophenolate mofetil (MMF) for systemic lupus erythematosus (SLE) with lupus nephritis and pancytopenia. When the steroid was reduced, she developed cytomegalovirus (CMV) enteritis, and her respiratory status rapidly deteriorated immediately after the withdrawal of Tac and MMF. It was difficult to distinguish immune reconstitution inflammatory syndrome from strongyloidiasis infection syndrome because stool cultures were negative and eosinophils were not increased. Bronchoscopy revealed viable Strongyloides, leading to a diagnosis of strongyloidiasis infection syndrome, but the patient died despite treatment. CONCLUSIONS: Both corticosteroid therapy and HTLV-1 infection can be associated with a decrease of eosinophils, despite the presence of parasitic infection. In conclusion, even if multiple culture tests are negative, the risk of parasitic infection should be assessed in patients receiving immunosuppressants and steroids even in non-endemic areas.

Strongyloides stercoralis: a rare and severe presentation in a pregnant woman.

Strongyloides stercoralis is a parasitic nematode with a worldwide distribution. It can go from an asymptomatic infection to a life-threatening hyperinfection syndrome. Here, we report a case of intestinal obstruction due to S. stercoralis in a pregnant woman. This condition, as well as severe strongyloidiasis in pregnant women, is seldomly reported. In this case, Human T-lymphotropic Virus 1 (HTLV-1) coinfection was confirmed, a well-known risk factor for a more severe presentation of strongyloidiasis. We suggest that HTLV status should be screened in every severe S. stercoralis infection, or when, despite a correct treatment, a relapse is observed.

Strongyloides hyperinfection in a patient with solid malignant tumor a case report.

Strongyloides stercoralis is unique among the nematodes, in which it completes its life cycle inside a single human host by causing autoinfection in the host, and it causes hyperinfection leading to persistent and fatal disseminated infections in immunocompromised hosts. The present case report is about strongyloidiasis fatal hyperinfection in a patient with malignant tumor of the tongue on radiotherapy treatment, to highlight the need for clinical suspicion of strongyloidiasis in an immunocompromised host. As per the Centers for Disease Control and Prevention, the mortality in strongyloides hyperinfection syndrome is alarmingly high, a case fatality rate that is almost 90%. Hence, the clinicians should be well equipped to diagnose, treat, and also prevent the fatal consequences of this lethal nematode. Detailed workup for this parasitic infection is crucial, and this case report emphasizes that a simple wet mount stool microscopic examination can clinch the diagnosis.

Metabolic Consequences of Concomitant Strongyloides stercoralis Infection in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Human and animal studies have demonstrated that helminth infections are associated with a decreased prevalence of type 2 diabetes mellitus (T2DM). However, very little is known about their biochemical and immunological interactions. METHODS: To assess the relationship between a soil-transmitted helminth, Strongyloides stercoralis (Ss), and T2DM, we examined analytes associated with glycemic control, metabolic processes, and T-cell-driven inflammation at the time of Ss diagnosis and 6 months after definitive anthelmintic treatment. We measured plasma levels of hemoglobin A1c, glucose, insulin, glucagon, adipocytokines, and T-helper (TH) 1-, 2-, and 17- associated cytokines in patients with T2DM with (INF group) or without (UN group) Ss infection. In INF individuals, we again assessed the levels of these analytes 6 months following anthelmintic treatment. RESULTS: Compared to UN individuals, INF individuals exhibited significantly diminished levels of insulin and glucagon that increased significantly following therapy. Similarly, INF individuals exhibited significantly diminished levels of adiponectin and adipsin that reversed following therapy. INF individuals also exhibited significantly decreased levels of the TH1- and TH17- associated cytokines in comparison to UN individuals; again, anthelmintic therapy augmented these levels. As expected, INF individuals had elevated levels of TH2-associated and regulatory cytokines that normalized following definitive therapy. Multivariate analysis revealed that these changes were independent of age, sex, body mass index, and liver and renal function. CONCLUSIONS: Strongyloides stercoralis infection is associated with a significant modulation of glycemic, hormonal, and cytokine parameters in T2DM and its reversal following anthelmintic therapy. Hence, Ss infection has a protective effect on diabetes-related parameters.

Influence of parasite load on the diagnosis and occurrence of eosinophilia in alcoholic patients infected with Strongyloides stercoralis.

Alcoholic patients are more susceptible to Strongyloides stercoralis infection. The chronic use of alcohol raises the levels of endogenous corticosteroids, which regulates the development of larvae and stimulates the differentiation of rhabditiform into infective filariform larvae, thus inducing internal autoinfection. Therefore, early diagnosis is important to prevent severe strongyloidiasis. The aim of this study was to evaluate the efficacy of parasitological methods, according to the parasite load and the number of stool samples, for diagnosis of S. stercoralis infection, as well the peripheral blood eosinophil count in alcoholic patients. A total of 330 patients were included in this study. The diagnosis was established using three parasitological methods: agar plate culture, Baermann-Moraes method and spontaneous sedimentation. Peripheral eosinophilia was considered when the level was >600 eosinophils/mm3. The agar plate culture (APC) had the highest sensitivity (97.3%). However, the analysis of multiple samples increased the sensitivity of all parasitological methods. The sensitivities of the methods were influenced by the parasite load. When the larval number was above 10, the sensitivity of APC was 100%, while in spontaneous sedimentation the sensitivity reached 100% when the larval number was above 50. In the present study, 15.4% of alcoholic patients infected with S. stercoralis (12/78) had increased peripheral blood eosinophil count (above 600 eosinophils/mm3). For an efficient parasitological diagnosis of S. stercoralis infection in alcoholic patients, repeated examination by two parasitological methods must be recommended, including agar plate culture due to its higher sensitivity. Moreover, S. stercoralis infection was associated with eosinophilia, mostly in patients excreting up to 10 larvae/g faeces.

[Acute renal failure and rare severe complication of systemic steroid treatment in a 73-year-old woman]. / Akutes Nierenversagen und seltene schwere Komplikation einer systemischen Steroidtherapie bei einer 73­Jährigen.

This article reports about a 73-year-old woman of Bosnian descent who presented with acute renal failure. A renal biopsy was diagnostic for a postinfect necrotizing and extracapillary proliferative glomerulonephritis. The patient reported a febrile infection fever 2 weeks previously. The diagnostics did not reveal any indications of an ongoing infection. The glomerulonephritis responded to treatment with systemic steroids. The patient was readmitted to hospital 6 weeeks later in a severely ill condition. A gastric biopsy revealed a Strongyloides stercoralis infestation. Due to the systemic steroid therapy the patient had developed a so-called hyperinfection syndrome and died despite treatment on the intensive care unit. This case illustrates the need for awareness of this rare parasitosis, particularly in patients from endemic areas. A likely causal relationship with the glomerulonephritis is discussed and an overview of the diagnostics, course of the disease and treatment of this parasitosis is given.

A case report suggestive of strongyloidiasis infection occurring in temperate Australia.

Strongyloides stercoralis is a nematode that can cause fatal systemic or disseminated infections in immunocompromised persons. It is known to be endemic in tropical Australia. Sporadic cases arising from temperate regions are reported in Russia and North America. An Aboriginal woman aged 71 years with ovarian carcinoma developed worsening lethargy and tiredness. She was diagnosed with strongyloidiasis based on serology in 2015. She had resided in the state of New South Wales all her life. This case report provides further evidence that strongyloides transmission is possible in temperate areas of Australia and has occurred in the past when sanitation was not as advanced as it is today.

Severe strongyloidiasis and systemic vasculitis: comorbidity, association or both? Case-based review.

A possible association between strongyloidiasis and systemic vasculitis is rarely reported in the literature. We report the case of a patient with severe strongyloidiasis and an angiographic finding consistent with polyarteritis nodosa. Diagnosis of strongyloidiasis was made by finding of larvae and adult parasites in samples of the upper gastrointestinal tract mucosa and stool. The patient was treated with albendazole, ivermectin and corticosteroid withdrawal. This therapy led to the resolution of symptoms, with repeated stool samples negative for S. stercoralis. However, the clinical course was complicated with pulmonary tuberculosis. Despite tuberculostatic therapy and supportive measures, a lethal outcome occurred. The report is followed by a focused review of the available literature on the association of strongyloidiasis and systemic vasculitis.

Selected aspects of helminth infections Schistosoma sp., Ascaris lumbricoides, Strongyloides stercoralis in individuals diagnosed with human immunodeficiency virus (HIV) infection

Co-infections of HIV and other pathogens constitute an important clinical and epidemiological problem. Many studies have played attention to opportunistic co-infections due to the fact that they are used as an indicator for development of AIDS and are present on the all continents. However, in HIV-infected patients helminth infections, which are not aetiologic agents of opportunistic infections, are becoming more and more important. Prevalence of helminth infection depends on parasite species, environmental and socio-economic factors, therefore the results of published research mainly refer to populations of patients in developing countries and endemic regions. In many cases, pathogenetic mechanisms of these co-infections are not fully recognized, and the obtained results are ambiguous. Thus we performed literature review concerning the course and implications of co-infections with three selected helminth species, of different tissue/organ tropism (Ascaris lumbricoides, Strongyloides stercoralis, Schistosoma sp.), in patients with HIV infection.

Efficacy of Moxidectin Versus Ivermectin Against Strongyloides stercoralis Infections: A Randomized, Controlled Noninferiority Trial.

BACKGROUND: Infections with Strongyloides stercoralis are of considerable public health relevance. Moxidectin, a well-established drug in veterinary medicine under consideration for regulatory submission for the treatment of onchocerciasis, might serve as an alternative to the widely used ivermectin. METHODS: We conducted an exploratory, randomized, single-blind trial to evaluate the efficacy and safety of moxidectin (8 mg) vs ivermectin (200 µg/kg) against S. stercoralis infections. Cure rate (CR) against S. stercoralis was the primary outcome. Safety and efficacy against coinfections with soil-transmitted helminths and Opisthorchis viverrini were secondary outcomes. Noninferiority required the lower limit of the 95% confidence interval (CI) of the differences in CRs not exceed 7 percentage points. RESULTS: A total of 127 participants were enrolled and randomly assigned to the 2 treatments whereby 1 participant per arm was lost to follow-up. We observed a CR of 93.7% (59/63) for moxidectin compared to 95.2% (59/62) for ivermectin. Differences between CRs were estimated as -1.5% percentage points (95% CI, -9.6 to 6.5), thus the lower limit of the CI exceeds the noninferiority margin of 7 percentage points. No side effects were observed. CRs against hookworm infection were 57% (moxidectin) and 56% (ivermectin). Low efficacy for both drugs against O. viverrini was observed. CONCLUSIONS: Moxidectin might be a safe and efficacious alternative to ivermectin for the treatment of S. stercoralis infection, given that only slight differences in CRs were observed. However, noninferiority could not be demonstrated. Larger clinical trials should be conducted once the drug is marketed. CLINICAL TRIALS REGISTRATION: Current Controlled Trials: ISRCTN11983645.