Strongyloides stercoralis is a zoonotic soil-transmitted nematode affecting mainly humans and dogs but identified also in non-human primates, cats and wild carnivores. It has a cosmopolitan distribution being endemic in tropical and subtropical areas. In Romania, the infection was reported on several occasions in dogs with low prevalence (3.5% -3.8%), assessed by coproscopy and it was confirmed in human patients with no travel history. A 2-year-old male Boston Terrier dog presented to a private clinic due to severe digestive problems, in July 2022. The animal had a long history of health problems. The dog was in a very bad clinical condition with severe abdominal pain, bloody diarrhea, and weight loss. Coproparasitological examinations using the saline flotation method and the modified Baermann\'s technique were done, both being negative. In addition, an intestinal biopsy was performed during the second endoscopy. Nematodes were collected and identified morphologically and molecularly confirmed. Histology revealed severe inflammation of the duodenal mucosa with areas of edema, necrosis, and hemorrhage, and in the intestinal glands, there were numerous nematodes suggesting a parasitic infection by Strongyloides spp. PCR followed by sequencing confirmed the infection with S. stercoralis. The dog was treated with a combination of oral fenbendazole and milbemycin oxime for 5 months. No relapse was observed 3 months after negativity was attained. This case describes a severe clinical infection by Strongyloides stercoralis in a domestic dog from Romania and the recovery after long-term treatment.

Rodents infected with Strongyloides venezuelensis are experimental models applied to strongyloidiasis research. This study evaluated oral and subcutaneous dexamethasone (DEX) treatments to establish immunosuppression in an experimental model of Strongyloides hyperinfection. Rattus norvegicus Wistar were divided: G I (-): untreated and uninfected animals, G II (+): untreated and infected, G III (o -) orally treated and uninfected, G IV (o +) orally treated and infected, G V (sc -) subcutaneously treated and uninfected, G VI (sc +) subcutaneously treated and infected. For oral administration, DEX was diluted in sterile water (5 µg/ml) and made available to the animals on intervals in experimental days - 5-0, 8-13 and 21-26. For subcutaneous administration, animals received daily injections of DEX disodium phosphate (2 mg/kg). Infection was established by the subcutaneous inoculation of 3000 S. venezuelensis filarioid larvae. Groups were evaluated by egg per gram of feces and parasite females counts and IgG, IgG1 and IgG2a detection. GIV (o +) had egg peaks count on days 13 and 26 and maintained egg elimination until the last experimental day. Parasitic females recovery at day 30 was significantly higher in G IV (o +) when compared to G VI (sc +). Levels of IgG, IgG1 and IgG2a of all groups, except the positive control GII (+), were below the detection threshold. Pharmacological immunosuppression induced by oral administration of DEX produced high parasitic burden, and is a noninvasive method, useful to establish immunosuppression in strongyloidiasis hyperinfection model in rats.

Strongyloides are small rhabditid nematodes primarily associated with enteric disease in a variety of animal species, including reptiles. Strongyloides spp life stages were associated with a disease outbreak in a large breeding colony of snakes. Multiple Pantherophis and Lampropeltis colubrids exhibited respiratory distress, anorexia, stomatitis, facial deformation, and waning body condition that resulted in death or necessitated euthanasia. Postmortem examinations of 13 snakes revealed epithelial hyperplasia and inflammation of the alimentary and respiratory tracts associated with varying numbers of adult and larval nematodes and embryonated or larvated ova. In a subset of snakes, aberrant nematode migration was also observed in the eye, genitourinary system, coelom, and vasculature. Histomorphology and gross examination of parasitic adult female nematodes from host tissues were consistent with a Strongyloides spp. Sedimented fecal material from 101/160 (63%) snakes housed in the affected facility was positive for nematodes and/or larvated ova. Polymerase chain reaction amplification and sequencing of portions of the 18S and 28S ribosomal ribonucleic acid (RNA) genes and the internal transcribed spacer region of adult female parasites and positive fecal samples supported the diagnosis of strongyloidiasis. Strongyloides spp possess a unique life cycle capable of alternating between parasitic (homogonic) and free-living (heterogonic) stages, resulting in the production of directly infective larvae. Commonly utilized husbandry practices in reptile collections can amplify the numbers of infective larvae generated in the captive environment, increasing the risk for rhabditid hyperinfections. This report documents morbidity, mortality, and non-enteric disease manifestations due to Strongyloides hyperinfections in a captive colubrid snake colony.

Severe cases of strongyloidiasis are most often associated with multiple causes of immune suppression, such as corticoid treatment and HTLV (human T-lymphotropic virus) coinfection. Diabetes is not traditionally considered a risk factor for the development of severe strongyloidiasis. We report a rare case of autochthonous severe strongyloidiasis in Romania, a European country with a temperate climate. A 71-year-old patient with no prior travel history was admitted with multiple gastrointestinal complaints and recent weight loss. CT (computed tomography) scans indicated duodenal wall thickening, and duodenal endoscopy evidenced mucosal inflammation, ulcerations and partial duodenal obstruction at D4. Microscopic examination of stool samples and biopsy specimens from the gastric and duodenal mucosa revealed an increased larval burden characteristic of Strongyloides stercoralis hyperinfection. Sequential treatment with albendazole and ivermectin achieved parasitological cure and complete recovery. The novelty of our case stems from the scarcity of severe strongyloidiasis cases reported in Europe and especially in Romania, the absence of other risk factors in our patient aside from diabetes, the involvement of the gastric mucosa and the rare presentation as partial duodenal obstruction. This case highlights the importance of considering strongyloidiasis as a differential diagnosis, even in temperate climates where cases are sporadic, in cases in which immune suppression is not evident and in the absence of eosinophilia. The case is presented in the context of the first literature review examining the relationship between severe strongyloidiasis and diabetes, emphasizing diabetes as a possible risk factor for severe strongyloidiasis.

Strongyloidiasis, an intestinal parasitic infection caused by Strongyloides stercoralis, rarely occurs in Japan. When treated with immunosuppressive drugs, two potentially lethal conditions, hyperinfection and dissemination, may develop in asymptomatic carriers of this parasite. We report the development of strongyloidiasis during treatment of polymyositis with glucocorticoids plus rituximab (RTX). A 44-year-old woman had been diagnosed with anti-signal recognition particle antibody-positive polymyositis with interstitial pneumonia 6 years previously, for which she had recently been receiving prednisolone at 5 mg/day and RTX at 375 mg/m2 twice every 3 months. Her condition appeared to be well controlled. She was admitted to our hospital with a 1-month history of chronic diarrhoea and epigastric pain. Standard microscopic examination of a sample of faeces revealed the presence of S. stercoralis; however, serologic testing for parasites was negative. Treatment with ivermectin alleviated her inflammatory diarrhoea and eradicated the faecal parasites. We believe that our patient had an exacerbation of S. stercoralis infection (hyperinfection syndrome) that was exacerbated by low-dose glucocorticoids plus RTX. Strongyloidiasis should be considered in immunocompromised individuals with unexplained diarrhoea, even in non-endemic areas.

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 Mihaljević\' 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.

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-PrkdcscidIl2rgtm1Wjl/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.

The aim of this study is to highlight the potentially fatal risk of Strongyloidiasis Hyperinfection Syndrome for hospitalized immigrant patients with moderate to severe COVID-19 disease and undiagnosed Strongyloidiasis. We reviewed electronic medical records of immigrants from 2010 to 2022 and extracted the number of patients with eosinophilia, strongyloidiasis and COVID-19 infection, outpatient and hospitalized. While 885 outpatients were diagnosed with eosinophilia, only 356 (40.2%) were tested for strongyloidiasis and 160 (44.9%) yielded a reactive serology. COVID-19 infection was reported in 6,412 patients. 1135 (17.7%) of these patients sought hospital care. Patients with undiagnosed strongyloidiasis are at risk for a potentially fatal parasitosis if treated with systemic corticosteroids for COVID-19. This supports clinical guidelines in hospital settings for those with severe COVID-19. Strongyloidiasis should be considered by taking a thorough travel or migration history and testing before giving immunosuppressive drugs.

OBJECTIVE: We described a case of Strongyloides hyperinfection syndrome, reported a case series, and reviewed published cases of strongyloidiasis in Taiwan.
METHODS: Confirmed cases of strongyloidiasis at the National Taiwan University Hospital (NTUH) and NTUH Hsin-Chu Branch from 1988 to 2020 were identified in the medical record database. Literature search was carried out through Pubmed, Google Scholar, and Index to Taiwan Periodical Literature System to identify published cases of strongyloidiasis in Taiwan from 1979 to 2020. Data pertaining to the demographics, underlying medical conditions, clinical manifestations, laboratory findings, and outcomes were extracted.
RESULTS: A total of 117 cases of strongyloidiasis were identified, including 20 previously unpublished cases from the two hospitals and 97 published cases in the literature. Overall, 85 (73%) were male and the mean age was 64 years (range, 6-95 years). Classical symptoms such as diarrhea, cough, and skin rash were only observed in 43%, 37%, and 18% of the patients, respectively, whereas eosinophilia at presentation was only found in 48%. Strongyloides hyperinfection syndrome and disseminated strongyloidiasis were identified in 41 (35%) and 4 (3%) patients, respectively. Four (3%) patients had concurrent meningitis. In univariable analysis, being older and having pre-existing chronic obstructive pulmonary disease or asthma were associated with hyperinfection or dissemination (p = 0.024 and 0.003, respectively). The mortality rate was 43% among those with hyperinfection or disseminated infection.
CONCLUSIONS: Strongyloidiasis can cause serious complications and mortality. Efforts to diagnose strongyloidiasis early are urgently needed to improve the outcome of patients with strongyloidiasis in Taiwan.

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.