Strongyloides stercoralis Infestation in a Child: How a Nematode Can Affect Gut Microbiota.

Background: Strongyloidiasis is a neglected tropical disease caused by the intestinal nematode Strongyloides stercoralis and characterized by gastrointestinal and pulmonary involvement. We report a pediatric case of strongyloidiasis to underline the response of the host microbiota to the perturbation induced by the nematode. Methods: We performed a 16S rRNA-metagenomic analysis of the gut microbiota of a 7-year-old female during and after S. stercolaris infection, investigating three time-point of stool samples' ecology: T0- during parasite infection, T1- a month after parasite infection, and T2- two months after parasite infection. Targeted-metagenomics were used to investigate ecology and to predict the functional pathways of the gut microbiota. Results: an increase in the alpha-diversity indices in T0-T1 samples was observed compared to T2 and healthy controls (CTRLs). Beta-diversity analysis showed a shift in the relative abundance of specific gut bacterial species from T0 to T2 samples. Moreover, the functional prediction of the targeted-metagenomics profiles suggested an enrichment of microbial glycan and carbohydrate metabolisms in the T0 sample compared with CTRLs. Conclusions: The herein report reinforces the literature suggestion of a putative direct or immune-mediated ability of S. stercolaris to promote the increase in bacterial diversity.

Strong-LAMP Assay Based on a Strongyloides spp.-Derived Partial Sequence in the 18S rRNA as Potential Biomarker for Strongyloidiasis Diagnosis in Human Urine Samples.

Human strongyloidiasis a soil-transmitted infection caused by Strongyloides stercoralis is one of the most neglected amongst the so-called Neglected Tropical Diseases (NTDs). S. stercoralis is a nematode, which is distributed worldwide; it has been estimated that it could affect millions of people, mainly in tropical and subtropical endemic regions. The difficulties of diagnosis lead to infection rates being underreported. Asymptomatic patients have chronic infections that can lead to severe hyperinfection syndrome or disseminated strongyloidiasis in immunocompromised patients. Strongyloidiasis can easily be misdiagnosed because conventional faecal-based techniques lack of sensitivity for the morphological identification of infective larvae in faeces. None of the currently used molecular methods have used urine samples as an alternative to faecal samples for diagnosing strongyloidiasis. This study was thus aimed at comparing, for the first time, the use of a new loop-mediated isothermal amplification (LAMP) molecular assay (Strong-LAMP) to traditional methods on patients' urine samples. Twenty-four urine samples were taken from patients included in a study involving two Spanish hospitals for strongyloidiasis screening using parasitological and serological tests. Strongyloides larvae were found in 11 patients' faecal samples, thereby ascertaining that they had the disease. Other patients had high antibody titres but no larvae were found in their faeces. All urine samples were analysed by PCR and Strong-LAMP assay. No amplification occurred when using PCR. Strong-LAMP led to detecting S. stercoralis DNA in urine samples from patients having previously confirmed strongyloidiasis by parasitological tests and/or a suspicion of being infected by serological ones. The Strong-LAMP assay is a useful molecular tool for research regarding strongyloidiasis in human urine samples. After further validation, the Strong-LAMP assay could also be used for complementary and effective diagnosis of strongyloidiasis in a clinical setting.

Transplant-related strongyloidiasis in solid organ transplant recipients in Saudi Arabia and the Gulf Cooperation Council countries.

BACKGROUND: Strongyloidiasis is a devastating disease with a mortality rate exceeding 50% in immunocompromised patients. The disease usually results from reactivation of a latent infection in a transplant patient. Alternatively, donor-derived transmission of Strongyloides may occur. METHODS: In this review, we report a case of Strongyloides hyperinfection syndrome in a liver transplant recipient to illustrate the severity of this infection. Following this, PubMed was searched for cases of transplant-related strongyloidiasis in the Gulf Cooperation Council (GCC) countries. Demographic data, the clinical presentation of recipients, and donor information were recorded. Methods of diagnosis, treatment planning, and clinical outcomes were documented. RESULTS: A total of 12 transplant-related strongyloidiasis cases were identified. Seventy-five percent of the patients were from Saudi Arabia. Three cases from Kuwait shared common donors. All donors were deceased and native to an area endemic for Strongyloides. Five of the patients shared common donors, raising the possibility of donor-derived infection. Neither the donors nor the recipients underwent screening tests for Strongyloides. Concomitant bacteremia and/or meningitis was seen in 50% of cases (6/12). Moreover, when documented, sepsis was detected in all of the patients who died (three cases). The mortality rate in this series was high (41.7%). CONCLUSIONS: Since this is a preventable condition, early diagnosis and treatment is essential. The screening and treatment of potential transplant recipients and donors proved to be an effective preventive measure. There is a growing need for further studies and implementation of screening policies in the GCC countries to prevent this fatal infection.

Helminth Coinfection Alters Monocyte Activation, Polarization, and Function in Latent Mycobacterium tuberculosis Infection.

Helminth infections are known to influence T and B cell responses in latent tuberculosis infection (LTBI). Whether helminth infections also modulate monocyte responses in helminth-LTBI coinfection has not been fully explored. To this end, we examined the activation, polarization, and function of human monocytes isolated from individuals with LTBI with (n = 25) or without (n = 25) coincident Strongyloides stercoralis infection (S. stercoralis-positive and S. stercoralis-negative respectively). Our data reveal that the presence of S. stercoralis infection is associated with lower frequencies of monocytes expressing CD54, CD80, CD86 at baseline (absence of stimulation) and in response to mycobacterial-Ag stimulation than monocytes from S. stercoralis-negative individuals. In contrast, S. stercoralis infection was associated with higher frequencies of M2-like monocytes, as determined by expression of CD206 and CD163. Monocytes from S. stercoralis-positive individuals had a reduced capacity to phagocytose or exhibit respiratory burst activity following mycobacterial-Ag or LPS stimulation and were less capable of expression of IL-1ß, TNF-α, IL-6, and IL-12 at baseline and/or following Ag stimulation compared with those without S. stercoralis infection. In addition, definitive treatment of S. stercoralis infection resulted in a significant reversal of the altered monocyte function 6 mo after anthelmintic therapy. Finally, T cells from S. stercoralis-positive individuals exhibited significantly lower activation at baseline or following mycobacterial-Ag stimulation. Therefore, our data highlight the induction of dampened monocyte activation, enhanced M2 polarization, and impaired monocyte function in helminth-LTBI coinfection. Our data also reveal a different mechanism by which helminth infection modulates immune function in LTBI.

Recurrent meningitis associated to Strongyloides hyperinfection / Meningitis recurrente asociada a hiperinfección por Strongyloides

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Strongyloides stercoralis larvae or egg: Which came first?

Strongyloides stercoralis (SS) hyperinfection is a well-documented condition. However, SS eggs in stool samples are not commonly observed during routine analysis. Here, we report a case on SS hyperinfection where both larvae and eggs were observed in the stool sample of an immunossupressed liver allograft transplanted patient.

Sequential Changes in the Host Gut Microbiota During Infection With the Intestinal Parasitic Nematode Strongyloides venezuelensis.

Soil-transmitted helminths (STHs) are medically important parasites that infect 1. 5 billion humans globally, causing a substantial disease burden. These parasites infect the gastrointestinal tract (GIT) of their host where they co-exist and interact with the host gut bacterial flora, leading to the coevolution of the parasites, microbiota, and host organisms. However, little is known about how these interactions change through time with the progression of infection. Strongyloidiasis is a human parasitic disease caused by the nematode Strongyloides stercoralis infecting 30-100 million people. In this study, we used a closely related rodent parasite Strongyloides venezuelensis and mice as a model of gastrointestinal parasite infection. We conducted a time-course experiment to examine changes in the fecal microbiota from the start of infection to parasite clearance. We found that bacterial taxa in the host intestinal microbiota changed significantly as the infection progressed, with an increase in the genera Bacteroides and Candidatus Arthromitus, and a decrease in Prevotella and Rikenellaceae. However, the microbiota recovered to the pre-infective state after parasite clearance from the host, suggesting that these perturbations are reversible. Microarray analysis revealed that this microbiota transition is likely to correspond with the host immune response. These findings give us an insight into the dynamics of parasite-microbiota interactions in the host gut during parasite infection.

Diagnóstico de las infecciones por geohelmintos. Un problema sin resolver en la era de las ómicas / Diagnosis of soil-transmitted helminth infections. An unsolved problemin the omics era

Las infecciones producidas por Strongyloides stercoralis y otros geohelmintos, como las uncinarias (Necator americanus y Ancylostoma duodenale), representan un importante problema a nivel mundial, especialmente en áreas en vías de desarrollo. Clínicamente son difíciles de sospechar ya que producen cuadros inespecíficos y muchas veces solapados entre ellos. Asimismo, los largos períodos prepatentes que presentan dificultan la detección de las formas parasitarias. El diagnóstico microscópico continúa siendo la herramienta más utilizada en los laboratorios asistenciales, pero aún dista mucho de ser la herramienta ideal para detectarlos debido a su baja sensibilidad. Además, morfológicamente estos nematodos presentan similitudes importantes, por lo que el diagnóstico microbiológico aún es un reto. La serología ha permitido avanzar en cuanto al diagnóstico de la infección por S. stercoralis, pero esta opción no está disponible todavía para las uncinarias. Las técnicas de biología molecular han demostrado aumentar discretamente esta falta de sensibilidad, pero al igual que en otras infecciones parasitarias, actualmente no están disponibles para su uso en los laboratorios de microbiología clínica. Información sobre el suplemento: este artículo forma parte del suplemento titulado "Programa de Control de Calidad Externo SEIMC. Año 2016", que ha sido patrocinado por Roche, Vircell Microbiologists, Abbott Molecular y Francisco Soria Melguizo, S.A

Infections caused by Strongyloides stercoralis and other soil-transmitted worms such as hookworms (Necator americanus and Ancylostoma duodenale) represent a major problem worldwide, especially in developing areas. They are difficult to suspect clinically since they produce non-specific and often overlapping signs and symptoms. Likewise, their long prepatent periods hamper the detection of parasitic structures. Microscopic diagnosis is still the most commonly used tool in healthcare laboratories but it is still far from being the ideal technique to detect these infections due to its low sensitivity. In addition, these nematodes have strong morphologic similarities and consequently microbiological diagnosis remains a challenge. Serology has made progress in the diagnosis of S. stercoralis infection but this option is not yet available for hookworms. Molecular biology techniques have been shown to slightly increase this lack of sensitivity, but as with other parasitic infections, they are not currently available for use in clinical microbiology laboratories. Supplement information: This article is part of a supplement entitled "SEIMC External Quality Control Programme. Year 2016", which is sponsored by Roche, Vircell Microbiologists, Abbott Molecular and Francisco Soria Melguizo, S.A

A comprehensive analysis of the faecal microbiome and metabolome of Strongyloides stercoralis infected volunteers from a non-endemic area.

Data from recent studies support the hypothesis that infections by human gastrointestinal (GI) helminths impact, directly and/or indirectly, on the composition of the host gut microbial flora. However, to the best of our knowledge, these studies have been conducted in helminth-endemic areas with multi-helminth infections and/or in volunteers with underlying gut disorders. Therefore, in this study, we explore the impact of natural mono-infections by the human parasite Strongyloides stercoralis on the faecal microbiota and metabolic profiles of a cohort of human volunteers from a non-endemic area of northern Italy (S+), pre- and post-anthelmintic treatment, and compare the findings with data obtained from a cohort of uninfected controls from the same geographical area (S-). Analyses of bacterial 16S rRNA high-throughput sequencing data revealed increased microbial alpha diversity and decreased beta diversity in the faecal microbial profiles of S+ subjects compared to S-. Furthermore, significant differences in the abundance of several bacterial taxa were observed between samples from S+ and S- subjects, and between S+ samples collected pre- and post-anthelmintic treatment. Faecal metabolite analysis detected marked increases in the abundance of selected amino acids in S+ subjects, and of short chain fatty acids in S- subjects. Overall, our work adds valuable knowledge to current understanding of parasite-microbiota associations and will assist future mechanistic studies aimed to unravel the causality of these relationships.

Helminth infection in mice improves insulin sensitivity via modulation of gut microbiota and fatty acid metabolism.

Intestinal helminths are prevalent in individuals who live in rural areas of developing countries, where obesity, type 2 diabetes, and metabolic syndrome are rare. In the present study, we analyzed the modulation of the gut microbiota in mice infected with the helminth Strongyloides venezuelensis, and fed either a standard rodent chow diet or high-fat diet (HFD). To investigate the effects of the microbiota modulation on the metabolism, we analyzed the expression of tight-junction proteins present in the gut epithelium, inflammatory markers in the serum and tissue and quantified glucose tolerance and insulin sensitivity and resistance. Additionally, the levels of lipids related to inflammation were evaluated in the feces and serum. Our results show that infection with Strongyloides venezuelensis results in a modification of the gut microbiota, most notably by increasing Lactobacillus spp. These modifications in the microbiota alter the host metabolism by increasing the levels of anti-inflammatory cytokines, switching macrophages from a M1 to M2 pattern in the adipose tissue, increasing the expression of tight junction proteins in the intestinal cells (thereby reducing the permeability) and decreasing LPS in the serum. Taken together, these changes correlate with improved insulin signaling and sensitivity, which could also be achieved with HFD mice treated with probiotics. Additionally, helminth infected mice produce higher levels of oleic acid, which participates in anti-inflammatory pathways. These results suggest that modulation of the microbiota by helminth infection or probiotic treatment causes a reduction in subclinical inflammation, which has a positive effect on the glucose metabolism of the host.

Strongyloides stercoralis en un hospital comarcal del Levante español: una enfermedad no solo importada / Strongyloides stercoralis infection in a Spanish regional hospital: Not just an imported disease

Introducción: La infestación por Strongyloides stercoralis es más prevalente en regiones tropicales, pero existen casos autóctonos en España, principalmente en La Safor (Valencia). Nuestro objetivo era estudiar los casos de un hospital de la provincia de Alicante y conocer si existían casos autóctonos. Procedimiento: Estudio retrospectivo de los casos diagnosticados de estrongiloidiasis en el Hospital Vega Baja (Orihuela, Alicante) entre enero de 1999 y marzo de 2016. Resultados: Se registraron 10 casos, 4 de ellos autóctonos, presentando 2 de ellos un cuadro de hiperinfestación con desenlace fatal. Todos los casos autóctonos fueron en personas ≥69años con síntomas digestivos, cutáneos y/o respiratorios. La serología fue positiva en los 8casos en los que se realizó. En 3 casos se visualizaron larvas en el estudio histopatológico. Conclusiones: Comunicamos los primeros casos autóctonos de estrongiloidiasis en la región Vega Baja. Se deben implantar programas de cribado principalmente en pacientes inmunosuprimidos o en tratamiento corticoideo (AU)

Introduction: Strongyloides stercoralis infection is more prevalent in tropical regions but autochthonous cases have been reported in Spain, mainly in La Safor (Valencia). The objective is to describe the strongyloidiasis cases registered in a regional hospital of Alicante province (Spain) and to determine if they were autochthonous cases. Methods: Retrospective study of all diagnosed cases of strongyloidiasis in Vega Baja Hospital (Orihuela, Alicante) between January 1999 and March 2016. Results: A total of 10 cases were found, four of which were autochthonous cases. Two of them presented with a hyper-infection syndrome, with a fatal outcome. All autochthonous cases were in patients ≥69years old with gastrointestinal, cutaneous, and/or respiratory symptoms. Serology was positive in the 8 cases studied. Larvae were found in histopathological samples of the gastrointestinal tract of three patients. Conclusions: We communicate the first autochthonous cases of strongyloidiasis in the region of Vega Baja. Screening programs should be implemented, especially in immunosuppressed patients or patients under chronic corticosteroid treatment (AU)

Estrongiloidiasis autóctona en Asturias / Strongyloidiasis native to Asturias

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Microbial Translocation Associated with an Acute-Phase Response and Elevations in MMP-1, HO-1, and Proinflammatory Cytokines in Strongyloides stercoralis Infection.

Microbial translocation, characterized by elevated levels of lipopolysaccharide (LPS) and related markers, is a common occurrence in HIV and some parasitic infections. This is usually associated with extensive inflammation and immune activation. To examine the occurrence of microbial translocation and the associated inflammatory response in asymptomatic Strongyloides stercoralis infection, we measured the plasma levels of LPS and other microbial translocation markers, acute-phase proteins, inflammatory markers, and proinflammatory cytokines in individuals with (infected [INF]) or without (uninfected [UN]) S. stercoralis infections. Finally, we also measured the levels of all of these markers in INF individuals following treatment of S. stercoralis infection. We show that INF individuals exhibit significantly higher plasma levels of microbial translocation markers (LPS, soluble CD14 [sCD14], intestinal fatty acid-binding protein [iFABP], and endotoxin core IgG antibody [EndoCAb]), acute-phase proteins (α-2 macroglobulin [α-2M], C-reactive protein [CRP], haptoglobin, and serum amyloid protein A [SAA]), inflammatory markers (matrix metalloproteinase 1 [MMP-1] and heme oxygenase 1 [HO-1]), and proinflammatory cytokines (interleukin-6 [IL-6], IL-8, monocyte chemoattractant protein 1 [MCP-1], and IL-1ß) than do UN individuals. INF individuals exhibit significantly decreased levels of tissue inhibitor of metalloproteinases 4 (TIMP-4). Following treatment of S. stercoralis infection, the elevated levels of microbial translocation markers, acute-phase proteins, and inflammatory markers were all diminished. Our data thus show that S. stercoralis infection is characterized by microbial translocation and accompanying increases in levels of acute-phase proteins and markers of inflammation and provide data to suggest that microbial translocation is a feature of asymptomatic S. stercoralis infection and is associated with an inflammatory response.

Enteric pathogens of food sellers in rural Gambia with incidental finding of Myxobolus species (Protozoa: Myxozoa).

BACKGROUND: Ongoing surveillance of enteric pathogens of public health significance among casual food sellers is undertaken in many resource-limited countries. We report the results of a survey in Kiang West province, The Gambia, and provide an exemplar methodology for such surveys in resource-limited laboratories. METHODS: Unpreserved, unrefrigerated stool samples were subjected to Salmonella, Shigella and agar plate culture for rhabditoid nematodes. Direct microscopy, formalin-ethyl acetate concentration and iron-hematoxylin staining was performed later, following preservation. RESULTS: Of 128 specimens received, no Shigella spp. was recovered, while four serovars of non-typhoidal Salmonella enterica, including Chandans, were isolated. Pathogenic parasitic infections were Necator americanus 10/128 (7.8%), Strongyloides stercoralis 3/128 (2.8%), Blastocystis species 45/128 (35.1%), Entamoeba histolytica complex 19/128 (14.8%) and Giardia intestinalis 4/128 (3.1%). A single case each of Hymenolepis diminuta and S. mansoni infection were detected. In one participant, myxozoan spores identical to those of Myxobolus species were found. CONCLUSIONS: Rare parasitoses and serovars of Salmonella enterica may occur relatively commonly in rural Africa. This paper describes intestinal pathogens found in a cohort of food sellers in such a setting. Furthermore, it describes two parasites rarely recovered from humans and demonstrates the need for methods other than microscopy to detect S. stercoralis infections.

Rash maculopapular pruriginoso y síndrome diarreico en paciente afecto de leucemia aguda linfoblástica en recaída / Pruritic maculopapular rash and diarrhea syndrome in a patient with acute lymphoblastic leukemia in relapse

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Meningitis associated with strongyloidiasis in an area endemic for strongyloidiasis and human T-lymphotropic virus-1: a single-center experience in Japan between 1990 and 2010.

Meningitis caused by enteric flora is a known complication of strongyloidiasis, and human T-lymphotropic virus-1 (HTLV-1) predisposes individuals to severe strongyloidiasis. We reviewed the clinical features of bacterial meningitis associated with strongyloidiasis seen at a single center in subtropical Japan, in an area endemic for both strongyloidiasis and HTLV-1. We found 33 episodes in 21 patients between 1990 and 2010. The results were remarkable for the high incidence of meningitis due to Gram-positive cocci (27.3 %), especially Streptococcus bovis, and culture-negative cases (42.4 %). Given the high incidence of Gram-positive meningitis, a modified approach to corticosteroid use would be advisable in areas where strongyloidiasis is endemic, due to the potentially adverse consequences of glucocorticoid therapy.

Role of IL-13 in a model of Strongyloides venezuelensis infection in rats.

IL-13 is a cytokine known to play a role in several pulmonary diseases, including asthma and fibrosis. The role of IL-13 in the context of pulmonary changes induced by helminth infection is unclear. Rats experimentally infected with Strongyloides venezuelensis and treated with anti-IL-13 neutralizing antibody were used to evaluate the role of IL-13 on functional and inflammatory changes of host lungs, and on parasite control. S. venezuelensis-induced airway hyperreactivity was IL-13-independent, but IL-13 played an essential role in driving airway mucus production and eosinophil infiltration. IL-13 was important for the control of egg production but not establishment in the intestine.