The detergent fraction is effective in the detection of IgG anti-Strongyloides stercoralis in serum samples from immunocompromised individuals

Human strongyloidiasis is an intestinal helminthiasis that can be fatal particularly in cases of immunosuppression. The aim of this study is to assess the diagnostic accuracy of the detergent fraction (D), purified from total saline extract (SE) of Strongyloides venezuelensis, in the detection of anti-Strongyloides stercoralis IgG antibodies in serum samples from individuals coming from endemic areas for strongyloidiasis and presenting immunocompromised conditions: human immunodeficiency virus (HIV⁺), diabetes mellitus type 2, cancer, tuberculosis and alcoholism. Serum samples from 93 individuals were analyzed by ELISA, as follows: Group 1: 30 immunocompromised individuals with strongyloidiasis; Group 2: 33 immunocompromised individuals without strongyloidiasis and Group 3: 30 healthy individuals. The total saline extract (SE) and detergent fraction (D) showed a sensitivity of 73.33 and 83.33%, and specificity of 82.15 and 86.36%, respectively. The detergent fraction was effective to detect anti-S. stercoralis IgG antibodies in immunocompromised individuals with strongyloidiasis and may be applied as an important tool in the immunodiagnosis of human strongyloidiasis related to immunosuppression.     

Strongy Detect: Preliminary Validation of a Prototype Recombinant Ss-NIE/Ss-IR Based ELISA to Detect Strongyloides stercoralis Infection

BackgroundStrongyloides stercoralis (Ss) is the etiological agent of strongyloidiasis, a neglected tropical disease of global concern. Laboratory diagnosis of strongyloidiasis is most often based on detection of antibodies against antigens in an enzyme linked immunosorbent assay (ELISA). Herein, we report a preliminary validation study of newly developed IgG4- and/or IgG- based ELISAs to detect strongyloidiasis (Strongy Detect, InBios) incorporating a cocktail of 2 previously described recombinant antigens, Ss-NIE and Ss-IR.MethodsThe sensitivity and specificity were determined by using the assay in 150 cryopreserved serum samples from humans known to be Ss infected (n = 74), helminth uninfected (n = 47), or infected with a helminth other than Ss [n = 29). The treatment associated dynamics of antibody detection were then assessed using 35 paired samples obtained before and after definitive therapy.ResultsThe IgG and IgG4 assays were 99% and 96% sensitive, respectively, and 99% and 100% specific, respectively. Neither the IgG or IgG4 assay showed cross reactions with sera from those infected with other helminths. Although ELISA values did decline post-treatment few returned to levels below the cutoff for infection.ConclusionStrongy Detect is the most sensitive and specific commercialized immunoassay for detection of strongyloidiasis. The assay remains positive for greater than a year post-treatment.     

Development of a Rapid Serological Assay for the Diagnosis of Strongyloidiasis Using a Novel Diffraction-Based Biosensor Technology

Background

Strongyloidiasis is a persistent human parasitic infection caused by the intestinal nematode, Strongyloides stercoralis. The parasite has a world-wide distribution, particularly in tropical and subtropical regions with poor sanitary conditions. Since individuals with strongyloidiasis are typically asymptomatic, the infection can persist for decades without detection. Problems arise when individuals with unrecognized S. stercoralis infection are immunosuppressed, which can lead to hyper-infection syndrome and disseminated disease with an associated high mortality if untreated. Therefore a rapid, sensitive and easy to use method of diagnosing Strongyloides infection may improve the clinical management of this disease.

Methodology/Principal Findings

An immunological assay for diagnosing strongyloidiasis was developed on a novel diffraction-based optical bionsensor technology. The test employs a 31-kDa recombinant antigen called NIE derived from Strongyloides stercoralis L3-stage larvae. Assay performance was tested using retrospectively collected sera from patients with parasitologically confirmed strongyloidiasis and control sera from healthy individuals or those with other parasitoses including schistosomiasis, trichinosis, echinococcosis or amebiasis who were seronegative using the NIE ELISA assay. If we consider the control group as the true negative group, the assay readily differentiated S. stercoralis-infected patients from controls detecting 96.3% of the positive cases, and with no cross reactivity observed in the control group These results were in excellent agreement (κ = 0.98) with results obtained by an NIE-based enzyme-linked immunosorbent assay (ELISA). A further 44 sera from patients with suspected S. stercoralis infection were analyzed and showed 91% agreement with the NIE ELISA.

Conclusions/Significance

In summary, this test provides high sensitivity detection of serum IgG against the NIE Strongyloides antigen. The assay is easy to perform and provides results in less than 30 minutes, making this platform amenable to rapid near-patient screening with minimal technical expertise.     

Prevalence of Strongyloides stercoralis infection and associated clinical symptoms among schoolchildren living in different altitudes of Amhara National Regional State,northwest Ethiopia

BackgroundStrongyloides stercoralis is a parasite that causes strongyloidiasis in humans. It is prevalent in the tropics and sub-tropics where poor sanitation is a common problem. The true prevalence of S. stercoralis in Ethiopia is underestimated due to the lack of a “Gold” standard diagnostic method. Moreover, its prevalence across altitudinal gradient in Amhara Region has not been studied.MethodsA cross-sectional study was conducted among 844 schoolchildren in Amhara Region from April to December 2019. A stool sample was collected from each study participant and processed using formol ether concentration technique (FECT), spontaneous tube sedimentation technique (STST), Baermann concentration technique (BCT), agar plate culture (APC) and real-time polymerase chain reaction (RT-PCR). Data were entered using EpiData and analyzed by SPSS version 23 statistical software. Prevalence of S. stercoralis infection was determined using a single diagnostic technique and combination of techniques. Association of clinical variables with S. stercoralis infection was assessed by logistic regression and independent variables with p<0.05 were considered statistically significant.ResultsPrevalence of soil-transmitted helminths (STHs) and S. mansoni infections was 38.0% and 20.4%, respectively. Among STHs, the prevalence of hookworm infection was 32.8%. Prevalence of S. stercoralis infection was 39.0%, 28.8%, 10.9%, 10.3%, 4.0% and 2.0% by the respective, combinations of the five methods, RT-PCR, APC, BCT, STST and FECT. The highest prevalence rates, 48.2%, 45.0% and 41.1% of S. stercoralis were recorded in the age group of 12–14 years, males and rural dwellers, respectively. Prevalence rates of S. stercoralis infection in highland, semi-highland and lowland areas were 40.4%, 41.8% and 25.9%, respectively. Having abdominal pain (AOR = 2.48; 95% CI:1.65–3.72), cough (AOR = 1.63;95%CI:1.09–2.42), urticaria (AOR = 2.49;95%CI:1.50–4.01) and being malnourished (AOR = 1.44;95%:1.10–2.01) were significantly associated with strongyloidiasis.ConclusionPrevalence of S. stercoralis infection was high and varied across different altitudes in Amhara Region. Some clinical syndromes were found to be significantly associated with S. stercoralis infection. Therefore, proper diagnosis and preventive strategies against S. stercoralis infection are highly recommended to be devised and implemented in Amhara Region.     

Seroepidemiology of strongyloidiasis in a Thai village

Strongyloidiasis is a potentially fatal disease for which existing methods of diagnosis lack sensitivity. A recently developed ELISA for IgG antibodies against the infective larval stage was used to screen a leprosy resettlement village in an area endemic for strongyloidiasis. The results of the ELISA were compared with the results of stool examination for 177 villagers. Eleven per cent of the village had S. stercoralis present on stool examination and 45% had antibodies detected by ELISA. Eighteen of 21 (85%) villagers with S. stercoralis infection proven by stool examination had positive ELISA values. No cross reactivity with intraluminal parasites was present. Linear correlation between per cent eosinophils and the ELISA revealed a correlation coefficient of 0.402 (P < 0.001). Forty-two days after sucessful treatment in 14 villagers, the IgG antibody levels had decreased (P < 0.001). Leprosy did not affect the sensitivity of the assay. These results suggest that ELISA is a simple, sensitive and specific method for surveying exposure to S. stercoralis in an endemic area.     

Intestinal strongyloidiasis and hyperinfection syndrome

In spite of recent advances with experiments on animal models, strongyloidiasis, an infection caused by the nematode parasite Strongyloides stercoralis, has still been an elusive disease. Though endemic in some developing countries, strongyloidiasis still poses a threat to the developed world. Due to the peculiar but characteristic features of autoinfection, hyperinfection syndrome involving only pulmonary and gastrointestinal systems, and disseminated infection with involvement of other organs, strongyloidiasis needs special attention by the physician, especially one serving patients in areas endemic for strongyloidiasis. Strongyloidiasis can occur without any symptoms, or as a potentially fatal hyperinfection or disseminated infection. Th₂ cell-mediated immunity, humoral immunity and mucosal immunity have been shown to have protective effects against this parasitic infection especially in animal models. Any factors that suppress these mechanisms (such as intercurrent immune suppression or glucocorticoid therapy) could potentially trigger hyperinfection or disseminated infection which could be fatal. Even with the recent advances in laboratory tests, strongyloidiasis is still difficult to diagnose. But once diagnosed, the disease can be treated effectively with antihelminthic drugs like Ivermectin. This review article summarizes a case of strongyloidiasis and various aspects of strongyloidiasis, with emphasis on epidemiology, life cycle of Strongyloides stercoralis, clinical manifestations of the disease, corticosteroids and strongyloidiasis, diagnostic aspects of the disease, various host defense pathways against strongyloidiasis, and available treatment options.     

Strongyloides stercoralis and HTLV-1 coinfection in CD34+ cord blood stem cell humanized mice: Alteration of cytokine responses and enhancement of larval growth

Viral and parasitic coinfections are known to lead to both enhanced disease progression and altered disease states. HTLV-1 and Strongyloides stercoralis are co-endemic throughout much of their worldwide ranges resulting in a significant incidence of coinfection. Independently, HTLV-1 induces a Th1 response and S. stercoralis infection induces a Th2 response. However, coinfection with the two pathogens has been associated with the development of S. stercoralis hyperinfection and an alteration of the Th1/Th2 balance. In this study, a model of HTLV-1 and S. stercoralis coinfection in CD34⁺ umbilical cord blood hematopoietic stem cell engrafted humanized mice was established. An increased level of mortality was observed in the HTLV-1 and coinfected animals when compared to the S. stercoralis infected group. The mortality was not correlated with proviral loads or total viral RNA. Analysis of cytokine profiles showed a distinct shift towards Th1 responses in HTLV-1 infected animals, a shift towards Th2 cytokines in S. stercoralis infected animals and elevated TNF-α responses in coinfected animals. HTLV-1 infected and coinfection groups showed a significant, yet non-clonal expansion of the CD4⁺CD25⁺ T-cell population. Numbers of worms in the coinfection group did not differ from those of the S. stercoralis infected group and no autoinfective larvae were found. However, infective larvae recovered from the coinfection group showed an enhancement in growth, as was seen in mice with S. stercoralis hyperinfection caused by treatment with steroids. Humanized mice coinfected with S. stercoralis and HTLV-1 demonstrate features associated with human infection with these pathogens and provide a unique opportunity to study the interaction between these two infections in vivo in the context of human immune cells.     

A Case of Fatal Strongyloidiasis in a Patient with Chronic Lymphocytic Leukemia and Molecular Characterization of the Isolate

Strongyloides stercoralis is a human intestinal parasite which may lead to complicated strongyloidiasis in immunocompromised. Here, a case of complicated strongyloidiasis in a patient with chronic lymphocytic leukemia is reported. Presence of numerous S. stercoralis larvae in feces and sputum confirmed the diagnosis of hyperinfection syndrome in this patient. Following recovery of filariform larvae from agar plate culture of the stool, the isolate was characterized for the ITS1 region of ribosomal DNA gene by nested-PCR and sequencing. Albendazole therapy did not have cure effects; and just at the beginning of taking ivermectin, the patient died. The most important clue to prevent such fatal consequences is early diagnosis and proper treatment.     

Regulatory T Cell Expansion in HTLV-1 and Strongyloidiasis Co-infection Is Associated with Reduced IL-5 Responses to Strongyloides stercoralis Antigen

Background

Human strongyloidiasis varies from a chronic but limited infection in normal hosts to hyperinfection in patients treated with corticosteroids or with HTLV-1 co-infection. Regulatory T cells dampen immune responses to infections. How human strongyloidiasis is controlled and how HTLV-1 infection affects this control are not clear. We hypothesize that HTLV-1 leads to dissemination of Strongyloides stercoralis infection by augmenting regulatory T cell numbers, which in turn down regulate the immune response to the parasite.

Objective

To measure peripheral blood T regulatory cells and Strongyloides stercoralis larval antigen-specific cytokine responses in strongyloidiasis patients with or without HTLV-1 co-infection.

Methods

Peripheral blood mononuclear cells (PBMCs) were isolated from newly diagnosed strongyloidiasis patients with or without HTLV-1 co-infection. Regulatory T cells were characterized by flow cytometry using intracellular staining for CD4, CD25 and FoxP3. PBMCs were also cultured with and without Strongyloides larval antigens. Supernatants were analyzed for IL-5 production.

Results

Patients with HTLV-1 and Strongyloides co-infection had higher parasite burdens. Eosinophil counts were decreased in the HTLV-1 and Strongyloides co-infected subjects compared to strongyloidiasis-only patients (70.0 vs. 502.5 cells/mm³, p = 0.09, Mann-Whitney test). The proportion of regulatory T cells was increased in HTLV-1 positive subjects co-infected with strongyloidiasis compared to patients with only strongyloidiasis or asymptomatic HTLV-1 carriers (median = 17.9% vs. 4.3% vs. 5.9 p<0.05, One-way ANOVA). Strongyloides antigen-specific IL-5 responses were reduced in strongyloidiasis/HTLV-1 co-infected patients (5.0 vs. 187.5 pg/ml, p = 0.03, Mann-Whitney test). Reduced IL-5 responses and eosinophil counts were inversely correlated to the number of CD4+CD25+FoxP3+ cells.

Conclusions

Regulatory T cell counts are increased in patients with HTLV-1 and Strongyloides stercoralis co-infection and correlate with both low circulating eosinophil counts and reduced antigen-driven IL-5 production. These findings suggest a role for regulatory T cells in susceptibility to Strongyloides hyperinfection.     

Phylogenetic Positioning of a Strongyloides stercoralis Isolate Recovered from a Korean Patient and Comparison with Other Asian Isolates

Strongyloidiasis is caused by Strongyloides stercoralis and is one of the most neglected tropical diseases in tropical and subtropical regions. Although several strongyloidiasis cases have been reported in Korea, genetic analysis of Korean isolates is still incomplete. In this study, a parasite was isolated from a 61-year-old man diagnosed with strongyloidiasis during the treatment of lymphoma on his retroperitoneal lymph node. Diffuse symmetric wall thickening from the ascending to descending colon and a nematode-infected intestine was observed following microscopic examination. Genomic DNA was isolated from a patient tissue block, and S. stercoralis was identified by PCR and sequencing (18S rDNA). In order to determine phylogenetic location of a Korean isolate (named KS1), we analyzed cox1 gene (500-bp) and compared it with that from 47 previous S. stercoralis isolates (28 human isolates and 19 canid isolates) from Asian countries. Our results showed that phylogenetic tree could clearly be divided into 5 different groups according to hosts and regions. KS1 was most closely related with the Chinese isolates in terms of genetic distance.     

Seroprevalence of Strongyloides stercoralis infection in a South Indian adult population

BackgroundThe prevalence of Strongyloides stercoralis infection is estimated to be 30–100 million worldwide, although this an underestimate. Most cases remain undiagnosed due to the asymptomatic nature of the infection. We wanted to estimate the seroprevalence of S. stercoralis infection in a South Indian adult population.MethodsTo this end, we performed community-based screening of 2351 individuals (aged 18–65) in Kanchipuram District of Tamil Nadu between 2013 and 2020. Serological testing for S. stercoralis was performed using the NIE ELISA.ResultsOur data shows a seroprevalence of 33% (768/2351) for S. stercoralis infection which had a higher prevalence among males 36% (386/1069) than among females 29.8% (382/1282). Adults aged ≥55 (aOR = 1.65, 95% CI: 1.25–2.18) showed higher adjusted odds of association compared with other age groups. Eosinophil levels (39%) (aOR = 1.43, 95% CI: 1.19–1.74) and hemoglobin levels (24%) (aOR = 1.25, 95% CI: 1.11–1.53) were significantly associated with S. stercoralis infection. In contrast, low BMI (aOR = 1.15, 95% CI: 0.82–1.61) or the presence of diabetes mellitus (OR = 1.18, 95% CI: 0.83–1.69) was not associated with S. stercoralis seropositivity.ConclusionsOur study provides evidence for a very high baseline prevalence of S. stercoralis infection in South Indian communities and this information could provide realistic and concrete planning of control measures.     

Evaluation of Strongyloides stercoralis infection in patients with HTLV-1

Introduction: Individuals infected with the human T-lymphotropic virus type 1 (HTLV-1) may present severe and disseminated forms of Strongyloides stercoralis infection with low therapeutic response.Objective: To investigate the S. stercoralis infection and the seroprevalence of IgG anti-S. stercoralis antibodies in individuals infected with HTLV-1 attending the Reference Center for HTLV-1 (CHTLV) in Salvador, Bahia, Brazil.Materials and methods: We conducted a cross-sectional study in 178 HTLV-1-infected individuals treated at the HTLV specialized center between January, 2014, and December, 2018. The parasitological diagnosis of S. stercoralis was performed using the Hoffman, Pons and Janer, agar plate culture, and Baermann-Morais methods. The IgG anti-S. stercoralis detection was performed using an in house enzyme-linked immunosorbent assay (ELISA). The HTLV-1 infection was diagnosed using a commercial ELISA and confirmed by Western blot.Results: The frequency of S. stercoralis infection was 3.4% (6/178). Individuals infected with S. stercoralis from rural areas (50.0%; 3/6) also showed S. stercoralis hyperinfection (>3,000 larvae/ gram of feces). The frequency of circulating anti-S. stercoralis IgG antibodies was 20.8% (37/178). Conclusions: HTLV-1-infected people living in precarious sanitary conditions are more prone to develop severe forms of S. stercoralis infection. Considering the high susceptibility and unfavorable outcome of the infection in these individuals, the serological diagnosis for S. stercoralis should be considered when providing treatment.     

Strongyloides stercoralis: Systematic Review of Barriers to Controlling Strongyloidiasis for Australian Indigenous Communities

Background

Strongyloides stercoralis infects human hosts mainly through skin contact with contaminated soil. The result is strongyloidiasis, a parasitic disease, with a unique cycle of auto-infection causing a variety of symptoms and signs, with possible fatality from hyper-infection. Australian Indigenous community members, often living in rural and remote settings, are exposed to and infected with S. stercoralis. The aim of this review is to determine barriers to control of strongyloidiasis. The purpose is to contribute to the development of initiatives for prevention, early detection and effective treatment of strongyloidiasis.

Methodology/Principle Findings

Systematic search reviewing research published 2012 and earlier was conducted. Research articles discussing aspects of strongyloidiasis, context of infection and overall health in Indigenous Australians were reviewed. Based on the PRISMA statement, the systematic search of health databases, Academic Search Premier, Informit, Medline, PubMed, AMED, CINAHL, Health Source Nursing and Academic was conducted. Key search terms included strongyloidiasis, Indigenous, Australia, health, and community. 340 articles were retrieved with 16 original research articles published between 1969 and 2006 meeting criteria. Review found barriers to control defined across three key themes, (1) health status, (2) socioeconomic status, and (3) health care literacy and procedures.

Conclusions/Significance

This study identifies five points of intervention: (1) develop reporting protocols between health care system and communities; (2) test all Indigenous Australian patients, immunocompromised patients and those exposed to areas with S. stercoralis; (3) health professionals require detailed information on strongyloidiasis and potential for exposure to Indigenous Australian people; (4) to establish testing and treatment initiatives within communities; and (5) to measure and report prevalence rates specific to communities and to act with initiatives based on these results. By defining barriers to control of strongyloidiasis in Australian Indigenous people, improved outcomes of prevention, treatment of strongyloidiasis and increased health overall are attainable.     

Bacteriophage-Fused Peptides for Serodiagnosis of Human Strongyloidiasis

Background

Strongyloidiasis, a human intestinal infection caused by the nematode Strongyloides stercoralis, is frequently underdiagnosed and although its high prevalence is still a neglected parasitic disease because conventional diagnostic tests based on parasitological examination (presence of Strongyloides larvae in stool) are not sufficiently sensitive due to the low parasitic load and to the irregular larval output. There is an urgent need to improve diagnostic assays, especially for immunocompromised patients with high parasitic load as consequence of self-infection cycle, which can disseminate throughout the body, resulting in a potentially fatal hyperinfection syndrome often accompanied by sepsis or meningitis.

Methods/Principal Findings

We have performed Phage Display technology to select peptides that mimic S. stercoralis antigens, capable of detecting a humoral response in patients with strongyloidiasis. The peptides reactivity was investigated by Phage-ELISA through different panels of serum samples. We have successfully selected five peptides with significant immunoreactivity to circulating IgG from patients'' sera with strongyloidiasis. The phage displayed peptides C9 and C10 presented the highest diagnostic potential (AUC>0.87) with excellent sensitivity (>85%) and good specificity (>77.5%), suggesting that some S. stercoralis antigens trigger systemic immune response.

Conclusions/Significance

These novel antigens are interesting serum biomarkers for routine strongyloidiasis screenings due to the easy production and simple assay using Phage-ELISA. Such markers may also present a promising application for therapeutic monitoring.     

Mesangial Cell-Binding Activity of Serum Immunoglobulin G in Patients with Lupus Nephritis

In vitro data showed that immunoglobulin G (IgG) from patients with lupus nephritis (LN) could bind to cultured human mesangial cells (HMC). The clinical relevance of such binding was unknown. Binding of IgG and subclasses was measured in 189 serial serum samples from 23 patients with Class III/IV±V LN (48 during renal flares, 141 during low level disease activity (LLDA)). 64 patients with non-lupus glomerular diseases (NLGD) and 23 healthy individuals were used as controls. HMC-binding was measured with cellular ELISA and expressed as OD index. HMC-binding index of total IgG was 0.12±0.09, 0.36±0.25, 0.59±0.37 and 0.74±0.42 in healthy subjects, NLGD, LN patients during LLDA, and LN flares respectively (P = 0.046, LN flare vs. LLDA; P<0.001, for healthy controls or NLGD vs. LN during flare or LLDA). Binding of serum IgG₁ to HMC was 0.05±0.05, 0.15±0.11, 0.41±0.38 and 0.55±0.40 for the corresponding groups respectively (P = 0.007, LN flare vs. remission; P<0.001, for healthy controls or NLGD vs. LN during flare or remission). IgG₂, IgG₃ and IgG₄ from patients and controls did not show significant binding to HMC. Total IgG and IgG₁ HMC-binding index correlated with anti-dsDNA level (r = 0.26 and 0.39 respectively, P<0.001 for both), and inversely with C3 (r = −0.17 and −0.45, P<0.05 for both). Sensitivity/specificity of total IgG or IgG₁ binding to HMC in predicting renal flares were 81.3%/39.7% (ROC AUC 0.61, P = 0.03) and 83.8%/41.8% (AUC 0.63, P = 0.009) respectively. HMC-binding by IgG_1, but not total IgG, correlated with mesangial immune deposition in LN renal biopsies under electron microscopy. Our results showed that binding of serum total IgG and IgG₁ in LN patients correlates with disease activity. The correlation between IgG₁ HMC-binding and mesangial immune deposition suggests a potential pathogenic significance.     

Trypanosoma lewisi: antibody classes which mediate precipitation, agglutination, and the inhibition of reproduction

Sera from Trypanosoma lewisi-infected and uninfected rats were applied to Protein A-Sepharose CL-4B columns. The absorbed fractions of antisera which contained only IgG molecules were reacted in microimmunodiffusion analyses with the exoantigens of T. lewisi in plasma collected from irradiated infected rats, and formed one precipitin line. These sera were also applied to T. lewisi extract immunoabsorbent columns and bound proteins were eluted and analyzed by immunodiffusion against antisera specific for rat immunoglobulins. IgG₁, IgG_2a, IgG_2b, IgG_2c, and IgM were absorbed by the immuno-absorbent columns. Absorption of the rat antisera with anti-rat IgG or anti-rat IgM removed one of the two precipitin lines against extracts prepared from parasites collected from irradiated infected animals. The absorbed IgG fractions and nonabsorbed fractions of antisera which were collected after Protein A-Sepharose CL-4B column chromatography agglutinated trypanosomes. After treatment of antisera with 2-mercaptoethanol, the agglutinin titers were lower than those of the control antisera suggesting both IgG and IgM are involved in the agglutination. The ablastic activity of the fractions eluted from Protein A-Sepharose CL-4B Chromatographic columns was assayed in cultures of bloodstream forms ofT. lewisi. Ablastic activity of proteins of antisera absorbed by the columns was demonstrated indicating they belonged to the IgG class of antibodies.     

Ivermectin Treatment and Sanitation Effectively Reduce Strongyloides stercoralis Infection Risk in Rural Communities in Cambodia

BackgroundStrongyloides stercoralis is the only soil-transmitted helminth with the ability to replicate within its host, leading to long-lasting and potentially fatal infections. It is ubiquitous and its worldwide prevalence has recently been estimated to be at least half that of hookworm. Information on the epidemiology of S. stercoralis remains scarce and modalities for its large-scale control are yet to be determined.Conclusions/SignificanceChemotherapy-based control of S. stercoralis is feasible and highly beneficial, particularly in combination with improved sanitation. The impact of community-based ivermectin treatment on S. stercoralis was high, with over 85% of villagers remaining negative one year after treatment. The integration of S. stercoralis into existing STH control programs should be considered without further delay.     

Strongyloides stercoralis and Trypanosoma cruzi coinfections in a highly endemic area in Argentina

BackgroundStrongyloidiasis and Chagas disease are endemic in northern Argentina. In this study we evaluate the association between S. stercoralis and T. cruzi infections in villages with diverse prevalence levels for these parasites. Further understanding in the relationship between these Neglected Tropical Diseases of South America is relevant for the design of integrated control measures as well as exploring potential biologic interactions.MethodologyCommunity based cross-sectional studies were carried in different villages of the Chaco and Yungas regions in Argentina. Individuals were diagnosed by serology for S. stercoralis and T. cruzi. The association between S. stercoralis and T. cruzi, and between anemia and the two parasites was evaluated using two approaches: marginal (Ma) and multilevel regression (Mu).ResultsA total of 706 individuals from six villages of northern Argentina were included. A total of 37% were positive for S. stercoralis, 14% were positive for T. cruzi and 5% were positive for both. No association was found between infection with S. stercoralis and T. cruzi in any of the models, but we found a negative correlation between the prevalence of these species in the different villages (r = -0.91). Adults (> 15 years) presented association with S. stercoralis (Ma OR = 2.72; Mu OR = 2.84) and T. cruzi (Ma OR = 5.12; Mu OR = 5.48). Also, 12% and 2% of the variance of infection with S. stercoralis and T. cruzi, respectively, could be explained by differences among villages. On the other hand, anemia was associated with infection with S. stercoralis (Ma OR = 1.73; Mu OR = 1.78) and was more prevalent in adults (Ma OR = 2.59; Mu OR = 2.69).ConclusionWe found that coinfection between S. stercoralis and T. cruzi is not more frequent than chance in endemic areas. However, the high prevalence for both parasites, raises the need for an integrated strategy for the control of STH and Chagas disease.     

Non-Immune Binding of Human IgG to M-Related Proteins Confers Resistance to Phagocytosis of Group A Streptococci in Blood

The non-immune binding of immunoglobulins by bacteria is thought to contribute to the pathogenesis of infections. M-related proteins (Mrp) are group A streptococcal (GAS) receptors for immunoglobulins, but it is not known if this binding has any impact on virulence. To further investigate the binding of immunoglobulins to Mrp, we engineered mutants of an M type 4 strain of GAS by inactivating the genes for mrp, emm, enn, sof, and sfbX and tested these mutants in IgG-binding assays. Inactivation of mrp dramatically decreased the binding of human IgG, whereas inactivation of emm, enn, sof, and sfbx had only minor effects, indicating that Mrp is a major IgG-binding protein. Binding of human immunoglobulins to a purified, recombinant form of Mrp indicated that it selectively binds to the Fc domain of human IgG, but not IgA or IgM and that it preferentially bound subclasses IgG₁>IgG₄>IgG₂>IgG₃. Recombinant proteins encompassing different regions of Mrp were engineered and used to map its IgG-binding domain to its A-repeat region and a recombinant protein with 3 A-repeats was a better inhibitor of IgG binding than one with a single A-repeat. A GAS mutant expressing Mrp with an in-frame deletion of DNA encoding the A-repeats had a dramatically reduced ability to bind human IgG and to grow in human blood. Mrp exhibited host specificity in binding IgG; human IgG was the best inhibitor of the binding of IgG followed by pig, horse, monkey, and rabbit IgG. IgG from goat, mouse, rat, cow, donkey, chicken, and guinea pig were poor inhibitors of binding. These findings indicate that Mrp preferentially binds human IgG and that this binding contributes to the ability of GAS to resist phagocytosis and may be a factor in the restriction of GAS infections to the human host.