Type 2 Diabetes Mellitus Is Associated with Strongyloides stercoralis Treatment Failure in Australian Aboriginals

Objective

To explore the efficacy of ivermectin in the treatment of serologically diagnosed cases of Strongyloides stercoralis (S. stercoralis) infection in an Aboriginal community and to describe factors that may influence the outcome of treatment.

Methods

Longitudinal study of a group of 92 individuals with serologically diagnosed S. stercoralis treated with ivermectin and followed up over a period of approximately 6 months. Main outcomes were serological titers pre and post treatment, diabetic status, and duration of follow up.

Findings

Treatment success was achieved in 62% to 79% of cases dependent on the methods employed for the diagnosis of infection and assessment of treatment outcome. Type 2 Diabetes Mellitus (T2DM) was found to be significantly associated with treatment failure in this group for two of the three methods employed.

Interpretation

Ivermectin has been confirmed as an effective treatment for S stercoralis infection in this setting. T2DM appears to be an independent risk factor for treatment failure in this population, and plausible mechanisms to explain this observation are presented.     

Diagnosis,Treatment and Risk Factors of Strongyloides stercoralis in Schoolchildren in Cambodia

Background

Worldwide, an estimated 30 to 100 million people are infected with Strongyloides stercoralis, a soil-transmitted helminth. Information on the parasite is scarce in most settings. In semi-rural Cambodia, we determined infection rates and risk factors; compared two diagnostic methods (Koga agar plate [KAP] culture and Baermann technique) for detecting S. stercoralis infections, using a multiple stool examination approach; and assessed efficacy of ivermectin treatment.

Methods/Principal Findings

We performed a cross-sectional study in 458 children from four primary schools in semi-rural villages in Kandal province, using three diagnostic procedures (Kato-Katz, KAP culture and Baermann technique) on three stool samples. Infected children were treated with ivermectin (100 µg/kg/day for two days) and re-examined three weeks after treatment. Hookworm, S. stercoralis, Trichuris trichiura, and small trematode eggs were most prevalent, with 24.4% of children being infected with S. stercoralis. The sensitivity of KAP culture and Baermann technique was 88.4% and 75.0%, respectively and their negative predictive values were 96.4% and 92.5%, respectively. The cumulative prevalence of S. stercoralis increased from 18.6% to 24.4%, after analyzing three stool samples, which was close to the modeled ‘true’ prevalence of 24.8%. Children who reported defecating in latrines were significantly less infected with S. stercoralis than those who did not use latrines (p<0.001). Itchy skin and diarrhea were significantly associated with S. stercoralis infection. The cure rate of ivermectin was 98.3%.

Conclusions/Significance

S. stercoralis infection is highly prevalent among semi-rural Cambodian schoolchildren. The sensitivity of KAP culture is higher than that of the Baermann technique. In the absence of a “gold standard”, analysis of multiple stool samples by different diagnostic methods is required to achieve a satisfactory level of sensitivity. Almost three-quarters of the infections could have been avoided by proper sanitation. Ivermectin is highly efficacious against S. stercoralis but prohibitive costs render the drug inaccessible to most Cambodians.     

Efficacy and safety of single and double doses of ivermectin versus 7-day high dose albendazole for chronic strongyloidiasis

Background

Strongyloidiasis, caused by an intestinal helminth Strongyloides stercoralis, is common throughout the tropics. It remains an important health problem due to autoinfection, which may result in hyperinfection and disseminated infection in immunosuppressed patients, especially patients receiving chemotherapy or corticosteroid treatment. Ivermectin and albendazole are effective against strongyloidiasis. However, the efficacy and the most effective dosing regimen are to be determined.

Methods

A prospective, randomized, open study was conducted in which a 7-day course of oral albendazole 800 mg daily was compared with a single dose (200 microgram/kilogram body weight), or double doses, given 2 weeks apart, of ivermectin in Thai patients with chronic strongyloidiasis. Patients were followed-up with 2 weeks after initiation of treatment, then 1 month, 3 months, 6 months, 9 months, and 1 year after treatment. Combination of direct microscopic examination of fecal smear, formol-ether concentration method, and modified Koga agar plate culture were used to detect strongyloides larvae in two consecutive fecal samples in each follow-up visit. The primary endpoint was clearance of strongyloides larvae from feces after treatment and at one year follow-up.

Results

Ninety patients were included in the analysis (30, 31 and 29 patients in albendazole, single dose, and double doses ivermectin group, respectively). All except one patient in this study had at least one concomitant disease. Diabetes mellitus, systemic lupus erythrematosus, nephrotic syndrome, hematologic malignancy, solid tumor and human immunodeficiency virus infection were common concomitant diseases in these patients. The median (range) duration of follow-up were 19 (2–76) weeks in albendazole group, 39 (2–74) weeks in single dose ivermectin group, and 26 (2–74) weeks in double doses ivermectin group. Parasitological cure rate were 63.3%, 96.8% and 93.1% in albendazole, single dose oral ivermectin, and double doses of oral ivermectin respectively (P = 0.006) in modified intention to treat analysis. No serious adverse event associated with treatment was found in any of the groups.

Conclusion/Significance

This study confirms that both a single, and a double dose of oral ivermectin taken two weeks apart, is more effective than a 7-day course of high dose albendazole for patients with chronic infection due to S. stercoralis. Double dose of ivermectin, taken two weeks apart, might be more effective than a single dose in patients with concomitant illness.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00765024","term_id":"NCT00765024"}}NCT00765024     

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.     

Central venous catheter related infections: Risk factors and the effect of glycopeptide antibiotics

Background

Invasive Aspergillus infections are frequently seen in immunocompromised patients but arthritis is a rare complication of Aspergillus infections in the absence of immune suppressive therapy, trauma or surgical intervention.

Case presentation

A 17 years old male patient with arthritis and patellar osteomyelitis of the left knee whose further investigations revealed chronic granulomatous disease as the underlying disease is followed. Aspergillus fumigatus was isolated from the synovial fluid and the tissue samples cultures. He was treated with Amphotericin B deoxicolate 0.7 mg/kg/day. Also surgical debridement was performed our patient. Amphotericin B nephrotoxicity developed and the therapy switched to itraconazole 400 mg/day. Itraconazole therapy were discontinued at the 6th month. He can perform all the activities of daily living including.

Conclusion

We think that, chronic granulomatous disease should be investigated in patients who have aspergillar arthritis and osteomyelitis.     

Mass Administration of Ivermectin for the Elimination of Onchocerciasis Significantly Reduced and Maintained Low the Prevalence of Strongyloides stercoralis in Esmeraldas,Ecuador

Objectives

To evaluate the effect of ivermectin mass drug administration on strongyloidiasis and other soil transmitted helminthiases.

Methods

We conducted a retrospective analysis of data collected in Esmeraldas (Ecuador) during surveys conducted in areas where ivermectin was annually administered to the entire population for the control of onchocerciasis.Data from 5 surveys, conducted between 1990 (before the start of the distribution of ivermectin) and 2013 (six years after the interruption of the intervention) were analyzed. The surveys also comprised areas where ivermectin was not distributed because onchocerciasis was not endemic.Different laboratory techniques were used in the different surveys (direct fecal smear, formol-ether concentration, IFAT and IVD ELISA for Strongyloides stercoralis).

Results

In the areas where ivermectin was distributed the strongyloidiasis prevalence fell from 6.8% in 1990 to zero in 1996 and 1999. In 2013 prevalence in children was zero with stool examination and 1.3% with serology, in adult 0.7% and 2.7%.In areas not covered by ivermectin distribution the prevalence was 23.5% and 16.1% in 1996 and 1999, respectively. In 2013 the prevalence was 0.6% with fecal exam and 9.3% with serology in children and 2.3% and 17.9% in adults.Regarding other soil transmitted helminthiases: in areas where ivermectin was distributed the prevalence of T. trichiura was significantly reduced, while A. lumbricoides and hookworms were seemingly unaffected.

Conclusions

Periodic mass distribution of ivermectin had a significant impact on the prevalence of strongyloidiasis, less on trichuriasis and apparently no effect on ascariasis and hookworm infections.     

Prevalence and risk factors of vertebral compression fractures in female SLE patients

Introduction

The present study objective was to evaluate the incidence of methotrexate (MTX)-specific liver lesions from the analysis of a liver biopsy of inflammatory arthritis patients with elevated liver enzymes.

Methods

A case-control study was performed with 1,571 arthritis patients on long-term low-dose MTX therapy. Results of liver biopsy were analyzed in 41 patients with elevated liver enzymes. The expression of autoimmune markers was also assessed. This population was compared with 41 disease control subjects obtained from the same database, also on MTX but without elevated liver enzymes, matched for age, sex and rheumatic disease.

Results

Compared with the disease controls, patients with liver biopsy showed lower disease duration and lower MTX exposure, weekly and cumulative doses, reflecting shorter treatment duration due to liver abnormalities. Liver biopsies showed 17 autoimmune hepatitis-like (AIH-like) lesions, 13 nonalcoholic steatohepatitis-like lesions, seven limited liver lesions, and two primary biliary cirrhoses. However, MTX-specific lesions with dystrophic nuclei in hepatocytes were seen in only two cases. Liver biopsy lesions were associated with autoimmune markers (P = 0.007); notably, AIH-like lesions were associated with rheumatoid arthritis and with the presence of the HLA-DR shared epitope.

Conclusions

MTX-specific liver lesions are rarely observed in arthritis patients under long-term MTX therapy and elevated liver enzymes.     

T-614, a novel immunomodulator, attenuates joint inflammation and articular damage in collagen-induced arthritis

Introduction

T-614 is a novel oral antirheumatic agent for the treatment of rheumatoid arthritis. Whether it has immunomodulatory or disease-modifying properties and its mechanism of action are largely undetermined.

Methods

Rats with collagen-induced arthritis (CIA) were treated with T-614 (5 and 20 mg/kg) daily. Animals receiving methotrexate (1 mg/kg every 3 days) and the nonsteroidal anti-inflammatory agent nimesulide (10 mg/kg per day) were used as controls. A combination therapy group was treated with both T-614(10 mg/kg per day) and methotrexate (1 mg/kg every 3 days). Hind paw swelling was evaluated and radiographic scores calculated. Serum cytokine levels were assessed by Bio-plex analysis. Quantitative PCR was used to evaluate expression of mRNA for interferon-γ, IL-4 and IL-17. Serum IL-17 and anti-type II collagen antibodies (total IgG, IgG₁, IgG_2a, IgG_2b and IgM) were measured using ELISA.

Results

Oral T-614 inhibited paw swelling and offered significant protection against arthritis-induced cartilage and bone erosion, comparable to the effects of methotrexate. CIA rats treated with T-614 exhibited decreases in both mRNA expression of IL-17 in peripheral blood mononuclear cells and lymph node cells, and circulating IL-17 in a dose-dependent manner. T-614 also reduced serum levels of tumor necrosis factor-α, IL-1β and IL-6. A synergistic effect was observed for the combination of methotrexate and T-614. In addition, T-614 (20 mg/kg per day) depressed production of anti-type II collagen antibodies and differentially affected levels of IgG_2a subclasses in vivo, whereas IgM level was decreased without any change in the IgG₁ level. Together, the findings presented here indicate that the novel agent T-614 has disease-modifying effects against experimental arthritis, as opposed to nimesulide.

Conclusions

Our data suggested that T-614 is an effective disease-modifying agent that can prevent bone/cartilage destruction and inflammation in in CIA rats. Combination with methotrexate markedly enhances the therapeutic effect of T-614.     

Estradiol ameliorates arthritis and protects against systemic bone loss in Staphylococcus aureus infection in mice

Introduction

Staphylococcus aureus is a common cause of bacterial arthritis, which is associated with progressive bone loss in affected joints. We recently showed that S. aureus infection also induces a significant systemic bone loss in mice. This study was performed to assess the effect of estradiol treatment on the clinical course and outcome of S. aureus arthritis and on infection-induced bone loss in experimental S. aureus infection.

Methods

Mice were ovariectomized, treated with estradiol or placebo, and S. aureus infection was established by intravenous inoculation of bacteria.

Results

Estradiol treatment was found to decrease significantly the frequency and clinical severity of S. aureus arthritis, a finding that was accompanied with significantly higher serum levels of interleukin-10 in estradiol-treated mice. Estradiol was also highly protective against S. aureus-induced systemic trabecular, and cortical bone loss. Lack of endogenous estrogens and S. aureus infection had additive effects on trabecular bone loss. The S. aureus-infected, ovariectomized mice lost as much as 76% of their trabecular bone mass.

Conclusions

Treatment with estradiol ameliorates S. aureus arthritis and is protective against infection-induced systemic bone loss in experimental S. aureus infection.     

Advances and challenges in predicting the impact of lymphatic filariasis elimination programmes by mathematical modelling

Background

Infection with the filarial nematode Onchocerca volvulus can lead to severe dermatitis, visual impairment, and ultimately blindness. Since the currently used drug, ivermectin does not have macrofilaricidal or strong permanent sterilising effects on the adult worm, more effective drugs are needed to complement the use of ivermectin alone. Wolbachia endosymbiotic bacteria in filariae have emerged as a new target for treatment with antibiotics which can lead to long -term sterilization of the adult female filariae.

Methods

In the Central Region of Ghana, 60 patients were recruited, allocated into four groups and treated with 200 mg doxycycline per day for 2 weeks, 4 weeks, 6 weeks respectively. Untreated patients served as controls. Some of the treated patients and the untreated controls were given 150 μg/kg ivermectin 8 months after the start of doxycycline treatment.

Results

A follow up study 18 months post treatment showed that when using doxycycline alone there was a significant reduction of microfilarial (mf) loads in patients treated for either 4 or 6 weeks. However, there was no significant difference between the untreated controls and those given the 2 weeks regimen. Although no significant difference was demonstrated between the 4 and 6 weeks regimens, there was a trend observed, in that, microfilarial reduction appeared to have been greater following the 6 weeks regimen. Twelve months after ivermectin (i.e. 20 months after doxycycline) treatment, 8 out of 11 ivermectin-alone treated patients were mf-positive. In contrast, 1 out of the 7 patients treated for 4 weeks with doxycycline and none of the 4 patients treated for 6 weeks doxycycline (who were available for re-examination) were mf-positive after the combined treatment of doxycycline plus ivermectin treatment.

Conclusion

Treatment of onchocerciasis with doxycycline for 4 weeks is effective. Nonetheless, mf reduction appeared to be greater in the 6 weeks regimen. It is recommended that until further studies are carried out i.e. 4 weeks treatment with doxycycline is proven equivalent to the 6 weeks, selected groups of onchocerciasis patients should be treated for 6 weeks with doxycycline. As discussed earlier, this treatment should be accompanied by two doses of ivermectin.     

Strongyloides ratti: in vitro and in vivo activity of tribendimidine

Background

Strongyloidiasis is a truly neglected tropical disease, but its public health significance is far from being negligible. At present, only a few drugs are available for the treatment and control of strongyloidiasis.

Methodology/Principal Findings

We investigated the activity of tribendimidine against third-stage larvae (L₃) of Strongyloides ratti in vitro and against juvenile and adult stages of the parasite in vivo. S. ratti larvae incubated in PBS buffer containing 10–100 µg/ml tribendimidine died within 24 hours. A single 50 mg/kg oral dose of tribendimidine administered to rats infected with 1-day-old S. ratti showed no effect. The same dose administered to rats harboring a 2-day-old infection showed a moderate reduction of the intestinal parasite load. Three days post-exposure a significant reduction of the immature worm burden was found. Administration of tribendimidine at doses of 50 mg/kg and above to rats harboring mature S. ratti resulted in a complete elimination of the larval and adult worm burden. For comparison, we also administered ivermectin at a single 0.5 mg/kg oral dose to rats infected with adult S. ratti and found a 90% reduction of larvae and a 100% reduction of adult worms.

Conclusion/Significance

Tribendimidine exhibits activity against S. ratti in vitro and in vivo. The effect of tribendimidine in humans infected with S. stercoralis should be assessed.     

Strongyloides stercoralis: Global Distribution and Risk Factors

Background

The soil-transmitted threadworm, Strongyloides stercoralis, is one of the most neglected among the so-called neglected tropical diseases (NTDs). We reviewed studies of the last 20 years on S. stercoralis''s global prevalence in general populations and risk groups.

Methods/Principal Findings

A literature search was performed in PubMed for articles published between January 1989 and October 2011. Articles presenting information on infection prevalence were included. A Bayesian meta-analysis was carried out to obtain country-specific prevalence estimates and to compare disease odds ratios in different risk groups taking into account the sensitivities of the diagnostic methods applied. A total of 354 studies from 78 countries were included for the prevalence calculations, 194 (62.4%) were community-based studies, 121 (34.2%) were hospital-based studies and 39 (11.0%) were studies on refugees and immigrants. World maps with country data are provided. In numerous African, Asian and South-American resource-poor countries, information on S. stercoralis is lacking. The meta-analysis showed an association between HIV-infection/alcoholism and S. stercoralis infection (OR: 2.17 BCI: 1.18–4.01; OR: 6.69; BCI: 1.47–33.8), respectively.

Conclusions

Our findings show high infection prevalence rates in the general population in selected countries and geographical regions. S. stercoralis infection is prominent in several risk groups. Adequate information on the prevalence is still lacking from many countries. However, current information underscore that S. stercoralis must not be neglected. Further assessments in socio-economic and ecological settings are needed and integration into global helminth control is warranted.     

Diagnostic Accuracy of Five Serologic Tests for Strongyloides stercoralis Infection

Background

The diagnosis of Strongyloides stercoralis (S. stercoralis) infection is hampered by the suboptimal sensitivity of fecal-based tests. Serological methods are believed to be more sensitive, although assessing their accuracy is difficult because of the lack of sensitivity of a fecal-based reference (“gold”) standard.

Methods

The sensitivity and specificity of 5 serologic tests for S. stercoralis (in-house IFAT, NIE-ELISA and NIE-LIPS and the commercially available Bordier-ELISA and IVD-ELISA) were assessed on 399 cryopreserved serum samples. Accuracy was measured using fecal results as the primary reference standard, but also using a composite reference standard (based on a combination of tests).

Results

According to the latter standard, the most sensitive test was IFAT, with 94.6% sensitivity (91.2–96.9), followed by IVD-ELISA (92.3%, 87.7–96.9). The most specific test was NIE-LIPS, with specificity 99.6% (98.9–100), followed by IVD-ELISA (97.4%, 95.5–99.3). NIE-LIPS did not cross-react with any of the specimens from subjects with other parasitic infections. NIE-LIPS and the two commercial ELISAs approach 100% specificity at a cut off level that maintains ≥70% sensitivity.

Conclusions

NIE-LIPS is the most accurate serologic test for the diagnosis of S. stercoralis infection. IFAT and each of the ELISA tests are sufficiently accurate, above a given cut off, for diagnosis, prevalence studies and inclusion in clinical trials.     

High Prevalence and Spatial Distribution of Strongyloides stercoralis in Rural Cambodia

Background

The threadworm, Strongyloides stercoralis, endemic in tropical and temperate climates, is a neglected tropical disease. Its diagnosis requires specific methods, and accurate information on its geographic distribution and global burden are lacking. We predicted prevalence, using Bayesian geostatistical modeling, and determined risk factors in northern Cambodia.

Methods

From February to June 2010, we performed a cross-sectional study among 2,396 participants from 60 villages in Preah Vihear Province, northern Cambodia. Two stool specimens per participant were examined using Koga agar plate culture and the Baermann method for detecting S. stercoralis infection. Environmental data was linked to parasitological and questionnaire data by location. Bayesian mixed logistic models were used to explore the spatial correlation of S. stercoralis infection risk. Bayesian Kriging was employed to predict risk at non-surveyed locations.

Principal Findings

Of the 2,396 participants, 44.7% were infected with S. stercoralis. Of 1,071 strongyloidiasis cases, 339 (31.6%) were among schoolchildren and 425 (39.7%) were found in individuals under 16 years. The incidence of S. stercoralis infection statistically increased with age. Infection among male participants was significantly higher than among females (OR: 1.7; 95% CI: 1.4–2.0; P<0.001). Participants who defecated in latrines were infected significantly less than those who did not (OR: 0.6; 95% CI: 0.4–0.8; P = 0.001). Strongyloidiasis cases would be reduced by 39% if all participants defecated in latrines. Incidence of S. stercoralis infections did not show a strong tendency toward spatial clustering in this province. The risk of infection significantly decreased with increasing rainfall and soil organic carbon content, and increased in areas with rice fields.

Conclusions/Significance

Prevalence of S. stercoralis in rural Cambodia is very high and school-aged children and adults over 45 years were the most at risk for infection. Lack of access to adequate treatment for chronic uncomplicated strongyloidiasis is an urgent issue in Cambodia. We would expect to see similar prevalence rates elsewhere in Southeast Asia and other tropical resource poor countries.     

Tumor necrosis factor α-induced adipose-related protein expression in experimental arthritis and in rheumatoid arthritis

Introduction

Broad-range rDNA PCR provides an alternative, cultivation-independent approach for identifying bacterial DNA in reactive and other form of arthritis. The aim of this study was to use broad-range rDNA PCR targeting the 16S rRNA gene in patients with reactive and other forms of arthritis and to screen for the presence of DNA from any given bacterial species in synovial fluid (SF) samples.

Methods

We examined the SF samples from a total of 27 patients consisting of patients with reactive arthritis (ReA) (n = 5), undifferentiated arthritis (UA) (n = 9), rheumatoid arthritis (n = 7), and osteoarthritis (n = 6) of which the latter two were used as controls. Using broad-range bacterial PCR amplifying a 1400 bp fragment from the 16S rRNA gene, we identified and sequenced at least 24 clones from each SF sample. To identify the corresponding bacteria, DNA sequences were compared to the EMBL (European Molecular Biology Laboratory) database.

Results

Bacterial DNA was identified in 20 of the 27 SF samples (74, 10%). Analysis of a large number of sequences revealed the presence of DNA from more than one single bacterial species in the SF of all patients studied. The nearly complete sequences of the 1400 bp were obtained for most of the detected species. DNA of bacterial species including Shigella species, Escherichia species, and other coli-form bacteria as well as opportunistic pathogens such as Stenotrophomonas maltophilia and Achromobacter xylosoxidans were shared in all arthritis patients. Among pathogens described to trigger ReA, DNA from Shigella sonnei was found in ReA and UA patients. We also detected DNA from rarely occurring human pathogens such as Aranicola species and Pantoea ananatis. We also found DNA from bacteria so far not described in human infections such as Bacillus niacini, Paenibacillus humicus, Diaphorobacter species and uncultured bacterium genera incertae sedis OP10.

Conclusions

Broad-range PCR followed by cloning and sequencing the entire 16S rDNA, allowed the identification of the bacterial DNA environment in the SF samples of arthritic patients. We found a wide spectrum of bacteria including those known to be involved in ReA and others not previously associated with arthritis.     

Strongyloides stercoralis infection and re-infection in a cohort of children in Cambodia

Information on Strongyloides stercoralis re-infection after ivermectin treatment is scarce in S. stercoralis endemic countries. In semi-rural Cambodia, we determined S. stercoralis infection and re-infection rates among schoolchildren, two years after ivermectin treatment (2 × 100 μg/kg PO, 24 h apart). The study was conducted among 484 children from four primary schools in semi-rural villages in Kandal province from 2009 to 2011, using Koga agar plate culture and the Baermann method on two stool samples per child. Complete data were available for 302 participants. We observed infections in 24.2% and 22.5% of the children at baseline and at follow-up, respectively. At baseline, 73 children were treated for S. stercoralis infection. At follow-up, one-third of those treated for S. stercoralis infection had been reinfected, while 19.6% of the 229 healthy children (at baseline) had been newly infected with S. stercoralis. Possession of shoes and defecation in toilet were negatively associated with S. stercoralis infection at follow-up. Infection and re-infection rates of S. stercoralis among schoolchildren are considerably high. However, 68.5% of infected children remained free of infection for at least two years. A large-scale cohort study is required to understand age-specific infection and re-infection dynamics in endemic countries.     

Occurrence of Strongyloides stercoralis in Yunnan Province, China, and comparison of diagnostic methods

Background

Strongyloides stercoralis is a neglected soil-transmitted helminth species, and there is a lack of parasitologic and epidemiologic data pertaining to this parasite in China and elsewhere. We studied the local occurrence of S. stercoralis in a village in Yunnan province, China, and comparatively assessed the performance of different diagnostic methods.

Methodology/Principal Findings

Multiple stool samples from a random population sample were subjected to the Kato-Katz method, an ether-concentration technique, the Koga agar plate method, and the Baermann technique. Among 180 participants who submitted at least 2 stool samples, we found a S. stercoralis prevalence of 11.7%. Males had a significantly higher prevalence than females (18.3% versus 6.1%, p = 0.011), and infections were absent in individuals <15 years of age. Infections were only detected by the Baermann (highest sensitivity) and the Koga agar plate method, but neither with the Kato-Katz nor an ether-concentration technique. The examination of 3 stool samples rather than a single one resulted in the detection of 62% and 100% more infections when employing the Koga agar plate and the Baermann technique, respectively. The use of a mathematical model revealed a ‘true’ S. stercoralis prevalence in the current setting of up to 16.3%.

Conclusions/Significance

We conclude that S. stercoralis is endemic in the southern part of Yunnan province and that differential diagnosis and integrated control of intestinal helminth infections needs more pointed emphasis in rural China.     

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.     

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.