Association between Toxoplasma gondii Infection and Nephrotic Syndrome Risk in Children: A Case-Control Study and Systematic Review.

Some evidence suggests toxoplasmosis as an etiology of nephrotic syndrome (NS) in children; however, no observational study evaluated this relationship. In a case-control study, we enrolled 35 children with NS and 37 healthy children. All participants were examined for anti-Toxoplasma immunoglobulin G and M (IgG and IgM) antibodies using enzyme-linked immunosorbent assay. We also systematically reviewed the literature to assess this relationship. Prevalence of anti-Toxoplasma IgG was 17.4% and 13.5% in cases and controls, respectively, indicating a non-significant association (adjusted odds ratio, 1.22, 95% confidence interval, 0.35-4.41). No subjects were seropositive for IgM. In a systematic review, we found that acute toxoplasmosis can induce NS in some children and anti-Toxoplasma treatment is effective in the remission of NS in these cases. In pediatrics with NS, acute toxoplasmosis should be considered as a neglected causative factor.

Toxoplasma infection and risk of epilepsy: A case-control study of incident patients.

We performed an age matched case-control study of incident epileptic patients to assess the relationship between Toxoplasma gondii seropositivity and epilepsy. Cases were 94 newly diagnosed patients (mean age, 36.7 ± 15.9) with unprovoked convulsive epilepsy of unknown etiology and controls were 88 healthy individuals (mean age, 37.5 ± 17.1) with no history of epilepsy or neurological disorders. Sera of all subjects were examined for anti-Toxoplasma IgG antibodies using commercially enzyme-linked immunoassays. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using univariate analysis and logistic regression, adjusted for potential confounders. The prevalence of anti-Toxoplasma IgG antibodies in epileptic patients (68.1%; 95%CI, 57.6-77.3%) was significantly higher than healthy controls (47.7%; 95%CI, 36.9-58.6%), indicating a significant relationship between Toxoplasma infection seropositivity and epilepsy (adjusted OR, 2.58; 95%CI, 1.16-5.72; P value < 0.05). The univariate analyses showed more than two-fold higher Toxoplasma seropositivity in patients with focal (OR, 2.31; 95%CI, 0.94-5.67) and generalized (OR, 2.35; 95%CI, 1.215-4.57) seizures versus healthy controls. Our findings support hypothesis that Toxoplasma infection/exposure may play an important role in development of epilepsy. Preventive measures to control of Toxoplasma infection especially in north of Iran and early treatment might be effective to reduce the occurrence of epilepsy in this region.

Case-Control Study to Assess the Association between Epilepsy and Toxocara Infection/Exposure.

Although causes and etiology of epilepsy are mostly obscure, some zoonotic parasites, such as Toxocara species, have been proposed as a risk factor for this disease. Here, we conducted an age-matched case-control study to evaluate whether there is an association between epilepsy and the presence of serum antibodies to Toxocara in incident cases. We included 94 idiopathic epileptic patients as cases, and-from the same geographical region-88 people with no own history of epilepsy or neurological disease as control subjects. Epilepsy was confirmed by a physician using the International League Against Epilepsy (ILAE) definition. All participants were screened for the anti-Toxocara IgG serum antibody by enzyme-linked immunosorbent assay (ELISA). Univariate and mutltivariate statistical analyses were applied to calculate the crude and adjusted odds ratios (OR) and 95% confidence intervals (CIs). Anti-Toxocara serum antibody was detected in 37 epileptic patients and in 23 control subjects, giving respective seroprevalences of 39.3% (95% CI, 29.4-49.9%) and 26.1% (95% CI, 17.3-36.5%), respectively. Adjusted multivariate logistic regression analysis estimated an OR of 2.38 (95% CI, 1.25-4.63), indicating a significant association between epilepsy and Toxocara seropositivity. There was also a significant association between seropositivity to Toxocara and partial (OR, 2.60; 95% CI, 1.14-6.04) or generalized (OR, 2.17; 95% CI, 1.09-4.40%) seizures. Findings from the present study of incident epileptic cases support previous studies proposing that Toxocara infection/exposure is a risk factor for epilepsy. However, further well-designed population-based surveys and mechanistic/experimental studies in animal models are required to better understand the reason(s) for this association.

The association between seropositivity to human toxocariasis and childhood asthma in northern Iran: a case-control study.

BACKGROUND: Besides the well-known risk factors, Toxocara infection is thought to play a significant etiological role in the development of childhood asthma. To further explore this association, the prevalence of Toxocara infection in sera of asthmatic children and healthy controls in northern Iran was investigated. METHODS: In this case-control study, cases were 145 physician-confirmed asthmatic children diagnosed according to the Global Initiative for Asthma (GINA) guidelines. Controls were 115 age-sex-residence-matched children who did not have physician-diagnosed asthma. The presence of anti-Toxocara immunoglobulin G (IgG) was tested using enzyme-linked immunosorbent assay. Univariate and multivariate logistic regression methods were used for case-control comparisons. RESULTS: Seropositivity rate was 4.1% (95% CI, 3.4-4.7%) in asthmatic children and 0.86% (95% CI, 0.71-1.0%) in controls, suggesting a strong association (P-value < 0.02). Moreover, Toxocara infection was not significantly more prevalent (P-value = 0.12) in children with moderate sustainable asthma (9.3%, 3/32) than in children with mild sustainable asthma (2.3%, 3/113). Mean total immunoglobulin E (IgE) level was significantly higher in Toxocara-infected children (222.3 ± 367.1) than in non-infected children (143.19 ± 218.05) in the case group (P-value < 0.05). CONCLUSIONS: Our findings indicated that Toxocara infection can play an important role in childhood asthma. Further experimental and epidemiological studies are needed to clarify this hypothesis.

The association between seropositivity to human toxocariasis and childhood asthma in northern Iran: a case-control study

BACKGROUND: Besides the well-known risk factors, Toxocara infection is thought to play a signif­icant etiological role in the development of childhood asthma. To further explore this associa­tion, the prevalence of Toxocara infection in sera of asthmatic children and healthy controls in northern Iran was investigated. METHODS: In this case-control study, cases were 145 physician-confirmed asthmatic children diag­nosed according to the Global Initiative for Asthma (GINA) guidelines. Controls were 115 age- sex-residence-matched children who did not have physician-diagnosed asthma. The presence of anti-Toxocara immunoglobulin G (IgG) was tested using enzyme-linked immunosorbent assay. Univariate and multivariate logistic regression methods were used for case-control comparisons. RESULTS: Seropositivity rate was 4.1% (95% CI, 3.4-4.7%) in asthmatic children and 0.86% (95% CI, 0.71-1.0%) in controls, suggesting a strong association (P-value < 0.02). Moreover, Toxocara infection was not significantly more prevalent (P-value = 0.12) in children with moderate sus­tainable asthma (9.3%, 3/32) than in children with mild sustainable asthma (2.3%, 3/113). Mean total immunoglobulin E (IgE) level was significantly higher in Toxocara-infected children (222.3 ± 367.1) than in non-infected children (143.19 ± 218.05) in the case group (P-value < 0.05). CONCLUSIONS: Our findings indicated that Toxocara infection can play an important role in child­hood asthma. Further experimental and epidemiological studies are needed to clarify this hypothesis

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Functional Deimmunization of Interferon Beta-1b by Identifying and Silencing Human T Cells Epitopes.

Interferonbeta-1b (IFNß-1b) developed as therapeutic protein for the treatment of multiple sclerosis (MS). Studies have been shown that Long-term usage of this protein can lead to the development of anti-drug antibodies (ADAs) and this phenomenon cause total loss or reduced efficacy of IFNß-1b. The aim of this study was to predict and silence IFNß-1b T-cells epitopes by in silico methods and genetic engineering. Based on bioinformatics studies we identified optimal sets of conservative point mutations for eliminating T-cells epitopes in IFNß-1b protein. Four synthetic genes with desirable mutation constructed and PET26b+ was used as an expression vector in E. coli. The expression of this proteins confirmed by SDS-PAGE and Western blotting, consequently, IFNß-1b proteins was purified by His-tag chromatography. To determined activity of mutants' variants anti-proliferative and anti-viral activity compared to wild form was evaluated using MTT assay in A549 and Vero cells lines respectively. Also the immunogenicity of mutant proteins compared with Betaseron measured in BALB/c mice. The in vitro bioactivity analysis demonstrated that functional activities of all mutant proteins were maintained and is the same as biological activity of Betaseron. Pharmacokinetic studies suggest that, in engineered proteins that contain substitution of Histidine to Glutamic Acid at position 131 (mut 2 and mut 1+2) antibodies response reduced by about 50%, as compared to that for Betaseron. Computational analysis expedites identification and prediction of epitopes in therapeutic protein, therefore, we used immunoinformatic tools for modification of dominant T-cell epitope in IFNß-1b protein, and this strategy has capacity to create proteins which have naturally reduced immunogenicity.

Exposure to Ascaris lumbricoides infection and risk of childhood asthma in north of Iran.

BACKGROUND: Asthma and Ascaris lumbricoides infection are common health issues affecting 250 and 700 million people worldwide, respectively. The relationship between ascariasis and asthma is a matter of substantial interest and research. METHODS: We performed a case-control study to evaluate whether the exposure to Ascaris infection is associated with asthma in children. We also assessed potential risk factors for Ascaris infection and asthma in study area. We enrolled 145 asthmatic children and 115 healthy controls. The Global Initiative for Asthma guideline was used to evaluate asthma symptoms and severity in study participants. Ascaris infection was assessed by the presence of anti-Ascaris IgG ≥ 11 IU/mL measured by enzyme-linked immunosorbent assay. RESULTS: We have found a significant relationship between exposure to Ascaris and asthma (odds ratio, 2.92; 95% CI 1.04-8.18; P value = 0.034), and this relationship remained significant after adjustment for covariates (adjusted OR, 3.36; 95% CI 1.04-13%; P value = 0.047). Ascaris infection was more frequent in children with mild sustainable asthma (13.2%; 15/113) than in children with moderate sustainable asthma (6.2%, 2/32), although there was a non-significant difference between these groups (OR, 2.3; 95% CI 0.5-10.1; P value = 0.35). Based on results of a multi-regression analysis, contact with soil (OR, 6.7; 95% CI 1.9-23.5), and drinking unsafe water (OR, 4.2; 95% CI 1.2-14.2) were significant risk factors for Ascaris infection in the study area. CONCLUSION: Results of this study suggest that A. lumbricoides infection might affect susceptibility to asthma in children. These results could be useful in prevention, early diagnosis and management of childhood asthma.

Seroepidemiology, modifiable risk factors and clinical symptoms of Toxocara spp. infection in northern Iran.

Toxocariasis is one of the most important and widespread neglected tropical infectious diseases. We designed a cross-sectional study to assess the seroepidemiological aspects of toxocariasis among the general population in northern Iran. A total of 630 rural subjects were enrolled to participate in the study. The presence of anti-Toxocara immunoglobulin G (IgG) was tested using a commercially available enzyme-linked immunosorbent assay. A structured questionnaire was also used to evaluate the potential risk factors and related clinical signs/symptoms. The presence of anti-Toxocara IgG antibodies was detected in 148 of the 630 rural subjects (23.5% [95% confidence interval {CI} 21.8 to 25.1]). By multivariate analysis, age (odds ratio [OR] 2.89 [95% CI 1 to -8.3], p=0.04), eating improperly washed vegetables (OR 4.05 [95% CI 2.47 to 6.64], p<0.001), contact with dogs (OR 3.31 [95% CI 2.13 to 5.12], p<0.001) and exposure to soil (OR 3.56 [95% CI 2.13 to 5.13], p<0.001) were significantly associated with the seroprevalence of Toxocara. The clinical study also demonstrated that the seroprevalence of Toxocara infection was significantly associated with asthma (OR 3.78 [95% CI 1.63 to 8.75], p<0.001) and ophthalmic disorder (OR 1.83 [95% CI 1.04 to 3.21], p=0.034). The findings proved that residents of rural communities in tropical regions may be heavily exposed to Toxocara spp. We highly recommend more investigations in high-risk groups.

Comparison of three cost effective staining methods for detection of Pneumocystis jirovecii.

Pneumocystis pneumonia due to Pneumocystis jirovecii infection is an emerging health problem not only for HIV-infected patients but also for other immunocompromised patients in many countries. We compared Gomori methenamine silver (GMS), Toluidine Blue O (TBO) and Giemsa staining methods using standard procedures. The sensitivity and specificity of GMS were 100 %. The sensitivity and specificity of TBO were 96 and 100 %, respectively. The sensitivity and specificity of Giemsa stain were 84 and 90 %, respectively. Only GMS had positive and negative predictive values of 100 % while PPV and NPV for TBO were 100 and 90.9 %, and for Giemsa stain were 95.4 and 69.2 %, respectively. Therefore, our results suggest that if TBO or Geimsa stains are used as the primary staining methods in a clinical laboratory, then confirmation with a GMS staining method should be performed to increase the sensitivity and specificity of the final test result.

SEROPREVALENCE AND RISK FACTORS ASSOCIATED WITH Toxoplasma gondii INFECTION AMONG RURAL COMMUNITIES IN NORTHERN IRAN.

Toxoplasmosis is the fourth most common cause of hospitalization and the second cause of death due to food-borne infections. We conducted a cross-sectional study to determine the prevalence, disease awareness and risk factors associated with toxoplasmosis among rural communities in Northern Iran. Data were obtained from serological testing and from participant's questionnaires and were analyzed using a logistic regression. Of the 630 participants, 465 (73.8%), and 12 (1.9%) had IgG and both IgG and IgM anti-Toxoplasma gondii antibodies, respectively. In the logistic regression analysis, T. gondii seropositivity was associated with the following factors: age, occupation, consumption of undercooked meat, and of unwashed raw vegetables or fruits (p < 0.001). Our study showed a high prevalence of T. gondii infection in the general population of Northern Iran. A health program is needed to increase the public awareness of toxoplasmosis, and its associated risk factors.

Contamination of commonly consumed raw vegetables with soil transmitted helminth eggs in Mazandaran province, northern Iran.

Soil-transmitted helminth (STH) infections are responsible for significant burden of morbidity and mortality worldwide. Consumption of raw vegetables without proper washing is one of the major routes of such infections. We evaluate the prevalence of STH contamination in commonly used vegetables in Mazandaran province, northern Iran. A total of 772 fresh raw vegetables were obtained from retail markets. Each sample was divided into two groups. One group was used as the unwashed sample and the second group was washed with standard washing procedures. Then, samples were examined for helminth eggs by using standard methods. Data analysis was performed using SPSS20. The overall prevalence of STHs was 14.89% (115/772). The rate of STH contamination was significantly higher in warm seasons (20.5%, 79/386) than in cold seasons (9.32%, 36/386) among the unwashed vegetables (OR=2.50; CI 95%=1.64-3.8; P<0.001). No parasites were observed in standard washed samples (OR=271.40; CI 95%=16.84-4373.64; P<0.001). Prevalence of STH contamination was significantly higher in leafy vegetables than root vegetables (OR=1.67; CI 95%=1.09-2.55; P<0.05). The prevalence of STHs species in all the vegetables were as follows: Ascaris lumbricoides (3.36%), Trichuris trichiura (2.2%), hookworms (2.9%), Toxocara spp. (1.68%), Trichostrongylus spp. (1.55), Taenia sp. (0.9%) and Hymenolepis nana (2.2%). The results of the present study emphasized that vegetables are potential risk factor for transmission of helminth infection to human in northern Iran. It is necessary that health authorities trained the consumers to proper and standard washing of vegetables before consumption.

Association of HLA class II (DRB1, DQA1, DQB1) alleles and haplotypes with myasthenia gravis and its subgroups in the Iranian population.

Heterogenic pattern of HLA associations with myasthenia gravis (MG) among different ethnicities and also among different MG subgroups has been the subject of debate in large series of many studies. One hundred and sixty Iranian MG patients were investigated for HLA class II (DRB1, DQA1, DQB1) associations compared to two hundred healthy controls from the same ethnic population. DRB1*11 DQA1*0501 DQB1*0301 haplotype was found to be protective for total (ocular plus generalized) MG (Pc=0.005, OR=0.49) and generalized MG (Pc=0.008, OR=0.49). DRB1*04 DQA1*0301 DQB1*0302 haplotype (Pc=0.03, OR=2.25) was predisposing for anti-acetylcholine receptor (AChR) antibody-positive MG, while DRB1*16 DQA1*0102 DQB1*05 (Pc=0.013, OR=4.28) was predisposing for anti-muscle specific tyrosine kinase (MuSK) antibody-positive MG. There was also a trend of positive association for DRB1*14 DQA1*0104 DQB1*05 haplotype with MuSK-positive MG (Pc=0.054, OR=3.97). Among other MG subgroups and with less significance, DRB1*0101 DQA1*0101 DQB1*05 haplotype (P=0.016, OR=3.68) had positive association with pure ocular MG, and DRB1*03 DQA1*0501 DQB1*0201 haplotype (P=0.024) had negative association with thymomatous MG. This study highlights the importance of appropriate MG subgrouping according to clinical and paraclinical characteristics in HLA studies among MG patients.