Human inherited CCR2 deficiency underlies progressive polycystic lung disease.

We describe a human lung disease caused by autosomal recessive, complete deficiency of the monocyte chemokine receptor C-C motif chemokine receptor 2 (CCR2). Nine children from five independent kindreds have pulmonary alveolar proteinosis (PAP), progressive polycystic lung disease, and recurrent infections, including bacillus Calmette Guérin (BCG) disease. The CCR2 variants are homozygous in six patients and compound heterozygous in three, and all are loss-of-expression and loss-of-function. They abolish CCR2-agonist chemokine C-C motif ligand 2 (CCL-2)-stimulated Ca2+ signaling in and migration of monocytic cells. All patients have high blood CCL-2 levels, providing a diagnostic test for screening children with unexplained lung or mycobacterial disease. Blood myeloid and lymphoid subsets and interferon (IFN)-γ- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-mediated immunity are unaffected. CCR2-deficient monocytes and alveolar macrophage-like cells have normal gene expression profiles and functions. By contrast, alveolar macrophage counts are about half. Human complete CCR2 deficiency is a genetic etiology of PAP, polycystic lung disease, and recurrent infections caused by impaired CCL2-dependent monocyte migration to the lungs and infected tissues.

Vitamin D in respiratory viral infections: a key immune modulator?

Respiratory viral infections are common respiratory diseases. Influenza viruses, RSV and SARS-COV2 have the potential to cause severe respiratory infections. Numerous studies have shown that unregulated immune response to these viruses can cause excessive inflammation and tissue damage. Therefore, regulating the antiviral immune response in the respiratory tract is of importance. In this regard, recent years studies have emphasized the importance of vitamin D in respiratory viral infections. Although, the most well-known role of vitamin D is to regulate the metabolism of phosphorus and calcium, it has been shown that this vitamin has other important functions. One of these functions is immune regulation. Vitamin D can regulate the antiviral immune response in the respiratory tract in order to provide an effective defense against respiratory viral infections and prevention from excessive inflammatory response and tissue damage. In addition, this vitamin has preventive effects against respiratory viral infections. Some studies during the COVID-19 pandemic have shown that vitamin D deficiency may be associated with a higher risk of mortality and sever disease in patients with COVID-19. Since, more attention has recently been focused on vitamin D. In this article, after a brief overview of the antiviral immune response in the respiratory system, we will review the role of vitamin D in regulating the antiviral immune response comprehensively. Then we will discuss the importance of this vitamin in influenza, RSV, and COVID-19.

COVID-19 and renal involvement in children: a retrospective study.

Background: The New coronavirus (SARS COV-2) can cause acute respiratory disease and also multiorgan dysfunction. There is insufficient data about kidney involvement in children. So, this study was done on children with COVID-19 to evaluate nephrological involvement. Methods: All children with confirmed or suspected COVID-19 who were admitted in Children Hospital .were enrolled. They were admitted in hospital from March 2020 to July 2020. Serum Blood Urea Nitrogen (BUN), creatinine, sodium, potassium, calcium and urinalysis were evaluated. Also, glomerular filtration rate (GFR) was calculated by Schertz's formula. All patients were evaluated by chest x-ray and/or computerized tomography scanning (CTS). The data were analyzed by SPSS software and P value less than 0.05 was determined as significant. Results: Forty-seven children with confirmed or suspected COVID-19 were enrolled to this study. At admission, 23.4% and 27.7% of children with COVID-19 infection had abnormal increase in serum BUN and creatinine, respectively. Also 78.8% and 25.5% of children had GFR less than 90 and 60 ml/min /1.732, respectively. Additionally, 13/47 (27.7%) of children had abnormal urine analysis (microscopic hematuria and/or proteinuria). There wasn't a significant relationship between pulmonary lesions and abnormal reduction of GFR (P<0/05). Conclusion: In the study, the risk of AKI (acute kidney injury) and decrease of GFR and also abnormal urinalysis is high in children with COVID-19. So, more attention for detection of kidney involvement is necessary and more conservative management for prevention of AKI and decrease of GFR are recommended.

Epidemiology, Sociodemographic Factors and Comorbidity for Allergic Rhinitis, Asthma, and Rhinosinusitis Among 15 to 65-year-Old Iranian Patients.

Background: It is well established that upper and lower airways are often clumped together when diagnosing and treating a disease. This study was designed to determine the prevalence of upper and lower airway diseases and to assess the effect of sociodemographic factors on the prevalence and the comorbidity of these disorders. Methods: This cross-sectional population-based study included patients with ages ranging between 15 to 65 years, who were referred to allergy outpatient clinics in various provinces of Iran from April to September 2020. A modified global Allergy and Asthma European Network (GA2LEN) screening questionnaire was filled out by local allergists of the 12 selected provinces in Iran. Information about the patients and sociodemographic factors was also recorded. Statistical analysis was done by univariate statistical analyses and multiple logistic regressions in SPSS software Version 26. Results: Out of 4988 recruited patients, 1078 (21.6%) had the symptoms of allergic rhinitis (AR) and 285 (5.7%) met the criteria of asthma. The prevalence of acute rhinosinusitis (ARS) and chronic rhinosinusitis (CRS) was 21.6 % and 22%, respectively. The highest prevalence of AR and ARS was in Tehran with the arateof of 33.9% each. Asthma was more prevalent in Khuzestan (14.2%) and CRS in Baluchestan (57.5%). Our analysis showed that the patients with asthma were most likely to have other allergic diseases as well-CRS (OR = 4.8; 95% CI, 2.02- 5.82), AR (OR= 2.5, 95% CI, 2.10-3), ARS (OR = 1.8; 95% CI, 2.10-3), followed by eczema (OR = 1.4; 95% CI, 1.13-1.67).We found that those individuals with CRS were most likely to have painkiller hypersensitivity (OR= 2.1; 95% CI, 1.21-3.83). Furthermore, smoking has been found more than 1.5 folds in patients with ARS. After adjusting variables, there was no correlation between education, occupation, and ethnicity with the studied diseases. Conclusion: Rhinosinusitis is a common condition among Iranian patients. This study confirmed that inflammation of the upper and lower airways can occur simultaneously. Gender, education, occupation, and ethnicity were found to be irrelevant in the development of either AR, asthma, ARS, or CRS.

Novel Variants of DOCK8 Deficiency in a Case Series of Iranian Patients.

BACKGROUND: Dedicator of Cytokinesis 8 (DOCK8) deficiency, the most frequent cause of autosomal recessive hyper immunoglobulin (Ig)E syndrome, is a rare combined immunodeficiency. OBJECTIVE: In this study, we report seven patients, with consanguineous parents, with five novel variants within the DOCK8 gene. METHODS: For genetic analysis, we performed Whole Exome Sequencing (WES) or targeted sequencing by means of Next-generation sequencing (NGS) for some of the patients. For others, Sanger sequencing, Fluorescence-activated cell sorting (FACS), or polymerase chain reaction (PCR) were used. RESULTS: We report five novel variants within the DOCK8 gene: three deletions (deletion of exons 4-12, 24-30, and 22-27), one frameshift (LRG_196:g.189315dup;p.(Leu1052Profs*7)), and a splice region variant (LRG_196t1:c.741+5G>T). Patients presented with skin lesions, food allergy, candidiasis, otitis, recurrent respiratory infections, short stature, aortic aneurism, gynecomastia, and coarse facial features. Patients had leukocytosis, eosinophilia, lymphopenia, and monocytosis, elevated IgE, IgG, IgA, reduced IgM and IgA levels. Patients had a low percentage of CD3+ and CD4+ cells and a high percentage of CD19+, CD27+CD19+, and recent thymic emigrants T cells. The percentage of natural killer cells was increased in one of the patients while it was decreased in another patient. One patient died due to disseminated intravascular coagulation after hematopoietic stem cell transplantation. CONCLUSION: We reported novel variants within the DOCK8 gene and highlighted the risk of aneurysms in these patients, which have been rarely reported in these patients.

Genetic Study of Hereditary Angioedema Type I and Type II (First Report from Iranian Patients: Describing Three New Mutations).

BACKGROUND: Hereditary Angioedema (HAE) is a rare autosomal dominant immunodeficiency disease with mutation in C1 inhibitor gene (SERPING1) which deficient and dysfunction of C1-INH protein result in HAE type I or type II, respectively. The present study aimed to define the genetic spectrum of HAE type I and type II among Iranian patients. METHODS: Thirty-four patients with clinical phenotype of recurrent edematous attacks in face, upper and lower limbs, hands, and upper airway entered the study. Mutations in SERPING1 were analyzed using PCR and Sanger Sequencing. In addition, Multiplex Ligation-dependent Probe Amplification (MLPA) was performed to discover large deletions or duplications in negative screening samples by Sanger. RESULTS: Twenty-three patients were diagnosed with HAE type I and 11 with HAE type II. Fourteen distinctive pathogenic variations including five frameshift (p.G217Vfs*, p.V454Gfs*18, p.S422Lfs*9, p.S36Ffs*21, p.L243Cfs*9), seven missense (p.A2V, p.G493R, p.V147E, p.G143R, p.L481P, p.P399H, p.R466C), one nonsense (p.R494*), and one splicing defect (C.51 + 2 T˃C), which three of these mutations were identified novel. However, no mutation was found in seven patients by Sanger sequencing and MLPA. CONCLUSION: Final diagnosis with mutation analysis of HAE after clinical evaluation and assessment of C1INH level and function can prevent potential risks and life-threatening manifestations of the disorder. In addition, genetic diagnosis can play a significant role in facilitating early diagnosis, pre-symptomatic diagnosis, early diagnosis of children, asymptomatic cases, and those patients who have the borderline biochemical results of C1-INH deficiency and/or C4.

Zinc and Respiratory Viral Infections: Important Trace Element in Anti-viral Response and Immune Regulation.

Influenza viruses, respiratory syncytial virus (RSV), and SARS-COV2 are among the most dangerous respiratory viruses. Zinc is one of the essential micronutrients and is very important in the immune system. The aim of this narrative review is to review the most interesting findings about the importance of zinc in the anti-viral immune response in the respiratory tract and defense against influenza, RSV, and SARS-COV2 infections. The most interesting findings on the role of zinc in regulating immunity in the respiratory tract and the relationship between zinc and acute respiratory distress syndrome (ARDS) are reviewed, as well. Besides, current findings regarding the relationship between zinc and the effectiveness of respiratory viruses' vaccines are reviewed. The results of reviewed studies have shown that zinc and some zinc-dependent proteins are involved in anti-viral defense and immune regulation in the respiratory tract. It seems that zinc can reduce the viral titer following influenza infection. Zinc may reduce RSV burden in the lungs. Zinc can be effective in reducing the duration of viral pneumonia symptoms. Zinc may enhance the effectiveness of hydroxychloroquine in reducing mortality rate in COVID-19 patients. Besides, zinc has a positive effect in preventing ARDS and ventilator-induced lung damage. The relationship between zinc levels and the effectiveness of respiratory viruses' vaccines, especially influenza vaccines, is still unclear, and the findings are somewhat contradictory. In conclusion, zinc has anti-viral properties and is important in defending against respiratory viral infections and regulating the immune response in the respiratory tract.

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.

BCGitis as the primary manifestation of chronic granulomatous disease.

Patients with primary immunodeficiency disease (PID) are not only vulnerable to mycobacterial disease, but are also more likely to develop adverse events following BCG vaccination. These events can range from regional disease (BCGitis) to disseminated disease (BCGosis). Chronic granulomatous disease (CGD), which is characterized by impaired leukocyte phagocytic function, is one of the many inherited PIDs that increase the body's susceptibility to recurrent bacterial and fungal infections. Here, we report a 6-year-old boy with no significant past medical history who presented with progressive lymphadenopathy six years after BCG vaccination. He was later diagnosed with CGD on further evaluation.

Exposure to Toxocara spp. and Ascaris lumbricoides infections and risk of allergic rhinitis in children.

BACKGROUND: Substantial experimental studies suggest a role for helminthes infections in the pathogenesis of allergies, but epidemiologic data have been inconsistent. Unlike to asthma, the association between helminthes infection and allergic rhinitis (AR) has been poorly studied. Therefore, we sought to evaluate the association between exposure to Ascaris and Toxocara infections and AR. METHODS: We did an age- and gender-matched case-control study of 81 children with physician-confirmed AR and 101 control subjects in a referral hospital for pediatric diseases in northern Iran. Exposure to Ascaris and Toxocara infections was evaluated by anti-A. lumbricoides- and anti-Toxocara- IgG antibodies using a commercial enzyme-linked immunosorbent assay. Associations were determined using multivariate logistic regression. RESULTS: Ascaris seropositivity was higher in children with rhinitis than in controls (12.34 vs. 3.96%). Ascaris seropositivity was positively associated with AR in univariate analysis (OR, 3.42; 95% CI 1.03-11.3; P value = 0.035), but this association was not significant after adjustment for potential confounders (OR, 1.85; 95% CI 0.42-8.18). Also Toxocara seropositivity was higher in children with AR than in healthy subjects (3.7% vs. 0.99), indicating non-significant association with AR in both univariate (OR, 3.84; 95% CI 0.39-37.7) and multivariate analyses (OR, 0.8; 95% CI 0.04-15.44). CONCLUSION: Our results revealed that AR is not associated with seropositivity to Ascaris and Toxocara infections in general; however, a higher seropositivity rate was found for both parasites in children with AR. More studies with longitudinal design and larger sample size are needed to elucidate this association.

CRISPR/Cas9 gene editing: A new therapeutic approach in the treatment of infection and autoimmunity.

CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein9) may be viewed as an adaptive bacterial immune system. When a virus infects a bacterium, a fragment of the virus genome is inserted into the CRISPR sequence of the bacterial genome as a memory. When the bacterium becomes infected again with the same virus, an RNA molecule that is a transcript of the memory sequence, directs Cas9, an endonuclease, to the complementary region of the virus genome, and Cas9 disables the virus by a double-strand break. In recent years, studies have shown that by designing synthetic RNA molecules and delivering them along with Cas9 into eukaryotic cells, different regions of the cell's genome can be targeted and manipulated. These findings have drawn much attention to this new technology and it has been shown that CRISPR/Cas9 gene editing can be used to treat some human diseases. These include infectious diseases and autoimmune diseases. In this review article, in addition to a brief overview of the biology of the CRISPR/Cas9 system, we collected the most recent findings on the applications of CRISPR/Cas9 technology for better investigation of the pathogenesis and treatment of viral infections (human immunodeficiency virus infection, hepatitis virus infections, and onco-virus infections), non-viral infections (parasitic, fungal, and bacterial infections), and autoimmune diseases.

Association of serum 25-OH vitamin D3 with serum IgE and the Pediatric Asthma Severity Score in patients with pediatric asthma.

Background: Pediatric asthma is a prevalent disease and has a significant immunologic and inflammatory nature. In recent years, the role of vitamin D3 in immunologic processes has been studied, and many aspects of this role have been clarified in some human diseases. Objective: The aim of this study was to evaluate the relationship among the vitamin D3 status, Pediatric Asthma Severity Score (PASS), and inflammatory indicators of pediatric asthma. Methods: Among all of the pediatric patients with asthma and with asthma exacerbation, 100 patients were randomly enrolled in the study and subdivided into three groups according to serum levels of 25-OH vitamin D3. The control group consisted of 100 sex- and age-matched healthy subjects. Asthma exacerbation severity was evaluated based on the PASS before starting the medical care. The count of the white blood cells, eosinophil count, and serum levels of total immunoglobulin E (IgE) plus 25-OH vitamin D3 were measured in all the subjects. The obtained data were then compared via proper statistical tests. A p value of <0.05 was considered as statistically significant. Results: The median level of serum IgE was increased in patients with vitamin D3 deficiency compared with other groups. There was a significant inverse correlation between serum levels of 25-OH vitamin D3 and IgE in pediatric patients with asthma (r = -0.483, p = 0.001). Furthermore, the serum levels of 25-OH vitamin D3 also significantly inversely correlated with the PASS (r = -0.285, p = 0.004). Conclusion: Vitamin D3 deficiency is associated with exacerbation severity and serum IgE levels in patients with pediatric asthma; hence, it can have an important role in pediatric asthma pathogenesis, possibly through IgE.

IgE level in newborn umbilical cord and its relationship with some maternal factors.

BACKGROUND AND OBJECTIVES: Allergic diseases are among major pediatric issues as they are highly prevalent and chronic. Therefore, identification of factors contributing to allergic disease could play a significant role in prevention of these conditions. This study aimed at investigating the IgE level in newborn's umbilical cord blood and its relationship with some maternal factors. METHODS: A cross-sectional study was conducted in 101 mothers and their newborns in Babol, Iran 2016. The samples were selected using non-probability convenience sampling. Information including newborn sex, gravidity, history of allergy before and during pregnancy (asthma, allergic rhinitis, eczema, hives, food allergy, and drug allergy), family history of allergy among mothers, history of exposure to secondhand smoke and pets, and delivery techniques was recorded. The IgE levels in newborn umbilical cord blood and maternal serum were measured using an IgE kit and ELISA technique. RESULTS: The newborns included 53 females (52.5%) and 29 mothers had vaginal birth (28.7%). History of exposure to secondhand smoke was found in 15 samples (14.9%), and 18 participants reported exposure to pets (17.8%). The median IgE levels in newborns and their mothers were 0.41 and 98.6, respectively. In general, IgE level in all newborns was within the normal range, but, it was higher than normal in 15 mothers (14.9%). The IgE level was significantly higher in male newborns than that of the female newborns (p = 0.011). There were no significant differences in the IgE levels of mothers and their newborns on the basis of delivery technique and history of exposure to pets (p > 0.05). CONCLUSION: In this study, the IgE level in all newborns was within the normal range, and sex was found to be an effective factor in IgE levels.

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.

Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort.

BACKGROUND: Predominantly antibody deficiencies (PADs) are the most common primary immunodeficiencies, characterized by hypogammaglobulinemia and inability to generate effective antibody responses. OBJECTIVE: We intended to report most common monogenic PADs and to investigate how patients with PAD who were primarily diagnosed as suffering from agammaglobulinemia, hyper-IgM (HIgM) syndrome, and common variable immunodeficiency (CVID) have different clinical and immunological findings. METHODS: Stepwise next-generation sequencing and Sanger sequencing were performed for confirmation of the mutations in the patients clinically diagnosed as suffering from agammaglobulinemia, HIgM syndrome, and CVID. RESULTS: Among 550 registered patients, the predominant genetic defects associated with agammaglobulinemia (48 Bruton's tyrosine kinase [BTK] and 6 µ heavy chain deficiencies), HIgM syndrome (21 CD40 ligand and 7 activation-induced cytidine deaminase deficiencies), and CVID (17 lipopolysaccharides-responsive beige-like anchor deficiency and 12 atypical Immunodeficiency, Centromeric instability, and Facial dysmorphism syndromes) were identified. Clinical disease severity was significantly higher in patients with µ heavy chain and CD40 ligand mutations compared with patients with BTK (P = .003) and activation-induced cytidine deaminase (P = .009) mutations. Paralysis following live polio vaccination was considerably higher in patients with µ heavy chain deficiency compared with BTK deficiency (P < .001). We found a genotype-phenotype correlation among patients with BTK mutations regarding clinical manifestation of meningitis and chronic diarrhea. Surprisingly, we noticed that first presentations in most patients with Immunodeficiency, Centromeric instability, and Facial dysmorphism were respiratory complications (P = .008), whereas first presentations in patients with lipopolysaccharides-responsive beige-like anchor deficiency were nonrespiratory complications (P = .008). CONCLUSIONS: This study highlights similarities and differences in the clinical and genetic spectrum of the most common PAD-associated gene defects. This comprehensive comparison will facilitate clinical decision making, and improve prognosis and targeted treatment.

Fourth Update on the Iranian National Registry of Primary Immunodeficiencies: Integration of Molecular Diagnosis.

BACKGROUND: The number of inherited diseases and the spectrum of clinical manifestations of primary immunodeficiency disorders (PIDs) are ever-expanding. Molecular diagnosis using genomic approaches should be performed for all PID patients since it provides a resource to improve the management and to estimate the prognosis of patients with these rare immune disorders. METHOD: The current update of Iranian PID registry (IPIDR) contains the clinical phenotype of newly registered patients during last 5 years (2013-2018) and the result of molecular diagnosis in patients enrolled for targeted and next-generation sequencing. RESULTS: Considering the newly diagnosed patients (n = 1395), the total number of registered PID patients reached 3056 (1852 male and 1204 female) from 31 medical centers. The predominantly antibody deficiency was the most common subcategory of PID (29.5%). The putative causative genetic defect was identified in 1014 patients (33.1%) and an autosomal recessive pattern was found in 79.3% of these patients. Among the genetically different categories of PID patients, the diagnostic rate was highest in defects in immune dysregulation and lowest in predominantly antibody deficiencies and mutations in the MEFV gene were the most frequent genetic disorder in our cohort. CONCLUSIONS: During a 20-year registration of Iranian PID patients, significant changes have been observed by increasing the awareness of the medical community, national PID network establishment, improving therapeutic facilities, and recently by inclusion of the molecular diagnosis. The current collective study of PID phenotypes and genotypes provides a major source for ethnic surveillance, newborn screening, and genetic consultation for prenatal and preimplantation genetic diagnosis.

The relationship between Toxocara species seropositivity and allergic skin disorders: a systematic review and meta-analysis.

We performed a systematic review and meta-analysis on observational studies to evaluate the possible associations between Toxocara species seropositivity and allergic skin disorders (ASDs). We searched the MEDLINE, ScienceDirect, Scopus, Web of Science and Google Scholar databases to 15 May 2018 to identify the relevant studies. We used a random effects meta-analysis model to generate the pooled odds ratio (OR) and 95% confidence intervals (CIs). Fifteen studies, including eight studies with a case-control design (735 patients and 1342 controls) and seven studies with a cross-sectional design (a total of 4804 participants, 1302 individuals with ASDs and 3502 without ASDs), were included in the meta-analysis. We found an increased risk for ASDs in individuals with Toxocara seropositivity (OR 1.75 [95% CI 1.16 to 2.64]). Subanalysis showed that Toxocara seropositivity was significantly associated with urticaria (OR 2.97 [95% CI 1.53 to 5.76]), however, it was not significantly associated with atopy (OR 1.08 [95% CI 0.55 to 2.15]) and eczema (OR 1.62 [95% CI 0.95 to 2.78]). Moreover, the pooled ORs were 2.34 (95% CI 1.32 to 4.15) and 1.27 (95% CI 0.69 to 2.35) for case-control and cross-sectional studies, respectively. The results of our study support hypotheses regarding the existence of a positive relationship between Toxocara infection and allergic disorders, although this association should be further investigated by longitudinal and mechanism studies.

Toxocara spp. infection and risk of childhood asthma: A systematic review and meta-analysis.

Asthma is one of the most common chronic respiratory disease worldwide, with a negative impact on quality of life and socio-economic status of patients. There are some evidences to suggest that Toxocara infection is a neglected risk factor for childhood asthma. We performed a systematic review and meta-analysis to further understanding of this relationship. Five databases include PubMed, Science Direct, Scopus, Web of Science (ISI), and Google scholar were searched (up to October 2017) to identify the relevant studies. We used random-effects meta-analysis model to estimate the pooled odds ratio (OR) and 95% confidence intervals (CI). Heterogeneity was assessed with the Q-test and I2 statistic. A total of 17 studies including 11 studies with case-control design (1139 patients and 1023 controls) and six studies with cross-sectional design (a total of 5469 participants, 872 asthmatics, and 4597 non-asthmatics children) met the eligibility criteria. An increased risk for asthma was observed in children with Toxocara infection seropositivity (OR, 1.91; 95% CI, 1.47-2.47). In sub-group analysis, the pooled ORs were (OR, 2.13; 95% CI, 1.43-3.15) and (OR, 1.73; 95% CI, 1.23-2.44) for case-control and cross-sectional studies, respectively. Moreover, considering to specific IgE seropositivity, a pooled OR of 2.36 (95% CI, 0.93-5.98) was observed. In conclusion, this meta-analysis revealed that children infected with Toxocara spp. are more likely to have asthma compared to non-infected children. More studies (especially longitudinal studies) are needed to further investigate the impact of Toxocara spp. infection on the onset or development of asthma.