ABSTRACT
Introduction:
The global protozoan parasite, Toxoplasma gondii, infects many warm-blooded animals and humans by employing different transmission routes. There have been some recent studies on the probable relevance of infectious agents and diabetes. Therefore, we conducted a systematic review and meta-analysis to identify the possible association between chronic toxoplasmosis and diabetes mellitus.
Methods:
This study was conducted following the general methodology recommended for systematic reviews and meta-analysis. Nine English literature databases (Google scholar, PubMed, Scopus, Web of science, Science Direct, Ovid, ProQuest, IngentaConnect, and Wiley Online Library) were searched, up to January 2016. Random effects model was used to determine odds ratios and their 95% confidence intervals.
Results:
Our review resulted in a total of seven publications meeting the inclusion criteria. Because of significant heterogeneity, we estimated a common OR by a random effects model at 1.10 (95% CI = 0.13-9.57) with p = 0.929 and 2.39 (95% CI = 1.20-4.75) with p = 0.013 for type 1 and type 2 diabetes mellitus, respectively.
Conclusion:
Despite the limitations such as low number of studies, this meta-analysis suggests chronic toxoplasmosis as a possible risk factor for type 2 DM. However, based on random effects model no statistically significant association was observed between T. gondii and type 1 DM. It is highly recommended for researchers to carry out more accurate studies aiming to better understand this association.
Keywords:
Toxoplasma gondii; Diabetes mellitus; Systematic review; Meta-analysis
Introduction
The ubiquitous parasitic protozoan, Toxoplasma gondii, is one of the most successful microorganism on the planet owing to quite a lot of compatibility to many host species, especially mammals, various transmission pathways (e.g. food, water, congenital, blood transfusion, organs transplant, etc.) and approximately involving one-third of the human population.11 Foroutan-Rad M, Majidiani H, Dalvand S, et al. Toxoplasmosis in blood donors: a systematic review and meta-analysis. Transfus Med Rev. 2016;30:116-22.
2 Foroutan-Rad M, Khademvatan S, Majidiani H, Aryamand S, Rahim F, Malehi AS. Seroprevalence of Toxoplasma gondii in the Iranian pregnant women: a systematic review and meta-analysis. Acta Trop. 2016;158:160-9.
3 Galvan-Ramirez Mde L, Troyo R, Roman S, Calvillo-Sanchez C, Bernal-Redondo R. A systematic review and meta-analysis of Toxoplasma gondii infection among the Mexican population. Parasit Vectors. 2012;5:271.-44 Daryani A, Sarvi S, Aarabi M, et al. Seroprevalence of Toxoplasma gondii in the Iranian general population: a systematic review and meta-analysis. Acta Trop. 2014;137:185-94. Being the category B priority pathogen with zoonotic significance, Toxoplasma has frequently been associated with congenital complications (such as hydrocephalus, stillbirth and abortion) as well as neuropathic anomalies, predominantly in high risk populations, i.e. pregnant women and immunocompromised hosts.22 Foroutan-Rad M, Khademvatan S, Majidiani H, Aryamand S, Rahim F, Malehi AS. Seroprevalence of Toxoplasma gondii in the Iranian pregnant women: a systematic review and meta-analysis. Acta Trop. 2016;158:160-9.,55 Sutterland AL, Fond G, Kuin A, et al. Beyond the association, Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: systematic review and meta-analysis. Acta Psychiatr Scand. 2015;132:161-79.
6 Ahmadpour E, Daryani A, Sharif M, et al. Toxoplasmosis in immunocompromised patients in Iran: a systematic review and meta-analysis. J Infect Dev Ctries. 2014;8:1503-10.-77 Galvan-Ramirez Mde L, Troyo-Sanroman R, Roman S, Bernal-Redondo R, Vazquez Castellanos JL. Prevalence of Toxoplasma infection in Mexican newborns and children: a systematic review from 1954 to 2009. ISRN Pediatr. 2012;2012:501216. While unusual, there are some evidence that T. gondii parasites may possibly have an undiscovered role in the putative pathogenesis of autoimmune diseases.88 Shapira Y, Agmon-Levin N, Selmi C, et al. Prevalence of anti-Toxoplasma antibodies in patients with autoimmune diseases. J Autoimmun. 2012;39:112-6.
A group of chronic metabolic disorders, specified as "Diabetes", are of medical importance with widespread distribution, especially in persons with high-calorie diets. They are distinguished by hyperglycemia elicited by the deficiencies in the insulin hormone release (type 1 diabetes) and/or failure to respond properly to insulin in target cells (type 2 diabetes), and this condition is probably overwhelmed by genetic elements, autoimmune processes, and environmental factors. According to scientific evaluations, it is anticipated that the number of diabetic patients will reach 522 million individuals by 2030.99 Canivell S, Gomis R. Diagnosis and classification of autoimmune diabetes mellitus. Autoimmun Rev. 2014;13:403-7. Recently, some reports have spotlighted the probable relevance of diabetes mellitus (DM) and infectious agents like Helicobacter pylori1010 Jeon CY, Haan MN, Cheng C, et al. Helicobacter pylori infection is associated with an increased rate of diabetes. Diabetes Care. 2012;35:520-5. and Coxsakie B4 virus.1111 Filippi CM, von Herrath MG. Viral trigger for type 1 diabetes: pros and cons. Diabetes. 2008;57:2863-71. In this case, the Apicomplexan parasite, T. gondii, has been proposed as a likely cause of diabetes, and existing information nearly predicate on this issue.1212 Saki J, Shafieenia S, Foroutan-Rad M. Seroprevalence of toxoplasmosis in diabetic pregnant women in southwestern of Iran. J Parasit Dis. 2016;:1-4, http://dx.doi.org/10.1007/s12639-015-0735-4.
http://dx.doi.org/10.1007/s12639-015-073...
13 Prandota J. T. gondii infection acquired during pregnancy and/or after birth may be responsible for development of both type 1 and 2 diabetes mellitus. J Diabetes Metab. 2013;4:1-55.
14 Gokce C, Yazar S, Bayram F, Gundogan K. Toxoplasma gondii antibodies in type 1 diabetes mellitus. Turk Klin Tip Bilim. 2008;28:619-22.
15 Kankova S, Flegr J, Calda P. An elevated blood glucose level and increased incidence of gestational diabetes mellitus in pregnant women with latent toxoplasmosis. Folia Parasitol (Praha). 2015;62:056.-1616 Flegr J, Prandota J, Sovickova M, Israili ZH. Toxoplasmosis - a global threat, correlation of latent toxoplasmosis with specific disease burden in a set of 88 countries. PLOS ONE. 2014;9:e90203. Hence, this review was intended to shed light on the possible association between toxoplasmosis and diabetes.
Methods
Ethical aspects
As this review did not involve any human or animal subjects, therefore ethical approval was not required.
Search strategy
A systematic review was premised on screening the literature published online in English language up to January 2016, in order to address the association between toxoplasmosis and diabetes. The search was conducted on Google scholar, PubMed, Scopus, Web of science, Science Direct, Ovid, ProQuest, IngentaConnect, and Wiley Online Library (Supplementary Fig. 1). Toward that end, the medical subject headings (MeSH) terms in PubMed and Scopus databases using the search keywords "Toxoplasmosis", "T. gondii", "Toxoplasma gondii", "Diabetes mellitus" and "Diabetic patients" combined together using OR and/or AND. Also reference lists of the primary relevance records found were explored manually. Corresponding authors of papers were contacted for more details, if deemed necessary.
Study selection and data extraction
Only case-control studies on seroepidemiology of toxoplasmosis in diabetic individuals around the world were included. Other inclusion criteria were as follows: diabetes as a disease and T. gondii as an exposure, presence of healthy individuals as control group, and serologic diagnostic test. Records were evaluated by two independent reviewers. The selected articles were scrutinized and contradictions among studies were obviated by discussion and consensus. The data were extracted carefully from databases on the basis of title, year of publication, first author, diagnostic method, type of investigation, type of disease, aim of study, main findings, exact number of participants both in case and control groups, and details of T. gondii positive individuals as well. The PRISMA (preferred reporting items for systematic reviews and meta-analysis) guideline1717 Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg. 2010;8:336-41. was followed in the reporting of current systematic review.
Meta-analysis
For each included study, the common odds ratio (OR) and respective 95% confidence interval (CI) on the association among toxoplasmosis and diabetes were calculated. The outcome of pool estimates of studies in addition to their 95% CI of independent records were depicted in a forest plot. Cochran's Q and I 2 statistics were applied to assess heterogeneity and inconsistency, respectively. Furthermore, small study effects and their publication bias were discerned by a funnel plot on the cornerstone of Egger's regression test. To comply with the results of heterogeneity test, either Der Simonian and Laird's random-effects method or Mantel-Haenszel's fixed-effects were employed to pool the approximations.
Results
Based on inclusion criteria, a total number of 7 out of 1377 studies were qualified to be ultimately included in this systematic review and meta-analysis,1212 Saki J, Shafieenia S, Foroutan-Rad M. Seroprevalence of toxoplasmosis in diabetic pregnant women in southwestern of Iran. J Parasit Dis. 2016;:1-4, http://dx.doi.org/10.1007/s12639-015-0735-4.
http://dx.doi.org/10.1007/s12639-015-073...
,1414 Gokce C, Yazar S, Bayram F, Gundogan K. Toxoplasma gondii antibodies in type 1 diabetes mellitus. Turk Klin Tip Bilim. 2008;28:619-22.,1818 Siyadatpanah A, Tabatabaie F, Oormazdi H, et al. Comparison of anti-Toxoplasma IgG and IgM antibodies determined by ELISA method in diabetic and non-diabetic individuals in west Mazandaran province, Iran, 2011-2012. Ann Biol Res. 2013;4:281-5.
19 Shirbazou S, Delpisheh A, Mokhetari R, Tavakoli G. Serologic detection of anti Toxoplasma gondii infection in diabetic patients. Iran Red Crescent Med J. 2013;15:701-3.
20 Abdelsalam DO. Investigation of anti-Toxoplasma antibodies and autoantibodies in patients with type 1 diabetes mellitus. Cairo University; 2013.
21 Krause I, Anaya JM, Fraser A, et al. Anti-infectious antibodies and autoimmune-associated autoantibodies in patients with type I diabetes mellitus and their close family members. Ann N Y Acad Sci. 2009;1173:633-9.-2222 Gokce C, Yazar S, Bayram F, Gundogan K, Yaman O, Sahin I. Anti-Toxoplasma gondii antibodies in type 2 diabetes. Natl Med J India. 2008;21:51. as demonstrated in Supplementary Fig. 1. The specifications of each study comprising the number of cases and controls as well as the number of IgG positive individuals, the utilized method and obtained p-value have been summarized in Table 1. Out of 2248 persons tested for toxoplasmosis infection, 717 were positive for T. gondii infection, 202 had type 1, and 1158 had type 2 DM; out of 888 healthy individuals 280 positive for T. gondii infection. The heterogeneity was statistically significant, for both type 1, I
2 = 94.7% and Q = 38.09 (p < 0.001), and type 2 DM, I
2 = 88.1% and Q = 25.26 (p < 0.001) (Table 2 and Supplementary Fig. 2). Accordingly, we calculated a common OR by random effects model at 1.10 (95% CI = 0.13-9.57) with p = 0.929 and 2.39 (95% CI = 1.20-4.75) with p = 0.013 for type 1 and type 2 DM, respectively (Table 2 and Supplementary Fig. 2). Also the calculated common OR (random effects model) for both type 1 and 2 diabetes was 1.86 (95% CI = 0.93-3.74) with p = 0.0796. The test of publication bias was clearly not significant in this case, p = 0.335 (Supplementary Fig. 3). Also, the chart of forest plot has been illustrated in supplementary Fig. 2. The status of toxoplasmosis infection was based on ELISA IgG, except for one paper in which the Bio-Plex 2200 kits were employed.
Prevalence of Toxoplasma infection among diabetic (cases) and healthy individuals (controls) included in the systematic review.
Discussion
A possible association between toxoplasmosis and DM would entail significant clinical consequences, shedding light on the complicated pathogenesis of DM. Overall, the current hypothesis suggests that toxoplasmosis increases susceptibility to acquiring diabetes and, on the other hand, diabetic patients are more vulnerable to opportunistic infections such as toxoplasmosis.1212 Saki J, Shafieenia S, Foroutan-Rad M. Seroprevalence of toxoplasmosis in diabetic pregnant women in southwestern of Iran. J Parasit Dis. 2016;:1-4, http://dx.doi.org/10.1007/s12639-015-0735-4.
http://dx.doi.org/10.1007/s12639-015-073...
13 Prandota J. T. gondii infection acquired during pregnancy and/or after birth may be responsible for development of both type 1 and 2 diabetes mellitus. J Diabetes Metab. 2013;4:1-55.-1414 Gokce C, Yazar S, Bayram F, Gundogan K. Toxoplasma gondii antibodies in type 1 diabetes mellitus. Turk Klin Tip Bilim. 2008;28:619-22.,2222 Gokce C, Yazar S, Bayram F, Gundogan K, Yaman O, Sahin I. Anti-Toxoplasma gondii antibodies in type 2 diabetes. Natl Med J India. 2008;21:51.
23 Zhu S, Lai DH, Li SQ, Lun ZR. Stimulative effects of insulin on Toxoplasma gondii replication in 3T3-L1 cells. Cell Biol Int. 2006;30:149-53.-2424 Gonzalez-Del Carmen M, Carino Calvo L, Vazquez Avila S, et al. The link between toxoplasmosis and diabetes: modifications of pancreatic beta cells TC-6 infected by Toxoplasma gondii tachyzoites. Trop Med Int Health. 2015. Subsequently, to elucidate this association, various empirical evidence have been appraised and proposed as plausible pathophysiological mechanisms, including: (1) infected white blood cells represent enhanced migratory feature, leading to the easier spread of Toxoplasma in body organs, e.g. pancreas1313 Prandota J. T. gondii infection acquired during pregnancy and/or after birth may be responsible for development of both type 1 and 2 diabetes mellitus. J Diabetes Metab. 2013;4:1-55.; (2) a clinically conspicuous autoimmune process could be ignited by T. gondii infection, trending immune machinery toward autoantibody production, for instance against β-cells of Langerhans islets1313 Prandota J. T. gondii infection acquired during pregnancy and/or after birth may be responsible for development of both type 1 and 2 diabetes mellitus. J Diabetes Metab. 2013;4:1-55.; (3) in light of ex vivo D-glucose and insulin dose-responsive experiment in 3T3-L1 cells, better replication of Toxoplasma occurs in insulin-producing β-cells, leading to activation of autoimmunity pathways as well as provoking the inflammation of Langerhans islets (insulitis) and ultimately developing diabetes2323 Zhu S, Lai DH, Li SQ, Lun ZR. Stimulative effects of insulin on Toxoplasma gondii replication in 3T3-L1 cells. Cell Biol Int. 2006;30:149-53.; (4) a possibility, is that T. gondii itself may invade and destroy pancreatic β-cells directly, instigating pancreatitis and more importantly, diabetes2525 Oz HS. Toxoplasmosis, pancreatitis, obesity and drug discovery. Pancreat Disord Ther. 2014;4.; (5) production of reactive oxygen species (ROS) and nitric oxide (NO) is induced by diabetes, and these agents, as stimulant for intra-cellular pathogens, can re-activate latent, cysts of parasites, again initiating acute infection2626 Hassanain MA, El-Fadaly HA, Hassanain NA. Toxoplasma gondii parasite load elevation in diabetic rats as latent opportunistic character. Ann Trop Med Public Health. 2014;7:110-5.; (6) given the inability of neutrophils to correctly perform phagocytosis and intra-cellular killing in progressive phase of diabetes, there may be increased responsiveness to intra-cellular pathogens such as Candida and Toxoplasma,2727 Wilson RM, Reeves WG. Neutrophil phagocytosis and killing in insulin-dependent diabetes. Clin Exp Immunol. 1986;63:478-84. and (7) the opsonization activity and leukocyte cytotoxicity of diabetic patients required for elimination of pathogens are considerably subsided, hence they would be more prone to opportunistic infections.1212 Saki J, Shafieenia S, Foroutan-Rad M. Seroprevalence of toxoplasmosis in diabetic pregnant women in southwestern of Iran. J Parasit Dis. 2016;:1-4, http://dx.doi.org/10.1007/s12639-015-0735-4.
http://dx.doi.org/10.1007/s12639-015-073...
,2727 Wilson RM, Reeves WG. Neutrophil phagocytosis and killing in insulin-dependent diabetes. Clin Exp Immunol. 1986;63:478-84.,2828 Rayfield EJ, Ault MJ, Keusch GT, Brothers MJ, Nechemias C, Smith H. Infection and diabetes: the case for glucose control. Am J Med. 1982;72:439-50.
In the included studies (Tables 1 and 2), the OR in type 1 DM individuals was 1.10 (95% CI = 0.13-9.57) with p = 0.929, while this ratio in type 2 DM patients was 2.39 (95% CI = 1.20-4.75) with p = 0.013. Thus, the risk of type 1 and 2 diabetes with previous Toxoplasma exposure would be 1.10 and 2.39 fold higher, respectively, than for unexposed persons. However, no statistically significant association between chronic toxoplasmosis and type 1 DM was held on random effects model. In this case, the highest OR (5.066) was reported in the study by Gokce et al.1414 Gokce C, Yazar S, Bayram F, Gundogan K. Toxoplasma gondii antibodies in type 1 diabetes mellitus. Turk Klin Tip Bilim. 2008;28:619-22. (p < 0.001) and the lowest OR (0.083) in the study by Krause et al.2121 Krause I, Anaya JM, Fraser A, et al. Anti-infectious antibodies and autoimmune-associated autoantibodies in patients with type I diabetes mellitus and their close family members. Ann N Y Acad Sci. 2009;1173:633-9. (p < 0.001). According to the estimated OR by Krause et al.2121 Krause I, Anaya JM, Fraser A, et al. Anti-infectious antibodies and autoimmune-associated autoantibodies in patients with type I diabetes mellitus and their close family members. Ann N Y Acad Sci. 2009;1173:633-9. there is no association between toxoplasmosis and diabetes and it is hypothesized that the patients’ younger ages as well as uncommon route of infection may have remarkably biased their results. Recently, some researchers have demonstrated the influence of parasite genotypes on behavior, psychomotor performance, physiology, and overall health of their host. Hence, the strain of Toxoplasma should be considered as an influential parameter in relation to diabetes.1515 Kankova S, Flegr J, Calda P. An elevated blood glucose level and increased incidence of gestational diabetes mellitus in pregnant women with latent toxoplasmosis. Folia Parasitol (Praha). 2015;62:056.,1616 Flegr J, Prandota J, Sovickova M, Israili ZH. Toxoplasmosis - a global threat, correlation of latent toxoplasmosis with specific disease burden in a set of 88 countries. PLOS ONE. 2014;9:e90203.,2929 Morisset S, Peyron F, Lobry JR, et al. Serotyping of Toxoplasma gondii: striking homogeneous pattern between symptomatic and asymptomatic infections within Europe and South America. Microbes Infect. 2008;10:742-7.
30 Kannan G, Moldovan K, Xiao JC, Yolken RH, Jones-Brando L, Pletnikov MV. Toxoplasma gondii strain-dependent effects on mouse behaviour. Folia Parasitol (Praha). 2010;57:151-5.
31 McLeod R, Boyer KM, Lee D, et al. Prematurity and severity are associated with Toxoplasma gondii alleles (NCCCTS, 1981-2009). Clin Infect Dis. 2012;54:1595-605.-3232 Flegr J, Zitkova S, Kodym P, Frynta D. Induction of changes in human behaviour by the parasitic protozoan Toxoplasma gondii. Parasitology. 1996;113:49-54.
Despite of the lack of remarkable correlation between chronic toxoplasmosis and type 1 diabetes in the current meta-analysis, ex vivo studies strongly demonstrate the presence of this relationship.1313 Prandota J. T. gondii infection acquired during pregnancy and/or after birth may be responsible for development of both type 1 and 2 diabetes mellitus. J Diabetes Metab. 2013;4:1-55.,2424 Gonzalez-Del Carmen M, Carino Calvo L, Vazquez Avila S, et al. The link between toxoplasmosis and diabetes: modifications of pancreatic beta cells TC-6 infected by Toxoplasma gondii tachyzoites. Trop Med Int Health. 2015. Therefore, further studies are needed in the future. There were several limitations in our study, including (1) small sample sizes in included studies and no further details about disease condition and duration in cases; (2) the variable quality of reporting of studies; (3) variable methodology to define Toxoplasma infection; and (4) lack of representativeness of cases and controls as they were selected from restricted communities, thus limiting external validity of the results.
Implications for research
Based on currently available results, no statistically significant association was observed between chronic toxoplasmosis and type 1 DM; of course there remain many questions to be answered in future investigations.
Acknowledgments
The authors would like to thank all staff of the Department of Medical Parasitology of Tarbiat Modares and Ahvaz Jundishapur Universities of Medical Sciences, Iran. We are very grateful to Dr Jasem Saki (Department of Medical Parasitology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran) and Hassan Niksima (Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran) for their helpful consultations.
Appendix A Supplementary data
Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.bjid.2016.09.002.
References
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1Foroutan-Rad M, Majidiani H, Dalvand S, et al. Toxoplasmosis in blood donors: a systematic review and meta-analysis. Transfus Med Rev. 2016;30:116-22.
-
2Foroutan-Rad M, Khademvatan S, Majidiani H, Aryamand S, Rahim F, Malehi AS. Seroprevalence of Toxoplasma gondii in the Iranian pregnant women: a systematic review and meta-analysis. Acta Trop. 2016;158:160-9.
-
3Galvan-Ramirez Mde L, Troyo R, Roman S, Calvillo-Sanchez C, Bernal-Redondo R. A systematic review and meta-analysis of Toxoplasma gondii infection among the Mexican population. Parasit Vectors. 2012;5:271.
-
4Daryani A, Sarvi S, Aarabi M, et al. Seroprevalence of Toxoplasma gondii in the Iranian general population: a systematic review and meta-analysis. Acta Trop. 2014;137:185-94.
-
5Sutterland AL, Fond G, Kuin A, et al. Beyond the association, Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: systematic review and meta-analysis. Acta Psychiatr Scand. 2015;132:161-79.
-
6Ahmadpour E, Daryani A, Sharif M, et al. Toxoplasmosis in immunocompromised patients in Iran: a systematic review and meta-analysis. J Infect Dev Ctries. 2014;8:1503-10.
-
7Galvan-Ramirez Mde L, Troyo-Sanroman R, Roman S, Bernal-Redondo R, Vazquez Castellanos JL. Prevalence of Toxoplasma infection in Mexican newborns and children: a systematic review from 1954 to 2009. ISRN Pediatr. 2012;2012:501216.
-
8Shapira Y, Agmon-Levin N, Selmi C, et al. Prevalence of anti-Toxoplasma antibodies in patients with autoimmune diseases. J Autoimmun. 2012;39:112-6.
-
9Canivell S, Gomis R. Diagnosis and classification of autoimmune diabetes mellitus. Autoimmun Rev. 2014;13:403-7.
-
10Jeon CY, Haan MN, Cheng C, et al. Helicobacter pylori infection is associated with an increased rate of diabetes. Diabetes Care. 2012;35:520-5.
-
11Filippi CM, von Herrath MG. Viral trigger for type 1 diabetes: pros and cons. Diabetes. 2008;57:2863-71.
-
12Saki J, Shafieenia S, Foroutan-Rad M. Seroprevalence of toxoplasmosis in diabetic pregnant women in southwestern of Iran. J Parasit Dis. 2016;:1-4, http://dx.doi.org/10.1007/s12639-015-0735-4
» http://dx.doi.org/10.1007/s12639-015-0735-4 -
13Prandota J. T. gondii infection acquired during pregnancy and/or after birth may be responsible for development of both type 1 and 2 diabetes mellitus. J Diabetes Metab. 2013;4:1-55.
-
14Gokce C, Yazar S, Bayram F, Gundogan K. Toxoplasma gondii antibodies in type 1 diabetes mellitus. Turk Klin Tip Bilim. 2008;28:619-22.
-
15Kankova S, Flegr J, Calda P. An elevated blood glucose level and increased incidence of gestational diabetes mellitus in pregnant women with latent toxoplasmosis. Folia Parasitol (Praha). 2015;62:056.
-
16Flegr J, Prandota J, Sovickova M, Israili ZH. Toxoplasmosis - a global threat, correlation of latent toxoplasmosis with specific disease burden in a set of 88 countries. PLOS ONE. 2014;9:e90203.
-
17Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg. 2010;8:336-41.
-
18Siyadatpanah A, Tabatabaie F, Oormazdi H, et al. Comparison of anti-Toxoplasma IgG and IgM antibodies determined by ELISA method in diabetic and non-diabetic individuals in west Mazandaran province, Iran, 2011-2012. Ann Biol Res. 2013;4:281-5.
-
19Shirbazou S, Delpisheh A, Mokhetari R, Tavakoli G. Serologic detection of anti Toxoplasma gondii infection in diabetic patients. Iran Red Crescent Med J. 2013;15:701-3.
-
20Abdelsalam DO. Investigation of anti-Toxoplasma antibodies and autoantibodies in patients with type 1 diabetes mellitus. Cairo University; 2013.
-
21Krause I, Anaya JM, Fraser A, et al. Anti-infectious antibodies and autoimmune-associated autoantibodies in patients with type I diabetes mellitus and their close family members. Ann N Y Acad Sci. 2009;1173:633-9.
-
22Gokce C, Yazar S, Bayram F, Gundogan K, Yaman O, Sahin I. Anti-Toxoplasma gondii antibodies in type 2 diabetes. Natl Med J India. 2008;21:51.
-
23Zhu S, Lai DH, Li SQ, Lun ZR. Stimulative effects of insulin on Toxoplasma gondii replication in 3T3-L1 cells. Cell Biol Int. 2006;30:149-53.
-
24Gonzalez-Del Carmen M, Carino Calvo L, Vazquez Avila S, et al. The link between toxoplasmosis and diabetes: modifications of pancreatic beta cells TC-6 infected by Toxoplasma gondii tachyzoites. Trop Med Int Health. 2015.
-
25Oz HS. Toxoplasmosis, pancreatitis, obesity and drug discovery. Pancreat Disord Ther. 2014;4.
-
26Hassanain MA, El-Fadaly HA, Hassanain NA. Toxoplasma gondii parasite load elevation in diabetic rats as latent opportunistic character. Ann Trop Med Public Health. 2014;7:110-5.
-
27Wilson RM, Reeves WG. Neutrophil phagocytosis and killing in insulin-dependent diabetes. Clin Exp Immunol. 1986;63:478-84.
-
28Rayfield EJ, Ault MJ, Keusch GT, Brothers MJ, Nechemias C, Smith H. Infection and diabetes: the case for glucose control. Am J Med. 1982;72:439-50.
-
29Morisset S, Peyron F, Lobry JR, et al. Serotyping of Toxoplasma gondii: striking homogeneous pattern between symptomatic and asymptomatic infections within Europe and South America. Microbes Infect. 2008;10:742-7.
-
30Kannan G, Moldovan K, Xiao JC, Yolken RH, Jones-Brando L, Pletnikov MV. Toxoplasma gondii strain-dependent effects on mouse behaviour. Folia Parasitol (Praha). 2010;57:151-5.
-
31McLeod R, Boyer KM, Lee D, et al. Prematurity and severity are associated with Toxoplasma gondii alleles (NCCCTS, 1981-2009). Clin Infect Dis. 2012;54:1595-605.
-
32Flegr J, Zitkova S, Kodym P, Frynta D. Induction of changes in human behaviour by the parasitic protozoan Toxoplasma gondii Parasitology. 1996;113:49-54.
Publication Dates
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Publication in this collection
Nov-Dec 2016
History
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Received
30 July 2016 -
Reviewed
28 Aug 2016