The authors have declared that no competing interests exist.
Conceived and designed the experiments: JF. Analyzed the data: JF. Contributed reagents/materials/analysis tools: JF. Wrote the paper: JF JP ZI. Data collection: MS.
Toxoplasmosis is becoming a global health hazard as it infects 30–50% of the world human population. Clinically, the life-long presence of the parasite in tissues of a majority of infected individuals is usually considered asymptomatic. However, a number of studies show that this ‘asymptomatic infection’ may also lead to development of other human pathologies.
The purpose of the study was to collect available geoepidemiological data on seroprevalence of toxoplasmosis and search for its relationship with mortality and disability rates in different countries.
Prevalence data published between 1995–2008 for women in child-bearing age were collected for 88 countries (29 European). The association between prevalence of toxoplasmosis and specific disease burden estimated with age-standardized Disability Adjusted Life Year (DALY) or with mortality, was calculated using General Linear Method with Gross Domestic Product per capita (GDP), geolatitude and humidity as covariates, and also using nonparametric partial Kendall correlation test with GDP as a covariate. The prevalence of toxoplasmosis correlated with specific disease burden in particular countries explaining 23% of variability in disease burden in Europe. The analyses revealed that for example, DALY of 23 of 128 analyzed diseases and disease categories on the WHO list showed correlations (18 positive, 5 negative) with prevalence of toxoplasmosis and another 12 diseases showed positive trends (p<0.1). For several obtained significant correlations between the seroprevalence of toxoplasmosis and specific diseases/clinical entities, possible pathophysiological, biochemical and molecular explanations are presented.
The seroprevalence of toxoplasmosis correlated with various disease burden. Statistical associations does not necessarily mean causality. The precautionary principle suggests however that possible role of toxoplasmosis as a triggering factor responsible for development of several clinical entities deserves much more attention and financial support both in everyday medical practice and future clinical research.
Toxoplasmosis, a disease caused by the obligate apicomplexan intracellular protozoan
Seroprevalence is a measure of the accumulated exposure during a person's lifetime in a particular social setting. Most of the more than one third of the world's human population who are infected with
Country | Prevalence (%) | Adj. Prevalence (%) | Reference | Period | No. |
Albania | 49 | 42 | 2004–2005 | 496 | |
Argentina | 60 | 53 | 2001 | 1007 | |
Australia | 23 | 16 | 2001 | 308 | |
Austria | 42 | 36 | 1997 | 4601 | |
Bahrain | 22 | 16 | 2005 | 3499 | |
Bangladesh | 38 | 38 | 1995–1996 | 286 | |
Belgium | 49 | 42 | 2004 | 16541 | |
Benin | 54 | 47 | 1993 | 211 | |
Brazil | 50 | 50 | 2012 | 2136 | |
Burkina Faso | 25 | 25 | 2006 | 336 | |
Cameroon | 77 | 70 | 1992 | 1014 | |
Canada | 20 | 17 | 2006 | NA | |
Colombia | 54 | 54 | 2006 | 630 | |
Costa Rica | 76 | 76 | 1996 | 1234 | |
Croatia | 29 | 24 | 2000 | 1109 | |
Cuba | 55 | 55 | 2004 | 526 | |
Czech Republic | 20 | 16 | 2007 | 1053 | |
Congo | 60 | 60 | 1990 | 2897 | |
Denmark | 28 | 20 | 1999 | 89873 | |
Egypt | 42 | 36 | 1995 | 62 | |
Estonia | 68.6 | 45 | 1999–2000 | 1277 | |
Ethiopia | 74 | 66 | 2012 | 1016 | |
Finland | 20 | 17 | 1989 | 16733 | |
France | 54 | 47 | 1995 | 13459 | |
Gabon | 71 | 71 | 1997 | 767 | |
Germany | 63 | 50 | 1999 | 4854 | |
Greece | 25 | 21 | 2004 | 5532 | |
Grenada | 57 | 50 | 2006 | 534 | |
Hungary | 45 | 39 | 2000 | 31759 | |
Chile | 39 | 33 | 1996 | 7536 | |
China | 11 | 11 | 2006 | 235 | |
Iceland | 13 | 8 | 1998 | 440 | |
India | 35 | 35 | 2003 | 180 | |
Indonesia | 53 | 46 | 2006 | 17735 | |
Iran | 39 | 33 | 2007 | 576 | |
Iraq | 49 | 42 | 2002 | 254 | |
Ireland | 34 | 25 | 2008 | 20252 | |
Israel | 21 | 17 | 1989 | 213 | |
Italy | 23 | 16 | 2004 | 3426 | |
Jamaica | 57 | 57 | 1986 | 1604 | |
Japan | 10 | 8 | 2011 | 4466 | |
Jordan | 47 | 40 | 2005 | 280 | |
Kuwait | 46 | 53 | 2002–2005 | 225 | |
Lebanon | 62 | 62 | 2010 | 232 | |
Libya | 45 | 34 | 2007 | 143 | |
Lithuania | 40 | 34 | 1991 | NA | |
Macedonia | 22 | 18 | 2005 | NA | |
Madagascar | 84 | 84 | 1992 | 599 | |
Malaysia | 49 | 42 | 2003 | 200 | |
Mexico | 49 | 49 | 2006 | NA | |
Montenegro | 27 | 23 | NA | NA | |
Morocco | 51 | 44 | 2007 | 2456 | |
Mozambique | 19 | 13 | 2008 | 150 | |
Nepal | 55 | 55 | 1998 | 345 | |
Netherlands | 35 | 26 | 2004 | 7521 | |
New Zealand | 35 | 26 | 2004 | 500 | |
Nigeria | 78 | 71 | 1992 | 352 | |
Norway | 11 | 9 | 1993 | 35940 | |
Pakistan | 33 | 28 | 1997 | 105 | |
Papua New Guinea | 18 | 15 | 1990 | 197 | |
Peru | 39 | 33 | NA | NA | |
Poland | 40 | 34 | 2003 | 4916 | |
Portugal | 24 | 17 | 2011 | 401 | |
Qatar | 35 | 30 | 2005–2008 | 1857 | |
South Korea | 4 | 3 | 2000 | NA | |
Romania | 44 | 38 | 2008 | 184 | |
Sao Tome and Principe | 75 | 68 | 2007 | 499 | |
Saudi Arabia | 32 | 27 | 1991 | 921 | |
Senegal | 40 | 34 | 1993 | 353 | |
Serbia | 31 | 26 | 2007 | 765 | |
Singapore | 17 | 14 | NA | 120 | |
Slovakia | 22 | 18 | 2008 | 656 | |
Slovenia | 25 | 21 | 2002 | 21270 | |
Spain | 32 | 23 | 2004 | 16362 | |
Sudan | 42 | 36 | 2003 | 487 | |
Sweden | 18 | 13 | 2001 | 40978 | |
Switzerland | 35 | 26 | 2006 | NA | |
Tanzania | 35 | 35 | 1991 | 549 | |
Thailand | 13 | 11 | 2001 | 1200 | |
Togo | 75 | 68 | 1991 | 620 | |
Trinidad and Tobago | 43 | 43 | 2008 | 450 | |
Tunisia | 43 | 37 | 1996 | 2231 | |
Turkey | 54 | 47 | 2005 | 1149 | |
United Arab Emirates | 23 | 19 | 1997 | 1503 | |
UK | 9 | 6 | 2005 | 1897 | |
USA | 11 | 9 | 2007 | NA | |
Venezuela | 38 | 38 | 2006 | 446 | |
Vietnam | 11 | 9 | 2003 | 300 |
The second and third column show prevalence of toxoplasmosis and prevalence adjusted to a standard age of 22 years to account for variation in childbearing age in across countries (column 1) using the formula Prevalenceadj = 1−(1−Prevalence)∧(22/childbearing age)
In the majority of the human populations, the parasite seroprevalence increases with age, and may vary by gender
The seroprevalence of toxoplasmosis is high in immunocompromised patients, such as those infected with human immunodeficiency virus (HIV), and transplant or cancer patients treated with immunosuppressive agents
It may be pointed out that the different serological methods used to obtain prevalence data are not standardized, and vary in sensitivity, specificity, and predictive values. As a consequence, no two tests produce the same results in all cases, even when carried out in the same laboratory
Animals are infected by eating infected animals, by ingestion of or coming in contact with feces of an infected cat, or by transmission from mother to fetus. In humans, cats are the primary source of infection (contact with fecal material), but other pets may also be the secondary source of infection
Contact with raw meat of infected animals, especially pork, is a more significant source of human infections in some countries, such as in Poland, where the majority of pigs, cattle and sheep (approximately 80%) test positive for
It is believed that the majority of immunocompetent individuals infected with
Symptomatic infection with the parasite can be categorized into four groups: 1) cervical lymphadenopathy, headache, fever, sore throat, and myalgia, with possibility of splenomegaly and brief erythematous (maculopapular) rash; 2) typhus-like exanthematous form with myocarditis, meningoencephalitis, atypical pneumonia and possibly death; 3) retinochoroiditis, which may be severe, requiring enucleation; and 4) central nervous system involvement
Disease/Clinical entity | References |
Congenital toxoplasmosis (encephalitis; chorioretinitis; neonatal mortality) | |
Psychosis; schizophrenia; bipolar disorder | |
Mood disorders; suicide; depression (?) | |
Obsessive-compulsive disorder | |
Attention/concentration deficit hyperactivity disorder | |
Anorexia | |
Autism spectrum disorders | |
Down's syndrome | |
Alzheimer's disease | |
Parkinson's disease | |
Migraine; other headaches | |
Idiopathic intracranial hypertension | |
Pseudotumor cerebri | |
Aseptic meningitis | |
Mollaret meningitis | |
Epilepsy | |
Aphasia and epilepsy (Landau-Kleffner syndrome) | |
Facial nerve palsy (Bell's palsy) | |
Hearing loss | |
Central diabetes insipidus; syndrome of inappropriate antidiuretic hormone secretion | |
Hypothalamo-pituitary dysfunction; panhypopituitarism | |
Brain tumors (meningioma; ependymoma; glioma) | |
Non-Hodgkin's lymphoma | |
Neoplasia | |
Melanoma | |
Breast cancer | |
Carcinoma of female genitalia, including cervical tissue | |
Chronic heart failure; myocarditis; arrhythmia | |
Inflammatory bowel disease | |
Ulcerative colitis | |
Crohn's disease | |
Celiac disease | |
Abdominal hernia | |
Hepatitis, including HCV infection | |
Granulomatous liver disease | |
Liver cirrhosis; granulomatous liver disease; impaired liver function | |
Primary biliary cirrhosis; biliary atresia; cholestatic disorders | |
Diabetes mellitus type 1 and 2 | |
Goitre; iodine deficiency | |
Hashimoto's thyroiditis | |
Graves' disease; thyroid adenoma | |
Rheumatoid arthritis; Still's disease | |
Polymyositis | |
Systemic sclerosis | |
Systemic lupus erythematosus | |
Wegener's granulomatosis; other vasculitides | 205; 215 |
Anti-phospholipid syndrome | |
Cryoglobulinemia | |
Ocular toxoplasmosis (retinochorioiditis; uveitis; blurred vision; floaters; macular scars; nystagmus; strabismus; reduced visual acuity; blindness; scleritis; papillitis; retinal necrosis; vasculitis; retinal detachment; vitritis; congenital cataract; neuroretinitis; atrophic optic papilla; retinitis pigmentosa) | |
Glaucoma | |
Ovarian dysfunction | |
Uterine atrophy | |
Impaired reproductive function ( |
|
Nephrotic syndrome; lipoid nephrosis | |
Schönlein-Henoch purpura | |
Glomerulonephritis (various forms; including these with development of fibrosis); impaired kidney function | |
Atherosclerosis; obesity; cardiovascular deaths; all-cause mortality | |
Diverse abnormalities in aggregate personality; including aggressive behavior in animals and humans |
Some of the clinical manifestations of
Due to the fact that
The data on disease burden, mortality and Disability Adjusted Life Year (DALY), were obtained from the table “Mortality and Burden of Diseases Estimates for WHO Member States in 2004” published by WHO
The Disability Adjusted Life Year (DALY) has been defined
In the literature, most of toxoplasmosis prevalence (seroprevalence) data are available only for women in childbearing age. Therefore, all available data collected for this population were published mostly between 1995–2008; the final database was obtained from 88 countries (29 European). When more than one estimation of prevalence of toxoplasmosis was available for a particular country, we gave priority to multicenter studies performed between 1998–2004. When the studies published different prevalence data for various regions or different years we calculated an unweighted arithmetic mean. The obtained data were adjusted to a standard age 22 years to eliminate differences in prevalence caused by different childbearing ages in various countries
All statistical tests except partial Kendall correlation test were performed independently with SPSS 21 and Statistica 10.0. The association between seroprevalence of toxoplasmosis and specific disease burden estimated with age standardized DALY was calculated using nonparametric partial Kendall correlation test
The medical importance of the association was expressed as regression coefficient ‘B’, the slope of the regression line. The higher is the absolute value of B the greater is the positive or negative impact of the predictor variable (here prevalence of toxoplasmosis) on the dependent variable (here DALY or mortality). The strength of statistical association is expressed as Eta2, which reflects the proportion of variance in the dependent variable (the DALY or mortality) associated with or accounted for by each of the main effects, interactions, and error in an ANOVA study (the prevalence of latent toxoplasmosis)
The GDP (1000 $), latitude (°) and relative humidity (%) data are shown only for the region or locality for which latent toxoplasmosis prevalence information (%) is reported.
The present study showed that prevalence of toxoplasmosis correlated with specific disease burden measured with age-standardized DALY or with specific mortality in particular countries (
The x-axes show prevalence of toxoplasmosis (%) in women of childbearing age and y-axes the number years of ‘healthy’ life lost by virtue of being in a state of poor health or disability due to particular disease per 100,000 inhabitants in 2004.
Because distribution of DALY and mortality for many diseases was not normal, the analysis of association of toxoplasmosis prevalence with disease burden was performed with two methods, nonparametric partial Kendall correlation test and GLM analysis.
Since, a nonparametric partial Kendall correlation test enables to control for one confounding variable, we controlled for the GDP per capita because this variable is known to be strongly correlated with the quality of health care and therefore with the burden associated with many diseases. The partial Kendall correlation test demonstrated that age standardized DALY of 57 of 128 diseases and disease categories on the WHO list showed significant correlation (53 positive and 4 negative) with prevalence of toxoplasmosis in all (n = 88) countries after the effect of GDP was controlled, and further 8 diseases showed such trends (p<0.1) (6 positive and 2), see
The correlations were estimated with partial Kendall correlation test with GDP per capita as covariate. Positive Kendall Taus (red) correspond to positive and negative Taus (blue) to negative correlations. Significant results (p<0.05) are labeled with yellow and trends (p<0.10) with green colors.
GLM analyses with GDP, latitude and humidity as covariates showed that age standardized DALY of 23 of 128 diseases and disease categories on the WHO list had significant correlation (18 positive and 5 negative) with prevalence of toxoplasmosis in all (n = 88) countries after the effect of GDP was controlled, and further 12 diseases showed such trends (p<0.1) (all positive), Similar analyses for 29 European countries showed 32 significant correlations (29 positive and 3 negative) and 18 trends (16 positive and 2 negative), and for 59 non-European countries had 18 significant correlations (13 positive and 5 negative) and 13 trends (9 positive and 4 negative),
The correlations were estimated with General Linear Model with GDP per capita, latitude humidity, as covariates. Positive B (red) correspond to positive, and negative B (blue) to negative correlations. Significant results (p<0.05) are labeled with yellow and trends (p<0.10) with green colors.
Partial Kendal correlation tests also showed that mortalities from 31 of 111 diseases and disease (WHO) categories with nonzero mortality had significant correlation (29 positive and 2 negative) with prevalence of toxoplasmosis in 88 countries after the effect of GNP was controlled, and further 6 diseases showed such trends (p<0.1) (5 positive and 2 negative), see
GLM analyses also showed that mortalities of 12 out of 111 diseases and disease categories (for 17 diseases the mortality data were available for less than 3 countries) revealed significant correlation (11 positive and 1 negative) with prevalence of toxoplasmosis in 88 countries after the effects of GDP, latitude humidity were controlled, and further 11 diseases showed such trends (10 positive and 1 negative), see
Several explanations may be put forward for positive correlation between prevalence of latent toxoplasmosis and the DALY or the morbidity from a particular disease: a)
In the present GLM analyses, three potential confounding factors, the GDP
In the next part of discussion, comments are made on the results obtained for particular diseases, mainly the results of GLM tests as the partial Kendall correlation tests can control for one confounding variable only and the regression coefficient (B-value) has more straightforward interpretation than Kendall Tau. We have concentrated on the age-standardized DALY data because only a subset of disease could result in the death of patients under normal conditions. The strength of correlation is usually estimated by Eta2, which reflects fraction of variability of dependent variable that can be explained by an independent variable (here, by the prevalence of toxoplasmosis). The clinical relevance of a particular association is however better reflected by the regression coefficient B, which shows an increase of a dependent variable (here, the age standardized DALY expressed in years of life lost due to premature death per 100 000 inhabitants) that corresponds to the increase of an independent variable per one unit (here, the increase of prevalence of toxoplasmosis by 1%). Therefore, the B-value reflects not only the strength of the correlation but also the incidence of particular disease.
Prevalence of toxoplasmosis explained about 23% of between-countries variability in mortality and age-standardized DALY in Europe (mortality: B = 3.538, Eta2 = 0.229, p = 0.024; DALY: B = 68.18, Eta2 = 0.227, p = 0.014). This association was not significant for non-European countries (mortality: B = 3.37, Eta2 = 0.026, p = 0.239; DALY: B = 92.49, Eta2 = 0.030, p = 0.204) or for all 88 countries (mortality: B = 3.78, Eta2 = 0.031, p = 0.104; DALY: B = 98.287, Eta2 = 0.034, p = 0.093). Both communicable and noncommunicable diseases were responsible for the observed association in Europe, however, for communicative infection was significant only for DALY (mortality: B = 0.024, Eta2 = 0.007, p = 0.878; DALY: B = 11.44, Eta2 = 0.166, p = 0.039).
The highest regression coefficient (B = 26.33, p = 0.019) was found for the entire category of noncommunicable diseases. In this case, a difference of 1% in the prevalence of toxoplasmosis corresponded to a difference of 26.33 DALY per 100,000 inhabitants. The prevalence of toxoplasmosis explained 6.4% of between countries variability in DALY.
The second highest regression coefficient (B = 12.49, p = 0.026, Eta2 = 0.058) was observed for cardiovascular diseases. However, prevalence of toxoplasmosis explained about 15% of variability in mortality attributed to cardiovascular diseases in European countries subset (B = 18.23, p = 0.048, Eta2 = 0.153). Also, in the European countries, the difference in prevalence of toxoplasmosis explained about 17% of variability of ischemic heart disease (B = 8.59, p = 0.039, Eta2 = 0.166). Stronger correlations between prevalence of toxoplasmosis and heart disease, especially inflammatory heart disease, were revealed with nonparametric partial Kendall test (comparing the data in tables shown in
Theoretically, the inability to control for more than one confounding variable (here, the latitude and annual precipitation) in the distribution-robust nonparametric tests could be responsible for the false positive results of the partial Kendall test. However, the present data do not support this explanation.
The third highest regression coefficient (B = 9.66) was demonstrated for this category, but, it explained only 3.3% of the variability making the correlation non-significant (p = 0.097). The important components of this category were prematurity and low birth weight (B = 3.43; Eta2 = 0.053; p = 0.034). Published data suggest that early development of embryos in mothers with latent toxoplasmosis was slower, although, the birth weight of newborns was approximately the same as those of infection-free mothers
The regression coefficient was only medium (B = 2.613; Eta2 = 0.133; p<0.001). The correlation was significant for the 88 countries, however, it was non-significant for the European countries (B = 1.970; Eta2 = 0.137; p = 0.062). Interestingly, more than 55 years ago, it was observed that children with Down syndrome had a much higher probability of having mothers with latent toxoplasmosis (84%) than normal children (32%)
Principally different explanation of the observed association suggest results of three studies on the influence of toxoplasmosis on secondary sex ratio and on the rate of prenatal and early postnatal development of children of infected mothers, These results indicate that latent toxoplasmosis could protect the embryos with less serious developmental disturbances against spontaneous abortion
The regression coefficient was medium (B = 4.534; Eta2 = 0.140, p = 0.072). This disease occurs in 27 countries of our data set and therefore the highly non-Gaussian distribution of DALY (and mortalities) makes the results of GLM analysis not fully credible. The nonparametric test showed no significant association between filariasis and toxoplasmosis. However, possible relationship between toxoplasmosis and filariasis could theoretically be explained by the fact that
The regression coefficient was medium (B = 4.124; Eta2 = 0.070; p = 0.137), and the correlation was not significant. A possible association, if it really exists, is difficult to rationalize, however, latent cerebral toxoplasmosis could influence susceptibility to measles because of changes in the immune status of the children (
The regression coefficient B was 1.290 (Eta2 = 0.071, p = 0.014). An opposite direction association was observed for European (B = −1.571, Eta2 = 0.096, p = 0.124) and non-European (B = 1.879, Eta2 = 0.158, p = 0.002) countries. We have no explanation for the positive association, but, the negative association between
Epilepsy had a small regression coefficient (B = 0.972; Eta2 = 0.112, p = 0.001), but the correlation was highly significant. This association was observed both in European (B = 0.816, Eta2 = 0.193, p = 0.025) and non-European countries (B = 0.967, Eta2 = 0.125, p = 0.007). The association between latent toxoplasmosis and cryptic epilepsy has already been suggested to exist on the basis of the case control studies – for example, see Ref.
Surprisingly, there was a strong association between toxoplasmosis and DALY for leukemia in European countries (B = 0.445, Eta2 = 0.216, p = 0.017) explaining about 22% of variability in DALY. In a small study performed in 15 patients with leukemia, 10 (66.7%) individuals had increased serum IgG, and 2 also had increased IgM antibodies to
The regression coefficient was small (B = 1.014; Eta2 = 0.132, p = 0.067) and the correlation was non-significant (positive for European but negative for non-European countries). A typical symptom of acute toxoplasmosis is tonsillitis. Thus, it is possible that tonsillitis leading to the development of local chronic inflammation may result in inducing precancerous changes in predisposed individuals. Association of prevalence of toxoplasmosis with cancer of the larynx in men and women, and lung cancer in men (but not with cancer of oropharynx), has been reported
Prostate cancer had a B of 0.667 (Eta2 = 0.093, p = 0.005). An association in opposite direction was observed for European (B = −0.235, Eta2 = 0.091, p = 0.133) and non-European (B = 0.820, Eta2 = 0.130, p = 0.006) countries. Benign prostate hypertrophy had a B of 0.214, (Eta2 = 0.482, p = 0.045) and this association was positive but non-significant for non-European countries (B = 0.062, Eta2 = 0.079, p = 0.165) and positive and significant (B = 0.284, Eta2 = 0.098, p = 0.018) for European countries. It is possible that the increased incidence of prostate cancer and hypertrophy could be related to the increased concentration of testosterone as observed in
Obsessive compulsive disorder (OCD) had a B value of 0.836, but the prevalence of toxoplasmosis explained 28.7% of total variability in DALY (p<0.001). For European countries the association was weaker (B = 0.681, Eta2 = 0.212, p = 0.018), but for non-European countries, it was nearly two times higher (B = 0.925, Eta2 = 0.358, p<0.001). The association between latent toxoplasmosis and OCD has already been suggested to exist on the basis of results of a case-control study
A regression coefficient (B) of 2.118 was observed for the category of ‘endocrine disorders’. The prevalence of toxoplasmosis explained about 5.8% of total variability (p = 0.028) and non-significant trends were observed for both European and non-European countries. The positive and negative associations between toxoplasmosis and testosterone concentration were observed for men and women, respectively. However, our unpublished data suggest that toxoplasmosis could also play a role in the production of thyroid hormones. This finding is supported by recent literature data demonstrating the prevalence of anti-
A regression coefficient (B) of 1.63 was observed for the general category of ‘sexually transmitted diseases except AIDS’. Prevalence of toxoplasmosis explained 4.1% of variability (p = 0.063). The association was stronger in European countries (B = 0.413, Eta2 = 0.215, p = 0.017) than in non-European countries (B = 1.699, Eta2 = 0.041, p = 0.133). Similar effects were observed for gonorrhea (B = 0.175, Eta2 = 0.213, p = 0.018) and chlamydia (B = 0.229, Eta2 = 0.209, p = 0.019) in Europe, but were different for non-European countries for gonorrhoea (B = 0.549, Eta2 = 0.069, p = 0.049) and chlamydia (B = 0.287, Eta2 = 0.050, p = 0.097). We believe that the correlation of both prevalence of toxoplasmosis and STD with other factor(s), such as a risky sexual behavior (promiscuity and frequent unprotected sex) is responsible for the observed positive association between prevalence of toxoplasmosis and age/controlled DALY for STDs. It has been suggested by other investigators
Pertussis had a regression coefficient (B) of 1.81. Prevalence of toxoplasmosis explained 10% of variability in DALY (p = 0.003). This correlation could, at least in part, be rationalized by the findings that in some instances immunization could shorten the incubation period of certain diseases or convert a latent infection/inflammation into clinically active disease. The necessary precondition for such an occurrence is the presence of latent infection or asymptomatic bacterial/viral/parasitic colonization
It has been reported that some infants and young children develop various urinary tract diseases, such as acute renal failure, nephrotic syndrome, or pyelonephritis, after the injection of the whole-cell DTP vaccine
The regression coefficient was high (B = 4.24), and it explained 4.9% of variability (p = 0.041). The high regression coefficient is not surprising because, for example, respiratory tract diseases are the most frequent cause of hospitalization and death in children and
There are many predisposing, provocative, facilitating, and other factors, such as chronic hypoxia, viral infections/bacterial toxins, inflammatory states, biochemical disorders, and genetic abnormalities that are the most likely triggers of development of respiratory tract diseases, including sudden infant death syndrome
Latent toxoplasmosis was found to be associated with an increased risk of attempted suicides
On the basis of four published case-control studies, a positive correlation was expected between the burden of traffic accidents and prevalence of latent toxoplasmosis. However, this correlation was significant in nonparametric tests (mortality: Tau = 0.148, p = 0.042; DALY: Tau = 0.164, p = 0.023). Weak correlation in other tests may be caused by the fact that the traffic accident rates depend on many confounding variables, including the number of vehicles in circulation, length of the road network, mean number of kilometers (miles) travelled by one inhabitant per year, driver behavior (alcohol/drug use, sleep deprivation, etc.), etc. Probably, much stronger correlations would be detected when these variables would be included into the models. Interestingly, the strongest association of latent toxoplasmosis and traffic accidents was found for RhD negative drivers
It is possible that some of the toxoplasmosis prevalence data are inaccurate, as there are no published national survey data of latent toxoplasmosis carried out systematically. In addition, surveys performed in a relatively small, and ethnically and sociologically homogeneous population, such as in the Czech Republic, demonstrate that seroprevalence of toxoplasmosis varies considerably in different regions of the country. Therefore, it is difficult to estimate the average prevalence of this clinical entity in women of child-bearing age in a particular country on the basis of one or two studies performed in one hospital or even in one city. Furthermore, it is important to point out that the different serological methods used to obtain toxoplasmosis seroprevalence data are not standardized, and vary in sensitivity, specificity, and predictive values. As a consequence, no two tests produce the same results in all cases, even when carried out in the same laboratory
For the present study, probably most of available data for the period 1995–2008 were collected, and published information for period prior to 1995 was also considered. To maximally avoid possible subjective bias, we completed our data set on January 2013 and did not change it after starting the analyses despite of the fact that data for other four countries appeared during 2013. To further decrease the risk of subjectivity in selection of countries, we included available data for all countries; our data set contained the prevalence of toxoplasmosis in 88 countries, which represented the largest ever data set analyzed in all toxoplasmosis correlation studies. To increase the reliability of our results, we confirmed the results of parametric GLM analysis with the nonparametric Kendall test, which is less sensitive to contamination of data with few incorrect values. It may be noted that lack of precision in the prevalence data increases the risk of false negative but not false positive results of correlation.
The existence of a factor correlating with both the prevalence of latent toxoplasmosis and the disease burden can lead to a false positive value in correlation studies. We controlled for one potential confounding variable (GDP) in partial Kendall test and for three potential confounding variables (GDP, latitude and humidity) in GLM tests. It is possible that some unknown factor(s), such as hygienic or eating habits, could influence both the prevalence of latent toxoplasmosis and incidence or morbidity of certain diseases. Existence of such factor(s) could be revealed by confirming present analyses with another set of countries. In the present study, data from all 88 countries were analyzed, and also separately for the European and non-European countries. It is important to repeat the correlation studies based upon independent data sets (if available) for particular regions (such as in France) or various states (such as in USA).
It is quite probable that the incidence of particular diseases reflects better the prevalence of latent toxoplasmosis in an unknown past, rather than the present prevalence. In many countries, the prevalence of latent toxoplasmosis in young women is changing: in some cases it is increasing (China, Korea and Mexico) and in some it is decreasing (most of European countries and USA). The prevalence of latent toxoplasmosis in a general population (the parameter which probably better correlates with disease burden) is more stable because it reflects past rather than present epidemiological situation in particular countries. Still, our lack of knowledge of optimal interval between toxoplasmosis survey and disease burden surveys increases the risk of false negative results of the obtained correlation studies.
The present results suggest that the prevalence of latent toxoplasmosis in particular countries correlated (mostly positively) with various disease burden measured with age standardized Disability Adjusted Life Years or with age standardized mortality. It must be emphasized that no epidemiological study and especially no correlation (ecological) study can prove existence of causal relation between the two factors. At the same time, results of such studies could indicate which hypothesis should be tested in the future. It is highly probable that some of the observed correlations represent “false correlations” – either the Type 1 errors of used statistical tests or the expression of existence of unknown factor(s) that correlates with both the risk of latent toxoplasmosis and incidence (or severity) of particular disease. However, it is also highly probable that at least some of the observed correlations do occur because toxoplasmosis is, up to now rarely suspected, etiological agent of particular diseases. Existence of some correlations could be expected to happen on the basis of our present knowledge for certain diseases (for example, epilepsy, obsessive compulsive disorder, congenital abnormalities). Some of the obtained correlations may be regarded as rather surprising and should therefore be studied in more detail in the future. In the opinion of the authors, slowly emerging important role of latent toxoplasmosis in etiology of several clinical entities deserves much more attention and financial support in future clinical research.