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Toxoplasmosis - A Global Threat. Correlation of Latent Toxoplasmosis with Specific Disease Burden in a Set of 88 Countries


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Background 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.Aims of the studyThe 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.Methods and findingsPrevalence 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
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Toxoplasmosis – A Global Threat. Correlation of Latent
Toxoplasmosis with Specific Disease Burden in a Set of
88 Countries
Jaroslav Flegr
*, Joseph Prandota
, Michaela Sovic
, Zafar H. Israili
1Department of Biology, Faculty of Science, Charles University in Prague, Prague, Czech Republic, 2Department of Social Pediatrics, Faculty of Health Sciences, Wroclaw
Medical University, Wroclaw, Poland, 3Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America
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.
Aims of the Study:
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.
Methods and Findings:
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 pathophysiolog-
ical, 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.
Citation: Flegr J, Prandota J, Sovic
´M, Israili ZH (2014) Toxoplasmosis – A Global Threat. Correlation of Latent Toxoplasmosis with Specific Disease Burden in a
Set of 88 Countries. PLoS ONE 9(3): e90203. doi:10.1371/journal.pone.0090203
Editor: Delmiro Fernandez-Reyes, National Institute of Medical Research, United Kingdom
Received December 25, 2013; Accepted January 22, 2014; Published March 24, 2014
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for
any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Funding: The authors’ work was supported by the Grand Agency of the Czech Republic (Grant No. P303/11/1398) and Charles University of Prague (grant UNCE
204004). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail:
Toxoplasmosis, a disease caused by the obligate apicomplexan
intracellular protozoan Toxoplasma gondii,isoneoftheworldsmost
common parasites infecting most genera of warm-blooded animals
(more than 30 species of birds and 300 species of mammals). It is the
most prevalent infection in humans (estimated to be 30–50% of the
world population), more than latent tuberculosis which infects about
one-third of the human population (WHO,
publications/2009/tbfactsheet_2009update_one_page.pdf, accessed
July 2013). The definitive hosts are representatives of the felid (cat)
family. Nicolle and Manceaux (1908) first observed the parasites in the
blood and tissues of a North African rodent, Ctenodactylus gondii,and
named it Toxoplasma (arclike form) gondii (after the rodent host) [1].
There are three infective stages of T. gondii: a) a rapidly dividing
invasive tachyzoite; b) a slowly dividing bradyzoite in tissue cysts,
which can persist inside human cells for protracted periods; and c) an
environmental stage, the sporozoite, protected inside an oocyst. The
oocysts, remarkably stable environmentally, are transmitted to other
hosts through inadvertent ingestion.
Seroprevalence of toxoplasmosis
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 T. gondii remain asymptomatic because the immune
system usually keeps the parasite from causing illness. Chronic,
usually lifelong, infection with Toxoplasma that is not accompanied
with overt clinical symptoms of toxoplasmosis disease is termed
latent toxoplasmosis while chronic infection associated with
PLOS ONE | 1 March 2014 | Volume 9 | Issue 3 | e90203
continuous or recurrent clinical symptoms is termed chronic
toxoplasmosis (this form of disease is relatively rare in Europe and
Northern America). Worldwide seroprevalence of the parasite
measured by specific anti-Toxoplasma IgG antibodies varies
between 1% and 100% depending on the environmental and
socioeconomic conditions, including eating habits and health-
related practices [2–5], general level of hygiene, host susceptibility,
geographical location (geolatitude) and humidity of the soil. The
incidence of infection is higher in warmer and humid climates and
increases with age [5]. The lowest seroprevalence (,1%) was
found in some countries in the Far East and the highest (.90%) in
some parts of European and South American countries. In the
United States, the Centers for Disease Control and Prevention
(CDC) reported an overall seroprevalence of 11% [National
Health and Nutritional Examination Survey between 1999 and
2004]; another survey reported a higher number (22.5%) [6].
Nevertheless, toxoplasmosis is one of the leading causes of death
attributed to foodborne illness [7]. In European countries, the
prevalence ranges between 10% to 60%, and in some regions as
high as 90% [8]. In one study, 84% of pregnant women had serum
antibodies against the parasite [3]. Data from 88 countries are
presented in Table 1; most of the published data on seropreva-
lence are in women of childbearing age and/or those who are
In the majority of the human populations, the parasite
seroprevalence increases with age, and may vary by gender
[6,94]. Latitudinal variability in the geoseroprevalence of the
parasite may be due to local rainy conditions (because oocysts live
longer in humid conditions), and low altitude regions (especially at
mid-latitudes); a north-south seroprevalence gradient has also been
reported in animals [9,95,96].
The seroprevalence of toxoplasmosis is high in immunocom-
promised patients, such as those infected with human immuno-
deficiency virus (HIV), and transplant or cancer patients treated
with immunosuppressive agents [5,97,98].
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 [5].
Genotypes and virulence of T. gondii
T. gondii strains are highly diverse but only a few lineages are
widely spread. Different genotypes of the parasite show great
diversity in pathogenicity and drug sensitivity. Some atypical
strains have also been detected. In Europe, North America, and
Africa, there are three dominant clonal lineages of T. gondii called
type I (RH, GT1,CAST), type II (ME49, WIL, HART), and type
III (VEG, MOO, SOU), as well as many atypical genotypes which
differ in prevalence, virulence, migratory capacity within the host,
and ability to convert to the bradyzoite cyst phase [99–101].
Different strains of the parasite induce different cytokine responses
[102], thus triggering development of various clinical and
biochemical disturbances in the host, including modulation of
the host cell proteome [103,104]. Mice fed as few as 1 oocyst of T.
gondii serotype I and several atypical strains died of acute
toxoplasmosis within 21 days post inoculation, while some T.
gondii type II, and III strains were less virulent [105]. In North
America, the parasite serotype II and NE-II causes congenital
toxoplasmosis, while prematurity and severity of disease at birth
was associated with the coccidian NE-II serotype [106]. This
serotype was also associated with rural residence, lower socioeco-
nomic status and Hispanic ethnicity (P,0.01–0.001) [106]. A
greater variety of genotypes are found in South America and
Africa than in North America and Europe [107,108], suggesting
that in these continents sexual replication of the parasite occurs
more frequently than in any other part of the world [109]. This
genetic divergence may contribute to the higher prevalence of
seropositivity and ocular disease due to T. gondii, as exemplified by
the higher prevalence of toxoplasmosis and Toxoplasma-induced
eye disease in southern Brazil than in any other part of the world
Transmission of T. gondii
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 [3,111,112].
The seroprevalence of toxoplasmosis in the Arctic region proves
that T. gondii can thrive in the absence of cats [113].
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 T. gondii [8,114]. Transmis-
sion of the parasite can also occur by drinking municipal/well
unboiled and unbottled water containing oocysts, exposure to
contaminated soil, contaminated milk, exposure of children
playing in sandpits, geophagia [115,116], eating raw or under-
cooked meat, especially venison [117] or rabbits [118], raw
oysters, clams, or mussels [119], consumption of unwashed raw
fruits and vegetables contaminated with the oocytes [117], blood
transfusion [120–122], maternal-fetal passage of blood cells
(including placental trophoblasts) [123,124], solid organ allografts
[125,126], bone marrow transplantation [127], allogeneic stem
cell transplantation [128], sputum [129], breast milk [130,131],
and semen [132] (thus, probably the infection may be transmitted
via both vaginal and oral sex, significantly more frequently from
seropositive to passive sex partner than vice-versa (P,0.001)
[133]). Poor hygiene, lower socioeconomic status and less
education, as well as exposure to certain strains of T. gondii may
also contribute to a higher rate of infection [134].
Cellular mechanism(s) of infection
T. gondii is remarkable in its ability to invade a wide variety of
host cells. Invasion is an active process relying on parasite motility
and the sequential secretion of proteins from secretory organelles,
the micronemes, rhoptries, and the dense granules. T. gondii can
invade and multiply inside any nucleated cell type including
epithelial cells and blood leukocytes [135]. A preference to infect
and multiply inside myeloid cells in vitro has also been reported
[136], and several studies in mice indicate that the dendritic cells
as well as monocytes/macrophages function as systemic parasite
transporters (‘‘Trojan horses’’) during infection [137–142]. The
parasite can be transmitted from infected dendritic cells to NK
cells [143], and thus, low levels of NK cells found in pregnant
women may suggest transmission of the parasite [144]. Differential
infectivity and division rate of intracellular tachyzoites in human
peripheral blood leukocytes and other primary human cells in vitro
has been demonstrated depending on the cell characteristics [136].
Clinical manifestations of toxoplasmosis
It is believed that the majority of immunocompetent individuals
infected with T.gondii remain asymptomatic or have a subclinical
course with minor symptoms [145]. It is nevertheless the most
common food-borne parasitic infection requiring hospital treat-
ment [146], and the third most common cause of hospitalization
due to food-borne infection [147]. Both competent and immuno-
Correlation of Toxoplasmosis with Disease Burden
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Table 1. Prevalence of latent toxoplasmosis in women of childbearing age in various countries.
Country Prevalence (%) Adj. Prevalence (%) Reference Period No.
Albania 49 42 [10] 2004–2005 496
Argentina 60 53 [11] 2001 1007
Australia 23 16 [12] 2001 308
Austria 42 36 [13] 1997 4601
Bahrain 22 16 [14] 2005 3499
Bangladesh 38 38 [15] 1995–1996 286
Belgium 49 42 [16] 2004 16541
Benin 54 47 [17] 1993 211
Brazil 50 50 [18] 2012 2136
Burkina Faso 25 25 [19] 2006 336
Cameroon 77 70 [20] 1992 1014
Canada 20 17 [21] 2006 NA
Colombia 54 54 [22] 2006 630
Costa Rica 76 76 [23] 1996 1234
Croatia 29 24 [24] 2000 1109
Cuba 55 55 [25] 2004 526
Czech Republic 20 16 [26] 2007 1053
Congo 60 60 [27] 1990 2897
Denmark 28 20 [28] 1999 89873
Egypt 42 36 [29] 1995 62
Estonia 68.6 45 [30] 1999–2000 1277
Ethiopia 74 66 [31] 2012 1016
Finland 20 17 [32] 1989 16733
France 54 47 [33] 1995 13459
Gabon 71 71 [34] 1997 767
Germany 63 50 [35] 1999 4854
Greece 25 21 [36] 2004 5532
Grenada 57 50 [37] 2006 534
Hungary 45 39 [38] 2000 31759
Chile 39 33 [39] 1996 7536
China 11 11 [40] 2006 235
Iceland 13 8 [30] 1998 440
India 35 35 [41] 2003 180
Indonesia 53 46 [42] 2006 17735
Iran 39 33 [43] 2007 576
Iraq 49 42 [44] 2002 254
Ireland 34 25 [45] 2008 20252
Israel 21 17 [46] 1989 213
Italy 23 16 [47] 2004 3426
Jamaica 57 57 [48] 1986 1604
Japan 10 8 [49] 2011 4466
Jordan 47 40 [50] 2005 280
Kuwait 46 53 [51] 2002–2005 225
Lebanon 62 62 [52] 2010 232
Libya 45 34 [53] 2007 143
Lithuania 40 34 [54] 1991 NA
Macedonia 22 18 [55] 2005 NA
Madagascar 84 84 [56] 1992 599
Malaysia 49 42 [57] 2003 200
Mexico 49 49 [58] 2006 NA
Correlation of Toxoplasmosis with Disease Burden
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compromised persons can develop the disease, especially retino-
choroiditis (ocular toxoplasmosis) [2,145,148]. In non-pregnant
immunocompetent adults, acute disease may also lead to impaired
eye sight [149,150]. For example, in the United States, one million
new infections occur each year, which result in approximately 20
000 cases of retinal pathology [151]. Primary infection in pregnant
women is a matter of great concern, since it can be transmitted to
the fetus leading to spontaneous abortion or stillbirth. A newborn
exposed to T. gondii in utero may develop congenital toxoplasmosis
with major ocular and neurological consequences. In immuno-
suppressed (HIV, organ transplant or cancer) patients, the
infection can lead to life-threatening cerebral toxoplasmosis
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
Table 1. Cont.
Country Prevalence (%) Adj. Prevalence (%) Reference Period No.
Montenegro 27 23 [55] NA NA
Morocco 51 44 [59] 2007 2456
Mozambique 19 13 [60] 2008 150
Nepal 55 55 [61] 1998 345
Netherlands 35 26 [62] 2004 7521
New Zealand 35 26 [63] 2004 500
Nigeria 78 71 [64] 1992 352
Norway 11 9 [65] 1993 35940
Pakistan 33 28 [66] 1997 105
Papua New Guinea 18 15 [67] 1990 197
Peru 39 33 [68] NA NA
Poland 40 34 [69] 2003 4916
Portugal 24 17 [70] 2011 401
Qatar 35 30 [71] 2005–2008 1857
South Korea 4 3 [72] 2000 NA
Romania 44 38 [73] 2008 184
Sao Tome and Principe 75 68 [74] 2007 499
Saudi Arabia 32 27 [75] 1991 921
Senegal 40 34 [76] 1993 353
Serbia 31 26 [55] 2007 765
Singapore 17 14 [77] NA 120
Slovakia 22 18 [78] 2008 656
Slovenia 25 21 [79] 2002 21270
Spain 32 23 [80] 2004 16362
Sudan 42 36 [81] 2003 487
Sweden 18 13 [82] 2001 40978
Switzerland 35 26 [83] 2006 NA
Tanzania 35 35 [84] 1991 549
Thailand 13 11 [83] 2001 1200
Togo 75 68 [85] 1991 620
Trinidad and Tobago 43 43 [86] 2008 450
Tunisia 43 37 [87] 1996 2231
Turkey 54 47 [88] 2005 1149
United Arab Emirates 23 19 [89] 1997 1503
UK 9 6 [90] 2005 1897
USA 11 9 [91] 2007 NA
Venezuela 38 38 [92] 2006 446
Vietnam 11 9 [93] 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 Prevalence
=12(12Prevalence)(22/childbearing age) [9]. Column 5 shows year(s) when the study was performed and
column 6 shows number of women in the sample. For Macedonia, the 2004 WHO data were not available therefore this 30
European country was not included in our
data set.
Correlation of Toxoplasmosis with Disease Burden
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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
[153]. In addition, several reports suggest that T. gondii infection
may be responsible for additional wide range of symptoms, and
development of several clinical entities (summarized in Table 2).
Some of the clinical manifestations of T. gondii infection may be
as a result of extensive interaction of the pathogen with
approximately 3000 host genes or proteins possibly because of
frequent host/pathogen antigen homology that disrupts/creates/
triggers host specific metabolic pathways, and finally contributes to
the development of endophenotypes of different diseases [154].
The parasite and concomitant viral and/or bacterial infections
scavenge important metabolites from host cells and/or donate
other compounds to the host causing unwanted effects. In
addition, T. gondii-derived autoantibodies also play an important
role in the pathology associated with the parasite [154].
Association of seroprevalence of toxoplasmosis with
other pathologies
Due to the fact that T. gondii infection is omnipresent and
associated with development of many pathologies in humans and
animals, including the disease burden of congenital toxoplasmosis,
as represented by disability-adjusted life years (DALY) being the
highest among all foodborne pathogens [149], the purpose of this
work was to collectively evaluate available geoepidemiological data
on the parasite worldwide national seroprevalence variations and
their relationship with mortality and disability rates. In the
analyses, gross domestic product (GDP) per capita as a covariate was
used because earlier it was argued and demonstrated that culture-
level correlations need to be controlled for regional socioeconomic
parameters [9,215,322]. If possible (i.e. in multivariate GLM
analyses), two potential confounding variables that could strongly
influence both the survival of Toxoplasma oocysts in soil and a
course of various diseases, namely the average latitude (proxy for
temperature) and the average relative humidity of particular
countries have also been included into the statistical models. In this
study we found many positive and some negative associations
between the prevalence of toxoplasmosis and various diseases
burdens. The number and strength of these associations were
much higher than could be expected by chance. Still, it must be
emphasized that statistical association does not mean causality.
Based on the finding of a statistical association between two
phenomena, one cannot determine which of them is the cause and
which is the effect – in other words, whether event A causes event
B, or whether event B causes event A. Not only we are unable to
determine whether event A causes B, or B causes A, but sometimes
there is an (unknown) event C that causes both A and B.
Therefore, all effects observed in the present exploratory study as
well as all suggested biological or medical interpretations must be
considered just as potential stimuli for the next, more focused
research (search for unknown confounders and for independent
evidence) that must follow.
Mortality and Burden of Diseases data
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 [323] and available at:
evidence/bod. The publication can be downloaded from the
2004_report_update/en/index.html; accessed July 2013). Sum-
mary tables present the best estimates of WHO – based on the
evidence available in mid-2008 – rather than from the official
estimates of Member States. Methods and data sources are
summarized in the Annexes of the ‘‘Global burden of disease:
2004 update’’ [323], and the methodology used is described in
more details elsewhere [324]; also available at: http://www.dcp2.
org/pubs/GBD; accessed July 2013.
The Disability Adjusted Life Year (DALY) has been defined
[323] as ‘‘a health gap measure that extends the concept of
potential years of life lost due to premature death and also to
include equivalent years of ‘healthy’ life lost by virtue of being in a
state of poor health or disability.’’ Thus, the DALY combines in
one measure the time lived with disability and the time lost due to
premature mortality. One DALY can be thought of as one lost
year of ‘healthy’ life, while the ‘burden of disease’ as a measure of
the gap between current health status and an ideal situation where
everyone lives into old age free of disease and disability. The
method of calculation of age-standardized DALY has been
described earlier [323].
Data collection for prevalence of toxoplasmosis
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 [325] were kindly provided by
Mudhakar Dama) using the formula:
Prevalenceadj ~1{1{PrevalenceðÞ
(22=child bearing age) 9½:
Statistical Methods
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
[326,327] with Gross Domestic Product per capita (GDP) as
covariate. Because the results of similar analyses performed with
the General Linear Model (GLM) method were qualitatively the
same, GLM data were primarily interpreted in the Discussion
section of present study. The GLM is more sensitive for the quality
of data (e.g. to presence of outliers and non-Gaussian distribution
of data, etc.), however, it enables to control for more than one
covariate. In the present analysis, we controlled for GDP,
geographical latitude and annual mean of relative humidity of
particular countries using data available at http://data.worldbank.
org/indicator/NY.GDP.PCAP.CD (accessed 10.12. 2013) and (accessed 2.4. 2013). No formal
corrections for multiple tests were carried out, however, the
fraction of significant results largely exceeded a theoretical value of
5 false positive results per 100 tests.
The medical importance of the association was expressed as
regression coefficient ‘B’, the slope of the regression line. The
Correlation of Toxoplasmosis with Disease Burden
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Table 2. Diseases and clinical entities associated with T. gondii infection.
Disease/Clinical entity References
Congenital toxoplasmosis (encephalitis; chorioretinitis; neonatal mortality) [100,149,155–158]
Psychosis; schizophrenia; bipolar disorder [159–166]
Mood disorders; suicide; depression (?) [167–174]
Obsessive-compulsive disorder [175,176]
Attention/concentration deficit hyperactivity disorder [175,177]
Anorexia [178–181]
Autism spectrum disorders [164,177,182–185]
Down’s syndrome [182,186–188]
Alzheimer’s disease [182,189–191]
Parkinson’s disease [192,193]
Migraine; other headaches [194–197]
Idiopathic intracranial hypertension [177,180,198]
Pseudotumor cerebri [180,198]
Aseptic meningitis [180,198]
Mollaret meningitis [199]
Epilepsy [200,201]
Aphasia and epilepsy (Landau-Kleffner syndrome) [202]
Facial nerve palsy (Bell’s palsy) [203]
Hearing loss [204,205]
Central diabetes insipidus; syndrome of inappropriate antidiuretic hormone secretion [156,206–209]
Hypothalamo-pituitary dysfunction; panhypopituitarism [209–211]
Brain tumors (meningioma; ependymoma; glioma) [196,212–216]
Non-Hodgkin’s lymphoma [217,218]
Neoplasia [216,219–221]
Melanoma [216,222–226]
Breast cancer [227]
Carcinoma of female genitalia, including cervical tissue [228]
Chronic heart failure; myocarditis; arrhythmia [229–231]
Inflammatory bowel disease [232–234]
Ulcerative colitis [232]
Crohn’s disease [232]
Celiac disease [232,235]
Abdominal hernia [233,236]
Hepatitis, including HCV infection [237–246]
Granulomatous liver disease [247,248]
Liver cirrhosis; granulomatous liver disease; impaired liver function [242–244,249–253]
Primary biliary cirrhosis; biliary atresia; cholestatic disorders [254–261]
Diabetes mellitus type 1 and 2 [189,262–264]
Goitre; iodine deficiency [265–268]
Hashimoto’s thyroiditis [269]
Graves’ disease; thyroid adenoma [269–271]
Rheumatoid arthritis; Still’s disease [272–277]
Polymyositis [231,278–283]
Systemic sclerosis [277,284,285]
Systemic lupus erythematosus [286]
Wegener’s granulomatosis; other vasculitides 205; 215 [277,287]
Anti-phospholipid syndrome [287]
Cryoglobulinemia [287]
Correlation of Toxoplasmosis with Disease Burden
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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
, 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) [328] pp. 54–55,
[329] pp. 317–319. The statistically significant results, i.e. the
associations with p value ,0.05 and trends, i.e. the associations
with p value ,0.1 (significant in one-sided but not in two-sided
tests) were listed in the tables and in the main text.
Results and Discussion
Correlation of toxoplasmosis prevalence with GDP per
capita, geolatitude and humidity
Fig. 1 suggests that the prevalence of toxoplasmosis correlates
with GDP, and possibly also with latitude and humidity for the
countries for which the information on toxoplasmosis prevalence is
reported. For the whole set of countries (n = 88), the prevalence of
toxoplasmosis correlated positively with GDP per capita (Spear-
man R = 20.484, p,0.001) and latitude (Spearman R = 20.449,
p,0.001), and non-significantly positively correlated with the
humidity (Spearman R = 0.180, p = 0.093) in the univariate
nonparametric Spearman test. For European countries (n = 29)
all three correlations were not significant (p.0.151) and for non-
European countries (n = 59) the prevalence of toxoplasmosis
correlated negatively with GDP per capita (Spearman R = 2
0.382, p = 0.003) and latitude (Spearman R = 20.396, p,0.002),
and positively with humidity (Spearman R = 0.308, p = 0.017).
The multivariate GLM analyses with GDP, latitude and humidity
as independent variables showed negative correlation with GDP
(all countries: p = 0.006, Eta
= 0.085; European: p = 0.044,
= 0.153; non-European: p = 0.022, Eta
= 0.092). For the
latitude and humidity, the results differed between European and
non-European countries (latitude all countries: p = 0.014,
= 0.070; European: p = 0.055, Eta
= 0.135; non-European:
p = 0.073, Eta
= 0.057; humidity all countries: p = 0.056,
= 0.043; European: p = 0.037, Eta
= 0.162; non-European:
p = 0.356, Eta
= 0.016). These results suggest that the GDP, and
possibly also the latitude and humidity, should be incorporated
into the statistical models as covariates.
Correlation of toxoplasmosis prevalence with age-
standardized DALY for diseases
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 (Fig. 2).
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 Fig. 3. Similar analyses for 29 European
countries showed 12 significant correlations (11 positive and 1
negative) and 11 trends (10 positive and 1 negative), and for 59
non-European countries test revealed 33 significant correlations
(29 positive and 4 negative) and 10 trends (all positive), Fig 3.
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), Fig 4.
Table 2. Cont.
Disease/Clinical entity References
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 [292,293]
Ovarian dysfunction [294–296]
Uterine atrophy [297]
Impaired reproductive function (T. gondii was present in testicles, epididymis, seminal vesicles,
prostate gland in rams, and caused abnormalities in sperm motility, viability and concentration
rates, weight of epididymis in rats, orchitis)
Nephrotic syndrome; lipoid nephrosis [250,251,255,301–306]
¨nlein-Henoch purpura [196,307,308]
Glomerulonephritis (various forms; including these with development of fibrosis); impaired kidney function [250,251,301,305,306,309–312]
Atherosclerosis; obesity; cardiovascular deaths; all-cause mortality [253,313–318]
Diverse abnormalities in aggregate personality; including aggressive behavior in animals and humans [9,319–321]
Correlation of Toxoplasmosis with Disease Burden
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Correlation of toxoplasmosis prevalence with disease
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 Fig. 3. Similar
analyses performed for 29 European countries demonstrated 6
significant correlations (all positive), and 11 trends (all positive)
(here only 90 diseases had the mortality data necessary for
analysis), and for 59 non-European countries showed 16 significant
correlations (14 positive and 2 negative) and 8 trends (7 positive
and 1 negative) (109 diseases had enough data for the analysis)
(Fig. 3).
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 Fig. 4. Similar analyses
performed for 29 European countries showed 11 significant
correlations (all positive) and 13 trends (all positive), and for 59
non-European countries had 11 significant correlations (8 positive
and 3 negative) and 8 trends (7 positive and 1 negative), Fig. 4.
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) T. gondii infection may
increase the risk of development of some diseases, b) certain
diseases may increase the risk of acquiring toxoplasmosis, or c)
some unknown factor(s) may increase both the risk of triggering
certain diseases and Toxoplasma infection. Similarly, there are
several possible explanations for the observed negative correla-
tions: a) infection with the parasite can increase resistance/
tolerance of the infected host to a certain disease by modulating its
innate and/or acquired cellular/humoral immunity. For example,
suppression of cellular immunity observed in in vivo as well as in
vitro systems can make the host more sensitive to infection by
certain pathogens, and at the same time protect it against
development of some autoimmune diseases. On the other hand,
chronic inflammation loci in tissues/organs can be responsible for
inducing health problems, including development of certain
tumors [214,215], and at the same time activation of the host
immune system can make local tissue environment unfavorable for
growing, proliferation and persistence of certain infectious agents.
For example, toxoplasmosis increases dopamine levels in the brain
tissue, which can protect the host against symptoms of certain
diseases, e.g. Parkinson’s disease, and at the same time it can
increase the risk for development of other pathologies, such as
schizophrenia [330,331].
In the present GLM analyses, three potential confounding
factors, the GDP per capita (which strongly correlates with quality of
health services and hygienic standards), the geolatitude (which
strongly correlates with temperature and quantity and quality of
sunlight) and humidity which influences survival of Toxoplasma
oocysts in soil), were controlled. However, many other factors,
such as cultural habits, can also influence the risk of Toxoplasma
infection, and/or other infections as well. It has been, for example,
suggested that toxoplasmosis could be a sexually transmitted
Figure 1. Correlation between prevalence of toxoplasmosis humidity, geolatitude and GDP per capita in all 88 countries. The GDP
(1000 $), latitude (u) and relative humidity (%) data are shown only for the region or locality for which latent toxoplasmosis prevalence information
(%) is reported.
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disease (STD) transferred from men to women with semen/
ejaculate [331,332]. This could explain the observed positive
correlation between the prevalence of latent toxoplasmosis and
DALY for several STDs. Finally, it is to be noted that the
incidence of a certain disease can be decreased by an increased risk
of death due to another concomitant disease.
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 Eta
, 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.
Association of seroprevalence of toxoplasmosis with
specific diseases in all 88 countries
All disease burden. Prevalence of toxoplasmosis explained
about 23% of between-countries variability in mortality and age-
standardized DALY in Europe (mortality: B = 3.538, Eta
= 0.229,
p = 0.024; DALY: B = 68.18, Eta
= 0.227, p = 0.014). This
association was not significant for non-European countries
(mortality: B = 3.37, Eta
= 0.026, p = 0.239; DALY: B = 92.49,
= 0.030, p = 0.204) or for all 88 countries (mortality: B = 3.78,
= 0.031, p = 0.104; DALY: B = 98.287, Eta
= 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, Eta
= 0.007, p = 0.878; DALY: B = 11.44,
= 0.166, p = 0.039).
Noncommunicable diseases. The highest regression coef-
ficient (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
Figure 2. Correlation of prevalence of toxoplasmosis with various disease-attributed DALY for 88 WHO-member 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.
Correlation of Toxoplasmosis with Disease Burden
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Correlation of Toxoplasmosis with Disease Burden
PLOS ONE | 10 March 2014 | Volume 9 | Issue 3 | e90203
DALY per 100,000 inhabitants. The prevalence of toxoplasmosis
explained 6.4% of between countries variability in DALY.
Cardiovascular diseases. The second highest regression
coefficient (B = 12.49, p = 0.026, Eta
= 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, Eta
= 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,
= 0.166). Stronger correlations between prevalence of toxo-
plasmosis and heart disease, especially inflammatory heart disease,
were revealed with nonparametric partial Kendall test (comparing
the data in tables shown in Fig. 3 and 4). One may suggest that the
non-Gaussian distributions of dependent variables, e.g. a bimodal
distribution for cerebrovascular and cardiovascular disease and
highly skewed distribution for hypertensive, rheumatic and
inflammatory heart diseases (results not shown), were responsible
for the false negative results of the GLM tests.
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. Fig. 1 shows that
the latitude correlates negatively and the humidity positively with
the prevalence of toxoplasmosis. The Kendall correlation test
showed, for example, the positive association between hyperten-
sive heart disease and prevalence of toxoplasmosis (DALY:
p = 0.06; mortality: p = 0.008), while GLM demonstrated lack of
such association (DALY: p = 0.345; mortality: p = 0.282). The
negative association between prevalence of toxoplasmosis and
latitude (see above) could explain the positive correlation between
the disease burden for hypertensive heart disease and prevalence
of toxoplasmosis, because the disease burden for hypertensive
heart disease correlated negatively with the latitude (DALY: B = 2
3.846, Eta
= 0.139, p,0.001), but also negatively with humidity
(B = 22.145, Eta
= 0.059, p = 0.024), which is in contradiction to
the explanation). However, the negative correlation between
prevalence of toxoplasmosis and latitude could not explain the
positive correlation between prevalence of toxoplasmosis and the
inflammatory heart disease (DALY: p = 0.012, mortality:
p = 0.006), because inflammatory heart disease correlated posi-
tively with latitude (B = 0.749, Eta
= 0.010, p = 0.362), and
negatively with humidity (B = 21.392, Eta
= 0.041, p = 0.060).
This contradicts the notion that the correlations with the latitude
or humidity could be responsible for the association between
toxoplasmosis and cardiovascular diseases detected with the partial
Kendall correlation tests.
Perinatal conditions. The third highest regression coeffi-
cient (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;
= 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 [26].
These studies were performed in Czech Republic, a developed
European country, with low frequency of virulent T. gondii strains.
It is possible that the effect of toxoplasmosis on development of
embryos is qualitatively different in other parts of the world. It is
indicative that the association between prevalence of toxoplasmo-
sis and DALY for prematurity and low birth weight is much
weaker for the European countries (B = 0.320; Eta
= 0.004;
p = 0.761) than for others. Once again, the correlation of DALY
for perinatal conditions with prevalence of toxoplasmosis detected
with nonparametric tests were stronger than those detected with
GLM. Here, however, the correlation observed in Kendall test (in
which the GDP but not the latitude and humidity was controlled)
can be explained by correlation of both prevalence of toxoplas-
mosis and the DALY for perinatal conditions, controlling for the
latitude, because the latter correlation is negative and relatively
strong (and significant).
Congenital abnormalities. The regression coefficient was
only medium (B = 2.613; Eta
= 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; Eta
= 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%) [333]; the probability of having fathers with latent
toxoplasmosis did not differ between children with and without
this disorder. Recently, it has been suggested that Down syndrome
may be caused by congenital T. gondii infection [182], Table 2.
This hypothesis is supported by the finding that T. gondii has a
specific protein transporter exposed at the parasite surface, with
high affinity for folic acid, which is responsible for the acquisition
and salvaging of exogenous folate compounds [187], thus leading
to folate deficiency in the host. The transport of folic acid across
the parasite plasma membrane was found to be rapid, biphasic,
bidirectional, specific, and concentration- and temperature-
dependent, and methotrexate, an antifolate, was found to be
internalized by the protozoan pathogen to the mitochondrion
[187]. In addition, it has been demonstrated that simultaneous
dietary restriction of folic acid and infection with T. gondii induces
DNA damage in peripheral blood cells of infected mice [186].
Furthermore, T. gondii infection was also associated with
nutritional deficiencies of iron and iodine [266,334,335], which
may lead to have adverse effect on the growth and development of
the fetus.
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 [26,336–338]. It is possible that such beneficial activity
of the parasite could translate into positive correlation between
prevalence of toxoplasmosis and incidence and severity of
congenital abnormalities.
Lymphatic filariasis. The regression coefficient was medi-
um (B = 4.534; Eta
= 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. How-
Figure 3. Correlation of mortality and Disability Adjusted Life Year (DALY) with prevalence of toxoplasmosis for all 88 WHO
member countries (29 European and 59 non-European countries). 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.
Correlation of Toxoplasmosis with Disease Burden
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Correlation of Toxoplasmosis with Disease Burden
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ever, possible relationship between toxoplasmosis and filariasis
could theoretically be explained by the fact that T. gondii usually
disseminates via lymphatic system in the infected patients, who
usually have symptomatic lymphadenopathy. In addition, possible
interactions exist between toxoplasmosis-associated changes in the
host lymphatic system and a progressive clinical picture of
lymphatic filariasis (Table 2). Filariasis may therefore represent
another co-morbidity of the host infected with T. gondii.
Measles. The regression coefficient was medium (B = 4.124;
= 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 suscepti-
bility to measles because of changes in the immune status of the
children (Table 2) [339,340] caused by the parasite or measles-
mumps-rubella (MMR) vaccination.
Asthma. The regression coefficient B was 1.290
= 0.071, p = 0.014). An opposite direction association was
observed for European (B = 21.571, Eta
= 0.096, p = 0.124) and
non-European (B = 1.879, Eta
= 0.158, p = 0.002) countries. We
have no explanation for the positive association, but, the negative
association between T. gondii infection and asthma could be, at
least partially, explained by the anti-inflammatory effect of
histamine produced in excess in asthmatic patients, since, asthma
is a chronic inflammatory disorder associated with an increased
number of T
2 (T helper type 2) cells producing anti-inflamma-
tory cytokines and decreased number of T
1 (T helper type 1)
cells generating pro-inflammatory cytokines. Histamine modulates
the cytokine T
2 balance because it enhances secretion of
2 cytokines, such as IL-4, IL-5, IL-10, and IL-13, and inhibits
production of T
1 interleukins (IL-2, IFN-c, and monokine IL-12)
[341], thus exerting beneficial anti-inflammatory effects.
Epilepsy. Epilepsy had a small regression coefficient
(B = 0.972; Eta
= 0.112, p = 0.001), but the correlation was highly
significant. This association was observed both in European
(B = 0.816, Eta
= 0.193, p = 0.025) and non-European countries
(B = 0.967, Eta
= 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. [342,343] Table 2.
Leukemia. Surprisingly, there was a strong association
between toxoplasmosis and DALY for leukemia in European
countries (B = 0.445, Eta
= 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 T. gondii
[219]. It is known that tachyzoites of T. gondii use a ‘‘Trojan horse’’
strategy to penetrate various tissues and organs of the infected
host. They even transform the phenotype of infected white cells
by, for example, increasing migratory activity of the infected
dendritic cells [344] and by inhibiting apoptotic activity of the
infected cells [345–349]. It is also possible that the increased risk of
various forms of cancer, including leukemia, could be as a result of
infection with T. gondii, which may cause a nonspecific chronic
local inflammation.
Cancer of the mouth/oropharynx. The regression coeffi-
cient was small (B = 1.014; Eta
= 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 individu-
als. 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 [214]. In addition, one
cannot exclude that frequent oral sex could, at least in part, affect
this correlation, since, the parasite has been found in the semen
and ejaculate of both animals and humans infected with T. gondii
[331,332], see also Table 2.
Prostate cancer. Prostate cancer had a B of 0.667
= 0.093, p = 0.005). An association in opposite direction
was observed for European (B = 20.235, Eta
= 0.091, p = 0.133)
and non-European (B = 0.820, Eta
= 0.130, p = 0.006) countries.
Benign prostate hypertrophy had a B of 0.214, (Eta
= 0.482,
p = 0.045) and this association was positive but non-significant for
non-European countries (B = 0.062, Eta
= 0.079, p = 0.165) and
positive and significant (B = 0.284, Eta
= 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 Toxoplasma-infected
male rats [350] and men [351,352]. Histopathologic studies of the
reproductive system in male sheep experimentally infected with
the parasite showed inflammatory process in the prostate gland
and seminal vesicles strongly suggestive of Toxoplasma infection
[300] (Table 2). Thus, persistent chronic inflammation caused by
the parasite also must be taken into account in the development of
prostate cancer, although perhaps having different clinical courses
in European versus non-European countries.
Obsessive compulsive disorder. 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, Eta
= 0.212, p = 0.018), but for non-European coun-
tries, it was nearly two times higher (B = 0.925, Eta
= 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 [176], in which the authors found 47.6% seroprev-
alence of toxoplasmosis among OCD patients (n = 42) and only
19% prevalence in controls (n = 100). Both neurotransmitters,
dopamine and serotonin, are expected to play an important role in
OCD. It is possible that either an increased concentration of
dopamine, synthesized by two enzymes encoded in T. gondii
genome, and a decreased level of serotonin, the metabolite of
tryptophan degradation – the part of the host defense against
parasitic infection – could be important etiologic factors in the
development of OCD. Incidentally, OCD is not an uncommon
disease (incidence of about 3%) and is probably associated with an
increased risk of suicide [353–356]. It can be speculated that an
association between toxoplasmosis and OCD could, in part, be
responsible for the increased risk of suicides reported in
Toxoplasma-infected individuals. It is possible that the nearly twice
stronger relationship between toxoplasmosis and OCD in Euro-
pean (Eta
= 0.202) than in non-European (Eta
= 0.360) countries
could somehow be related with the negative, not positive,
relationship between the prevalence of toxoplasmosis and
incidence of suicides in non-European countries observed in our
study, see below.
Figure 4. Correlation of mortality and Disability Adjusted Life Year (DALY) with prevalence of toxoplasmosis for all 88 WHO
member countries (29 European and 59 non-European countries). 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.
Correlation of Toxoplasmosis with Disease Burden
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Endocrine disorders. 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-Toxoplasma IgG antibodies in patients with
thyroid autoimmunity [277,357] as well as in many other
autoimmune diseases, as compared with controls (Table 2). The
autoantibody burden has also been demonstrated even in non-
autoimmune individuals during infections [358]. Patients with
autoimmune diseases frequently present neurologic manifestations
[359], and this may further support the significant prevalence of
toxoplasmosis in patients with endocrine disorders, because central
nervous system is the most immunoprivileged organ for T. gondii
dissemination and settlement in the host. Fetal [360] and maternal
microchimerism, acting as a ‘‘Trojan horse’’ in dissemination of
the parasite, could play an important role in endocrine and other
health disorders [361].
Sexually transmitted diseases (STDs). A regression coef-
ficient (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, Eta
= 0.215,
p = 0.017) than in non-European countries (B = 1.699,
= 0.041, p = 0.133). Similar effects were observed for gonor-
rhea (B = 0.175, Eta
= 0.213, p = 0.018) and chlamydia
(B = 0.229, Eta
= 0.209, p = 0.019) in Europe, but were different
for non-European countries for gonorrhoea (B = 0.549,
= 0.069, p = 0.049) and chlamydia (B = 0.287, Eta
= 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 [332] that Toxoplasma is frequently
transmitted by ejaculate in several animal species. An indirect
evidence exists that the same could also occur in humans [331].
Practicing oral sex or even kissing may also be another important
route of wide dissemination of the parasite among sexual partners,
in addition to intercourse.
Pertussis. 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 neces-
sary 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 [363]. Administration of DTP vaccine
caused dose-, and time-dependent biological changes in animals,
including increased hepatic mRNA expression for several cyto-
kines, marked inhibition of liver CYP450 enzymes activity,
induction of IFN-c, and enhanced NOS mRNA expression
[364,365]. In addition, a significant increase in toxoplasma-cysts
was observed in brain tissues of mice exposed to both T. gondii
infection and methylmercury (thimerosal, a vaccine preservative)
versus the parasite alone [366]. Thus, it seems that a concomitant
use of strong lipopolysaccharide antigen (a component of the
whole-cell pertussis) and thimerosal exerted serious synergistic
adverse health effects when given to individuals with latent central
nervous system T. gondii infection [184,340]. It is not clear,
however, whether the incidence of pertussis correlates with
intensity of DPT vaccination.
Childhood cluster diseases. 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 T. gondii infection is
extensively prevalent worldwide [148,367].
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
[368]. For example, exposure of children to cigarette smoke
(second-hand) increased their susceptibility to viral and bacterial
infections because children who died of sudden infant death
syndrome had markedly higher concentration of cotinine (a
metabolite of nicotine) in their lung tissue and pericardial fluid
than in controls [369,370]. Thus, negative effects of latent
toxoplasmosis on children’s physiology, including function of the
immune system, may markedly affect clinical course of diseases in
children and might significantly affect disease severity and
Suicides. Latent toxoplasmosis was found to be associated
with an increased risk of attempted suicides [161,170,171,371].
The results of earlier correlation studies performed for 17–20
European countries [172,173] were confirmed by the present
study, wherein a positive trend was observed for the 29 European
countries (B = 4.05, p = 0.065, Eta
= 0.135), but, this correlation
could not be detected for the entire 88 countries. In fact, a
negative correlation between risk of suicide and prevalence of
latent toxoplasmosis was found for the 59 non-European countries
(B = 22.157, p = 0.012, Eta
= 0.11). We have no explanation for
this qualitative difference between European and non-European
countries. However, the existence of positive correlation between
the prevalence of latent toxoplasmosis and violence [174] was
confirmed by partial Kendall correlation for all countries
(Tau = 0.244, p = 0.001) and non-European countries
(Tau = 0.276, p = 0.002), but not for European countries
(Tau = 0.065, p = 0.619), the GLM method showed just a trend
for European countries (see tables shown in Fig. 3 and Fig. 4).
Traffic accidents. 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 toxoplas-
mosis and traffic accidents was found for RhD negative drivers
[372], while the RhD positive subjects, especially RhD positive
heterozygotes seem to be relatively protected against impairment
of reaction times [373,374] as well as against traffic accidents [372]
Correlation of Toxoplasmosis with Disease Burden
PLOS ONE | 14 March 2014 | Volume 9 | Issue 3 | e90203
(the RhD refers to ‘‘Rhesus factor’’ with immunogenic D antigen,
while RhAG indicates no Rh antigens on red blood cell
membranes). The lack or deficiency of RhAG proteins in the host
red blood cell membrane and an impaired function of aquaporin
P1 and P4 water/gas channels in the central nervous system could
be associated with various degrees of brain hypoxia [339], thus
affecting usual driving performance possibly in synergy with the
effects of toxoplasmosis on reaction times and ability of long-term
concentration [3732375]. Since RhD negative individuals are
rare in African and Asian populations [376], an association
between traffic accidents and prevalence of toxoplasmosis can be
expected mainly in countries inhabited by Caucasians.
Limitations of the study
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 consider-
ably 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. Further-
more, 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 [5].
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 indepen-
dent 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.
Author Contributions
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.
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Correlation of Toxoplasmosis with Disease Burden
PLOS ONE | 22 March 2014 | Volume 9 | Issue 3 | e90203
... Bradyzoites can persist inside human cells during protracted periods of time. Remarkably stable oocysts are transmitted to other hosts through inadvertent ingestion [1]. Domestic cats and other felids are the known definitive hosts of the agent and can eliminate viable oocysts through their feces [2]. ...
... T. gondii prevalence in humans varies across countries and regions [2][3][4]. A possible explanation is that T. gondii incidence is higher in regions with higher humidity and temperature, such as South America (prevalence in Brazil reaches 77.5%) [2,4], in the same way that infection by the parasite is lower in some European countries and the Far East [1,4]. This is because the oocysts are more long-lived in humid environments during the parasite's reproduction cycle [1]. ...
... A possible explanation is that T. gondii incidence is higher in regions with higher humidity and temperature, such as South America (prevalence in Brazil reaches 77.5%) [2,4], in the same way that infection by the parasite is lower in some European countries and the Far East [1,4]. This is because the oocysts are more long-lived in humid environments during the parasite's reproduction cycle [1]. ...
Full-text available
Toxoplasmosis is caused by the protozoan parasite Toxoplasma gondii (T. gondii), which is one of the most widespread zoonotic pathogens known today. It is a global health hazard as they infect 30-50% of the world's human population. Acute toxoplasmosis is usually asymptomatic and self-limited in immunocompetent people, recovering without treatment and do not require specific therapy. Therefore, rare complications are associated with infection in the individuals with normal immune systems. However, we present a rare case of an immunocompetent man with acute T. gondii infection confirmed by serology, subsequently presented with two life-threatening organ dysfunctions: severe renal and pulmonary involvement, requiring hospitalization and anti-parasitic treatment.
... Upon contact with oxygen, oocysts will sporulate and lead to infective environmentally resistant oocysts (Ferguson, 2002) that can be consumed by intermediate hosts, including pregnant women. Altogether, these characteristics make T. gondii one of the most successful zoonotic parasites worldwide (Flegr et al., 2014). ...
Full-text available
Toxoplasma gondii is a ubiquitous apicomplexan parasite that can infect virtually any warm-blooded animal. Acquired infection during pregnancy and the placental breach, is at the core of the most devastating consequences of toxoplasmosis. T. gondii can severely impact the pregnancy’s outcome causing miscarriages, stillbirths, premature births, babies with hydrocephalus, microcephaly or intellectual disability, and other later onset neurological, ophthalmological or auditory diseases. To tackle T. gondii’s vertical transmission, it is important to understand the mechanisms underlying host-parasite interactions at the maternal-fetal interface. Nonetheless, the complexity of the human placenta and the ethical concerns associated with its study, have narrowed the modeling of parasite vertical transmission to animal models, encompassing several unavoidable experimental limitations. Some of these difficulties have been overcome by the development of different human cell lines and a variety of primary cultures obtained from human placentas. These cellular models, though extremely valuable, have limited ability to recreate what happens in vivo. During the last decades, the development of new biomaterials and the increase in stem cell knowledge have led to the generation of more physiologically relevant in vitro models. These cell cultures incorporate new dimensions and cellular diversity, emerging as promising tools for unraveling the poorly understood T. gondii´s infection mechanisms during pregnancy. Herein, we review the state of the art of 2D and 3D cultures to approach the biology of T. gondii pertaining to vertical transmission, highlighting the challenges and experimental opportunities of these up-and-coming experimental platforms.
... Humans, as IH, present a third or more people who have been exposed to infection with T. gondii. The prevalence ranges widely (10-85%) between nations, geographical areas within a country [7], socioeconomic conditions, climate (warm, humid tropical areas, cold-temperate, or desert regions), poor sanitation, a lack of clean water, and poor hygiene [44]. Toxoplasmosis is classified into an acute acquired infection (horizontal transmission) and a congenital infection (CT) [45] with an incubation period from 10 to 23 days after consuming tissue cysts and from 5 to 10 days following the consumption of oocysts [10,46]. ...
... Humans, as IH, present a third or more people who have been exposed to infection with T. gondii. The prevalence ranges widely (10-85%) between nations, geographical areas within a country [7], socioeconomic conditions, climate (warm, humid tropical areas, cold-temperate, or desert regions), poor sanitation, a lack of clean water, and poor hygiene [44]. Toxoplasmosis is classified into an acute acquired infection (horizontal transmission) and a congenital infection (CT) [45] with an incubation period from 10 to 23 days after consuming tissue cysts and from 5 to 10 days following the consumption of oocysts [10,46]. ...
... Humans, as IH, present a third or more people who have been exposed to infection with T. gondii. The prevalence ranges widely (10-85%) between nations, geographical areas within a country [7], socioeconomic conditions, climate (warm, humid tropical areas, cold-temperate, or desert regions), poor sanitation, a lack of clean water, and poor hygiene [44]. Toxoplasmosis is classified into an acute acquired infection (horizontal transmission) and a congenital infection (CT) [45] with an incubation period from 10 to 23 days after consuming tissue cysts and from 5 to 10 days following the consumption of oocysts [10,46]. ...
Full-text available
Since the first isolation over a century ago, Toxoplasma gondii has been extensively studied to understand its biology, transmission, life cycle, and implications for the health of its definitive hosts and intermediate hosts, including the human being. The life cycle of this protozoan of the phylum Apicomplexa presents different stages (sexual and asexual), which, in combination with a capacity for resistance to the environment and multiple hosts, makes this organism highly adaptable and easy to transmit and spread. Sequencing of the T. gondii genome allowed the development of databases applied to the study, diagnosis, and typification, as well as the analysis of pathogenic factors associated with the capacity. Particularly, T. gondii is mainly mentioned in the literature due to its potential effect on various species, including humans. The DH-environment-IH interactions form the essential ecological components for its dissemination, mainly by fecal material/oral cycle. Human infection is highly impacted worldwide since it is presumed that more than a third of the human population has been infected by this protozoan. Due to the immune system being actively involved in controlling infection, clinical signs range from a simple cold to severe illness in the case of an immunodeficient situation (eye lesions, lymphopathy, embryonic damage, and mental disorders). Its study demonstrated its presence in many foods of animal and vegetable origin, placing this infection as one of the main risks of food-borne diseases. Its presence in wildlife is also an intrinsically related factor in its worldwide distribution. Due to this, T. gondii represents a high risk for humans and a great variety of IHs that can be affected by this parasite; therefore, the study is highly relevant for its control and research worldwide.
... No entanto, a incidência de infecção é mais elevada em regiões de clima quente e úmido e quando associada às condições precárias de saneamento básico a transmissão do T. gondii se torna mais comum. Estima-se que 30 a 50% da população mundial esteja infectada com o parasito, sendo a toxoplasmose, uma das infecções com maior soroprevalência em humanos [3][4][5] . No Brasil, até 50% das crianças e 80% das mulheres em idade fértil podem apresentar anticorpos para esse protozoário, dependendo da região geográfica 6 . ...
A toxoplasmose é uma zoonose causada pelo Toxoplasma gondii, um protozoário com ampla distribuição mundial. Essa infecção apresenta maior impacto em indivíduos imunocomprometidos e nas infecções congênitas. Objetivou-se avaliar o perfil sorológico para toxoplasmose de mulheres em idade reprodutiva (15-49 anos) atendidas em uma maternidade-escola de Santa Cruz, Rio Grande do Norte (RN). Foi realizado um estudo descritivo, retrospectivo e quantitativo em que se analisou os laudos de 274 mulheres, do período de janeiro a maio de 2018. As variáveis estudadas foram: resultado das sorologias IgG e IgM anti-Toxoplasma, idade, zona e bairro de residência e método(s) de diagnóstico(s) utilizado(s). Dos 274 laudos, 40,1% apresentaram sorologia reagente para IgG anti-T. gondii. Apresentaram IgM anti-T.gondii reagente, 0,7%, enquanto 47,8% eram suscetíveis à toxoplasmose. Dos 241 laudos com sorologias conclusivas (soropositivas ou suscetíveis), as mulheres na faixa etária 31-42 anos apresentaram associação estatisticamente significativa com soropositividade e uma ocorrência 1,4 vezes maior que as de 15-30 anos (p = 0,014; RP=1,420, IC = 1,086-1,859). O maior percentual de soropositivas foi na zona urbana (72,2%) e bairro Paraíso (43,2%) da cidade de Santa Cruz. Desse modo, verificou-se que há necessidade de programas de promoção a saúde e melhorias sanitárias e ambientais para as mulheres da região.
... [1] More than one-third of the world's population is estimated to be infected with this parasite. [2] T. gondii infection is generally asymptomatic DOI: 10.1002/advs.202206595 in people with normal immunity. However, it can be fatal to infants and immunosuppressed patients, such as organ transplant recipients and patients with AIDS or cancer. ...
Full-text available
Toxoplasma gondii (T. gondii) is the causative agent of toxoplasmosis and can infect numerous warm‐blooded animals. An improved understanding of the fine structure of this parasite can help elucidate its replication mechanism. Previous studies have resolved the ultrastructure of the cytoskeleton using purified samples, which eliminates their cellular context. Here the application of cryo‐electron tomography to visualize T. gondii tachyzoites in their native state is reported. The fine structure and cellular distribution of the cytoskeleton are resolved and analyzed at nanometer resolution. Additionally, the tachyzoite structural characteristics are annotated during its endodyogeny for the first time. By comparing the structural features in mature tachyzoites and their daughter buds, it is proposed that the conoid fiber of the Apicomplexa originates from microtubules. This work represents the detailed molecular anatomy of T. gondii, particularly during the budding replication stage of tachyzoite, and provides a reference for further studies of this fascinating organism. This study utilized advanced cryo‐ET technology to provide a detailed molecular anatomy of T. gondii, with a particular focus on the budding endodyogeny stage of tachyzoites. In addition to confirming previous research, this study uncovered significant new features. Based on these findings, the study proposes that the conoid fiber, a critical component of the conoid, may have microtubule origins.
Full-text available
Toxoplasmosis is an infection of vast worldwide distribution whose etiologic agent is Toxoplasma gondii. This disease can cause problems ranging from mild symptoms to serious conditions, such as encephalitis, miscarriage and blindness. Therefore, it is of utmost importance to perform a diagnosis with reproducible techniques in order to obtain a good prognosis. The aim of this review was to analyze the efficiency of toxoplasmosis diagnostic techniques based on sensitivity and specificity results. Five research platforms in English language were used (Eric, Elsevier, Google Scholar, PubMed and SciELO), which contained data on the diagnosis of toxoplasmosis. The search and selection were performed for studies published prior to June 2021. The search resulted in the inclusion of 13 articles published from 2005 to 2020. The data revealed the use of different samples in the standardization of techniques such as serum, total blood, colostrum and amniotic fluid. The flow cytometry, lateral flow immunoassay and qPCR techniques showed 100% sensitivity, whereas the ELISA, western blotting, qPCR and RE-LAMP techniques achieved 100% specificity. Significantly, the qPCR and LAMP techniques were more accurate when the likelihood ratio was assessed. The meta-analysis identified that ISAGA and western blotting have low sensitivity values and LIASON, ELFA and ELISA, using a silica bioconjugate, also have low specificity values. It was noted that a wide range of methods have high values of sensitivity and specificity. Therefore, the choice of the method will be based on the conditions and its financial viability.
La toxoplasmosis es una enfermedad de alta prevalencia y distribución mundial que puede cursar de forma asintomática, aunque también puede ocasionar clínica grave en personas inmunocomprometidas e incluso ser mortal. Este libro compila información desde la perspectiva “Una salud” contando con la visión de diferentes profesionales implicados en el área: clínicos, epidemiólogos y microbiólogos, lo que proporciona una perspectiva altamente enriquecedora y de gran utilidad para todos aquellos profesionales interesados en esta temática.
La toxoplasmosis es una enfermedad de alta prevalencia y distribución mundial que puede cursar de forma asintomática, aunque también puede ocasionar clínica grave en personas inmunocomprometidas e incluso ser mortal. Este libro compila información desde la perspectiva “Una salud” contando con la visión de diferentes profesionales implicados en el área: clínicos, epidemiólogos y microbiólogos, lo que proporciona una perspectiva altamente enriquecedora y de gran utilidad para todos aquellos profesionales interesados en esta temática.
Full-text available
Although parasitic infections do not usually present with disturbance in renal function, glomerular lesions can be seen in most of these infections. The glomerular lesions observed in parasitic infections cover the whole range of glomerular lesions known, but most of them are proliferative. Little is known of the exact pathogenic mechanisms. In this review, we try to explain the glomerular lesions associated with parasitic infections in terms of the specific immunologic events observed during these diseases against the background of recent developments in the general knowledge of the pathogenesis of glomerular disease.
Full-text available
Toxoplasma gondii (T. gondii) infections can cause serious complications in HIV-infected pregnant women, leading to miscarriage, stillbirth, birth defects (e.g., mental retardation, blindness, epilepsy etc.) and could favor or enhance the mother-to-child transmission of HCV, HBV, and HIV vertical transmission. From May 20, 2004 to August 3, 2005, 336 18–45 years aged pregnant women, were enrolled for an investigation of the prevalence of serum antibodies against T. gondii, HCV, HBV, and HIV using ELISA. The prevalence of T. gondii, HCV, and HBV in pregnant women was 25.3%, 5.4%, and 9.8%, respectively and the HIV serostatus (61.6%) seems to be associated with greater prevalence rates of both T. gondii (28.5% vs. 20.2%) and HBV (11.6% vs. 7.0%). Without taking into account HIV, only 65.5% (220 of 336) of the women were not infected with these agents. The co-infection rate between HIV-infected and -negative women was different statistically: T. gondii/HBV 0.048 versus 0.015, T. gondii/HCV 0.014 versus 0.008, and HCV/HBV 0.005 versus 0.008, respectively. The elevated co-infection rate in HIV-positive women demonstrated that they are exposed to T. gondii, HCV, and HBV infections prevalently by sexual contact. J. Med. Virol. 78:730–733, 2006. © 2006 Wiley-Liss, Inc.
Background: Toxoplasma gondii is found worldwide, but distribution of its genotypes as well as clinical expression of human toxoplasmosis varies across the continents. Several studies in Europe, North America and South America argued for a role of genotypes in the clinical expression of human toxoplasmosis. Genetic data concerning T. gondii isolates from Africa are scarce and not sufficient to investigate the population structure, a fundamental analysis for a better understanding of distribution, circulation, and transmission. Methodology/Principal Findings: Seropositive animals originating from urban and rural areas in Gabon were analyzed for T. gondii isolation and genotyping. Sixty-eight isolates, including one mixed infection (69 strains), were obtained by bioassay in mice. Genotyping was performed using length polymorphism of 13 microsatellite markers located on 10 different chromosomes. Results were analyzed in terms of population structure by Bayesian statistical modeling, Neighbor-joining trees reconstruction based on genetic distances, F-ST and linkage disequilibrium. A moderate genetic diversity was detected. Three haplogroups and one single genotype clustered 27 genotypes. The majority of strains belonged to one haplogroup corresponding to the worldwide Type III. The remaining strains were distributed into two haplogroups (Africa 1 and 3) and one single genotype. Mouse virulence at isolation was significantly different between haplogroups. Africa 1 haplogroup was the most virulent. Conclusion: Africa 1 and 3 haplogroups were proposed as being new major haplogroups of T. gondii circulating in Africa. A possible link with strains circulating in South and Central America is discussed. Analysis of population structure demonstrated a local spread within a rural area and strain circulation between the main cities of the country. This circulation, favored by human activity could lead to genetic exchanges. For the first time, key epidemiological questions were addressed for the West African T. gondii population, using the high discriminatory power of microsatellite markers, thus creating a basis for further epidemiological and clinical investigations.