The questions that led us to achieve this study were if Mexico had a significant prevalence of toxoplasmosis, and if there have been changes in the epidemiology of this disease from 1951 to date. Five databases were searched, and 132 studies were selected involving 70,123 individuals and 19,262 positive cases.
This study showed that the WP of toxoplasmosis in Mexico was 20.26%, which is relatively low compared to the mean prevalence of 32% reported in 1991 . This can be explained if we note that variations between methodologies can result in heterogeneity of the estimations. However, despite this situation, at least 20.26% of Mexicans may have been exposed to toxoplasmosis.
Between 1951 and 1958, the STA was an appropriate test since, at that time, it was a rapid and sensitive assay for epidemiological studies. It did not give cross-reactions with other parasites, but it did make a fair amount of false-negatives in mild infections. This was one of its disadvantages when used for a survey in the general population in Tamaulipas, Campeche and Mexico City (1953). The WP was 21.31% in 11 study groups with 1846 cases [16–20]. Since only one study was performed by the FL test with 367 individuals, and another study included 58 cases tested by fixation complement, we were not able to compare these results against the SF or IFI assays.
The SF test was used in epidemiological studies carried out between 1961 and 1966. The CP and WP was 30% and 35.12%, respectively . The advantage of this test is that it is a gold standard, and it is highly sensitive, although the disadvantage is that it requires live parasites. The global prevalence during that time was 14.92%, which is closer, to the prevalence of 8.26% aforementioned. In the same period, the IFI test was introduced and was then used in the largest survey carried out in Mexico (1992) with 29, 279 people with a mean prevalence of 32.0% . The meta-analysis of all tests performed with IFI was 29.32%, because the majority of studies have used this method (31,412 cases).
In the 80s, the ELISA methods were introduced with higher sensitivity and specificity that reduced the number of cross-reactions. Interestingly, the WP was lower, ranging from 8.92% to 17.66%, which may have been caused by the lower number of cases, (8256 cases), less than one-third of the studies, when compared to the 26,751 cases tested with SF and the 30,485 cases with IFI.
The general population involved 61,536 cases with a WP of 20.26%, while the mean prevalence was reported as 32% in 1991 . This discrepancy may be caused by the differences in the diagnostic methods that are then adjusted when the weighted prevalence was estimated .
Pregnant women presented a WP of 15.62% with an upper limit of 16.93% that is closer to the general population prevalence (20.26%), which is reasonable since these women did not have obstetric complications. These values were lower compared to 45.8% and 30.5%, respectively for specific IgG antibodies detected by the Sabin-Feldman dye test in two separate studies among pregnant women , however, our results were higher than 0.6% among pregnant women in Norway .
In the four studies performed in blood donors, the WP was 17.03% among 1123 cases. This prevalence is also closer to the general population prevalence, despite that each one of them was carried out with different diagnostic tests (one with SF , one not reported , one with IFAT  and one with ELISA, respectively ).
Regarding the blood donors group, this group has a lower WP when compared to the general population. Transfusion Medicine guidelines have pronounced that donated blood should be screened for toxoplasmosis, because of the potential risk for blood receptors receiving transfusions from subjects in the acute phase of infection. Therefore, testing of toxoplasmosis in blood donations should be mandatory in the country [5, 46–48].
Three studies performed in Mexico were in women with miscarriages having primary infection during pregnancy. There were clear differences between the WP of pregnant women 15.62% whereas those with miscarriages had 35.96% (p <0.05). These results are concordant with other studies that have shown an association between high prevalence of miscarriages and Toxoplasma infection [39, 44, 45].
Another risk group was the immunocompromised patients. Among 627 cases, the WP of 20.2% was the same as in the general population. One explanation is that the patients were diagnosed by different methods, and two studies performed in Durango had the lowest prevalence [47, 49–52].
The highest WP was 37.24% in the mentally-ill patients, at least 18.27% higher than the general population . Several authors have reported a high prevalence of Toxoplasma antibodies in patients with schizophrenia, although other factors such as genetic may be present in the schizophrenia, different reports have shown that Toxoplasma is somehow associated with cases of schizophrenia. This finding justifies the need to examine the relationship between toxoplasmosis and schizophrenia with pre-clinical and clinical trials aimed to improve prevention and treatment programs in patients with psychiatric illness [71, 72]. On the other hand, a meta-analysis of latent Toxoplasma gondii infection in immunocompetent hosts and cryptogenic epilepsy showed a strong association between seroprevalence rates for toxoplasmosis and prevalence rates of epilepsy. If an etiological connection can be proven, it would have implications for the implementation of prevention and treatment strategies for Toxoplasma disease .
Cat owners and slaughterhouse workers presented both a CP and WP of 21.88% each. This may be because only five studies with 501 individuals with this attribute were analyzed. Regarding patients with nonrelated comorbidity, WP was 12.28%, lower than in the general population. Three groups were studied with STA and four more from Durango had the lowest prevalence in the country, which may show that their comorbidity was not related to the risk of infection.
Another important factor is the difference in the prevalence of T. gondii infections due to the sensitivity and specificity of diagnostic tests, since there are several methods to identify and evaluate antibodies in individuals who were infected by the parasite. Over time, at least four different diagnostic assays have been used worldwide that range from the lowest specificity and sensitivity like the STA progressing on to the SF Dye Test and other similar tests up to the improved ELISA (Table 2) [7, 74].
In regards to the analysis of the study groups adjusted by risk factors (with or without) and diagnostic test, we found that only those tested by ELISA showed a WP of 17.66% in the risk factor groups against a WP of 8.92% in the groups without risk factors. However, with the other methods, both crude and weighted prevalence were reduced; however, the number of studied individuals was higher. This analysis demonstrates that the prevalence varies according to the diagnostic method and by the number of individuals tested in each study group (Figure 2).
The epidemiological behavior of Toxoplasma infection showed a negative slope of -0.1%/year, which represented an accumulated decrement of nearly 6% in the prevalence of infection in Mexico after 60 years. This may suggest that we have not paid enough attention to T. gondii infection as a public health problem though it tends to decrease. However, another key issue is that if the studies carried out in the first 10 years had been tested with ELISA then the decrement would have been even lower (Figure 2).
In this study, stratification of studies based on molecular assays was not feasible because none was reported. However, genotyping has been reported in other Latin American populations, such as Colombia where a virulent strain (LD100 of 10 tachyzoites) was identified as clonal type 1 (CIBMUQ/HDC) . Additionally, in another study, the GRA6 type I/III profile was the most frequent among asymptomatic cases (68/148, 45.9%) and in severe multi visceral cases (2/4, 50%). Furthermore, GRA6 type II, was found in one case of congenital toxoplasmosis, one case of severe multi visceral infection, one case of ocular infection, and in five cases (5/148,3.4%) of asymptomatic patients . Further studies based on genetic-based diagnostic assays will be relevant in the future, since Toxoplasma gondii isolates from Latin America have mixed/ recombinant genetic structure.
A 6% decrement in the prevalence of Toxoplasma infection after 60 years of studies was detected. This decrement is quite low after a relatively long period, contrary to what has been reported in the United States, with a 14% decrement in only one decade . Therefore, our data warrants that researchers must pay more attention to this disease and to communicate to the medical community the need of improvement of the prevention strategies, together with effective diagnostic testing and management of patients in high risk of infection such as immunocompromised patients and pregnant women.
Further research is still required to understand and clarify the role of T. gondii in its diverse routes of transmission, as well as to design better control measures that focus on minimizing the risk of infection. The purpose of such studies should be to aid in the monitoring of changes in the epidemiology of T. gondii infection, and to strengthen educational efforts in order to avoid the transmission of infection in populations that cannot be controlled by drugs alone.
Implications for research
A crucial factor is the difference in the prevalence of T. gondii infections due to the sensitivity and specificity of the diagnostic tests, since there are several methods to identify and evaluate antibodies in individuals who were infected by the parasite. At least four different diagnostic assays have been used in this study, that range from the lowest specificity and sensitivity like the CF, progressing on to the SF dye test and other similar tests up to the improved ELISA.