Abstract
Abdominal pain has been rarely reported in individuals infected with Toxoplasma gondii (T. gondii). The aim of this study was to determine the association between T. gondii infection and abdominal pain. Two hundred and ninety-nine patients with abdominal pain (cases) and 299 age- and gender-matched people without abdominal pain (controls) were tested for anti-T. gondii IgG and IgM antibodies. Twenty-four (8.0%) of the 299 cases and 12 (4.0%) of the 299 controls were positive for anti-T. gondii IgG antibodies (OR: 2.08; 95% CI: 1.02–4.25; P = 0.03). The seroprevalence of T. gondii infection was significantly higher in women with frequent abdominal pain than in women without this clinical feature (OR: 2.30; 95% CI: 1.06–4.96; P = 0.02). Twelve (4.0%) of the 299 cases and 7 (2.3%) of the 299 controls had high (>150 IU mL−1) anti-T. gondii IgG antibody levels (OR: 1.74; 95% CI: 0.67–4.49; P = 0.24). Seven (29.2%) of the 24 cases with anti-T. gondii IgG antibodies and 3 (25.0%) of the 12 controls with anti-T. gondii IgG antibodies were positive to anti-T. gondii IgM antibodies (OR: 1.23; 95% CI: 0.25–5.97; P = 1.00). Results suggest an association between T. gondii infection and frequent abdominal pain. Further research to confirm this association should be conducted.
Introduction
Toxoplasma gondii (T. gondii) is a parasite causing infections all around the world [1]. One-third of humanity is likely infected by T. gondii [2]. Infection with T. gondii mainly occurs orally through contaminated food or water [3]. Primary infection with T. gondii is usually subclinical [4], but during pregnancy may cause severe damage to the fetus [3]. Infection with T. gondii causes several clinical syndromes including encephalitis, chorioretinitis [5], and lymphadenopathy [3]. In addition, infection with T. gondii has been associated with neuropsychiatric disorders [6–9]. Furthermore, T. gondii exposure has been linked to traffic accidents [10], and suicide attempts [11, 12].
After ingestion, T. gondii invades the small intestine inducing an inflammatory response [13]. Experimental oral infection with T. gondii in mice leads to bowel inflammation [14]. At least 70 reports of animal species indicate that infection with T. gondii causes gastrointestinal inflammation [15]. In addition, T. gondii may affect other abdominal organs and tissues. For instance, infection with T. gondii has been associated with liver disease in humans [16, 17], and pathology in liver, pancreas, spleen, and mesenteric lymph nodes in some animal species [17–20]. Therefore, it would be expected that infection with T. gondii induces abdominal pain in the host. However, abdominal pain in T. gondii infected individuals has been rarely reported. Abdominal pain was reported in 3 immunocompromised patients with gastrointestinal toxoplasmosis [21–23]. In a study of 14 cases of toxoplasmosis in travelers, researchers found that 14% of the patients had abdominal pain [24]. In a cross-sectional seroprevalence study of Yoremes in Mexico, an association between T. gondii infection and frequent abdominal pain was found [25]. To the best of our knowledge, no case-control study on the evaluation of the epidemiological link between T. gondii infection and abdominal pain exist. Therefore, we determined the association between the seroprevalence of T. gondii infection and frequent abdominal pain in people in Durango, Mexico.
Materials and methods
Study design and study population
We performed a case-control study of 299 patients with frequent abdominal pain (cases) and 299 people without abdominal pain (controls). Participants were enrolled consecutively at the Clinical Laboratory in a public primary health care center in Durango City, Mexico from September 2015 to July 2019. Cases included patients suffering from frequent abdominal pain aged 18 years and older. Controls were patients without frequent abdominal pain, randomly selected, and matched with cases by age (±2 years) and gender. Each group of cases and controls included 277 women and 22 men. Mean age in controls was comparable to that in controls (38.03 ± 14.99 vs 38.16 ± 14.96, respectively; P = 0.91).
Laboratory tests
A single blood sample was obtained from participants. Blood samples were centrifuged, and sera obtained were stored at −20 °C until analyzed. Serum samples were analyzed for T. gondii infection markers as described elsewhere [9].
Statistical analysis
Statistical analysis was performed using the software IBM SPSS version 20 and Epi Info version 7. For calculation of the sample size, we used the following parameters: a two-sided confidence level of 99.9%, a power of 80%, a ratio of unexposed/exposed of 1, and a reference seroprevalence of T. gondii infection in Durango City of 6.1% [26]. A sample size of 270 cases and 270 controls was obtained. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to estimate the association between T. gondii exposure and other variables. The Pearson's chi-square test and the Fisher exact test (when values were 5 or less) were used to compare categorical variables. Statistical significance was set at a P < 0.05.
Ethical aspects
Written informed consent was obtained from all cases and controls. The study was approved by the Institutional Review Boards of the General Hospital of the Secretary of Health and the Institute of Security and Social Services for the State Workers in Durango City, Mexico.
Results
Twenty-four (8.0%) of the 299 patients with frequent abdominal pain and 12 (4.0%) of the 299 controls were positive for anti-T. gondii IgG antibodies. The rate of T. gondii exposure was significantly higher in cases than in controls (OR: 2.08; 95% CI: 1.02–4.25; P = 0.03). Thus, the frequency of abdominal pain was significantly higher in individuals with positive test for anti-T. gondii IgG antibodies (24/36: 66.7%) than in individuals with negative test for anti-T. gondii IgG antibodies (275/562; 48.9%). Table 1 presents an age and sex stratification and rates of T. gondii IgG seropositivity in cases and controls. The rate of T. gondii seropositivity was significantly higher in women with frequent abdominal pain than in women without this symptom. Stratification by age groups showed no statistically significant differences in the seroprevalence of T. gondii infection among cases and controls. Twelve (4.0%) of the 299 cases and 7 (2.3%) of the 299 controls had high (>150 IU mL−1) anti-T. gondii IgG antibody levels (OR: 1.74; 95% CI: 0.67–4.49; P = 0.24). Table 2 presents an age and sex stratification and rates of high anti-T. gondii IgG antibody levels in cases and controls. This stratification showed no statistically significant differences in the rates of high anti-T. gondii IgG antibody levels among cases and controls. Seven (29.2%) of the 24 cases with anti-T. gondii IgG antibodies and 3 (25.0%) of the 12 controls with anti-T. gondii IgG antibodies showed reactivity to anti-T. gondii IgM antibodies (OR: 1.23; 95% CI: 0.25–5.97; P = 1.00).
Stratification by sex and age and seroprevalence of T. gondii exposurein cases and controls
| Characteristic | Cases | Controls | OR | 95% confidence interval | P value | ||||
| No. | Seropositivity to T. gondii | No. | Seropositivity to T. gondii | ||||||
| tested | No. | % | tested | No. | % | ||||
| Sex | |||||||||
| Male | 22 | 2 | 9.1 | 22 | 2 | 9.1 | 1.00 | 0.12–7.81 | 1.00 |
| Female | 277 | 22 | 7.9 | 277 | 10 | 3.6 | 2.30 | 1.06–4.96 | 0.02 |
| Age (years) | |||||||||
| ≤30 | 113 | 3 | 2.7 | 114 | 1 | 0.9 | 3.08 | 0.31–30.08 | 0.36 |
| 31–50 | 117 | 12 | 10.3 | 117 | 8 | 6.8 | 1.55 | 0.61–3.96 | 0.34 |
| >50 | 69 | 9 | 13.0 | 68 | 3 | 4.4 | 3.25 | 0.84–12.57 | 0.12 |
| All | 299 | 24 | 8.0 | 299 | 12 | 4.0 | 2.08 | 1.02–4.25 | 0.03 |
Stratification by sex and age and frequency of high (>150 IU mL−1) levels of anti-T. gondii IgG antibodies in cases and controls
| Characteristic | Cases | Controls | OR | 95% confidence interval | P value | ||||
| No. tested | >150 IU mL−1 of IgG | No. Tested | >150 IU mL−1 of IgG | ||||||
| No. | % | No. | % | ||||||
| Sex | |||||||||
| Male | 22 | 1 | 4.5 | 22 | 2 | 9.1 | 0.47 | 0.04–5.67 | 1.00 |
| Female | 277 | 11 | 4.0 | 277 | 5 | 1.8 | 2.24 | 0.77–6.56 | 0.20 |
| Age (years) | |||||||||
| ≤30 | 113 | 1 | 0.9 | 114 | 0 | 0.0 | – | – | 0.49 |
| 31–50 | 117 | 6 | 5.1 | 117 | 4 | 3.4 | 1.52 | 0.41–5.55 | 0.74 |
| >50 | 69 | 5 | 7.2 | 68 | 3 | 4.4 | 1.69 | 0.38–7.37 | 0.71 |
| All | 299 | 12 | 4.0 | 299 | 7 | 2.3 | 1.74 | 0.67–4.49 | 0.24 |
Discussion
Abdominal pain is not currently recognized as a typical symptom of toxoplasmosis. Descriptions on clinical manifestations of toxoplasmosis in the medical literature usually include only lymphadenopathy, chorioretinitis, encephalitis and congenital disease [3, 5]. However, it is likely that more and yet unrecognized clinical manifestations can be present during infection with T. gondii. Occult effects of infection could increase the importance of toxoplasmosis as a public health problem [6]. In this study, we assessed the association between T. gondii seropositivity and abdominal pain. We observed that patients with frequent abdominal pain had a significantly higher rate of anti-T. gondii IgG seropositivity than individuals without this clinical manifestation. Therefore, our results suggest that seropositivity to T. gondii is associated with frequent abdominal pain. The finding of this current age- and gender-matched case-control study supports the association between T. gondii exposure and frequent abdominal pain reported in a cross-sectional study of Yoremes in Mexico [25]. There are only few more reports on the presence of abdominal pain in individuals infected with T. gondii. Abdominal pain was present in 3 isolated cases of immunocompromised patients with gastrointestinal toxoplasmosis [21–23], and in 14% of 14 cases of toxoplasmosis in immunocompetent travelers [24]. The mechanisms underlying abdominal pain during T. gondii infection in humans are largely unknown. Abdominal pain during T. gondii infection might be explained by the gastrointestinal pathology induced by T. gondii as observed in animal models. Oral infection with T. gondii causes intestinal pathology in mice and many other animal species. At least 70 publications have reported the development of gastrointestinal inflammation following oral infection with T. gondii in 63 animal species [15]. Small intestinal immunopathology is mediated by local overproduction of Th1-type cytokines referred as “cytokine storm” [15]. Abdominal pain could also be explained by the involvement of abdominal organs and tissues during T. gondii infection. Liver disease has been linked to T. gondii infection in humans [16, 17]. In addition, T. gondii causes pathology in liver, pancreas, spleen, and mesenteric lymph nodes in several animal species [18–20]. Furthermore, T. gondii infection was associated with abdominal inflammation in women [27]. Interestingly, in the current study, stratification by gender showed an association between T. gondii infection and frequent abdominal pain in women. There was a small number of men in our study, and further research to determine the association between T. gondii infection and abdominal pain in men should be conducted. In this study, abdominal pain was associated with the latency of anti-T. gondii IgG antibodies but not with high (>150 IU mL−1) levels of anti-T. gondii IgG antibodies nor with the existence of anti-T. gondii IgM antibodies. Therefore, results suggest that abdominal pain was associated with “latent” infection. However, a limitation of the study was that a small number of likely recent cases of T. gondii infection was included. Further studies to assess the association between T. gondii infection and abdominal pain including a large sample of cases with recent infection should be conducted.
Conclusions
Our results suggest that seropositivity to T. gondii is linked with frequent abdominal pain. However, further studies to confirm this association are needed.
Funding
The Secretary of Public Education, Mexico (Grant No. DSA/103.5/14/11311) financed this study.
Authors contributions
ARN, SMCS, CAGA and LSS obtained blood samples and summited questionnaires. SEM, AOAF, GAAF and CAE carried out data analysis. CAE designed the study, preformed laboratory tests, and wrote the manuscript.
Conflict of interest
The authors declare that there is an absence of conflict of interest.
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