Sero-epidemiology of Toxoplasma gondii and risk factors among pregnant women in Africa

Introduction Infections caused by Toxoplasma gondii is a great public health concern worldwide. Toxoplasma gondii infection in pregnant women may result in abortion, stillbirth, or lifelong disabilities of the fetus. Serologic studies have reported various estimates for seroprevalence of toxoplasmosis among African pregnant women. Estimation of the pooled seroprevalence of this infection is necessary for policy-making and target intervention. Methods We conducted this systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A rigorous literature selection was performed by using the databases of PubMed, Google Scholar, and ScienceDirect for the period Jan 1, 2001, to July 31, 2019. Sero-prevalence with 95% CI was presented for each study, and point estimates and their 95% CIs of pooled seroprevalence was then calculated. Findings The search process resulted in the inclusion of a total of 36 studies in the systematic review and meta-analysis. The pooled seroprevalence of Toxoplasma gondii Immunoglobulin G (IgG) in Africa was found to be 46.7% (95%CI: 37.0, 56.4). Geographical-based subgroup analysis showed that the seroprevalence of T. gondii among pregnant women was found to be 65.1% (95% CI: 44.7, 85.5), 50.2% (95% CI: 32.0, 68.3), 47.8% (95% CI: 31.7, 63.8), 38.3% (95% CI: 25.2, 51.4) and 5.8% (95% CI: 3.6, 8.1) in Central, Eastern, Northern, Western and Southern Africa respectively. The most common risk factors for T. gondii were living or contact with cat and consumption of raw vegetables or fruits. Conclusion The current systematic review and meta-analysis revealed a high seroprevalence of Toxoplasma gondii infection among pregnant women. There is a


Introduction
Toxoplasma gondii (T. gondii) an apicomplexan, unicellular parasite, is one of the most common zoonoses around the world, affecting warm-blooded animals, including humans [1].
It is approximated that up to one-third of the world's human population is infected with T. gondii [2]. Moreover, T. gondii is considered as the third most common foodborne pathogen of which patients are infected [3].
Human can be infected with T. gondii through one of three ways: 1) by eating raw or undercooked meat containing T. gondii tissue cysts or eating food that has been cross-contaminated with raw/undercooked meat; 2) by ingesting oocysts from soil (through gardening, handling/eating unwashed vegetables, or infected cat feces); or 3) by acquiring congenital infection through the placenta [4,5] when a woman gets an infection during pregnancy [6,7] In most cases, infection in humans is asymptomatic or mild symptoms including malaise, swelling of lymph nodes and fever [8], however, when infection occurs in pregnant women several health problems can affect the fetuses, including mental retardation, blindness, epilepsy, abortion and death [1,9]. Moreover, In a systematic review and meta-analysis, it was reported that T. gondii causes severe encephalitis via acute infection or reactivation of latent infection among immune-suppressed individuals, including those with acquired immunodeficiency syndrome (AIDS), immunosuppressive cancer, and transplant recipients on immunosuppressive drugs [10].
In Africa, the prevalence of T. gondii among pregnant women varies greatly, the lowest prevalence has been reported in Zambia (0.6%) [11] and the highest in Ghana (92.5%) [12].
The wide prevalence range might be due to the different factors that might influence the probability of infection by T. gondii among pregnant women, these factors include environmental, socioeconomic, geographical location, health care facilities, individuals factors such as behavioral and habits [13][14][15]. The present systematic review and meta-analysis were therefore carried out to establish T. gondii seroprevalence among pregnant women, and to evaluate the possible risk factors associated with T. gondii seroprevalence among pregnant women across diverse settings and sampling time periods in Africa. For public health actions, understanding the prevalence and associated risk factors can aid in the analysis of the epidemiological pattern of disease among pregnant women and in Africa.

Search strategy
This study was a systematic review and meta-regression analysis of the seroprevalence of T. gondii and the risk of infection among pregnant women. We searched for studies in PubMed, Google Scholar, and ScienceDirect for the period Jan 1, 2001, to July 31, 2019. Checklist for Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [16] was followed. We used the search term "Toxoplasma gondii",","Toxoplasmosis"pregnant women", "prevalence" and seroprevalence" with the search restricted to records in English.

Data extraction and management
For data extraction, the detailed characteristics of each published study were extracted using a data-collection form. Information was recorded as follows: study characteristics such as the first author, year of publication, year of study, country, study design sample size; the number of the positives cases and seroprevalence of T. gondii of each study.

Data analysis
We analyzed data within sub-regions of sub-Saharan Africa: eastern Africa, southern Africa, and west and central Africa. Data were entered in Microsoft Excel and then exported to OpenMeta [Analyst] advanced software (http://www.cebm.brown.edu/openmeta) for analyses of a pooled estimate of outcome measures, as well as subgroup analysis. Heterogeneity was checked by using an I 2 test statistic. Forest plots were used to visualize the presence of heterogeneity. To confirm the results, two authors independently computed the statistical analyses and checked for uniformity. The effect size estimates were converted to odds ratios. A statistical test with a p-value less than 0.05 (one-tailed) was considered statistically significant. 6

Characteristics of Included Studies
The search information is summarized in Figure 1 following PRISMA guidelines [16].
We identified 161,589 articles, with 107 articles plus 11 additional articles found via reference proceeding to full-text review and finally 36 meets the inclusion criteria.
Most of the studies included in this systematic review and meta-analysis had crosssectional study design (n = 25), and one was retrospective and in other studies (n = 10) the design was not stated. The minimum sample size was 110 participants in a study conducted in Cameroon [17], while the highest sample size was 718 in a study conducted in DRC [18].
The studies qualified for the review were conducted in 12 countries in Africa.
The overall number of study participants included in this meta-analysis was 10,701 and 4,242 pregnant women for IgG and IgM respectively.

The pooled prevalence of Toxoplasmosis based in IgG measurement
Thirty-six published studies were included in this systematic review and metaanalysis and all of these studies were used to estimate the pooled prevalence of T.
gondii among pregnant women as measured by IgG. The minimum prevalence of anti-T. gondii IgG was 0.6% and it was found in Zambia [11]. On the other hand, the maximum T. gondii prevalence was found to be 92.5% in a study conducted in Ghana [12]. Using the random effect analysis, the pooled prevalence of T. gondii among pregnant women in Africa was 46.7% (95% CI (37.0, 56.4). The I 2 test result 7 showed high heterogeneity (I 2 99.3%, P = <0.000), Figure 1 Sub-group analysis showed that the seroprevalence of T. gondii among pregnant women was found to be 50 in Eastern, Western, Central, Southern and Northern Africa respectively, (Figure 2).

The pooled prevalence of Toxoplasmosis based in IgM measurement
Eighteen published studies were included in the meta-analysis to estimate the pooled prevalence of T. gondii among pregnant women as measured by IgM.
Likewise, the minimum prevalence of anti-T. gondii IgM was 0.7% in a study conducted in Tanzania [19] while the maximum T. gondii seroprevalence was found to be 76.1% in a study conducted in Ghana [12]. The pooled prevalence of T. gondii among pregnant women in Africa was 8.40% (95% CI (5.20, 11.6). The I 2 test result showed high heterogeneity (I 2 96.7%, P = <0.000), Figure 3 Subgroup analysis showed varied seroprevalence of T. gondii in four geographical zones of Africa with the highest and lowest prevalence observed in Western 14.8% (95% CI: 5.6, 24.0) and Central 2.7% (95% CI: 0.3%-5.8), respectively (Figure 4).

Discussion
The objective of the present systematic review and meta-analysis was to assess the seroprevalence of T. gondii infection and associated risk factors among pregnant women in Africa. T. gondii infection during pregnancy results in mental retardation, premature birth, low birth weight, blindness, epilepsy, and death [9]. Moreover a number of published studies have shown that T. gondii infection in pregnancy is associated with increased risk of miscarriages, hearing loss, hematological 8 abnormalities and death as a major determinant of infant mortality and increased risk of maternal morbidity and mortality [51][52][53].

Pooled Prevalence
In a meta-analysis, the pooled prevalence of IgG against T. gondii infections among pregnant women in Africa was 46.7%. This is higher than the study conducted in China and Iran which showed a seroprevalence of 5.0% [54] and 38% [55] respectively among pregnant women. However, relatively similar seroprevalence (41.3%) has been reported in Iranian pregnant women [56]. The high seroprevalence of T. gondii among pregnant women could be due to decreased immunity and physiological changes during pregnancy, decreased awareness, as well as increased risk of exposure.

Risk factors
In this review, a number of studies reported the assessment of risk factors of T.
gondii infection in pregnant women. Cat is the final host of T. gondii and various warm-blooded animals and humans are the intermediate hosts. It is reported that the sexual multiplication of T. gondii takes place in cats and hence cats excrete the unsporulated oocysts with faeces in the environments [4,57]. Living or contact with cat were found to be the independent predictors of T. gondii infection (p<0.05) [11,21,23,27,29,34]. Whereas only one study did not find any association of living or contact with domestic animals such as cat and being infected with T. gondii among pregnant women [45]. As per the WHO recommendations on the prevention of T. gondii infections; hygiene including hand-washing and the use of clean water in food production and preparation is critical. Pregnant women should avoid undercooked meat [58]. Moreover, It is advisable that pregnant women wear gloves when gardening and during contact with soil or sand because they might be 9 contaminated with cat feces that contain Toxoplasma [58].
In this review, other predictors of T. gondii seropositivity were the consumption of raw vegetables or fruits. A significant association was observed between T. gondii seropositivity and eating raw or unwashed vegetables or fruits [20,21,28,30,35,37,44].

Continue Health Education for toxoplasmosis control
Reviewed studies concluded that there is the need of implanting a community education among pregnant women [11,21,22,[27][28][29][30]33,35,44,46,50]. Since there is no vaccine against T. gondii, prevention depends only on increasing the pregnant women's knowledge about toxoplasmosis, its origin, transmission and prevention.

Conclusion
The current systematic review and meta-analysis showed that the pooled prevalence of T. gondii in Africa among pregnant women is relatively higher compared with the other review and meta-analysis conducted in other parts of the world. Therefore, there is a need to establish prevention and control measures that should be directed to educational programs. We recommend that periodic screenings for T.
gondii infection among pregnant women should be incorporated into routine clinical care in order to avoid serious clinical complications of mother and fetus.

Consent for publication
Not applicable.

Availability of data and materials
Data will be available upon request to the corresponding author.

Competing interests
None to declare     Forest plot depicting sub-group analysis of T. gondii among pregnant women measured by Ig 23 Figure 4 Forest Plot depicting the polled analysis of 18 studies reporting sero-prevalence of T. gondii Forest plot depicting sub-group analysis of T. gondii among pregnant women measured by Ig