Toxoplasmosis in Pregnant Women and HIV/AIDS Patients in Ethiopia: A Systematic Review and Meta-Analysis

Background Although Toxoplasma gondii infection in immune-competent individuals is usually asymptomatic or causes a mild flu-like illness, it may become severe and can occasionally be fatal in immune-compromised people, such as AIDS patients or pregnant women. Method Electronic English databases (Pubmed, Google Scholar, Science Direct, and Scopus), parasitology congresses, and theses of Ethiopian medical universities, were systematically searched (published or unpublished data). Full-length articles and abstracts were collected using keywords such as Toxoplasma gondii, Toxoplasmosis, pregnant women, HIV/AIDS, and Ethiopia. Results Analysis of seroprevalence estimates was pooled using a random effects meta-analysis. Seventeen studies were included in the present systematic review and meta-analysis. One of these studies reported seroprevalence of T. gondii in HIV/AIDS patients and pregnant women. In this review, a total of 4,030 individuals were included and analyzed. The pooled prevalence of T. gondii in this review was 81.00% (95% CI = 69.10–89.78). Sub-group analysis showed that 2,557 pregnant women were evaluated. In pregnant women, the pooled sero-prevalence was 71.2 (95% CI = [51.9%, 87.1%]. In HIV/AIDS patients, 1,473 individuals were evaluated and the pooled seroprevalence was 88.45 (95% CI = 80.87%–94.31%). Conclusion This systematic review and meta-analysis identified a high seroprevalence of Toxoplasma infection of 81% among immunocompromised patients. Scaling up prevention and control methods mainly strengthening educational efforts are necessary to avoid reactivation and to stop the spread of T. gondii infection.


Introduction
Toxoplasma gondii is one of the most prevalent obligate intracellular protozoan parasites of man and livestock [1][2][3][4][5]. Feline species are definitive hosts for Toxoplasma gondii and a wide range of animals serve as intermediate hosts. Globally, it is estimated that about one-third of the population is infected with T. gondii [3]. Although T. gondii infection in immune-competent individuals is usually asymptomatic or causes a mild flu-like illness [4], it may become severe and can occasionally be fatal in immune-compromised people, such as AIDS patients or pregnant women [2,6]. Toxoplasma gondii infection in AIDS patients and pregnant women causes severe encephalitis, and neurologic diseases, and can affect the heart, liver, inner ears, and eyes (chorioretinitis) [2]. Infection with T. gondii during pregnancy can result in spontaneous abortion, still-birth, fetal death, neonatal death, or various congenital defects, such as hydrocephalus, central nervous system abnormalities, and chorioretinitis [7]. HIV infected individuals are at risk of acute toxoplasmosis due to reactivation of T. gondii. It also causes cervical lymphadenopathy or ocular disease in HIV infected immune competent individuals.
Serological methods used for T. gondii diagnosis such as enzyme-linked immunesorbent assay (ELISA) and indirect immunofluorescence assay (IFA) are considered as gold standard for the detection of Toxoplasma-specific antibodies (IgG or IgM) [4].
In Ethiopia, human toxoplasmosis infection is a neglected disease [7]. e prevalence of T. gondii infection in Ethiopia has been reported in some populations; mainly in HIV infected individuals, pregnant women, child bearing age women, and in general population [4].
For appropriate diagnosis, treatment, and control of T. gondii infections, information about the seroprevalence of toxoplasmosis in different special populations is very important. So, this systematic review of the literature aimed to evaluate the sero-prevalence of T. gondii among pregnant women and HIV/AIDS patients in Ethiopia.

Literature Search and Data Extraction.
Relevant literatures were searched on Pubmed, Pubmed central, Google scholar, science direct databases, Scopus, theses of Ethiopian medical universities, and Ethiopian journals such as Ethiopia journal of health development and proceedings of professional associations from May, 2018 to June, 2018. Full-length articles and abstracts were collected using keywords such as Toxoplasma gondii, Toxoplasmosis, pregnant women, HIV/ AIDS, and Ethiopia.
ese key words were also used in combination using boolean operators. Overlapped articles found in more than one databases were excluded. Annual research conferences and preceding of Ethiopian medical laboratory association (EMLA), and Ethiopian public health laboratory associations' (EPHLAs) records were reviewed to identify relevant unpublished articles. e reference lists of published studies included in this meta-analysis were searched for additional articles. Two authors independently reviewed all collected studies for eligibility and they extracted the required information based on the objective this meta-analysis.

Data Collection.
Pre-designed data extraction form was developed by authors based on the objective of this review. Studies conducted in Ethiopia to estimate the sero-prevalence of T. gondii infection in pregnant women and HIV/AIDS patients were included. All collected studies were assessed by two authors for eligibility to be included in this review. In case of disagreement on the eligibility of identified studies, authors held discussion to resolve the issue by considering the quality of identified study and the aim of the present review. Studies performed in study groups other than pregnant women, and HIV/AIDS and those studies that did not use random sampling methods as a sampling technique were excluded ( Figure 1). Information about year of publication, first author, study area, study design, total sample size, number of seropositive individuals, and laboratory methods used for T. gondii diagnoses was carefully investigated.

Statistical Analysis.
Point estimates and 95% confidence intervals of seroprevalence of all included studies were calculated. An overall seroprevalence and group-specific seroprevalences were calculated among HIV/AIDS patients and pregnant women. Heterogeneity among studies was visualized using a forest plot chart. e I 2 and Cochran's Q tests were used to quantify the variations between studies. e heterogeneity was considered not significant when 푃 > 0.1 and 퐼 2 < 50%. Due to the heterogeneity of studies included in this metaanalysis, random effect model was used by considering the included studies used random samples from a population.
is meta-analysis was performed using the trial version of StatsDirect statistical so ware (https://statsdirect.com).

Results
Out of 65 studies from literature searches using key words, 17 studies were eligible and included in the present systematic review and meta-analysis. Eight studies described the sero-prevalence of T. gondii in pregnant women, whereas 8 studies reported T. gondii infection in HIV/AIDS patients.
ere was also one study which reported seroprevalence of T. gondii in HIV/AIDS patients and pregnant women. is study was considered in both pregnant women and HIV/AIDS patient groups during analysis. e study designs of all eligible and included studies were cross-sectional. In this review, Enzyme-linked immunosorbent assay (ELISA) and latex agglutination slide tests were the commonly used methods for the detection of T. gondii antibodies. e higher seroprevalence of T. gondii (96.7% and 93.6%) was reported in HIV/AIDS patients from Mizan Aman Hospital and selected areas of Ethiopia, respectively. On the other hand the lower seroprevalence (18.5% and 34.9%) reported in this study was in pregnant women from Felege Hiwot Hospital from Jigjiga Hospital (Tables 1, 2 and 3).
Detection of T. gondii IgG and IgM is one of the commonest serologic diagnoses. IgG detection indicates either past or present infection while the detection of IgM showed early infection of T. gondii. Based on IgG assessment, most of the current reviewed studies reported above 95% T. gondii IgG sero-prevalence. In general, the sero-prevalence of IgG is higher than IgM in pregnant women and HIV/AIDS patients (Tables 1 and 2).
In general, in this review a total of 4,030 individuals were included and analyzed. e pooled prevalence of toxoplasmosis in this review was 81.00% (95% CI = 69.10-89.78).
Begg and Egger tests were used for evaluating publication bias. Significant publication bias was not revealed in studies Sub-group analysis showed that 2,557 pregnant women were included and evaluated. Random effect analysis was used due to the heterogeneity between studies. e Q statistic and the pooled sero-prevalence were Cochran Q = 845.808548 (df = 8, 푃 < 0.0001) and 71.2 (95% CI = [51.9%, 87.1%] respectively ( Figure 3). I 2 (inconsistency) = 99.1% (95% CI = [98.9%, 99.2%] (Figure 3).  [16] women and HIV/AIDS patients was higher than 70%, and there is a risk of reactivation of T.gondii in this group of population. Toxoplasmosis is an opportunistic disease that can cause very severe illness and fatality in immune compromised individuals. Pregnant women and HIV/AIDS patients are immune deficient individuals. is immune inefficiency could be the main risk factor for the higher sero-prevalence of T. gondii. Toxoplasmosis is mainly transmitted to human by ingestion of oocysts with contaminated food and drinks, by consumption raw or undercooked meat contain bradyzoites. It can also be transmitted during blood transfusion and organ transplantation.
Immunocompromised patients are highly vulnerable groups for toxoplasmosis infection due to debilitated immune system.
In Ethiopia, human toxoplasmosis infection is a neglected disease [7]. Some studies were conducted on the seroprevalence of toxoplasmosis. e study group of majority of the studies was on pregnant women, general population, and HIV/ included about pregnant women (P-value >0.05). ere was significant bias among studies included about HIV/AIDS patients (P-value >0.05).

Discussion
Toxoplasma gondii infection is usually asymptomatic in immune-competent individuals or causes a mild illness [4]. However, it may become severe and can occasionally be fatal in immune-compromised people, such as HIV/AIDS patients or pregnant women [2,6].
is is the first systematic review and meta-analysis of toxoplasmosis in pregnant women and HIV/AIDS patients in Ethiopia. Among 2,557 pregnant women in Ethiopia, the sero-prevalence of T. gondii was 71.1%. Furthermore, the seroprevalence of T. gondii in 1,473 HIV/AIDS patients was 88.45%. Immune compromised patients are at high risk of toxoplasmosis reactivation [17]. e finding of this meta-analysis showed that the seroprevalence of T. gondii in pregnant     and Enzyme linked immune sorbent assay (ELISA) methods for diagnosis. e highest prevalence of toxoplasmosis was observed in individuals diagnosed with ELISA. For instance, in HIV/AIDS patients, 96.70% sero-prevalence of T. gondii was observed using ELISA. e incidence and prevalence of T. gondii infection varies depending on geographic areas, weather conditions, and age groups in Ethiopia. In Ethiopia, a review studied on the sero-prevalence of T. gondii in general population revealed the overall pooled prevalence was 74.73% [18]. e seropositivity in pregnant women and HIV/AIDS patients in the present study was 71.1% and 88.45%, respectively. e seroprevalence in HIV/AIDS patients was higher than reported from general population and pregnant women sero-prevelence in the present study.

Conclusions
As far as we know and our literature search, this is the first systematic review and meta-analysis that provides information about the seroprevalence of T. gondii in pregnant women and HIV/AIDS patients in Ethiopia. Our finding indicates that researchers must give attention to the seroprevalence of toxoplasmosis in immunocompromised patients especially in HIV/AIDS patients, and pregnant women. Scaling up prevention and control methods and mainly strengthening educational efforts are necessary to avoid reactivation and to stop the spread of T. gondii infection.
Data Availability e authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the manuscript.

Ethical Approval
A er discussing the aim and the information required for this systematic review and meta-analysis, a letter of approval was obtained from the Department of Medical Laboratory Sciences Research Committee, College of Medicine and Health Science, Wollo University.

Conflicts of Interest
e authors declare that they have no conflicts of interest.

Authors' Contributions
DG, GZ, and AG were involved in proposal writing; they designed the study and participated in all implementation stages of the project. DGF and GZ also analyzed the data and finalized the write up of the manuscript. DGF, GZ, and AG were responsible for critically revising the proposal and the manuscript. All authors reviewed and approved the final manuscript.