Background
People with severe mental disorders (SMDs), including schizophrenia, bipolar disorder and psychotic depression, are associated with increased risk of infectious disease including human immunodeficiency virus infection (HIV) and hepatitis viruses, such as hepatitis B virus (HBV), hepatitis C virus (HCV), and other types of hepatitis viruses because of high-risk behaviors compared to the general population [
1‐
6].
A significant proportion of people with SMDs, are infected with HIV at some time in their lives with epidemiologically representative studies finding around 6.2–29.10% of people with SMDs had comorbid HIV infections [
2,
7,
8]. The prevalence of hepatitis B and hepatitis C viruses in people with SMDs is significantly higher. According to different studies, the prevalence ranges from 7.45 to 47.5% [
9‐
11] and 6.2–29.8% [
2,
11,
12] for hepatitis B and hepatitis C, respectively.
The prevalence and risk of HIV, HBV, and HCV infections in people with SMDs differs by gender [
8,
13,
14]. Studies indicated that the prevalence of HIV in people with SMDs is higher in females than in males. In one study, the prevalence of HIV was 33% in women and 19.7% in men [
13]. Unlike HIV, the prevalence of hepatitis B and hepatitis C virus in people with SMDs is higher in males than in females. A study found that the rate of HCV infection among men was nearly twice that among women: 19.6% for male and 9.8% for female [
14]. In another study, the prevalence of HBV was 12.6% for men and 7% for women [
7]. A considerable gender differences in infection rates among people with SMDs might reflect differences in the patterns of risk behaviors as well as in the risk associated with a given behaviors.
Although it has been suggested that sex differences in the prevalence and risk of HIV, HBV, and HCV among people with SMDs exist, to date no systematic review or meta-analysis has examined this question. We therefore aimed to carry out a systematic review and meta-analysis to determine the prevalence and estimated gender difference in the risk of HIV, HBV, and HCV in people with SMDs.
Methods/design
A systematic literature search was conducted on three databases, including EMBASE, PubMed, and Scopus. PubMed was searched using the following terms and keywords: epidemiology OR prevalence OR magnitude) AND (HIV OR human immune deficiency virus OR HBV OR HCV OR hepatitis OR AIDS) AND (severe mental illness OR mental disorder OR schizophrenia OR psychosis OR major depression OR bipolar disorder OR depressive disorder OR mental illness OR severe mental disorder). EMBASE and SCOPUS were searched as data-base specific subject headings (where applicable) associated with the above keywords used in PubMed. We scanned the reference lists of eligible studies to identify additional studies of relevance to this review. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a checklist of 27 items that ensures the quality of systematic review or meta-analysis was used [
15]. This review protocol was written and presented according to PRISMA-P 2015 guidelines [
16].
Eligibility criteria
Included in this systematic review and meta-analysis were studies that fulfill the following criteria. First, the study was done in people with SMDs; second, the study design was observational studies, including cross-sectional and case–control study design; third, the outcome of interest was infectious disease (HIV, HBV and HCV); fourth, the study reported the prevalence of HIV, HBV and HCV as well as risk in men and women. In additions, we excluded editorials, reviews, studies with nonhuman subjects, and those not published in English language. The identified studies were initially filtered with a title search by two reviewers before the retrieval of full-text articles for further screening. Rigorous inclusion criteria were adhered to. In the second step, the two reviewers independently read the full texts of the articles that were not excluded in the initial stage, then selected the studies that met the inclusion criteria. Disagreements were discussed during a consensus meeting with a third reviewer for final selection of studies to be included in the review. All differences of opinion regarding the selection of articles were resolved through discussion and consensus.
Data extraction from source documents was done independently by two investigators. Disagreements were resolved by consensus. The investigators used a specific form specifically designed to extract data of methodological and scientific quality. Data from the included papers were extracted to summary tables containing information on: population, study design, background information, sample size study setting, year of publication, authors, and tools used for assessing outcome and predisposing factors results. Information about design and participants was extracted as recommended by PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines [
16].
A modified version of the Newcastle–Ottawa Scale was used to assess the quality studies included in our systematic reviews and meta-analyses [
17]. This scale assesses quality in several domains: sample representativeness and size, comparability between participants, ascertainment of cases, and statistical quality. Moreover, the agreement between the two reviewers was assessed by actual agreement and by agreement beyond chance (unweighted Kappa) and these were interpreted as: # 0 = poor agreement, 0.01–0.20 = slight agreement, 0.21–0.40 = fair agreement, 0.41–0.60 = moderate agreement, 0.61–0.80 = substantial agreement, and 0.81–1.00 = almost perfect agreement [
18].
Data synthesis and analysis
Studies were pooled to calculate pooled prevalence, odds ratios, and 95% CIs using a random-effect model [
19]. Comprehensive meta-analysis software version 3 was used for meta-analysis and forest plots that showed combined estimates with 95% CI. Heterogeneity was evaluated using
Q statistic and the
I2 statistics [
19]. The magnitude of statistical heterogeneity between studies was assessed using
I2 statistic and values of 25, 50, and 75% were considered to represent low, medium, and high, respectively [
20]. For the data identified as heterogeneous, a random-effects model was used during analysis. When statistical pooling was not possible, non-pooled data were presented in table form. Meta-regression was performed to explore the potential source of heterogeneity. A leave-one-out sensitivity analysis was carried out to evaluate the key studies that exert major impact on between-study heterogeneity. Publication bias was assessed by funnel plot and Egger’s regression tests.
Discussion
In this study, we computed the pooled estimate of prevalence of infectious disease (HIV, HBV and HCV) as well as odds ratio (OR) of gender and infectious disease in people with SMDs. To our knowledge, this is the first systematic review and meta-analysis of gender difference in epidemiology of HIV, hepatitis B, and hepatitis C infections in people with SMDs. Based on the results from a meta-analysis, we identified a significant increase in risk and prevalence of hepatitis B and C viruses in men compared to women, but the prevalence of HIV in people with SMD was higher in women than in men.
The results of meta-analysis show that the pooled prevalence of HIV in people with SMDs was 7.59% (95% CI 4.82–11.75). Our finding of HIV was significantly higher than the 0.87, 0.00 (95% CI 0.00–0.003), and 0.6% of the general population in Niger [
31], Iran [
32], and the USA [
5], respectively. The difference might be due to a significantly increased use of psychoactive substance and injective drugs as well as risky sexual behaviors in people with severe mental illness, which considerably increased the risk of having HIV infections.
In our stratified analysis of 13 studies which reported the prevalence of HIV in people with SMDs in a specific sex group, we found that the prevalence of HIV was higher in women, 8.25% (95% CI 4.25–15.40), than in men, 7.04% (95% CI 3.75–12.82). This difference might be because women with SMDs are more likely to experience violence, exploitation, abuse, or sexual assault than men. Nevertheless, in our meta-analysis of the risk of being female, the crude odds ratio (OR) demonstrated no significant association between being female and having HIV (OR 1.42; 95% CI 0.96–2.10) in people with SMDs.
The pooled results of our meta-analysis give the prevalence of hepatitis B virus in people with SMDs, 15.63% (95% CI 7.19–30.69). This prevalence was considerably higher than the general population prevalence of 0.4 and 0.9% in the USA [
33] and Europe [
6], respectively. The increased prevalence might be because people with SMDs are more likely to engage in risky sexual behavior including not using condom during sexual intercourse as well as an increased use of psychoactive substance and injective drugs, which are the major means of transmission of HBV.
In addition, in our study the pooled prevalence of HCV in people with SMDs r was 7.21% (95% CI 4.44–11.50). Our findings were significantly higher than the findings from the general population prevalence of 1.1% (95% CI 0.9–1.4) and 3.1% (95% CI 2.2–4.4) in Europe [
6] and Ethiopia [
34], respectively. The difference might be due to a considerably increased use of psychoactive substance and injective drugs as well as risky sexual behaviors in people with SMDs, which significantly increased the risk of having HCV infections.
Furthermore, the results of meta-analysis demonstrated a significantly increased risk of HBV (OR 1.72; 95% CI 1.17–2.53) and HCV (OR 2.01; 95% CI 1.16–3.20) infections in men compared to women in people with SMDs. The possible explanation might be due to men having significantly higher rates of lifetime substance and drug risks than women, including needle use, needle sharing, and crack cocaine use. Studies have indicated that people who inject drugs (PWID) are at risk for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection through the sharing of needles and drug preparation equipment [
35‐
37].
Unlike hepatitis virus, our meta-analysis of crude odds ratio (OR) demonstrated no significant association between being female and having HIV (OR 1.42; 95% CI 0.96–2.10) in people with SMDs. This might be because the rates of hepatitis virus transmission following needlestick injury are significantly higher than the rate of HIV transmissions through needles. In addition, hepatitis B virus can survive outside the body for at least 7 days, which might increase the risk of transmission [
38,
39].
Difference between studies
The difference between the 18 studies led to a high level of heterogeneity in our meta-analysis. The type of specific SMD, sample size, the setting, and the study populations differed on a number of characteristics, which will have contributed to the variance in the prevalence rates of HIV, HBV, and HCV in people with SMD. For the purpose of further investigating the potential source of heterogeneity in the analysis of the prevalence of HIV, HBV, and HCV, we performed leave-one-out sensitivity analysis. Our sensitivity analysis showed that our findings were strong and not dependent on a single study.
In addition, the robustness of our findings is indicated by our stratified analysis based on the quality of the included studies. The results were in line with our findings after removal of the poor quality studies [
13,
22] for HIV [5.88% (3.61–9.45%)] and HBV [17.01% (6.58–37.36%)] for overall prevalence as well as 5.64% (2.97–10.46%) versus 6.23% (2.91–12.84%) for HIV and 21.11% (6.01–52.47%) versus 12.62% (2.76–42.30%) for HBV for men versus women, respectively.
Furthermore, for making the results of our meta-analysis meaningful, we used random-effects model where summary effect estimates are more conservative than fixed-effects summaries in epidemiologic meta-analysis.
Strength and limitations
Our study has several strengths: First, we used predefined search strategy and data extraction, and quality assessment was performed by two independent reviewers to minimize the possible reviewer bias; Second, we performed sensitivity and subgroup analysis to identify the small study effect and the risk of heterogeneity. Third, we evaluated the quality of the included studies, and the result from the assessment of the study quality indicated that the methodological quality was generally good. However, we identified considerable heterogeneity among the studies which we considered as limitations of the current study.
Conclusions
Results from this systematic review and meta-analysis suggest that: (1) the prevalence of HIV (7.59%), HBV (15.63%), and HCV (7.21%) was high; (2) the prevalence of HBV is significantly higher than HIV and HCV in people with SMDs; (3) there was a significantly increased risk of HBV and HCV infections in men compared to women; (4) there is no significant association between gender and HIV in people with SMDs; (5) prevention and routine screening of HIV, HBV, and HCV are warranted in people with SMDs; (6) the integrated management of SMDs and of HIV, HBV, and HCV is warranted; (7) psychiatry professionals should give attention to prevention, screening, and management of HIV, HBV, and HCV in people with SMDs; (8) further studies focusing on the incidence and outcomes of HIV, HBV, and HCV are recommended in people with SMDs; (9) finally, studies focusing on the reasons or factors related to significantly high prevalence and risk of HIV, HBV, and HCV in people with SMDs than the general population as well as the gender difference in association are warranted.
Authors’ contributions
The author GA performed the search, data extraction, analyses, and draft and approval of the final manuscript. MA performed search, data extraction, and approved the final manuscript. KY participated in discussion and consensus and approved the final manuscript. All authors read and approved the final manuscript.