Incidence and Prevalence of Multiple Sclerosis in the Americas a Systematic Review

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Peer-reviewed

Enquiry Article

Epidemiology of multiple sclerosis in Iran: A systematic review and meta-analysis

• Milad Azami,
• Mohammad Hossein YektaKooshali,
• Masoumeh Shohani,
• Ali Khorshidi,
• Leily Mahmudi

ten

• Published: Apr 9, 2019
• https://doi.org/ten.1371/journal.pone.0214738

Figures

Abstruse

Groundwork

Multiple sclerosis (MS) is one of the near common neurological disorders and is one of the main causes of disability. The prevalence and incidence of MS in Iran is reported to range from 5.3 to 89/ 100,000and 7 to 148.1/ 100,000, respectively. There are no systematic and meta-analysis studies on MS in Iran. Therefore, this report was conducted to investigate the prevalence and incidence of MS in Iran using meta-assay.

Method

A systematic review of the present study focused on MS epidemiology in Islamic republic of iran based on PRISMA guidelines for systematic review and meta-assay. We searched eight international databases including Scopus, PubMed, Science Direct, Cochrane Library, Web of Science, EMBASE, PsycINFO, Google Scholar search engine and half-dozen Persian databases for peer-reviewed studies published without time limit until May 2018. Data were analyzed using Comprehensive meta-assay ver. 2 software. The review protocol has been registered in PROSPERO with ID: CRD42018114491.

Results

According to searching on different databases, 39 (15%) articles finalized. The prevalence of MS in Iran was estimated 29.three/ 100,000 (95%CI: 25.6–33.five) based on random effects model. The prevalence of MS in men and women was estimated to exist xvi.5/ 100,000 (95%CI: 13.7–23.four) and 44.viii/ 100,000 (95%CI: 36.three–61.6), respectively. The incidence of MS in Iran was estimated to exist iii.4/ 100,000 (95%CI: 1.8–6.2) based on random furnishings model. The incidence of MS in men was estimated to be 16.5/ 100,000 (95%CI: 13.7–23.4) and the incidence of MS in women was 44.8/ 100,000 (95%CI: 36.three–61.half dozen). The meta-regression model for prevalence and incidence of MS was significantly higher in terms of year of study (p<0.001).

Conclusions

The results of this written report tin can provide a full general picture of MS epidemiology in Islamic republic of iran. The current meta-analysis showed that the prevalence and incidence of MS in Islamic republic of iran is high and is rising over fourth dimension.

Citation: Azami M, YektaKooshali MH, Shohani G, Khorshidi A, Mahmudi L (2019) Epidemiology of multiple sclerosis in Islamic republic of iran: A systematic review and meta-analysis. PLoS Ane 14(4): e0214738. https://doi.org/10.1371/periodical.pone.0214738

Editor: Aristeidis H. Katsanos, University of Ioannina School of Medicine, Hellenic republic

Received: November 1, 2018; Accepted: March nineteen, 2019; Published: April nine, 2019

Copyright: © 2019 Azami et al. This is an open up access article distributed under the terms of the Artistic Eatables Attribution License, which permits unrestricted apply, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are inside the manuscript and its Supporting Data files.

Funding: About funding, honestly we didn't fund by whatever institutions and individual persons.

Competing interests: The authors accept declared that no competing interests be.

1. Introduction

Multiple sclerosis (MS) is a neurodegenerative and allowed-mediated demyelinating disease of the human being central nervous arrangement[ane–4]. The clinical manifestations of MS include opiate neuritis, primal paralysis, sensory imbalance, balance disorder, cognitive impairment, fatigue and sleep disorders[5]. Women are approximately ii–iii times more probable to suffer from MS[6], and most patients are xx to l years erstwhile. Residents of Eastern Europe are more likely to suffer from MS compared with residents of Asia, Africa and Latin America[seven, 8].

Iran is muslim country in the Middle East with a breadth of 32°00 and a longitude of 53°00 and has 31 provinces. In that location are diverse ethnic groups in Iran, including Fars, Kurds, Mazani, Gilak, Lor, Turks, Arabs, and Baluch, and are now united by Iranian culture. Co-ordinate to the World Health Organization (WHO) in 2008, around 1.three million people had MS worldwide, while in 2013, the prevalence of MS was 73 per 100,000 in the earth and was 60 per 100,000 in Islamic republic of iran[9, 10]. At the moment, Islamic republic of iran is well known for its high prevalence of MS in the world, whereas xv years ago, it was assumed based on the MS slope hypothesis that Islamic republic of iran could be a low-risk area for MS with an incidence of less than five per 100,000 people[11–13].

Despite numerous studies, the principal cause of MS is nevertheless unknown. According to a hypothesis, MS carries out an autoimmune set on against cocky-myelin or oligodendrocytic antigens by macrophages, deadly T cells, Lymphokines, and antibodies when they enter the brain[xiv]. A combination of genetic and environmental factors such every bit latitude, vitamin D use, skin color, migration, meal, smoking, occupational exposure to toxins, stress, or even contempo studies of specific viral infections such as Epstein-Barr virus (EBV)[fifteen] and bacterial infections similar mycoplasma pneumonia [sixteen, 17] may affect this illness[half-dozen, 15–nineteen].

Basic epidemiological information helps to speedily identify, diagnose and control the disease complications[20]. Ane of the nigh important goals of meta-analysis, which results from the combination of existing studies, is to increase the volume of samples and the number of studies, to reduce the difference betwixt the available parameters and the confidence interval, which ultimately leads to solving a problem, specially in the field of medicine. In fact, such studies are a vital link between research studies and decision-making at the bedside or policies[21–23].

The prevalence of MS in Iran has been reported to exist 5.3–89 per 100,000[2, 5, x, 11, 13, 21, 22, 24–46]. Because the to a higher place-mentioned issues, controversy in the prevalence of MS, the lack of global access to the precise prevalence of MS in Islamic republic of iran, as well equally expressing the final determination for policy making and operational planning in Iran, this study was conducted to approximate the prevalence and incidence of MS in Islamic republic of iran by systematically reviewing all available documentations and their combination through meta-analysis.

2. Materials and methods

2.1. Study protocol

The present systematic review focused on MS epidemiology in Iran based on PRISMA guidelines [47](S1 File) for systematic review and meta-analysis. All the steps of research, including search, option of studies, qualitative assessment, and data extraction were done independently by two researchers. The agreement was reached by group discussion. The protocol of this review registered at: International Prospective Register of Systematic Reviews(PROSPERO) (https://world wide web.crd.york.air-conditioning.uk/PROSPERO/) Identifier: CRD42018114491 [48, 49](S2 File).

2.2. Search strategy

The search was performed by ii researchers independently. We searched the titles and abstracts of articles in six Farsi databases including Scientific Information Database (SID) (http://www.sid.ir/), Barakat Knowledge Network System (http://wellness.barakatkns.com), (Iranian Research Institute for Information Science and Technology (IranDoc) (https://irandoc.ac.ir), Regional Information Eye for Science and Technology (RICST) (http://en.ricest.ac.ir/), Magiran (http://www.magiran.com/), Iranian National Library (http://www.nlai.ir/) and eight international databases including Scopus, PubMed/Medline, Science Directly, Cochrane Library, Web of Science, Embase, PsycINFO every bit well every bit Google Scholar search engine for peer-reviewed studies published without time limit until May 2018. The keywords used were 'incidence', 'prevalence', 'epidemiology', 'MS', 'multiple sclerosis' and 'Iran'. Boolean operators (AND & OR) were used to search by a combination of words. A sample of search strategy in PubMed database is shown in Appendix 1. The list of references of the studies was searched manually for additional reports.

two.three. Inclusion criteria (PICO)

Inclusion criteria according to PICO (Trouble or Population, Interventions, Comparing and Outcome) [50, 51]: (1) P opulation: all Iranian population, in all historic period ranges and both genders; (ii) I ntervention: diagnosis of MS past Poser or McDonald criteria for confirmed MS; (three) C omparison: variable aimed for incidence and prevalence of MS such every bit gender, province, year of study and etc; (4) O utcome: Judge the prevalence and incidence of MS.

2.4. Exclusion criteria

The inclusion criteria were all epidemiological studies on MS. The exclusion criteria included: ane. not-random sample size; 2. sample size other than Iranian population; 3. Articles published in languages other than Persian and English; iv. Not relevant to the subject; 5. qualitative studies; instance study; review articles, case reports and interventional studies, and vi. duplicate manufactures.

2.5. Quality assessment

Researchers assessed the quality of the selected manufactures using a scoring system based on the 8-item the modified Newcastle Ottawa Scale (NOS) for non-randomized studies [52] (S2 File). Each question was given a score between 0 and 1. Points 0–5, 6–7 and 8–9 were considered low quality, moderate quality and high quality, respectively. The minimum score for inbound the quantitative meta-assay procedure was 5 and the articles that acquired the minimum qualitative assessment score entered the process of data extraction and meta-analysis.

2.6. Screening and data extraction

Two independent researchers (Azami Yard, YektaKooshali MH) screened all the articles retrieved by the search strategy based on championship and abstract for eligibility co-ordinate to inclusion and exclusion criteria. Any contradiction betwixt the two researchers was discussed and finally, a consensus was reached. In addition, if necessary, the full text was examined further for more clarification at this stage. In the next pace, the researchers were provided with the full text of eligible manufactures. Each qualified full text was reviewed independently by two researchers and a 3rd adept (Expert-epidemiologist) was in that location to provide consultations on disagreements between the ii researchers.

Data extraction was done past the researchers using a pre-prepared grade. The data for the study included the first author, year of publication, year of report, written report setting, location, sample size, geographical area, province, the prevalence of MS and MS diagnostic method, which was extracted independently by ii researchers and blinded to the writer's proper name, plant, and journal. If necessity, further information, and raw data were requested by contacting the author (first writer, corresponding author or contacting the authors' department) (Tabular array 1).

2.7. Data analysis

To evaluate the heterogeneity of the studies, Cochran'south Q and I² tests were used. Heterogeneity was defined as I²> l% and the Cochran's Q test was defined as < 0.05. Therefore, the random effects model was used to estimate the prevalence and incidence of MS with high heterogeneity. To estimate the effect of gender, nosotros used the total number and the number of events (MS) in men and women groups and we calculated the odds ratio (OR) and 95% CI. In this report, a sensitivity analysis was also performed to verify the stability of the data. In social club to observe the source of heterogeneity, a subgroup analysis was conducted in terms of geographic area, year of study, province, and study setting while a meta-regression model was used for the prevalence and incidence of MS in terms of year of studies. Begg and Egger's tests were used to assess publication bias. Data were analyzed using Comprehensive meta-analysis ver. 2 software. P<0.05 was considered significant.

three. Results

three.1. Study characteristics and methodological quality

Of 392 studies found in the initial search using the search strategy, 138 potentially relevant studies were constitute to be eligible for retrieval and evaluation. By examining the full text of the studies, 65 studies were excluded due to not-MS or non-Iranian patients (27), non-randomized (18) and inadequate data according to the data extraction checklist (fourteen), articles to the editor without original data, review and case report (5) and low quality (ane). Finally, 39 manufactures (included 103 studies for prevalence and 34 studies for incidence) entered the meta-analysis process afterward qualitative cess. The catamenia diagram of the identification and pick of studies is illustrated in (Fig 1) and the characteristics of studies are shown in (Table 1) [2, 5, 13, 25, 26, 31–37, 39, 40, 42–46, 53–71].

three.2. Pooled prevalence of MS and sensitivity analysis

The total heterogeneity was loftier (I² = 99.92% and P< 0.001). The prevalence of MS in Iran was estimated to be 29.iii/ 100,000 (95% CI: 25.6–33.5) based on random effects model (Fig 2). The lowest and highest prevalence was found in studies in Southern Khorasan in 2009 (v.iii/ 100,000) and Isfahan in 2013 (89/ 100,000), respectively (Figs 2 and 3). The sensitivity assay of the prevalence of MS and its 95% CI was estimated irrespective of one study at a time, and the results showed that the pooled gauge was robust (S1 Fig).

3.3. Subgroup analysis of MS prevalence based on region, province, written report design, and year of study

The Subgroup analysis of MS prevalence in Islamic republic of iran is shown in (Table 2) and (S1–S6 Figs). Meaning deviation was observed in the prevalence of MS in the geographical regions (P< 0.001) (S2 Fig), province (P< 0.001) (S3 Fig), study design (P = 0.015) (S4 Fig), and twelvemonth of study (P< 0.001) (S5 Fig).

3.iv. Prevalence of MS based on gender

The prevalence of MS in men and women was estimated to exist 16.5/ 100,000 (95% CI: xiii.7–23.four) and 44.eight/ 100,000 (95% CI: 36.three–61.6), respectively (Fig 4). The OR female/ male person of MS prevalence was estimated to be iii.01 (95% CI: 2.79–3.24, P< 0.001) (Table 2) (S6 Fig).

iii.5. Pooled incidence of MS and sensitivity assay

The total heterogeneity was high (Iⁱⁱ = 99.96% and P< 0.001). The incidence of MS in Iran was estimated according to 34 studies to exist 3.4/ 100,000 (95% CI: 1.8–6.2) based on random effects model (Fig 5). The sensitivity analysis results are shown in (S7 Fig).

3.6. Subgroup analysis of MS incidence based on region, province, written report design, and year of report

The Subgroup analysis of MS incidence in Iran is shown in (Table 3). Significant difference was observed in the prevalence of MS in the geographical regions (P < 0.001) (S8 Fig), province (P< 0.001) (S9 Fig) and year of study (P< 0.001) (S10 Fig), but study design was no significant difference (P = 0.123) (S11 Fig).

three.vii. Incidence of MS based on gender

The incidence of MS in men was estimated to be xvi.5/ 100,000 (95% CI: 13.7–23.4) and the incidence of MS in women was 44.8/ 100,000 (95% CI: 36.three–61.6) (Fig six). The OR female/male of MS incidence was estimated to be three.04 (2.85–3.24, P< 0.001) (Table two) (S12 Fig).

three.8. Meta-regression

The meta-regression model for prevalence and incidence of MS was significantly higher in terms of year of study [(meta-regression coefficient: 0.065, 95% CI 0.053 to 0.077, P< 0.001) for prevalence of MS and (meta-regression coefficient: 0.100, 95% CI 0.063 to 0.136, P< 0.001) for incidence of MS] (Fig 7). Moreover, the meta-regression model for prevalence and incidence of MS based on the year was too studied in men [(meta-regression coefficient: 0.202, 95% CI 0.157 to 0.248, P< 0.001) for prevalence of MS and (meta-regression coefficient: 0.065, 95% CI 0.046 to 0.0840, P< 0.001) for incidence of MS] and women [(meta-regression coefficient: 0.216, 95% CI 0.169 to 0.264, P< 0.001) for prevalence of MS and (meta-regression coefficient: 0.219, 95% CI 0.176 to 0.263, P< 0.001) for incidence of MS] and it was increasing significantly (S13 and S14 Figs).

3.9. Publication bias

Publication bias in the studies of incidence (Egger< 0.001, and Begg's< 0.001) and prevalence (Egger< 0.001, and Begg'south = 0.045) of MS was meaning (S15 Fig).

4. Word

The nowadays study is the first systematic review and meta-analysis on the epidemiology of MS in Islamic republic of iran. According to the results of the present meta-assay, the prevalence and incidence of MS in Iran is estimated to be 29.iii/ 100,000 and 3.4/ 100,000, which is more than some Middle Eastern countries (Oman, Great socialist people's libyan arab jamahiriya, Lebanon, Iraq, Kuwait, and Tunisia)[73–78] and less than some other countries (UAE, city of Amman in Jordan and Saudi Arabia) [79–81]. However, information technology should be noted that virtually studies in our meta-analysis process were based on data from MS centers, and the lack of recording the information of some people with MS was due to non-compulsory membership in this centre and the real prevalence of MS is expected to be greater than this figure. In 2016, Nasr et al. [41] investigated the prevalence of MS among Iranian migrants. The prevalence of MS amongst Iranian migrants was 21/ 100,000 in Mumbai (India) in 1985 and 433/ 100,000 in British Columbia (Canada) in 2012. In five unlike studies, the MS prevalence in the studied areas was reported from i.33 in Bombay (India) to 240 in British Columbia (Canada)[82–86]. The acculturative stress in migrants may help to relate the onset of illness and migration. The acculturative stress is the tension or pressure associated with the experience of a 2d culture that may have agin effects on physical or mental wellness [87] and shows that stress and anxiety have a potential role in MS development[88]. Nish et al. recently showed in a study that acculturative stress is related to higher inflammatory markers in a Chinese migrant population[89].

In the past, the behavior and distribution of MS disease were associated with latitude and was reported to be lower in areas with a higher latitude. Overall, according to a report by WHO in 2008, the highest reported MS prevalence was in North America and Europe, and the lowest reported MS prevalence was in countries about the equator. However, this pattern is changing and areas with lower prevalence are irresolute to areas with higher prevalence[10, 15, 18, xc]. In the present study, there was a significant difference betwixt the 5 geographical regions of Iran in terms of the prevalence and incidence of MS based on the results of the initial studies.

Based on the present meta-analysis, the OR of prevalence and incidence of MS in women was two.52 and iii.04, respectively compared with men, which was a significant relationship (P< 0.001). This result is similar to the results in previous studies [21, 38, 55, 91–93].

Co-ordinate to the meta-regression model, the prevalence and incidence of MS in Iran increased significantly (p< 0.001) with an increment in year of studies[21, 38, 91–93].

Various factors such as the lack of prevention and screening programs tin exist important factors in increasing the prevalence of the affliction. In addition to changes in the pattern of nutrient consumption, nutrient quality has also changed a lot recently [10, 13, 30]. According to the WHO, the utilize of tobacco, fat, salt and sugar higher than the limit in foods that crusade overweight and obesity, industrialization, urbanization and economic development tin can play a significant office in the development of chronic diseases[94]. In a written report in the United states of america on 8983 MS patients, it was institute that 25% of patients were obese and 31.3% were overweight. In addition, eighteen.2% were at risk of alcohol misuse by themselves or their relatives[95].

Since at that place are no particular laws and regulations on the purchase and use of chemicals in Iran, they are easily accessible to people and this may increase the take chances of diseases such as MS, which is caused by exposure to chemicals. Although in some studies, contact with industrial solvents has been identified equally a risk factor for MS, it has non withal been confirmed for certain[96–98].

The existence of particles such as PM10 in the air of Iranian cities[x, 28, thirty, 99–102], natural radiation of radon from soil (Ramsar, Iran) [103] and unsupervised utilise of decorative stones and granite in Islamic republic of iran[27, 104] may increase the risk of MS. However, few studies have been conducted regarding the relationship betwixt the to a higher place parameters and MS.

According to the Ministry of Wellness in Islamic republic of iran, the rate of smoking has risen to about 60 billion cigarettes per yr[29, 105]. Inhaling cigarette smoke exacerbates the effect on chronic diseases [106, 107]. According to an ecological study by Dehghani et al. in Iran, the prevalence of affliction is higher in provinces where cigarette smoking is college among males[xiii]. Since cigarette smoking increases the frequency and elapsing of respiratory infections and it causes MS relapse[37], the run a risk of cigarette smoking for MS with an OR of ane.55, 95% CI [ane.48–1.62], P<0.001 was confirmed in the recent meta-analysis.

According to the WHO, the prevalence of MS is higher in countries with higher income levels. Nevertheless, the diseases may progress more in less developed countries due to less access to diagnostic facilities, although the disparity is and so high that deficient diagnostic facilities cannot be considered as the principal cistron[108].

Studies accept shown that vitamin D deficiency is inversely related to the risk of MS [109, 110] and its deficiency is an epidemic, which affects 20–25% of the population in Asia, America, Canada, Europe and Australia[111]. This is becoming acuter in the Middle E considering of changes in lifestyle conditions and less sunlight[112]. Systematic reviews and meta-analyses in Iran take reported a loftier prevalence of vitamin D deficiency[91, 92].

The period of MS is often unpredictable, but some factors tin predict a patient'southward prognosis. The indicators of a good prognosis tin exist female gender, those with a history of affliction before the historic period of 35, those who were merely attacked in 1 area of the encephalon, those who had no brain stalk involvement and patients who had recovered afterwards the attacks[10]. To achieve successful symptom control, multiple controls are needed to forestall or end the symptoms. Effective communication, training, exercise, professional support, and pharmacological interventions are vital for effective control of multiple sclerosis symptoms.

5. Limitations

1. The insensitivity of internal databases to operators "AND" and "OR" to search for the combination. 2. Since Tehran is the main medical centre of many cities and provinces, patients in the studies in Tehran, are non just from Tehran.

3. No separation of rural and urban prevalence of MS

6. Conclusion

The nowadays meta-analysis showed that the prevalence and incidence of MS in Iran is high (every bit Wade scaled prevalence of MS globally[72]) and is rising over time. The results of this study provide useful data for neurologists and health policy makers and can provide a full general overview of MS epidemiology in Iran.

Appendix 1: PubMed search strategy

1. Exp. 'Epidemiology'
2. Exp.'Prevalence'
3. Exp.'Incidence''
4. Exp.MS'
5. Exp.'Multiple Sclerosis '
6. Exp.'Islamic republic of iran'
7. 1 OR ii OR 3
8. 4 OR v
9. 7 AND 8 AND 9

Supporting data

Acknowledgments

Hereby, we limited our deepest sense of gratitude to Ilam University of Medical Sciences for their scientific supports.

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