Multiple Sclerosis and Related Disorders (2014) 3, 48–60

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journal homepage: www.elsevier.com/locate/msard

MS incidence and prevalence in Africa, Asia, Australia and New Zealand: A systematic review N. Makhania,b,n, S.A. Morrowc, J. Fiskd,e,f, C. Evansg, S.G Belandh, S. Kulagah, E. Kingwelli, J.J. Marriottj, J Dykemanf, N. Jettéf,k,l, T. Pringsheimk,l,m, C. Wolfsoni,n,o, R.A. Marriej, M.W. Kochk,l a

Department of Pediatrics, Division of Neurology, The Hospital for Sick Children, Toronto, Canada Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, Canada c Department of Clinical Neurological Sciences, University of Western Ontario, London, Canada d Department of Psychiatry, Dalhousie University, Halifax, Canada e Department of Medicine, Dalhousie University, Halifax, Canada f Department of Community Health Sciences, University of Calgary, Calgary, Canada g College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Canada h Research Institute of the McGill University Health Centre, McGill University, Montreal, Canada i Division of Neurology, University of British Columbia, Vancouver, Canada j Department of Internal Medicine, University of Manitoba, Winnipeg, Canada k Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, Canada l Institute for Public Health, University of Calgary, Calgary, Canada m Department of Pediatrics, University of Calgary, Calgary, Canada n Department of Epidemiology & Biostatistics, McGill University, Canada o Department of Medicine, McGill University, Canada b

Received 10 May 2013; accepted 27 June 2013

KEYWORDS Multiple sclerosis; Incidence; Prevalence; Epidemiology; Asia, Africa

Abstract Objectives: Studies of multiple sclerosis (MS) incidence and prevalence from Africa, Asia, Australia and New Zealand are relatively scarce. We systematically reviewed MS incidence and prevalence in these regions including a standardized evaluation of study quality. Methods: We searched MEDLINE and EMBASE databases for studies of MS prevalence or incidence in Africa, Asia, Australia and New Zealand published in English or French between January 1, 1985 and January 31, 2011. Study quality was assessed using a standardized tool. All steps of the review were performed in duplicate. Results: Of 3925 citations identified, 28 studies met inclusion criteria and 21 of these were from Asia. Quality scores ranged from 1/8 to 8/8; the lowest scores were observed in studies

n

Corresponding author at: Division of Neurology, 555 University Ave., Toronto, ON Canada M5G 1X8. Tel.: +1 416 813 6660; fax: +1 416 813 6334. E-mail address: [email protected] (N. Makhani). 2211-0348/$ - see front matter & 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.msard.2013.06.015

MS incidence and prevalence in Africa, Asia, Australia, and New Zealand

49

from Asia (median 4/8, IQR 3,6). Prevalence was lowest in South African Blacks (0.22/100,000) and highest amongst Australian-born individuals in Australia (125/100,000). Prevalence increased over time in many countries. MS prevalence increased with increasing latitude only in some regions, and prevalence varied significantly with ethnicity. Eight studies reported incidence, which ranged from 0.67/100,000/year in Taiwan to 3.67/100,00/year in Australia. Conclusions: This comprehensive study provides an update of MS epidemiology in Africa, Asia, Australia, and New Zealand. Incidence and prevalence were lowest in Africa and Asia and highest in Australia, but many Asian studies were of poor quality. Use of consistent case ascertainment methods, standardized data collection tools, and similar outcomes would all improve study quality and comparability. The underlying basis of observed ethnic differences is an important area for future study. & 2013 Elsevier B.V. All rights reserved.

1.

Introduction

Studies of the incidence and prevalence of multiple sclerosis (MS) have largely come from Europe and North America, and have provided important insights into MS epidemiology, including increased MS risk with increasing latitude (Simpson et al., 2011a). Recent studies suggest that MS prevalence is increasing in several regions (Simpson et al., 2011a). Epidemiological studies in Asia, Africa, Australia and New Zealand have been relatively scarce and it is unclear whether similar geographic and temporal trends apply to these regions. Therefore, we conducted a systematic review of studies reporting the incidence and prevalence of MS in Africa, Asia, and Australia or New Zealand, including a standardized evaluation of study quality, which has rarely been done in previous reviews.

2. 2.1.

Methods Study selection

This review is a part of a larger study on worldwide epidemiology of neurologic diseases, including MS. We searched MEDLINE and EMBASE databases for “multiple sclerosis”, “incidence”, “prevalence” and “epidemiology” and identified peer-reviewed articles published anywhere in English or French between January 1, 1985 and January 31, 2011. This time limit was chosen because the introduction of magnetic resonance imaging (MRI) in 1985 substantially influenced diagnosis of neurologic disorders including MS, and likely the reliability of included cases. Eligible studies had to include original data; articles that presented updates of previously reported results were treated as a single study and only one quality assessment was performed. Studies in which data collection occurred exclusively prior to January 1, 1985 and those in which results were presented only in posters, abstracts, or presentations were excluded. Following the literature review, two reviewers independently screened each title and abstract for relevance. If relevance could not be confirmed from the abstract alone, two reviewers independently screened the full text article. All articles deemed relevant by consensus were retained. Bibliographies of all relevant articles and review articles were hand-searched to identify additional potentially relevant studies. To allow for a meaningful examination and

discussion, studies from Africa, Asia, and Australia or New Zealand were identified for this review (Fig. 1).

2.2.

Data extraction

For all studies, two trained reviewers independently abstracted data into a standardized form using the DistillerSR system (Evidence Partners, Ottawa, Canada). Reviewers were provided printed materials regarding the review process and an orientation to form completion; each also received feedback on training articles. Data collection forms have been previously published (Evans et al., 2013). We recorded crude and standardized (if available) incidence and prevalence for the population overall and by sex, ethnic sub-groups, across multiple time periods and for geographical sub-regions when reported. Sex ratios for incidence studies, which are less prone to survival bias than prevalence studies, were calculated when possible.

2.3.

Quality assessment

Two reviewers independently assessed quality for each study and conflicts were resolved by consensus. Study quality was evaluated using a quality assessment tool that was developed for the larger worldwide study (Evans et al., 2013), and created based on published guidelines (Boyle, 1998). Each study was given a quality score of up to eight points with one point given per affirmative answer to each of the following: (1) Was the target population clearly described?, (2) Were cases ascertained either by survey of the entire population or by probability sampling?, (3) Was the response rate 470%?, (4) Were the non-responders clearly described?, (5) Was the sample representative of the population?, (6) Were data collection methods standardized?, (7) Were validated criteria used to assess the presence/absence of disease?, and (8) Were the estimates of prevalence or incidence given with confidence intervals?. For studies based solely on national, population-based administrative health claims data, reviewers were asked to mark “yes” for questions 3–6. This applied to only a single included study.

50

N. Makhani et al.

Fig. 1

2.4.

Flow diagram of study selection process.

Data analysis

We examined the I2 statistic, a statistic describing the proportion of variation in point estimates due to heterogeneity of studies rather than to sampling error; a chi-square test of homogeneity was performed to determine strength of evidence that heterogeneity is genuine. Given the heterogeneity between studies (I2 =99.9), a meta-analysis was not performed.

3. 3.1.

Results Study characteristics

The search strategy yielded 3925 studies, 28 of which met our inclusion criteria (Fig. 1). Of these, 21 studies were from Asia, 2 from Africa, and 5 from Australia or New Zealand (Figs. 2 and 3). Prevalence and incidence findings were highly variable. Crude prevalence ranged from 0.22/

100,000 in South African Blacks (Bhigjee et al., 2007) to 125/100,000 amongst Australian-born Australians (Simpson et al., 2011b). Crude annual incidence ranged from 0.67/ 100,000 in Taiwan (Lai and Tseng, 2009) to 3.67/100,000 in Australia (Simpson et al., 2011b). Female to male incidence ratios ranged from 1.42 in Taiwan (Lai and Tseng, 2009) to 2.1 in Newcastle, Australia (Barnett et al., 2003). Case ascertainment methods varied across studies (Tables 1 and 2), but most often included multiple methods (16/28), or a review of hospital and clinic data (5/28). Neurologist reports, database review, surveys, and review of health insurance (administrative) data alone were less commonly employed (total 7/28). The most commonly used diagnostic criteria were those of Poser (12/28) (Poser et al., 1983), followed by McDonald 2005 (5/28) (McDonald et al., 2001), McDonald 2001 (4/28) (Polman et al., 2005), or Schumacher (1/28) criteria (Schumacher et al., 1965). Two studies used the authors' own criteria (essentially the same as either McDonald 2001 or Schumacher criteria) (Chancellor et al., 2003;

MS incidence and prevalence in Africa, Asia, Australia, and New Zealand

51

Fig. 2 MS Prevalence in Africa, Asia, Australia and New Zealand. Smaller circles represent studies conducted in a single city. Larger circles represent studies conducted in a region or country.

Fig. 3 MS Incidence in Africa, Asia, Australia and New Zealand. Smaller circles represent studies conducted in a single city. Larger circles represent studies conducted in a region or country.

Osoegawa et al., 2009), one study employed Rose criteria (Barnett et al., 2003) and three studies did not report the criteria utilized (Lai and Tseng, 2009; Lau et al., 2002; Sahraian et al., 2010). More recent studies were more likely to use the McDonald 2001 (McDonald et al., 2001) or 2005 (Polman et al.,

2005) criteria that include MRI assessments. Most studies utilized multiple methods to confirm diagnoses (14/28), while some used only clinical assessments (4/28), chart reviews (4/28), administrative data codes (without validation, 1/28) (Lai and Tseng, 2009), or health care professional questionnaires

Table 1

Africa Bhigjee et al. (2007)

Quality score /8

6

Country Case ascertainment method Region Subpopulation

South Africa KwaZuluNatal Indians Blacks

Hospitals or clinics; neurologists; patient associations; media campaign

Diagnostic criteria (established by)

McDonald 2005 (medical chart review; phone call to patient)

Australia Newcastle

Chancellor et al. (2003)

4

New Zealand Bay of Plenty

Simmons et al. (2001)

6

Simpson et al. (2011b)

4

Australia Australian Capital Territory Australia Greater Hobart, Tasmania Overall Overseas-born Australianborn New Zealand Overall

Taylor et al. 7 (2010)

6

07-2005

Standard population (date)

World (not reported)

Prevalence in males/ Prevalence in 100,000 females/100,000 (95% C.I.) (95% C.I.) Crude AgeCrude standardized

Agestandardized

–

–

–

–

105 (409,554)

Hospitals or clinics; neurologists; other physicians; patient associations; participants of a previous survey; participants in an interferon trial Hospitals or clinics; neurologists; other physicians; administrative database; patient associations; chronic care facilities Neurologists

Neurologists; patient associations; participants in other MS research studies at the Menzies Research Institute'

Agestandardized overall Prevalence/ 100,000 (95% CI)

7.59 (5.6– 10.07)

7.15

0.22 (0.12– 0.40) 25.63 (20.97– 31.04)

0.23

79 (133,686)

08-08-1996

Australian population (1996)

33.7 33.1 (20.6– 50.2)

83.7 (62.9– 108.4)

83.4

59.1 (46.3– 73.2)

58.6

86 (171,147)

01-15-2001

–

–

–

–

–

50 (40–60)

–

155 (308,025)

08-06-1996

Australian population (1996)

–

28.0 (20.3– 37.8)

–

70.6 (58.4– 85.3)

–

49.5 (42.2– 58.2)

McDonald 2005 (clinical assessment)

265 (212,959)

01-01-2009

Greater Hobart population (1961)

71.9 54.8 (57.2– 90.3)

175.8 145.0 (152.5– 202.6)

125.2 (111.0– 141.3)

99.6 (82.9– 119.7)

–

26.7 63.25

–

86.4 160.3

–

56.4 111.4

European population (not reported)

–

–

–

–

72.4

73.1 (70.5– 75.8)

24.2 (18.9– 29.5) 78.7 (75.7– 81.6) 82.4 (79.4– 85.5) 101.9 (98– 105.8)

McDonald 2005 (clinical assessment; medical chart review)

2917 (4,027,950)

03-07-2006

Maori

90 (565,323)

–

–

–

–

–

15.9

Non-Maori

2827 (3,462,606)

–

–

–

–

–

81.6

Non-Maori/ Pacific Peoples European

2823 (3,215,667)

–

–

–

–

–

87.8

Kuwait Overall Kuwaitis Non-Kuwaitis

2699 (2,609,586)

Hospitals or clinics; patient associations; registry

25.64

Rose definite, probable, and possible (clinical assessment; medical chart review; administrative data codes; enrollment in interferon trial) Criteria created by the authors essentially the same as McDonald 2001 definite and probable (clinical assessment; medical chart review) Poser definite and probable (medical chart review)

33 231 Mailed survey; hospitals or clinics; neurologists; patient associations; media campaign; telephone or in-person survey; health administrative databases; MS care providers

Crude overall prevalence/ 100,000 (95% CI)

Poser definite (medical chart review)

333 (not reported)

103.4

2000

–

10.06 – (8.38– 11.73) 26.65

22.09 – (18.99– 25.19) 35.54

14.77 (13.18– 16.35) 31.15 5.55

–

N. Makhani et al.

Asia Alshubaili et al. (2005)

48 (632,262)

Prevalence day/period

12 (5,316,060)

Whites

Australia and New Zealand Barnett 6 et al. (2003)

Number of MS Cases (population/ denominator)

52

Study (year)

Prevalence of multiple sclerosis in Africa, Asia, Australia and New Zealand from January 1, 1985 to January 31, 2011.

Alter et al. (2006)

Karni et al. (2003)

Turk Boru et al. (2006) El-Salem et al. (2006)

5

4

4

6

Kuwait Kuwaitis Palestinians Israel Israeli-born Jews Jews born in Europe/ America Jews born in Africa or Asia Christian Arabs Moslem Arabs Israel Greater Jerusalem Israeli-born Arabs Israeli-born European/ American Jews Immigrant European/ American Jews Israeli-born African/Asian Jews Immigrant African/Asian Jews Turkey Maltepe, Istanbul Jordan Irbid

Hospitals or clinics; neurologists; other physicians

Poser definite and probable (not reported)

Hospital or clinics, neurologists; patient associations; CSF Laboratory

Poser definite and probable (not reported)

Ghandehari et al. (2010)

12-31-1988

72 (302,000) 1497 (3,165,200)

06-30-2000

352 (1,402,000)

Hospitals or clinics; patient associations; registry

Door-to-door survey

Hospitals or clinics

Amman

Sahraian et al. (2010) Etemadifar et al. (2006)

51 (535,000)

Poser not specified (medical chart review)

–

7.2

– 20.5 Israeli Jewish – population (1960) –

–

11.8

–

9.5

–

– –

27.5 –

– –

23.8 47.3

– 61.6 (58.06– 65.06)

–

–

–

67.9

53.7 (50.11– 57.37) 27.9 (22.92– 32.92) 35.3 (24.03– 46.51) 14.7 (11.73– 17.77) 19.2

248 (555,600)

–

–

–

–

44.6

43 (210,000)

–

–

–

–

38.2

106 (952,200)

–

–

–

–

11.1

–

–

–

–

–

19 (167,300)

12-31-1995

Residents of Greater Jerusalem (December 31, 1995)

65 (137,458)

63.5

88 (114,966)

64.3

79 (202,872)

52.1

21 (54,945)

22.1

Poser definite and probable (clinical 33 (316,028) assessment; medical chart review; imaging; CSF; EP) McDonald 2001 (clinical assessment; 38 (99,440) medical chart review; imaging; CSF; use of interferon) 39 (402,960)

From 112002 to 052003 From 092004 to 082005

–

76.0

–

118.7

–

101.4

–

–

11 – (3.6– 25.6) 21 – (15.2– 28.4) – –

61 (42.2– 86.1) 57 (46.8– 68.3) –

–

38 (32.9– 45.3)

–

–

39 (32.9– 45.3)

–

–

51.9

–

15.3 17.0 (8.9– (13.6– 25.1) 17.0)

56.7 (53.3– 60.1)

59.5 (44.8– 75.2)

–

–

8.27

–

5.34

–

–

Iran Tehran

Patient associations

Not reported (not reported)

7320 (14,103,853) 12-2008

–

3

Iran Isfahan Province

Patient associations; registry

McDonald 2001 (clinical assessment)

1391 (3,923,255)

2004–2005

3

Iran Khorasan region Southern Khorasan province Northern Khorasan province

Patient associations; registry

McDonald 2005 (clinical assessment; imaging; CSF)

34 (636,420)

2009

WHO European standard population (not reported) –

71 (811,572)

2.48

6.22

–

11.22

8.74

53

2

MS incidence and prevalence in Africa, Asia, Australia, and New Zealand

al-Din et al. 4 (1990)

54

Table 1 (continued ) Study (year)

Quality score /8

Country Case ascertainment method Region Subpopulation

Diagnostic criteria (established by)

Number of MS Cases (population/ denominator)

Prevalence day/period

Standard population (date)

Prevalence in males/ Prevalence in 100,000 females/100,000 (95% C.I.) (95% C.I.) Crude AgeCrude standardized

Saadatnia 4 et al. (2007) Bharucha 5 et al. (1988) Cheng et al. 6 (2007) Lau et al. (2002) Yu et al. (1989)

1 4

Osoegawa et al. (2009)

2

Houzen et al. (2008)

3

Houzen et al. (2003)

5

Itoh et al. (2003)

Rasavi province Iran Patient associations Isfahan province India Door-to-door survey Bombay Parsis

721 (5,593,079) McDonald 2001; Thomson (PPMS) (clinical 1718 (3,923,255) assessment; imaging) Schumacher definite (clinical assessment)

3 (14,010)

From 042003 to 072006 03-01-1985

–

Agestandardized

Crude overall prevalence/ 100,000 (95% CI)

Agestandardized overall Prevalence/ 100,000 (95% CI)

5.91

19.94

12.89

43.8 – (41.7– 46) – –

69.6 (66– 73.4) –

–

43.8 (41.7– 46)

–

–

21 (4.4– 62.5)

15 (3.1–43.8)

1.80 (1.43– 2.25) –

–

1.39 (1.16– 1.66)

–

–

0.77

– –

China Shanghai

Hospitals or clinics; neurologists; other physicians; registry

McDonald 2001 (clinical assessment; medical chart review; imaging; CSF; EP)

123 (8,860,000)

12-31-2004

US population (1960) –

China Hong Kong China Hong Kong Chinese Japan

Neurologists; other physicians

Not reporteda (imaging; EP; questionnaire Poser definite and probable (clinical assessment; imaging; EP; CSF; blood tests) Criteria created by the authors essentially the same as Schumacher definite and possible; McDonald 2001 (PPMS) (health care professionals’ questionnaire) Poser not specified (clinical assessment; medical chart review)

53 (6,800,000)

1999

–

0.98 – (0.71– 1.31) – –

43 (4,900,000)

12-31-1987

–

–

–

–

–

0.88

9900b(not reported)

From 01-012003 to 1231-2003

–

–

–

–

7.7 (7.1– 8.4)

47 (358,439)

03-31-2006

–

7.0 (9.6– 17.4)

–

18.8 (13.1– 26.1)

–

13.1 (9.6– 17.4)

13.6

–

12.3 (7.8– 18.5)

–

8.57 (5.82– 12.17)

–

Neurologists; other physicians

Hospitals or clinics

Hospitals or clinics

Poser definite (clinical assessment; medical chart review)

31 (361,726)

03-31-2001

–

4.6 (2.0– 9.0)

3

Japan Tokachi province, Hokkaido Japan Tokachi province, Hokkaido Japan

Hospitals or clinics

Hospitals or clinics

Poser definite (not reported)

37 (363,526)

05-01-2002

–

10.18 (7.17– – 14.03)

8

Korea

Hospitals or clinics; administrative database

–

3.6 (3.2– 4.0)

–

Lai and Tseng (2009) Tsai et al. (2004)

6

Taiwan

Administrative database

McDonald 2005 (medical chart review; 1681b(47,041,434) 12-31-2005 administrative data codes; review of registry data) Not reported (administrative data codes) 674 (22,770,000) 2005

–

12.55 (8.04– 18.16) 3.9 (2.4– 5.1) 4.65

–

Kim et al. (2010)

7.54 – (4.02– 12.90) 3.1 – (1.5– 3.7) 1.32 –

–

2.96

–

6

Taiwan Chinese

Bureau of National Health Insurance

–

–

–

–

1.9

–

Poser not specified (medical chart review)

429 (22,405,000)

Unclear

–

N. Makhani et al.

Abbreviations: CSF =cerebrospinal fluid, EP=evoked potentials, PPMS=primary-progressive MS. a No diagnostic criteria were reported in Methods section. While this paper states in Results section that Poser criteria were used to classify clinical course, the classification method is different from that described by Poser et al. suggesting an incorrect reference. b Estimated.

Incidence of multiple sclerosis in Africa, Asia, Australia and New Zealand from January 1, 1985 to January 31, 2011.

Study (year)

Africa Rosman et al. (1985)

Quality Country Region Case ascertainment score/ subpopulation method 8

4

Australia and NewZealand Barnett et al. 6 (2003)

Simpson et al (2011b)

4

Asia Alshubaili et al. 6 (2005)

Number of MS cases (population/ denominator)

Neurologists; South Africa EP referrals Pretoria and Wonderboom White Afrikaansspeaking residents

Poser not specified (clinical assessment)

Australia Newcastle

Rose definite, probable, and 33 (131,303) possible (clinical assessment; medical chart review; administrative data codes; enrollment in interferon trial)

Hospitals or clinics; neurologists; other physicians; patient associations; participants of a previous survey; participants in an interferon trial Australia Neurologists; patient Greater Hobart, associations; participants in Tasmania other MS research studies at the Menzies Research Institute'

Kuwait

Hospitals or clinics; patient associations; registry

El-Salem et al. (2006)

6

Jordan Irbid and Amman

Hospitals or clinics

Houzen et al. (2008)

3

Japan Tokachi province Taiwan

Hospitals or clinics

Lai and Tseng 6 (2009) Saadatnia et al. 4 (2007)

Diagnostic criteria (established by)

Iran Isfahan province

Administrative database Patient associations

McDonald 2005 (clinical assessment)

5 (319,868)

Study Standard Incidence in Males/ interval population 100,000 (95% CI) (Incidence (date) type) Crude Agestandardized

Incidence in females/100,000 (95% C.I.)

– From 0301-1984 to 02–28-1985 (annual)

–

–

Mid-1986 to Australian population mid-1996 (1996) (mean annual)

1.56 1.52 (0.74– 2.85)

3.27 3.36 (2.07– 5.02)

Greater Hobart population (1954)

–

–

–

1.18 – (0.96– 1.39) – –

2.35 – (1.97– 2.74) – –

Japanese population (2005) –

–

–

–

–

0.67

–

0.95

–

–

–

–

–

–

Not reported 2001–2009 (mean annual)

Poser definite (medical chart 256 review)

1993–2000 (mean annual) 194 (502,400) From 09McDonald 2001 (clinical 2004 to 08assessment; medical chart 2005 review; imaging; CSF; use of (annual) interferon) Poser not specified (clinical 14 (360,992) 2000–2004 (mean assessment; medical chart annual) review) Not reported (administrative 107 2005 data codes) (22,770,000) (annual) McDonald 2001; Thomson 143 2005 (PPMS) (clinical assessment; (3,923,255) (annual) imaging)

–

–

–

Crude Agestandardized

Female: Crude male overall ratio Incidence/ 100,000 (95% CI)

–

1.6

2.1

–

1.42

–

2.44 (1.68– 2.45 3.47)

3.7 (2.8– 4.8)

1.99

Agestandardized overall incidence/ 100,000 (95% CI)

3.7 (2.5–5.4)

1.63 (1.43– – 1.83) 1.14

–

.78 (.43– 1.31)

.78

0.67

–

3.64

–

MS incidence and prevalence in Africa, Asia, Australia, and New Zealand

Table 2

Abbreviations: CSF=cerebrospinal fluid, EP=evoked potentials, PPMS=primary-progressive MS.

55

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N. Makhani et al.

(1/28) (Osoegawa et al., 2009). Four studies did not report how diagnoses were confirmed (al-Din et al., 1990; Alter et al., 2006; Itoh et al., 2003; Sahraian et al., 2010). Study quality also varied (see Supplementary Tables S1– S3). The lowest quality studies tended to arise from Asia (Tables 1 and 2), where the median quality score was 4/8 (IQR 3,6) versus a median of 6/8 (IQR 4,6) for studies from Africa, Australia, or New Zealand.

3.2.

MS incidence and prevalence

3.2.1. Africa 3.2.1.1. South Africa. Both African studies were regional studies from South Africa. The first study relied on neurologists for case ascertainment, and clinical assessments based on Poser criteria to confirm diagnosis and found a crude annual incidence of 1.6/100,000 between 1984 and 1985 (prevalence not determined) amongst white Afrikaans-speaking residents of Pretoria and Wonderboom (Rosman et al., 1985). The quality score was 4/8. In contrast, a more recent study from the KwaZulu-Natal province used multiple sources of ascertainment, McDonald 2005 diagnostic criteria, and confirmation via medical chart reviews and patient phone calls (Bhigjee et al., 2007). Age-standardized prevalence in Whites (25.63/100,000) was higher than amongst the South East Asian Indians (7.15/ 100,000) and Blacks (0.23/100,000). The quality score was 6/8. 3.2.2. Australia and New Zealand The highest observed incidence and prevalence occurred in these regions. 3.2.2.1. Australia. Three Australian studies estimated prevalence (Barnett et al., 2003; Simmons et al., 2001; Simpson et al., 2011b) two of which also estimated incidence (Barnett et al., 2003; Simpson et al., 2011b). None of these were performed nationwide. The first study was from the Australian Capital Territory region including the city of Canberra. Using neurologists' reports to identify cases diagnosed based on Poser criteria (probable and definite) and medical chart reviews for confirmation, the agestandardized prevalence was 49.5/100,000 (95% C.I. 42.2– 58.2) in 1996 (Simmons et al., 2001). In the same study, agestandardized prevalence using the criteria of Rose et al. (1976) was 56.7/100,000 (95% C.I. 43.1–74.1). The quality score was 6/8. In the second study, from the city of Newcastle, multiple sources of ascertainment were used including an ongoing clinical trial (Barnett et al., 2003). Diagnoses were confirmed by a clinical assessment, medical chart review, review of diagnostic codes and clinical trial participation, based on the Rose criteria (Rose et al., 1976). Agestandardized prevalence in Newcastle in 1996 was similar to that observed in the Australian Capital Region at 58.6/ 100,000. Standardized average annual incidence was 3.36/ 100,000 between 1986 and 1996 and the female to male incidence ratio was 2.1. The quality score was 6/8. The most recent study from Hobart, Tasmania also utilized multiple sources of ascertainment (Simpson et al., 2011b). Using McDonald 2005 diagnostic criteria and case confirmation by clinical assessment, age-standardized prevalence in 2009 was found to be higher than that reported earlier in other parts of Australia at 99.6/100,000 (95% C.I.

82.9–119.7). Standardized average annual incidence was 3.7/100,000 (95% C.I. 2.8–4.8) between 2001 and 2009. The quality score was 4/8. 3.2.2.2. New Zealand. Two studies reported prevalence (Chancellor et al., 2003; Taylor et al., 2010), and both used multiple sources for ascertainment. The first study was regional, from the Bay of Plenty, and used diagnostic criteria created by the authors (essentially the same as the McDonald 2001 criteria) (Chancellor et al., 2003). Diagnoses were confirmed by clinical assessments and chart reviews. Crude prevalence was estimated at 50/100,000 (95% C.I. 40–60) in 2001. The quality score was 4/8. The only national study was conducted in 2006 (Taylor et al., 2010). Using more recent McDonald 2005 diagnostic criteria, age-standardized prevalence was found to be higher than the earlier regional study at 73.1/100,000 (95% C.I. 70.5–75.8). Age-standardized prevalence was highest in Europeans at 101.9/100,000 (95% C.I. 98–105.8) and lowest in Maoris (24.2/100,000 [95% C.I. 18.9–29.5]). The quality score was 7/8. 3.2.3. Asia Twenty-one Asian studies (from Kuwait, Israel, Turkey, Jordan, Iran, India, China, Japan, and Taiwan) estimated prevalence, four of which also reported incidence. Prevalence in this region was highly variable, and was lowest in Hong Kong, China (0.77/100,000) and highest in Istanbul, Turkey (101.4/100,000). 3.2.3.1. Kuwait. Both studies from Kuwait were national studies that utilized multiple case ascertainment methods and Poser diagnostic criteria (al-Din et al., 1990; Alshubaili et al., 2005). The earlier study included individuals residing in Kuwait for at least two years and both probable and definite MS cases while the later study included only definite MS cases and there was no minimum time of residency required for inclusion. In 1988, crude prevalence amongst Kuwaitis was 9.5/100,000, which was lower than amongst Palestinians (23.8/100,000) (al-Din et al., 1990). In 2000, an opposite pattern to the prior study was observed with crude prevalence amongst Kuwaitis rising to 31.15/100,000, higher than the prevalence amongst non-Kuwaitis (5.5/ 100,000) (Alshubaili et al., 2005). Crude mean annual incidence between 1993 and 2000 was 1.63/100,000 (95% C.I. 1.43–1.83) and the female to male incidence ratio was 1.99. The study quality scores were 4/8 and 6/8 respectively. 3.2.3.2. Israel. Two studies reported prevalence. Both studies used multiple methods of case ascertainment and Poser diagnostic criteria. In 1995, age-standardized prevalence in Greater Jerusalem amongst immigrant European or American Jews (64.3/100,000) was higher than the prevalence in immigrant African or Asian Jews (22.1/100,000) (Karni et al., 2003). In contrast, prevalence in Israeli-born European or American Jews (63.5/100,000) was only slightly higher than that of Israeli-born African or Asian Jews (52.1/100,000). Prevalence was lowest in Israeli-born Arabs (19.2/100,000). A nationwide study conducted in 2000 found that agestandardized prevalence amongst Israeli-born Jews was 61.6/ 100,000 (95% C.I. 58.06–65.06) (Alter et al., 2006). Similar to the earlier study from Greater Jerusalem, prevalence in Jews born in Europe or America (53.7/100,000 [95% C.I. 50.11– 57.37]) was higher than that of Jews born in Africa or Asia

MS incidence and prevalence in Africa, Asia, Australia, and New Zealand (27.9/100,000 [95% C.I. 22.92–32.92]). Christian Arabs had a higher prevalence (35.3/100,000 [95% C.I. 24.03–46.51]) than Muslim Arabs (14.7/100,000 [95% C.I. 11.73–17.77]). Quality scores for these studies were 4/8 and 5/8. 3.2.3.3. Turkey. The sole Turkish study was conducted in the district of Maltepe, Istanbul. Using Poser criteria, patients with definite or probable MS were identified using a door-to-door survey. Prevalence was reported to be 101.4/ 100,000 (Turk Boru et al., 2006). The quality score was 4/8. 3.2.3.4. Jordan. The only study from Jordan was conducted in the cities of Irbid and Amman using hospital and clinic records to identify cases of definite or probable MS based on McDonald 2001 criteria. The estimated crude prevalence in 2004 was 38/100,000 (95% C.I. 32.9–45.3) in Irbid and similarly 39/1000 (95% C.I. 32.9–35.3) in Amman (El-Salem et al., 2006). The quality score was 6/8. 3.2.3.5. Iran. The four prevalence studies from Iran, none of which was national, all used patient association membership lists to identify MS patients and clinical assessments with or without spinal fluid analysis to confirm diagnoses. Using McDonald 2001 criteria for definite MS, the standardized prevalence in Isfahan province was 59.5/100,000 (95% C.I. 44.8–75.2) in women and similarly 56.7/100,000 (95% C. I. 53.3–60.1) in men between 2004 and 2005 (Etemadifar et al., 2006). A second study from Isfahan that utilized both McDonald 2001 criteria and Thompson criteria for primaryprogressive MS (Thompson et al., 1997) reported a slightly lower crude prevalence (43.8/100,000 [95% C.I. 41.7–46]) between 2003 and 2006 (Saadatnia et al., 2007), and a oneyear crude incidence of 3.64/100,000. A study in the Northeastern region of Iran reported a much lower crude prevalence rates than studies from Ifsahan at 5.34/100,000 in Southern Khorasan province, 8.74/100,000 in Northern Khorasan province, and 12.89/100,000 in Razavi province in 1999 (Ghandehari et al., 2010). Finally, a study conducted in the city of Tehran reported a crude prevalence of 51.9/ 100,000 in 2008 (Sahraian et al., 2010). The quality of studies ranged from 2/8 to 4/8. 3.2.3.6. India. In the sole study from India, a door-to-door survey was conducted amongst Parsis in the city of Bombay to identify cases, which were confirmed to meet Schumacher diagnostic criteria based on clinical assessments (Bharucha et al., 1988). In 1985, the age-standardized prevalence was 15/100,000 (95% C.I. 3.1–43.8). The quality score was 5/8. 3.2.3.7. China. Three regional studies examined MS prevalence in China; there were no national studies. All studies similarly used information from neurologists or clinics for case ascertainment (Cheng et al., 2007; Lau et al., 2002; Yu et al., 1989), and the most recent study also utilized a patient registry (Cheng et al., 2007). Using Poser criteria to define probable and definite cases, confirmed with clinical assessments and laboratory results, crude prevalence in Hong Kong Chinese individuals was 0.88/100,000 in 1987 (Yu et al., 1989). A second study (diagnostic criteria not specified)1 from Hong Kong found a crude prevalence of 1 No diagnostic criteria were reported in the Methods section. While the article states in the Results section that Poser criteria were used to classify clinical course, the classification method is different from that described by Poser et al. suggesting an incorrect reference.

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0.77/100,000 in 1999 (Lau et al., 2002). A more recent study conducted in Shanghai that utilized newer McDonald 2001 diagnostic criteria with clinical assessments, chart reviews, and laboratory results to confirm diagnoses, found a slightly higher crude prevalence of 1.39/100,000 (95% C.I. 1.16–1.66) between 2004 and 2005 (Cheng et al., 2007). The quality scores varied between 1/8 and 6/8. 3.2.3.8. Japan. Four Japanese studies reported prevalence, and all used hospital and clinic data for case ascertainment (Houzen et al., 2008, 2003; Itoh et al., 2003; Osoegawa et al., 2009). Using Poser criteria for definite MS, a national study reported a crude prevalence of 10.18/100,000 (95% C.I. 7.17–14.03) in 2002 (Itoh et al., 2003), similar to that determined in 2003 using McDonald 2001 criteria (7.7/100,000 [95% C.I. 7.1–8.4]) (Osoegawa et al., 2009). Two regional studies estimated prevalence in Tokachi province. Crude prevalence was estimated at 8.57/ 100,000 (95% C.I. 5.82–12.17) in 2001 (Houzen et al., 2003) and was similarly 13.1/100,000 (95% C.I. 9.6–17.4) in 2006 (Houzen et al., 2008). Age- and sex-adjusted annual incidence in the latter study was 0.78/100,000 (95% C.I. 0.43– 1.31) between 2000 and 2004 and the female to male incidence ratio was 1.42. The quality scores ranged from 2/8 to 5/8. 3.2.3.9. Korea. A single, national study from Korea ascertained cases using hospital or clinic data, and an administrative database (Kim et al., 2010). Applying McDonald 2005 criteria to clinical information retrieved from medical charts, registry data, and using administrative data codes, crude prevalence was estimated at 3.6/100,000 (95% C.I. 3.2–4.0). The quality score was 8/8. 3.2.3.10. Taiwan. Two national studies estimated MS prevalence, while one also estimated incidence (Lai and Tseng, 2009; Tsai et al., 2004). Using National Health Insurance administrative data to identify patients, followed by a chart review to confirm the diagnosis according to Poser criteria, crude prevalence amongst Taiwanese individuals of Chinese descent was 1.9/100,000 between 1995 and 2002 (Tsai et al., 2004). Using only an administrative database for case ascertainment, crude prevalence amongst all Taiwanese individuals was slightly higher in 2005 (2.96/100,000) although neither study reported confidence intervals (Lai and Tseng, 2009). The second study reported a crude incidence of 0.67/100,000 in 2005. Both studies had quality scores of 6/8.

4.

Discussion

We identified 28 studies reporting incidence, prevalence, or both, from Asia, Africa, and Australia or New Zealand. Overall, study methods were highly heterogeneous, as reported in a systematic review of MS epidemiology in the Americas, but quality was more highly variable than in the Americas (Evans et al., 2013). While most studies (21/28) were conducted in Asia, these studies were generally of lower quality than those conducted in other areas, suggesting their findings should be interpreted cautiously. Lower quality studies occurred for several reasons. Studies from Asia often did not report response rates (18/21 either not reported or not clear) or clearly describe what types of patients may not have been captured by the ascertainment

58 method (19/21 either not reported or not clear). Standardized data collection methods were utilized by only half of all Asian studies (11/21) and only 13 of 21 studies were deemed likely to have captured the entire MS population of interest. Only 10 of 21 Asian studies reported incidence or prevalence with appropriate confidence intervals. There were some high quality studies from Asia (quality score≥6/8) conducted in Kuwait (Alshubaili et al., 2005), Jordan (El-Salem et al., 2006), China (Cheng et al., 2007), Korea (Kim et al., 2010), and Taiwan (Lai and Tseng, 2009; Tsai et al., 2004), providing the most reliable estimates for prevalence in this region. Study quality was generally high in studies originating outside of Asia, suggesting that the estimated incidence and prevalence in these regions are reasonably accurate. The criteria used to diagnose MS varied across studies and changed over time with more recent studies being more likely to employ McDonald 2001 or McDonald 2005 criteria (McDonald et al., 2001; Polman et al., 2005). The effect of diagnostic criteria on reported MS prevalence and incidence has not been precisely determined; however, two prior studies suggested that using Poser criteria for definite and probable MS might lead to slightly higher prevalence estimates as compared to the newer McDonald criteria (Fangerau et al., 2004; Fox et al., 2004). Of all the regions examined, prevalence was lowest in South African Blacks (Bhigjee et al., 2007). Prevalence was also low in many parts of Asia, especially China and Taiwan. Prevalence was highest in Australian-born individuals from Australia (Simpson et al., 2011b). Lower quality studies and varied case ascertainment and data collection methods may have contributed to the lower prevalence estimates observed in Asia, but even using only the highest quality studies (score≥6) prevalence in Asia ranged from 1.39/ 100,00 to 39/100,000 (Alshubaili et al., 2005; Cheng et al., 2007; El-Salem et al., 2006; Kim et al., 2010; Lai and Tseng, 2009; Tsai et al., 2004), as compared to 49.5/ 100,000 to 109.5/100,000 observed in similarly defined high quality studies from Australia and New Zealand (Barnett et al., 2003; Simmons et al., 2001; Taylor et al., 2010). Japan had the highest prevalence amongst the eastern Asian countries. Two distinct MS phenotypes have been recognized in Japan: “opticospinal” MS (with symptom predilection for the optic nerves and spinal cord) and classical relapsing-remitting (or “Western”) MS. Interestingly, in Japan there has been an apparent increase in the proportion of MS patients with classical relapsing-remitting MS (Houzen et al., 2008, 2003; Itoh et al., 2003), suggesting the influence of environmental factors that are possibly related to the “Westernization” of Japan. Similar temporal changes in disease phenotypes have been also observed in other autoimmune conditions such as inflammatory bowel disease in Asia, supporting a role for environmental factors in modulating the clinical expression of autoimmunity (Prideaux et al., 2012). It is likely that many individuals classified as having opticospinal MS, would now be considered to have the distinct disease neuromyelitis optica (NMO) (Wingerchuk et al., 2006). Prevalence appeared to increase over time in Taiwan, China, Israel and Kuwait, consistent with findings from a recent meta-analysis, although this meta-analysis did not consider study quality (Simpson et al., 2011a). The observed

N. Makhani et al. increasing prevalence may reflect a true increase in MS risk, but may also be a result of longer survival time, greater diagnostic accuracy, and/or improved case ascertainment methods. In Kuwait, the rising prevalence may in part be due to changes in the population's ethnic composition after the 1990 Gulf War and may also reflect that, due its broader inclusion criteria, the most recent study was more likely to capture MS cases in temporary workers (Alshubaili et al., 2005). Latitude appeared to be associated with prevalence differences. For instance, Australia had a relatively high MS prevalence, with a significant difference between Newcastle (3310′S latitude with prevalence ∼60/100,000) and Greater Hobart, Tasmania (latitude 42150′S with prevalence ∼100/100,000) (Barnett et al., 2003; Simpson et al., 2011b). These findings are consistent with other reports that MS prevalence increases with increasing distance away from the equator (Simpson et al., 2011a). Latitude differences were not, however, seen in all regions. For example in Iran, overall prevalence was relatively high (between 44 and 60/100,000), with the notable exception of the Khorasan province (prevalence between 5 and 13/100,000), despite its northern location (Etemadifar et al., 2006; Ghandehari et al., 2010; Saadatnia et al., 2007). While study quality may have contributed, regional ethnic differences, genetic susceptibility, or environmental factors other than latitude likely contribute to MS risk in Iran. Incidence sex ratios revealed increased MS incidence in women as compared to men, consistent with expectations (Alonso and Hernan, 2008). The small number of incidence studies, however, precluded definitive conclusions as to geographic differences in sex ratios or temporal trends. In several instances, MS risk appeared to differ substantially between different ethnic groups living within the same geographic region. In South Africa, Blacks had a much lower prevalence than Whites (Bhigjee et al., 2007). In Israel, prevalence was lower in Israeli-born Arabs than in Israeli-born Jews (Alter et al., 2006; Karni et al., 2003). Similarly in Australia, prevalence was higher in Australianborn individuals compared to those born overseas (Simpson et al., 2011b). In New Zealand, prevalence was lowest in Maoris and highest in Europeans (Taylor et al., 2010). Thus far, differences in prevalence between ethnic groups living in a common shared environment have not been investigated extensively. These differences may reflect differing genetic susceptibilities or exposure to different environmental factors. Given the apparent ethnic differences in MS risk, we suggest that ethnicity should be captured in future MS incidence and prevalence studies.

5.

Conclusions

An understanding of MS epidemiology is essential for generating hypotheses related to underlying genetic and environmental risk factors. In this review we provide an updated overview of MS incidence and prevalence in Africa, Asia, Australia, and New Zealand including standardized assessments of study quality. Many of these regions remain understudied and further epidemiological studies are required. The use of consistent case ascertainment methods, standardized data collection methods, and uniform

MS incidence and prevalence in Africa, Asia, Australia, and New Zealand outcome metrics would all contribute to better study quality, enhance study comparability, and improve our understanding of worldwide MS epidemiology.

Conflict of interest/Role of Funding Source Study Funding This study is part of the National Population Health Study of Neurological Conditions. We wish to acknowledge the membership of Neurological Health Charities Canada and the Public Health Agency of Canada for their contribution to the success of this initiative. Funding for the study was provided by the Public Health Agency of Canada. The funding agency had no involvement in study design, data acquisition, data analysis, or in the decision to submit this manuscript for publication.

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Services, the University of Calgary, the Hotchkiss Brain Institute and Alberta Health and Wellness. Dr. Pringsheim reports no disclosures. Dr. Wolfson received research funding from the Canadian Institutes of Health Research, the Canada Foundation for Innovation, Veterans Affairs Canada, MS Society of Canada, the Public Health Agency of Canada, and the Quebec Ministry of Economic Development, Innovation and Export Trade. Dr. Marrie received research funding from the Canadian Institutes of Health Research, the Public Health Agency of Canada, the Manitoba Health Research Council, the Health Sciences Centre Foundation, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Rx & D Health Research Foundation, and has conducted clinical trials funded by Bayer Inc. and Sanofi-Aventis. She is on the Editorial Boards of Neurology and the Multiple Sclerosis Journal. Dr. Koch reports no disclosures.

Disclaimer The opinions expressed in this publication are those of the authors/researchers and do not necessarily reflect the official views of the Public Health Agency of Canada.

Author Financial Disclosures Dr. Makhani received fellowship funding from the Canadian Network of MS Clinics and has received research support from the Dairy Farmers of Ontario. She has received speaker's honoraria from EMD Serono and Teva Neuroscience. Dr. Morrow received research funding from Biogen Idec and Novartis. She has participated in speaker's bureaus and has served as consultant for Biogen Idec, EMD Serono, Teva Neurosciences and Novartis. Dr. Fisk received research funding from the Canadian Institutes of Health Research, the Capital Health Research Fund, the Dalhousie University Department of Psychiatry Research Fund and the endMS Network via the MS Society of Canada Research Foundation. He has also conducted research under contract for Heron Evidence Development Limited. Dr. Evans reports no disclosures. Dr. Beland reports no disclosures. Dr. Kulaga reports no disclosures. Dr. Kingwell received research funding from the Multiple Sclerosis Society of Canada and the Michael Smith Foundation for Health Research (Postdoctoral Fellowships). Dr. Marriott received research funding from the Consortium of MS Centers and the Manitoba Medical Service Foundation. He has also received research support for MS trials from Biogen Idec, Roche and Sanofi-Aventis and speaker's honoraria from Biogen Idec, Roche and EMD Serono. Mr. Dykeman reports no disclosures. Dr. Jetté holds a Canada Research Chair in Neurological Health Services Research and a Population Health Investigator Award from Alberta Innovates Health Solutions. She currently holds research funding from the Canadian Institutes of Health Research, the Public Health Agency of Canada, Alberta Innovates Health Solutions, Alberta Health

Acknowledgments Thanks to Ms. Diane Lorenzetti, Librarian at University of Calgary who conducted the searches and to MS. Ingrid Dixon at the McGill's Life Sciences Library who obtained copies of the papers that were not available online. Thanks to Dr. Parminder Raina and Ms. Mary Gauld, at the Evidence Review and Synthesis Centre of McMaster University for kindly hosting us on the DistillerSR system and thanks to Mr. Henry Ebron and Mr. Ian Stefanison from DistillerSR for patiently guiding us through the conduct of a first project on the DistillerSR system.

Appendix A.

Supporting information

Supplementary data associated with this article can be found in the online version at http://dx.doi.org/10.1016/ j.msard.2013.06.015.

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