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Latitudinal prevalence gradient of multiple sclerosis in Latin America

J Risco, H Maldonado, L Luna, J Osada, P Ruiz, A Juarez and D Vizcarra
Mult Scler 2011 17: 1055 originally published online 6 May 2011
DOI: 10.1177/1352458511405562

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Americas Committee for Treatment and Research in Multiple Sclerosis

Pan-Asian Committee for Treatment and Research in Multiple Sclerosis

Latin American Committee on Treatment and Research of Multiple Sclerosis

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Research Paper
Multiple Sclerosis Journal
17(9) 1055–1059
Latitudinal prevalence gradient of ! The Author(s) 2011
Reprints and permissions:
multiple sclerosis in Latin America sagepub.co.uk/journalsPermissions.nav
DOI: 10.1177/1352458511405562
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J Risco1, H Maldonado2, L Luna2, J Osada2, P Ruiz2, A Juarez1

and D Vizcarra1,2,3

Abstract
Background: Multiple sclerosis (MS) has a unique geographical distribution that reflects both genetic and environmental
factors. Many studies have shown a positive correlation between MS frequency and latitude across both large and small
geographical regions. However, scarce data have been published on the epidemiology of MS in Latin America and no
study has evaluated latitudinal variation.
Objective: To evaluate the effect of latitude on MS prevalence in Latin America.
Methods: We conducted a systematic review of MS prevalence during January 2011. Prevalence rates were collected
from eligible publications. The effect of latitude on prevalence was analyzed using linear regression.
Results: A total of ten studies were eligible for analysis, corresponding to six countries, spanning from Panama to
Argentina. The crude prevalence of MS ranged from 0.75 to 21.5 per 100,000. We found a strong and significant
association between prevalence and latitude (r2 0.8; p < 0.001) and determined an increase in prevalence of 0.33 per
100,000 per degree latitude.
Conclusion: Our findings suggest a latitudinal prevalence gradient of MS in Latin American countries between Panama
and Argentina.

Keywords
epidemiology, Latin America, latitude, multiple sclerosis, prevalence, South America

Date received: 3rd November 2010; revised: 13th February 2011; accepted: 7th March 2011

Introduction
Multiple sclerosis (MS) has a unique geographical dis-
tribution that reflects both genetic and environmental
factors. Substantial differences in prevalence exist
between regions of the world, which Kurtzke stratified
into three groups: high >30 per 100,000), medium (5–30
per 100,000) and low (<5 per 100,000 inhabitants).1
The northern parts of Europe and North America are
in a high range; Southern Europe and USA are in a
medium range; whereas Asia is in a low range. Data
published on South America reveals prevalence in a low
to medium range.2
Many studies have shown a positive correlation
between MS frequency and latitude. This correlation
has been described across both large3,4 and small5,6 geo-
graphical regions. Recently, evidence has challenged
the widely accepted notion of the latitudinal gradient.
A systematic review on incidence across time
demonstrated an attenuated latitudinal gradient after
1980.3 This study included mainly European countries.
Another systematic review found a weak association
between latitude and prevalence in Europe and North
America, a trend that vanished when evaluating inci-
dence.4 In the southern hemisphere, New Zealand and
Australia showed a clear trend of increasing incidence
with latitude. Conversely, the prevalence did not vary
significantly with latitude. These studies show a
1
Hypnos Instituto del Sueño, Peru.
2
Universidad Peruana Cayetano Heredia, Peru.
3
Clinica San Felipe, Peru.
Corresponding author:
Darwin Vizcarra, Universidad Peruana Cayetano Heredia, Juan Dellepiani
326, Lima 27, Peru
Email: dvizcarra@yahoo.com

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1056
discrepancy between prevalence and incidence for the
northern and southern hemispheres.
Scarce data have been published on the epidemiol-
ogy of MS in Latin America, and no study has evalu-
ated latitudinal variation. We conducted a systematic
review of the prevalence of MS in this region. Our
objective was to evaluate the latitudinal variation
of MS.
Methods
We conducted a search of MS prevalence in ‘Scielo’,
‘PubMed’, ‘Biblioteca Virtual de Salud’ and
‘EBSCOhost’ during January 2011, for the keywords:
‘multiple sclerosis’ and ‘epidemiology’ or ‘prevalence’
or ‘the name of Latin American countries’. Both
English and Spanish terms were used. No time period
restriction was placed on the search. Finally, the search
was supplemented by reviewing references from
retrieved articles.
We included published articles on prevalence in
Latin American countries south of and including
Panama. No poster abstracts or information from con-
ference proceedings were included. We excluded those
that did not mention diagnostic criteria, prevalence
date and study design. When multiple studies were con-
ducted for the same geographical region, the older ones
were excluded.
We retrieved crude and adjusted prevalence from
selected studies. Google Earth was used to obtain lati-
tude. For small geographical regions, a precise value
was used. For larger regions, the midpoint was deter-
mined by averaging the northern and southern limits.
Missing prevalence 95% confidence intervals were
calculated using the number of ascertained cases and
total population with the Mid P-exact method
(OpenEPI v.2). Some studies had multiple prevalence
determinations for different geographical regions,
which were analyzed as individual points. The effect
of latitude on prevalence was analyzed with linear
regression (STATA v. 11.0).
Results
The search yielded 20 references. It is worth noting that
many references cited in review articles were not found
in their respective journals. Eleven studies were
included. Of these, a study conducted in Sao Paulo
(1990) was excluded on account of there being a more
recent prevalence determination.7 A total of 10 studies
eligible for analysis were found.8–17
Analyzed studies corresponded to six countries,
spanning from Panama to Argentina (Figure 1), and
were conducted between 1991 and 2007. The diagnostic
criteria used to determine MS cases included: Poser,
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Multiple Sclerosis Journal 17(9)
MacDonald, Fazekas Paty, University of Boston
Workshop Criteria or a combination of the aforemen-
tioned. Regarding study design, the capture and recap-
ture method was applied for the prevalence
determination of Lima, Perú;14 Buenos Aires,
Argentina;12 Santander, Antioquia, Caldas and
Risaralda, Colombia;15 Quito, Guayaquil and
Cuenca, Ecuador.17 The rest used the conventional
method of determining all possible cases and dividing
by the total population.
The crude prevalence of MS ranged from 0.75 per
100,000 in Cuenca, Ecuador17 to 21.5 per 100,000 in
Rio Gallegos, Argentina8 (Figure 2). Because age-
adjusted prevalence rates were presented in only one
study,8 we used crude prevalence rates for all subse-
quent analyses. Linear regression analysis revealed a
strong and significant association between prevalence
and latitude (r2 ¼ 0.8; p < 0.001). We determined an
increase in prevalence of 0.33 per 100,000 per degree
latitude.
Discussion
Our findings suggest a latitudinal prevalence gradient in
Latin American countries between Panama and
Argentina. The variation is small when compared to
that of the northern hemisphere; Europe and North
America have a gradient of 1.29 per 100,000 per
degree latitude,4 whereas our study yielded 0.33 per
100,000 per degree latitude. The observed difference
reflects a wider range in prevalence. At high latitudes,
prevalence can exceed 200 per 100,000 in the northern
hemisphere,18 whereas at similar latitudes 20 per
100,000 is barely reached in Latin America. When
interpreting the latitudinal prevalence gradient, both
genetic and environmental factors should be
considered.
The distribution of population genetics in Latin
America could account for the observed latitudinal gra-
dient. A complex mixture between Andean natives with
European and African immigrants resulted in a concen-
tration of the Caucasian population in the southern
regions of the continent.19 For example, in Argentina
the population is predominantly Caucasian, whereas in
Colombia the population is predominately mestizo. It is
possible that the Argentinean population has a higher
risk of MS than the Colombian population because of
their genetic background. Most studies analyzed in our
review make no mention of ethnicity, obstructing fur-
ther interpretation on the subject.
As latitude increases, the intensity and duration of
sunlight decrease. Many studies have suggested that a
lower exposure to sunlight in high latitudes is associ-
ated with a greater risk of MS.20–22 To the best of the
authors’ knowledge, no MS study involving sunlight
Risco et al.
Figure 1. Included studies per geographical region. Analyzed studies are shown with: prevalence date, diagnostic criteria, prevalence
estimate and 95% CI.8–17
exposure or vitamin D has been conducted in the
region. Sunlight exposure and subsequent production
of vitamin D appear to be important environmental
factors in MS susceptibility.23–25 However, the relative
contribution of each is unknown as both have indepen-
dent immunomodulatory effects.26–28
Factors other than latitude are known to influence
effective sunlight exposure. Exposure decreases with
increasing altitude. Thus, altitude is inversely correlated
with MS prevalence.29 The Andes is the world’s longest
continental mountain range, providing diverse geo-
graphical distribution. The locations analyzed in our
review range from 7 to 2800 metres above sea level,
making altitude a potential confounding factor.
Three of the analyzed studies had multiple preva-
lence determinations across different geographical
regions. Having a uniform population, time frame,
diagnostic criteria and methodology within each study
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1057
provides important insight into an explanation of our
results. We did not find a clear trend of increasing MS
prevalence and latitude within Colombia,15 Ecuador17
or Argentina.8 This observation suggests that the con-
tinental gradient could be explained by differences
between countries. Thus, country to country variation
in the quality of medical care, population genetics and
age should be considered as an explanation of our
findings.
An important limitation to our study was the use of
prevalence as a marker of MS frequency. Prevalence
can reflect diagnostic accuracy, survival time and ascer-
tainment probability. These factors vary according to
the quality of medical care, which in turn differs greatly
across Latin American countries. Incidence, on the
other hand, is a better measure of MS risk; however,
few studies are available, impeding analysis of latitudi-
nal variation in Latin America.
1058
Figure 2. Prevalence by latitude in Latin America. Prevalence
estimates and 95% CI are shown per corresponding latitude. The
dotted line indicates the line of regression.
Other limitations include the use of diverse diagnos-
tic criteria to identify MS cases, making a comparison
of prevalence between regions difficult. Furthermore,
the included studies were conducted in a period span-
ning 15 years. A recent meta-analysis has proven the
importance of examining MS epidemiological studies in
similar time periods.3 Finally, we used crude prevalence
rates to study latitudinal variation, where age-adjusted
prevalence would have been more appropriate in com-
parisons between different studies.30
The information presented is incomplete, with most
countries in the region not represented. This results in
discontinuous data across latitudes with a noticeable
gap around 20 . All limitations considered, this is the
best information currently attainable.
This study is the first to report a latitudinal gradient
of MS in Latin America. The cause of the observed
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Multiple Sclerosis Journal 17(9)
variation is not known. Our results should prompt a
prospective multi-centric epidemiological study to con-
firm and explain our findings. This would entail setting
up an international surveillance and registry system for
MS patients. The use of standardized diagnostic crite-
ria, recollection of ethnic and sunlight exposure infor-
mation should be included. Ideally, objective
measurements such as HLA determination, actinic
damage from skin samples and vitamin D serum
levels should be considered. Finally, we suggest
the inclusion of detailed information on local medical
services in order to adjust for a disparity in MS ascer-
tainment probability. Such an undertaking would
answer important epidemiological questions and raise
the standard of care in MS patients across Latin
America.
Acknowledgements
We wish to thank Camille Webb and Nicolas Barros for their
helpful discussions and support.
Funding
This research received no specific grant from any funding
agency in the public, commercial or not-for-profit sectors.
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