Incidence of multiple sclerosis in Buenos Aires: a 16-year health maintenance organization-based study.

Abstract

The present study was undertaken to determine the incidence of MS in a health maintenance organization from Buenos Aires, the largest populated area in Argentina.
Population was all members of a hospital-based health maintenance organization who were affiliated since January 1992 up to December 2007. Each person was followed contributing time at risk since January 1992 or enrollment date to the final date. Patients with definite diagnosis according to Poser's criteria were included. Incidence density was calculated with 95% confidence intervals.
A total of 145,000 patients were followed for a total of 1,021,515 person-years, of whom 18 developed the disease. Incidence density (ID): 1.76 /100 000 person-years (95% CI: 1.1-2.8/100,000 person-years).
The incidence density of 1.76 per 100,000 suggests a low-median risk area for MS. This study constitutes the first of its kind to cover data of MS incidence in Argentina.

Full text

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Incidence of multiple sclerosis in Buenos Aires: a 16-year health
maintenance organization–based study
E. Cristianoa, L. Patruccoa, D. Giuntab, G. Videlaa, E. R. Sorianocand J. I. Rojasa
aNeurology Department, Hospital Italiano Buenos Aires, Buenos Aires;bEpidemiology Section, Hospital Italiano de Buenos Aires, Buenos
Aires; andcSeccio ´n Reumatologı´a, Servicio de Clı´nica Me´dica, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
Keywords:
Argentina, epidemiology,
incidence, multiple
sclerosis, South America
Received 6 June 2009
Accepted 1 October 2009
Objective: The present study was undertaken to determine the incidence of MS in a
health maintenance organization from Buenos Aires, the largest populated area in
Argentina.
Methods: Population was all members of a hospital-based health maintenance
organization who were affiliated since January 1992 up to December 2007. Each
person was followed contributing time at risk since January 1992 or enrollment date
to the final date. Patients with definite diagnosis according to Poser?s criteria were
included. Incidence density was calculated with 95% confidence intervals.
Results: A total of 145 000 patients were followed for a total of 1 021 515 person-
years, of whom 18 developed the disease. Incidence density (ID): 1.76 /100 000 person-
years (95% CI: 1.1–2.8/100 000 person-years).
Conclusion: The incidence density of 1.76 per 100 000 suggests a low-median risk
area for MS. This study constitutes the first of its kind to cover data of MS incidence
in Argentina.
Introduction
Multiple sclerosis (MS) is a complex demyelinating
disease of the CNS in which several environmental
factors act together in a genetically susceptible indi-
vidual to cause disease [1].
Kurtzke [2] classified regions of the world according
to prevalence: a low prevalence was considered less than
five cases per 100 000 persons; an intermediate preva-
lence 5–30 per 100 000 persons; and a high prevalence
more than 30 per 100 000 persons.
Over the past years, several studies on MS epidemi-
ology have been published as part of an attempt to
better define the distribution of the disease and thus
clarify its occurrence around the world [3–12]. The
prevalence reported by these studies demonstrated a
higher frequency of MS cases in northern Europe,
southern Australia, the central region of North Amer-
ica [13] and lower frequencies of MS cases in tropical
areas like South America [14].
Despite this wealth of data, current knowledge of
MS epidemiology is based mostly on North American
or European studies whilst scarce data have been
published from South America [3,4,15–19]. In Argen-
tina, the southernmost country of South America, there
are few studies reporting MS prevalence [17,20], and
there are none concerning MS incidence.
As epidemiological and clinical characteristics of MS
may vary according to environmental, racial, climatic
and genetic factors, epidemiological characteristics of
MS in South America should contribute to elucidate
the disease pattern in this population. This step would
allow us to better understand associated environmental
factors of the disease, such as viral infections, popu-
lation movements, exposure to UV radiation and
geographic location (latitude and socioeconomic con-
ditions) [3–7,21].
Thus, considering the relevance of epidemiological
data, the present study was undertaken to determine the
incidence of MS in a health care organization from
Buenos Aires, the largest populated area in Argentina.
Methods
Setting
The population studied was the membership of the
Italian Hospital Medical Care Program (IHMCP), a
prepaid health maintenance organization. IHMCP
provides comprehensive medical and health services
through two main hospitals and 24 medical office
Correspondence: E. Cristiano, MS Section, Italian Hospital of Buenos
Aires, Gasco ´ n 450 C1181ACH Buenos Aires, Argentina (tel.: +54 11
4959 0322; fax: +54 11 4959-0322; e-mail: edgardo.cristiano@
hospitalitaliano.org.ar).
? 2009 The Author(s)
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buildings to over 145 000 members primarily located in
the urban areas around the Autonomous City of Bue-
nos Aires, Argentina. The Autonomous City of Buenos
Aires straddles the tropic of Capricorn at latitude 34ºS
and longitude 58ºW. The city covers an area of 202 km2
and has a subtropical climate. It is located on the
western bank of the Rı´o de la Plata and has a popu-
lation of 2 965 403 inhabitants. Ninety-seven percent of
the population is white and of European descent and
the remaining 3% is a mixture of native Indians and
other ethnicities.
Argentina has an extremely segmented health system
consisting of three large sectors: public, private and
social security (the last two covering a population of
nearly 18.3 million people, distributed amongst close to
300 entities of varying scope and size). Beneficiaries of
the private system can freely choose their health
maintenance organization (HMO). The IHMCP is a
private health system insurance, selected by many
metropolitan inhabitants because of the excellence and
responsibility of the services provided as well as the
affordability of the insurance. Approximately 5–7% of
the population in these geographic areas are affiliated to
the IHMCP. The IHMCP population characteristics are
highly representative of the metropolitan population of
the Autonomous City of Buenos Aires, as demonstrated
by 2001 census data [22] (Table 1 and 2) covering a
number of demographic and socioeconomic categories.
The present study was conducted with approval by
the Institutional Review Board of the Italian Hospital
of Buenos Aires.
Case definition
In order to assess the incidence, the medical records
obtained during a 16-year period (1 January 1992 to 31
December 2007) at IHMCP were retrospectively
examined. Those satisfying the Poser?s criteria [23] for
clinically or laboratory definite MS were accepted as
incidence cases. The incidental year for each patient was
considered when the Poser?s criteria [23] were fulfilled.
To be considered an incident case, the person must
have been affiliated to the IHMCP for at least
12 months before the diagnosis of MS was made. Pa-
tients with clinically isolated syndromes (CIS) diag-
nosed during the 16-year period were excluded from the
analysis if they did not convert to MS during the study
period.
Case ascertainment
Multiple methods for case finding were used to ensure
complete ascertainment: a) patients included in neurol-
ogist databases; b) patients with the ICPS (International
Classification of Primary Care) code N86 in the HMO
computer-based patient record system; c) patients with
ICD 9 (International Classification of Diseases) codes
340/341 on admission to hospital; and d) patients
receivinginterferonbeta
(Anatomical Therapeutic Chemical codes L03AB07,
L03AB08, L03AX13). All neurologists in IHMCP were
notified of the study and were asked to refer newly
diagnosed or suspected MS patients.
A list of cases was obtained from sources outlined
earlier. Confirmation of residence and affiliation status
was obtained from the HMO registers. Each potentially
eligible subject underwent a standard process to
confirm the diagnosis by two MS experts (EC and LP)
who subsequently determined whether patients fulfilled
Poser?s definite MS criteria [23].
or glatirameracetate
Table 1 Demographic data of the Autonomous City of Buenos Aires
and IHMCP based on 2001 Argentinean census
City of Buenos Aires IHMCP data
Age group
0–14 years
15–24 years
25–34 years
35–44 years
45–54 years
55–64 years
‡ 65 years
Total
Overall (%)
468 961 (17)
414 621 (14.8)
435 963 (15.7)
356 261 (12.8)
350 165 (12.2)
281 722 (10.1)
488 505 (17.3)
2 965 403
Overall (%)
26 100 (18)
18 995 (13.1)
20 735 (14.3)
17 400 (12)
16 385 (11.3)
17 110 (11.8)
28 275 (19.5)
145 000
IHMCP, Italian Hospital Medical Care Program.
Table 2 Socioeconomic level and ethnic origin of Autonomous City of
Buenos Aires inhabitants and IHMCP affiliates, based on 2001
Argentinean census
Socioeconomic class
City of Buenos
Aires (%)IHMCP (%)
Upper class
Upper middle class
Middle class
Lower middle class
Lower class
Poor
Total
Ethnic origin
10
16
30
21
17
13
5
19.4
37.5
25.6
12.5
0
100
IHMCP (%)
100
City of Buenos
Aires (%)
Caucasian
Asian
African American
Mestizo*
9295.5
2
0.5
2
4
1
3
IHMCP, Italian Hospital Medical Care Program; *Mestizo (Spanish
term used to designate people of mixed European and Amerindian
ancestry living in the region of Latin America).
2
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Data collection
Data regarding demographic characteristics (age at
onset, age at diagnosis and follow-up status) were
obtained from medical records of each patient. Each
person was followed during the study period until vol-
untary disenrollment, death or finalization of the study
(31 December 2007).
Because of fluctuations in enrollment and disenroll-
ment in the health plan, person-years were calculated
from monthly membership records and used as the
denominator in all calculations.
Statistical analysis
Analysis was performed using STATA 9.1 version [24].
Incidence density (ID) for MS were calculated per
100 000 person-years. Rates were adjusted using direct
standardization with the age and gender distribution of
the 2000 world population and the 2001 Argentinean
population [22,25–27].
Results
During the 16-year study period, 145 000 patients were
followed for a total of 1 021 515 person-years, of whom
18developedMS(11women).Themeanageatdiagnosis
was 35.7 years (range 21–48). The ID was 1.76 per
100 000 person-years (95% CI 1.1–2.8/100 000 person-
years): 1.86 for women (95% CI 1.03–2.36/100 000 per-
son-years) and 1.62 for men (95% CI 0.77–3.39/100 000
person-years). The female-to-male ratio was 1.14. The
overall ID was 2.7 per 100 000 (95% CI 2.4–3.1 per
100 000) when adjusted to the world standard popula-
tion and 2.5 per 100 000 (95% CI 2.1–2.8 per 100 000)
when adjusted to the 2001 Argentinean population.
Regarding the annual ID, we observed a stable dis-
ease frequency through the study period, ranging from
1.1 to 2.6 per 100 000 person-years. Eight patients with
CIS were excluded from the analysis because they did
not convert to clinically definite multiple sclerosis
during the study period.
Discussion
Valuable information can be obtained from South
America, where scarce publications exist about MS
epidemiology. This study constitutes the first of its kind
to cover MS incidence in a well-defined area of South
America.
The incidence density of 1.76 per 100 000 found,
shows a low-median risk area for MS. Significant dif-
ferences exist between our findings and incidence from
European and North American countries [2].
We adjusted our findings to the 2000 world standard
population and the 2001 Argentinean population to
increase the accuracy of the data [22,25,26]. After
adjustment, ID values did not significantly change our
initial findings.
When we analyzed the annual ID, we did not detect
any significant temporal trend over the study period. It
is important to remark that issue in order to discard
information bias. The sex ratio found in our study was
intriguingly low (female-to-male 1.14:1), in accordance
with countries from eastern Europe [28,29] and with
significant differenceswith
western European countries [30], where an increase in
female to male sex ratio has been reported over the last
years. The reason for the low ratio is still unknown, but
it may be because of the low number of ascertained
cases found during the study period.
This study supports that the MS incidence for the
area of Autonomous City of Buenos Aires in which the
study was carried out, is in accordance with its preva-
lence [31]. We believe that the study?s most important
contribution is that it expands knowledge on the pat-
tern of geographic differences in MS distribution
around the world.
We are well aware that the low incidence rate could be
because of the under-ascertainment of MS cases in the
study, a potentially confounding factor. However, the
manner in which the cases were ascertained makes this
highly improbable (neurologist databases, HMO com-
puter-basedpatient record system, admission tohospital
registries, etc.). Of course, another limitation of these
results could be that they are drawn from an HMO and
therefore contain a selection bias; nonetheless, compar-
isonofthisHMOpopulation withtheAutonomousCity
of Buenos Aires census data demonstrates that it is rep-
resentative of the general population in demographic,
ethnicandsocioeconomiccharacteristics.Itisalsoworth
to mention that the HMO covers a wide area from the
Autonomous City of Buenos Aires. For that reason, re-
sults obtained could be cautiously generalized to the
AutonomousCityofBuenos.Furtherstudieswillhelpus
to confirm our initial findings.
NorthAmerican and
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