INT J TUBERC LUNG DIS 8(11):1321–1324

© 2004 IUATLD

Effect of altitude on the frequency of pulmonary tuberculosis

M. H. Vargas,*† M. E. Y. Furuya,‡ C. Pérez-Guzmán†§

* Unidad de Investigación Médica en Epidemiología Clínica, Instituto Mexicano del Seguro Social, Hospital de Pediatría,
Centro Médico Nacional Siglo XXI, Mexico DF, † Instituto Nacional de Enfermedades Respiratorias, México DF, ‡ División
de Especialidades Médicas, Instituto Mexicano del Seguro Social, Hospital de Pediatría, Centro Médico Nacional
Siglo XXI, México DF, § Departamento de Neumología, Instituto Mexicano del Seguro Social, Hospital General
Gaudencio González Garza, Centro Médico Nacional La Raza, México DF, Mexico

SUMMARY

S E T T I N G : Pulmonary tuberculosis (PTB) incidence
greatly varies around the world, a phenomenon usually
attributed to socio-economic factors or health service avail-
ability. A recent study, however, indicated that PTB was
inversely related to altitude.
O B J E C T I V E : To evaluate factors associated with PTB
notification rates in Mexico.
M E T H O D S : Annual notification rates (1998–2002) of
PTB in each of the 32 Mexican states were analysed, and
likely factors were assessed through correlation and mul-
tiple regression analyses.
R E S U L T S : Most variables lacked association with PTB
rates, including percentage of population aged >65
years, population density, percentage of population with
<2 minimum salaries, percentage of population with so-
cial security, level of education, diabetes incidence, per-
centage of immigration, percentage of rural population
and a global marginalisation index. Only altitude above
sea level correlated with tuberculosis incidence (r 5
20.74, P , 0.0001). Likewise, in the multiple regression
analysis only altitude reached a statistically significant
association.
C O N C L U S I O N : Our results showed that altitude had a
strong inverse relationship to PTB notification rates in
Mexico, which might be related to the well known
changes in alveolar oxygen pressure at different alti-
tudes. Interestingly, several factors traditionally consid-
ered as predisposing conditions for the development of
PTB did not correlate with the disease.
K E Y W O R D S : pulmonary tuberculosis; altitude; geography

THERE ARE WIDE VARIATIONS in the incidence of
pulmonary tuberculosis (PTB) among different coun-
tries,1 and even among different regions within the
same country.2 This phenomenon occurs in Mexico,
where PTB notification rates vary greatly among differ-
ent states. This variability has usually been attributed
to differences in local socio-economic conditions and/
or in the availability of health services.3–6 However, a
recent study reported an inverse relationship between
altitude above sea level and tuberculosis,7 indicating
that other factors might also determine PTB incidence.
To explore factors related to this variability, annual
notification rates of PTB in Mexico were analysed,
and factors likely to be involved were assessed through
correlation and multiple regression analyses.
METHODS
Annual notification rates of PTB cases for each of the
32 Mexican states (including the Distrito Federal)
were obtained from the Health Ministry through the
Dirección General de Epidemiología.8 This database
contains the official national statistics related to med-
ical services provided by all Mexican health institu-
tions. From this database, the rates of PTB occurring
in subjects of all ages, of both sexes, from 1998 to
2002 were averaged and taken into account for the
analysis.
Variables that were selected according to their po-
tential influence on the incidence of PTB included eco-
nomic (percentage of working population with <2
minimum salaries), medical (percentage of popula-
tion with social security, diabetes mellitus incidence
rate), demographic (population density, percentage of
rural population, percentage of immigration, percent-
age of population >65 years), educational (level), and
geographical (altitude) factors, as well as living con-
ditions potentially leading to overcrowding and facil-
itation of transmission of mycobacteria (percentage
of single-room houses). Most variables were obtained
from the 2000 Population and Housing Census,9 ex-
cept for altitude above sea level, which was obtained

Correspondence to: Dr Mario H Vargas, Instituto Nacional de Enfermedades Respiratorias, Unidad de Investigación, Tlal-
pan 4502, México DF, CP 14080, Mexico. Tel: (152) 55 5665-0043. Fax: (152) 55 5665-4623. e-mail: mhvargasb@
yahoo.com.mx or mhvargas@conacyt.mx
Article submitted 16 July 2003. Final version accepted 24 March 2004.
1322 The International Journal of Tuberculosis and Lung Disease

from the Instituto Nacional de Estadistica, Geografía e Table Relationship between the variables analysed and
Informática,10 and the diabetes rate (1998–2002 av- the annual incidence rate of pulmonary tuberculosis
in the 32 Mexican states
erage), which was obtained from the Dirección Gen-
eral de Epidemiología.8 In addition, a marginalisa- Variable r 95%CI P
tion index was obtained from the Consejo Nacional Altitude above sea level 20.74 20.87–20.53 ,0.0001
de la Población.11 This index includes nine variables Population >65 years old, % 20.27 20.57–0.08 0.14
which were selected from the 2000 Population and Population density 20.24 20.54–0.12 0.19
Working population with <2
Housing Census and weighted according to a princi- minimum salary income, % 20.20 20.51 to 0.16 0.27
pal components analysis (percentage of illiterate pop- Level of education 20.06 20.40 to 0.29 0.74
ulation, percentage of population with less than full Population with social
security, % 0.08 20.27 to 0.42 0.66
primary education, percentage of occupants of houses Rural population, % 0.09 20.27 to 0.42 0.62
without drainage or exclusive toilet, percentage with- Immigrant population, % 0.14 20.22 to 0.46 0.44
out electricity, percentage of houses without indoor Marginalisation index 0.15 20.21 to 0.47 0.41
Diabetes mellitus incidence 0.16 20.20 to 0.48 0.38
water, percentage with crowding, percentage with Single-room houses, % 0.31 20.04 to 0.60 0.08
earth floor, percentage of population living in commu-
CI 5 confidence interval.
nities with less than 5000 inhabitants, percentage of
working population with less than two minimum sal-
aries). For each state, altitude was calculated by aver-
aging the individual altitudes of the counties, weighted dent that the states with the highest incidence rates of
according to the percentage of population living in PTB were located in coastal regions of the country,
them. while those states with the lowest rates were located
To assess the relationship of predictive variables in the central region of the country.
with PTB rate, data were analysed using Pearson’s As can be seen in the Table, individual correlation
correlation coefficient (with Muddapur two-sided coefficients relating the PTB rate to each of the vari-
95% confidence interval [CI]) and multiple regression ables studied revealed that altitude (r 5 20.74,
analysis with the forward method to evaluate statisti- 95%CI 20.87–20.53, P , 0.0001, Figure 2) was the
cal significance. Data were processed using SPSS v10.0 only variable that achieved statistical significance,
(SPSS Inc, Chicago, IL, USA) and Prophet v5.0 (BBN followed by percentage of single-room houses (r 5
Technologies, Cambridge, MA, USA). Statistical sig- 0.31, 95%CI 20.04–0.60, P 5 0.08). Likewise, when
nificance was set at P , 0.05 bimarginally. multiple regression analysis was applied, altitude was
the only factor that obtained a statistically significant
relationship with PTB rates. All remaining variables
RESULTS
were excluded from the regression model.
Wide variability was found in the notification rates of
new cases of PTB among the 32 Mexican states, rang-
DISCUSSION
ing from 4.16 (Zacatecas) to 41.54 (Baja California)
cases per 100 000 population, with a national average PTB is traditionally considered as being strongly as-
rate of 18.14 6 1.79 (mean 6 standard error of mean sociated with socio-economic conditions. It has been
[SEM]). The geographical distribution of this disease is suggested to be more prevalent among the poorest peo-
shown in Figure 1. From this distribution it was evi- ple, who are more likely to be undernourished, have
less access to medical services and live in crowded con-
ditions.3–6 In addition, people with relative immuno-

Figure 1 Geographical distribution of pulmonary tuberculosis

rates by state in Mexico. Data correspond to annual notification Figure 2 Relationship between geographical altitude and pul-
rates averaged from 1998 to 2002. monary tuberculosis rates in 32 Mexican states.

compromise such as diabetics and aged subjects also
seem to have a higher risk of developing tuberculosis.
Our study indicates that altitude is also associated
with the tuberculosis notification rate—i.e., the lower
the altitude, the higher the notification rate of PTB—
and that this relationship is stronger than any of the
above mentioned factors. This finding is in agreement
with the study by Mansoer et al.,7 who showed a high
negative correlation (r 5 20.71) between altitude and
the rate of new smear-positive tuberculosis cases in 41
districts in Kenya. Similarly to our findings, the au-
thors reported that the effect of altitude greatly sur-
passed the influence of confounding factors such as
literacy, urbanisation or household size.
The cause of the close inverse relationship of alti-
tude and PTB was not specifically investigated in our
study, but it might be related to the well known fact
that in vitro multiplication of Mycobacterium tuber-
culosis is greatly favoured by a high oxygen tension.12
This concept is also supported by a large number of
studies in animal models (reviewed by Goodwin et
al.,13 Meylan et al.14 and Balasubramanian et al.15).
This oxygen dependence has been postulated as the
main cause for the greater frequency of upper lung in-
volvement in reactivation PTB, as the upper regions
of the lung have a higher alveolar pressure of oxygen
than the lower zones.16 In this context, the progres-
sive increment of the barometric pressure as altitude
decreases leads to higher alveolar oxygen pressure,
which in turn favours the development of tuberculous
lesions.
As expected, there was a very close relationship be-
tween altitude and average annual temperature (r 5
20.92, data not shown). It has been argued that cold
climates might be more likely to favour the transmis-
sion of PTB than warm climates,17 mainly due to a
higher risk of spread of bacilli (because people tend to
gather in closed spaces with scanty ventilation) or be-
cause bacilli are maintained in aerosolised particles
for longer periods. Our results did not support this last
hypothesis, as those states at higher altitude (and hence
with lower temperatures) had lower tuberculosis rates.
Although we tried to include some factors that
have a possible role in the development of PTB, we
cannot definitively exclude that other factors that
were not evaluated in our study might also influence
notification rates. In addition, our study was carried
out only using indicators for the whole state. It is
therefore possible that smaller locations with specific
conditions (extreme poverty or social marginalisa-
tion, for example) exist in any state. Such small loca-
tions would probably not impact on state statistics,
but many of the PTB cases may have developed in
them. Thus, further studies with more detailed data
(e.g., at county level) would be needed to corroborate
our findings.
Altitude and pulmonary tuberculosis 1323
In conclusion, we found that altitude above sea
level had an inverse correlation with PTB notification
rates in Mexico, which was notably stronger than
several factors traditionally considered as predispos-
ing conditions for the development of PTB.
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1324 The International Journal of Tuberculosis and Lung Disease
O B J E C T I F : L’incidence de la tuberculose pulmonaire
(TBP) varie largement dans le monde, un phénomène ha-
bituellement attribué à des facteurs socio-économiques
ou à la disponibilité des services de santé. Toutefois, une
étude récente a insisté sur le fait que la TBP était en
relation inverse avec l’altitude.
O B J E C T I F : Evaluer les facteurs associés aux taux de
déclaration de la TBP au Mexique.
M É T H O D E S : Nous avons analysé les taux annuels de dé-
claration de TBP entre 1998 et 2002 dans chacun des 32
Etats du Mexique et nous avons évalué par des analyses
de corrélation et de régression multiple les facteurs sus-
ceptibles d’être impliqués.
R É S U L T A T S : La plupart des variables n’ont pas montré
d’association avec les taux de TBP, notamment le
pourcentage de la population âgée de >65 ans, la den-
sité de population, le pourcentage de la population avec
des salaires minimum <2, le pourcentage de population
MARCO DE REFERENCIA : La incidencia de tuberculosis
pulmonar (TBP) varía mucho alrededor del mundo, fe-
nómeno que habitualmente se atribuye a factores so-
cioeconómicos o a la disponibilidad de servicios médi-
cos. Sin embargo, un estudio reciente encontró que la
TBP estaba en relación inversa con la altitud.
O B J E T I V O : Evaluar los factores asociados a las tasas de
notificación de tuberculosis pulmonar en México.
M É T O D O S : Se analizaron las tasas anuales de notifica-
ción (1998–2002) de TBP en cada uno de los 32 estados
mexicanos, y se investigaron mediante análisis de corre-
lación y de regresión múltiple los factores posiblemente
implicados.
R E S U L T A D O S : La mayoría de las variables carecieron de
asociación con las tasas de TBP, incluyendo : porcentaje
de población >65 años de edad, densidad de población,
porcentaje de población con <2 salarios mínimos, por-
RÉSUMÉ
couvert par la sécurité sociale, la fréquentation scolaire,
l’incidence du diabète, le pourcentage d’immigration, le
pourcentage de population rurale et un index global de
marginalisation. Seule l’altitude au-dessus du niveau de
la mer a été en corrélation avec l’incidence de la tubercu-
lose (r 5 20,74, P , 0.0001). De la même manière, dans
une analyse de régression multiple, une association
statistiquement significative n’a été obtenue que pour
l’altitude.
C O N C L U S I O N : Non résultats montrent qu’il y a une
puissante relation inverse entre l’altitude et les taux de
déclaration de la TBP au Mexique, ce qui pourrait être
en relation avec les modifications bien connues de la
pression alvéolaire en oxygène aux différentes altitudes.
Il est intéressant de noter que les différents facteurs tra-
ditionnellement considérés comme des éléments prédis-
posant au développement de la tuberculose ne sont pas
en corrélation avec cette maladie.
RESUMEN
centaje de población con seguridad social, escolaridad,
incidencia de diabetes, porcentaje de inmigración, por-
centaje de población rural y un índice global de margi-
nación. Solamente la altitud sobre el nivel del mar se
correlacionó con la incidencia de tuberculosis (r 5
20.74, P , 0.0001). Asimismo, en el análisis de regre-
sión múltiple solamente la altitud alcanzó asociación es-
tadísticamente significativa.
C O N C L U S I Ó N : Nuestros resultados muestran que la al-
titud tiene una fuerte relación inversa con las tasas de
notificación de TBP en México, lo que podría estar rela-
cionado con los bien conocidos cambios en la presión al-
veolar de oxígeno en diversas altitudes. Interesantemente,
varios factores considerados de forma tradicional como
predisponentes para el desarrollo de tuberculosis pulmo-
nar no tuvieron una correlación con esta enfermedad.