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ABSTRACT |
 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Peru is one of the resource-limited countries in which TB is endemic. The estimated prevalence of active TB in Peru is 233 cases per 100,000 inhabitants in 2004,3 despite a low prevalence of HIV infection of 0.5% among adults.4
In a previous study, we observed a lower TB transmission in high altitude rural communities compared with both urban and rural sea level communities in Peru.5 This study tested four additional communities at varying altitudes to examine the effects of high altitude and urban environment on tuberculin skin test (TST) positivity.
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MATERIALS AND METHODS |
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Study sites.
Nine communities were studied (Figure 1
). Five of these have been described in detail in a previous study5. Two urban non-highland (altitude < 3,000 m) shantytowns, Sachaca, and Cerro Colorado, and two highland (altitude 
3,000 m) peri-urban shantytowns, San Jeronimo and Huascahura, were newly studied.
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Urban highland communities. Huascahura is a peri-urban village with ~1,760 inhabitants located near Ayacucho (population: 140,500). San Jeronimo is a peri-urban shantytown with 19,120 habitants located in the southern part of the center of Cusco (population: 342,000).
Rural non-highland communities. Buen Villa Pastor is a rural jungle village with ~270 inhabitants in the Amazon basin.5 San Carlos is a rural jungle village with 176 inhabitants similar to Buen Villa Pastor.5
Urban non-highland communities. Las Pampas is an urban desert shantytown with > 40,000 inhabitants in southern Lima.5 Sachaca is an urban town with 16,570 inhabitants near the southern part of Arequipa, the second largest city of Peru (population: 677,000). Cerro Colorado is an urban shanty-town (population: 70,000) located in the northern area of Arequipa.
Residents in the shantytowns are impoverished, earning money from temporary small businesses, selling seasonal agricultural products, or working for construction companies. Their houses have few windows and are made of stones or adobe. Populations living in these nine sites are nearly all Mestizo, descendants of mixed European and Native American ancestry. Climate in the highlands is relatively dry and cold, with a rainy season lasting for 3 mo/yr. The jungle areas are humid. The geographic characteristics of each site are shown in Table 1 and Figure 1
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A household was defined as persons who share common living space such as a kitchen, living room, and bathroom. All family members excluding infants < 6 months of age and people who were temporally staying in the house (< 6 months) were invited to the study. Written informed consent was obtained from all adult participants ( 18 years of age) and from the parents or guardians of children. All participants were interviewed with structured questionnaires regarding recent (within 5 years) exposure to active TB cases and general conditions of health.
Trained field workers performed the TST using an intra-dermal injection of 5 tuberculin units (Tubersol; Connaught Laboratories, Ontario, Canada) in 0.1 mL on the volar surface of the forearm. Tuberculin vials (1 mL) were kept refrigerated and carried in a cooler box with ice packs. Induration produced by injections was measured 48–72 hours after administration using the pen method.6 Induration size 10 mm was considered to be TST positive, according to the Peruvian Ministry of Health7 and American Thoracic Society recommendations for people born in countries with high prevalence of TB.8 Although different field workers worked in different study sites, all fieldworkers underwent standardized training for reading the TST by an experienced research nurse, and the field work was supervised by one of the authors (M.S.). Participants with a positive TST were evaluated for evidence of active TB as described in the previous study.5
This study was approved by the ethical review boards of Asociación Benéfica PRISMA, Lima, Peru, and the Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Statistical analysis.
Demographic characteristics of the study population and TST results were compared among study sites. Differences in continuous variables were evaluated by Kruskal-Wallis and Mann-Whitney U tests. 
2 tests were used to test differences in categorical or binary variables. Educational level was categorized as no education (< 6 years), primary education (6 years completed), and secondary education ( 12 years completed). Body mass index (BMI) was calculated for six communities (data in San Carlos, Huascahura, and Vichaycocha were not available). The positive TST prevalence was compared between rural highland, rural non-highland, urban highland, and urban non-highland communities using a Wald 2 test computed from a generalized estimating equations (GEE) model to account for the family clustering effect.9
Characteristics of the study population were compared between individuals living in the highland ( 3,000 m) and non-highland (< 3,000 m) communities. Populations were also divided into rural or urban based on distance and ease of travel to the city center. Additional background information such as experience of living with other person with active TB, presence/absence of Bacillus Calmette-Guérin vaccination (BCG) scar, and living in an urban area or rural area was also compared. The Wald 2 test computed from GEE was used to test differences to account for community clustering.
To find factors associated with positive TST prevalence, univariate analyses were performed on the entire study sample for sex, age, history of living with a person with active TB, presence/absence of BCG scar, number of people per household, and living in rural highland compared with living in urban highland, living in rural non-highland, and living in urban non-highland. Educational level and BMI were analyzed only for adults 18 years of age. Multiple analyses were performed on 3,161 people (1,466 adults and 1,695 children) from eight communities except Vichaycocha, because data from Vichaycocha lacked household information and was thus excluded from the regression model. Model estimation was performed using GEE to account for community clustering. Adjusted odds ratios (AORs) were compared between each of the different types of communities (rural highland, rural non-highland, urban highland, and urban non-highland).
Non-parametric tests, 2 test, and GEE models for family clustering were performed using Stata 8.0 (Stata Corp., College Station, TX). GEE models for community clustering were computed using SAS statistical software 9.1 (SAS Institute, Cary, NC).
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RESULTS |
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. Median age in years, proportion of the child population, educational level, BMI, and the median number of people per household were significantly different among the study sites (Table 1). When we compare the background characteristics among the study population from the four highland communities and five non-highland communities, there was no significant difference in the demographic factors such as sex, age, living with other person with active TB or not, educational level, BMI, presence/absence of a BCG scar, number of person within the household, and living in an urban area or rural area.
Positive TST prevalence.
Overall positive TST prevalence in the study population was 21.1% (95% confidence interval [CI]: 19.7–22.3). The lowest positive TST prevalence was found in Vichaycocha (6%, rural highland), and the highest prevalence was in Buen Villa Pastor (33%, rural non-highland; Table 1). Positive TST prevalence was lower in rural highland communities compared with rural non-highland communities (OR = 0.14, P < 0.001); however, there was no significant difference between urban highland and urban non-highland communities (OR = 0.92, P = 0.500; Figure 2). In highland communities, positive TST prevalence was significantly higher in urban communities than in rural communities (OR = 2.84, 95% CI: 2.00–4.03, P < 0.001). In contrast, in the non-highland sites, positive TST prevalence was higher in rural than urban communities (OR = 1.43, 95% CI: 1.09–1.89, P = 0.011; Figure 2).
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). This trend was constant when adults 18 years of age and children < 18 years old were analyzed separately (Tables 3 and 4).
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–4). In contrast, among the urban communities, the differences between non-highland and highland were not significant in the total population (difference in the AOR = 1.12, 95% CI: 0.95–1.33) and the adult population (difference in the AOR = 1.13, 95% CI: 0.98–1.30). In the children, however, the AOR of positive TST prevalence was lower in the non-highland community group than in highland group (difference in the AOR = 0.82, 95% CI: 0.71–0.94). Comparison of positive TST prevalence between rural and urban communities. The positive TST prevalence was significantly higher in urban communities than in rural communities in the highlands (difference in the AOR = 3.52, 95% CI: 3.03–4.09), whereas in the non-highland environment, the positive TST prevalence was higher in rural communities than in the urban communities. The difference in AOR of these non-highland communities was significant for the whole population (1.30, 95% CI: 1.14–1.49) and adults (1.45, 95% CI: 1.27–1.66), but not for children (1.30, 95% CI: 0.81–2.09).
Other factors associated with positive TST results.
In adults, male sex, older age group ( 32 years old), living with another person with a positive TST, having lived with another person with active TB, and having a BCG scar were all associated with a positive TST in both univariate and multiple regression analyses (Table 3). In children, univariate analysis indicated all variables were positively associated with a positive TST except male sex (Table 3). After adjusting for all variables, having contact with a family member with active TB and the number of persons within the same family were not associated.
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DISCUSSION |
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Using GEE to estimate model parameters to account for community clustering effects, the effects of associated factors were tested. High altitude had strong association with a decreased rate of TST positivity even after adjusting for age, household active TB contacts, household positive TST contacts, BCG vaccination status, and community clustering. The finding of greater TB infection risk in rural versus urban at low altitude, with the opposite finding at high altitude, may be caused by the high humidity present in the jungle and the relative lack of health care facilities.
Limitations of this study are that the number of sites was not large enough to show if there was a linear or threshold protective effect of high altitude in rural areas. Even though we accounted for the effect of contact with a known active TB patient or another person with a TST-positive result in the same household, it was not possible to account for the risk of acquiring MTB infection from visitors, temporal immigrants to the community, or unknown contacts. The non-significant effect of an active TB contact (AOR = 2.4) in children was most likely caused by a small sample size for this variable. In addition, the relatively wide CIs for the adult TST prevalence data are also probably related to a low sample size in each community.
The mechanism of the high altitude effect on TB disease or MTB infection has not been fully established. The number of studies on this topic decreased after the discovery of the anti-TB drugs in the 1940s. Altitude effects on TB transmission rates have only been examined in one previous study in Darjeeling10 reported that positive TST prevalence was decreased in villages above 1,000 m compared with those below this altitude. That study, however, did not control for confounding factors. In terms of TB disease, which our study did not examine, two recent studies from Mexico showed an inverse relationship between altitude and TB disease morbidity11 and mortality.12 Although the Mexican findings of an association between TB disease and altitude could be caused by a decreased severity of the TB disease at high altitude, an effect of altitude on MTB transmission is equally likely.
There are several mechanisms by which MTB infection might be prevented in high altitude climate, such as lower oxygen tensions13 or stronger exposure to ultraviolet (UV) light, which may inhibit MTB growth.14 However, houses in the highland have relatively small and few windows; therefore, UV rays may not reach inside houses, where transmission is most likely to occur. The dry climate in high altitude may increase the susceptibility of Mycobacterium to UV light,15 reducing TB transmission. Further detailed studies are needed to determine which mechanism(s) are primarily responsible for the decreased transmission of TB in the highlands.
The protective effect of high altitude on MTB infection found in rural highland communities was not found in urban highland communities. Assuming that high TB transmission rates reflect high rates of active TB, urban highland communities will require the same measures against TB as non-highland communities.
Received December 19, 2005. Accepted for publication March 9, 2006.
Acknowledgments: We thank L. Cabrera, R. Montoya, and P. Maguiña for study coordination, M. Varela for data management, and A. Griffin, J. B. Phu, D. Sarah, and A. Sebastian for technical support. We also thank the communities of Quilcas, Vichaycocha, Las Pampas de San Juan de Miraflores, San Carlos, Buen Villa Pastor, Sachaca, Cerro Colorado, San Jeronimo, and Huascahura for cooperation. Portions of the data contained in this manuscript were presented at the ASTMH 53th Annual Meeting, Miami Beach, Florida, November 7–11, 2004.
Financial support: These studies were supported by D43 TW07646-5 Tutorial in Tropical Health at JHU/Peru Overseas Site NIH/NIAID, D43 TW066581 Infections Diseases Training Program in Peru-Global Research Fund DHHS/Fogarty International, and Research Support Grant from St. Luke’s Life Science Institute.
Disclaimer: The opinions and assertions made by the authors do not reflect the official position or opinion of the US Department of the Army or of any of the other organizations listed.
* Address correspondence to Robert H. Gilman, Department of International Health, The Johns Hopkins School of Pubic Health, 615 North Wolfe Street, Room W5515, Baltimore, MD 21205. E-mail: rgilman{at}jhsph.edu 
Authors’ addresses: Mayuko Saito, Will K. Pan, and Robert H. Gilman, Department of International Health, The Johns Hopkins School of Public Health, 615 North Wolfe Street, Room W5515, Baltimore, MD 21205, E-mails: msaito{at}jhsph.edu and rgilman{at}jhsph.edu. Christian T. Bautista (present affiliation), Department of Epidemiology and Threat Assessment, The US Military HIV Research Program, and the Henry M. Jackson Foundation, 1 Taft Court, Suite 250, Rockville, MD 20850, E-mail: cbautista{at}hivresearch.org. Sapna Bamrah, Christopher A. Martín, Simon J. Tsiouris, D. Fermín Argüello, and Gabriela Martinez-Carrasco, Asociación Benéfica, Proyectos En Informática, Salud, Medicina y Agricultura (A.B. PRISMA), Carlos Gonzales 251, Urb. Maranga, San Miguel, Lima 32, Peru.
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| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
18 years old)*