IJE Advance Access published online on August 13, 2008
International Journal of Epidemiology, doi:10.1093/ije/dyn161
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Risk factors associated with HIV in a population-based study in Andhra Pradesh state of India
1George Institute for International Health – India, Hyderabad, India.
2Health Studies Area, Administrative Staff College of India, Hyderabad, India.
3George Institute for International Health and School of Public Health, University of Sydney, Sydney, Australia.
4Department of Microbiology, Nizam's Institute of Medical Sciences, Hyderabad, India.
*Corresponding author. George Institute for International Health – India, 839C, Road No. 44A, Jubilee Hills, Hyderabad–500 033, Andhra Pradesh, India. E-mail: ldandona{at}george.org.in; ldandona{at}health.usyd.edu.au
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Abstract |
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Background Population-based data on risk factors associated with HIV are not readily available from India. This understanding, and an estimate of the impact of addressing behavioural factors on reducing HIV, would be useful.
Methods We interviewed a population-based sample of 12 617 persons 15–49 years old from 66 rural and urban clusters in Guntur district in the south Indian state of Andhra Pradesh and tested their dried blood spots for HIV. We used multiple logistic regression to assess the association of risk factors with HIV, and calculated population impact numbers for HIV reduction if behavioural factors were addressed.
Results Among men, there was significant association between HIV and history of sex with men, blood transfusion, having ever visited sex worker or multiple lifetime women sex partners, consuming alcohol before sex, recreational drug use, male non-circumcision and tattooing (odds ratios 5.74–1.97, P < 0.03, R2 = 0.11). Among women, the only identified behavioural factor associated with HIV was multiple lifetime men sex partners (P = 0.001, R2 = 0.10). Taking into account the relative risk and prevalence of risk factors, the highest impact on reducing the HIV number per unit population was for male circumcision.
Conclusions Among the identified factors, male circumcision was estimated to have the highest relative impact on reducing HIV per unit population, but the feasibility of this intervention in India needs further investigation. The low explanatory power in the regression models of the usually considered risk factors for HIV suggests that better understanding of HIV dynamics at the population level in India is needed.
Keywords HIV, India, male circumcision, population impact number, risk factors
Accepted 14 July 2008
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Introduction |
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Although the estimate of HIV burden in India has been a matter of debate in recent years, India is estimated to have one of the highest number of persons with HIV in the world.1–4 An important knowledge base needed for developing effective HIV control strategies in the population is population-based data on the risk factors explaining HIV. Such data from large sample, scientifically rigorous studies are not readily available from India. We conducted a population-based study of HIV in Guntur district in the southern Indian state of Andhra Pradesh.3 This district and state are estimated to have one of the highest relative HIV prevalence in the country by sentinel surveillance.2 In this article, we report an assessment of the risk factors associated with prevalent HIV at the population level, and estimate the relative impact of addressing behavioural risk factors, which could help in further planning of HIV control in India.
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Methods |
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Details of the sampling, field procedures and laboratory analysis for HIV in this population-based study have been reported earlier.3 The methods relevant for this report follows.
Population sample
We sampled 13 838 persons 15–49 years old from 32 rural and 34 urban clusters using a stratified random method to represent adults in Guntur district in the south Indian state of Andhra Pradesh. Guntur district, which had a population of 4.5 million in the 2001 census with 29% urban, was stratified into three regions with different levels of development, and rural and urban areas selected that together would be representative of the district.3 Within these areas, clusters of 1300–1600 population were selected randomly, and systematic sampling was done to select households in order to get 200–230 eligible persons 15–49 years old in each cluster.3 All residents in this age group in each selected household were considered eligible, with a resident defined as someone who had lived in the selected area for the past 6 months or more and a household defined as persons eating from the same kitchen. Assuming a participation rate of 90% of the eligible persons based on pilot studies, we estimated a final sample of about 12 400 persons with approximately equal men–women and rural–urban distribution. The sample size, which was calculated to compare population-based HIV prevalence with that at antenatal clinics, would have 93% power to detect a 20% difference from the 3% antenatal clinic HIV prevalence at the 95% confidence level assuming a cluster design effect of 2.5 for the sampling strategy.3 Data were collected between September 2004 and September 2005. Trained field investigators obtained informed consent from eligible persons for participation in the study, followed by interview and blood sample collection.
Interviews
Confidential interviews were conducted in person with participants in a private setting inside or near the house of the participant to obtain information about their socio-demographic background and behavioural variables that may be associated with the occurrence of HIV. Socio-demographic information included age, gender, rural–urban residence, education, standard of living index, occupation and marital status. The standard of living index was based on living conditions and ownership of assets, which was adapted from an index used previously by the National Family Health Survey in India.3
Information related to sex behaviour included history of age at first sex, number of lifetime sex partners, frequency of condom use for sex in last 6 months and frequency of alcohol use before having sex. The frequency of condom use for sex and alcohol use before sex was categorized as never, sometimes or often/usually/always by the respondent. Men were also asked if they had visited sex workers, had had sex with men and had been circumcised. Information was obtained about history of blood transfusion, tattooing, use of injection or other recreational drugs and smoking or chewing tobacco.
Blood samples
Finger prick method with a safety lancet was used to take blood sample from each respondent on Whatman No. 3 filter paper (Whatman International Ltd, Maidstone, UK), preferably six drops which were allowed to dry. These dried blood spots were stored in sealed polythene bags with desiccant in the field office at room temperature for a maximum of a week before being transported to the laboratory in Hyderabad. The dried blood samples were stored under refrigeration at 2–8°C in the laboratory until testing for HIV. Testing was done using standard methods and kits to detecting HIV antibody, p24 antigen or viral nucleic acid (Murex HIV Combi Assay, Murex Biotech, Dartford, UK; Murex HIV, Murex Biotech; HIV Tridot, J. Mitra, New Delhi, India; Vidas HIV Duo Ultra, bioMérieux, Marcy-l’Etoile, France; Vidas HIV p24, bioMérieux; Amplicor 1.5, Roche Molecular Diagnostics, Branchburg, USA).3 Confirmed presence of the antibody, antigen or nucleic acid using a previously described algorithm was considered evidence of HIV infection.3
As HIV test results were unlinked with respondent identity, those interested in knowing their HIV status were referred to the nearest voluntary counselling and testing centre.
Statistical analysis
We used multiple logistic regression models to assess the association of socio-demographic variables, behavioural variables and all variables together with prevalent HIV. We analysed these associations separately for men and women, and for behavioural variables also with inclusion of the significant variables for the spouse of married persons. The variables found significant at the 95% confidence level in bivariate analysis were included in the initial multiple regression model. The variables that became not significant at the 95% confidence level in the initial multiple regression model were excluded in the final multiple regression model.
We calculated population impact numbers for those sex behaviours or other modifiable risk variables that had significant association with HIV in the multiple logistic regression model. We adapted the method suggested by Heller et al.5 for calculating population impact numbers. Heller et al.'s method:
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We used current HIV prevalence and history of exposure to risk variables to calculate the number of HIV cases that would not have occurred if that risk variable had not existed, which is an adaptation of the PIN calculation suggested by Heller et al.5 that prospectively calculates the number of cases that could be prevented by eliminating a risk factor based on the estimated incidence of the disease in the exposed and unexposed.
We used the highest PIN estimate that we obtained for the HIV risk variables as a reference, and calculated the relative impact of the other risk variables. We used this relative impact as the main finding of this report instead of the absolute PIN due to the limitations of PIN and our adaptation of it, which we discuss later in the Discussion section.
Statistical analyses were done using SPSS (SPSS Inc., Chicago, USA) software.
Ethics approval for this study was obtained from the institutional ethics committees of the Administrative Staff College of India and Nizam's Institute of Medical Sciences, Hyderabad, India. This study complied with the principles expressed in the Declaration of Helsinki.
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Results |
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Of the 13 838 eligible persons 15–49 years of age, 12 617 (91.2%) gave a blood sample of which 12 612 also responded to the interview questionnaire, including 6312 (50%) rural residents and 6381 (50.6%) women.3 Evidence for HIV was found in 241 participants, a prevalence of 1.72% [95% confidence interval (CI) 1.36–2.04%] adjusted for the age, gender and rural–urban distribution of the population of Guntur district.3
Socio-demographic variables
Table 1 shows that for men the socio-demographic variables that were significantly associated with having prevalent HIV were age (peaking at 30–39 years), certain occupations (begging, sex work, unemployment, transport related), marital status (previously married: divorced, separated, widowed), lower education level (Class 10 or less) and place of residence (urban) using multiple logistic regression (model R2 = 0.11). The socio-demographic variables significantly associated with having HIV among women were marital status (previously married, currently married) and certain occupations (begging, sex work, occupations involving regular mobility, unskilled labour) using multiple logistic regression (model R2 = 0.09).
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Behavioural variables
Table 2 shows that for men there was significant association between prevalent HIV and history of having had sex with men, blood transfusion, having ever visited a sex worker or having had more than one lifetime women sex partners, consuming alcohol before sex, drug use, male non-circumcision and tattooing (odds ratios 5.74–1.97, P < 0.03, model R2 = 0.11). For women, the only identified behavioural variable significantly associated with HIV was having had more than one lifetime men sex partners (P = 0.001, model R2 = 0.07). The odds of having HIV were significantly higher for both men and women reporting condom use for sex in the last 6 months than those who did not (Table 2).
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For men, keeping all other behavioural variables the same in the multiple logistic regression model, if having ever visited a sex worker or having had more than one lifetime women sex partners was compared with all other men together including those who had not had sex, the odds of the former for having HIV were 1.70 (95% CI 1.04–2.77) as compared with the latter. If the former category was changed to ever visited sex worker or having had more than two lifetime women sex partners (n = 2375), the odds of having HIV increased only slightly (1.82, 95% CI 1.19–2.78) as compared with all other men combined. For women who had more than one lifetime male sex partner the odds of having HIV were 2.63 (95% CI 1.65–4.19) as compared with all other women combined.
On including the variables significant for men in the multiple logistic regression model for women as spouse variable for married women, the only spouse variable that had significant association at the 95% confidence level with HIV in women was if the husband had had tattooing (odds ratio 3.14, 95% CI 1.66–5.95). Two other spouse variables had an odds ratio of >2 but were not statistically significant at the 95% confidence level: husband had used recreational drugs (odds ratio 2.43, 95% CI 0.70–8.39) and husband had had blood transfusion (odds ratio 2.35, 95% CI 0.70–7.94). The R2 of the model for women increased to 0.10 with inclusion of spouse variables. If the number of lifetime sex partners of women was included in the multiple logistic regression model for men as spouse variable for married men, this variable was not significant at the 95% confidence level and the R2 of the model remained 0.11.
If all significant socio-demographic and behavioural variables were combined in a single multiple logistic regression model, the R2 of the model for men was still only 0.17 and that for women only 0.11. In the combined model for men, the number/type of women sex partners was not associated with prevalent HIV (Table 3), suggesting effect modification by socio-demographic variables. The trends for other variables did not change for men or women in the combined model as compared with the separate socio-demographic and behavioural models, but the magnitude and significance level of the association with prevalent HIV increased or decreased for the variables, becoming not significant for a few at the 95% confidence level (Table 3).
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Population impact of eliminating risk factors
Taking into account the relative risk and prevalence of the variables identified to be significantly associated with prevalent HIV in the behavioural model, the highest relative population impact on reducing HIV number per unit population was estimated for circumcision in urban men, followed by avoiding multiple sex partners or visiting sex workers among urban men, avoiding sex after consuming alcohol among urban men, and avoiding multiple sex partners or visiting sex workers among rural men (Table 4). If the only significant variable for women in the behavioural model, having multiple lifetime men sex partners, was theoretically eliminated, the relative population impact of this on reducing HIV number per unit population was much less than that for avoiding multiple sex partners or visiting sex workers by men (Table 4). It is important to note that the estimated number of HIV reduction due to the possible elimination of a variable would generally not be accurate, as the variables associated with HIV often co-exist in the same individual.
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Discussion |
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The striking finding in this analysis is that the usually considered behavioural risk variables for HIV, which are the focus of prevention efforts, explained a disappointingly small fraction of the variability of prevalent HIV in this Indian population, 11% for men and 10% for women.
Risk variables related to sex behaviour among men, including men having sex with men, multiple women sex partners and visiting sex workers, having sex after consumption of alcohol and lack of circumcision, were significantly associated with a higher risk of HIV in the behavioural multivariate regression model. Among women, having had multiple men sex partners was associated with a significantly higher risk of having HIV in the model for behavioural variables. However, the proportion of women who reported having had sex with more than one man in their life was only 8.8% versus 43.4% of men reporting having had sex with more than one woman or having visited a woman sex worker. Inclusion of significant variables among men in the women regression model as variables for spouses of married women increased the explanatory power of the model slightly from 7% to 10%. The same inclusion in the men regression model had no effect on the model.
Interestingly, for both men and women, the odds of having prevalent HIV were significantly higher for those who reported condom use for sex always or often in the last 6 months. Possible explanations for this finding include a higher frequency of condom use currently by those who were at high risk of HIV, a phenomenon referred to as risk compensation, and/or a bias towards higher reporting of condom use by those who are at higher risk of HIV. This highlights the need for caution against using this indicator simplistically while assessing the risk of HIV. In addition, both men and women who reported not having had sex in the last 6 months had significantly higher odds of having prevalent HIV as compared with those who had sex in the last 6 months and had not used condom. This, combined with the finding that both men and women who were previously married had the highest odds of having HIV, suggests that HIV status in them or their spouse previously may be linked with their lack of recent sex and/or spouse.
A history of having had blood transfusion, used recreational drugs (injection or other) and tattooing were also significantly associated with having HIV among men by multivariate analysis. Although in this cross-sectional study it is not possible to link presence of HIV with the timing of the exposure to the risk variable, this finding highlights the need to examine the blood transfusion safety practices. It is still common practice in India to use HIV detection kits in blood banks that detect antibodies only. As the antibody to HIV appears about 3 weeks after infection,6–8 HIV infection in this window period is being missed in blood banks in India, leading to possible transmission to blood recipients. The ideal blood banking practice is to test for HIV nucleic acid in pooled samples from donated blood, as nucleic acid starts appearing within the first week of infection.7 However, this is a tedious process which will take time to get established in India. In the meanwhile, the risk of HIV transmission through blood transfusion can be cut down by using HIV detection kits in blood banks that detect both HIV antibody and antigen (that starts appearing in the second or third week after infection).6 These kits are now available in India and have been demonstrated to have excellent sensitivity and specificity.9
There was significant association of the use of recreational drugs with HIV among men. The majority of this was non-injection drugs, with only a small fraction of men reported injecting drugs (0.1%). The significant association of tattooing with HIV in this study suggests the need to understand better the degree to which this relation is causal or a surrogate marker for other causal variables. A limitation of this study is that we did not take history of injection by healthcare providers to test its association with HIV. There is debate in the literature about the contribution of poor injection practices to HIV,10,11 but the lack of these data in our study prevents us from examining this association. A previous study in India reported a positive association of prevalent HIV with history of injections that was of borderline significance at the 95% confidence level, but the poor participation rate of 59.8% in this population-based study from among the eligible persons poses substantial difficulties in interpretation of data from this study.12
Among occupations, the highest association of HIV with sex work and begging among both men and women is not surprising. Transport-related occupation among men was also associated with higher risk of HIV, which too is a known association. The significantly higher risk of HIV among women who were unskilled labourers or had other occupations associated with regular mobility, but not among men (except for transport related mobility), suggests the particular vulnerability of women in these occupations to high-risk sex practices, which needs focus in HIV prevention efforts in India. We have previously reported that women struggling with illiteracy, lower social status and less economic opportunities have a relatively higher representation among sex workers in Andhra Pradesh, making them more vulnerable to HIV.13
The use of PIN to estimate the impact of addressing behavioural risk factors should be interpreted with caution. First, our use of current HIV prevalence and history of exposure to risk variables to calculate the number of HIV cases that would have been avoided if that risk variable had not existed is an adaptation of the PIN calculation suggested by Heller et al.5 that prospectively calculates the number of cases that could be prevented by eliminating a risk factor. Second, often risk factors for HIV co-exist in an individual and not in isolation, and their interaction in determining the composite risk of HIV can be complex. Third, it is generally not possible to eliminate or totally address a risk variable. The interpretation of addressing a risk variable needs special mention for these variables: men who have sex with men, multiple sex partners, having sex with sex workers and having sex after consuming alcohol. These are choices that people have the right to make, and therefore, for these variables addressing them means making such sex practices as safe as possible. In this background, we have interpreted the PIN for addressing a risk variable for HIV only as a relative ratio and not as an absolute number. We used the relative impact per unit population for comparison as it makes more practical sense to compare prevention efforts per unit population. The interpretation of this for some variables, men who have sex with men and use of recreational drugs, needs to be clarified. The PIN calculated by us for these variables is based on the number of men who have sex with men and users of recreational drugs in a unit population. The impact number would be much larger if the denominator used were men who have sex with men and users of recreational drugs instead of the entire population. This is relevant as there are targeted HIV prevention programs for men who have sex with men and injection drug users.
In the background of these explanations and caveats, our analysis suggests that for a unit population the highest relative impact in reducing the number of persons with HIV would have been through circumcision of men in this population. This is an interesting finding in the background of recent evidence from sub-Saharan Africa showing the protective effect of male circumcision against HIV in randomized control trials,14–16 with a modelling study suggesting maximum benefit in risky males in their 20 s in sub-Saharan Africa.17 A previous hospital-based case control study in India also suggested protective effect of male circumcision against HIV.18 Our population-based data support this protective association at the population level. However, there are several dimensions to be considered before male circumcision is considered as an HIV prevention tool in any population.19 India is a deeply religious society where circumcision is associated with religious identity. Therefore, recommendation of circumcision as a HIV prevention tool in India without taking into account these sensitivities would be contentious and counterproductive. Our data suggest that a few persons in India get circumcision for reasons other than religion—2.9% of non-Muslims and 96.4% of Muslims were circumcised in our study. It is however unclear whether circumcision would be an acceptable HIV prevention tool in India. Understanding this will require extensive probing into this issue from a social perspective. We suggest substantive study of the sensitivities around male circumcision in India to examine its feasibility before it can be considered as an HIV prevention intervention in India.
The poor explanatory power of the usually considered risk factors for HIV among both men and women in this population-based study in India suggests the need to explore associations with HIV beyond the recognized risk factors and to also improve the ability to get reliable information about sensitive risk behaviour in surveys. This is particularly relevant as effective prevention of HIV, which requires adequate scientific information about the dynamics of HIV spread in specific settings, is widely recognized as the key to controlling the HIV epidemic.20
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Acknowledgement |
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The authors would like to thank the study participants.
Conflict of interest: None declared.
KEY MESSAGES
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References |
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1 Joint United Nations Programme on HIV/AIDS, World Health Organization. AIDS Epidemic Update (2007) Geneva: UNAIDS, WHO.
2 National AIDS Control Organization, Ministry of Health & Family Welfare, Government of India. HIV Sentinel Surveillance and HIV Estimation, 2006. (2007) (Accessed May 21, 2008). Available at: http://www.nacoonline.org/upload/Publication/M&E%20Surveillance,%20Research/HIV%20Sentinel%20Surveillance%20and%20HIV%20Estimation,%202006.pdf.
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7 Kolk DP, Dockter J, Linnen J, et al. Significant closure of the human immunodeficiency virus type 1 and hepatitis C virus preseroconversion detection windows with a transcription-mediated-amplification-driven assay. J Clin Microbiol (2002) 40:1761–66.
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14 Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R, Puren A. Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 Trial. PLoS Med (2005) 2:e298. Erratum in: PLoS Med 2006;3:e298.[CrossRef][Medline]
15 Gray RH, Kigozi G, Serwadda D, et al. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomized trial. Lancet (2007) 369:657–66.[CrossRef][Web of Science][Medline]
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17 Londish GJ, Murray JM. Significant reduction in HIV prevalence according to male circumcision intervention in sub-Saharan Africa. Int J Epidemiol (2008); [Epub ahead of print, March 3, 2008], doi:10.1093/ije/dyn038.
18 Reynolds SJ, Shepherd ME, Risbud AR, et al. Male circumcision and risk of HIV-1 and other sexually transmitted infections in India. Lancet (2004) 363:1039–40.[CrossRef][Web of Science][Medline]
19 World Health Organization and Joint United Nations Programme on HIV/AIDS. New data on male circumcision and HIV prevention: policy and programme implications. (2007) March 28. (Accessed May 21, 2008). Available at: http://data.unaids.org/pub/Report/2007/mc_recommendations_en.pdf.
20 Global HIV Prevention Working Group. Bringing HIV prevention to scale: an urgent global priority. (2007) (Accessed May 21, 2008). Available at: http://www.globalhivprevention.org/pdfs/PWG-HIV_prevention_report_FINAL.pdf.
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