Risk for developing tuberculosis among intravenous drug users with human immunodeficiency virus ( HIV ) infection

Department of Microbiology, BP Koirala Institute of Health Sciences, Dharan, Nepal. School of Medical & Applied Sciences, Central Queensland University, Rockhampton, Australia. Department of Microbiology, Chitwan Medical College Teaching Hospital, Bharatpur, Nepal. Department of Operation Theatre, Grande International Hospital, Kathmandu, Nepal. Department of Microbiology, Nepal Medical College, Kathmandu, Nepal.


INTRODUCTION
Tuberculosis (TB) and human immunodeficiency virus (HIV) infection both remain a very serious public health problem.Despite the fact that TB is a preventable, treatable and curable disease, it is a major infectious disease with high prevalence.One of the reasons behind the failure to control TB burden is the impact of HIV on TB.World Health Organization (WHO) has estimated 9.27 million incident cases of TB where 1.37 million (14.8%) were HIV-seropositive (Guelar et al., 1993).Persons coinfected with HIV and Mycobacterium tuberculosis are at much greater risk of developing active TB than HIVseronegative individuals (Guelar et al., 1993).Synergistic action of HIV and TB is defined in such a way that HIV infection weakens the immune system of a person and tubercle bacilli can grow more easily resulting in active TB disease in persons with recently acquired or latent TB infection (WHO Regional Strategic Plan on HIV/TB SEA/TB/261.SEA/AIDS/140, 2003).The life time risk of developing TB in HIV negative is 5.0 to 10.0% but the risk may increase up to 60% in HIV positives (Dhungana et al., 2008).
A metaphor is apt: this is a time when oil (HIV) is poured into the fire (TB-infected persons) in Asia (Vermund and Yamamoto, 2007).The synergy of HIV and TB takes several forms: M. tuberculosis infection increases viral load; immunosuppression from advancing HIV disease increases the risk of tuberculosis, new as well as re-infection (quiescent M. tuberculosis will reactivate) (Selwyn et al., 1989).Preventive therapy with isoniazid (INH) can be initiated if co-infected individuals are identified as soon as possible.
Although Center for Disease Control and Prevention (CDC) has reported high rates of TB among HIV-seropositive intravenous drug users (IVDUs) (Centers for Disease Control and Prevention, 2005), clear differentiation has not been defined among IVDUs and non-IVDUs with HIV seropositivity.Therefore, we aimed to determine the prevalence of people infected with tuberculosis (PTB) among HIV seropositive IVDUs attending BP Koirala Institute of Health Sciences, Dharan, Nepal.

MATERIALS AND METHODS
A cross-sectional study was conducted during three year period (January, 2009to December, 2011).Equal numbers of HIV seropositive patients with and without history of IVDU attending Department of Microbiology, BPKIHS for CD4 cells counting were enrolled to study the prevalence of PTB.The nature and purpose of the study were explained to all the participants and they were assured of their confidentiality and anonymity.Written consent was obtained from all the participants.The participants were provided standard sputum containers and instructed to collect early morning sputum specimens on three consecutive days.The specimens were transported to laboratory and processed for microscopy [using Auramine-O fluorescent staining for screening of acid fast bacilli, Poudyal et al. 105 and Ziehl-Neelsen (Z-N) staining for their confirmation] and culture (World Health Organization, 1998).At least 100 oil immersion fields were on Lowenstein-Jensen (L-J) media.Acid fast bacilli (AFB) detected on the smear were graded according to WHO guideline (World Health Organization, 1998).About 300 OIF were examined to declare a slide negative.Growth on L-J media was identified.

Research ethics
Ethical clearance for conducting the study was obtained from the Institutional Review Committee of BP Koirala of Institute of Health Sciences, Dharan, Nepal.

Statistical analysis
The data obtained from questionnaire and CD4 cells counting were entered in Microsoft Excel and analyzed using SPSS version 16.0 software.Frequency of demographic variables was calculated.Association of CD4 cells count and M. tuberculosis positivity was determined using chi-square test.(Getahun et al., 2010).However, a range of figure (14 to 46%) can be seen in different studies conducted in different settings (Corbett et al., 2003;World Health Organization, 2009).The findings of this study is in contrast with the lower rates reported in earlier publications from Nepal (Dhungana et al., 2008;(Sharma et al., 2010;Ghimire et al., 2004).The prevalence seemed to be fairly high (23%)

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in the capital's (Kathmandu, Nepal) tertiary care center (Dhungana et al., 2008), whereas low prevalence (10.8%) had been reported from the cities with low population outside the capital (Ghimire et al., 2004).High prevalence in our study corresponds to our selection of sample population.Most of the participants were from HIV/AIDS living care homes which may provide the suitable environment for household contact of TB.High occurrence of TB in a setting of HIV prevalence has been reported from various parts of the world: South Africa (17.3%) (Lawn et al., 2011), Cambodia, Thailand, and Vietnam (15%) (Cain et al., 2010) and China (22.9%) (Yu et al., 2009).A Meta analysis (Gao et al., 2010) from china has shown a range of prevalence of TB: 0.5% (Cao et al., 2006) to 35% (Wang et al., 2007) among HIV positive people.
Our finding strongly indicated higher prevalence of PTB among HIV positive IVDUs as compared to HIV positive non-IVDUs.Effects of drug use in human physiology and varieties of risk factors (such as cluster of vulnerable people to acquire infection; smoking and alcohol use; and poor nutrition) may be responsible for high prevalence of TB among drug users.Significant relation of alcohol and smoking with the prevalence of TB has already been reported from the same place where this study was conducted (Gyawali et al., 2013).Deleterious effect of drug use on the immune system has been shown by in vitro studies (Friedman et al., 2003;Wei et al., 2003).
In our study, majority of participants in both groups were young (20 to 40 years), unemployed and have completed only secondary level of education.Drug use and intensity of HIV and TB were not observed to go parallel with higher education and employment status.We observed no significant relation (P > 0.05) between duration of drug use and finding of TB.However, few studies have reported their positive relations (Brassard et al., 2004;Grimes et al., 2007;Glynn JR., 1998).With the already discussed results, it can be summarized that HIVinduced immune-suppression along with the physiological effect of drug use and the associated risk factors play important role for the high prevalence of TB among IVDUs rather than the single effect of drug use.
Many studies have highlighted that HIV infection increases the risk of tuberculosis by approximately 7folds, though this may vary with the stage of the HIV epidemic, the prevalence of TB, and the age groups considered (Glynn JR., 1998).And, dually infected individuals develop TB at a rate of 5 to 10% per year (Deiss et al., 2009).These conditions may be due to HIV-TB co-infection with degraded humoral and cell mediated immune responses.
Although higher proportion of TB was observed in group I patients than the group II patients with respect to all three categories of CD4+ cell counts (< 200, 200 to 400 and > 400), significant association was not proved (P > 0.05).However, the higher prevalence of TB in group I than group II patients in the present study alarms the risk of drug use for development of TB among HIV people.Hence, it demands longitudinal studies to be conducted in the future covering large population setting.Furthermore, drug abuse may increase the chances of crossinfection and it may also become important treatment barrier because of the escaping behaviours of the abusers from social network.Hence the barriers, including poor adherence and limited access to care, pose unique challenges for their treatment.It is a proved fact that treatment failure is the primary risk factor for the development of drug resistance.Thus increased attention should be paid to such group while making policies to control TB and HIV infection.

Conclusion
Drug abuse remains a risk for HIV people to develop TB.Adults of 20 to 40 years age are at risk for both illicit drug use and HIV infection among them.Rate of tuberculosis is high in such drug users infected with HIV.So, to strengthen the health policy to control HIV infection and TB, IDVUs should be screened for both of these diseases.

Table 1 .
Table 3 shows positivity of M. tuberculosis among HIV patients with (group I) and without (group II) intravenous drug use and their CD4 + cell counts.Corresponding author.E-mail: n.gyawali@cqu.edu.au.Tel: 61749306966.Author(s) agree that this article remain permanently open access under the terms of the Creative Commons Attribution License 4.0 International License Demographic variables.
a total of 336 HIV positive patients divided into two groups in our study, group I comprised of patients with IVDU (n = 168) and group II without IVDU (n = 168).*

Table 2 .
Duration of intravenous drug use and finding of M. tuberculosis positivity.

Table 3 .
Positivity of M. tuberculosis among HIV patients with (group I) and without (group II) intravenous drug use and their CD4 + cell counts.