Background: The Human Immunodeficiency Virus (HIV) epidemic has posed major challenges to tuberculosis (TB) control efforts globally. The combined TB-HIV epidemic demands effective and urgent action. Aim: To estimate the prevalence of HIV infection among patients reporting at TB clinic and prevalence of TB infection among patients reporting at the Integrated Counseling and Treatment Center (ICTC). Setting and Design: Longitudinal study of 6 months duration from August 2010 to January 2011 at Urban Health Center located in an urban slum of Malwani, Mumbai. Materials and Methods: All patients attending ICTC who were diagnosed as seropositive and those with HIVnegative status but considered as TB suspects based on symptoms of TB were referred to TB clinic for ruling out TB. Similarly, all patients attending TB clinic who were diagnosed with TB (sputum positive TB/sputum negative TB/extra-pulmonary TB [EPTB]) were referred to ICTC for their HIV status. Both categories of patients were followed up till initiation of their treatment. Statistical Analysis: SPSS version 16 using Chi-square test and percentages. Results: Out of the 305 patients referred from ICTC to TB clinic, 61 (20%) were diagnosed with TB. Out of 264 TB patients referred from TB clinic to ICTC, 27 (10.2%) were diagnosed as seropositive. Married subjects and subjects staying with their family were having less chances of TB or HIV than unmarried subjects or those who were staying away from their family. Conclusion: Referral of seronegative TB suspects from ICTC to TB clinic should be strengthened as it was found in the study that prevalence of seronegative TB was higher in TB suspects than in HIVpositive patients.
Keywords: Extra-pulmonary tuberculosis, Human Immunodeficiency Virus, Integrated Counseling and Treatment Center, seropositive, tuberculosis and Human Immunodeficiency Viruscoinfection, tuberculosis
Globally, estimated number of tuberculosis and human immunodeficiency virus (TB-HIV) cases and deaths in 2009 was 1.1 million and 0.4 million, respectively.  At least, one-third of the 34 million people living with HIV worldwide are infected with TB. Persons coinfected with TB and HIV are 21-34 times more likely to develop active TB disease than persons without HIV.  Catalyzing collaborative TB/HIV activities in the Asia and Pacific region is a priority. This region has more than half the global burden of TB and 12% of the global burden of HIV.  TB remains a serious public health threat and economic burden in Russia with escalating rates of drug resistance against a background of growing HIV-epidemic. 
HIV infection is the most powerful risk factor for the progression of latent Mycobacterium tuberculosis (MTB) infection to TB disease. An HIVpositive person coinfected with MTB has 50-60% lifetime risk of developing TB disease, as compared to an HIV-negative person who has a 10% lifetime risk of developing TB disease.  TB is one of the earliest and commonest opportunistic diseases to develop among persons infected with HIV. , TB is a leading killer among people living with HIV. At least, one in four deaths among people living with HIV can be attributed to TB, and many of these deaths occur in resource-limited settings.  Operational research is necessary to improve the access to and delivery of TB prevention, diagnosis, and treatment interventions for people living withHIV.  There is considerable scientific evidence supporting the use of anti-retroviral therapy (ART) in prevention of HIV and TB infections. 
TB/HIV collaborative activities have been incorporated as major components of the stop TB strategy and the global plan to stop TB.  There is a need to improve service delivery coordination and crossreferrals between integrated counseling and treatment center (ICTC) and TB clinic. In India, strategy for TB-HIV care was considered and Joint Action Plan for TB-HIV was developed by Revised National Tuberculosis Control Program (RNTCP) and National AIDS Control Program (NACP).  To deliver services properly, service providers are trained in all aspects of both diseases and their management. To tackle TB-HIV coinfection, it requires a policy addressing need for continued capacity building programs and a system of regular, interactive sessions between the NACP and the RNTCP personnel. 
In a research conducted in Southern Africa with the purpose to report the findings of a broad-based study, it was concluded that there is a disjuncture between the global and local level that affects project delivery.  According to British HIV Association guidelines for the treatment of TB/HIV coinfection, it was recommended that coinfected patients should be managed by a multidisciplinary team.  Increasing rates of TB in people with HIV emphasize the importance and inadequacies of available diagnostic tools.  In a study carried out in Tamil Nadu to assess the crossreferral between HIV counseling and testing centers and smear microscopy centers, out of 18,329 clients counseled, 6% were identified as TB suspects and referred to designated microscopy centers (DMCs).  In a similar study in Maharashtra, 3% of voluntary counselingtesting (VCT) patients were identified as TB suspects and 29% were diagnosed with TB disease. Of the 765 selectively referred TB cases, 24% were found to be HIVpositive. 
With the growing incidence and prevalence of HIV and TB infections globally, there has been a rise in HIV-TB coinfections too. Hence, this study was planned to assess the HIV-TB collaborative activities and to study the epidemiological and socio-demographic factors associated with TB-HIV coinfection while estimating the prevalence of HIV among the patients reporting at the TB clinic and the prevalence of TB among the patients reporting at the ICTC.
It was a longitudinal descriptive study conducted in an urban health center. The study was conducted for a period of 6 months. The study methodology was based on guidelines by the National Framework for Joint HIV/TB Collaborative Activities, 2009.  Due approval was taken from the Institutional Ethics Committee for carrying out the study.
Referral of patients from ICTC to TB clinic
All clients coming to ICTC during the study period were screened by the ICTC counselors for the presence of the symptoms of TB disease (at the time of pre-, post-, and follow-up counseling). Those who were identified as TB suspects based on symptoms or signs of TB disease, irrespective of their HIV status, were referred to the TB clinic for ruling out TB disease. All such subjects were allotted personal identification number and then referred to the TB clinic for doing their sputum examination (or chest X-ray/fine needle aspiration cytology (FNAC) of lymph nodes, if necessary) and clinical assessment so as to estimate the prevalence of TB in HIV-positive patients. In our study, diagnosis of pulmonary TB was based on the diagnostic algorithm devised by RNTCP (The diagnostic algorithm used was as follows: Patient with cough more than two weeks duration was subjected to two sputum smear examinations, if one or both samples were positive then patient was labeled as sputum positive TB. If both the samples were negative, patients were given broad spectrum antibiotic for 14 days, and if the symptoms persisted again two sputum samples were examined. At this juncture, if either of the two samples came positive, patient was labeled as smear positive TB otherwise subjected to chest X-ray. If chest X-ray showed findings suggestive of TB, patient was labeled as sputum negative TB and if chest X-ray was normal then patient was labeled as non-TB).  At the time of referral, all clients were informed in the local language of the purpose of the study, and written consent was obtained before proceeding to the interview. The subjects were interviewed using a pre-tested semi-structured questionnaire to obtain detailed information about their socio-demographic profile. The subjects were assured about the confidentiality of data and data management. The referred patients were then followed up in TB clinic and in case they were diagnosed with TB (sputum positive/sputum negative/extra-pulmonary) they were started with anti-Koch’s treatment (AKT) (Category-I/II whichever being applicable based on the type of patient-new/retreatment). In the study, TB suspect was defined as the one who has at least two of the following symptoms, viz. cough formore than 2 weeks/weight loss/loss of appetite/low-grade fever with evening rise, irrespective of their HIV status (in case of seropositive patients cough of any duration was considered as being TB suspect).
Referral of patients from TB clinic to ICTC
All patients who were newly diagnosed with any form of TB, during the study period, based on sputum microscopy/chest X-ray/FNAC, etc. were also allotted personal identification number and then referred for their HIV testing to ICTC. At the time of referral, all subjects were informed in the local language regarding the purpose of the study, and written consent was obtained before proceeding to the interview. The subjects were then interviewed using a pre-tested semi-structured questionnaire to obtain detailed information about their socio-demographic profile. On referral to ICTC, all the subjects were given pre-test counseling with the help of a trained counselor, informed consent was taken, and HIV testing was done. This was followed by posttest counseling, and patients whose HIV reports were positive were utilized to estimate prevalence of HIV in TB patients. These coinfected patients were then referred to higher centers for their CD4 count, and in subjects with the CD4 count<350 cells/mm 3 , anti-retroviral therapy (ART) was started.  cotrimoxazole prophylaxis therapy (CPT) was started in subjects whose CD4 count was>350 cells/mm 3 for the management of opportunistic infections.
All the collected data were analyzed with SPSS version 16. Variables analyzed were:
Referral of patients from ICTC to TB clinic:Number of clients referred from ICTC to TB clinic, Number of patients diagnosed with TB among the referred clients and classification of TB (pulmonary: Sputum positive or sputum negative/extra-pulmonary) using frequency and percentages. Association between various socio-demographic variables (age, sex, marital status, education, staying with their family, addiction with tobacco/alcohol) and HIV-positive/negative patients with or without TB infection using Chi-square test of association at significance levels of P=0.05/0.01. Also treatment categories offered to the subjects were studied (based on new case or retreatment case).
Referral of patients from TB clinic to ICTC:Total number of confirmed TB patients who were tested for their HIV status and prevalence of HIV among TB was estimated using frequency and percentages. Association between various socio-demographic variables (age, sex, marital status, education, staying with their family, addiction with tobacco/alcohol) and HIV status among TB clinic referrals using Chi-square test of association at significance levels of P=0.05/0.01.
[Table 1] shows that during the study period, total 1446 clients were counseled out of which 305(21%) clients were referred to TB clinic. Out of 132 seropositive TB suspects, 21(16%) were diagnosed with any form of TB (TB-HIV coinfection=16%), while among the seronegative TB suspects, 40(23.1%) were confirmed TB cases. Out of the 32 sputum positive TB patients, 24(75%) were diagnosed with the initial two sputum examination while remaining 8(25%) were diagnosed on the basis of repeat sputum examination done after 10-14 days of administration of broad spectrum antibiotics. All the eightextrapulmonary cases were cases of TB lymph node which were diagnosed by FNAC. Forty one(67%) were new cases of TB,whereas remaining 20(33%) had a past history of TB and were thus put on category II treatment regimen.
[Table 2] shows the relationship between socio-demographic parameters and clients (HIV-positive/HIV negative) who were referred from ICTC to TB clinic for ruling out TB. Out of the 1446 clients counseled at ICTC, 132(9%) clients were HIV-positive TB suspects and 173(14%) were HIV-negative TB suspects. Out of the 305 subjects (132+173) referred, 190(62%) were from 20 to 40 year age group, 175(57%) male subjects, 191(63%) married, 239(78%) were educated till primary and secondary school, 158(52%) were staying with their family, 152(50%) were addicted to tobacco/alcohol or both. The diagnosis of TB was highest among the 15(37%) trans-genders followed by 16(18%) females and 30(17%) male clients. It was observed that the proportion of subjects who were single/unmarried had much higher chances of having TB among both HIV-positive 13(28%) and HIV-negative 24(35%) subjects.
[Table 3] shows the number of confirmed cases of TB who were referred to ICTC for their HIV status. TB-HIV coinfection was present in 27(10%) of subjects. Out of the 33 extra-pulmonary TB (EPTB) cases, majority were 25(76%) TB lymph node followed by 4(12%) of bone TB and 4(12%) of central nervous system TB. HIV-positive serostatus was found in 15(56%) sputum positive TB cases, 8(30%) sputum negative TB cases, and 4(15%) of EPTB cases. These coinfected patients were referred to higher centers for their CD4 count. Twenty five(93%) patients had CD4 count>350 cells/mm 3 and was thus started on CPT simultaneously with anti-Koch’s treatment (AKT). Two(7%) patients had CD4 count<350 cells/mm 3 and so they were started on ART along with AKT.
[Table 4] shows the socio-demographic parameters of TB patients who were referred to ICTC for their HIV testing. Out of the 264 subjects referred, 146(55%) were from 20 to 40 year age group, 130(49%) male subjects, 150(57%) married, 175(66%) were educated till primary and secondary school, 166(63%) were staying with their family, 142(54%) were addicted to tobacco/alcohol or both. TB patients who were either single/unmarried 17(63%) or who were not staying with their family members 17(63%) had more chances of having HIV infection, and both these parameters were found to be statistically significant.
In this study, it was observed that the prevalence of TB among HIV-positive patients was 15.9%. The diagnosis of TB was found to be highest among the 15(37.5%) trans-genders followed by 16(17.7%) females and 30(17.1%) male clients. It was observed that the proportion of subjects who were single/unmarried had much higher chances of having TB among both HIV-positive 13(28.3%) and HIV-negative 24(35.3%) subjects. The prevalence of HIV among TB patients was 10.2%. HIV-positive status was found in 15(55.6%) sputum positive TB cases, 8(29.6%) sputum negative TB cases, and 4 (14.8%) of EPTB cases. TB patients who were either single/unmarried 17(63%) or who were not staying with their family members 17(63%) had more chances of having HIV infection, and both these parameters were found to be statistically significant.
In a study on improving the diagnosis of pulmonary TB in HIV-infected individuals done in Vietnam, it was observed that clinical findings alone had poor sensitivity, but combination of CD4+cell count, AFB sputum smear, and CXR had a more accurate diagnostic performance.  In a study in South African population of gold miners who undergo regular radiological screening, it was found that presence of at least one of a trio of symptoms (new or worsening cough, night sweats, or weight loss) had similar sensitivity (29.4%) to either chest radiograph (25.5%) or sputum smear (25.5%). Hence, it was concluded that the addition of chest radiography to symptom screening substantially improved the sensitivity and positive predictive value. HIV infection did not alter the sensitivity of the screening tool.  However, in this study, we used detailed history, two sputum examinations, chest X-ray, FNAC, and various other diagnostic techniques for the diagnosis of EPTB. The diagnosis of TB in our study was based on the diagnostic algorithm devised by RNTCP. 
In a study conducted in Cape Town to estimate the burden of new and recurrent TB stratified by HIV status, retreatment TB cases comprised 30% of theHIV-associatedTBburden.  In this study, 305 subjects were referred to TB clinic from ICTC, out of which 132 were seropositive, of them 21(15.9%) were HIV-TB coinfected and retreatment TB cases contributed to 7(33.3%) of the TB-HIV coinfection. Similarity of results suggests a rising trend in the number of retreatment TB cases among HIV-positive patients in both India and South Africa.
In a study done on TB-HIV coinfection, TB was found in 55% of HIV-infected patients compared to 25% in seronegative patients, which was statistically significant at P<0.001.  In contrast to that in the present study, 21(15.9%) subjects had TB among HIV-infected patients as compared to 40 (23.1%) among HIV-negative patients emphasizing the fact that ICTC counselors should have a high index of suspicion for TB even among HIV-negative clients.
In a study carried out in Tamil Nadu to assess the crossreferral between HIV counseling and testing centers and smear microscopy centers, out of 18329 clients counseled, 6% were identified as TB suspects and referred to DMCs.  In a study in Maharashtra to evaluate crossreferral between voluntary HIV counseling and testing centers and TB services, it was observed that 3% of 9921 VCT patients were identified as TB suspects and 29% were diagnosed with TB disease. Of the 765 selectively referred TB cases, 24% were found to be HIVpositive.  However, in this study, out of the 1446 clients counseled, 9.1% were found to be seropositive TB suspects and of the remaining 1314 subjects, 13.2% were seronegative TB suspects and were referred to TB clinic for ruling out TB. In this study, out of the 173 TB suspects, 40(23.1%) were diagnosed with TB. The main reason for the identification of higher number of TB suspects (22.3%) in our study is mainly because of study settings, i.e. an urban slum area with overcrowding which favors the spread of TB.
In a study done in Cambodia to evaluate collaborative TB and HIV activities, it was revealed that 86% of newly registeredTBpatients underwentHIVtesting.  However, in this study, 100% of the newly registered TB patients were referred to ICTC for their HIV testing. This was because of the strict implementation of intensified TB-HIV collaborative activities in the city of Mumbai.
In a study done in India the most common affected age group was 31-40 years. EPTB was the commonest form of TB detected in 65 patients.  In our study, out of the 264 newly registered TB patients at TB clinic, 146(55.3%) were from 20 to 40 year age group. Sputum positive pulmonary TB 137(51.9%) was the most common form of TB most probably because of overcrowding, ill ventilation in the slum area coupled with improper airborne infection control measures, and minimal use of cough etiquettes due to lower level of education and lower socio-economic status in the study setting.
In a study done across all districts in India, HIV seroprevalence in TB patients was highest in the groups aged 25-34 years (11.0%) and 35-44 years (10.6%). HIV sero-prevalence was higher among male TB patients than among female TB patients (8.4% vs. 5.6%, relative risk (RR) 1.28, 95% confidence interval (CI) 1.04-1.59).  In an another study to find out the HIV risk factors among patients with TB, it was found that HIV-positive patients were more likely thanHIV-negative patients to: be female (45% vs. 26% (adjusted prevalence odds ratio [aPOR])=3.8; be 26-35 years old (50% vs. 19% (aPOR=2.7) be unmarried (91% vs. 71% (aPOR=13.3); have higher income (24% vs. 10% (aPOR=8.2); report separation from spouse/partner for work (63% vs. 52% (aPOR=1.8).  In our study, it was observed that TB patients who were either single/unmarried 17(63%) or who were not staying with their family members 17(63%) had more chances of having HIV infection and vice versa, and both these parameters were found to be statistically significant. The probable reason for such finding is the importance of family support in the form that patients living alone are more prone to addictions, having illicit sexual relationships, poor treatment seeking behavior, and having improper dietary habits.
This study highlights the significant role of ICTCs and TB clinics in diagnosing TB or HIV among the patients who have been collaterally referred. It also emphasizes the need for further strengthening the partnership between RNTCP and NACP to extend and expand diagnostic services to both cadres of patients. In this study, it was observed that overall 40(65.6%) cases of diagnosed TB were from TB suspects (HIV status negative) emphasizing the need of strengthening of referral of seronegative TB suspects by the ICTC counselor.
This study had limitations in the form that it was a single center-based study which could result in selection bias. Reasons for sero-positive status could not be elicited as the patients were reluctant. Impact of chest X-ray as an additional tool for the diagnosis of TB was not assessed separately.
Referral of seronegative TB suspects from ICTC to TB clinic should be strengthened as it was found in the study that prevalence of TB was higher in seronegative TB suspects than in HIV-positive patients. Unmarried subjects and those who were not staying with their family had much higher chances of having TB-HIV coinfection. Being an urban slum community with presence of overcrowding and poor ventilation, awareness regarding airborne infection control measures, cough etiquettes, and cough hygiene should be promoted with the help of intensified information, education, and counseling activities.
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2], [Table 3], [Table 4]