ORIGINAL ARTICLE * Department of Medicine, Regional Institute of Medical Sciences, Imphal, Manipur. HIV and TB Co-infection (A Study from RIMS Hospital, Manipur) S Bhagyabati Devi*, Santa Naorem*, T Jeetenkumar Singh*, Ksh Birendra Singh*, Lallan Prasad*, Th Shanti Devi* Abstract Background and objectives: Human immunodeficiency virus (HIV) and Tuberculosis (TB) co-infection is emerging as a serious threa globally. This study was done in Manipur, which has the highest HIV seropositivity rate in India, in an attempt to document the vulnerability of the HIV infected persons to tuberculosis in this State. Methods: 100 HIV positive patients of 30.27 ± 5.5 years of age and 100 HIV negative patients of 31.13 ± 8.54 years of age who willingly consented to participate in the study were selected after proper counselling. Confirmation of HIV status was done acc to NACO guidelines, and diagnosis of TB as per the RNTCP guidelines. Their mode of clinical presentation, site of TB, CD4 cell count, etc., were studied. Results: TB was found in 55% of HIV infected patients compared to 25% in seronegative patients, which was significant statistic (p < 0.001). Combined pulmonary and extrapulmonary form of TB were significantly more common in HIV seropositive patients (p < 0.02) in whom the CD4 cell count was also low (less than 100/cmm). Interpretation and conclusion: The result of this study showed the increased vulnerability of the HIV infected persons to TB in as seen in other studies in India and abroad. Disseminated TB with lower CD4 cell count is also shown. Further strengthening of the joint action plan on HIV and TB is suggested. Key words: AIDS, HIV, Tuberculosis, NACO, RNTCP. Introduction The emergence of human immunodeficiency virus (HIV) has paved the way for the resurgence of Mycobacterium tuberculosis infection – pulmonary as well as extrapulmonary. Multidrug resistant (MDR) and other rarer forms of TB have also become more prevalent. As a result, HIV and TB co-infection is on the rise, more so in the developing countries like India. HIV is the most powerful risk factor for progression from M. tuberculosis infection to TB disease. The risk of development of TB in HIV infected patients in India is 6.9/ 100 person years as compared to 10% lifetime risk of developing TB in HIV negative persons. This is especially important in India where 40% of adult population is latently infected with M. tuberculosis1. TB, in turn, accelerates the progression of HIV infection to AIDS defining stage and shortens the survival of such patients and is the leading cause of death, accounting for one-third of deaths due to AIDS worldwide2. Despite the existence of effective drugs, TB continues to be a major health problem and kills more than a million people every year. The World Health Organisation (WHO) declared TB a global emergency in 1993 and Govt of India has launched a Revised National Tuberculosis Control Programme (RNTCP) with directly observed therapy, short course (DOTS) as a solution for its control3. The magnitude of HIV infection is alarming in Manipur, a small state with a population of about 25 lakhs. In 1989 October, out of 828 blood samples screened, only 6 persons were found to be seropositive, but at present it is disturbing to note that Manipur has the highest seropositive rate of 157.92 per 1,000 blood samples screened4 as against the national figure of 40.63. The present study was undertaken to document the vulnerability of the HIV infected patients in Manipur to TB, and to study the present status of this common co- infection. Materials and methods The regional Institute of Medical Sciences Hospital (RIMS) JIACM 2005; 6(3): 220-3 is a referral teaching hospital in the North-Eastern part of India. This cross sectional study was conducted on the patients admitted to the Medicine ward of RIMS hospital from January, 2002 to January, 2003, mostly for the evaluation of fever. Patients who were earlier treated or were continuing treatment for TB were excluded from the study. Patients with high risk behaviour for HIV exposure like intravenous drug abuse, multipartner sex, transfusion of blood or blood products, sharing of razor blades, having tattoo mark, etc., were given proper counselling and their blood samples were tested for HIV serology. 240 patients were found to be seropositive out of 1,100 such cases (21.8%). Out of these, 100 patients who consented to participate in the study were randomly selected. Another 100 patients of comparable age with no history of high risk behaviour for HIV exposure were also selected. After proper counselling and due consent, they were subjected to HIV serology testing and were also investigated for tuberculosis. Screening and confirmation for HIV status were done in Voluntary Counselling and Testing Centre (VCTC) in the Dept of Microbiology, RIMS, as per NACO guidelines4. The centre is also a recognised National Reference Centre where CD4 lymphocyte count is also done by using Becton Dickinson FAC Scan. Diagnosis of TB was made according to the RNTCP guidelines5 by positive sputum AFB smear for pulmonary TB and by fine needle aspiration cytology or biopsy showing caseating granuloma, positive chest x- ray, pleural or ascitic fluid examination, etc., for extrapulmonary tuberculosis. Statistical Evaluation Mean and standard deviations were worked out for all numerical variables. Statistical association between variables was established by applying the chi-square test on a 2 x 2 table. Degree of freedom and significance of statistical association were calculated from standard probability (p-value) chart. Results Of the 100 seropositive cases, 94 (94%) were males and 6 (6%) were females. 87 (87%) patients including one female were intravenous drug users (IDUs), the remaining consisted of 10 male heterosexuals with multiple sexual partners and 3 homosexuals. The age range for seropositive patients was from 16 - 46 years with a mean and SD of 30.27 ± 5.5 years. For the seronegative patients it was from 15 to 48 years with mean ± SD of 31.13 ± 8.54 years. The highest number of HIV infection was found in the age group of 21 - 30 years (63%) as shown in Table I. Table I: Showing age distribution of the patients. Age (years) HIV Status (+ve) (-ve) n = 100 n = 100 Below 20 3 8 21 – 30 63 40 31 – 40 30 30 Above 40 4 22 The seropositivity rate was highest among those who were unemployed (40%); they were all IDUs (including 1 female). The second highest positivity was found among the business professionals (35%) among whom 30 were also IDUs. Tuberculosis was found in 55 patients (55%) in the seropositive group (age ranged from 21 - 36 years) and 25 (25%) patients in the seronegative group (age ranged from 22 - 46 years). Combined (pulmonary and extrapulmonary) lesions were more commonly seen in the HIV infected patients as shown in Table II. Table II: Showing distribution of TB among the patients (numbers in brackets denote percentage of the total TB cases detected). Koch’s No. of Patients Significance Lesion with TB in HIV (+) HIV (-) Patients Patients n = 55 n = 25 Pulmonary 18 (32.70) 11 (44) P > 0.05 Extra-pulmonary 12 (21.82) 09 (36) P > 0.05 Combined 25 (45.46) 05 (20) P < 0.02 The commonest extrapulmonary lesion in the HIV Journal, Indian Academy of Clinical Medicine circle6 Vol. 6, No. 3 circle6 July-September, 2005 221 222 Journal, Indian Academy of Clinical Medicine circle6 Vol. 6, No. 3 circle6 July-September, 2005 seropositive patients was in the lymph nodes (n = 15; 27.27%), followed by pleural effusion (n = 11; 20%), abdominal (n = 7; 12.72%) and CNS involvement (n = 4; 7.27%). AFB culture and sensitivity tests were not done because of non-availability of the facilities in our Institute. Sputum for AFB was positive in 16 (29%) of the seropositive cases and AFB was present in plenty in the lymph gland aspiration cytology in 12 (21.81%) seropositive cases. CD4 cell count was done in the seropositive patients with TB. It was lowest (less than 100/ cmm) in those patients with combined (pulmonary and extrapulmonary) lesions, less than 200/cmm in extrapulmonary lesions, and less than 300/cmm in pulmonary TB. Fever was present in all the patients of TB in both the study groups, cough of more than 3 weeks duration was present more in the seronegative group (80%) and involuntary weight loss of more than 10% in the past 6 months was commoner in the seropositive group (38.18%) as shown in Table III. Pulmonary infiltrates in the chest x-ray were found in 38 (69%) cases in the seropositive and in 17 (68%) cases in the seronegative patients. In 12 (21.81%) patients of the seropositive group, lower zone involvement was seen in the chest skiagram, a feature not present among the seronegative patients. Table III: Showing frequency of symptoms of TB (numbers in brackets denote the percentage value). Symptoms HIV Status (+ve) (-ve) n = 55 n = 25 Fever > 3 weeks 55 (100) 25 (100) Cough > 3 weeks 26 (47.27) 20 (80) Weight loss > 10% 21 (38.18) 4 (16) Haemoptysis 10 (18.18) 12 (48) Chest pain 10 (18.18) 11 (44) Shortness of breath 8 (114.54) 9 (36) Lymphadenopathy 15 (27.27) 4 (16) Discussion HIV seropositivity rate is on the rise in the State of Manipur6 as in rest of India and world. The sexually active age group of 20 - 40 years (93%) is the most commonly affected with the mean age of 30.27 ± 5.5 years. This is consistent with the findings of other studies8. For the seronegative controls also, the mean age was a comparable one of 31.13 ± 8.54 years. The incidence of HIV infection was highest among the unemployed youth (49%) and business personnel (35%). In other studies in India9 it was highest among the manual labourers, followed by truck drivers. IDU was the most common risk factor in the present study (87%) and it was most commonly found among the unemployed youths sharing the needless. In this study, TB was found in 55 % of the HIV positive patients and in 25% of the HIV negative patients which was significant statistically (p < 0.001). This is consistent with the findings in another study7, but higher than that of a Kolkata study with 27.7% only9. Our study was based on the patients admitted in the hospital for evaluation of fever. This may explain the higher incidence of TB in those seronegative patients. NACO, Govt. of India also has reported TB as the commonest opportunistic infection (62.3%) in the HIV infected persons4. The incidence of combined pulmonary and extrapulmonary TB infection was significantly higher (P<0.02) in the seropositive patients, a finding that is consistent with a study by Jones et al10. This shows that in immunocompromised patients TB may get disseminated early in comparison to their immunocompetent counterparts. The commonest clinical presentations were low grade fever, weight loss, cough, and lymphadenopathy which were consistent with studies by Kumar et al11 and by Putong et al12. But Dey et al9 found rapid weight loss was most common prsentation in seropositive patients, and cough was the most common symptom of TB in immunocompetent subjects. In our study, sputum for AFB was positive in 16 (29%) of seropositive patients and infiltrative lesions in chest skiagram were seen in 32 (58%) of seropositive patients which were 30.4% and 95.6% respectively in another study9. The CD4 cell count vis-à-vis the HIV – TB lesion in its different forms in this study is in tune with the findings in other studies10, 13, 14. Thus TB and HIV infection have a common interaction. HIV infection increases the individuals’ susceptibility to TB by impairing the immune response to mycobacterial infection15. Forte Journal, Indian Academy of Clinical Medicine circle6 Vol. 6, No. 3 circle6 July-September, 2005 223 et al16 have documented the declining proliferative and cytolytic T-cell mediated responses in HIV patients with progression of immunodeficiency. Recognising this serious threat, a joint action plan on HIV- TB was developed by the Government of India in November, 2001 between the National AIDS Control Organisation (NACO) and the Central TB Division8. The initial focus of the plan was on the six high HIV burden States of India which includes Manipur, a focus of HIV infection with the highest percentage of seropositivity where the present work was undertaken to study the current status of HIV and TB co-infection in this state. We humbly suggest the need for strengthening the joint action plan on HIV and TB, and also the ART (anti-retroviral treatment) services. Acknowledgement We are indebted to the Medical Superintendent and Microbiology Deptt. of Regional Institute of Medical Sciences and Hospital, Imphal for their guidance and kind permission to publish this study. References 1. Swaminathan S, Ramachandra R, Baskaran G. Risk of development of TB in HIV infected patient. Int J Tuberc Lung Dis 2000; 4: 844-9. 2. WHO-TB-Group at risk: WHO report on the global tuberculosis epidemic 1996. < www.who.int/gtb/ publications/therp-96> 3. Golhi G, Joshi JM. Clinical and laboratory observations of tuberculosis at Mumbai, India. Clinic Postgraduate Med J 2004; 51-3. 4. National guidelines for clinical management of HIV/ AIDS, Govt. of India, Ministry of Health and Family Welfare, National AIDS Control Organisation, 2003. www.nacoindia.org 5. Managing the Revised National Tuberculosis Control Programme in your area, Central TB Division, Directorate Gen. Health Services, Ministry of Health and Family Welfare, New Delhi, 1999. 6. MACS, Imphal, Manipur: Epidermidological analysis of HIV/ AIDS in Manipur, 1986 to 2002. 7. Kothari K, Goyal S. Clinical Profile of AIDS. JAPI 2001; 49: 435-8. 8. Pathni AK, Chauhan LS. HIV/TB in India: A Public Health Challenge. Special article. JIMA 2003; 101: 148-9. 9. Dey SK, Pal NK, Chakrabarty MS. Cases of Immunodeficiency virus infection and Tuberculosis – Early experiences of different aspects. JIMA 2003; 101: 291-8. 10. Jones BE, Young SM, Antoniskis D et al. Relationship of the manifestations of tuberculosis to CD4 counts in patients with HIV infection. Am Rev Respir Dis 1993; 148 (5): 1292-7. 11. Kumar P, Sharma N, Sharma NC, Patnaik S. Clinical profile of tuberculosis in patients with HIV infection/AIDS. Indian J Chest Dis Allied Sci 12. Putong NM, Pitisuttithum P, Supanaranond W et al. Mycobacterium tuberculosis infection among HIV/AIDS patients in Thailand: Clinical manifestations and outcomes. South east Asian J Trop Med Pub Health 13. Heyderman RS, Makunike R, Muza T et al. Pleural Tuberculosis in Harare, Zimbabwe: The relationship between human immunodeficiency virus, CD4 lymphocyte count, granuloma formation and disseminated disease. Trop Med Int Health 1998; 3 (1): 14-20. 14. Post FA, Wood R, Pillary GP. Pulmonary tuberculosis in HIV infection: radiographic appearance is related to Cd4 + T lymphocyte count. Tuber Lung Dis 1995; 76 (6): 518-21. 15. Giradi E, Goletti D, Antonucci G, Ipolito G. Tuberculosis and HIV: a deadly interaction. J Biol Regul Homcost Agents 2001; 15 (3): 218-23. 16. Forte M, Maartens G, Rahelu M et al. Cytolytic T cell activity against mycobacterium antigens in HIV. AIDS 1992; 6 (4): 407-11. ANNOUNCEMENT 13th Annual Conference of the Indian Association of Clinical Medicine October 15 - 16, 2005 Patna (Bihar) Dr. Arun Tiwary Chairman, Organising Committee Dr. Ajay Kumar Organising Secretary Dr. R. P. Srivastava Chairman, Reception Committee Conference Secrerariat: Dr. Ajay Kumar 22, Nehru Nagar, Patna - 800 013 (Bihar) Phone: 0621-2265715/2350434 Mobile: 09431020510, Fax: 0612-2278945 E-mail: drajaykr@yahoo.com