Indian J. Prev. Soc. Med. Vol. 40 No.1 &

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1 Indian J. Prev. Soc. Med. Vol. 40 No.1 & THE EPIDEMIOLOGY OF OPPORTUNISTIC INFECTIONS IN HIV/AIDS CASES IN NEPAL B.N. Mishra 1, Nidhi D. Sinha 2, S.K. Shukla 3 & R.N.Das 4 ABSTRACT Irrespective of the achievements of highly active antiretroviral therapy (HEERT) era; the global gloomy picture of HIV /AIDS is due to a high prevalence of opportunistic infections (OIs). In Nepal the scenario is even worst because of prolong civil unrest, political instability, high male workforce migration, low literacy level, high level of socially acceptable polygamy & virtual nonexistence of HEERT scheme. To compound the problem studies on the spectrum of pathogens causing OIs is virtually nonexistent. In the present study sero-screening of 363 clinically suspected cases was done out of which 53 (14.6%) were found HIV positive & 34 (64.15%) positive for opportunistic pathogens. The HIV & OI positive status for males was significantly higher (P<0.001,at c 2 = ). Clinical presentations of HIV/AIDS cases were diverse; like fever, weight loss, cough & dyspnoea, dysphagia, chronic diarrhoea etc. On microbiological investigation Mycobacterium tuberculosis was found in 16 (47%) cases; followed by Cryptosporidium spp 06 (17.6%) and Candida spp 05(14.7%). Other opportunistic pathogens were also detected with varying frequency.. There is a need for more local/regional studies to establish the epidemiology of opportunistic infections in HIV/AIDS cases in Nepal. Keywords- HIV/AIDS; Male sex, Opportunistic infections; high risk behavior ; Nepal INTRODUCTION Most researchers believe that HIV originated in Sub-Saharan Africa during the twentieth century. 1 It is now a pandemic, with an estimated 38.6 million people now living with the disease worldwide. (2) As of January 2006, the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the World Health Organization(WHO) estimate that AIDS has killed more than 25 million people since it was first recognized, making it one of the most destructive epidemic in recorded history. In 2005 alone, AIDS claimed an estimated million lives, of which more than 570,000 were children. 2 In south East Asia region, the number of reported cases continue to increase alarmingly imposing new demands on health care systems. 3 The first case of AIDS in Nepal was reported in The National Center for AIDS and STD Control (NCASC) has formulated a policy requiring all cases of HIV / AIDS to be reported to its center at Kathamandu. HIV doesn't kill anybody directly. Instead, it weakens the body's ability to fight disease. Infections which are rarely seen in those with normal immune systems are deadly to those with HIV. People with HIV can get many infections (called opportunistic infections, or OIs). ¹ Professor, Dept. of PSM (Community Medicine), Rural Medical College; Pravara Rural University ² Dept. of Prosthodontics; Rural Dental College; Pravara Rural University ³ Associate Professor, Dept. of PSM (Community Medicine), Rural Medical College; Pravara Rural University 4. Associate Professor, Dept. of Medicine, MCOMS, Pokhara. Indexed in : Index Medicus (IMSEAR), INSDOC, NCI Current Content, Database of Alcohol & Drug Abuse, National Database in TB & Allied Diseases, IndMED, Entered in WHO CD ROM for South East Asia.

2 Opportunistic infections caused by devastation of host immune system by HIV are the major cause of morbidity and mortality in AIDS cases. Many common organisms are responsible for these easily treatable infections in immuno-deficient patients and mimic one another in clinical presentation (Fig.1). Despite observing an increasing trend in the reported HIV / AIDS cases in Nepal, the existence of any association of high risk behavior with HIV & OI positive status and the actual spectrum of opportunistic pathogens are not very clear. Unfortunately there is no available database on this regard, with a view to regional distribution in this country. Fig. 1 shows different sites & organisms responsible for OIs. The Aim & Objectives of the study 1. To Study the baseline characteristics of HIV/AIDS suspected cases visiting HIV clinics. 2. To demonstrate the existence of any association of high risk behavior with HIV & OI positive status. 3. To identify the commonly occurring opportunistic pathogens, recovered from different clinical specimens of suspected AIDS patients. MATERIALS & METHODS A) Study group: Based on high index of clinical suspicion, total of 363 clinically suspected cases attending AIDS clinic at Manipal Teaching Hospital, Pokhara, Nepal during Jan' 2004 to Jan' 2005 were considered for the study purpose. The sexual and other high risk behavior was systematically probed. Their diverse presentation was investigated for various infectious agents including those causing opportunistic infections. B) Detection of HIV infection: HIV infections in patients were confirmed according to WHO strategy II, 1993, when at least two of the following tests were positive: HIV 1 & 2 (Tri Dot, ELISA, J Mitraa & Co. Ltd, New Delhi, India) HIV Spot (Eliscan, Ranbaxy, New Delhi) and HIV 1 & 2 Western Blot (Gene Lab Diagnostics, Singapore). C) Collection and processing of clinical specimens: Various representative specimens e.g. sputum, CSF, Blood, Urine, Stool, Bronchoalveolar lavage, Esophageal brush, Lymph node aspirate were collected as per clinical presentation. They were transported to department of microbiology and were processed for different pathogens using universal precautions. Various media which ones were used for isolation of pathogens following standard procedure. Emphasis was led on Indian J. Prev. Soc. Med Vol. 40 No.1 & 2 97

3 conventional method of diagnostic approach, which is possible in most of the diagnostic laboratory set up in Nepal. Staining methods e.g. Gram, Giemsa, Ziehl Neelsen, modified Zeihl Neelsen were used and microscopic examinations were carried out including wet preparation as indicated 5,6. RESULT The study registered a male to female ratio of 1.37: 1 for suspected cases, 1.12: 1 for HIV positive status & 2.80:1 for OI positive status. Table -1: Baseline characteristics of the MTH (Manipal Teaching Hospital) HIV/AIDS Clinic Cohort. The HIV & OI positive status for males was significantly higher (P<0.001, c 2 = ) in comparison to female. Gurung community; a part of the Budishit religion reflected the highest case burden at 41(77.35%) in comparison to other religious group. HIV/AIDS cases with highest number (28(82.35%)) of OI was found in Gurung males. Other relevant baseline characteristics of suspected cases attending the MTH (Manipal Teaching Hospital) HIV/AIDS Clinic are displayed in table -1. Variable No. % Male Female Gurungs (Buddhist) Hindus Christians Others Heterosexual Injectable drug users Homosexual Others HIV +VE OIs Suspect cases demonstrating high risk behavior like homosexuality and injectable drug use were not significantly associated with HIV & IO positivity (p>0.05, c 4= ). The HIV & OI positive status of different groups is presented in table -2. Table -2: Different groups and their HIV & OI positive status. Variable Total number HIV +ve OI +ve No. % No. % No. % Injectable drug users Heterosexual Homosexual Others Total of the 53 patients presented with more than one sign which included fever in 36 (67.9%), weight loss in 27 (50.9%) cases, cough and dyspnoea 27 (50.9%), dysphagia 14 (26.4%), chronic diarrhoea in 12 (22.6%), generalized lymphadenopathy in 10 (18.9%) cases, while 6 (11.3%) patients suffered from meningitis, 2 (3.7%) patients presented with pyrexia of unknown origin. Distribution of pathogens in different specimens is presented in table - 3. Table- 3: Distribution of pathogens detected in HIV infected patients Organisms Specimens No. of patients Mycobacterium tuberculosis Sputum 11 Lymph node 3 CSF 2 Cryptosporidium spp Stool 6 Candida albicans Oesophageal brush 5 Cryptococcus neoformans CSF 3 Isospora belli Stool 1 Pneumocystis carinii BAL(Broncho Alveolar 1 Lavage) Strongyloides stercoralis Stool 1 Cyclospora spp Stool 1 Indian J. Prev. Soc. Med Vol. 40 No.1 & 2 98

4 A total of 34 infectious pathogens were detected in 53 patients. Among the pathogens detected, Mycobacterium tuberculosis was the most common pathogen (16/34; 47%) followed by Cryptosporidium spp (6/34; 17.6%) was isolated. The third commonest pathogen was Candida spp (5/34; 14.7%) followed by Cryptococccus neoformans (3/14; 8.8%) were ordered. Cyclospora spp (1/34; 2.9%), Strongyloides stercoralis (1/34; 2.9%), Isospara belli (1/34; 2.9%) and Pneumocystic carinii (1/34; 2.9%) were cultured as a single isolate from each patient (Table 4). DISCUSSION Table -4: Types of pathogens isolated from 34 clinical specimens Pathogens No. of isolates % Mycobacterium tuberculosis Cryptosporidium spp Candida albicans Cryptococcus neoformans Isospora belli Pneumocystis carinii Strongyloides stercoralis Cyclospora spp Ignorance, prejudice, workforce migration & separation from family are fuelling the spread of a preventable disease. In the era of civil unrest, Maoist insurgency and political uncertainty; Nepal has experienced high mobility of the young and adult male members. Pokhra being a tourist hotspot recorded high percentage of workforce migration (42%)(9). The high percentage of migration coupled with low level of knowledge of HIV / AIDS and its preventions leading to promiscuous behaviour were some of the discernible factors and are consistent with other reports from Nepal and bordering Indian states. 7,8,9 Pokhra and the adjoining moutainous districts like Mustang & Manang are dominated by Gurung community a sub type of buduisim followers. The majority of male members of this community work in countries like Honkong, Malaysia, Philippines, and Thailand etc. with high prevalence of HIV. This is amply reflected by significant level of association of HIV and OI status in male members (p<0.001, c 2 = ). The non-significant association of HIV/OI status in high risk groups like injectable drug users & homosexuals is the reflection of socially acceptable polygamous & polyandrous relationship in Gurung community which represented 260(71.62%) cases to the study population. In resource-poor nations, TB is the most common opportunistic infection associated with HIV and a leading cause of death among people living with AIDS. Many experts consider the two diseases twin epidemics. 2,10,11 In our study, we had a similar conclusion with OI due to Tuberculosis being the commonest in the HIV infected patients at (47%). Pulmonary tuberculosis was present in (11/34; 32.3%) while it was extra pulmonary in (05/34; 23.5%). The reported annual incidence rate of Tuberculosis is more than 1% and an estimated 2% of total population is having active Tuberculosis in Nepal. With an estimated population of 23.2 million (2001 census) in Nepal, Tuberculosis threatens to spread at an alarming rate. Pulmonary tuberculosis was present in (11/34; 32.3%) while it was extra pulmonary in (8/34; 23.5%). These findings are somewhat similar or different, compared to studies in Nepal and abroad. 7,11 Cryptosporidium related diarrhoea was found to be the second most common infection (7/34; 20.5%). Prevalence of Cryptosporidiosis in Nepal is not known. Esophageal candidiasis was another common infection (5/34; 14.70%) in the present study. It has been recognized as a common infection among HIV infected persons and who form an important group to be screened for HIV infection. 12 Meningitis due to Cryptococcus neoformas occurred in 3 patients (08.80%). Isospora associated diarrhoea was observed in 1 (2.9%) patients, which is discordant with 21 % prevalence reported from Indian study. 13 In studies in Haiti and Los Angeles, USA the prevalence is reported to be 15% and less than 1% respectively. 14 Cyclospora and Strognyloides stercoralis associated diarrhoea were detected in 2 patients (5.8%). Other pathogen namely Isopora belli and Pneumocystic carinii associated pneumonia was seen in one cases each (2.9%). Prevalence of these pathogens in HIV patients is variable as per published reports. 12,14,15,16 The present study documents that Tuberculosis, Cryptosporadiosis and Candidiasis are the most predominant opportunistic infections in the HIV infected patients in the Pokhara valley (Western Region) of Nepal. To the best of our knowledge Indian J. Prev. Soc. Med Vol. 40 No.1 & 2 99

5 it is the first study of its kind in the region highlighting epidemiological nature and spectrum of opportunistic infections in HIV/AIDS. The OI pattern of HIV/AIDS is ever changing and differs from country to country. So the need for timely diagnosis and intervention and constant monitoring of magnitude of the problem is necessary for better patient care and management. Further studies involving different regions of Nepal with inclusion of greater number of HIV patients and an accurate analysis of spectrum of infection in them will go a long way in establishing the disease epidemiology and OI spectrum. CONCLUSION In a poor, backward nation like Nepal with a crippled economy due to civil, political and maiosit unrest and virtually nonexistent Anti-retroviral treatment, OIs are treated symptomatically. Public awareness about the disease is at all time low health care facilities and HIV/AIDS management has to go miles to come at par with international standard. TB & HIV/AIDS; the most common combination is treated with conventional anti-tubercular drugs. The other groups like Cryptosporidium, Candida, Cryptococcus etc. face the same destiny. The least common isolated documented in this study were Pneumocystis carinii pneumonia and Isospora induced chronic diarrhoea which reflects the disease status of western world in 1990s. 2 So there is a lot to be done in the field of HIV/AIDS in Nepal. Aknowledgement Our special thanks to Dr.S. Sivananda then Prof. & Head, Department of Microbiology for his kind permission and constant encouragement. REFERENCES 1. Gao F, Bailes E, Robertson DL, Chen Y, Rodenburg CM, Michael SF, Cummins LB, Arthur LO, Peeters M, Shaw GM, Sharp PM and Hahn BH (1999). "Origin of HIV-1 in the Chimpanzee Pan troglodytes". Nature 397 (6718): UNAIDS (2006). Overview of the global AIDS epidemic, 2006 Report on the global AIDS epidemic. 3. World Health Organization: The Current Global Situation of HIV / AIDS pandemic. Wkly Epedemiol Res 1993, 68: WHO 1999; Health Situation in the South- East Asia Region , Regional Office for SEAR, New Delhi. 5. Subedi BK, Presentation of AIDS in Nepal, J Inst Med 1998: Baron EJ, Finegold SM, Baily and Scott's Diagnostic Microbiology, 8 th edn. Mosby: St Louis, Uma Banerjee; Progress in diagnosis of opportunistic infections in HIV/AIDS. Indian J Med Res 121, April 2005, pp Gradon JD, Timpone JG and Schintman SM, Emernence of Unusual Opportunistic pathogen in AIDS; a review. Clin Infect Dis 1992, 15: Subedi B K, Gurubacharya V L, Sexual behaviour pattern in Nepal J Inst Med, 1994; 14: Ayyagiri A, Sharma A K, Prasad KN, Dhole T N, Kishore J and Chowdhary G. Spectrum of opportunistic G I pathogens in AIDS patients. Ind J Med Microbiol 1999: Kumaraswamy N and Solomon S et al. Spectrum of opportunistic infections among AIDS patients in Tamil Nadu, India. Inst J STD AIDS 1995; 6: Lopez Dupla and Mora Sanz Pet et al. Clinical, endoscopic, immunological and therapeutic aspects of oropharyngeal and oescophageal candidiasis in HIV infected patients; a survey of 114 cases. Am J Gastroenterol 1992; 87: Sorvillo FJ, Lieb LE, Siedel J et al. Epidemiology of Isosporiasis among patients with acquired immunodeficiency syndrome in Los Angeles Country. Am J Trop Hyg Med 1995; 53: Prasad KN. Gastroenteritis in immuno compromised host. In proceeding of Current concept of microbial infection in immuno-compromised host of Indo-US CME, Prasad K N and Ayyagiri A (ed) Department of Microbiology, SGPGIMS, Lucknow, 1996; Sharma SK, Pande JN. HIV infection and tuberculosis. Ind J Chest Dis Allied Sci 1994; 36: Lanjeshwar D N, Rodriguez C et al. Cryptosporidium, Isopora and Strongyloides in AIDS. N Med J Ind, 1996: Indian J. Prev. Soc. Med Vol. 40 No.1 & 2 100

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