Drug trafficking routes and hepatitis B in injection drug users, Manipur, India.Prevalence of hepatitis B Hepatitis B Definition Hepatitis B is a potentially serious form of liver inflammation due to infection by the hepatitis B virus (HBV). It occurs in both rapidly developing (acute) and long-lasting (chronic) forms, and is one of the most common chronic genotype C in injection drug users in the northeastern Indian state of Manipur, neighboring the "Golden Triangle Golden Triangle can refer to:
********** Injection drug use is common in countries neighboring the "Golden Triangle" (Myanmar, Laos, and Thailand), known for heroin export to other countries. HIV and injection drug use outbreaks in countries neighboring the Golden Triangle, including the northeastern Indian state of Manipur, have been associated with drug-trafficking routes (1). Manipur shares a 358-km porous border with Myanmar. According to according to prep. 1. As stated or indicated by; on the authority of: according to historians. 2. In keeping with: according to instructions. 3. the National AIDS Control Organization, India (www.nacoonline.org), HIV infection rates among injection drug users in Manipur increased from 2%-3% in 1989 to >50% in 1991 and [approximately equal to] 64% in 2000. In addition, exposure rates of 100% for hepatitis B virus (HBV HBV hepatitis B virus. HBV abbr. hepatitis B virus ) and 92% for hepatitis C virus
abbr. hepatitis C virus HCV 1 Hepatitis C virus, see there 2. Human coronavirus. See Coronavirus. ) have been detected among injection drug users in Manipur, and 95% of wives of injection drug users had HBV exposure (2). However, among both the users and their wives, prevalence of HBV genotypes and occult HBV infection (3), a known risk factor for hepatocellular carcinoma hep·a·to·cel·lu·lar carcinoma n. A carcinoma derived from parenchymal cells of the liver. Also called hepatocarcinoma, malignant hepatoma. (HCC HCC Hepatocellular Carcinoma (liver cancer) HCC Hertfordshire County Council (administrative region of south eastern England UK) HCC Harford Community College (Maryland) ) (4), remained unknown. HBV is classified into 8 genotypes, HBV/A through HBV/H, and is further divided into subgenotypes (5) that have a distinct geographic distribution and are associated with different disease outcomes. The geographic distribution of HBV is known to correlate with the anthropologic history of migration (5) and to the origin and routes of spread of HBV infection. In addition, behavioral patterns are known to change HBV genotype distribution in a region (6). Manipur is an important location, where mainland India (prevalent genotypes HBV/A, HBV/D) geographically meets China and Southeast Asia Southeast Asia, region of Asia (1990 est. pop. 442,500,000), c.1,740,000 sq mi (4,506,600 sq km), bounded roughly by the Indian subcontinent on the west, China on the north, and the Pacific Ocean on the east. (prevalent genotypes HBV/B, HBV/C). Our study was designed to detect HBV DNA DNA: see nucleic acid. DNA or deoxyribonucleic acid One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes. among injection drug users in Manipur and to analyze HBV genotypes for correlation with injection drug use and the HIV epidemic. The Study We examined HIV-positive injection drug users from Manipur who had been identified as anti-HBc-positive during previous serosurveys conducted by the National Institute of Cholera and Enteric enteric /en·ter·ic/ (en-ter´ik) within or pertaining to the small intestine. en·ter·ic adj. 1. Of, relating to, or within the intestine. 2. Diseases (2). Serum samples (stored at 80[degrees]C) taken from 63 men 18-25 years of age were available for the study. HBsAg detection was repeated with a monoclonal antibody-based Hepanostika hepatitis B surface antigen hepatitis B surface antigen n. Abbr. HBsAg An antigen derived from the surface of the hepatitis B virus that is present in the blood in active hepatitis B infection. Also called Australia antigen. (HBsAg) kit (bioMerieux, Marcy l'Etoile, France). Anti-HCV antibody was detected using the Ortho HCV 3.0 test (Ortho-Clinical Diagnostics Ortho Clinical Diagnostics is a Johnson & Johnson company. It was created following Johnson and Johnson's acquiring of Ortho Diagnostic Systems in 1994, which was then merged with Johnson & Johnson Clinical Diagnostics in 1997. , Raritan, N J, USA). We completed HBV DNA isolation, PCR PCR polymerase chain reaction. PCR abbr. polymerase chain reaction Polymerase chain reaction (PCR) amplification, genotype/subgenotype/subtype identification, recombination recombination, process of "shuffling" of genes by which new combinations can be generated. In recombination through sexual reproduction, the offspring's complete set of genes differs from that of either parent, being rather a combination of genes from both parents. detection, and HBV DNA quantification with methods described earlier (7-9). We also compared nucleotide (online Appendix Table, available at http://www.cdc.gov/ncidod/EID/vol 12no 12/06-0425 appT.htm) and deduced amino acid amino acid (əmē`nō), any one of a class of simple organic compounds containing carbon, hydrogen, oxygen, nitrogen, and in certain cases sulfur. These compounds are the building blocks of proteins. sequences (Table) with consensus sequence of amino acids of corresponding genotypes to detect substitutions (GenBank accession nos. DQ356432-DQ356441). All those tested were HBsAg negative, and only 10 (15.9%) had detectable HBV DNA. Anti-HCV was detected in all but 1 sample (no. 4). Serum HBV DNA level was detectable in 5 of 10 samples (Table); the rest were below the detection limit of our assay. HBV/C (all subtype (programming) subtype - If S is a subtype of T then an expression of type S may be used anywhere that one of type T can and an implicit type conversion will be applied to convert it to type T. adr except 1 adw2) was the predominant genotype, with 4 subgenotype C 1 (HBV/C 1) and 3 subgenotype C2 (HBV/C2) isolates. HBV/A1 adw2 was found in 1 of the isolates. Two other isolates (nos. 1 and 3, subtype adw2) indicated a possibility of intergenotypic recombination (Figure 1), but subgenotype could not be assigned for them. [FIGURE 1 OMITTED] BLASTN search (www.incogen.com/public_documents/vibe/details/NcbiBlastn.html) of sequence from sample no. 1 showed similarity to HBV/D as well as to HBV/A sequences from European countries. On the other hand, sequences from sample no. 3 showed similarity to HBV/C and HBV/A sequences from Southeast Asian countries and India. Simplot analysis confirmed recombination in these 2 isolates (Figure 2). Apart from the genotype-specific substitutions, deduced amino acid sequences did not have any remarkable escape mutant other than G145R in 2 isolates (Table). [FIGURE 2 OMITTED] Conclusions The data from this study showed occult HBV infection in 15.9% of the injection drug users tested. The rate of HBV DNA detection (10%-45%) was considerably different in studies reported from different cohorts of injection drug users in different countries, a finding that has been attributed to coinfection with HCV or low HBV DNA levels (3). Apart from H1V, our study group had a high frequency of HCV infection and low HBV DNA levels. Undetectable HBsAg, except in 2 cases with G145R substitution, may also be a result of the above-mentioned factors. Although the importance of occult HBV infection is not well understood, a recent study reported occult HBV to be a significant risk factor for HCC, especially among persons who were anti-HBc--positive (4). Another recent study among HIV-infected patients documented death due to liver disease Liver Disease Definition Liver disease is a general term for any damage that reduces the functioning of the liver. Description The liver is a large, solid organ located in the upper right-hand side of the abdomen. in 22% who were HBV coinfected, 44% who were HCV/HBV coinfected, and l 5% who were HBV coinfected and had HCC (10). Thus, the clinical relevance in our study group also needs to be followed. Although we detected a 100% prevalence of anti-HBc in our serosurveys (2), only 1 was HBsAg-positive. Therefore, the distribution of genotypes among those who were HBsAg positive could not be determined. Findings of HBV/C1 (prevalent in China) appear to support the history of human migration from China to northeastern India. However, we did not detect HBV/B, also prevalent in China. Further, we did detect HBV/C2, which has close similarity to strains from Southeast Asian countries. The presence of HBV/C correlated well with drug-trafficking routes and the injection drug use epidemic. The geographic proximity of Manipur to the Golden Triangle, needle sharing Needle sharing is the colloquialism for the reuse of syringes by multiple illegal drug users to administer intravenous drugs, and is a primary vector for diseases which can be transmitted through blood, including hepatitis and AIDS. among injection drug users, and drug traders thus contributed to the spread of HBV through drug-trafficking routes, similar to HIV (1). In Manipur, HIV subtypes C and Thai B are prevalent (11); these are also prevalent in the India-Myanmar and China-Myanmar border regions. The presence of similar HIV subtypes among injection drug users in Manipur supports the presence of similar HBV strains (e.g., HBV/C1, HBV/C2) and their cotransmission through drug-trafficking routes. In addition, circulation of recombinant HBV is common among injection drug users because of repeated exposure (12). The intergenotypic HBV recombinants found in this study are thus expected. HBV/C has been associated with advanced liver disease and poses a higher risk for HCC in Asians (13) than does HBV/B. However, the clinical relevance of HBV recombinants and their pathogenesis is not well understood and needs further investigation. Poor, unemployed youths in the northeastern states of India are being recruited for drug trafficking to other regions (www.ipcs.org). Furthermore, national highways are associated with the prevalence of injection drug use in rural Manipur (14). As these highways connect Manipur with other parts of India, HBV/C may spread from Manipur to other parts of the country through persons who travel regularly, such as truck drivers and drug traffickers. Presence of HBV genotypes A and D among patients from northern and western India is well documented. Recent research reported HBV/C with close similarity to Southeast Asian strains only from eastern India (9,15) and suggested injection drug users as a possible route of introduction (15). In addition, persons from northeastern India frequent Kolkata for education, employment, medical treatment, and other purposes. Studies on these mobile populations might provide further important information on the route, population at risk for infection, and changing epidemiology of these viral infections in other regions. In conclusion, HBV/C, associated with severe liver disease in Southeastern Asia, may be emerging in the Manipur state of India through the trafficking routes of injection drugs. This genotype could spread to the general population through different modes. In light of growing information on the severity of liver disease in HBV-infected HIV/HCV patients, injection drug users should be the focus of additional education and healthcare efforts. The possibility of further spread of HIV/HBV/HCV through mobile populations to other regions of India warrants attention and further investigation. Acknowledgments We thank Tapan Kumar Chakrabarti for technical assistance. The University Grants Commission, New Delhi New Delhi (dĕl`ē), city (1991 pop. 294,149), capital of India and of Delhi state, N central India, on the right bank of the Yamuna River. , India, and Indian Council of Medical Research The Indian Council of Medical Research (ICMR), New Delhi, the apex body in India for the formulation, coordination and promotion of biomedical research, is one of the oldest medical research bodies in the world. , New Delhi, provided research fellowships. Mr Datta is senior research fellow at the ICMR ICMR Indian Council of Medical Research ICMR Institute for Coastal and Marine Resources ICMR Interagency Committee on Medical Records Virus Unit, Kolkata, India. His research interests include the molecular epidemiology molecular epidemiology Molecular medicine An evolving field that combines the tools of standard epidemiology–case studies, questionnaires and monitoring of exposure to external factors with the tools of molecular biology–eg, restriction endonucleases, of HBV, its transmission among family members, genetic variability Introduction Genetic Variability
adj. Originating or occurring outside the liver. sites in persons with HIV/HCV coinfection. References (1.) Beyrer C, Razak MH, Lisam K, Chen J, Lui W, Yu XF. Overland heroin trafficking routes and HIV-1 spread in south and south-east Asia South-East Asia n → le Sud-Est asiatique South-East Asia south n → Südostasien nt South-East Asia n → . AIDS. 2000;14:75-83. (2.) Saha MK, Chakrabarti S, Panda S, Naik TN, Manna B, Chatterjee R, et al. Prevalence of HCV and HBV infection amongst HIV seropositive seropositive /se·ro·pos·i·tive/ (-poz´i-tiv) showing positive results on serological examination; showing a high level of antibody. se·ro·pos·i·tive adj. intravenous drag users and their non-injecting wivcs in Manipur, India. Indian J Med Res. 2000;111:37-9. (3.) Torbenson M, Kannangai R, Astemborski J, Strathdee SA, Vlahov D, Thomas DL. High prevalence of occult hepatitis B in Baltimore injection drug users. Hepatology. 2004;39:51-7. (4.) Pollicino T, Squadrito G, Cerenzia (3, Cacciola 1, Raffa G, Crax A, et al. Hepatitis B virus maintains its pro-oncogenic properties in the case of occult HBV infection. Gastroenterology gastroenterology Medical specialty dealing with digestion and the digestive system. In the 17th century Jan Baptista van Helmont conducted the first scientific studies in the field; William Beaumont published his own observations in 1833. . 2004; 126:102-10. (5.) Norder H, Courouce AM, Coursaget JME JME Journal of Medical Ethics JME Juvenile Myoclonic Epilepsy JME Jones Matrix Eigenanalysis (method to measure polarization mode dispersion, ITU-T) JME Java Management Environment JME Java Management Extensions , Lee SD, Mushahwar IK, Robertson BH, et al. Genetic diversity of hepatitis B virus strains derived worldwide: genotypes, subgenotypes and HBsAg subtypes. Intervirology. 2004;47:289-309. (6.) Kidd-Ljunggren K, Miyakawa Y, Kidd AH. Genetic variability in hepatitis B viruses. J Gen Virol. 2002;83:1267-80. (7.) Datta S, Banerjee A, Chandra PK, Chowdhury A, Chakravarty R. Genotypc, phylogenetic phy·lo·ge·net·ic adj. 1. Of or relating to phylogeny or phylogenetics. 2. Relating to or based on evolutionary development or history. analysis, and transmission pattern of occult hepatitis B virus (HBV) infection in families of asymptomatic HBsAg carriers. J Med Virol. 2006;78:53-9. (8.) Lole KS, Bollinger RC, Paranjape RS, Gadkari D, Kulkarni SS, Novak NG, et al. Full length human immunodefficiency virus type 1 genomes from subtype C infected seroconverters in India, with evidence of intersubtypc recombination. J Virol. 1999;73:152-60. (9.) Banerjee A, Kurbanov F, Datta S, Chandra PK, Tanaka Y, Mizokami M, et al. Phylogenetic relatedness and genetic diversity of hepatitis B virus isolates in Eastern India. J Med Virol. 2006;78:1164-74. (10.) Salmon-Ceron D, Lewden C, Morlat P. Bevilacqua S, Jougla E, Bonnet F, et al. The Mortality 2000 Study Group. Liver disease as a major cause of death among HIV infected patients: role of hepatitis C Hepatitis C Definition Hepatitis C is a form of liver inflammation that causes primarily a long-lasting (chronic) disease. Acute (newly developed) hepatitis C is rarely observed as the early disease is generally quite mild. and B viruses and alcohol. J Hcpatol. 2005;42:799-805. (11.) Mandal D, Jana S, Bhattacharya SK, Chakrabarti S. HIV type 1 subtypes circulating in eastern and northeastern regions of India. AIDS Res Hum Retroviruscs. 2002; 18:1219-27. (12.) Chen BF, Kao JH, Liu CJ, Chen DS, Chen PJ. Genotypic dominance and novel recombinations in HBV genotype B and C coinfected intravenous drug users. J Med Virol. 2004;73:13-22. (13.) Chan HLY, Hui AY, Wong ME, Tse AML AML - A Manufacturing Language , Hung LCT LCT abbr. 1. land conservation trust 2. local civil time , Wong VWS VWS Volksgezondheid, Welzijn en Sport (Dutch ministry) VWS Views (US Postal service standard street suffix) VWS Ventana Wildlife Society (Salinas, California) , ct al. Genotype C hepatitis B virus infection is associated with an increased risk of hepatocellular carcinoma. Gut. 2004;53:1494-8. (14.) Sarkar Sarkar could mean:
(15.) Vivekanandan P, Abraham P, Sridharan G, Chandy G, Daniel D, Raghuraman S, et al. Distribution of hepatitis B virus genotypes in blood donors and chronically infected patients in a tertiary care tertiary care Managed care The most specialized health care, administered to Pts with complex diseases who may require high-risk pharmacologic regimens, surgical procedures, or high-cost high-tech resources; TC is provided in 'tertiary care centers', often hospital in southern India. Clin Infect Dis. 2004;38:e81-6. Sibnarayan Datta,* Arup Banerjee,* Partha K. Chandra,* Pradip K. Mahapatra, ([dagger]) Shekhar Chakrabarti, ([double dagger]) and Runu Chakravarty * * ICMR Virus Unit, Kolkata, India; ([dagger]) Jadavpur University, Kolkata, India; and ([double dagger]) National Institute of Cholera and Enteric Diseases, Kolkata, India Address for correspondence: Runu Chakravarty, ICMR Virus Unit, ID and BG Hospital Campus, GB-4, 1st Floor (East Wing), Beliaghata, Kolkata 700 010, India; email: runugc@hotmail.com
Table. Serum HBV DNA levels and amino acid variability in the partial
s gene, including the region encoding the major hydrophillic loop,
compared with consensus sequences *
Serum HBV DNA
(x [10.sup.3] 110 113 114
Isolate copies/mL) ([dagger]) ([dagger]) ([dagger])
Cn A -- I S T
Cn D -- - - S
Cn C -- L T S
IDU1 ND -- -- --
IDU2 ND -- -- --
IDU3 45.0 -- -- --
IDU4 14.0 L -- S
IDU5 1.05 L T S
IDU6 ND L T S
IDU7 ND L T S
IDU8 9.0 L T S
IDU9 ND L T S
IDU10 64.0 L T S
122 126 131 134
Isolate ([double dagger]) ([dagger]) ([dagger]) ([dagger])
Cn A K T N F
Cn D -- -- T Y
Cn C -- I T --
IDU1 -- -- -- --
IDU2 -- -- -- --
IDU3 -- -- T --
IDU4 -- I T --
IDU5 -- I - --
IDU6 -- I T --
IDU7 -- I T --
IDU8 -- I T --
IDU9 -- I T --
IDU10 -- I T --
143 145 159
Isolate ([dagger]) ([dagger]) ([dagger])
Cn A T G A
Cn D S -- G
Cn C S -- --
IDU1 S -- G
IDU2 - -- --
IDU3 S -- --
IDU4 S -- --
IDU5 S -- --
IDU6 S R --
IDU7 S R T
IDU8 S -- --
IDU9 S -- --
IDU10 S -- --
160 161 163
Isolate ([double dagger]) ([dagger]) ([dagger])
Cn A K Y W
Cn D -- F --
Cn C R F --
IDU1 -- F --
IDU2 -- F --
IDU3 -- F --
IDU4 R F --
IDU5 - F --
IDU6 R F R
IDU7 R F R
IDU8 R F --
IDU9 R F --
IDU10 R F --
* Indicated by Cn, followed by genotype. HBV, hepatitis B virus,
IDU, injection drug user; ND, not detectable by the assay.
([dagger]) Genotype-specific sites.
([double dagger]) Subtype-specific sites.
|
|
||||||||||||||||||||
Printer friendly
Cite/link
Email
Feedback
Reader Opinion