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Molecular surveillance of hepatitis and tuberculosis infections in a cohort exposed to methyl isocyanate

  • Original Papers
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International Journal of Occupational Medicine and Environmental Health

Abstract

Objective

The potential toxic effects on the immune system exerted by occupational and accidental environmental exposures and underlying molecular regulatory mechanisms involved in the etiology and progression of infectious diseases are now being characterized. The Bhopal gas tragedy is undoubtedly one of the worst industrial disasters in the history of mankind. After 25 years of accidental exposure to methyl isocyanate (MIC), severe systemic ailments still continue to preoccupy the lives of the affected population that survived this tragedy. We have performed a molecular surveillance study to characterize hepatitis and tuberculosis infections amongst the first and the second generation of survivors exposed to MIC.

Materials and Methods

Both outdoor and indoor patients referred for molecular diagnosis of hepatitis B virus (HBV), hepatitis C virus (HCV) and Mycobacterium tuberculosis (MTB) were examined. Qualitative analysis for HBsAg, anti-HBc, anti-HCV through ELISA was performed, while BacT/ALERT and Ziehl-Neelson technique were utilized for the assessment of tuberculosis. Detection and quantification of viral and bacterial nucleic acid and characterization of hepatitis genotypes were analyzed using real-time and end-point PCR techniques.

Results

The results suggest that HBV infections are most common among the MIC-exposed cohort, followed by extra-pulmonary and pulmonary MTB and HCV infections. Genotype 3 is the most prevalent HCV genotype among the survivors. Failure to detect HBsAg, anti-HBc and anti-HCV through ELISA, and tuberculosis by culture and Ziehl-Neelson stain, indicates higher prevalence of occult hepatitis and latent tuberculosis in the affected population.

Conclusions

Our study underscores the importance of hospital-based records used as a data source for monitoring possible environmental health hazards. As the risk of progress of infection is often influenced by conditions and periods of environmental chemical exposure, therefore, insights of interconnected molecular pathways will further illuminate the gene-environment association and might offer valuable information for rational drug design.

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References

  1. Crinnion WJ. Environmental medicine, part one: the human burden of environmental toxins and their common health effects. Altern Med Rev 2000;5:52–63.

    PubMed  CAS  Google Scholar 

  2. Inadera H. The immune system as a target for environmental chemicals: Xenoestrogens and other compounds. Toxicol Lett 2006;164:191–206.

    Article  PubMed  CAS  Google Scholar 

  3. Faust F, Kassie F, Knasmüller S, Kevekordes S, Mersch-Sundermann V. Use of primary blood cells for the assessment of exposure to occupational enotoxicants in human biomonitoring studies. Toxicology 2004;198:341–350.

    Article  PubMed  CAS  Google Scholar 

  4. Battershill JM, Burnett K, Bull S. Factors affecting the incidence of genotoxicity biomarkers in peripheral blood lymphocytes: impact on design of biomonitoring studies. Mutagenesis 2008;23:423–437.

    Article  PubMed  CAS  Google Scholar 

  5. Coronas MV, Pereira TS, Rocha JA, Lemos AT, Fachel JM, Salvadori DM, et al. Genetic biomonitoring of an urban population exposed to mutagenic airborne pollutants. Environ Int 2009;35:1023–1029.

    Article  PubMed  CAS  Google Scholar 

  6. Mishra PK, Samartha RS, Pathak N, Jain SK, Banerjee S, Maudar KK. Bhopal gas tragedy: review of clinical and experimental findings after 25 years. Int J Occup Med Environ Health 2009;22:193–202. DOI 10.2478/v10001-009-0028-1.

    Article  PubMed  Google Scholar 

  7. Crabb C. Revisiting the Bhopal tragedy. Science 2004;306:1670–1671.

    Article  PubMed  CAS  Google Scholar 

  8. Mishra PK, Gorantla VR, Akhtar N, Tamrakar P, Jain SK, Maudar KK. Analysis of cellular response to isocyanate using N-succinimidyl N-methylcarbamate exposure in cultured mammalian cells. Environ Mol Mutagen 2009;50:328–336.

    Article  PubMed  CAS  Google Scholar 

  9. Mishra PK, Raghuram GV, Panwar H, Jain D, Pandey H, Maudar KK. Mitochondrial oxidative stress elicits chromosomal instability after exposure to isocyanates in human kidney epithelial cells. Free Radic Res 2009;43:718–728.

    Article  PubMed  CAS  Google Scholar 

  10. Mishra PK, Bhargava A, Raghuram GV, Jatawa SK, Akhtar N, Khan S, et al. Induction of genomic instability in cultured human colon epithelial cells following exposure to isocyanates. Cell Biol Int 2009;33:675–683.

    Article  PubMed  CAS  Google Scholar 

  11. Mishra PK, Bhargava A, Raghuram GV, Gupta S, Tiwari S, Upadhyaya R, et al. Inflammatory response to isocyanates and onset of genomic instability in cultured human lung fibroblasts. Genet Mol Res 2009;8:129–143.

    Article  PubMed  CAS  Google Scholar 

  12. Raghuram GV, Pathak N, Jain D, Panwar H, Pandey H, Mishra PK, et al. Molecular mechanisms of isocyanate induced oncogenic transformation in ovarian epithelial cells. Rep Toxicol 2010;30:377–386.

    Article  CAS  Google Scholar 

  13. Sriramachari S, Chandra H. The lessons of Bhopal [toxic] MIC gas disaster scope for expanding global biomonitoring and environmental specimen banking. Chemosphere 1997;34:2237–2250.

    Article  PubMed  CAS  Google Scholar 

  14. Mishra PK, Jatawa SK, Raghuram GV, Pathak N, Jain A, Tiwari A, et al. Correlation of aberrant expression of p53, Rad50, and cyclin-E proteins with microsatellite instability in gallbladder adenocarcinomas. Genet Mol Res 2009;8:1202–1210.

    Article  PubMed  CAS  Google Scholar 

  15. Mishra PK, Panwar H, Bhargava A, Gorantla VR, Jain SK, Banerjee S, et al. Isocyanates induces DNA damage, apoptosis, oxidative stress, and inflammation in cultured human lymphocytes. J Biochem Mol Toxicol 2008;22:429–440.

    Article  PubMed  CAS  Google Scholar 

  16. Mishra PK, Khan S, Bhargava A, Panwar H, Banerjee S, Jain SK, et al. Regulation of isocyanate-induced apoptosis, oxidative stress, and inflammation in cultured human neutrophils: Isocyanate-induced neutrophils apoptosis. Cell Biol Toxicol 2010;26:279–291.

    Article  PubMed  CAS  Google Scholar 

  17. Balmes J, Rempel D, Alexander M, Reiter R, Harrison R, Bernard B, et al. Hospital records as a data source for occupational disease surveillance: a feasibility study. Am J Ind Med 1992;21:341–351.

    Article  PubMed  CAS  Google Scholar 

  18. Mishra PK, Bhargava A, Punde RP, Pathak N, Desikan P, Jain A, et al. Diagnosis of gastrointestinal tuberculosis: combining cytomorphology, microbiology, immunology & molecular techniques — a study from Central India. Ind J Clin Biochem 2010;25:68–73.

    Article  Google Scholar 

  19. Mishra PK, Gorantla VR, Bhargava A, Varshney S, Vashistha P, Maudar KK. Molecular detection of Mycobacterium tuberculosis in formalin-fixed, paraffin-embedded tissues and bio psies of gastrointestinal specimens using real-time polymerase chain reaction system. Turk J Gastroenterol 2010;21:129–134.

    PubMed  Google Scholar 

  20. Khan S, Bhargava A, Pathak N, Maudar KK, Varshney S, Mishra PK. Circulating biomarkers and their possible role in pathogenesis of chronic hepatitis B and C viral infections. Ind J Clin Biochem. In press 2011. DOI 10.1007/s12291-010-0098-7.

  21. Bhargava A, Khan S, Panwar H, Pathak N, Punde RP, Varshney S, et al. Occult hepatitis B virus infection with low viremia induces DNA damage, apoptosis and oxidative stress in peripheral blood lymphocytes. Virus Res 2010;153:143–150.

    Article  PubMed  CAS  Google Scholar 

  22. Mishra PK, Bhargava A, Khan S, Pathak N, Punde RP, Varshney S. Prevalence of hepatitis C virus genotypes and impact of T helper cytokines in achieving sustained virological response during combination therapy: a study from Central India. Indian J Med Microbiol 2010;28:358–362.

    Article  PubMed  CAS  Google Scholar 

  23. Black H. Bringing the Bugs Back In: Environmental Health Research Model Combines Toxicology and Infectious Disease. Environ Health Perspect 2010;118:a353.

    Article  PubMed  Google Scholar 

  24. Rieder HL. Socialization patterns are key to the transmission dynamics of tuberculosis. Int J Tuberc Lung Dis 1999;3:177–178.

    PubMed  CAS  Google Scholar 

  25. Pokhrel AK, Bates MN, Verma SC, Joshi HS, Sreeramareddy CT, Smith KR. Tuberculosis and indoor biomass and kerosene use in Nepal: a case-control study. Environ Health Perspect 2010;118:558–564.

    Article  PubMed  CAS  Google Scholar 

  26. Mishra PK, Dabadghao S, Modi G, Desikan P, Jain A, Mittra I, et al. In-utero exposure to methyl isocyanate in the Bhopal gas disaster: evidence of persisting hyper-activation of immune system two decades later. Occup Environ Med 2009;66:279.

    Article  PubMed  CAS  Google Scholar 

  27. Bhargava A, Punde RP, Pathak N, Dabadghao S, Desikan P, Mishra PK, et al. Status of inflammatory biomarkers in the population that survived the Bhopal gas tragedy: a study after two decades. Ind Health 2010;48:204–208.

    Article  PubMed  CAS  Google Scholar 

Download references

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Authors and Affiliations

  1. India Research Wing Bhopal Memorial Hospital & Research Centre, Bhopal, India

    Pradyumna K. Mishra, Arpit Bhargava, Neelam Pathak & Rahul Shrivastava

  2. India Division of Translational Research, Tata Memorial Centre, ACTREC, Navi, Mumbai, India

    Pradyumna K. Mishra & Arpit Bhargava

  3. India Department of Microbiology, Bhopal Memorial Hospital & Research Centre, Bhopal, India

    Prabha Desikan

  4. Department of Surgical & Medical Gastroenterology, Bhopal Memorial Hospital & Research Centre, Bhopal, India

    Kewal K. Maudar & Subodh Varshney

  5. Department of Bioinformatics, Maulana Azad National Institute of Technology, Bhopal, India

    Rahul Shrivastava

  6. Department of Pathology, Bhopal Memorial Hospital & Research Centre, Bhopal, India

    Aruna Jain

  7. Scientific Officer — E, Division of Translational Research, Tata Memorial Centre, ACTREC, Navi Mumbai, 410 210, India

    Pradyumna K. Mishra

Authors
  1. Pradyumna K. Mishra
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  2. Arpit Bhargava
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  3. Neelam Pathak
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  5. Kewal K. Maudar
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  8. Aruna Jain
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Correspondence to Pradyumna K. Mishra.

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Mishra, P.K., Bhargava, A., Pathak, N. et al. Molecular surveillance of hepatitis and tuberculosis infections in a cohort exposed to methyl isocyanate. IJOMEH 24, 94–101 (2011). https://doi.org/10.2478/s13382-011-0006-2

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  • DOI: https://doi.org/10.2478/s13382-011-0006-2

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