|
|
EDITORIAL |
|
|
|
Year : 2012 | Volume
: 44
| Issue : 1 | Page : 1-3 |
|
Trends in tropical medicine research in India
Krishnangshu Ray
Director, Calcutta School of Tropical Medicine, 108 CR Avenue, Kolkata - 700 073, India
Date of Web Publication | 14-Jan-2012 |
Correspondence Address: Krishnangshu Ray Director, Calcutta School of Tropical Medicine, 108 CR Avenue, Kolkata - 700 073 India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0253-7613.91857
How to cite this article: Ray K. Trends in tropical medicine research in India. Indian J Pharmacol 2012;44:1-3 |
Tropical diseases attacked more than one-fourth of the total population in the tropics during the nineteenth century. The tropical region is burdened with vast population, poor socio-economic resources and temperate climate which collectively expose the inhabitants to many etiological agents. In the good old days the research was exemplified by studies on parasites and vectors, and the emerging role of laboratory in the field of medical practice, teaching and research. Horizontal growth in Pharmacology research in the field of tropical medicine started its journey from 1920 onwards. Newly discovered molecule urea-stibamine was chosen for clinical efficacy and safety at the Calcutta School of Tropical Medicine (CSTM). This was followed by outstanding work of Col. RN Chopra on indigenous drugs, venoms, wasps and substance abuse. He pioneered the spread of research in medical, dental, pharmacy and veterinary colleges in India. The vertical growth in this area started from 1960 onwards by the establishment of centers at New Delhi, Lucknow, Mumbai, Varanasi, Chandigarh, Ahmedabad, Jaipur, Vadodara and Puducherry. This write up briefly attempts to reiterate the trends in tropical medicine research in India with a brief mention of some related issues.
With the passing away of UN Brahmachari, the secret formulation of urea-stibamine was lost. This inspired the researchers to develop alternatives like mycollin, amphotericin B, hamycin, acivin and their newer delivery models like liposome, miosome, microsphere and nanoparticles. [1] BHU Varanasi group could succeed to develop a five-day low dose therapy of amphotericin B. [2] CDRI, Lucknow, elicited the molecular mechanism of drug resistance by searching new drug targets by using the microarray technology. [3] The institute had also undertaken couple of drug development projects starting from identification of a new chemical entity and ending with phase III clinical trials and licensing. Antimalarial drug, artether, a rapidly acting schinzonticidal for chloroquine resistant malaria and primaquine analogue, elubaquin (compound 80/53), are a few examples. CDRI also developed an efficient process technology of anti-leprosy drug clofazimine, which was adopted by a multinational drug house. On the other hand, Haffkine Institute, Mumbai, has been producing lyophilized polyvalent antivenins against venoms of cobra, krait, Russel viper and Echis Carinatus snakes for last 56 years and anti-rabies vaccine for last 89 years. [3] Indigenous drugs like berberine and wild banana seeds were screened here by using rabbit cholera model. The Central Research Institute, Kasauli, has primarily conducted researches on immunobiologicals like vaccines and sera in accordance with the current GMP standards. The Pasteur Institute, Coonoor, manufactures DPT group of vaccines and BPL inactivated Rabies vaccine which are potent as well as cheap. The Pasteur Institute, Shillong, is a manufacturer of tetanus toxoid and its unique cold chain system is popular for preservation of EPI/UIP vaccines.
Out of 2.5 million reported cases of malaria in South East Asia, India contributes about 70%. [4] In 50s and 60s, the malaria control was successful due to global initiative program of WHO. The disease staged a reemergence from 1970 onwards possibly due to the appearance of new malaria ecotypes and antimalarial drug resistance. The first chloroquine resistance against Plasmodium falciparum was detected in 1973 which initiated National Vector Borne Disease Control Program (NVBDCP) in India. A breakthrough in malaria research came from the National Institute of Malaria Research (ICMR) by the introduction of artemisinin-chloroquine-trimethoprim (ACT) combination as the first line therapy. The NIMR is completely devoted for malaria research in India since 1977. A major interest of its research has been the usage of genomics and bioinformatics to study the interaction between host, parasite and vector. Some of this includes development of genetic and molecular markers, cytaxonomic studies of vector species, a study of the climate change and its impact on malaria by remote sensing, biolarvicides, drugs, insecticide impregnated bednets and diagnostic kits. [5] A study from CSTM had established the efficacy of chloroquine and sulphadoxine either alone or in combination before the introduction of ACT as first line therapy in uncomplicated falciparum malaria. [6] The molecular marker study of drug resistance could detect mutations in all patients. [7] Detailed studies on vector biology in the form of chromosomal analysis, enzymatic details and identification of molecular tools by using PCR-RFLP (restriction fragment length polymorphism) are in progress. [8] Insecticide resistance is also detected that may influence the National Malaria Control Program. [9] Future research could be targeted toward a comparative genome information of human malarial parasites and the genetic differences that could result in larger phenotypic differences. [10]
India is the highest tuberculosis burden country accounting for one fifth (21%) of the global incidence. It is 17 th among 22 high burden countries in terms of TB incidence rate. [11] Recent understanding of the molecular basis of drug resistance has led to the development of advanced methods to detect the mechanism of mutation. Phenotype methods include culturing M. tuberculosis in the presence of drugs and comparing the growth inhibition with that of drug-free controls. Genotype methods include di-deoxy fingerprinting, hybridization protection assay, PCR-heteroduplex formation and denaturing gradient gel electrophoresis. An automated molecular test for Mycobacterium and resistance to rifampicin (RIF) has been standardized by a multicountry study where India did participate significantly. This MTB/RIF test provides a sensitive detection of tuberculosis and rifampicin resistance directly from untreated sputum in less than 2 h with minimal hands-on time. [11] To combat the MDR-TB (rifampicin and INH) situation, additional drugs and strategies had led to "DOTS PLUS" program. Salient features of the strategy are individualized rather than the standardized treatment, facilities for improving on-site culture and susceptibility testing, reliable supplies of a wide range of expensive second line drugs, operational studies to monitor/evaluate the effect of this shift and adequate financial and technical support to international organizations. [12] Central TB Division (CTD), Government of India, has conducted a few operational research projects at the national level to ascertain the success and failure of RNTP and identify the modalities to reach out all TB patients in the country. [13],[14] The present interest on leprosy research in India is mainly based upon clinico-immuno-epidemiology, chemotherapy and prevention of disabilities. [15],[16] Identification of newer antigen markers, chemokines and cytokines are some of the notable advancements in leprosy research from JALMA (ICMR) Institute, Agra. [17] Multidrug (MDT) combination of rifampicin (900 mg) + moxifloxacin (400 mg) + cycloserine (1000 mg), once monthly, under supervision, bears good prospects in leprosy control program. Drug development research should target simpler regimen for better adherence and monitoring. Superior experimental models over the existing mouse foot-pad system need to be developed in future for urgent screening of bactericidal properties of newer anti-leprosy drugs. [18]
In the post-independence period, the Calcutta School of Tropical Medicine (CSTM) paved the way of research in tropical diseases as evidenced by its association with great scientists. Studies on anthelmintic property of cashew nut shell oil by PK Sanyal, antimony test by Col. RN Chopra and lepromin test by Dharmendra are some of them. [19] The popular rabbit ileal experiment was used to elicit the E. coli enterotoxin and detection of entero-invasive shigellosis by two bacteriologists, SN De and BD Chatterjee, during the diarrhea epidemic in Bengal. [20] The premier Virology department of the country could establish strain by strain difference of virulence and pathogenicity of dengue hemorrhagic fever and Chikungunya. Research projects on 'complementary medicine' supported by AYUSH are on progress to elicit the antiviral efficacy of homeopathic medicines. [21],[22] CSTM is the center of excellence for HIV research by NACO since 1980s and its major research priority is sero-surveillance of AIDS in various socio-economic groups. The School is the lone center in India for conducting the MD course in Tropical Medicine. From this year, DM in Clinical Pharmacology has also been initiated for the first time in the Eastern region.
Tropical medicine has emerged as an independent specialty. Its public health importance has been addressed by studying the sentinel cases, passive and active surveillance, antimicrobial resistance patterns, new drug developments and changes in vital statistics. In depth analysis of multidrug resistance cases by genetic sequencing and mutational studies bear the future prospects. Conserved functional genes between two species of microbes could be utilized in targeting common drugs and may act as a store house of information which could be a tool for effective disease control program. Advanced diagnostic tools like nucleic acid hybridization, nucleic acid amplification (PCR) and DNA microarray technology are necessary support systems. Some Indian laboratories are working on reverse molecular pharmacology and functional genomics in the form of cloning, expression of G-protein coupled receptors and development of peptide library. Commercial houses are interested in vaccine development by using recombinant biotechnology, nanotechnology and screening of interleukin-2 as antiviral agents. Initiatives to start the postgraduate courses in tropical medicine and infectious diseases at other centers are the need of the hour. A greater funding for tropical disease research (TDR) shall also produce the add-on effects.
» References | |  |
1. | Roy S. Discovery of urea stibamine by UN Brahmachari: A reappraisal. Sci Cult 1998;64:157-8.  |
2. | Roy S. Kala Azar: An Odyssey into the past. Sci Cult 1998;64:11-4.  |
3. | Roy S. Research in tropical diseases in India with special reference to leishmaniasis and filaria. In: Burma DP, Chakravorty M, editors. History of Science, philosophy and culture in Indian civilization. New Delhi: Pearson Longman; 2010. p. 33-66.  |
4. | Dash AP, Valecha N, Anvikar AR, Kumar A. Malaria in India: Challenges and opportunities. J Biosci 2008;33:583-92.  [PUBMED] [FULLTEXT] |
5. | Singh V, Mishra N, Awasthi G, Dash AP. Why is it important to study malaria epidemiology in India? Trends Parasitol 2009;25:453-7.  |
6. | Mullick S, Das S, Guha SK, Bera DK, Sengupta S, Roy D, et al. Efficacy of chloroquine and sulphadoxine-pyrimethamine either alone or in combination before introduction of ACT as first line therapy in uncomplicated Plasmodium falciparum malaria in Jalpaiguri district, West Bengal, India. Trop Med Int Health 2011;16:929-35.  |
7. | Shah NK, Dhillon GP, Dash AP, Arora U, Meshnick S, Valecha N. Antimalarial drug resistance of Plasmodium falciparum in India: Changes over time and space. Lancet Infect Dis 2011;11:57-64.  |
8. | Sharma VP. Fighting malaria in India. Curr Sci 1998;75:1127-40.  |
9. | Subbarao S. Responses of An. Culicifacies sibling species A and B to DDT and HCH in India implications in malaria control. Med Vet Entomol 1998;2:219-23.  |
10. | Das A, Sharma M, Gupta B, Dash AP. Plasmodium falciparum and Plasmodium vivax: So similar yet very difficult. Parasitol Res 2009;105:1169-71.  [PUBMED] [FULLTEXT] |
11. | Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, et al. Rapid molecular detection of tuberculosis and rifampicin resistance. N Engl J Med 2010;363:1005-15.  [PUBMED] [FULLTEXT] |
12. | TB India 2011, (Revised National Tuberculosis Control Programme) Annual Status Report, 2011. Available from: http://www.fbcindia.org. [Last Accessed on 2011 Sep 20].  |
13. | Sharma S, Sarin R, Khalid UK, Singla N, Sharma PP, Behera D. Clinical profile and treatment outcome of tuberculous lymhadenitis in children using DOTS strategy. Indian J Tuberc 2010;57:4-11.  [PUBMED] |
14. | Paramasivan CN, Rehman F, Wares F, Sundar Mohan N, Sundar S, Devi S, et al. First and second line drug resistance patterns among previously treated tuberculosis patients in India. Int J Tuberc Lung Dis 2010;14:243-6.  [PUBMED] [FULLTEXT] |
15. | Singal A, Mehta S, Pandhi D. Immune reconstitution inflammatory syndrome in an HIV seropositive leprosy patient. Lepr Rev 2006;77:76-80.  [PUBMED] |
16. | Sharma P, Mukherjee R, Talwar GP. Immunoprophylactic effects of the anti-leprosy Mw vaccine in household contacts of leprosy patients: Clinical field trials with a follow up of 8-10 years. Lepr Rev 2005;76:127-43.  |
17. | Katoch VM, Lavania M, Chauhan DS, Sharma R, Hirawati, Katoch K. Recent advances in molecular biology of leprosy. Indian J Lepr 2007;79:151-66.  [PUBMED] |
18. | Ji B, Perani C, Grosset JH. Bactericidal activities of combination of new drugs against Mycobacterium Leprae in nude mice. Antimirob Chemother 2009;40:393-9.  |
19. | Sanyal A, Patil PN. An autobiography of Pramode Kumar Sanyal. In: Patil PN, Gulati OD, Balaraman R, editors. Topics in the History of Pharmacology. Ahmedabad: BS Shah Prakashan; 2005. p. 341-6.  |
20. | Roy S. Research in tropical diseases in India with special reference to leishmaniasis and filaria. In: Burma DP, Chakravorty M, editors. History of science, philosophy and culture in Indian civilization. New Delhi: Pearson Longman; 2010. p. 56-8.  |
21. | Bandyopadhyay B, Das S, Sengupta M, Saha C, Das KC, Sarkar D, et al. Decreased intensity of Japanese Encephalitis virus infection in chick chorioallantoic membrane under influence of ultra-diluted belladonna extract. Am J Infect Dis 2010;2:24-8.  |
22. | Bandyopadhyay B, Das S, Sengupta M, Saha C, Bhattacharya N, Ravinder C, et al. Suckling mice of belladonna 200 fed mice mothers evade virulent Nakayama strain Japanese Encephalitis virus infection. Int J Micro Res 2011;2:252-7.  |
|
 |
|
|
|
|