Shambu Nath De Memorial Lecture 2002
Professor RC Mahajan, FNA, delivered Shambu Nath De Memorial Lecture on “Perspectives of Amoebiasis – Diagnosis & Drug Resistance” at

The artistes performing the dance recital
 

University of Guwahati, Guwahati on 19th
October 2005.

Professor Mahajan described in his lecture how parasitic diseases continue to be a major public health problem all over the world with associated high degree of mortality, morbidity & man day loss. WHO statistics put parasites as leading cause of death after HIV/AIDS and Tuberculosis. One out of 10 living persons suffer from one or more of seven major tropical diseases of which five are parasitic in nature.Amoebiasis caused by cytolytic enteric protozoan, E. histolytica, occurs world wide affecting nearly 500 million persons and is regarded as the second most important cause of death due to protozoal infection next to malaria morphologically similar E.dispar is nonpathogenic and does not require antiamoebic drugs to treat. By biochemical and molecular biological techniques, these two species can be differentiated.For intestinal infections, conventional microscopic stool examination continues to be best diagnostic approach. However, for extra-intestinal infections, indirect methods like amoebic antigen/antibody detection and molecular techniques have proved to be highly sensitive and specific both as diagnostic and prognostic tools. Judicious use of currently available very few antiamoebic drugs is important to avoid increased MIC value against the parasite & treatment failure because of drug resistance, which could seriously pose problem in controlling this disease. Development of new drugs and vaccine appear to be distant dream. Understanding the mechanism of drug resistance development is thus important. We have reported significantly higher IC50 value of all the four antiamoebic drugs, metronidazole, tinidazole, choroquine and emetine to the clinical isolates compared to the reference strain HM1:1MSS. E. histolytica has several features common with MDR phenotype described in mammalian tumor cells. These are cross resistance to unrelated drugs,increased efflux and decreased accumulation of radiolabelled drugs, reversal of resistance by calcium channel blockers and overexpression of 4.5 kb long mRNA homologous to the mammalian P glycoprotein. Six Pgps like genes have been cloned and sequenced. Entamoeba Pgps are more related to human and mouse Pgps. Differential gene expression has been detected in emetine resistant mutants. We have shown overexpression of MDR gene in resistant mutant with no mRNA expression in clinical E. histolytical & E. dispar isolates and known sensistieve strain suggesting thereby that more than one mechanism may be operating in E. histolytica for drug resistance development. Further studies to evaluate the MDR phenotype in clinical isolates are therefore desired.