The changing epidemiology, clinical syndrome and antibiotic resistance patterns of shigellosis in Vietnamese children

Abstract

Diarrhoeal diseases remain the second most common cause of death among children under-five globally, following closely behind pneumonia. In developing countries, rotavirus and Shigella spp. are thought to be the most important enteropathogens causing acute childhood diarrhoea. Systematicd ata on diarrhoea)diseases. particularly Shigella infection, in southern Viet Nam is lacking. An analysis of the historical trends in epidemiology, antibiotic susceptibility, and clinical features of Shigella infection and contemporary clinical studies of the response to antibiotic treatment in Vietnamese children were the central aims of this thesis. By analysing Shigella strains isolated from children between 1995 and 2009 I documented a transition in the dominant Shigella species causing diarrhoea from S.flexneri to S.sonnei, a change previously linked with industrialisation and economic development. During the same period there was a sharp increase of nalidixic acid resistant Shigella strains from approximately 7% to 70%. In addition, the clinical presentation appeared to be more severe and the duration of hospital stays longer. During the course of this thesis I also documented for the first time in Viet Nam Shigella spp. which harboured the plasmid-transferable drug resistance blaCTX-M genes. The occurrence of this plasmid-transferable gene may endanger the use of betalactams for this infection in the future. In a large randomised controlled trial, gatifloxacin, a new 8-methoxy-fluoroquinolone antibiotic proved comparable to ciprofloxacin for the treatment of acute dysentery including those caused by multiresistant Shigella. Although gatifloxacin has been associated with dysglycaemic side-effects in adults, this adverse effect was not observed in this study