Antibiotic resistance and molecular characterization of shigella isolates recovered from children aged less than 5 years in Manhiça, Southern Mozambique
Introduction
According to the World Health Organization, diarrhoeal diseases remain among the most common and major causes of infant mortality in children in developing countries. Despite advances in understanding of the disease and management strategies, 0.75 million children die globally each year as a consequence of diarrhoea [1], and 165 million cases of dysentery each year are estimated to occur due to Shigella spp. [2]. More recent estimations place the disease burden of Shigella spp. at approximately 90 million episodes with 108 000 deaths per year [3], which is still high. The wide spread of this disease can be explained by the low infectious dose of the bacterium (10–100 cells) required to develop disease, direct person-to-person transmission, contaminated food and water transmission, and the low susceptibility of Shigella spp. to stomach acids [4]. In terms of clinical impact, shigella is the Enterobacteriaceae with the most serious outcome, with fever, abdominal cramps, and blood and mucus in the stools. The contribution of vectors, such as house flies, has also been assessed and may contribute to the spread of the disease [5].
The role of Shigella spp. as a cause of childhood diarrhoea in developing areas is probably the most recognized context in the epidemiology of shigellosis. A recently published 3-year, multi-centre, prospective, matched case–control study of moderate-to-severe diarrhea (MSD) [the Global Enteric Multicenter Study (GEMS)] [6] evaluated the cause and impact of diarrhoeal diseases in over 22 000 children under 5 years of age from seven different sites of Asia and Africa, including Mozambique. The study confirmed Shigella spp. among the top five important pathogens associated with childhood diarrhoea [6]. Furthermore, several other studies have reported shigella-associated diarrhoea in children living in areas with poor resources [7], [8], [9]. In developed countries, Shigella spp. have been isolated, especially during outbreaks of gastroenteritis following the ingestion of contaminated food or water [10], [11].
Four species of shigella including 50 serotypes are currently recognized; these are Shigella dysenteriae (15 serotypes), Shigella flexneri (15 serotypes), Shigella boydii (19 serotypes) and Shigella sonnei (one serotype) [12], among which S. flexneri and S. sonnei are responsible for endemic forms of disease and S. dysenteriae accounts for devastating epidemics [13]. Although the epidemiology of Shigella spp. may vary from region to region, S. sonnei is predominant in developed countries while S. flexneri is more common in less developed countries [14]. However, a change in trend has been reported in developing countries, where S. flexneri serotypes have been replaced by S. sonnei in areas undergoing economic development and improvements in hygiene [15], [16]. This supports the importance of continuous surveillance to track epidemiological changes in disease.
In addition to the diversity of Shigella spp., there is an increasing rate of antibiotic resistance to the most commonly used therapy (ampicillin, tetracycline, chloramphenicol, sulfonamides, sulphamethoxazole-trimethoprim and nalidixic acid) with the subsequent serious threat to patient management. This scenario has led to the use of more expensive new-generation antibiotics such as fluoroquinolones, although resistance to these agents has also been reported [17]. The rapid emergence of multi-drug-resistant (MDR) strains is largely due to their ability to acquire and disseminate exogenous genes associated with mobile genetic elements, such as transposons, integrons, plasmids and other genomic islands [18]. Thus, the ability to recognize and characterize MDR clones will favour the development of preventive measures for infection control. Although shigella infections have been reported previously in Mozambique [19], including data from GEMS [12], the molecular epidemiology and the impact of MDR of these infections on patient outcome remain unknown. Therefore, this study analysed the trends in antibiotic resistance and clonal relatedness of shigella isolates from children aged less than 5 years in Manhiça district, enrolled as part of GEMS from December 2007 to November 2012. With this information, it will be possible to evaluate the presence of a particular clone showing antibacterial resistance in the study area.
Section snippets
Study area
The study was conducted by the Manhiça Health Research Centre [Centro de Investigação em Saúde de Manhiça (CISM)] in Manhiça district, a rural area of Maputo province in southern Mozambique. Since 1996, CISM has been running a health demographic surveillance system (HDSS) for vital events and migrations in the population living within the study area, covering approximately 95 000 inhabitants. In 2014, the study area was expanded to the whole district, currently covering 183 000 inhabitants.
Species prevalence and antibiotic resistance
Among the 67 isolates analysed, three different Shigella spp. were found: S. flexneri (70.1%; 47/67), S. sonnei (23.9%; 16/67) and S. boydii (3%; 2/67). In addition, the species could not be identified for two isolates (3%). The most prevalent S. flexneri serotypes were 2a (38.3%; 18/47), 6 (19.1%; 9/47) and 1b (14.9%; 7/47). Antimicrobial resistance was observed for both cases and controls, with high rates for trimethoprim-sulfametoxazole (92.5%; 62/67), tetracycline (68.7%; 46/67),
Discussion
The present study characterized a collection of Shigella spp. recovered from a case–control study of diarrhoea in children aged less than five years in Manhiça district, southern Mozambique from 2007 to 2012. The findings demonstrate that the main burden of shigella infections is in children aged 1–5 years, with S. flexneri predominating compared with other species. This observation supports the idea that Shigella spp. are geographically stratified based on the level of economic development in
Acknowledgments
The authors wish to thank all the children and their parents for participating in the surveillance; clinicians, nurses and other staff from CISM and Manhiça District Hospital for collecting and processing the data; and the district health authorities and the Ministry of Health for their collaboration in the research activities ongoing in Manhiça district.
Funding: This study was supported, in part, through GEMS funded by the Bill and Melinda Gates Foundation. CISM receives core funds from the
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