Shigellosis and enterotoxigenic Escherichia coli (ETEC)
Shigella and enterotoxigenic Escherichia coli (ETEC) are two of the leading causes of diarrhea worldwide, and, together, they account for at least one billion cases of diarrhea annually. Insufficient data exist, but conservative estimates suggest that, combined, these two bacteria are responsible for more than 15 percent of the approximately 500,000 child deaths due to diarrhea each year, as well as many deaths in older age groups. Repeated infections and symptomatic episodes due to these pathogens can also contribute to deficits in physical and cognitive development. Shigellosis and illness from ETEC usually follow the ingestion of contaminated food or water. Shigella can also be transferred by person-to-person contact. ETEC can be treated through rehydration therapy and, for travelers to ETEC-endemic areas, with antibiotics. Shigella can be treated with oral rehydration solution and antibiotics, although the rate of resistance to the most commonly used antibiotics is sharply on the rise. Currently, no licensed vaccines targeting Shigella or ETEC exist; however, vaccines against both bacteria are in development.
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Shigellosis and ETEC disease
- Shigella and ETEC are two of the leading causes of diarrhea worldwide. Insufficient data exist, but conservative estimates suggest that, combined, these two bacteria are responsible for more than 15 percent of the approximately 500,000 child deaths due to diarrhea each year. Millions more are hospitalized with these infections, which can lead to dehydration and malnutrition as well as impaired physical and cognitive development in young children.
- Results from the Global Enterics Multicenter Study (GEMS) confirmed that both ETEC and Shigella are among the top four pathogens causing moderate-to-severe diarrhea among children in Africa and South Asia. A recent reanalysis of GEMS samples using new, highly sensitive genetic analysis techniques indicate that the current disease burden estimates for Shigella- and ETEC-associated illness are likely to be significant underestimates of the true incidence of morbidity and mortality.
- Shigella and ETEC may also be important causes of diarrhea and dysentery in age groups older than 5 years, with an estimated 100 million episodes occurring annually among children and adolescents in the 5 to 14 year age group.
- Shigellosis is endemic worldwide and is responsible for millions of cases of severe dysentery annually, the overwhelming majority of which occur in children in the developing world. Additionally, it is a major illness among military personnel, and travelers from industrialized countries are also at risk.
- ETEC may be the first enteric illness encountered by many infants, and it causes several hundred million cases of diarrhea each year, mostly in children. Repeated ETEC infections among children in developing countries are not rare, and the peak incidence of ETEC diarrhea in these areas occurs in the first two years of life. ETEC is also the most common cause of travelers' diarrhea that affects individuals from industrialized countries visiting endemic areas.
- Based on estimates from the Institute of Health Metrics and Evaluation, Shigella and ETEC are responsible for 15 million “disability-adjusted life years” (DALYs) annually (16 percent of all diarrhea-associated DALYs) and 1.8 million “years lived with disability” (YLDs) annually (20 percent of diarrhea-associated YLDs).
- Shigella and ETEC infections usually follow the ingestion of contaminated food or water. Shigella can also be transferred by person-to-person contact. ETEC can be treated through rehydration therapy and, for travelers to ETEC-endemic areas, with antibiotics. Shigella can be treated with oral rehydration solution and antibiotics, although the rate of resistance to the most commonly used antibiotics is sharply on the rise.
Shigella and ETEC vaccines
- Prevention through vaccination is a critical part of the strategy to reduce the incidence and severity of diarrheal disease, particularly among children in low-resource settings.
- Both Shigella and ETEC have been longstanding World Health Organization targets for vaccine development, and sharp declines in age-specific diarrhea/dysentery attack rates for each pathogen indicate that natural immunity does develop following exposure; thus, vaccination to prevent disease should be feasible.
- Currently, no licensed vaccines targeting Shigella or ETEC exist. The development of vaccines against these infections has been hampered by technical constraints, insufficient support for coordination, and a lack of market forces for research and development.
- Most vaccine development efforts are taking place in the public sector or as research programs within biotechnology companies. Several vaccine candidates against Shigella and ETEC are currently in various phases of research and development, including a number of ongoing clinical trials.
- Another approach being investigated is the concept of a combined Shigella-ETEC vaccine, or potentially combining a Shigella or ETEC vaccine with another vaccine against a cause of diarrheal disease (like rotavirus). There may be advantages to this approach, such as the potential cost-effectiveness and easier logistics of introducing a combined vaccine instead of standalone products in low-resource countries. Given this, many of the major donors contributing to this field are also pursuing the development of combination vaccines that could address different causes of diarrheal disease at the same time.
Diarrheal disease is a leading cause of death in children in developing countries. In addition to Shigella and ETEC, there are many other pathogens that contribute to morbidity and mortality from diarrheal disease, including rotavirus, which is the leading viral cause of severe diarrheal disease in infants. Learn more about rotavirus.
- Bourgeois AL, Wierzba TF, Walker RI. Status of Vaccine Research and Development for Enterotoxigenic Escherichia coli.
- Global Burden of Disease Study Collaborators. Global Burden of Disease.
- Kotloff KL, Nataro JP, Blackwelder WC, et al. Burden and Aetiology of Diarrhoeal Disease in Infants and Young Children in Developing Countries (the Global Enteric Multicenter Study, GEMS): A Prospective, Case-Control Study.
- Lamberti LM, Bourgeois AL, Fischer-Walker CL, Black RE, Sack D. Estimating Diarrheal Illness and Death Attributable to Shigellae and Enterotoxigenic Escherichia coli Among Older Children, Adolescents and Adults in South Asia and Africa.
- Liu J, Platts-Mills JA, Juma J, et al. Use of Quantitative Molecular Diagnostic Methods to Identify Causes of Diarrhoea in Children: A Reanalysis of the GEMS Case-Control Study.
- Mani S, Wierzba T, Walker RI. Status of Vaccine Research and Development for Shigella.
- PATH. Innovation in Enteric Vaccine Development: Addressing Bacterial Causes of Diarrhea.
- Walker RI, Clifford A. Recommendations Regarding the Development of Combined Enterotoxigenic Eschericha coli and Shigella Vaccines for Infants.
Page last updated: December 2016.
Photo: PATH/Mike Wang.