The light of hope: focusing on shigella and ETEC infections
Authors: Karen H Keddy
Journal: The Lancet Global Health (2019)

“…the light of hope that once burned so brightly has faded as a dream of a summer night.”1Shiga K The trend of prevention, therapy, and epidemiology of dysentery since the discovery of its causative organism. 1936; 215: 1205-1211Google Scholar So commented Kiyoshi Shiga in 1936, regarding his dream of eradicating shigellosis. More than 100 years after Shiga first recognised the role of the eponymous bacterium causing dysentery, Karoun Bagamian and colleagues, in their Article in The Lancet Global Health,2Bagamian K Anderson J Muhib F et al.Heterogeneity in enterotoxigenic Escherichia coli and shigella infections in children under 5 years of age from 11 African countries: a subnational approach quantifying risk, mortality, morbidity, and stunting.Lancet Glob Health. 2019; (published online Nov 13)https://doi.org/10.1016/S2214-109X(19)30456-5Google Scholar have ambitiously modelled crucial features of risk, impact, and sequelae of two important diseases in children younger than 5 years of age—shigellosis and enterotoxigenic Escherichia coli (ETEC) diarrhoea—at a subnational level in 11 eastern and central sub-Saharan African countries. This information has the potential to foster highly focused programmes in addressing disease burdens due to these pathogens and provides a baseline against which programmatic success can be measured. Using data produced in-country from Demographic and Health Surveys (DHS), the authors developed a series of models to calculate morbidity, mortality, and childhood stunting at the provincial or administrative-unit level.2Bagamian K Anderson J Muhib F et al.Heterogeneity in enterotoxigenic Escherichia coli and shigella infections in children under 5 years of age from 11 African countries: a subnational approach quantifying risk, mortality, morbidity, and stunting.Lancet Glob Health. 2019; (published online Nov 13)https://doi.org/10.1016/S2214-109X(19)30456-5Google Scholar Generally, they found little heterogeneity in morbidity within the 11 countries studied, with the exception of Zimbabwe, where the number of annual episodes of moderate-to-severe diarrhoea in Mashonaland Central, which borders the capital city-province of Harare, was almost double the number in the city of Bulawayo (2879 episodes [947–4436] vs 1621 episodes [95% CI 534–2498] per 100 000 due to ETEC; and 3147 episodes [1059–4744] vs 1772 episodes [596–2672] per 100 000 due to shigella).2Bagamian K Anderson J Muhib F et al.Heterogeneity in enterotoxigenic Escherichia coli and shigella infections in children under 5 years of age from 11 African countries: a subnational approach quantifying risk, mortality, morbidity, and stunting.Lancet Glob Health. 2019; (published online Nov 13)https://doi.org/10.1016/S2214-109X(19)30456-5Google Scholar Conversely, clear differences were seen in the burden of subnational stunting in children attributable to both ETEC and shigella in most of the countries, with some interesting results: in the Democratic Republic of the Congo, the stunting rate in the capital, Kinshasa, was approximately half the national stunting rate (156 cases [51 245] vs 370 cases [121–580] per 100 000 due to ETEC; 205 cases [67–312] vs 486 cases [160–743] per 100 000 due to shigella), whereas in Mozambique, the northern areas had high stunting rates compared with Maputo province in the southwest, where the capital is situated and bordering South Africa.2Bagamian K Anderson J Muhib F et al.Heterogeneity in enterotoxigenic Escherichia coli and shigella infections in children under 5 years of age from 11 African countries: a subnational approach quantifying risk, mortality, morbidity, and stunting.Lancet Glob Health. 2019; (published online Nov 13)https://doi.org/10.1016/S2214-109X(19)30456-5Google Scholar Mortality rates in children younger than 5 years were generally comparable between the two pathogens at a provincial level, but showed variation within and between countries. Total mortality was highest in the Burundian province of Muramvya (28·5 deaths [95% CI 19·0–38·5] due to ETEC and 32·2 deaths [22·5–42·0] due to shigella per 100 000 vs a national average of 22·7 deaths [15·1–30·6] and 25·7 deaths [17·9–33·5], respectively). Great variation in total mortality was noted in Mozambique, being highest in Cabo Delgado (19·8 deaths [13·1–26·7] due to ETEC and 22·4 deaths [15·5–29·4] due to shigella per 100 000 vs a national average of 9·9 deaths [6·5–13·4] and 11·4 deaths [7·8–15·0], respectively).2Bagamian K Anderson J Muhib F et al.Heterogeneity in enterotoxigenic Escherichia coli and shigella infections in children under 5 years of age from 11 African countries: a subnational approach quantifying risk, mortality, morbidity, and stunting.Lancet Glob Health. 2019; (published online Nov 13)https://doi.org/10.1016/S2214-109X(19)30456-5Google Scholar Against a calculated global mortality of 3·0 deaths per 100 000 for ETEC and 10·1 per 100 000 for shigella,3Khalil IA Troeger C Blacker BF et al.Morbidity and mortality due to shigella and enterotoxigenic Escherichia coli diarrhoea: the Global Burden of Disease Study 1990–2016.Lancet Infect Dis. 2018; 18: 1229-1240Google Scholar these results emphasise the vulnerability of children younger than 5 years in these provinces and countries generally. Bearing in mind the obvious constraints associated with modelling and interpreting such data,4Lanata CF Black RE Estimating the true burden of an enteric pathogen: enterotoxigenic Escherichia coli and Shigella spp.Lancet Infect Dis. 2018; 18: 1165-1166Google Scholar the question now is how to turn the data into action. For a cost-effective vaccine rollout for ETEC and shigella, a threshold must be attained, limiting vaccines to countries where the incremental cost-effectiveness ratio (ICER; the aggregated country-level incremental costs associated with each vaccine introduction proportional to the aggregated country-level health benefit) is less than the country-level gross domestic product.5Anderson JD Bagamian KH Muhib F et al.Potential impact and cost-effectiveness of future ETEC and Shigella vaccines in 79 low- and lower middle-income countries.Vaccine X. 2019; 2100024Google Scholar Over a 10-year period, an ICER of US$1061 per disability-adjusted life-year (DALY) for ETEC and $1002 per DALY for shigella in the WHO-defined AFRO region should then be achieved, dependent predominantly on vaccine costs, among other factors.5Anderson JD Bagamian KH Muhib F et al.Potential impact and cost-effectiveness of future ETEC and Shigella vaccines in 79 low- and lower middle-income countries.Vaccine X. 2019; 2100024Google Scholar Two countries in this study, Mozambique and Kenya, have respective household costs of approximately $5 and $15, respectively, calculated per childhood diarrhoeal episode for either pathogen.6Zimmermann M Kotloff K Nasrin D et al.Household costs of diarrhea by etiology in 7 countries, the Global Enterics Multicenter Study (GEMS).Open Forum Infect Dis. 2019; 6ofz150Google Scholar Despite this, a previous analysis in Bangladesh,7Arvelo W Blum LS Nahar N et al.Community perceptions of bloody diarrhoea in an urban slum in South Asia: implications for introduction of a Shigella vaccine.Epidemiol Infect. 2011; 139: 599-605Google Scholar where the household costs lie between those of Kenya and Mozambique,6Zimmermann M Kotloff K Nasrin D et al.Household costs of diarrhea by etiology in 7 countries, the Global Enterics Multicenter Study (GEMS).Open Forum Infect Dis. 2019; 6ofz150Google Scholar suggested that households would not be prepared to pay more than $0·15 per vaccine—less than 1% of the median weekly household income.7Arvelo W Blum LS Nahar N et al.Community perceptions of bloody diarrhoea in an urban slum in South Asia: implications for introduction of a Shigella vaccine.Epidemiol Infect. 2011; 139: 599-605Google Scholar Since the 11 countries studied are eligible for support from Gavi, the Vaccine Alliance,8GAVIEligibility. 2019.https://www.gavi.org/support/sustainability/eligibilityDate accessed: October 31, 2019Google Scholar these concerns might be negligible, should vaccines become available. To reduce the combined burden of shigella and ETEC, modalities besides vaccination must be considered. Other interventions have been shown to significantly affect overall diarrhoea mortality rates in children younger than 5 years. The 20% of countries that showed the greatest decrease in diarrhoeal mortality in children younger than 5 years benefited most from improvements in childhood undernutrition, whereas water, sanitation, and hygiene interventions benefited those 20% of countries that showed the next greatest decrease.9GBD 2017 Diarrhoeal Disease CollaboratorsQuantifying risks and interventions that have affected the burden of diarrhoea among children younger than 5 years: an analysis of the Global Burden of Disease Study 2017.Lancet Infect Dis. 2019; (published online Oct 30)https://doi.org/10.1016/S1473-3099(19)30401-3Google Scholar Shiga concluded his monograph by stating that “We believe that the suppression of intestinal infectious diseases like typhoid and dysentery must rely upon the progress of modern public health practices. Here we find a beam of light directing us toward the goal which I had sought many years ago”.1Shiga K The trend of prevention, therapy, and epidemiology of dysentery since the discovery of its causative organism. 1936; 215: 1205-1211Google Scholar Recent analysis of census data has shown that, despite an overall decline in all-cause national mortality in children younger than 5 years in low-to-middle-income countries, subnational inequalities remained between 2000 and 2017 and were comparatively consistent over the study period,10Burstein R Henry NJ Collison ML et al.Mapping 123 million neonatal, infant and child deaths between 2000 and 2017.Nature. 2019; 574: 353-358Google Scholar arguing generally for in-country attention to underserved areas. Bagamian and colleagues have highlighted where public health practices need to be enhanced at a subnational level in 11 African countries, while vaccines for ETEC and shigella are awaited. Once these vaccines are available, the question of whether these vaccines should be rolled out nationally or first in areas of greatest need will require further analysis and debate. I declare no competing interests. Heterogeneity in enterotoxigenic Escherichia coli and shigella infections in children under 5 years of age from 11 African countries: a subnational approach quantifying risk, mortality, morbidity, and stuntingUnderstanding the indirect mortality and morbidity of diarrhoeal pathogens on a subnational level will strengthen disease control strategies and could have important implications for the relative impact and cost-effectiveness of new enteric vaccines. Because our methods rely on publicly available data, they could be employed for national planning. Full-Text PDF Open Access