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      Geographical distribution of risk factors for invasive non-typhoidal Salmonella at the subnational boundary level in sub-Saharan Africa

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          Abstract

          Background

          Invasive non-typhoidal Salmonella (iNTS) is a growing health-concern in many parts of sub-Saharan Africa. iNTS is associated with fatal diseases such as HIV and malaria. Despite high case fatality rates, the disease has not been given much attention. The limited number of population-based surveillance studies hampers accurate estimation of global disease burden. Given the lack of available evidence on the disease, it is critical to identify high risk areas for future surveillance and to improve our understanding of iNTS endemicity.

          Methods

          Considering that population-based surveillance data were sparse, a composite index called the iNTS risk factor (iNRF) index was constructed based on risk factors that commonly exist across countries. Four risk factors associated with the prevalence of iNTS were considered: malaria, HIV, malnutrition, and safe water. The iNRF index was first generated based on the four risk factors which were collected within a 50 km radius of existing surveillance sites. Pearson product-moment correlation was used to test statistical associations between the iNRF index and the prevalence of iNTS observed in the surveillance sites. The index was then further estimated at the subnational boundary level across selected countries and used to identify high risk areas for iNTS.

          Results

          While the iNRF index in some countries was generally low (i.e. Rwanda) or high (i.e. Cote d’Ivoire), the risk-level of iNTS was variable not only by country but also within a country. At the provincial-level, the highest risk area was identified in Maniema, the Democratic Republic of Congo, whereas Dakar in Senegal was at the lowest risk.

          Conclusions

          The iNRF index can be a useful tool to understand the geographically varying risk-level of iNTS. Given that conducting a population-based surveillance study requires extensive human and financial resources, identifying high risk areas for iNTS prior to a study implementation can facilitate an appropriate site-selection process in the future.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12879-021-06198-1.

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          Most cited references20

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          World Health Organization Estimates of the Global and Regional Disease Burden of 22 Foodborne Bacterial, Protozoal, and Viral Diseases, 2010: A Data Synthesis

          Background Foodborne diseases are important worldwide, resulting in considerable morbidity and mortality. To our knowledge, we present the first global and regional estimates of the disease burden of the most important foodborne bacterial, protozoal, and viral diseases. Methods and Findings We synthesized data on the number of foodborne illnesses, sequelae, deaths, and Disability Adjusted Life Years (DALYs), for all diseases with sufficient data to support global and regional estimates, by age and region. The data sources included varied by pathogen and included systematic reviews, cohort studies, surveillance studies and other burden of disease assessments. We sought relevant data circa 2010, and included sources from 1990–2012. The number of studies per pathogen ranged from as few as 5 studies for bacterial intoxications through to 494 studies for diarrheal pathogens. To estimate mortality for Mycobacterium bovis infections and morbidity and mortality for invasive non-typhoidal Salmonella enterica infections, we excluded cases attributed to HIV infection. We excluded stillbirths in our estimates. We estimate that the 22 diseases included in our study resulted in two billion (95% uncertainty interval [UI] 1.5–2.9 billion) cases, over one million (95% UI 0.89–1.4 million) deaths, and 78.7 million (95% UI 65.0–97.7 million) DALYs in 2010. To estimate the burden due to contaminated food, we then applied proportions of infections that were estimated to be foodborne from a global expert elicitation. Waterborne transmission of disease was not included. We estimate that 29% (95% UI 23–36%) of cases caused by diseases in our study, or 582 million (95% UI 401–922 million), were transmitted by contaminated food, resulting in 25.2 million (95% UI 17.5–37.0 million) DALYs. Norovirus was the leading cause of foodborne illness causing 125 million (95% UI 70–251 million) cases, while Campylobacter spp. caused 96 million (95% UI 52–177 million) foodborne illnesses. Of all foodborne diseases, diarrheal and invasive infections due to non-typhoidal S. enterica infections resulted in the highest burden, causing 4.07 million (95% UI 2.49–6.27 million) DALYs. Regionally, DALYs per 100,000 population were highest in the African region followed by the South East Asian region. Considerable burden of foodborne disease is borne by children less than five years of age. Major limitations of our study include data gaps, particularly in middle- and high-mortality countries, and uncertainty around the proportion of diseases that were foodborne. Conclusions Foodborne diseases result in a large disease burden, particularly in children. Although it is known that diarrheal diseases are a major burden in children, we have demonstrated for the first time the importance of contaminated food as a cause. There is a need to focus food safety interventions on preventing foodborne diseases, particularly in low- and middle-income settings.
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            The global burden of non-typhoidal salmonella invasive disease: a systematic analysis for the Global Burden of Disease Study 2017

            Summary Background Non-typhoidal salmonella invasive disease is a major cause of global morbidity and mortality. Malnourished children, those with recent malaria or sickle-cell anaemia, and adults with HIV infection are at particularly high risk of disease. We sought to estimate the burden of disease attributable to non-typhoidal salmonella invasive disease for the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017. Methods We did a systematic review of scientific databases and grey literature, and estimated non-typhoidal salmonella invasive disease incidence and mortality for the years 1990 to 2017, by age, sex, and geographical location using DisMod-MR, a Bayesian meta-regression tool. We estimated case fatality by age, HIV status, and sociodemographic development. We also calculated the HIV-attributable fraction and estimated health gap metrics, including disability-adjusted life-years (DALYs). Findings We estimated that 535 000 (95% uncertainty interval 409 000–705 000) cases of non-typhoidal salmonella invasive disease occurred in 2017, with the highest incidence in sub-Saharan Africa (34·5 [26·6–45·0] cases per 100 000 person-years) and in children younger than 5 years (34·3 [23·2–54·7] cases per 100 000 person-years). 77 500 (46 400–123 000) deaths were estimated in 2017, of which 18 400 (12 000–27 700) were attributable to HIV. The remaining 59 100 (33 300–98 100) deaths not attributable to HIV accounted for 4·26 million (2·38–7·38) DALYs in 2017. Mean all-age case fatality was 14·5% (9·2–21·1), with higher estimates among children younger than 5 years (13·5% [8·4–19·8]) and elderly people (51·2% [30·2–72·9] among those aged ≥70 years), people with HIV infection (41·8% [30·0–54·0]), and in areas of low sociodemographic development (eg, 15·8% [10·0–22·9] in sub-Saharan Africa). Interpretation We present the first global estimates of non-typhoidal salmonella invasive disease that have been produced as part of GBD 2017. Given the high disease burden, particularly in children, elderly people, and people with HIV infection, investigating the sources and transmission pathways of non-typhoidal salmonella invasive disease is crucial to implement effective preventive and control measures. Funding Bill & Melinda Gates Foundation.
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              Invasive non-typhoidal salmonella disease: an emerging and neglected tropical disease in Africa

              Summary Invasive strains of non-typhoidal salmonellae have emerged as a prominent cause of bloodstream infection in African adults and children, with an associated case fatality of 20–25%. The clinical presentation of invasive non-typhoidal salmonella disease in Africa is diverse: fever, hepatosplenomegaly, and respiratory symptoms are common, and features of enterocolitis are often absent. The most important risk factors are HIV infection in adults, and malaria, HIV, and malnutrition in children. A distinct genotype of Salmonella enterica var Typhimurium, ST313, has emerged as a new pathogenic clade in sub-Saharan Africa, and might have adapted to cause invasive disease in human beings. Multidrug-resistant ST313 has caused epidemics in several African countries, and has driven the use of expensive antimicrobial drugs in the poorest health services in the world. Studies of systemic cellular and humoral immune responses in adults infected with HIV have revealed key host immune defects contributing to invasive non-typhoidal salmonella disease. This emerging pathogen might therefore have adapted to occupy an ecological and immunological niche provided by HIV, malaria, and malnutrition in Africa. A good understanding of the epidemiology of this neglected disease will open new avenues for development and implementation of vaccine and public health strategies to prevent infections and interrupt transmission.
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                Author and article information

                Contributors
                jungseoklee@gmail.com
                vmogasale@ivi.int
                fmarks@ivi.int
                jerome.kim@ivi.int
                Journal
                BMC Infect Dis
                BMC Infect Dis
                BMC Infectious Diseases
                BioMed Central (London )
                1471-2334
                5 June 2021
                5 June 2021
                2021
                : 21
                : 529
                Affiliations
                GRID grid.30311.30, ISNI 0000 0000 9629 885X, International Vaccine Institute, SNU Research Park, ; 1 Gwanak-ro, Gwanak-gu, Seoul, 08226 South Korea
                Author information
                http://orcid.org/0000-0002-1038-8948
                Article
                6198
                10.1186/s12879-021-06198-1
                8180173
                34090380
                a31d6a89-d006-4bd1-a561-c1a4e89e91fd
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 11 March 2020
                : 17 May 2021
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2021

                Infectious disease & Microbiology
                invasive non-typhoidal salmonella,risk factors for ints,geographical variation of risk factors,composite index for ints risk factors

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