. 2021 Aug;6(8):e005659.

doi: 10.1136/bmjgh-2021-005659.

The genomic epidemiology of multi-drug resistant invasive non-typhoidal Salmonella in selected sub-Saharan African countries

Se Eun Park^#^{1

2}, Duy Thanh Pham^#^{3

4}, Gi Deok Pak¹, Ursula Panzner¹, Ligia Maria Cruz Espinoza¹, Vera von Kalckreuth¹, Justin Im¹, Ondari D Mogeni¹, Heidi Schütt-Gerowitt^{1

5}, John A Crump^{6

7

8

9}, Robert F Breiman^{10

11}, Yaw Adu-Sarkodie^{12

13}, Ellis Owusu-Dabo^{12

13}, Raphaël Rakotozandrindrainy¹⁴, Abdramane Bassiahi Soura¹⁵, Abraham Aseffa¹⁶, Nagla Gasmelseed^{17

18}, Arvinda Sooka¹⁹, Karen H Keddy²⁰, Jürgen May^{21

22}, Peter Aaby^{23

24}, Holly M Biggs^{7

9}, Julian T Hertz^{7

9}, Joel M Montgomery¹⁰, Leonard Cosmas¹⁰, Beatrice Olack²⁵, Barry Fields¹⁰, Nimako Sarpong^{12

22}, Tsiriniaina Jean Luco Razafindrabe¹⁴, Tiana Mirana Raminosoa¹⁴, Leon Parfait Kabore²⁶, Emmanuel Sampo²⁶, Mekonnen Teferi¹⁶, Biruk Yeshitela¹⁶, Muna Ahmed El Tayeb¹⁷, Ralf Krumkamp^{21

22}, Denise Myriam Dekker^{21

22}, Anna Jaeger^{21

22}, Adama Tall²⁷, Amy Gassama^{27

28}, Aissatou Niang²⁷, Morten Bjerregaard-Andersen^{23

24}, Sandra Valborg Løfberg^{23

24}, Jessica Fung Deerin¹, Jin Kyung Park¹, Frank Konings¹, Megan E Carey²⁹, Sandra Van Puyvelde^{30

31

32}, Mohammad Ali^{1

33}, John Clemens^{1

34

35}, Gordon Dougan²⁹, Stephen Baker³⁶, Florian Marks¹

Affiliations

¹ International Vaccine Institute, Seoul, Republic of Korea.
² Graduate School of Public Health, Yonsei University, Seoul, Republic of Korea.
³ The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
⁴ Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
⁵ Institute of Medical Microbiology, University of Cologne, Cologne, Germany.
⁶ Centre for International Health, University of Otago, Dunedin, New Zealand.
⁷ Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina, USA.
⁸ Duke Global Health Institute, Duke University, Durham, North Carolina, USA.
⁹ Kilimanjaro Christian Medical Centre, Moshi, Tanzania.
¹⁰ Centers for Disease Control and Prevention, KEMRI Complex, Nairobi, Kenya.
¹¹ Global Health Institute, Emory University, Atlanta, Georgia, USA.
¹² Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
¹³ Kumasi Centre for Collaborative Research in Tropical Medicine, Kumasi, Ghana.
¹⁴ University of Antananarivo, Antananarivo, Madagascar.
¹⁵ Institut Supérieur des Sciences de la Population, University of Ouagadougou, Ouagadougou, Burkina Faso.
¹⁶ Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
¹⁷ Faculty of Medicine, University of Gezira, Wad Medani, Sudan.
¹⁸ Faculty of Science, University of Hafr Al Batin, Hafr Albatin, Saudi Arabia.
¹⁹ National Institute for Communicable Diseases, Johannesburg, South Africa.
²⁰ School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
²¹ Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
²² German Center for Infection Research, Braunschweig, Germany.
²³ Bandim Health Project, Bissau, Guinea-Bissau.
²⁴ Research Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark.
²⁵ Kenya Medical Research Institute, Nairobi, Kenya.
²⁶ Schiphra Hospital, Ouagadougou, Burkina Faso.
²⁷ Institute Pasteur de Dakar, Dakar, Senegal.
²⁸ Université Cheikh Anta Diop de Dakar, Dakar, Senegal.
²⁹ Department of Medicine, University of Cambridge, Cambridge, Cambridgeshire, UK.
³⁰ Medicine, Cambridge University, Cambridge, UK.
³¹ Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
³² Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
³³ Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
³⁴ International Centre for Diarrheal Disease Research, Dhaka, Bangladesh.
³⁵ University of California, Fielding School of Public Health, Los Angeles, California, USA.
³⁶ Department of Medicine, University of Cambridge, Cambridge, Cambridgeshire, UK sgb47@medschl.cam.ac.uk.

^# Contributed equally.

PMID: 34341020
PMCID: PMC8330565
DOI: 10.1136/bmjgh-2021-005659

The genomic epidemiology of multi-drug resistant invasive non-typhoidal Salmonella in selected sub-Saharan African countries

Se Eun Park et al. BMJ Glob Health. 2021 Aug.

. 2021 Aug;6(8):e005659.

doi: 10.1136/bmjgh-2021-005659.

Authors

Affiliations

¹ International Vaccine Institute, Seoul, Republic of Korea.
² Graduate School of Public Health, Yonsei University, Seoul, Republic of Korea.
³ The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
⁴ Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
⁵ Institute of Medical Microbiology, University of Cologne, Cologne, Germany.
⁶ Centre for International Health, University of Otago, Dunedin, New Zealand.
⁷ Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina, USA.
⁸ Duke Global Health Institute, Duke University, Durham, North Carolina, USA.
⁹ Kilimanjaro Christian Medical Centre, Moshi, Tanzania.
¹⁰ Centers for Disease Control and Prevention, KEMRI Complex, Nairobi, Kenya.
¹¹ Global Health Institute, Emory University, Atlanta, Georgia, USA.
¹² Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
¹³ Kumasi Centre for Collaborative Research in Tropical Medicine, Kumasi, Ghana.
¹⁴ University of Antananarivo, Antananarivo, Madagascar.
¹⁵ Institut Supérieur des Sciences de la Population, University of Ouagadougou, Ouagadougou, Burkina Faso.
¹⁶ Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
¹⁷ Faculty of Medicine, University of Gezira, Wad Medani, Sudan.
¹⁸ Faculty of Science, University of Hafr Al Batin, Hafr Albatin, Saudi Arabia.
¹⁹ National Institute for Communicable Diseases, Johannesburg, South Africa.
²⁰ School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
²¹ Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
²² German Center for Infection Research, Braunschweig, Germany.
²³ Bandim Health Project, Bissau, Guinea-Bissau.
²⁴ Research Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark.
²⁵ Kenya Medical Research Institute, Nairobi, Kenya.
²⁶ Schiphra Hospital, Ouagadougou, Burkina Faso.
²⁷ Institute Pasteur de Dakar, Dakar, Senegal.
²⁸ Université Cheikh Anta Diop de Dakar, Dakar, Senegal.
²⁹ Department of Medicine, University of Cambridge, Cambridge, Cambridgeshire, UK.
³⁰ Medicine, Cambridge University, Cambridge, UK.
³¹ Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
³² Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
³³ Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
³⁴ International Centre for Diarrheal Disease Research, Dhaka, Bangladesh.
³⁵ University of California, Fielding School of Public Health, Los Angeles, California, USA.
³⁶ Department of Medicine, University of Cambridge, Cambridge, Cambridgeshire, UK sgb47@medschl.cam.ac.uk.

^# Contributed equally.

PMID: 34341020
PMCID: PMC8330565
DOI: 10.1136/bmjgh-2021-005659

Abstract

Background: Invasive non-typhoidal Salmonella (iNTS) is one of the leading causes of bacteraemia in sub-Saharan Africa. We aimed to provide a better understanding of the genetic characteristics and transmission patterns associated with multi-drug resistant (MDR) iNTS serovars across the continent.

Methods: A total of 166 iNTS isolates collected from a multi-centre surveillance in 10 African countries (2010-2014) and a fever study in Ghana (2007-2009) were genome sequenced to investigate the geographical distribution, antimicrobial genetic determinants and population structure of iNTS serotypes-genotypes. Phylogenetic analyses were conducted in the context of the existing genomic frameworks for various iNTS serovars. Population-based incidence of MDR-iNTS disease was estimated in each study site.

Results: Salmonella Typhimurium sequence-type (ST) 313 and Salmonella Enteritidis ST11 were predominant, and both exhibited high frequencies of MDR; Salmonella Dublin ST10 was identified in West Africa only. Mutations in the gyrA gene (fluoroquinolone resistance) were identified in S. Enteritidis and S. Typhimurium in Ghana; an ST313 isolate carrying bla_CTX-M-15 was found in Kenya. International transmission of MDR ST313 (lineage II) and MDR ST11 (West African clade) was observed between Ghana and neighbouring West African countries. The incidence of MDR-iNTS disease exceeded 100/100 000 person-years-of-observation in children aged <5 years in several West African countries.

Conclusions: We identified the circulation of multiple MDR iNTS serovar STs in the sampled sub-Saharan African countries. Investment in the development and deployment of iNTS vaccines coupled with intensified antimicrobial resistance surveillance are essential to limit the impact of these pathogens in Africa.

Keywords: cross-sectional survey; epidemiology; medical microbiology; typhoid and paratyphoid fevers.

PubMed Disclaimer

Conflict of interest statement

Competing interests: None declared.

Figures

**Figure 1**
Geographical distribution of iNTS genotypes and serotypes in the sampled countries in sub-Saharan Africa. Different colours in the pie charts correspond to different sequence types and serovars of iNTS isolates in our study sites. The size of the pie charts corresponds to the numbers of isolates in each country. Countries coloured in grey highlight the study sites, while red and white circles indicate countries with and without MDR iNTS isolates, respectively.

**Figure 2**
Antimicrobial resistance genes and plasmids associated with iNTS isolates circulating in sampled sub-Saharan African countries. Midpoint-rooted maximum likelihood phylogenetic tree based on the core genes of iNTS isolates sequenced in this study and their corresponding metadata. The first column shows the sequence types in different colours. The second column corresponds to the countries where our iNTS isolates were detected. The remaining columns exhibit a heatmap of detected AMR genes and plasmid replicons. The tree scale bar indicates the number of substitutions per variable site.

**Figure 3**
Novel IncI1 virulence-resistance plasmid (pSEP) in an S. Enteritidis ST11 isolate. Plasmid comparison analyses between the novel virulence-resistance IncI1 plasmid pSEP (bottom) and the reference virulence IncF plasmid pSENV (top). The grey blocks show the BLASTn comparison between the two plasmids using the bl2seq feature from the web-based BLAST. Some annotations are added for both plasmids. Red-coloured arrows are genes associated with virulence and AMR. Blue-coloured arrows are genes associated with conjugation. Grey-coloured arrows correspond to plasmid replication and stability. Green-coloured genes are associated with transposon elements.

**Figure 4**
Phylogenetics of S. Typhimurium ST313 lineage II and S. Enteritidis ST11 in sub-Saharan Africa. (A) Maximum likelihood phylogenetic tree of S. Typhimurium-ST313 lineage II isolates from this study in the context of the sub-Saharan African continent; lineage I was pruned to enhance the visualisation of the tree. Red circles at the terminal leaves correspond to our study isolates. The first column shows different colour-coded countries from where all analysed isolates originate. The second column shows MDR and non-MDR isolates in red and grey, respectively. (B) Maximum likelihood phylogenetic tree of our S. Enteritidis-ST11 isolates in the global context of S. Enteritidis. Red circles at the terminal leaves correspond to our study isolates. The first and second columns show regions and resistant phenotypes in different colours. The tree scale bar indicates the number of substitutions per variable site.

See this image and copyright information in PMC

References

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The genomic epidemiology of multi-drug resistant invasive non-typhoidal Salmonella in selected sub-Saharan African countries

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The genomic epidemiology of multi-drug resistant invasive non-typhoidal Salmonella in selected sub-Saharan African countries

Authors

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Abstract

Conflict of interest statement

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