Pathogen surveillance in the informal settlement, Kibera, Kenya, using a metagenomics approach

Autoři: Rene S. Hendriksen aff001;  Oksana Lukjancenko aff001;  Patrick Munk aff001;  Mathis H. Hjelmsø aff001;  Jennifer R. Verani aff002;  Eric Ng’eno aff004;  Godfrey Bigogo aff004;  Samuel Kiplangat aff004;  Traoré Oumar aff004;  Lasse Bergmark aff001;  Timo Röder aff001;  John C. Neatherlin aff002;  Onyango Clayton aff002;  Tine Hald aff001;  Susanne Karlsmose aff001;  Sünje J. Pamp aff001;  Barry Fields aff002;  Joel M. Montgomery aff002;  Frank M. Aarestrup aff001
Působiště autorů: National Food Institute, WHO Collaborating Center for Antimicrobial Resistance in Foodborne Pathogens and Genomics and European Union Reference Laboratory for Antimicrobial Resistance, Technical University of Denmark, Kgs. Lyngby, Denmark aff001;  Division of Global Health Protection, Center for Global Health, Centers for Disease Control and Prevention, Nairobi, Kenya aff002;  Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA, United States of America aff003;  Kenya Medical Research Institute, Center for Global Health Research (KEMRI-CGHR), Nairobi, Kenya aff004
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article



Worldwide, the number of emerging and re-emerging infectious diseases is increasing, highlighting the importance of global disease pathogen surveillance. Traditional population-based methods may fail to capture important events, particularly in settings with limited access to health care, such as urban informal settlements. In such environments, a mixture of surface water runoff and human feces containing pathogenic microorganisms could be used as a surveillance surrogate.


We conducted a temporal metagenomic analysis of urban sewage from Kibera, an urban informal settlement in Nairobi, Kenya, to detect and quantify bacterial and associated antimicrobial resistance (AMR) determinants, viral and parasitic pathogens. Data were examined in conjunction with data from ongoing clinical infectious disease surveillance.


A large variation of read abundances related to bacteria, viruses, and parasites of medical importance, as well as bacterial associated antimicrobial resistance genes over time were detected. Significant increased abundances were observed for a number of bacterial pathogens coinciding with higher abundances of AMR genes. Vibrio cholerae as well as rotavirus A, among other virus peaked in several weeks during the study period whereas Cryptosporidium spp. and Giardia spp, varied more over time.


The metagenomic surveillance approach for monitoring circulating pathogens in sewage was able to detect putative pathogen and resistance loads in an urban informal settlement. Thus, valuable if generated in real time to serve as a comprehensive infectious disease agent surveillance system with the potential to guide disease prevention and treatment. The approach may lead to a paradigm shift in conducting real-time global genomics-based surveillance in settings with limited access to health care.

Klíčová slova:

Antimicrobial resistance – Bacterial pathogens – Diarrhea – Disease surveillance – Infectious disease surveillance – Metagenomics – Sewage


1. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. (2012) Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380: 2095–2128. doi: 10.1016/S0140-6736(12)61728-0 23245604

2. Feikin DR, Olack B, Bigogo GM, Audi A, Cosmas L, Aura B, et al. (2011) The burden of common infectious disease syndromes at the clinic and household level from population-based surveillance in rural and urban Kenya. PLoS One 6: e16085. doi: 10.1371/journal.pone.0016085 21267459

3. Braden CR, Dowell SF, Jernigan DB, Hughes JM (2013) Progress in global surveillance and response capacity 10 years after severe acute respiratory syndrome. Emerg Infect Dis 19: 864–869. doi: 10.3201/eid1906.130192 23731871

4. Nieuwenhuijse DF, Koopmans MP (2017) Metagenomic Sequencing for Surveillance of Food- and Waterborne Viral Diseases. Front Microbiol 8:230. doi: 10.3389/fmicb.2017.00230 eCollection@2017.: 230. 28261185

5. World Health Organization (2003) Guidelines for environmental surveillance of poliovirus circulation.

6. Fernandez-Cassi X, Timoneda N, Martinez-Puchol S, Rusinol M, Rodriguez-Manzano J, Figuerola N, et al. (2018) Metagenomics for the study of viruses in urban sewage as a tool for public health surveillance. Sci Total Environ 618:870–880. doi: 10.1016/j.scitotenv.2017.08.249 Epub@2017 Nov 4.: 870–880. 29108696

7. Newell DG, Koopmans M, Verhoef L, Duizer E, Aidara-Kane A, Sprong H, et al. (2010) Food-borne diseases—the challenges of 20 years ago still persist while new ones continue to emerge. Int J Food Microbiol 139 Suppl 1: S3–15.

8. Aarestrup FM, Koopmans MG (2016) Sharing Data for Global Infectious Disease Surveillance and Outbreak Detection. Trends Microbiol 24: 241–245. doi: 10.1016/j.tim.2016.01.009 26875619

9. Pehrsson EC, Tsukayama P, Patel S, Mejia-Bautista M, Sosa-Soto G, Navarrete KM, et al. (2016) Interconnected microbiomes and resistomes in low-income human habitats. Nature 533: 212–216. doi: 10.1038/nature17672 27172044

10. Nordahl PT, Rasmussen S, Hasman H, Caroe C, Baelum J, Schultz AC, et al. (2015) Meta-genomic analysis of toilet waste from long distance flights; a step towards global surveillance of infectious diseases and antimicrobial resistance. Sci Rep 5:11444. doi: 10.1038/srep11444 26161690

11. Hendriksen RS, Munk P, Njage P, van Bunnik B, McNally L, Lukjancenko O, et al. (2019) Global monitoring of antimicrobial resistance based on metagenomics analyses of urban sewage. Nat Commun 10: 1124–08853. doi: 10.1038/s41467-019-08853-3 30850636

12. Hjelmso MH, Mollerup S, Jensen RH, Pietroni C, Lukjancenko O, Schultz AC, et al. (2019) Metagenomic analysis of viruses in toilet waste from long distance flights-A new procedure for global infectious disease surveillance. PLoS One 14: e0210368. doi: 10.1371/journal.pone.0210368 30640944

13. Scott AA, Misiani H, Okoth J, Jordan A, Gohlke J, Ouma G, Arrighi J, et al. (2017) Temperature and heat in informal settlements in Nairobi. PLoS One 12: e0187300. doi: 10.1371/journal.pone.0187300 29107977

14. Njuguna HN, Cosmas L, Williamson J, Nyachieo D, Olack B, Ochieng JB, et al. (2013) Use of population-based surveillance to define the high incidence of shigellosis in an urban slum in Nairobi, Kenya. PLoS One 8: e58437. doi: 10.1371/journal.pone.0058437 23505506

15. Akullian A, Ng'eno E, Matheson AI, Cosmas L, Macharia D, Fields B, et al. (2015) Environmental Transmission of Typhoid Fever in an Urban Slum. PLoS Negl Trop Dis 9: e0004212. doi: 10.1371/journal.pntd.0004212 26633656

16. Silas Kiruki (2006) Prevalence of multidrug resistant enteropathogenic bacteria causing diarrhea in Kibera community in Nairobi, Kenya. 1 2: 24–30.

17. Knudsen BE, Bergmark L, Munk P, Lukjancenko O, Prieme A, Aarestrup FM, et al. (2016) Impact of Sample Type and DNA Isolation Procedure on Genomic Inference of Microbiome Composition. mSystems 1: e00095–16. doi: 10.1128/mSystems.00095-16 27822556

18. Martin M (2016) Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet J 2011;17:10–2.

19. Petersen TN, Lukjancenko O, Thomsen MCF, Maddalena SM, Lund O, Moller AF, et al. (2017) MGmapper: Reference based mapping and taxonomy annotation of metagenomics sequence reads. PLoS One 12: e0176469. doi: 10.1371/journal.pone.0176469 28467460

20. Zankari E, Hasman H, Cosentino S, Vestergaard M, Rasmussen S, Lund O, et al. (2012) Identification of acquired antimicrobial resistance genes. J Antimicrob Chemother 67: 2640–2644. doi: 10.1093/jac/dks261 22782487

21. Majowicz SE, Musto J, Scallan E, Angulo FJ, Kirk M, O'Brien SJ, et al. (2010) The global burden of nontyphoidal Salmonella gastroenteritis. Clin Infect Dis 50(6): 882–889. doi: 10.1086/650733 20158401

22. Crump JA, Luby SP, Mintz ED (2004) The global burden of typhoid fever. Bull World Health Organ 82: 346–353. 15298225

23. Kotloff KL, Winickoff JP, Ivanoff B, Clemens JD, Swerdlow DL, Sansonetti PJ, et al. (1999) Global burden of Shigella infections: implications for vaccine development and implementation of control strategies. Bull World Health Organ 77(8): 651–666. 10516787

24. Murray CJ, Lopez AD (1997) Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study. Lancet 349: 1498–1504. doi: 10.1016/S0140-6736(96)07492-2 9167458

25. Wickham H. (2016) ggplot2: Elegant Graphics for Data Analysis. Springer; 2009.

26. R Core Team (2014) (2014) R: A language and enviroment for statistical computing. R Foundation for Statistical Computing

27. Hacek DM, Cordell RL, Noskin GA, Peterson LR (2004) Computer-assisted surveillance for detecting clonal outbreaks of nosocomial infection. J Clin Microbiol 42: 1170–1175. doi: 10.1128/JCM.42.3.1170-1175.2004 15004070

28. Munk P, Andersen VD, de Knegt L, Jensen MS, Knudsen BE, Lukjancenko O, et al. (2017) A sampling and metagenomic sequencing-based methodology for monitoring antimicrobial resistance in swine herds. J Antimicrob Chemother 72: 385–392. doi: 10.1093/jac/dkw415 28115502

29. Kazimierczak KA, Rincon MT, Patterson AJ, Martin JC, Young P, Flint HJ, et al. (2008) A new tetracycline efflux gene, tet(40), is located in tandem with tet(O/32/O) in a human gut firmicute bacterium and in metagenomic library clones. Antimicrob Agents Chemother 52: 4001–4009. doi: 10.1128/AAC.00308-08 18779355

30. Tate JE, Burton AH, Boschi-Pinto C, Parashar UD (2016) Global, Regional, and National Estimates of Rotavirus Mortality in Children <5 Years of Age, 2000–2013. Clin Infect Dis 62 Suppl 2:S96–S105. doi: 10.1093/cid/civ1013.: S96-S105 27059362

31. Jiang V, Jiang B, Tate J, Parashar UD, Patel MM (2010) Performance of rotavirus vaccines in developed and developing countries. Hum Vaccin 6: 532–542. doi: 10.4161/hv.6.7.11278 20622508

32. O'Ryan M, Giaquinto C, Benninghoff B (2015) Human rotavirus vaccine (Rotarix): focus on effectiveness and impact 6 years after first introduction in Africa. Expert Rev Vaccines 14: 1099–1112. doi: 10.1586/14760584.2015.1059282 26098566

33. Lamberti LM, Ashraf S, Walker CL, Black RE (2016) A Systematic Review of the Effect of Rotavirus Vaccination on Diarrhea Outcomes Among Children Younger Than 5 Years. Pediatr Infect Dis J 35: 992–998. doi: 10.1097/INF.0000000000001232 27254030

34. Shioda K, Cosmas L, Audi A, Gregoricus N, Vinje J, Parashar UD, et al. (2016) Population-Based Incidence Rates of Diarrheal Disease Associated with Norovirus, Sapovirus, and Astrovirus in Kenya. PLoS One 11: e0145943. doi: 10.1371/journal.pone.0145943 27116458

35. Meyer CT, Bauer IK, Antonio M, Adeyemi M, Saha D, Oundo JO, et al. (2015) Prevalence of classic, MLB-clade and VA-clade Astroviruses in Kenya and The Gambia. Virol J 12:78. doi: 10.1186/s12985-015-0299-z 25975198

36. Smits SL, Osterhaus AD, Koopmans MP (2016) Newly Identified Viruses in Human Gastroenteritis: Pathogens or Not? Pediatr Infect Dis J 35: 104–107. doi: 10.1097/INF.0000000000000950 26461227

37. Santos N, Mendes GS, Silva RC, Pena GA, Rojas M, Amorim AR, et al. (2015) Salivirus and aichivirus A infections in children with gastroenteritis in Brazil. Clin Microbiol Infect 21: 799–3.

38. Mmbaga BT, Houpt ER (2017) Cryptosporidium and Giardia Infections in Children: A Review. Pediatr Clin North Am 64: 837–850. doi: 10.1016/j.pcl.2017.03.014 28734513

39. Mbae CK, Nokes DJ, Mulinge E, Nyambura J, Waruru A, Kariuki S (2013) Intestinal parasitic infections in children presenting with diarrhoea in outpatient and inpatient settings in an informal settlement of Nairobi, Kenya. BMC Infect Dis 13:243. doi: 10.1186/1471-2334-13-243 23705776

40. Davis SM, Worrell CM, Wiegand RE, Odero KO, Suchdev PS, Ruth LJ, et al. (2014) Soil-transmitted helminths in pre-school-aged and school-aged children in an urban slum: a cross-sectional study of prevalence, distribution, and associated exposures. Am J Trop Med Hyg 91: 1002–1010. doi: 10.4269/ajtmh.14-0060 25157123

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2019 Číslo 10
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