1. Epidemiology and Global Health
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Effects of an urban sanitation intervention on childhood enteric infection and diarrhea in Maputo, Mozambique: a controlled before-and-after trial

  1. Jackie Knee
  2. Trent Sumner
  3. Zaida Adriano
  4. Claire Anderson
  5. Farran Bush
  6. Drew Capone
  7. Veronica Casmo
  8. David A Holcomb
  9. Pete Kolsky
  10. Amy MacDougall
  11. Evgeniya Molotkova
  12. Judite Monteiro Braga
  13. Celina Russo
  14. Wolf Peter Schmidt
  15. Jill Stewart
  16. Winnie Zambrana
  17. Valentina Zuin
  18. Rassul Nalá
  19. Oliver Cumming
  20. Joe Brown  Is a corresponding author
  1. London School of Hygiene and Tropical Medicine, United Kingdom
  2. Georgia Institute of Technology, United States
  3. WE Consult, Mozambique
  4. Instituto Nacional de Saúde, Mozambique
  5. University of North Carolina at Chapel Hill, United States
  6. Yale-NUS College, Singapore
Research Article
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Cite this article as: eLife 2021;10:e62278 doi: 10.7554/eLife.62278

Abstract

We conducted a controlled before-and-after trial to evaluate the impact of an onsite urban sanitation intervention on the prevalence of enteric infection, soil transmitted helminth re-infection, and diarrhea among children in Maputo, Mozambique. A non-governmental organization replaced existing poor-quality latrines with pour-flush toilets with septic tanks serving household clusters. We enrolled children aged 1-48 months at baseline and measured outcomes before and 12 and 24 months after the intervention, with concurrent measurement among children in a comparable control arm. Despite nearly exclusive use, we found no evidence that intervention affected the prevalence of any measured outcome after 12 or 24 months of exposure. Among children born into study sites after intervention, we observed a reduced prevalence of Trichuris and Shigella infection relative to the same age group at baseline (<2 years old). Protection from birth may be important to reduce exposure to and infection with enteric pathogens in this setting.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files and code have been provided for all analyses and specifically for Figure 1 and Tables 1, 2, and 3. Additionally, we have archived all data and code at Open Science Framework (https://osf.io/me2tx, DOI 17605/OSF.IO/ME2TX).

The following data sets were generated

Article and author information

Author details

  1. Jackie Knee

    Department of Disease Control, London School of Hygiene and Tropical Medicine, London, United Kingdom
    Competing interests
    Jackie Knee, As we have indicated on the ICMJE COI form, attached, this authors's time working on this study was funded in part by the study's funders, the United States Agency for International Development and the Bill and Melinda Gates Foundation..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0834-8488
  2. Trent Sumner

    School of Civil and Environmental Engineering, Georgia Institute of Technology, Atlanta GA, United States
    Competing interests
    Trent Sumner, As we have indicated on the ICMJE COI form, attached, this authors's time working on this study was funded in part by the study's funders, the United States Agency for International Development and the Bill and Melinda Gates Foundation..
  3. Zaida Adriano

    ltd, WE Consult, Maputo, Mozambique
    Competing interests
    Zaida Adriano, As we have indicated on the ICMJE COI form, attached, this authors's time working on this study was funded in part by the study's funders, the United States Agency for International Development and the Bill and Melinda Gates Foundation..
  4. Claire Anderson

    School of Civil and Environmental Engineering, Georgia Institute of Technology, Atlanta, United States
    Competing interests
    Claire Anderson, As we have indicated on the ICMJE COI form, attached, this authors's time working on this study was funded in part by the study's funders, the United States Agency for International Development and the Bill and Melinda Gates Foundation..
  5. Farran Bush

    School of Civil and Environmental Engineering, Georgia Institute of Technology, Atlanta GA, United States
    Competing interests
    Farran Bush, As we have indicated on the ICMJE COI form, attached, this authors's time working on this study was funded in part by the study's funders, the United States Agency for International Development and the Bill and Melinda Gates Foundation..
  6. Drew Capone

    School of Civil and Environmental Engineering, Georgia Institute of Technology, Atlanta GA, United States
    Competing interests
    Drew Capone, As we have indicated on the ICMJE COI form, attached, this authors's time working on this study was funded in part by the study's funders, the United States Agency for International Development and the Bill and Melinda Gates Foundation..
  7. Veronica Casmo

    Instituto Nacional de Saúde, Instituto Nacional de Saúde, Maputo, Mozambique
    Competing interests
    Veronica Casmo, As we have indicated on the ICMJE COI form, attached, this authors's time working on this study was funded in part by the study's funders, the United States Agency for International Development and the Bill and Melinda Gates Foundation..
  8. David A Holcomb

    Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, United States
    Competing interests
    David A Holcomb, As we have indicated on the ICMJE COI form, attached, this authors's time working on this study was funded in part by the study's funders, the United States Agency for International Development and the Bill and Melinda Gates Foundation..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4055-7164
  9. Pete Kolsky

    Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill NC, United States
    Competing interests
    Pete Kolsky, As we have indicated on the ICMJE COI form, attached, this authors's time working on this study was funded in part by the study's funders, the United States Agency for International Development and the Bill and Melinda Gates Foundation..
  10. Amy MacDougall

    Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom
    Competing interests
    No competing interests declared.
  11. Evgeniya Molotkova

    School of Biological Sciences, Georgia Institute of Technology, Atlanta GA, United States
    Competing interests
    Evgeniya Molotkova, As we have indicated on the ICMJE COI form, attached, this authors's time working on this study was funded in part by the study's funders, the United States Agency for International Development and the Bill and Melinda Gates Foundation..
  12. Judite Monteiro Braga

    Instituto Nacional de Saúde, Instituto Nacional de Saúde, Maputo, Mozambique
    Competing interests
    Judite Monteiro Braga, As we have indicated on the ICMJE COI form, attached, this authors's time working on this study was funded in part by the study's funders, the United States Agency for International Development and the Bill and Melinda Gates Foundation..
  13. Celina Russo

    School of Civil and Environmental Engineering, Georgia Institute of Technology, Atlanta GA, United States
    Competing interests
    Celina Russo, As we have indicated on the ICMJE COI form, attached, this authors's time working on this study was funded in part by the study's funders, the United States Agency for International Development and the Bill and Melinda Gates Foundation..
  14. Wolf Peter Schmidt

    Department of Disease Control, London School of Hygiene and Tropical Medicine, London, United Kingdom
    Competing interests
    Wolf Peter Schmidt, As we have indicated on the ICMJE COI form, attached, this authors's time working on this study was funded in part by the study's funders, the United States Agency for International Development and the Bill and Melinda Gates Foundation..
  15. Jill Stewart

    Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill NC, United States
    Competing interests
    Jill Stewart, As we have indicated on the ICMJE COI form, attached, this authors's time working on this study was funded in part by the study's funders, the United States Agency for International Development and the Bill and Melinda Gates Foundation..
  16. Winnie Zambrana

    School of Civil and Environmental Engineering, Georgia Institute of Technology, Atlanta GA, United States
    Competing interests
    Winnie Zambrana, As we have indicated on the ICMJE COI form, attached, this authors's time working on this study was funded in part by the study's funders, the United States Agency for International Development and the Bill and Melinda Gates Foundation..
  17. Valentina Zuin

    Division of Social Science, Yale-NUS College, Singapore, Singapore
    Competing interests
    No competing interests declared.
  18. Rassul Nalá

    Instituto Nacional de Saúde, Instituto Nacional de Saúde, Maputo, Mozambique
    Competing interests
    Rassul Nalá, As we have indicated on the ICMJE COI form, attached, this authors's time working on this study was funded in part by the study's funders, the United States Agency for International Development and the Bill and Melinda Gates Foundation..
  19. Oliver Cumming

    Department of Disease Control, London School of Hygiene and Tropical Medicine, London, United Kingdom
    Competing interests
    Oliver Cumming, As we have indicated on the ICMJE COI form, attached, this authors's time working on this study was funded in part by the study's funders, the United States Agency for International Development and the Bill and Melinda Gates Foundation..
  20. Joe Brown

    Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill NC, United States
    For correspondence
    joebrown@unc.edu
    Competing interests
    Joe Brown, As we have indicated on the ICMJE COI form, attached, this authors's time working on this study was funded in part by the study's funders, the United States Agency for International Development and the Bill and Melinda Gates Foundation..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5200-4148

Funding

Bill and Melinda Gates Foundation (OPP1137224)

  • Oliver Cumming
  • Joe Brown

United States Agency for International Development (GHS-A-00-09-00015-00)

  • Oliver Cumming
  • Joe Brown

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: The study protocol was approved by the Comité Nacional de Bioética para a Saúde (CNBS),Ministério da Saúde (333/CNBS/14), the Research Ethics Committee of the London School of Hygiene & Tropical Medicine (reference # 8345), and the Institutional Review Board of theGeorgia Institute of Technology (protocol # H15160).

Reviewing Editor

  1. Joseph Lewnard, University of California Berkeley, United States

Publication history

  1. Received: August 20, 2020
  2. Accepted: April 3, 2021
  3. Accepted Manuscript published: April 9, 2021 (version 1)
  4. Accepted Manuscript updated: April 15, 2021 (version 2)
  5. Version of Record published: May 14, 2021 (version 3)

Copyright

© 2021, Knee et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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Further reading

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    The human microbiome can protect against colonization with pathogenic antibiotic-resistant bacteria (ARB), but its impacts on the spread of antibiotic resistance are poorly understood. We propose a mathematical modelling framework for ARB epidemiology formalizing within-host ARB-microbiome competition, and impacts of antibiotic consumption on microbiome function. Applied to the healthcare setting, we demonstrate a trade-off whereby antibiotics simultaneously clear bacterial pathogens and increase host susceptibility to their colonization, and compare this framework with a traditional strain-based approach. At the population level, microbiome interactions drive ARB incidence, but not resistance rates, reflecting distinct epidemiological relevance of different forces of competition. Simulating a range of public health interventions (contact precautions, antibiotic stewardship, microbiome recovery therapy) and pathogens (Clostridioides difficile, methicillin-resistant Staphylococcus aureus, multidrug-resistant Enterobacteriaceae) highlights how species-specific within-host ecological interactions drive intervention efficacy. We find limited impact of contact precautions for Enterobacteriaceae prevention, and a promising role for microbiome-targeted interventions to limit ARB spread.

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    Background: Identifying environmentally responsive genetic loci where DNA methylation is associated with coronary heart disease (CHD) may reveal novel pathways or therapeutic targets for CHD. We conducted the first prospective epigenome-wide analysis of DNA methylation in relation to incident CHD in the Asian population.

    Methods: We did a nested case-control study comprising incident CHD cases and 1:1 matched controls who were identified from the 10-year follow-up of the China Kadoorie Biobank. Methylation level of baseline blood leukocyte DNA was measured by Infinium Methylation EPIC BeadChip. We performed the single cytosine-phosphate-guanine (CpG) site association analysis and network approach to identify CHD-associated CpG sites and co-methylation gene module.

    Results: After quality control, 982 participants (mean age 50.1 years) were retained. Methylation level at 25 CpG sites across the genome was associated with incident CHD (genome-wide false discovery rate [FDR] < 0.05 or module-specific FDR <0.01). One SD increase in methylation level of identified CpGs was associated with differences in CHD risk, ranging from a 47% decrease to a 118% increase. Mediation analyses revealed 28.5% of the excessed CHD risk associated with smoking was mediated by methylation level at the promoter region of ANKS1A gene (P for mediation effect = 0.036). Methylation level at the promoter region of SNX30 was associated with blood pressure and subsequent risk of CHD, with the mediating proportion to be 7.7% (P = 0.003) via systolic blood pressure and 6.4% (P = 0.006) via diastolic blood pressure. Network analysis revealed a co-methylation module associated with CHD.

    Conclusions: We identified novel blood methylation alterations associated with incident CHD in the Asian population and provided evidence of the possible role of epigenetic regulations in the smoking- and BP-related pathways to CHD risk.

    Funding: This work was supported by National Natural Science Foundation of China (81390544 and 91846303). The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (202922/Z/16/Z, 088158/Z/09/Z, 104085/Z/14/Z), grant (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904) from the National Key and Program of China, and Chinese Ministry of Science and Technology (2011BAI09B01).