7
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Genomics of Ocular Chlamydia trachomatis After 5 Years of SAFE Interventions for Trachoma in Amhara, Ethiopia

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          To eliminate trachoma as a public health problem, the World Health Organization recommends the SAFE (surgery, antibiotics, facial cleanliness, and environmental improvement) strategy. As part of the SAFE strategy in the Amhara Region, Ethiopia, the Trachoma Control Program distributed >124 million doses of antibiotics between 2007 and 2015. Despite this, trachoma remained hyperendemic in many districts and a considerable level of Chlamydia trachomatis ( Ct) infection was evident.

          Methods

          We utilized residual material from Abbott m2000 Ct diagnostic tests to sequence 99 ocular Ct samples from Amhara and investigated the role of Ct genomic variation in continued transmission of Ct.

          Results

          Sequences were typical of ocular Ct at the whole-genome level and in tissue tropism–associated genes. There was no evidence of macrolide resistance in this population. Polymorphism around the ompA gene was associated with village-level trachomatous inflammation–follicular prevalence. Greater ompA diversity at the district level was associated with increased Ct infection prevalence.

          Conclusions

          We found no evidence for Ct genomic variation contributing to continued transmission of Ct after treatment, adding to evidence that azithromycin does not drive acquisition of macrolide resistance in Ct. Increased Ct infection in areas with more ompA variants requires longitudinal investigation to understand what impact this may have on treatment success and host immunity.

          Abstract

          Whole-genome sequencing of ocular Chlamydia trachomatis from Amhara, Ethiopia, found no evidence of macrolide resistance, despite 5 years of trachoma control interventions, including mass distribution of azithromycin. Polymorphisms in ompA were associated with prevalence of ocular infection and trachomatous disease.

          Related collections

          Most cited references52

          • Record: found
          • Abstract: found
          • Article: not found

          Polymorphisms in Chlamydia trachomatis tryptophan synthase genes differentiate between genital and ocular isolates.

          We previously reported that laboratory reference strains of Chlamydia trachomatis differing in infection organotropism correlated with inactivating mutations in the pathogen's tryptophan synthase (trpBA) genes. Here, we have applied functional genomics to extend this work and find that the paradigm established for reference serovars also applies to clinical isolates - specifically, all ocular trachoma isolates tested have inactivating mutations in the synthase, whereas all genital isolates encode a functional enzyme. Moreover, functional enzyme activity was directly correlated to IFN-gamma resistance through an indole rescue mechanism. Hence, a strong selective pressure exists for genital strains to maintain a functional synthase capable of using indole for tryptophan biosynthesis. The fact that ocular serovars (serovar B) isolated from the genital tract were found to possess a functional synthase provided further persuasive evidence of this association. These results argue that there is an important host-parasite relationship between chlamydial genital strains and the human host that determines organotropism of infection and the pathophysiology of disease. We speculate that this relationship involves the production of indole by components of the vaginal microbial flora, allowing chlamydiae to escape IFN-gamma-mediated eradication and thus establish persistent infection.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Antimicrobial resistance following mass azithromycin distribution for trachoma: a systematic review

            Mass azithromycin distribution is a core component of trachoma control programmes and could reduce mortality in children younger than 5 years in some settings. In this systematic review we synthesise evidence on the emergence of antimicrobial resistance after mass azithromycin distribution. We searched electronic databases for publications up to June 14, 2018. We included studies of any type (excluding modelling studies, surveillance reports, and review articles) on community-wide distribution of oral azithromycin for the prevention and treatment of trachoma that assessed macrolide resistance, without restrictions to the type of organism. We extracted prevalence of resistance from published reports and requested unpublished data from authors of included studies. Of 213 identified studies, 19 met inclusion criteria (12 assessed Streptococcus pneumoniae) and were used for qualitative synthesis. Macrolide resistance after azithromycin distribution was reported in three of the five organisms studied. The lack of resistance in Chlamydia trachomatis suggests that azithromycin might remain effective for trachoma programmes, but evidence is scarce. As mass azithromycin distribution for trachoma continues and is considered for other indications, ongoing monitoring of antimicrobial resistance will be required.
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              Gut microbiome alteration in MORDOR I: a community-randomized trial of mass azithromycin distribution

                Bookmark

                Author and article information

                Journal
                J Infect Dis
                J Infect Dis
                jid
                The Journal of Infectious Diseases
                Oxford University Press (US )
                0022-1899
                1537-6613
                15 March 2022
                09 October 2020
                09 October 2020
                : 225
                : 6
                : 994-1004
                Affiliations
                [1 ] Department of Clinical Research, London School of Hygiene and Tropical Medicine , London, United Kingdom
                [2 ] The Carter Center , Addis Ababa, Ethiopia
                [3 ] Division of Infection and Immunity, University College London , London, United Kingdom
                [4 ] The Carter Center , Atlanta, Georgia, USA
                [5 ] Amhara Public Health Institute , Bahir Dar, Ethiopia
                Author notes
                Correspondence: Harry Pickering, PhD, LSHTM, Keppel Street, London, WC1E 7HT, UK ( harrycpickering@ 123456gmail.com ).

                M. J. H. and S. D. N. contributed equally to this work.

                Article
                jiaa615
                10.1093/infdis/jiaa615
                8922003
                33034349
                4d558e2f-bcb3-4a50-91a1-98cbb4d7e93c
                © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 July 2020
                : 22 September 2020
                : 30 September 2020
                : 18 November 2020
                Page count
                Pages: 11
                Funding
                Funded by: Bill and Melinda Gates Foundation, DOI 10.13039/100000865;
                Funded by: International Trachoma Initiative, DOI 10.13039/100002152;
                Award ID: 733373
                Categories
                Major Articles and Brief Reports
                Bacteria
                AcademicSubjects/MED00290

                Infectious disease & Microbiology
                trachoma,chlamydia trachomatis,antimicrobial resistance,genomics,whole-genome sequencing,mass drug administration,azithromycin,neglected tropical disease

                Comments

                Comment on this article