Aetiological Characterization of the Cutaneous Ulcer Syndrome in Papua New Guinea using Shotgun Metagenomics

Aetiological Characterization of the Cutaneous Ulcer Syndrome in Papua New Guinea using Shotgun Metagenomics

Data de publicació online: 16/06/2018 Data de publicació en paper: 1 Agost 2018 Revista: Clinical Infectious Diseases

Abstract:

Background

Treponema pallidum subsp. pertenue and Haemophilus ducreyi are causative agents of cutaneous ulcer (CU) in yaws endemic regions in the tropics. However, a significant proportion of CU patients remain PCR-negative for both bacterial agents. We aimed to identify potential additional aetiological agents of CU in a yaws-endemic region.

Methods

This population-based cohort study included children in Lihir Island (Papua New Guinea) examined during a yaws eradication campaign in Oct 2013-Oct 2014. All consenting patients with atraumatic exudative ulcers of more than 1 cm diameter were enrolled. Lesional swabs were collected for Real-Time PCR testing for T. p .pertenue and H. ducreyi. We then performed shotgun whole DNA metagenomics sequencing on extracted DNA and taxonomically assigned shotgun sequences using a human microbiome reference.

Findings

Sequence data was available for 122 samples. Shotgun sequencing showed high classification agreement relative to PCR testing: AUC for T. pallidum/H. ducreyi: 0.92/0.85 respectively. Clustering analysis of shotgun data revealed compositional clusters where the dominant species (median relative abundance ranged 32%-66%) was: H. ducreyi (23% of specimens), T. p. pertenue (16%), Streptococcus dysgalactiae (12%), Arcanobacterium haemolyticum (8%) and Corynebacterium diptheriae (8%). Sample clustering derived from ulcer microbial composition did not show geographical patterns.

Conclusion

These data suggest a diverse aetiology of skin ulcers in yaws-endemic areas, which may help design more accurate diagnostic tools and more effective antimicrobial treatment approaches to the cutaneous ulcer syndrome.

Autors: Marc Noguera-Julian, Camila González-Beiras, Mariona Parera, August Kapa, Roger Paredes, Oriol Mitjà

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