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

Online publication: 16/06/2018 Printed publication: 1 August 2018 Journal: 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.

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

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