# The Role of the Skin Microbiome in Cutaneous Ulcers in Children in the Tropics

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $534,977

## Abstract

Exudative cutaneous ulcers (CU) in the tropics are usually attributed to attributed to Treponema
pallidum subsp. pertenue (TP), or yaws, which primarily affects children 6-10 years old in poor rural
communities and leads to chronic disfigurement and disability. The World Health Organization
(WHO) has led several campaigns to eliminate yaws, but the global prevalence of CU is substantial,
with ~100 million children at risk for infection. Surprisingly, data from the current yaws elimination
campaign shows that the etiology of CU is multifactorial. On Lihir island in Papua New Guinea,
Haemophilus ducreyi (HD) and / or TP are detected in ~70% of CU cases, but up to ~30% have no
discernable etiology; this group is defined as having idiopathic ulcers (IU). Mass drug administration
(MDA) of azithromycin and subsequent case finding and treatment reduced the prevalence of CU from
~10% to 1-2% after 42 mo. of follow-up, at which time the trial was halted due to futility. Since a 1-2%
prevalence of CU is unacceptable, WHO has proposed an Integrated Disease Management
Strategy (IDM), which requires the development of common clinical and laboratory diagnostic
platforms for CU so that individuals can be treated with targeted and effective therapeutic agents.
Thus, there is a pressing need to determine the microbial etiology of IU, so that the IDM
strategy can be developed. We assembled a team of scientists who are highly skilled in the studies
of CU and of the skin microbiome. Our team will examine several hypotheses about the etiology of CU
by determining the microbiomes of paired skin swabs that were prospectively obtained 36, 42, and 48
months after MDA on Lihir island in children with CU (N = 274) and asymptomatic, gender and age-
matched household or community controls without CU. We hypothesize that some cases of IU are
caused by previously unidentified pathogens that may be part of the normal skin microbiota or are
caused by high loads of microorganisms not known to be ulcer pathogens. Our specific aims are to 1)
identify IU associated microorganisms using a combination of deep 16S rRNA gene sequencing and
metagenomic sequencing; 2) demonstrate that IU associated taxa are present in higher loads in IU vs.
HD, TP or HD/TP ulcers by quantitative PCR. Our preliminary data show that 16S rRNA gene and
metagenomic sequencing are feasible on the collected samples and suggest that the CU microbiome
is less diverse and has a different community structure than that of its corresponding asymptomatic
controls. The importance of this study is that it will be the first to characterize the microbiome of CU in
children using skin swabs prospectively collected after implementation of the yaws elimination
program. Identification of the agents of IU and determination of whether they are part of the normal
flora is critical for the development of diagnostic tests that will lead to selective therapies as part of the
IDM strategy.

## Key facts

- **NIH application ID:** 9952321
- **Project number:** 5R01AI134727-03
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Stanley M. Spinola
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $534,977
- **Award type:** 5
- **Project period:** 2018-07-13 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9952321

## Citation

> US National Institutes of Health, RePORTER application 9952321, The Role of the Skin Microbiome in Cutaneous Ulcers in Children in the Tropics (5R01AI134727-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9952321. Licensed CC0.

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