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WHAT'S NEW THIS TUESDAY: TWO ON ONCHOCERCIASIS

Monday, 25th of March 2013

Source

Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. l.coffeng@erasmusmc.nl

BACKGROUND:

Onchocerciasis causes a considerable disease burden in Africa, mainly through skin and eye disease. Since 1995, the African Programme for Onchocerciasis Control (APOC) has coordinated annual mass treatment with ivermectin in 16 countries. In this study, we estimate the health impact of APOC and the associated costs from a program perspective up to 2010 and provide expected trends up to 2015.

METHODS AND FINDINGS:

With data on pre-control prevalence of infection and population coverage of mass treatment, we simulated trends in infection, blindness, visual impairment, and severe itch using the micro-simulation model ONCHOSIM, and estimated disability-adjusted life years (DALYs) lost due to onchocerciasis. We assessed financial costs for APOC, beneficiary governments, and non-governmental development organizations, excluding cost of donated drugs. We estimated that between 1995 and 2010, mass treatment with ivermectin averted 8.2 million DALYs due to onchocerciasis in APOC areas, at a nominal cost of about US$257 million. We expect that APOC will avert another 9.2 million DALYs between 2011 and 2015, at a nominal cost of US$221 million.

CONCLUSIONS:

Our simulations suggest that APOC has had a remarkable impact on population health in Africa between 1995 and 2010. This health impact is predicted to double during the subsequent five years of the program, through to 2015. APOC is a highly cost-effective public health program. Given the anticipated elimination of onchocerciasis from some APOC areas, we expect even more health gains and a more favorable cost-effectiveness of mass treatment with ivermectin in the near future.

Daniel Globisch^a, Amira Y. Moreno^a, Mark S. Hixon^a,^b, Ashlee A. K. Nunes^a, Judith R. Denery^a, Sabine Specht^c, Achim Hoerauf^c, and Kim D. Janda^a,¹

Edited* by Peter G. Schultz, The Scripps Research Institute, La Jolla, CA, and approved January 29, 2013 (received for review December 18, 2012)

Onchocerciasis, also known as “river blindness”, is a neglected tropical disease infecting millions of people mainly in Africa and the Middle East but also in South America and Central America. Disease infectivity initiates from the filarial parasitic nematode Onchocerca volvulus, which is transmitted by the blackfly vector Simulium sp. carrying infectious third-stage larvae. Ivermectin has controlled transmission of microfilariae, with an African Program elimination target date of 2025. However, there is currently no point-of-care diagnostic that can distinguish the burden of infection—including active and/or past infection—and enable the elimination program to be effectively monitored. Here, we describe how liquid chromatography-MS–based urine metabolome analysis can be exploited for the identification of a unique biomarker, N-acetyltyramine-O,β-glucuronide (NATOG), a neurotransmitter-derived secretion metabolite from O. volvulus. The regulation of this tyramine neurotransmitter was found to be linked to patient disease infection, including the controversial antibiotic doxycycline treatment that has been shown to both sterilize and kill adult female worms. Further clues to its regulation have been elucidated through biosynthetic pathway determination within the nematode and its human host. Our results demonstrate that NATOG tracks O. volvulus metabolism in both worms and humans, and thus can be considered a host-specific biomarker for onchocerciasis progression. Liquid chromatography-MS–based urine metabolome analysis discovery of NATOG not only has broad implications for a noninvasive host-specific onchocerciasis diagnostic but provides a basis for the metabolome mining of other neglected tropical diseases for the discovery of distinct biomarkers and monitoring of disease progression.

Footnotes

• ¹To whom correspondence should be addressed. E-mail: kdjanda@scripps.edu.

• Author contributions: D.G., A.Y.M., A.A.K.N., J.R.D., and K.D.J. designed research; D.G., A.Y.M., M.S.H., and A.A.K.N. performed research; D.G., M.S.H., S.S., and A.H. contributed new reagents/analytic tools; D.G., A.Y.M., A.A.K.N., J.R.D., and K.D.J. analyzed data; and D.G. and K.D.J. wrote the paper.
• The authors declare no conflict of interest.
• *This Direct Submission article had a prearranged editor.
• This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1221969110/-/DCSupplemental.