Suspected malaria cases in Africa increasingly receive a rapid diagnostic test (RDT) before antimalarials are prescribed. While this ensures efficient use of resources to clear parasites, the underlying cause of the individual's fever remains unknown due to potential coinfection with a non-malarial febrile illness. Widespread use of RDTs does not necessarily prevent over-estimation of clinical malaria cases or sub-optimal case management of febrile patients. We present a new approach that allows inference of the spatiotemporal prevalence of both Plasmodium falciparum malaria-attributable and non-malarial fever in sub-Saharan African children from 2006-2014. We estimate that 35.7% of all self-reported fevers were accompanied by a malaria infection in 2014, but that only 28.0% of those (10.0% of all fevers) were causally attributable to malaria. Most fevers among malaria-positive children are therefore caused by non-malaria illnesses. This refined understanding can help improve interpretation of the burden of febrile illness and shape policy on fever case management.
- Ursula Dalrymple
- Ewan Cameron
- Samir Bhatt
- Daniel J Weiss
- Peter W Gething
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Mark Jit, London School of Hygiene & Tropical Medicine, and Public Health England, United Kingdom
© 2017, Dalrymple et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Downloads (link to download the article as PDF)
Download citations (links to download the citations from this article in formats compatible with various reference manager tools)
Open citations (links to open the citations from this article in various online reference manager services)
Parasitic helminths use two benzoquinones as electron carriers in the electron transport chain. In normoxia they use ubiquinone (UQ), but in the anaerobic conditions inside the host, they require rhodoquinone (RQ) and greatly increase RQ levels. We previously showed the switch from UQ to RQ synthesis is driven by a change in substrates by the polyprenyltransferase COQ-2 (Del Borrello et al., 2019; Roberts Buceta et al., 2019) - how this substrate choice is made is unknown. Here, we show helminths make two coq-2 splice forms, coq-2a and coq-2e, and the coq-2e-specific exon is only found in species that make RQ. We show that in C. elegans COQ-2e is required for efficient RQ synthesis and for survival in cyanide. Crucially, parasites switch from COQ-2a to COQ-2e as they transition into anaerobic environments. We conclude helminths switch from UQ to RQ synthesis principally via changes in the alternative splicing of coq-2.