Multi-method assessment of patients with febrile illness reveals over-diagnosis of malaria in rural Uganda

• Type of Material: Article
• Authors: Ria R. Ghai, Emory University; Mary I. Thurber, University of California Davis; Azza El El Bakry, McGill University; Colin A. Chapman, McGill University; Tony L. Goldberg, Makerere University Biological Field Station
• Language: English
• Date: 2016-09-07
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2016
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://malariajournal.biomedcentral.com/articles/10.1186/s12936-016-1502-4
• Title of Journal or Parent Work: Malaria Journal
• ISSN: 1475-2875
• Volume: 15
• Issue: 1
• Start Page: 460
• End Page: 460
• Grant/Funding Information: This research was supported by a Natural Sciences and Engineering Research Council of Canada Discovery Grant (CAC) and the Fonds de Recherche du Quebec Nature et Technologies International Internship award (RRG), as well as by NIH Grant TW009237 as part of the joint NIH-NSF Ecology of Infectious Disease program and the UK Economic and Social Research Council.; This work was partially funded from Emory University's Open Access Publishing Fund.
• Keywords: Plasmodium; Misdiagnosis; Malaria; Rapid diagnostic tests; Uganda
• Research Categories: Health Sciences, General; Health Sciences, Epidemiology

Abstract

Background Health clinics in rural Africa are typically resource-limited. As a result, many patients presenting with fever are treated with anti-malarial drugs based only on clinical presentation. This is a considerable issue in Uganda, where malaria is routinely over-diagnosed and over-treated, constituting a wastage of resources and an elevated risk of mortality in wrongly diagnosed patients. However, rapid diagnostic tests (RDTs) for malaria are increasingly being used in health facilities. Being fast, easy and inexpensive, RDTs offer the opportunity for feasible diagnostic capacity in resource-limited areas. This study evaluated the rate of malaria misdiagnosis and the accuracy of RDTs in rural Uganda, where presumptive diagnosis still predominates. Specifically, the diagnostic accuracy of “gold standard” methods, microscopy and PCR, were compared to the most feasible method, RDTs. Methods Patients presenting with fever at one of two health clinics in the Kabarole District of Uganda were enrolled in this study. Blood was collected by finger prick and used to administer RDTs, make blood smears for microscopy, and blot Whatman FTA cards for DNA extraction, polymerase chain reaction (PCR) amplification, and sequencing. The accuracy of RDTs and microscopy were assessed relative to PCR, considered the new standard of malaria diagnosis. Results A total of 78 patients were enrolled, and 31 were diagnosed with Plasmodium infection by at least one method. Comparing diagnostic pairs determined that RDTs and microscopy performed similarly, being 92.6 and 92.0 % sensitive and 95.5 and 94.4 % specific, respectively. Combining both methods resulted in a sensitivity of 96.0 % and specificity of 100 %. However, both RDTs and microscopy missed one case of non-falciparum malaria (Plasmodium malariae) that was identified and characterized by PCR and sequencing. In total, based on PCR, 62.0 % of patients would have been misdiagnosed with malaria if symptomatic diagnosis was used. Conclusions Results suggest that diagnosis of malaria based on symptoms alone appears to be highly inaccurate in this setting. Furthermore, RDTs were very effective at diagnosing malaria, performing as well or better than microscopy. However, only PCR and DNA sequencing detected non-P. falciparum species, which highlights an important limitation of this test and a treatment concern for non-falciparum malaria patients. Nevertheless, RDTs appear the only feasible method in rural or resource-limited areas, and therefore offer the best way forward in malaria management in endemic countries.