Date Published: March 13, 2017
Publisher: Public Library of Science
Author(s): Clare I. R. Chandler, Emily L. Webb, Catherine Maiteki-Sebuguzi, Susan Nayiga, Christine Nabirye, Deborah D. DiLiberto, Emmanuel Ssemmondo, Grant Dorsey, Moses R. Kamya, Sarah G. Staedke, David Joseph Diemert.
Rapid diagnostic tests for malaria (mRDTs) have been scaled-up widely across Africa. The PRIME study evaluated an intervention aiming to improve fever case management using mRDTs at public health centers in Uganda.
A cluster-randomized trial was conducted from 2010–13 in Tororo, a high malaria transmission setting. Twenty public health centers were randomized in a 1:1 ratio to intervention or control. The intervention included training in health center management, fever case management with mRDTs, and patient-centered services; plus provision of mRDTs and artemether-lumefantrine (AL) when stocks ran low. Three rounds of Interviews were conducted with caregivers of children under five years of age as they exited health centers (N = 1400); reference mRDTs were done in children with fever (N = 1336). Health worker perspectives on mRDTs were elicited through semi-structured questionnaires (N = 49) and in-depth interviews (N = 10). The primary outcome was inappropriate treatment of malaria, defined as the proportion of febrile children who were not treated according to guidelines based on the reference mRDT.
There was no difference in inappropriate treatment of malaria between the intervention and control arms (24.0% versus 29.7%, adjusted risk ratio 0.81 [95% CI: 0.56, 1.17] p = 0.24). Most children (76.0%) tested positive by reference mRDT, but many were not prescribed AL (22.5% intervention versus 25.9% control, p = 0.53). Inappropriate treatment of children testing negative by reference mRDT with AL was also common (31.3% invention vs 42.4% control, p = 0.29). Health workers appreciated mRDTs but felt that integrating testing into practice was challenging given constraints on time and infrastructure.
The PRIME intervention did not have the desired impact on inappropriate treatment of malaria for children under five. In this high transmission setting, use of mRDTs did not lead to the reductions in antimalarial prescribing seen elsewhere. Broader investment in health systems, including infrastructure and staffing, will be required to improve fever case management.
In 2010, the World Health Organization changed guidelines for management of malaria, recommending that all suspected cases be confirmed by a parasitological test before treatment, when possible . Subsequently, there has been a strong drive to scale-up use of rapid diagnostic tests for malaria (mRDTs) in areas where microscopy is unavailable or unreliable, with a goal of providing universal access to malaria diagnosis . Testing for malaria is now considered one of the central pillars of malaria control, aiming to target effective antimalarials to those with laboratory confirmed malaria , and allowing for improved management of non-malarial fevers as well as reduced selection pressure for resistant parasites . Increased testing is also promoted for surveillance purposes , particularly as the burden of malaria has been declining in many countries [6,7]. Implementation of rapid testing for malaria is paving the way for other point of care tests to target antibiotic use. Much hope is pinned on diagnostic technologies to turn the tide of antimicrobial resistance around the globe [8,9].
The trial protocols have been published previously [19,22]. The original and final versions of the protocols can be found in S1, S2, S3 and S4. The trial was approved by the Ugandan National Council for Science and Technology (UNCST Ref HS 794), the Makerere University School of Medicine Research & Ethics Committee (SOMREC Ref 2010–108), The London School of Hygiene and Tropical Medicine Ethics Committee (LSHTM Ref 5779), and the University of California San Francisco Committee on Human Research (UCSF CHR Ref 006160). The trial profile is shown in Fig 1.
In this cluster-randomized trial, we found that the PRIME intervention’s programme of training workshops and supervision, plus provision of mRDTs and AL when stocks ran low, increased uptake of mRDTs but did not have the desired impact on treatment of malaria. Although a reduction in inappropriate antimalarial treatment of 6% was observed in the intervention arm compared to the control arm, this difference was not statistically significant. In this high malaria transmission setting, we did not see the substantial reductions in antimalarial prescribing that have been observed in other scenarios with similarly intensive interventions but lower levels of malaria [16,17]. Concerningly, some patients with positive mRDT results did not receive the first-line antimalarial treatment. These findings demonstrate that diagnostic tests are not a straightforward solution to improving medicines use in all settings.
Although the PRIME intervention did not have the desired impact on inappropriate treatment of malaria, our results suggest that mRDTs have the capacity to improve targeting of ACTs. However, achieving this will require further efforts in supporting infrastructure as well as training and supervision programmes to ensure all eligible patients are tested. Such investments would also reap benefits in supporting the case management of other non-malarial illnesses amongst febrile patients, which is especially important if the specificity of mRDTs is low. In this high malaria transmission setting, benefits of mRDTs in terms of reducing ACT wastage are likely to be small. Rather, the benefit of mRDTs should be viewed in light of broader improvements to fever case management.