Evelyn K. Ansah

Rapid testing for malaria in settings where microscopy is available and peripheral clinics where only presumptive treatment is available: a randomised controlled trial in Ghana.

Objective To test in West Africa the impact of rapid diagnostic tests on the prescription of antimalarials and antibiotics both where microscopy is used for the diagnosis of malaria and in clinical (peripheral) settings that rely on clinical diagnosis. Design Randomised, controlled, open label clinical trial. Setting Four clinics in the rural Dangme West district of southern Ghana, one in which microscopy is used for diagnosis of malaria (“microscopy setting”) and three where microscopy is not available and diagnosis of malaria is made on the basis of clinical symptoms (“clinical setting”). Participants Patients with suspected malaria. Interventions Patients were randomly assigned to either a rapid diagnostic test or the current diagnostic method at the clinic (microscopy or clinical diagnosis). A blood sample for a research microscopy slide was taken for all patients. Main outcome measures The primary outcome was the prescription of antimalarials to patients of any age whose double read research slide was negative for malaria. The major secondary outcomes were the correct prescription of antimalarials, the impact of test results on antibiotic prescription, and the correct prescription of antimalarials in children under 5 years. Results Of the 9236 patients screened, 3452 were randomised in the clinical setting and 3811 in the microscopy setting. Follow-up to 28 days was 97.6% (7088/7263). In the microscopy setting, 722 (51.6%) of the 1400 patients with negative research slides in the rapid diagnostic test arm were treated for malaria compared with 764 (55.0%) of the 1389 patients in the microscopy arm (adjusted odds ratio 0.87, 95% CI 0.71 to 1.1; P=0.16). In the clinical setting, 578 (53.9%) of the 1072 patients in the rapid diagnostic test arm with negative research slides were treated for malaria compared with 982 (90.1%) of the 1090 patients with negative slides in the clinical diagnosis arm (odds ratio 0.12, 95% CI 0.04 to 0.38; P=0.001). The use of rapid diagnostic tests led to better targeting of antimalarials and antibiotics in the clinical but not the microscopy setting, in both children and adults. There were no deaths in children under 5 years at 28 days follow-up in either arm. Conclusion Where microscopy already exists, introducing rapid diagnostic tests had limited impact on prescriber behaviour. In settings where microscopy was not available, however, using rapid diagnostic tests led to a significant reduction in the overprescription of antimalarials, without any evidence of clinical harm, and to better targeting of antibiotics. Trial registration ClinicalTrials.gov NCT00493922.

Deployment of ACT antimalarials for treatment of malaria: challenges and opportunities.

Following a long period when the effectiveness of existing mono-therapies for antimalarials was steadily declining with no clear alternative, most malaria-endemic countries in Africa and Asia have adopted artemisinin combination therapy (ACT) as antimalarial drug policy. Several ACT drugs exist and others are in the pipeline. If properly targeted, they have the potential to reduce mortality from malaria substantially. The major challenge now is to get the drugs to the right people. Current evidence suggests that most of those who need the drugs do not get them. Simultaneously, a high proportion of those who are given antimalarials do not in fact have malaria. Financial and other barriers mean that, in many settings, the majority of those with malaria, particularly the poorest, do not access formal healthcare, so the provision of free antimalarials via this route has only limited impact. The higher cost of ACT creates a market for fake drugs. Addressing these problems is now a priority. This review outlines current evidence, possible solutions and research priorities.

Effect of Removing Direct Payment for Health Care on Utilisation and Health Outcomes in Ghanaian Children: A Randomised Controlled Trial

Background Delays in accessing care for malaria and other diseases can lead to disease progression, and user fees are a known barrier to accessing health care. Governments are introducing free health care to improve health outcomes. Free health care affects treatment seeking, and it is therefore assumed to lead to improved health outcomes, but there is no direct trial evidence of the impact of removing out-of-pocket payments on health outcomes in developing countries. This trial was designed to test the impact of free health care on health outcomes directly. Methods and Findings 2,194 households containing 2,592 Ghanaian children under 5 y old were randomised into a prepayment scheme allowing free primary care including drugs, or to a control group whose families paid user fees for health care (normal practice); 165 children whose families had previously paid to enrol in the prepayment scheme formed an observational arm. The primary outcome was moderate anaemia (haemoglobin [Hb] < 8 g/dl); major secondary outcomes were health care utilisation, severe anaemia, and mortality. At baseline the randomised groups were similar. Introducing free primary health care altered the health care seeking behaviour of households; those randomised to the intervention arm used formal health care more and nonformal care less than the control group. Introducing free primary health care did not lead to any measurable difference in any health outcome. The primary outcome of moderate anaemia was detected in 37 (3.1%) children in the control and 36 children (3.2%) in the intervention arm (adjusted odds ratio 1.05, 95% confidence interval 0.66–1.67). There were four deaths in the control and five in the intervention group. Mean Hb concentration, severe anaemia, parasite prevalence, and anthropometric measurements were similar in each group. Families who previously self-enrolled in the prepayment scheme were significantly less poor, had better health measures, and used services more frequently than those in the randomised group. Conclusions In the study setting, removing out-of-pocket payments for health care had an impact on health care-seeking behaviour but not on the health outcomes measured. Trial registration: ClinicalTrials.gov (#NCT00146692).

How can malaria rapid diagnostic tests achieve their potential? A qualitative study of a trial at health facilities in Ghana

BackgroundRapid diagnostic tests (RDTs) for malaria are at the early stages of introduction across malaria endemic countries. This is central to efforts to decrease malaria overdiagnosis and the consequent overuse of valuable anti-malarials and underdiagnosis of alternative causes of fever. Evidence of the effect of introducing RDTs on the overprescription of anti-malarials is mixed. A recent trial in rural health facilities in Ghana reduced overprescription of anti-malarials, but found that 45.5% patients who tested negative with RDTs were still prescribed an anti-malarial.MethodsA qualitative study of this trial was conducted, using in-depth interviews with a purposive sample of health workers involved in the trial, ranging from those who continued to prescribe anti-malarials to most patients with negative RDT results to those who largely restricted anti-malarials to patients with positive RDT results. Interviews explored the experiences of using RDTs and their results amongst trial participants.ResultsMeanings of RDTs were constructed by health workers through participation with the tests themselves as well as through interactions with colleagues, patients and the research team. These different modes of participation with the tests and their results led to a change in practice for some health workers, and reinforced existing practice for others. Many of the characteristics of RDTs were found to be inherently conducive to change, but the limited support from purveyors, lack of system antecedents for change and limited system readiness for change were apparent in the analysis.ConclusionsWhen introduced with a limited supporting package, RDTs were variously interpreted and used, reflecting how health workers had learnt how to use RDT results through participation. To build confidence of health workers in the face of negative RDT results, a supporting package should include local preparation for the innovation; unambiguous guidelines; training in alternative causes of disease; regular support for health workers to meet as communities of practice; interventions that address negotiation of health worker-patient relationships and encourage self-reflection of practice; feedback systems for results of quality control of RDTs; feedback systems of the results of their practice with RDTs; and RDT augmentation such as a technical and/or clinical troubleshooting resource.

Strategies to improve adherence to recommended chloroquine treatment regimes: a quasi-experiment in the context of integrated primary health care delivery in Ghana

This paper presents the results of an intervention study carried out as part of the activities of a District Health Management Team responsible for integrated primary health care delivery in a rural district in Ghana. The aim was to test the impact of a combination of improved information provision to patients and drug labeling on adherence to recommended anti-malarial treatment regimens focusing on oral chloroquine, for the outpatient management of acute uncomplicated malaria. The study had a quasi-experimental pre-test post-test control group design with partly random allocation by clinic. The results show that the intervention resulted in an improved flow of information to clients prescribed chloroquine, and better labeling of drugs for the home treatment of acute clinical episodes of malaria in the intervention area. Improvements in adherence occurred in all clinics. However, improvements in adherence were most marked in the clinic that was worst performing at the start of the intervention. Implications of the results for improving adherence to chloroquine therapy on an outpatient basis are discussed.

Malaria eradication and elimination: views on how to translate a vision into reality

Although global efforts in the past decade have halved the number of deaths due to malaria, there are still an estimated 219 million cases of malaria a year, causing more than half a million deaths. In this forum article, we asked experts working in malaria research and control to discuss the ways in which malaria might eventually be eradicated. Their collective views highlight the challenges and opportunities, and explain how multi-factorial and integrated processes could eventually make malaria eradication a reality.

The impact of providing rapid diagnostic malaria tests on fever management in the private retail sector in Ghana: a cluster randomized trial.

Objective To examine the impact of providing rapid diagnostic tests for malaria on fever management in private drug retail shops where most poor rural people with fever present, with the aim of reducing current massive overdiagnosis and overtreatment of malaria. Design Cluster randomized trial of 24 clusters of shops. Setting Dangme West, a poor rural district of Ghana. Participants Shops and their clients, both adults and children. Interventions Providing rapid diagnostic tests with realistic training. Main outcome measures The primary outcome was the proportion of clients testing negative for malaria by a double-read research blood slide who received an artemisinin combination therapy or other antimalarial. Secondary outcomes were use of antibiotics and antipyretics, and safety. Results Of 4603 clients, 3424 (74.4%) tested negative by double-read research slides. The proportion of slide-negative clients who received any antimalarial was 590/1854 (32%) in the intervention arm and 1378/1570 (88%) in the control arm (adjusted risk ratio 0.41 (95% CI 0.29 to 0.58), P<0.0001). Treatment was in high agreement with rapid diagnostic test result. Of those who were slide-positive, 690/787 (87.8%) in the intervention arm and 347/392 (88.5%) in the control arm received an artemisinin combination therapy (adjusted risk ratio 0.96 (0.84 to 1.09)). There was no evidence of antibiotics being substituted for antimalarials. Overall, 1954/2641 (74%) clients in the intervention arm and 539/1962 (27%) in the control arm received appropriate treatment (adjusted risk ratio 2.39 (1.69 to 3.39), P<0.0001). No safety concerns were identified. Conclusions Most patients with fever in Africa present to the private sector. In this trial, providing rapid diagnostic tests for malaria in the private drug retail sector significantly reduced dispensing of antimalarials to patients without malaria, did not reduce prescribing of antimalarials to true malaria cases, and appeared safe. Rapid diagnostic tests should be considered for the informal private drug retail sector. Registration Clinicaltrials.gov NCT01907672

Even if the test result is negative, they should be able to tell us what is wrong with us: a qualitative study of patient expectations of rapid diagnostic tests for malaria

BackgroundThe debate on rapid diagnostic tests (RDTs) for malaria has begun to shift from whether RDTs should be used, to how and under what circumstances their use can be optimized. This has increased the need for a better understanding of the complexities surrounding the role of RDTs in appropriate treatment of fever. Studies have focused on clinician practices, but few have sought to understand patient perspectives, beyond notions of acceptability.MethodsThis qualitative study aimed to explore patient and caregiver perceptions and experiences of RDTs following a trial to assess the introduction of the tests into routine clinical care at four health facilities in one district in Ghana. Six focus group discussions and one in-depth interview were carried out with those who had received an RDT with a negative test result.ResultsPatients had high expectations of RDTs. They welcomed the tests as aiding clinical diagnoses and as tools that could communicate their problem better than they could, verbally. However, respondents also believed the tests could identify any cause of illness, beyond malaria. Experiences of patients suggested that RDTs were adopted into an existing system where patients are both physically and intellectually removed from diagnostic processes and where clinicians retain authority that supersedes tests and their results. In this situation, patients did not feel able to articulate a demand for test-driven diagnosis.ConclusionsImprovements in communication between the health worker and patient, particularly to explain the capabilities of the test and management of RDT negative cases, may both manage patient expectations and promote patient demand for test-driven diagnoses.

Antimalarial treatment with artemisinin combination therapy in Africa

Desirable, achievable, but not easy T he steady increase of drug resistant malaria across Africa is a crisis for which there are achievable solutions, but no easy ones. The scale of the problem is not in doubt. In Africa malaria remains one of the commonest causes of death and serious morbidity, especially for children and pregnant women.1 Despite a decision in principle by many countries in Africa to use artemisinin based combination therapies (ACTs), most cases of malaria are still treated with monotherapy and in many areas most of these treatments will fail.2 3 Drug combinations, rather than monotherapy, are now seen to be the best solution for treating malaria, and artemisinin based drug combinations are highly effective, with cure rates similar to that of chloroquine 30 years ago. They seem to be a good long term choice for most African countries, being safe and well tolerated (with the caveat that their safety in early pregnancy is not yet clear). Compared with other antimalarials, ACTs can reduce gametocyte carriage and thereby lower the risk of infectiousness in those who take treatment. In areas of relatively low malaria transmission in South East Asia and South Africa, widespread use of ACTs has reduced significantly the burden of malaria.4 This benefit is …

Cost-Effectiveness Analysis of Introducing RDTs for Malaria Diagnosis as Compared to Microscopy and Presumptive Diagnosis in Central and Peripheral Public Health Facilities in Ghana

Cost-effectiveness information on where malaria rapid diagnostic tests (RDTs) should be introduced is limited. We developed incremental cost-effectiveness analyses with data from rural health facilities in Ghana with and without microscopy. In the latter, where diagnosis had been presumptive, the introduction of RDTs increased the proportion of patients who were correctly treated in relation to treatment with antimalarials, from 42% to 65% at an incremental societal cost of Ghana cedis (GHS)12.2 (US