Targeting

Wherever overdiagnosis is looked for in Africa it is found; in most settings a substantial proportion of those treated for malaria do not have any parasites, and in many low-transmission settings and in adults it can be the great majority (over 75%). This practice was reasonable during an era of very cheap antimalarials, of known safety in target populations, and has now become ingrained in the behaviour of patients, carers and prescribers. In an era of much more costly drugs, maintaining this approach is very wasteful, thus threatening the long-term viability of any programme which uses them, and substantially reducing the cost-effectiveness of any programme. It also leads to serious alternative causes of mortality, many of which are bacterial, being treated as malaria with fatal consequences, increases the risks of drug resistance, and will substantially reduce the apparent impact of newer drugs. Improving microscopy is possible but hard to sustain, and in many settings most diagnosis is syndromic.

Sensitive and specific RDTs are now available. At a cost of around $1 each, they were clearly not cost-effective when drugs were around $0.15, but potentially become economically more viable with more expensive drugs, at least at low and moderate transmission intensities. RDTs are therefore being considered for deployment in areas where ACTs are used. Their potential cost-effectiveness is likely to vary by transmission intensity and age group. In particular it may be less in areas of intense transmission (because many patients with low parasitaemias may not have malaria as their primary problem) and very low transmission (because the chance that an individual patient has malaria is very low, so many tests need to be performed to detect one case). Transmission intensity may also affect prescribing habits amongst clinicians, depending on their usual case mix. However there is currently no direct evidence to test under what circumstances rapid diagnostic tests and other new diagnostic methods may be effective and cost-effective for directing treatment. The value of RDTs depends not only on their sensitivity, specificity and stability and on transmission intensity, but also on whether prescribers actually change their prescription habits based on test results. If RDTs are theoretically cost-effective but ignored in practice, their impact will be small. Several factors suggest this may be a likely outcome, including long-standing diagnostic habit and patient expectations of receiving an antimalarial, so new methods to change prescribing habits in support of new diagnostic tests need to be developed.

Research questions to be addressed by the consortium

Will the deployment of RDTs lead to an improvement in case identification and rational prescription of antimalarials and antibiotics at an individual level where microscopy already exists, but is ignored? This needs to be addressed in settings with different transmission intensities and healthcare systems, and can be addressed using relatively simple individually-randomised trials.
Will the deployment of RDTs lead to an improvement in case identification and rational prescription of antimalarials and antibiotics at an individual level where microscopy does not exist and diagnosis is currently syndromic (eg most dispensaries)?
Does using RDTs to limit prescriptions of antimalarials have a positive or negative impact on morbidity, both malaria-specific (such as anaemia) and from other causes of febrile illness (eg bacterial diseases) at the population level? This will need to be addressed using cluster randomised trials.
Can rational prescribing of antimalarials be improved by behavioural interventions targeting both patients and healthcare workers? This will need to be addressed using cluster randomised trials.
What is the impact of RDTs on prescribing rationally for falciparum malaria in settings where vivax malaria is the predominant species? This is a major problem in much of South Asia and parts of the Horn of Africa.
How cost-effective are these diagnostic interventions?

Target outputs

Quantification of the impact of deploying RDTs on the proper targeting of antimalarials for individuals in different healthcare settings and transmission intensities.
Assessment of the impact of RDTs on malaria-specific and general morbidity at population level.
Assessment of the relative impact on appropriate use of antimalarials of strategies that target both prescriber and patient behaviour
Quantification of the cost-effectiveness and acceptability of these approaches.