FUTURE DIRECTIONS
The evidence base for the treatment of severe malaria is
lamentably small given the global importance of the disease
and the number of deaths it causes. Fewer than 10,000 patients have ever been randomized into treatment trials of severe malaria, an astonishingly small figure given the ≈ 10 million cases of severe malaria annually and our inadequate
knowledge of how it should best be managed. Clearly, underfunding has played a major role in the past, but in recent years
this problem has begun to be addressed as the global community has started making major investments in tackling the
main infectious-disease killers. There has been an associated
slow but steady development of clinical research capacity in
the malaria-endemic world, and although there is a long way
to go, it is for the first time becoming practical to conduct
large, adequately powered clinical trials of candidate treatments for severe malaria. Major funding and logistical challenges are still associated with such projects, and research
capacity building has to be an integral part of the planning.
The considerable problem of agreeing on the research agenda
must also be kept in mind, as only a limited number of such
multicenter trials can be conducted at any one time. Only by
forming multinational collaborations can we hope to address
important clinical research questions with sufficient statistical
power.
Which new treatments or clinical management strategies
warrant assessment in these multi-center studies? In Table 3
we list a number of candidates along with a subjective assessment of the evidence supporting their inclusion and the level
of controversy such a trial is likely to generate. Several have
been mentioned already in this review, whereas others are
more speculative and may require study in smaller trials with
surrogate marker endpoints before a larger study can be justified. This is necessarily a personal list, and we are sure to
have omitted a number of worthy contenders. The main objective is to stimulate debate and, ultimately, some degree of
agreement. This is a prerequisite for the development of collaborations and networks to carry out the studies.