Feb 22, 2016
In 2013, ~500,000 children in sub-Saharan Africa died as a
direct result of Plasmodium falciparum malaria, accounting for 90%
of global malaria mortality. The scale-up of control efforts has
led to some reductions in malaria incidence in parts of Africa, but
countries where transmission is high malaria continues to be a
major public health problem. Early optimism that the most promising
malaria vaccine candidate (RTS,S) would reduce the burden of
malaria proved premature since following (3-dose) vaccination since
immunity rapidly wanes >20 months post-vaccination. Severe
malaria remains a major cause of hospital admission and paediatric
death across sSA. Nevertheless, clinical research has been
fragmented, resulting in only two large Phase III clinical trials -
both with landmark results. The AQUAMAT trial, enrolling 5425
children demonstrated significantly lower in-hospital mortality in
those receiving artesunate (8.5%) versus quinine (10.9%) (relative
risk reduction 22.5%). Second, FEAST a pragmatic trial of fluid
resuscitation as a supportive treatment in 3141 African children
with shock, of whom 57% had severe malaria; this trial was stopped
early due to higher 48-hour mortality in bolus arms (RR increase
45%) than no bolus (control) across all sub-groups.
Even with artesunate as standard antimalarial treatment, overall
mortality remains ~10%, but includes large sub-groups with
substantially higher case fatalities (15-20%) with 3 key prognostic
markers (coma, metabolic acidosis or a high blood urea nitrogen)
and/or bacterial co-infection (CF ~24%). There seems little
prospect for further reducing the substantial mortality of severe
malaria within the foreseeable future without a concerted and
strategic effort from funders and researchers. SMAART (a nascent
consortium for research and trials) aims to catalyse and accelerate
the severe malaria research agenda. SMAART will formulate and
coordinate seamless Phase I/II to large multi-centre Phase III
trials using efficient trial designs to inform treatment guidelines
and ultimately the outcome amongst African children