An evaluation of rectal artesunate for the pre-hospital management of severe malaria.

INTRODUCTION: Severe falciparum malaria stills accounts for around half a million childhood deaths per year in sub-Saharan Africa. Prompt treatment of sick children close to home starting with artesunate given rectally by appropriately trained people can be lifesaving. AREAS COVERED: Rectal artesunate (RAS) has been developed for use in the WHO approved strategy of pre-referral intervention. This review covers the formulation, pharmacokinetics, safety, efficacy, and implementation of this drug. There is little RCT evidence and the only RCT has been controversial. It is unlikely that there will be further randomized studies in the field. There is a concern that the administration of a single dose of artesunate without adequate follow up therapy may encourage the emergence of artemisinin resistance. EXPERT OPINION: Artesunate is an essential drug and RAS is a very useful, potentially lifesaving formulation designed to be quickly administered in remote areas to severely unwell children by non-medical personnel. However, its use needs to be monitored and onward referral for definitive antimalarial treatment ensured.

Malaria: fluid therapy in severe disease.

INTRODUCTION: Severe malaria mainly affects children aged under 5 years, non-immune travellers, migrants to malarial areas, and people living in areas with unstable or seasonal malaria. Cerebral malaria, causing encephalopathy and coma, is fatal in around 20% of children and adults, and may lead to neurological sequelae in survivors. Severe malarial anaemia may have a mortality rate of over 13%. The role of fluid resuscitation in severe malaria is complex and controversial. Volume expansion could help to improve impaired organ perfusion and correct metabolic acidosis. However, rapid volume expansion could aggravate intracranial hypertension associated with cerebral malaria, leading to an increased risk of cerebral herniation. METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the following clinical question: What is the optimal method of fluid resuscitation in patients with severe malaria? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). RESULTS: At this update, searching of electronic databases retrieved 187 studies. After deduplication and removal of conference abstracts, 93 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 82 studies and the further review of 11 full publications. Of the 11 full articles evaluated, two systematic reviews and three RCTs were added at this update. We performed a GRADE evaluation for seven PICO combinations. CONCLUSIONS: In this systematic overview, we categorised the efficacy for three interventions based on information about the effectiveness and safety of human albumin, intravenous fluids, and whole blood or plasma.

Malaria: severe, life-threatening.

INTRODUCTION: Severe malaria mainly affects children under 5 years old, non-immune travellers, migrants to malarial areas, and people living in areas with unstable or seasonal malaria. Cerebral malaria, causing encephalopathy and coma, is fatal in around 20% of children and adults, and neurological sequelae may occur in some survivors. Severe malarial anaemia may have a mortality rate of over 13%. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of antimalarial treatments and adjunctive treatment for complicated falciparum malaria in non-pregnant people? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 33 systematic reviews, RCTs, or observational studies that met our inclusion criteria. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: dexamethasone, exchange blood transfusion, initial blood transfusion, intramuscular artemether, intravenous and intramuscular artesunate, intravenous and intramuscular dihydroartemisinin, quinine, and rectal/intravenous/intramuscular artemisinin and its derivatives.