Severe malaria is commonly misdiagnosed in Africa, leading to a failure to treat other life-threatening illnesses. In malaria-endemic areas, parasitemia does not ensure a diagnosis of severe malaria because parasitemia can be incidental to other concurrent disease. The detection of malarial retinopathy is a candidate diagnostic test for cerebral malaria. Malarial retinopathy consists of a set of retinal abnormalities that is unique to severe malaria and common in children with cerebral malaria. Its presence and severity are related to risk of death and length of coma in survivors. A large, prospective autopsy study of children dying with cerebral malaria in Malawi found that malarial retinopathy was better than any other clinical or laboratory feature in distinguishing malarial from non-malarial coma. However, visualization has to date relied on specialist examination techniques. Further studies are planned to evaluate the usefulness of funduscopy by general clinicians in a variety of settings across Africa. Studies of the retina and retinal blood vessels provide an unparalleled opportunity to visualize an infected microvasculature and its effect on neural tissue in vivo. This report reviews current knowledge of malarial retinopathy, including its use as a diagnostic test in the comatose child, and its value as a tool for research into the pathophysiology of cerebral malaria.

Azithromycin when used in combination with faster acting antimalarials has proven efficacious in treating P. falciparum malaria in Phase 2 clinical trials. The aim of this study was to establish optimal combination ratios for azithromycin in combination with either dihydroartemisinin or quinine, to determine the clinical correlates of in vitro drug sensitivity for these compounds, and to assess cross sensitivity patterns. Seventy three fresh P. falciparum isolates originating from patients from the western border regions of Thailand were successfully tested for their drug susceptibility in the HRP2 assay. With overall mean fractional inhibitory concentrations of 0.84 (95%CI: 0.77-1.08) and 0.78 (95%CI: 0.72-0.98) the interaction between azithromycin and dihydroartemisinin as well as quinine were classified as additive with a tendency towards synergism. The strongest tendency towards synergy was seen with a combination ratio of 1:547 for the combination with dihydroartemisinin and 1:44 with quinine. Geometric mean azithromycin IC50s were 2570.3 (95% CI: 2175.58 - 3036.58) ng/ml. IC50s for mefloquine were 11.42 ng/ml, for quinine 64.4 ng/ml, and 54.4 ng/ml for chloroquine suggesting a relatively high level of background resistance in this patient population. Distinct correlations (R=0.53; P=0.001) between quinine in vitro results and parasite clearance may indicate a compromised sensitivity to this drug. The correlation with dihydroartemisinin data was weaker (R=0.34; P=0.038) and no such correlation was observed for azithromycin. This in vitro data confirm that azithromycin in combination with artemisinin derivatives or quinine exerts additive to synergistic interactions, shows no cross-sensitivity with traditional antimalarials, and has substantial antimalarial activity on its own.