Severe falciparum malaria is a medical emergency characterised by potentially lethal vital organ dysfunction. Patient fatality rates even with parenteral artesunate treatment remain high. Despite considerable research into adjuvant therapies targeting organ and tissue dysfunction, none have shown efficacy apart from renal replacement therapy. Understanding the causal contributions of clinical and laboratory abnormalities to mortality is essential for the design and evaluation of novel therapeutic interventions.
Artemether–lumefantrine (AL) and dihydroartemisinin–piperaquine (DHA/PPQ) are the recommended first- and second-line treatments, respectively, for uncomplicated falciparum malaria in Somalia. The studies reported here were conducted to assess the efficacy of these artemisinin-based combinations and the mutations in Plasmodium falciparum K13-propeller (Pfk13) domain and amplification in Pfplasmepsin 2 (Pfpm2) gene in Somalia.
The population pharmacokinetic models developed for both AS/DHA and MQ showed a large variability in drug exposure in the investigated African paediatric population.
Reduced total oxygen delivery is not a major contributor to lactic acidosis in severe falciparum malaria.
Correlating aberrant miRNA levels with imported malaria during the blood stage is required to better understand the in vivo biological and molecular processes that are involved in the response to Plasmodium falciparum infection and to find new biomarkers and diagnosis tools.
The proposed model identifies patients with severe malaria at risk of developing clinical sepsis, potentially benefiting from antibiotic treatment in addition to anti-malarials.
The pharmacokinetic parameters of mefloquine determined in the study suggest an adequate exposure of parasite to mefloquine in the multiple oral dose regimen of the fixed dose combination of mefloquine and artesunate.
Despite a high prevalence of k13 mutations, the current first-line treatment, AL, was still highly effective in this area of South-East Myanmar.
The C580Y finding from outside of the greater Mekong subregion supports the consensus to upscale molecular surveillance of artemisinin resistance outside of South East Asia.
Both plasma and urine concentrations of pHPLA closely correlate with AKI in patients with severe falciparum malaria.