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Subject: Artesunate

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    PublicationOpen Access
    Introducing the concept of a new pre-referral treatment for severely ill febrile children at community level: a sociological approach in Guinea-Bissau.
    (2014-02-06) Vermeersch, Audrey; Libaud-Moal, Anaëlle; Rodrigues, Amabelia; White, Nicholas J; Olliaro, Piero; Gomes, Melba; Ashley, Elizabeth A; Millet, Pascal; Millet, Pascal; Mahidol University. Faculty of Tropical Medicine.
    BACKGROUND: Innovative strategies are needed to tackle childhood mortality in the rural tropics. Artesunate suppositories were developed to bring emergency treatment closer to severely ill children with malaria in rural areas where injectable treatment is not possible for several hours. Adding an antibacterial rectal drug would extend this strategy to treat non-malarial febrile illness as well. The objective of these studies was to assess acceptability of such a new pre-referral strategy by healthcare providers and likely uptake by the population. METHODS: Two qualitative studies were conducted between May and July 2009. Study 1 investigated the acceptability of introducing a combined antimalarial-antibacterial suppository by interviewing 27 representatives of the three administrative levels (central government, regional, local) of the health sector; Study 2 investigated treatment-seeking behaviour and acceptability of this intervention at community level by interviewing 74 mothers in 2 villages. RESULTS AND CONCLUSIONS: Up to 92% of health representatives were in favour of introducing a new pre-referral strategy to tackle both malaria and non-malaria related severe illnesses in Guinea-Bissau, provided it was endorsed by international health authorities. The main obstacles to implementation were the very limited human and financial resources. In the two villages surveyed, 44% of the mothers associated severe illness with fever only, or fever plus one additional symptom. Mothers' judgement of severity and ensuing decisions were not specific for serious illness, indicating that initial training to recognize signs of severe disease and treatment availability for non-severe, fever-associated symptoms will be required to prevent overuse of a new intervention designed as a pre-referral treatment for severely ill children. Level C health centres were the first resort in both villages (50% and 87% of respondents respectively). This information is encouraging for the implementation of a pre-referral treatment.
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    PublicationOpen Access
    Pharmacokinetics and pharmacodynamics of intravenous artesunate during severe malaria treatment in Ugandan adults.
    (2012-04-27) Byakika-Kibwika, Pauline; Lamorde, Mohammed; Mayito, Jonathan; Nabukeera, Lillian; Mayanja-Kizza, Harriet; Katabira, Elly; Warunee Hanpithakpong; วารุณี หาญพิทักษ์พงศ์; Obua, Celestino; Pakker, Nadine; Lindegardh, Niklas; Tarning, Joel; de Vries, Peter J.; Merry, Concepta; Byakika-Kibwika, Pauline; Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit.
    BACKGROUND: Severe malaria is a medical emergency with high mortality. Prompt achievement of therapeutic concentrations of highly effective anti-malarial drugs reduces the risk of death. The aim of this study was to assess the pharmacokinetics and pharmacodynamics of intravenous artesunate in Ugandan adults with severe malaria. METHODS: Fourteen adults with severe falciparum malaria requiring parenteral therapy were treated with 2.4 mg/kg intravenous artesunate. Blood samples were collected after the initial dose and plasma concentrations of artesunate and dihydroartemisinin measured by solid-phase extraction and liquid chromatography-tandem mass spectrometry. The study was approved by the Makerere University Faculty of Medicine Research and Ethics Committee (Ref2010-015) and Uganda National Council of Science and Technology (HS605) and registered with ClinicalTrials.gov (NCT01122134). RESULTS: All study participants achieved prompt resolution of symptoms and complete parasite clearance with median (range) parasite clearance time of 17 (8-24) hours. Median (range) maximal artesunate concentration (Cmax) was 3260 (1020-164000) ng/mL, terminal elimination half-life (T1/2) was 0.25 (0.1-1.8) hours and total artesunate exposure (AUC) was 727 (290-111256) ng·h/mL. Median (range) dihydroartemisinin Cmax was 3140 (1670-9530) ng/mL, with Tmax of 0.14 (0.6 - 6.07) hours and T1/2 of 1.31 (0.8-2.8) hours. Dihydroartemisinin AUC was 3492 (2183-6338) ng·h/mL. None of the participants reported adverse events. CONCLUSIONS: Plasma concentrations of artesunate and dihydroartemisinin were achieved rapidly with rapid and complete symptom resolution and parasite clearance with no adverse events.