A Simplified Intravenous Artesunate Regimen for Severe Malaria

Kremsner, Peter G.; Taylor, Terrie E.; Issifou, Saadou; Kombila, Maryvonne; Chimalizeni, Yamikani; Kawaza, Kondwana; Akotet, Marielle Karine Bouyou; Duscha, Mattias; Mordmüller, Benjamin; Kösters, Katrin; Humberg, Alexander; Miller, Raymond; Weina, Peter J.; Duparc, Stephan; Möhrle, Jörg J.; Kun, Jürgen F. J.; Planche, Tim; Teja‐Isavadharm, Paktiya; Simpson, Julie A; Köhler, Carsten; Krishna, Sanjeev

doi:10.1093/infdis/jir724

Cited by 36 publications

(43 citation statements)

References 14 publications

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“…Thus, after several years of extensive use of artesunate plus amodiaquine and of artemether plus lumefantrine as first-line treatments for P. falciparum malaria in Niger, there is no evidence of a decline in sensitivity to artemisinin. Our data are similar to those reported in Senegal and Congo and are consistent with findings of studies indicating a lack of decrease in sensitivity to artesunate in Gabon, Senegal, and Djibouti despite the extensive and growing use of ACT in these regions (12)(13)(14)(15)(16)(17)(18). A decrease in parasite susceptibility to artemisinin derivatives has been reported to date only in Southeast Asia along the border between Thailand and Cambodia.…”

supporting

confidence: 92%

Ex Vivo Responses of Plasmodium falciparum Clinical Isolates to Conventional and New Antimalarial Drugs in Niger

Issaka

Salissou

Aliyu

et al. 2013

Antimicrob Agents Chemother

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Little is known about resistance of Plasmodium falciparum to antimalarials in Sahelian countries. Here we investigated the drug susceptibilities of fresh isolates collected in Niger post-deployment of artemisinin-based combination therapies (ACTs). We found that the parasites remained highly susceptible to new (dihydroartemisinin, lumefantrine, pyronaridine, and piperaquine) and conventional (amodiaquine and chloroquine) antimalarial drugs. The introduction of ACTs in 2005 and their further deployment nationwide have therefore not resulted in a decrease in P. falciparum susceptibilities to these antimalarials. The WHO estimates that 50% of the world's population is exposed to malaria. In 2010, 216 million cases and more than 650,000 deaths from malaria were reported. Despite a decrease in the number of confirmed cases in some parts of the world, the situation remains heterogeneous and worrying in Africa (1). Together with respiratory infections and diarrheal diseases, malaria is one of the leading causes of death in Niger. Malaria transmission rates are high, with a mean incidence of 80 cases per 1,000 inhabitants. Despite the complementary nature of interventions in the field, which have strengthened in recent years, the number of cases has steadily risen over the last 20 years, reaching three million in 2010 (2, 3). There are several reasons for the deterioration of the public health situation with regard to malaria, and the increase in resistance to antimalarial drugs is considered a key factor. In Niger, infections are currently treated with combinations of drugs including an artemisinin (ART) derivative (artemisinin-based combination treatment, or ACT) (4). Since 2005, ACT has been proposed as the first-line treatment for the management of uncomplicated malaria. The use of such treatments throughout Niger was greatly expanded in 2010 by the implementation of a Global Fund Affordable Malaria Facility mechanism (5). Thereby, the drug pressure exerted on Plasmodium falciparum increases the risk of selection of parasites with altered susceptibility to antimalarials. This seems to be inevitable, as demonstrated by recent observations in Asia, which have revealed the presence of parasites less sensitive to artemisinins (6). The risk of emerging resistance to ACT makes it necessary to monitor the susceptibilities of parasites to antimalarial drugs, particularly those used in combination with artemisinin derivatives, on a regular basis and to search for new molecules with antimalarial activity.In this context, a study was carried out in Niger in 2011, at Gaya in the Dosso region, 250 km south of Niamey (3.44°N, 11.9°E), to evaluate the response of P. falciparum isolates to lumefantrine (LUM) and amodiaquine diphosphate (AQ), both of which are widely used in the ACTs distributed in Niger. In addition, responses to alternative molecules, such as pyronaridine (PYD) and piperaquine (PIP), both currently not available in Niger, as well as dihydroartemisinin (DHA) and chloroquine (CQ), were investigated. P. falciparum is...

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supporting

confidence: 92%

Ex Vivo Responses of Plasmodium falciparum Clinical Isolates to Conventional and New Antimalarial Drugs in Niger

Issaka

Salissou

Aliyu

et al. 2013

Antimicrob Agents Chemother

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“…Any new medicine would therefore have to free up the microvasculature, either by disengaging or killing the parasites; the drug’s speed of onset of activity is therefore of paramount concern. The AQUAMAT and SEAQUAMAT studies that compared intravenous artesunate and intravenous quinine [74, 75] and other studies that compared intravenous or intramuscular artesunate [76, 77] showed that injected artesunate reduces the overall severe malaria patient mortality by between a third and a quarter. From a safety viewpoint, quinine use has been associated with injection-site pathologies, cinchonism [78, 79] and also risks of hypoglycemia.…”

Section: Severe Malariamentioning

confidence: 99%

New developments in anti-malarial target candidate and product profiles

Burrows

Duparc

Gutteridge

et al. 2017

Malar J

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410

480

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A decade of discovery and development of new anti-malarial medicines has led to a renewed focus on malaria elimination and eradication. Changes in the way new anti-malarial drugs are discovered and developed have led to a dramatic increase in the number and diversity of new molecules presently in pre-clinical and early clinical development. The twin challenges faced can be summarized by multi-drug resistant malaria from the Greater Mekong Sub-region, and the need to provide simplified medicines. This review lists changes in anti-malarial target candidate and target product profiles over the last 4 years. As well as new medicines to treat disease and prevent transmission, there has been increased focus on the longer term goal of finding new medicines for chemoprotection, potentially with long-acting molecules, or parenteral formulations. Other gaps in the malaria armamentarium, such as drugs to treat severe malaria and endectocides (that kill mosquitoes which feed on people who have taken the drug), are defined here. Ultimately the elimination of malaria requires medicines that are safe and well-tolerated to be used in vulnerable populations: in pregnancy, especially the first trimester, and in those suffering from malnutrition or co-infection with other pathogens. These updates reflect the maturing of an understanding of the key challenges in producing the next generation of medicines to control, eliminate and ultimately eradicate malaria.

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“…A CDC evaluation reported no case of haemolysis after the use of intravenous artesunate preparations produced under strict good manufacturing practice (GMP) conditions by the US Army Medical Material Development Activity in 2013, including a study in 197 African children with severe malaria treated with GMPcompliant intravenous artesunate. 25,27 However, Bryan et al subsequently identified one case of artemisinin-associated haemolysis in the USA and two cases in Canada, both following the use of the GMP-compliant drug formulation. 26 Both cases of haemolysis associated with the use of oral artemether-lumefantrine involved a GMP-compliant product from Novartis.…”

Section: Description Of Pharmaceutical Productsmentioning

confidence: 99%