Artemisinin derivatives for treatment of uncomplicated Plasmodium falciparum malaria in Sudan: too early for too much hope

Abstract

The artemisinin-based combination therapy (ACT) is adopted by several countries as first line for malaria treatment in the last decade. Concomitantly, the World Health Organization and other research reports showed a dramatic decline in malaria burden in terms of morbidity, mortality and treatment failure (TF). The optimistic features of ACT are regularly reported with great hopes, while the pessimistic facets either not existing or underreported. However, the dependence on ACT as a single chemotherapeutic agent for malaria control bears considerable risks. Occurrence and spread of artemisinin derivatives (AD) TF will be a major threat, whether it is due to parasite drug resistance or use of poor drug quality. In addition, the safety of AD is not yet fully known. In this short review, two clinical trials performed to evaluate the efficacy and safety of AD, dihydroartemisinin (DHA) plus chloroquine and artesunate (AS) plus fansidar, in Sudan are critically discussed. The conclusions from both studies were that, the TF rate of DHA indicates arrival of counterfeit AD to Africa, and both rate of TF and undesirable effects of AS/SP were recognized. Both findings indicate that it is too early for too much hope on AD.

Antiplasmodial activity of Xanthium strumarium against Plasmodium berghei-infected BALB/c mice

“…There are approximately 300-500 million clinical cases and 1.2-2.8 million deaths each year due to this devastating disease (Chandel and Bagai 2011). The rising problem of resistance to the classical drugs (chloroquine and sulphadoxine/ pyrimethamine) and the problem of recrudescence of artemisinin stress the need to look for new antimalarial agents (Giha 2011). Natural product scaffolds have been the basis of the majority of current antimalarial medicines.…”

Monitoring artemisinin resistance in Plasmodium falciparum: comparison of parasite clearance time by microscopy and real-time PCR and evaluation of mutations in Pfatpase6 gene in Odisha state of India

“…To sum up, the study provides evidence that though the study site from Odisha attained 100 % ACPR, there is a need for continuous monitoring of artemisinin-resistant malaria as urged otherwise also (Jambou et al 2005). The evidence of relative increase in PCT as determined by real-time PCR in significant number of samples along with the prevalence of E431K mutation in Pfatpase6 gene further emphasizes the outcome.…”

“…This is definitely suggestive of reduced susceptibility to artemisinin partner (White 2012). Nevertheless, risks and threats involved with too much dependence on ACT have also been discussed in the past (Giha 2010). Finding the way out of these controversies, in the present study we aimed to monitor artemisinin resistance by monitoring day 3 positivity and correlating it with the clinical efficacy of AS+SP after 42-day follow-up.…”

“…Also, in Southern-Iran, L263 and A623 were reported to be wild type (Zakeri et al 2012). The presence of S769N also made occasional impacts from few studies (Jambou et al 2005;Pillai et al 2012;Zakeri et al 2012) like that of the French Guiana (Legrand et al 2008) while there are reports which observed its absence in the P. falciparum isolates that were analyzed (Mugittu et al 2006;Sisowath et al 2007;Zhang et al 2008;Ferreira et al 2008;Menegon et al 2009;Wangai et al 2011;Kwansa-Bentum et al 2011;Tanabe et al 2011;Brasil et al 2012;Saha et al 2013) or even denied the association of this SNP with artemisinin resistance (Phompradit et al 2011;Cui et al 2012). Another study from Yaounde, Cameroon, where all these four mutations were tested, high prevalence of E431K was warranted and alarmed (Tahar et al 2009).…”

“…Furthermore, based on preliminary results of this comparison, promising strains were analyzed for L263E, E431K, A623E, and S769N SNPs in Pfatpase6 gene, which is thought to be a candidate gene involved in playing a pivotal role in artemisinin resistance (Eckstein-Ludwig et al 2003;Jambou et al 2005;Li and Zhou 2010;Ding et al 2011) in studies conducted across the globe. These studies are focussed on analyzing mutations in this gene, the major reports being those of the above-stated SNPs (Tahar et al 2009;Jambou et al 2010;Krishna et al 2010;Zakeri et al 2012).…”