Clinical practice

Maltha, Jessica; Jacobs, Jan

doi:10.1007/s00431-011-1451-4

Cited by 14 publications

(2 citation statements)

References 56 publications

(106 reference statements)

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“…Malaria is a disease caused by an eukaryote parasite of the genus Plasmodium and remains a major global public health problem, that was responsible for 584,000 deaths in 2013, with most occurring in Africa and most deaths in children under 5 years of age [ 1 , 2 ]. Plasmodium falciparum and Plasmodium vivax , are responsible for most cases of malaria and the control of these parasites by chloroquine and other known anti-malarial drugs has been compromised by the emergence and spread of drug resistance in many parts of the world, primarily in P. falciparum strains [ 3 , 4 ]. This has severely limited the use of many effective anti-malarials, and has become a major threat to malaria elimination efforts, causing increased morbidity and mortality and a financial burden due to sustenance of replacement therapy [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Antiplasmodial activity, in vivo pharmacokinetics and anti-malarial efficacy evaluation of hydroxypyridinone hybrids in a mouse model

Dambuza

Smith

Evans

et al. 2015

Malar J

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BackgroundDuring the erythrocytic stage in humans, malaria parasites digest haemoglobin of the host cell, and the toxic haem moiety crystallizes into haemozoin. Chloroquine acts by forming toxic complexes with haem molecules and interfering with their crystallization. In chloroquine-resistant strains, the drug is excluded from the site of action, which causes the parasites to accumulate less chloroquine in their acid food vacuoles than chloroquine-sensitive parasites. 3-Hydroxylpyridin-4-ones are known to chelate iron; hydroxypyridone-chloroquine (HPO-CQ) hybrids were synthesized in order to determine whether they can inhibit parasites proliferation in the parasitic digestive vacuole by withholding iron from plasmodial parasite metabolic pathway.MethodsTwo HPO-CQ hybrids were tested against Plasmodium falciparum chloroquine-sensitive (D10 and 3D7) and -resistant strains (Dd2 and K1). The pharmacokinetic properties of active compounds were determined using a mouse model and blood samples were collected at different time intervals and analysed using LC–MS/MS. For in vivo efficacy the mice were infected with Plasmodium berghei in a 4-day Peters’ test. The parasitaemia was determined from day 3 and the course of the infection was followed by microscopic examination of stained blood films every 2–3 days until a rise in parasitaemia was observed in all test subjects.ResultsIC50 values of the two compounds for sensitive and resistant strains were 0.064 and 0.047 µM (compound 1), 0.041 and 0.122 µM (compound 2) and 0.505 and 0.463 µM (compound 1), 0.089 and 0.076 µM (compound 2), respectively. Pharmacokinetic evaluation of these compounds showed low oral bioavailability and this affected in vivo efficacy when compounds were dosed orally. However, when dosed intravenously compound 1 showed a clearance rate of 28 ml/min/kg, an apparent volume of distribution of 20 l/kg and a half-life of 4.3 h. A reduction in parasitaemia was observed when compound 1 was dosed intravenously for four consecutive days in P. berghei-infected mice. However, a rise in parasitaemia levels was observed on day 6 and on day 9 for chloroquine-treated mice.ConclusionThe hybrid compounds that were tested were able to reduce parasitaemia levels in P. berghei-infected mice when dosed intravenously, but parasites recrudesced 24 h after the administration of the least dose. Despite low oral bioavailability, the IV data obtained suggests that further structural modifications may lead to the identification of more HPO-CQ hybrids with improved pharmacokinetic properties and in vivo efficacy.

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Section: Introductionmentioning

confidence: 99%

Antiplasmodial activity, in vivo pharmacokinetics and anti-malarial efficacy evaluation of hydroxypyridinone hybrids in a mouse model

Dambuza

Smith

Evans

et al. 2015

Malar J

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“…Most of the currently marketed RDTs are so-called one-step RDTs that are more simple and user-friendly [5] compared to the multi-step RDT products evaluated in previous studies. Malaria RDTs are now easy to use handheld cassettes detecting antigens produced by the Plasmodium parasite which become visible as colored (mostly red) test lines within 20 minutes [6].…”

Section: Introductionmentioning

confidence: 99%

Self-Diagnosis of Malaria by Travelers and Expatriates: Assessment of Malaria Rapid Diagnostic Tests Available on the Internet

et al. 2013

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IntroductionIn the past malaria rapid diagnostic tests (RDTs) for self-diagnosis by travelers were considered suboptimal due to poor performance. Nowadays RDTs for self-diagnosis are marketed and available through the internet. The present study assessed RDT products marketed for self-diagnosis for diagnostic accuracy and quality of labeling, content and instructions for use (IFU).MethodsDiagnostic accuracy of eight RDT products was assessed with a panel of stored whole blood samples comprising the four Plasmodium species (n = 90) as well as Plasmodium negative samples (n = 10). IFUs were assessed for quality of description of procedure and interpretation and for lay-out and readability level. Errors in packaging and content were recorded.ResultsTwo products gave false-positive test lines in 70% and 80% of Plasmodium negative samples, precluding their use. Of the remaining products, 4/6 had good to excellent sensitivity for the diagnosis of Plasmodium falciparum (98.2%–100.0%) and Plasmodium vivax (93.3%–100.0%). Sensitivity for Plasmodium ovale and Plasmodium malariae diagnosis was poor (6.7%–80.0%). All but one product yielded false-positive test lines after reading beyond the recommended reading time. Problems with labeling (not specifying target antigens (n = 3), and content (desiccant with no humidity indicator (n = 6)) were observed. IFUs had major shortcomings in description of test procedure and interpretation, poor readability and lay-out and user-unfriendly typography. Strategic issues (e.g. the need for repeat testing and reasons for false-negative tests) were not addressed in any of the IFUs.ConclusionDiagnostic accuracy of RDTs for self-diagnosis was variable, with only 4/8 RDT products being reliable for the diagnosis of P. falciparum and P. vivax, and none for P. ovale and P. malariae. RDTs for self-diagnosis need improvements in IFUs (content and user-friendliness), labeling and content before they can be considered for self-diagnosis by the traveler.

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