Specifically Targeting Metacaspases of : A New Therapeutic Opportunity.

The World Health Organization (WHO) recently published a list of fungal priority pathogens, including and . The increased level of resistance of is raising concern, considering the availability of only four classes of medicine. The WHO is seeking novel agent classes with different targets and mechanisms of action.

Nanoparticle tracking analysis of natural hemozoin from Plasmodium parasites.

Background: Hemozoin is a byproduct of hemoglobin digestion crucial for parasite survival. It forms crystals that can be of interest as drug targets or biomarkers of malaria infection. However, hemozoin has long been considered as an amorphous crystal of simple morphology.

Structural and molecular determinants of Candida glabrata metacaspase maturation and activation by calcium.

Metacaspases are caspase-like homologs which undergo a complex maturation process involving multiple intra-chain cleavages resulting in a composite enzyme made of a p10 and a p20 domain. Their proteolytic activity involving a cysteine-histidine catalytic dyad, show peptide bond cleavage specificity in the C-terminal to lysine and arginine, with both maturation- and catalytic processes being calcium-dependent. Here, we present the structure of a metacaspase from the yeast Candida glabrata, CgMCA-I, in complex with a unique calcium along with a structure in which three magnesium ions are bound.

Pre-referral intranasal artesunate powder for cerebral malaria: a proof-of-concept study.

Background: Malaria still kills young children in rural endemic areas because early treatment is not available. Thus, the World Health Organization recommends the administration of artesunate suppositories as pre-referral treatment before transportation to the hospital in case of severe symptoms with an unavailable parenteral and oral treatment. However, negative cultural perception of the rectal route, and limited access to artesunate suppositories, could limit the use of artesunate suppositories.

Evaluation of ferrocenyl-containing γ-hydroxy-γ-lactam-derived tetramates as potential antiplasmodials.

A series of ferrocenyl-containing γ-hydroxy-γ-lactam tetramates were prepared in 2-3 steps through ring opening-ring closure (RORC) process of γ-ylidene-tetronate derivatives in the presence of ferrocenyl alkylamines. The compounds were screened in vitro for their antiplasmodial activity against chloroquine-sensitive (3D7) and chloroquine-resistant (W2) clones of P. falciparum, displaying activity in the range of 0.

Paper functionalization for detection of Plasmodium falciparum DNA using square waves voltammetry.

Malaria elimination is a major goal to be reached in the next decade. Significant progress were made in the past, and the prevalence decreased in many areas while the positive trend stalled in the last years. The exact number of asymptomatic carriers of Plasmodium parasites is unknown since this population is not detected by conventional diagnosis methods and participate in the maintenance of transmission.

The first case of artemisinin treatment failure of Plasmodium falciparum imported to Oman from Tanzania.

We present the clinical and genomic epidemiological perspective of the first case of Artesunate treatment failure in an Omani citizen admitted to a hospital in Muscat who originally contracted malaria during travel to Dar Es Salaam, Tanzania.

Assessment of quantitative and semi-quantitative biological test methods of artesunate in vitro.

Artesunate is the current most potent antimalarial drug widely used for the treatment of malaria. Considering the emergence of artemisinin resistance, several situations may require a simple method for artesunate quantification. We thus developed a quantitative and a semi-quantitative biological method for the determination of artesunate in liquid samples.

Drug resistant parasites and fungi from a one-health perspective: A global concern that needs transdisciplinary stewardship programs.

Antimicrobials including antibiotics, antiparasitic, and antifungals, are subjected to resistance. In this context, Public Health Organizations called for a One Health approach because antimicrobials used to treat different infectious diseases in animals and plants may be the same than those used in humans. Whereas mechanisms of resistance transmission from animals or environment to humans should be considered differently if related to prokaryotic or eukaryotic pathogens, their impact can be considered as a whole.

Recrudescence of a high parasitaemia, severe Plasmodium falciparum malaria episode, treated by artesunate monotherapy.

A patient presenting with severe malaria, with hyperparasitaemia, received 7-day artesunate monotherapy. A severe recrudescence was detected and attributed to hyperparasitaemia, monotherapy and a polyclonal infection without Kelch 13 gene mutation. A second treatment with artesunate, then quinine, followed by artemether-lumefantrine, was successful.

An insight on drug resistance in Plasmodium vivax, a still neglected human malaria parasite.

Plasmodium vivax has been considered for years as responsible for a mild form of malaria, due to the absence in the majority of its infections of the severe form of the disease, typical instead of the deadly human parasite P. falciparum. In the last decade, studies on vivax malaria have had a partial step ahead especially after the completion of the whole genome project, but there is still a gap of knowledge in the biology of this parasite.

Mycetoma and Chromoblastomycosis: Perspective for Diagnosis Improvement Using Biomarkers.

Background: Mycetoma and chromoblastomycosis are both chronic subcutaneous infectious diseases that pose an obstacle to socioeconomic development. Besides the therapeutic issue, the diagnosis of most neglected tropical diseases (NTD) is challenging. Confirmation using direct microscopy and culture, recognized as WHO essential diagnostic tests, are limited to specialized facilities.

Cryptosporidiosis in HIV-positive patients and related risk factors: A systematic review and meta-analysis.

Cryptosporidium is one of the major causes of diarrhea in HIV-positive patients. The aim of this study is to systematically review and meta-analyze the prevalence of Cryptosporidium in these patients. PubMed, Science Direct, Google Scholar, Web of Science, Cochrane and Ovid databases were searched for relevant studies dating from the period of 1 January 2000 to 31 December 2017.

Coalition: Advocacy for prospective clinical trials to test the post-exposure potential of hydroxychloroquine against COVID-19.

Our coalition of public health experts, doctors, and scientists worldwide want to draw attention to the need for high-quality evaluation protocols of the potential beneficial effect of hydroxychloroquine (HCQ) as a post-exposure drug for exposed people. In the absence of an approved, recognized effective pre or post-exposure prophylactic drug or vaccine for COVID-19, nor of any approved and validated therapeutic drug, coupled with social and political pressure raised by publicity both regarding the potential beneficial effect of hydroxychloroquine (HCQ) as well as potential risks from HCQ, we urge the immediate proper clinical trials. Specifically, we mean using HCQ for post-exposure of people with close contact with patients with positive COVID19 rtPCR, including home and medical caregivers.

Flagging performance of Sysmex XN-10 haematology analyser for malaria detection.

Aim: The aim was to assess the flagging performance of Sysmex XN-10 haematology analyser for malaria detection through the parasitic red blood cell ('pRBC') alarm.

Methods: We retrospectively studied 584 blood samples performed on the Sysmex XN-10 analyser that were tested for malaria. Sensitivity, specificity, positive and negative predictive values, and prevalence were established for the pRBC alarm.

Interactions between hydatid cyst and regulated cell death may provide new therapeutic opportunities.

Cystic echinococcosis and alveolar echinococcosis are chronic zoonotic infections, transmitted throughout the world. Development of the cestode larval stages in the liver and lungs causes damage to intermediate hosts, including humans. Several pathways leading to the suppression of host immune response and the survival of the cysts in various hosts are known.

Systematic review of artesunate pharmacokinetics: Implication for treatment of resistant malaria.

Background: Artesunate (ART) is an artemisinin derivative used as monotherapy for the treatment of severe malaria and in combination with a partner drug for non-severe malaria. Resistance of malaria parasites to artemisinins have emerged in Southeast Asia. Adjustment of drug regimen may be an option to prevent therapeutic failures considering the relative favourable safety profile of ART high doses.

Comparison of fks gene mutations and minimum inhibitory concentrations for the detection of Candida glabrata resistance to micafungin: A systematic review and meta-analysis.

Candida resistance to antifungals impaired invasive candidiasis outcome. In a context of echinocandin resistance development, we aimed to evaluate the association between phenotypic resistance to micafungin and fks mutations of Candida glabrata. For this systematic review and meta-analysis, we searched MEDLINE, Scopus and Web of Science for reports published up to December 2017.

Antimalarial stewardship programs are urgently needed for malaria elimination: a perspective.

Global malaria cases have not been significantly reduced over the last three years although more than USD 3 billion was invested in malaria control and elimination. The reasons for this stagnation are highly complex and multi-factorial. It remains that almost three billion treatment courses were supplied over the period 2010-2017: 30% of them without malaria tests, and some with suboptimal doses leading to the risk of selection of resistant parasites.