Early and effective malaria diagnosis is vital to control the disease spread and to prevent the emergence of severe cases and death. Currently, malaria diagnosis relies on optical microscopy and immuno-rapid tests; however, these require a drop of blood, are time-consuming, or are not specific and sensitive enough for reliable detection of low-level parasitaemia. Thus, there is an urge for simpler, prompt, and accurate alternative diagnostic methods. Particularly, hemozoin has been increasingly recognized as an attractive biomarker for malaria detection. As the disease proliferates, parasites digest host hemoglobin, in the process releasing toxic haem that is detoxified into an insoluble crystal, the hemozoin, which accumulates along with infection progression. Given its magnetic, optical, and acoustic unique features, hemozoin has been explored for new label-free diagnostic methods. Thereby, herein, we review the hemozoin-based malaria detection methods and critically discuss their challenges and potential for the development of an ideal diagnostic device.

for regulatory and ethical submission. We declare no competing interests.

Background: Delayed parasite clearance and, consequently, reduced efficacy of artemisinin-based combination therapies have been linked with Plasmodium falciparum K13 gene SNPs in Southeast Asia. In Africa, significantly prolonged clearance has not yet been observed and the presently restricted variation in parasite clearance cannot be explained by K13 polymorphisms. Objectives: Our aim was to study the in vivo pfK13 transcriptional response in patients treated with artemetherlumefantrine and explore whether the pfk13 transcripts can explain the patients' parasite clearance outcomes. Patients and methods: A total of 47 Tanzanian children with microscopically confirmed uncomplicated P. falciparum malaria were hospitalized and received artemether-lumefantrine treatment (clinical trial ID: NCT00336375). RNA was extracted from venous blood samples collected before treatment initiation and at five more timepoints after treatment. cDNA was synthesized and pfk13 transcripts measured by real-time PCR. Results: A wide range of pfk13 transcript variation was observed throughout all timepoints after artemetherlumefantrine treatment. Taking parasite clearance data together with the pfk13 transcripts profile, we observed a negative correlation inferring that pfk13 down-regulation is associated with longer parasite clearance time. Conclusions: The findings suggest that a reduced PfK13 transcriptional response may represent a first step towards artemisinin tolerance/resistance.

Dihydroartemisinin/piperaquine (DHA/PPQ) is increasingly deployed as an antimalaria drug in Africa. We report the detection in Mali of Plasmodium falciparum infections carrying plasmepsin 2 duplications (associated with piperaquine resistance) in 7/65 recurrent infections within 2 months after DHA/PPQ treatment. These findings raise concerns about the long-term efficacy of DHA/PPQ treatment in Africa.

In the last decade, genome-scale metabolic models have been increasingly used to study plant metabolic behaviour at the tissue and multi-tissue level in different environmental conditions. Quercus suber (Q. suber), also known as the cork oak tree, is one of the most important forest communities of the Mediterranean/Iberian region. In this work, we present the genome-scale metabolic model of the Q. suber (iEC7871), the first of a woody plant. The metabolic model comprises 7871 genes, 6230 reactions, and 6481 metabolites across eight compartments. Transcriptomics data was integrated into the model to obtain tissue-specific models for the leaf, inner bark, and phellogen. Each tissue's biomass composition was determined to improve model accuracy and merged into a diel multi-tissue metabolic model to predict interactions among the three tissues at the light and dark phases. The metabolic models were also used to analyze the pathways associated with the synthesis of suberin monomers. Nevertheless, the models developed in this work can provide insights about other aspects of the metabolism of Q. suber, such as its secondary metabolism and cork formation.