Correlation between antifungal clinical practices and a new clinical decision support system ANTIFON-CLIC® for the treatment of invasive candidiasis: a retrospective multicentre study.

BACKGROUND: Invasive candidiasis is still recognized as a major cause of morbidity and mortality. To support clinicians in the optimal use of antifungals for the treatment of invasive candidiasis, a computerized decision support system (CDSS) was developed based on institutional guidelines. OBJECTIVES: To evaluate the correlation of this newly developed CDSS with clinical practices, we set-up a retrospective multicentre cohort study with the aim of providing the concordance rate between the CDSS recommendation and the medical prescription (NCT05656157). PATIENTS AND METHODS: Adult patients who received caspofungin or fluconazole for the treatment of an invasive candidiasis were included. The analysis of factors associated with concordance was performed using mixed logistic regression models with department as a random effect. RESULTS: From March to November 2022, 190 patients were included from three centres and eight departments: 70 patients from centre A, 84 from centre B and 36 from centre C. Overall, 100 patients received caspofungin and 90 received fluconazole, mostly (59%; 112/190) for empirical/pre-emptive treatment. The overall percentage of concordance between the CDSS and medical prescriptions was 91% (173/190) (confidence interval 95%: 82%-96%). No significant difference in concordance was observed considering the centres (P > 0.99), the department of inclusion (P = 0.968), the antifungal treatment (P = 0.656) or the indication of treatment (P = 0.997). In most cases of discordance (n = 13/17, 76%), the CDSS recommended fluconazole whereas caspofungin was prescribed. The clinical usability evaluated by five clinicians was satisfactory. CONCLUSIONS: Our results demonstrated the high correlation between current antifungal clinical practice and this user-friendly and institutional guidelines-based CDSS.

Specifically Targeting Metacaspases of Candida: A New Therapeutic Opportunity.

The World Health Organization (WHO) recently published a list of fungal priority pathogens, including Candida albicans and C. auris. The increased level of resistance of Candida 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. Targeting Candida metacaspases to control intrinsic cell death could provide new therapeutic opportunities for invasive candidiasis. In this review, we provide the available evidence for Candida cell death, describe Candida metacaspases, and discuss the potential of Candida metacaspases to offer a new specific target. Targeting Candida cell death has good scientific rationale given that the fungicidal activity of many marketed antifungals is mediated, among others, by cell death triggering. But none of the available antifungals are specifically activating Candida metacaspases, making this target a new therapeutic opportunity for non-susceptible isolates. It is expected that antifungals based on the activation of fungi metacaspases will have a broad spectrum of action, as metacaspases have been described in many fungi, including filamentous fungi. Considering this original mechanism of action, it could be of great interest to combine these new antifungal candidates with existing antifungals. This approach would help to avoid the development of antifungal resistance, which is especially increasing in Candida.

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. Studying the consequences of biomineralization of this crystal during the parasite growth may provide more comprehensive evidence of its role during malaria. OBJECTIVES: This study aimed to investigate the interest of nanoparticles tracker analysis for measuring the concentration and size of hemozoin particles produced from different parasite sources and conditions. METHODS: Hemozoin was extracted from several clones of Plasmodium falciparum both asexual and sexual parasites. Hemozoin was also extracted from blood samples of malaria patients and from saliva of asymptomatic malaria carriers. Nanoparticles tracking analysis (NTA) was performed to assess the size and concentration of hemozoin. RESULTS: NTA data showed variation in hemozoin concentration, size, and crystal clusters between parasite clones, species, and stages. Among parasite clones, hemozoin concentration ranged from 131 to 2663 particles/infected red blood cell (iRBC) and size ranged from 149.6 ± 6.3 nm to 234.8 ± 40.1 nm. The mean size was lower for Plasmodium vivax (176 ± 79.2 nm) than for Plasmodium falciparum (254.8 ± 74.0 nm). Sexual NF54 parasites showed a 7.5-fold higher concentration of hemozoin particles (28.7 particles/iRBC) compared to asexual parasites (3.8 particles/iRBC). In addition, the mean hemozoin size also increased by approximately 60 % for sexual parasites. Compared to in vitro cultures of parasites, blood samples showed low hemozoin concentrations. CONCLUSIONS: This study highlights the potential of NTA as a useful method for analyzing hemozoin, demonstrating its ability to provide detailed information on hemozoin characterization. However, further research is needed to adapt the NTA for hemozoin analysis.

Outcome of patients with cystic fibrosis colonized by Scedosporium and Lomentospora species: A longitudinal cohort study.

Scedosporium and Lomentospora species rank second among the filamentous fungi colonizing the airways of cystic fibrosis (CF) patients. These fungi could be responsible for allergic bronchopulmonary mycosis (ABPM) and bronchitis before lung transplantation and invasive infections after. However, their role in CF lung disease is debated. This study aimed to identify clinical or environmental factors associated with an airway colonization by Scedosporium/Lomentospora species in patients with CF over a period of 7 years. A longitudinal cohort study was conducted from 2008 to 2014 in the CF reference centre in Lyon, France, to compare the characteristics of patients with Scedosporium/Lomentospora colonized and non-colonized patients. During the study period, 283 patients completed the clinical and microbiological follow-up. The analysis revealed that a higher number and duration of hospitalizations, an increased number of courses of parenteral antibiotic therapy, a history of ABPA, and treatment by itraconazole were significantly associated with an airway colonization by Scedosporium/Lomentospora species. The rate of decline of forced expiratory volume in the first second was not statistically different between colonized and non-colonized patients. This study provides evidence that patients colonized by Scedosporium/Lomentospora species require more medical care than non-colonized patients. Additional care could be in part explained by the management of Scedosporium/Lomentospora-related diseases such as ABPM or bronchitis. However, we did not demonstrate a faster rate of decline of respiratory function or body mass index in colonized patients, suggesting, as previously reported, that colonization of the airways by these fungi does not play a significant role in the progression of CF disease.

This prospective study did not demonstrate a faster rate of decline of respiratory function or body mass index in cystic fibrosis (CF) patients colonized by Scedosporium/Lomentospora species compared to non-colonized patients, suggesting that these fungi do not play a significant role in the progression of CF disease.

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. Molecular methods to detect low parasitemia are not available at point-of-care in low-income countries of malaria endemic areas. Adaptation of molecular methods such as loop-mediated isothermal amplification of DNA may provide effective tools but it required simplification of DNA detection. Square waves voltammetry, easily imbedded in small device such as cell phone, was largely described for DNA detection but support for reaction was an issue to address. Here we used an efficient functionalization method of paper-based material to facilitate the interactions between isothermal amplification product and methylene blue for easy-to-use DNA detection. The proof-of-concept of qualitative detection of very low parasitemia from malaria infected patients using newly chemically treated paper for square waves voltammetry was obtained with a sensitivity and specificity of 100% and a limit-of-detection of 0.1 parasite. µL-1 corresponding to a parasitemia of 0.000002%.

Protocols for Plasmodium gametocyte production in vitro: an integrative review and analysis.

BACKGROUND: The production of Plasmodium gametocytes in vitro is a real challenge. Many protocols have been described, but few have resulted in the production of viable and infectious gametocytes in sufficient quantities to conduct research on-but not limited to-transmission-blocking drug and vaccine development. The aim of this review was to identify and discuss gametocyte production protocols that have been developed over the last two decades. METHODS: We analyzed the original gametocyte production protocols published from 2000 onwards based on a literature search and a thorough review. A systematic review was performed of relevant articles identified in the PubMed, Web of Sciences and ScienceDirect databases. RESULTS: A total 23 studies on the production of Plasmodium gametocytes were identified, 19 involving in vitro Plasmodium falciparum, one involving Plasmodium knowlesi and three involving ex vivo Plasmodium vivax. Of the in vitro studies, 90% used environmental stressors to trigger gametocytogenesis. Mature gametocytemia of up to 4% was reported. CONCLUSIONS: Several biological parameters contribute to an optimal production in vitro of viable and infectious mature gametocytes. The knowledge gained from this systematic review on the molecular mechanisms involved in gametocytogenesis enables reproducible gametocyte protocols with transgenic parasite lines to be set up. This review highlights the need for additional gametocyte production protocols for Plasmodium species other than P. falciparum.

Impact of COVID-19 pandemic on antifungal consumption: a multicenter retrospective analysis.

BACKGROUND: In the context of COVID-19 pandemic, antifungal overuse may have occurred in our hospitals as it has been previously reported for antibacterials. METHODS: To investigate the impact of COVID-19 on antifungal consumption, a multicenter retrospective study including four medical sites and 14 intensive care units (ICU) was performed. Antifungal consumption and incidences of invasive fungal diseases before and during COVID-19 pandemic, for non-COVID-19 patients and COVID-19 patients, were described. RESULTS: An increase in voriconazole consumption was observed in 2020 compared with 2019 for both the whole hospital and the ICU (+ 40.3% and + 63.7%, respectively), whereas the incidence of invasive aspergillosis significantly increased in slightly lower proportions in the ICU (+ 46%). Caspofungin consumption also increased in 2020 compared to 2019 for both the whole hospital and the ICU (+ 34.9% and + 17.0%, respectively) with an increased incidence of invasive candidiasis in the whole hospital and the ICU but in lower proportions (+ 20.0% and + 10.9%, respectively). CONCLUSIONS: We observed an increased consumption of antifungals including voriconazole and caspofungin in our hospital during the COVID-19 pandemic and explained in part by an increased incidence of invasive fungal diseases in COVID-19 patients. These results are of utmost importance as it raises concern about the urgent need for appropriate antifungal stewardship activities to control antifungal consumption.

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. We show that the Ca2+ ion interacts with a loop in the vicinity of the catalytic site. The reorganization of this cation binding loop, by bringing together the two catalytic residues, could be one of the main structural determinants triggering metacaspase activation. Enzymatic exploration of CgMCA-I confirmed that the maturation process implies a trans mechanism with sequential cleavages.

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. There is, therefore, a need for an alternative route for malaria pre-referral treatment. The aim of this study was to assess the potential of intranasal route for malaria pre-referral treatment. METHODS: The permeability of artesunate through human nasal mucosa was tested in vitro. The Transepithelial Electrical Resistance (TEER) of the nasal mucosa was followed during the permeation tests. Beside, regional deposition of artesunate powder was assessed with an unidose drug delivery device in each nostril of a nasal cast. Artesunate quantification was performed using Liquid Chromatography coupled to tandem Mass Spectrometry. RESULTS: The experimental model of human nasal mucosa was successfully implemented. Using this model, artesunate powder showed a much better passage rate through human nasal mucosa than solution (26.8 ± 6.6% versus 2.1 ± 0.3%). More than half (62.3%) of the artesunate dose sprayed in the nostrils of the nasal cast was recovered in the olfactory areas (44.7 ± 8.6%) and turbinates (17.6 ± 3.3%) allowing nose-to-brain and systemic drug diffusion, respectively. CONCLUSION: Artesunate powder showed a good permeation efficiency on human nasal mucosa. Moreover it can be efficiently sprayed in the nostrils using unidose device to reach the olfactory area leading to a fast nose-to-brain delivery as well as a systemic effect. Taken together, those results are part of the proof-of-concept for the use of intranasal artesunate as a malaria pre-referral treatment.

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 0.12-100 µM, with generally good resistance index. The most active ferrocene in these series exhibited IC50 equal to 0.09 µM (3D7) and 0.12 µM (W2). The low cytotoxicity of the ferrocenyl-containing γ-hydroxy-γ-lactam tetramates against Human Umbilical Vein Endothelial (HUVEC) cell line demonstrated selective antiparasitic activity. The redox properties of these ferrocene-derived tetramates were studied and physico-biochemical studies evidenced that these derivatives can exert potent antimalarial activities via a mechanism distinct from ferroquine.

Systematic review of Plasmodium knowlesi in Indonesia: a risk of emergence in the context of capital relocation to Borneo?

BACKGROUND: The Indonesian Republic plans to relocate its capital from Jakarta to East Kalimantan, Borneo Island, in the next few years. This relocation may be associated with deforestation, decreased biodiversity, and an increased risk of emerging zoonotic infections, including Plasmodium knowlesi malaria. The Malaysian part of Borneo Island is one of the main hotspots of P. knowlesi malaria. METHODS: Considering this risk, we evaluated the transmission dynamics of P. knowlesi in the Indonesian Archipelago based on a literature search and extensive review of data from the Indonesian Ministry of Health. RESULTS: We report that 545 P. knowlesi cases were documented in Indonesia, mainly in the Aceh and North Sumatra provinces, with 95% of these occurring in the last 4 years. CONCLUSIONS: The main P. knowlesi vectors are present in the area of the future capital, requiring strengthened surveillance to reduce the risk of emerging cases in a rapidly growing population.

Practical checklist for implementation of antifungal stewardship programmes.

Introduction. Antifungal stewardship programmes are needed in healthcare facilities to limit the overuse or misuse of antifungals, which are responsible for an increase in antifungal resistance.Hypothesis/Gap Statement. Core recommendations for antifungal stewardship were published by the Mycoses Study Group Education and Research Consortium, while the Centers for Disease Control and Prevention (CDC) provided a Core Elements of Hospital Antibiotic Stewardship Programs checklist. The recommendations offer global core elements for best practices in antifungal stewardship, but do not provide a framework for the implementation of antifungal stewardship programmes in healthcare facilities.Aim. In line with the recommendations, it is of the utmost importance to establish a practical checklist that may be used to implement antifungal stewardship programmes.Methodology. The practical checklist was established by a national consensus panel of experts involved in antifungal stewardship activities. A preliminary checklist was sent to all experts. The final document was approved by the panel after discussion and the resolution of any disagreements by consensus.Results. The final checklist includes the following items: leadership support; actions to support optimal antifungal use; actions to monitor antifungal prescribing, use and resistance; and an education programme.Conclusion. This antifungal stewardship checklist offers opportunities for antifungal resistance containment, given that antifungal stewardship activities promote the optimal use of antifungals.

Diagnostic accuracy of fluorescence flow-cytometry technology using Sysmex XN-31 for imported malaria in a non-endemic setting.

Malaria diagnosis based on microscopy is impaired by the gradual disappearance of experienced microscopists in non-endemic areas. Aside from the conventional diagnostic methods, fluorescence flow cytometry technology using Sysmex XN-31, an automated haematology analyser, has been registered to support malaria diagnosis. The aim of this prospective, monocentric, non-interventional study was to evaluate the diagnostic accuracy of the XN-31 for the initial diagnosis or follow-up of imported malaria cases compared to the reference malaria tests including microscopy, loop mediated isothermal amplification, and rapid diagnostic tests. Over a one-year period, 357 blood samples were analysed, including 248 negative and 109 positive malaria samples. Compared to microscopy, XN-31 showed sensitivity of 100% (95% CI: 97.13-100) and specificity of 98.39% (95% CI: 95.56-100) for the initial diagnosis of imported malaria cases. Moreover, it provided accurate species identification asfalciparumor non-falciparumand parasitaemia determination in a very short time compared to other methods. We also demonstrated that XN-31 was a reliable method for patient follow-up on days 3, 7, and 28. Malaria diagnosis can be improved in non-endemic areas by the use of dedicated haematology analysers coupled with standard microscopy or other methods in development, such as artificial intelligence for blood slide reading. Given that XN-31 provided an accurate diagnosis in 1 min, it may reduce the time interval before treatment and thus improve the outcome of patient who have malaria.

Title: Précision diagnostique de la technique de cytométrie de flux en fluorescence utilisant le Sysmex XN-31 pour le paludisme d'importation en zone non endémique. Abstract: Le diagnostic du paludisme basé sur la microscopie est rendu difficile par la disparition progressive des microscopistes expérimentés en zone non-endémique. À côté des méthodes conventionnelles, la technique de cytométrie de flux en fluorescence utilisant le Sysmex XN-31, un automate d'analyse hématologique, a été enregistrée pour participer au diagnostic du paludisme. L'objectif de cette étude prospective, monocentrique et non-interventionelle était d'évaluer la précision diagnostique du XN-31 pour le diagnostic initial et le suivi des cas de paludisme d'importation en comparaison des tests de référence dont la microscopie, l'amplification isothermale en boucle, et des tests de diagnostic rapide. Durant une période d'un an, 357 échantillons de sang ont été analysés, dont 248 négatifs et 109 positifs pour le paludisme. En comparaison de la microscopie, le XN-31 a montré une sensibilité de 100 % (95 % CI : 97.13-100) et une spécificité de 98.39 % (95 % CI : 95.56-100) pour le diagnostic initial des cas de paludisme d'importation. De plus, l'identification des espècesfalciparumet non-falciparumainsi que la parasitémie ont été précises dans un temps très court en comparaison des autres méthodes. Nous avons aussi démontré que le XN-31 était une méthode fiable pour le suivi des patients à J3, J7 et J28. Le diagnostic du paludisme peut être amélioré en zone non-endémique par l'utilisation d'automates d'hématologie spécialisés, associés à la microscopie standard ou d'autres méthodes en développement telle que l'intelligence artificielle appliquée à la lecture des lames de sang. Dans la mesure où le XN-31 produit un diagnostic précis en une minute, cela peut réduire le délai avant le traitement et donc améliorer l'issue pour les patients souffrant de paludisme.

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. The tests are based on the measurement of samples' antimalarial activity on Plasmodium falciparum 3D7 using a modified SYBR Green I drug susceptibility test. For the quantitative test, we established a standard curve that resulted from a dose-response curve and evaluated its performances using controls samples. Whereas the linear regression analysis between artesunate concentration and antimalarial activity showed promising results (linearity range 1.5-24.6 ng/mL, r2 = 0.9373), we found that artesunate content of the controls was significantly overestimated (p = 0.0313). For the semi-quantitative test, we compared the antimalarial activities of samples collected during permeation studies of artesunate to that of a reference (artesunate IC50) by statistical analysis. We demonstrated that antimalarial activities of samples from permeation tests using a powder formulation of artesunate were greater than those of samples from tests using a solution formulation. Bioassays can be simple techniques to assess artesunate in liquid samples, particularly in resource-limited settings. Comparison with reference methods is still recommended when accurate drug quantification is required.

Title: Évaluation de méthodes de tests biologiques quantitatives et semi-quantitatives de l'artésunate in vitro. Abstract: L'artésunate est le médicament antipaludique le plus puissant actuellement, largement utilisé pour le traitement du paludisme. Compte tenu de l'émergence de la résistance à l'artémisinine, plusieurs situations peuvent nécessiter une méthode simple de quantification de l'artésunate. Nous avons ainsi développé un test biologique quantitatif et un test semi-quantitatif pour le dosage de l'artésunate dans des échantillons liquides. Les méthodes sont basées sur la mesure de l'activité antipaludique des échantillons sur Plasmodium falciparum 3D7 à l'aide d'un test de sensibilité aux médicaments SYBR Green I modifié. Pour le test quantitatif, nous avons établi une courbe standard issue d'une courbe dose-réponse et évalué ses performances à l'aide d'échantillons témoins. Alors que l'analyse de régression linéaire entre la concentration d'artésunate et l'activité antipaludique a montré des résultats prometteurs (gamme de linéarité de 1,5 à 24,6 ng/mL, r2 = 0,9373), nous avons constaté que la teneur en artésunate des témoins était significativement surestimée (p = 0,0313). Pour le test semi-quantitatif, nous avons comparé les activités antipaludiques d'échantillons collectés lors des études de perméation de l'artésunate à celle d'une référence (artésunate IC50) par analyse statistique. Nous avons démontré que les activités antipaludiques des échantillons provenant de tests de perméation utilisant une formulation en poudre d'artésunate étaient supérieures à celles des échantillons provenant de tests utilisant une formulation en solution. Les dosages biologiques peuvent être des techniques simples pour évaluer l'artésunate dans des échantillons liquides, en particulier dans les milieux à ressources limitées. La comparaison avec des méthodes de référence est toujours recommandée lorsqu'une quantification précise du médicament est requise.

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. In that respect, we discussed the use of anti-parasitic in animals including anticoccidials, anthelmintics, and insecticides-acaricides, and the use of azoles in the environment that may both favor the development of drug resistance in humans. In light of the current situation, there is an urgent need for a transdisciplinary approach through anti-parasitic and antifungal stewardship programs in humans, animals, and environment, especially in the era of COVID-19 pandemic that will probably aggravate antimicrobial resistance.

Association between voriconazole exposure and Sequential Organ Failure Assessment (SOFA) score in critically ill patients.

Therapeutic drug monitoring (TDM) is essential for voriconazole to ensure optimal drug exposure, mainly in critically ill patients for whom voriconazole demonstrated a large variability. The study aimed at describing factors associated with trough voriconazole concentrations in critically ill patients and evaluating the impact of voriconazole concentrations on adverse effects. A 2-year retrospective multicenter cohort study (NCT04502771) was conducted in six intensive care units. Adult patients who had at least one voriconazole TDM were included. Univariable and multivariable linear regression analyses were performed to identify predictors of voriconazole concentrations, and univariable logistic regression analysis, to study the relationship between voriconazole concentrations and adverse effects. During the 2-year study period, 70 patients were included. Optimal trough voriconazole concentrations were reported in 37 patients (52.8%), subtherapeutic in 20 (28.6%), and supratherapeutic in 13 (18.6%). Adverse effects were reported in six (8.6%) patients. SOFA score was identified as a factor associated with an increase in voriconazole concentration (p = 0.025), mainly in the group of patients who had SOFA score ≥ 10. Moreover, an increase in voriconazole concentration was shown to be a risk factor for occurrence of adverse effects (p = 0.011). In that respect, critically ill patients who received voriconazole treatment must benefit from a TDM, particularly if they have a SOFA score ≥ 10. Indeed, identifying patients who are overdosed will help to prevent voriconazole related adverse effects. This result is of utmost importance given the recognized COVID-19-associated pulmonary aspergillosis in ICU patients for whom voriconazole is among the recommended first-line treatment.

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.

Systematic review and meta-analysis of diagnostic accuracy of loop-mediated isothermal amplification (LAMP) methods compared with microscopy, polymerase chain reaction and rapid diagnostic tests for malaria diagnosis.

BACKGROUND: Diagnosis is a challenging issue for eliminating malaria. Loop-mediated isothermal amplification (LAMP) could be an alternative to conventional methods. This study aimed to evaluate the diagnostic accuracy of LAMP for malaria compared with microscopy, polymerase chain reaction (PCR) and rapid diagnostic tests (RDTs). METHODS AND DESIGN: MEDLINE, Web of Science and Scopus were searched from inception to 1 July 2019. Prospective and retrospective, randomised and non-randomised, mono-center and multi-center studies, including symptomatic or asymptomatic patients, that reported one LAMP method and one comparator (microscopy, RDT or PCR) were included. PROSPERO registration number: CRD42017075186. RESULTS: Sixty-six studies published between 2006 and 2019 were included, leading to the analysis of 30,641 LAMP tests. The pooled sensitivity of LAMP remained between 96% and 98%, whichever the comparator. The pooled specificity of LAMP was around 95%, but was a little higher if the best PCR studies were considered. The AUC was found to be >0.98, whichever the subgroup of studies was considered. Diagnostic odds ratio (DOR) was found to be around 1000 for all subgroups, except for Plasmodium vivax. CONCLUSION: This meta-analysis confirmed that the LAMP method is robust for diagnosing malaria, both in symptomatic and asymptomatic people. Thus, the impact of LAMP for controlling malaria is expected to be important.