Background The epidemiology of pediatric yeast bloodstream infections remains poorly characterized in high-income settings despite global shifts over the past two decades. As fungal species distribution varies geographically, national surveillance is essential. In France, recent reports have focused predominantly on adults, leaving a significant evidence gap for children. Methods We analyzed data from the YEASTS program, a prospective multicentre hospital-based surveillance study conducted in 27 hospitals in the Paris area, France, between Oct 1, 2002, and Dec 31, 2022. All incident episodes of yeast bloodstream infection diagnosed during this period, were eligible. For the primary analysis, we included children and adolescents aged 6 months to 16 years; neonates and recurrent episodes were excluded. Adult cases (>16 years) recorded during the same period were included for comparison. Species identification and antifungal susceptibility testing, using EUCAST standardized method, were performed at the National Reference Center of invasive Mycoses and Antifungals (NRCMA). The primary objective was to describe the epidemiology of yeast bloodstream infections in children and adolescents and compare findings with those observed in adults (>16 years). The main outcomes assessed were species distribution, antifungal susceptibility patterns, treatment strategies, and 30-day all-cause mortality. Findings Among 346 pediatric episodes, hematological malignancy was the main underlying condition (20.5%). Candida albicans predominated (42%), although non-albicans Candida species collectively accounted for a larger proportion of episodes, notably Candida parapsilosis (23.5%) and Candida tropicalis (10%). Species distribution varied by age: younger children had more C. parapsilosis, older more Pichia kudriavzevii (syn. Candida krusei) and Nakaseomyces glabratus (syn. Candida glabrata). Trichosporon asahii represented 2%. Resistance rates remained low (4% to caspofungin, 8.1% fluconazole) including 4 echinocandin-resistant isolates that harbored S645P mutations in the Fks coding region. 30-day mortality was 13.5%, independently associated with C. tropicalis, N. glabratus, T. asahii, female sex, and ICU admission. Compared with 5889 adult cases, pediatric patients had a distinct species distribution, more frequent prior antifungal exposure, greater use of liposomal amphotericin B, and significantly lower adjusted 30-day mortality. Interpretation Pediatric yeast bloodstream infections exhibit distinct epidemiological characteristics, species distribution, antifungal exposure patterns, and outcomes compared with adult infections. Future research should focus on prospective age-stratified studies to better define optimal antifungal treatment strategies, evaluate the clinical significance of emerging and resistant yeast species, and identify factors associated with poor outcomes in pediatric patients. Funding Santé Publique France and Institut Pasteur.

Understanding the genetic relatedness of Plasmodium vivax recurrences is essential for distinguishing between relapse, reinfection, and recrudescence-a distinction critical for evaluating treatment efficacy and transmission dynamics. We developed P. vivax AmpSeq (PvAmpSeq), an amplicon sequencing assay targeting 11 single-nucleotide polymorphism (SNP)-rich genomic regions. PvAmpSeq was applied to field isolates from a clinical trial in the Solomon Islands and a longitudinal cohort in Peru, and statistical models were applied for the genetic classification of recurrences. In the Solomon Islands trial, where participants received antimalarials at baseline, half of the recurrent infections showed >50% identity-by-descent relatedness to baseline parasites, allowing statistical classification as probable relapses and recrudescences, although with wide uncertainty. In the Peruvian cohort, 68% of the recurrences exhibited <25% relatedness. PvAmpSeq provides high-resolution genotyping to characterize P. vivax recurrences, offering insights into transmission and treatment outcomes. We also discuss the nuances and limitations of available statistical methods for the classification of P. vivax genotyping data.

Invasive fungal diseases are life-threatening complications, particularly in immunocompromised patients, and require rapid and accurate diagnosis to improve clinical outcomes. Although major advances in fungal diagnostics that includes antigen detection, molecular assays, and Matrix-Assisted Laser Desorption/Ionization - Time Of Flight (MALDI-TOF) mass spectrometry, have transformed diagnostic strategies, access to these tools remains heterogeneous. In France, national data on diagnostic capacities for invasive fungal diseases have been lacking. Using the framework of the national prospective surveillance program for invasive fungal diseases (SINFONI network), we conducted a survey to assess laboratory diagnostic practices in France. A secured 116-item questionnaire was distributed to 58 participating laboratories, of which 48 responded (83%). Automated blood culture systems and MALDI-TOF mass spectrometry for yeast identification were universally available, with 40 (83%) of the 48 participating laboratories also using MALDI-TOF for mould identification. Antifungal susceptibility testing was performed on-site in 47 (98%) centres for yeasts and in 37 (77%) for moulds. Antigen-based biomarkers were widely available on-site, particularly cryptococcal antigen (n = 43, 90%) and Aspergillus galactomannan (n = 39, 81%), whereas β-D-glucan testing was available in only 26 (54%) of the centres. PCR-based diagnostics were implemented on-site in 43 (88%) centres, most commonly for Pneumocystis jirovecii, Aspergillus spp., and Mucorales. Systematic screening for Candidozyma auris colonization in at-risk patients was performed in 30 (63%) centres, predominantly using culture-based methods (n = 24). Overall, this survey provides the first national overview of diagnostic capacities for invasive fungal diseases in France, highlighting a strong laboratory mycology infrastructure while identifying remaining gaps in access to specific biomarkers, molecular assays, and mould antifungal susceptibility testing.

BACKGROUND:Pneumocystis pneumonia (PCP) is a well-known infectious complication of organ transplantation requiring prophylaxis at least within the first 6 month to 1 year post transplantation. RESEARCH QUESTION:Few data exist comparing the characteristics of Pneumocystis pneumonia associated with kidney, heart, liver or lung transplant recipients. STUDY DESIGN & METHOD:We here conducted a cross-sectional study nested within the surveillance of our national reference center for invasive mycoses to analyze the prospectively declared cases of PCP occurring in solid organ transplant recipients over a period of 11 years. RESULTS:We found that the median occurrence of PCP post-transplantation varies from the organ recipients with PCP occurring earlier in liver recipients and later in other organs reaching a median of 3.9 years in kidney recipients. We also found a clear increase the proportion of positive mycological criteria in PCP cases occurring within 2 years post-transplantation. Age and ICU hospitalization were major variables associated with 3 month-mortality with liver and lung recipient having a better outcome than renal transplant patients upon adjustment including age. A trend toward the role of additional risk factors (such as HIV, Cancer of hematological malignancy) in the outcome of PCP was also observed. INTERPRETATION:Altogether, this study described on a large patient cohort, some key mycological and clinical information associated with PCP in solid organ transplant patients. The characteristics of PCP in kidney and heart recipients seems similar.

The advent of multiplexing technologies, allowing antibodies to hundreds of antigens to be measured in a single test, has led to enormous increases in the amount of data generated by serological surveys. New modelling methods are required to exploit this data. This study extends serocatalytic models to consider up to three antibody responses targeting the same pathogen simultaneously. These models were fitted to data from cross-sectional serological surveys of Plasmodium falciparum malaria in the Senegalese villages of Dielmo and Ndiop, and model predictions were validated against 22 years of longitudinal epidemiological data. The most accurate reconstruction of historical clinical incidence of P. falciparum was provided by a combination of antibodies to Apical Membrane Antigen 1 (PfAMA1) and Glutamate-Rich Protein (PfGlurpR2). This model estimated a 76% (95% CrI: 61% - 86%) drop in transmission in 2004 (95% CrI: 2001 - 2008) coinciding with changing anti-malarial treatment. Multiplex serocatalytic models provided more accurate estimates of past clinical incidence than singleplex serocatalytic models, with the most accurate multiplex model (PfAMA1 + PfGlurpR2) outperforming all singleplex models (KruskalWallis p < 0.01). Finally, models with three antigens did not provide more accurate estimation than models with two antigens.

OBJECTIVES:Plasmodium vivax relapses can lead to episodes of recurrent parasitemia. We longitudinally assessed parasite and gametocyte kinetics and infectivity to mosquitoes during P. vivax recurrent infections in Ethiopia. METHODS:Patients presenting with clinical P. vivax infections were enrolled at Shele health center in Arba Minch Zuria district, Ethiopia. All participants received chloroquine plus 14-day primaquine for radical cure, and were subsequently followed for one year with scheduled monthly visits. Parasite and gametocyte densities were quantified using molecular assays, and infectivity was assessed through mosquito feeding assays. RESULTS:Over the follow-up period, 54.6% (96/176) of patients experienced at least one recurrent parasitemia. Gametocyte density was similar between baseline and recurrent symptomatic episodes but lower during asymptomatic parasitemia (p<0.001). Across all mosquito feeding assays, 167 (70.2%) of 238 feedings resulted in at least one infected mosquito, with similar proportions between baseline (117 [70.5%] of 166) and recurrent symptomatic infections (50 [69.4%] of 72). Mosquito infection rates were strongly associated with both asexual parasite density (ρ=0.29; p<0.0001; n=166) and gametocyte density (ρ=0.32; p<0.0001) at baseline. Genotyping a subset of recurrent infections indicated 45.7% (42/92) of recurrences were likely to be relapses. After adjusting for gametocyte density, mosquito infection rates appeared lower when feeding on blood of relapsing infections as opposed to new infections (Odds Ratio 0.48, 95% CI 0.26-0.87, p=0.016). CONCLUSIONS:This comprehensive assessment of parasite kinetics and transmissibility over the course of infections uncovers a high frequency of recurring episodes of parasitemia that are accompanied by infectious gametocytes. This work further supports the need to strengthen radical cure to prevent relapsing infections and sustain malaria transmission control.

Following infection with SARS-CoV-2, patients may experience with one or more symptoms that appear or persist over time. Neurological symptoms associated with long COVID include anxiety, depression, and memory impairment. However, the exact underlying mechanisms are not yet fully understood. Using golden hamsters as a model, we provide further evidence that SARS-CoV-2 is neuroinvasive and can persistently infect the brain, as viral RNA and replicative virus are detected in the brainstem 80 days after the initial infection. Infected hamsters exhibit a neurodegenerative signature in the brainstem, characterized by overexpression of innate immunity genes, and altered expression of genes involved in the dopaminergic and glutamatergic synapses, in energy metabolism, and in proteostasis. These infected animals exhibit persistent depression-like behavior, impaired short-term memory, and late-onset signs of anxiety. Finally, we provide evidence that viral and immunometabolic mechanisms coexist in the brainstem of SARS-CoV-2-infected hamsters, contributing to the manifestation of neuropsychiatric and cognitive symptoms.

Primaquine (PQ) remains the only 8-aminoquinoline endorsed by the WHO for treatment of latent Plasmodium vivax liver-stage parasites. PQ is a prodrug, with metabolism and therapeutic activity influenced by inherent human CYP2D6 polymorphisms and by poorly understood interactions with variably co-administered blood schizontocidal therapies. With widespread chloroquine resistance in P. vivax, radical cure now requires use of one of several artemisinin-based combination therapies (ACTs). From September 2017 to February 2019, a randomised clinical trial was conducted in Guadalcanal, Solomon Islands, to evaluate the safety and efficacy of PQ (0·25 mg/kg/day × 14 days) given concurrently with standard doses of either dihydroartemisinin–piperaquine (DP) or artemether–lumefantrine (AL). A relapse control arm received AL without PQ. The 384 enrolled subjects were followed for 180 days to assess efficacy against relapse, along with CYP2D6 genotyping, methaemoglobin monitoring, and measurement of PQ absorption and metabolism. Both PQ treatment arms had significantly reduced rates of current P. vivax parasitamiea (PQ-AL: HR=0·50, CI95[0·33–0·75], PQ-DP: HR=0·34, CI95[0·22–0·52] P < 0·001) relative to no PQ. However, neither regimen provided adequate clinical efficacy (PQ-AL: 43·7%, PQ-DP: 34·1%). No significant differences were observed between PQ-AL and PQ-DP in CYP2D6 genotype-predicted activity scores, methaemoglobin levels, or concentrations of PQ and its metabolites (5,6-OQ and CPQ) on day 7 post-initation of dosing. The dose of PQ administered in this study appears equally inadequate when used in combination with either DP or AL for radical cure. Higher PQ doses are required for effective radical cure in the Western Pacific, where PQ-tolerant Chesson-like strains still appear to commonly occur. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372150, identifier ANZCTR 12617000329369, Universal Trial Number (UTN) U1111-1191-4968.

Background:Establishing correlates of protection often requires large cohorts. A rapid and adaptable case-control study design can be used to identify antibody correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in serum and saliva. Methods:We designed a case-control study to compare antibody levels between cases of SARS-CoV-2 infection within 5 days of symptom onset and uninfected controls. Controls were matched on age, number of coronavirus disease 2019 vaccine doses, time since last dose, and past episodes of infection. We quantified anti-SARS-CoV-2 and seasonal coronavirus immunoglobulin (Ig) G in serum and saliva at inclusion, 1 month, and 6 months. Results:We included 90 cases and 62 controls between February and September 2022. A boost and decay pattern of serum antibodies was observed in cases at 1 and 6 months, respectively, but not in controls. Anti-SARS-CoV-2 antibody levels were significantly higher in controls at inclusion both in serum (particularly antinucleocapsid IgG: 4.14 times higher compared with cases; 95% CI, 2.46-6.96) and saliva (particularly antispike for Delta variant IgG: 4.89 times higher compared with cases; 95% CI, 2.91-9.89). Saliva antibodies generally outperformed serum antibodies for case/control differentiation. Conclusions:In this case-control study, we provided evidence of correlates of protection of anti-SARS-CoV-2 IgG in saliva and serum, with saliva antibodies often outperforming serum. The finding that antibodies in saliva are a better correlate of protection than antibodies in serum may inform vaccine development by highlighting the importance of robust induction of mucosal immune responses. This study design may be used during future epidemics for the prompt assessment of correlates of protection.

Background While invasive fusariosis and lomentosporiosis are known to be associated with fungemia, overall data on mold-related fungemia are limited, hampering early management. This study aimed to describe the epidemiology of mold-positive blood cultures.Methods Epidemiological and clinical data on mold-positive blood cultures from 2012 to 2022 were obtained from the RESSIF database. Pseudofungemia was excluded using modified Duthie and Denning criteria. Univariable and multivariable Firth logistical regression was used to study factors associated with 90-day mortality.Results Fusarium spp accounted for 67.5% of the 80 events, involving predominantly Fusarium fujikuroi spp complex (FFSC), Neocosmospora spp, and Fusarium oxysporum spp complex (FOSC). Lomentospora prolificans was the second most frequent (10%), followed by Trichoderma spp, Aspergillus spp, and Mucorales (5% each). Most patients had a history of hematological malignancy (HM) (70%). Forty-three percent had undergone allogeneic hematopoietic stem cell transplantation. Cutaneous and pulmonary lesions were common (43% each). Median time to blood culture positivity was 72 hours. HM and neutropenia were commonly reported in patients with FFSC, Neocosmospora spp, and L. prolificans fungemia. Pulmonary lesions were frequent in cases of L. prolificans fungemia. Patients with gastrointestinal conditions were frequently diagnosed with FOSC molds. HM (75%), particularly acute myeloblastic leukemia, was frequent in patients with Aspergillus spp fungemia. All patients with Trichoderma spp fungemia were exposed to corticosteroids. Day 90 mortality was 53%. Independent predictive factors of day 90 mortality included L. prolificans (odds ratio [OR], 33.3), Aspergillus spp fungemia (OR, 14.2), and corticosteroid exposure (OR, 7.85).Results Fusarium spp accounted for 67.5% of the 80 events, involving predominantly Fusarium fujikuroi spp complex (FFSC), Neocosmospora spp, and Fusarium oxysporum spp complex (FOSC). Lomentospora prolificans was the second most frequent (10%), followed by Trichoderma spp, Aspergillus spp, and Mucorales (5% each). Most patients had a history of hematological malignancy (HM) (70%). Forty-three percent had undergone allogeneic hematopoietic stem cell transplantation. Cutaneous and pulmonary lesions were common (43% each). Median time to blood culture positivity was 72 hours. HM and neutropenia were commonly reported in patients with FFSC, Neocosmospora spp, and L. prolificans fungemia. Pulmonary lesions were frequent in cases of L. prolificans fungemia. Patients with gastrointestinal conditions were frequently diagnosed with FOSC molds. HM (75%), particularly acute myeloblastic leukemia, was frequent in patients with Aspergillus spp fungemia. All patients with Trichoderma spp fungemia were exposed to corticosteroids. Day 90 mortality was 53%. Independent predictive factors of day 90 mortality included L. prolificans (odds ratio [OR], 33.3), Aspergillus spp fungemia (OR, 14.2), and corticosteroid exposure (OR, 7.85).Results Fusarium spp accounted for 67.5% of the 80 events, involving predominantly Fusarium fujikuroi spp complex (FFSC), Neocosmospora spp, and Fusarium oxysporum spp complex (FOSC). Lomentospora prolificans was the second most frequent (10%), followed by Trichoderma spp, Aspergillus spp, and Mucorales (5% each). Most patients had a history of hematological malignancy (HM) (70%). Forty-three percent had undergone allogeneic hematopoietic stem cell transplantation. Cutaneous and pulmonary lesions were common (43% each). Median time to blood culture positivity was 72 hours. HM and neutropenia were commonly reported in patients with FFSC, Neocosmospora spp, and L. prolificans fungemia. Pulmonary lesions were frequent in cases of L. prolificans fungemia. Patients with gastrointestinal conditions were frequently diagnosed with FOSC molds. HM (75%), particularly acute myeloblastic leukemia, was frequent in patients with Aspergillus spp fungemia. All patients with Trichoderma spp fungemia were exposed to corticosteroids. Day 90 mortality was 53%. Independent predictive factors of day 90 mortality included L. prolificans (odds ratio [OR], 33.3), Aspergillus spp fungemia (OR, 14.2), and corticosteroid exposure (OR, 7.85).Results Fusarium spp accounted for 67.5% of the 80 events, involving predominantly Fusarium fujikuroi spp complex (FFSC), Neocosmospora spp, and Fusarium oxysporum spp complex (FOSC). Lomentospora prolificans was the second most frequent (10%), followed by Trichoderma spp, Aspergillus spp, and Mucorales (5% each). Most patients had a history of hematological malignancy (HM) (70%). Forty-three percent had undergone allogeneic hematopoietic stem cell transplantation. Cutaneous and pulmonary lesions were common (43% each). Median time to blood culture positivity was 72 hours. HM and neutropenia were commonly reported in patients with FFSC, Neocosmospora spp, and L. prolificans fungemia. Pulmonary lesions were frequent in cases of L. prolificans fungemia. Patients with gastrointestinal conditions were frequently diagnosed with FOSC molds. HM (75%), particularly acute myeloblastic leukemia, was frequent in patients with Aspergillus spp fungemia. All patients with Trichoderma spp fungemia were exposed to corticosteroids. Day 90 mortality was 53%. Independent predictive factors of day 90 mortality included L. prolificans (odds ratio [OR], 33.3), Aspergillus spp fungemia (OR, 14.2), and corticosteroid exposure (OR, 7.85).Conclusions Underlying conditions and clinical presentation vary between genera and could be considered to guide early management. Fusarium species were the most common cause of mold-related fungemia. Patients' underlying conditions and clinical presentation differed between genera. Pulmonary and cutaneous lesions were common. Day 90 mortality was high and associated with corticosteroid exposure, Aspergillus spp, and Lomentospora prolificans infection.

Background:Intravenous injection drug use (IVDU) is an established but infrequent risk factor for yeast fungaemia. We aimed to identify features and outcomes of yeast fungaemia associated with IVDU in a nationwide surveillance network in France. Methods:We prospectively included episodes of yeast fungaemia in adults between 2012 and 2022. Episodes with any history of IVDU were considered IVDU-associated. We compared clinical characteristics, infecting species, antifungal treatments, and 90-day mortality between groups. We used Fisher's exact test for categorical variables and the Kruskal-Wallis test for continuous variables. Findings:We recorded 9549 episodes of yeast fungaemia among 9132 adults. Among these, 183 (1·9%) were IVDU-associated. Compared with non-IVDU, individuals with IVDU-associated fungaemia were younger and less likely to have a history of malignancy (13·8%, 20/145 vs. 49·5%, 4447/8987, p < 0·0001) or recent surgery (24·3%, 34/140 vs. 37·3%, 3261/8,733, p = 0·0014), and more likely to have deep-seated infections (14·5%, 21/145 vs. 3·4%, 307/8987, p < 0·0001). IVDU cases less often involved Candida albicans (30·1%, 55/183 vs. 47·6%, 4458/9366, p < 0·0001) and more often involved mixed-species infections (13·1%, 24/183 vs. 4·3%, 402/9366), p < 0·0001. Meyerozyma guilliermondii and Wickerhamomyces anomalus were overrepresented among IVDU cases (6·0%, 11/183 vs. 0·5%, 48/9366, p < 0·0001 and 5·5%, 10/183 vs. 0·05%, 5/9366, p < 0·0001, respectively). The crude 90-day case-fatality ratio was 20·7% (95% CI: 13·7%-29·2%) in the IVDU group versus 48·4% (95% CI: 47·3-49·5%) for non-IVDU. Interpretation:IVDU-associated yeast fungaemia presents distinct clinical and microbiological characteristics, highlighting the need for tailored diagnosis and management. Funding:Financial support from Santé Publique France and Institut Pasteur, Paris.

Large transcellular pores elicited by bacterial mono-ADP-ribosyltransferase (mART) exotoxins inhibiting the small RhoA GTPase compromise the endothelial barrier. Recent advances in biophysical modeling point toward membrane tension and bending rigidity as the minimal set of mechanical parameters determining the nucleation and maximal size of transendothelial cell macroaperture (TEM) tunnels induced by bacterial RhoA-targeting mART exotoxins. We report that cellular depletion of caveolin-1, the membrane-embedded building block of caveolae, and depletion of cavin-1, the master regulator of caveolae invaginations, increase the number of TEMs per cell. The enhanced occurrence of TEM nucleation events correlates with a reduction in cell height due to the increase in cell spreading and decrease in cell volume, which, together with the disruption of RhoA-driven F-actin meshwork, favor membrane apposition for TEM nucleation. Strikingly, caveolin-1 specifically controls the opening speed of TEMs, leading to their dramatic 5.4-fold larger widening. Consistent with the increase in TEM density and width in siCAV1 cells, we record a higher lethality in CAV1 KO mice subjected to a catalytically active mART exotoxin targeting RhoA during staphylococcal bloodstream infection. Combined theoretical modeling with independent biophysical measurements of plasma membrane bending rigidity points toward a specific contribution of caveolin-1 to membrane stiffening in addition to the role of cavin-1/caveolin-1-dependent caveolae in the control of membrane tension homeostasis.

The mosquito-borne disease, Yellow fever (YF), has been largely controlled via mass delivery of an effective vaccine and mosquito control interventions. However, there are warning signs that YF is re-emerging in both Sub-Saharan Africa and South America. Imported from Africa in slave ships, YF was responsible for devastating outbreaks in the Caribbean. In Martinique, the last YF outbreak was reported in 1908 and the mosquito Aedes aegypti was incriminated as the main vector. We evaluated the vector competence of fifteen Ae. aegypti populations for five YFV genotypes (Bolivia, Ghana, Nigeria, Sudan, and Uganda). Here we show that mosquito populations from the Caribbean and the Americas were able to transmit the five YFV genotypes, with YFV strains for Uganda and Bolivia having higher transmission success. We also observed that Ae. aegypti populations from Martinique were more susceptible to YFV infection than other populations from neighboring Caribbean islands, as well as North and South America. Our vector competence data suggest that the threat of re-emergence of YF in Martinique and the subsequent spread to Caribbean nations and beyond is plausible.

After infection with SARS-CoV-2, patients may present with one or more symptoms that appear or persist over time, including fatigue, respiratory, cardiovascular and neurological disorders. Neurological symptoms include anxiety, depression and impaired short-term memory. However, the exact underlying mechanisms of long Covid are not yet decrypted. Using the golden hamster as a model, we provide further evidence that SARS-CoV-2 is neuroinvasive and can persist in the central nervous system, as we found viral RNA and replicative virus in the brainstem after 80 days of infection. Infected hamsters presented a neurodegenerative signature in the brainstem, with overexpression of innate immunity genes, impacted dopaminergic and glutamatergic synapses, altered energy metabolism. Finally, the infected hamsters manifested persistent signs of depression and impaired short-term memory, as well as late-onset signs of anxiety, as a valuable model to study long Covid. Conclusively, we provide evidence that virus-related and neurodegenerative and immunometabolic mechanisms coexist in the brainstem of infected hamsters and contribute to the manifestation of neuropsychiatric and cognitive symptoms. ### Competing Interest Statement The authors have declared no competing interest.

Background Mucormycosis is a deadly invasive fungal infection recently included in the WHO priority pathogen list. Here we sought to describe epidemiological trends of mucormycosis in France, and to evaluate factors associated with mortality. Methods From 2012 to 2022, we implemented a nationwide prospective surveillance programme for mucormycosis in France, focusing on epidemiology, species, seasonal variations. Factors associated with 3-month mortality were studied by univariable and multivariable logistic regression. Findings Among 550 cases of mucormycosis, the main underlying conditions were haematological malignancy (HM, 65.1%, 358/550), trauma (8%, 44/550), diabetes (7.5%, 41/550) and solid-organ transplants (6.5%, 36/550). Site of infection was pulmonary in 52.4% (288/550), rhinocerebral in 14.5% (80/550), and cutaneo-articular in 17.1% (94/550). Main species identified were Rhizopus arrhizus (21%, 67/316), Rhizopus microsporus (13.6%, 43/316), Lichtheimia corymbifera and Mucor circinelloides (13.3%, 42/316 each), Rhizomucor pusillus (12%, 38/316), and Lichtheimia ramosa (10.8%, 34/316). We found associations between underlying condition, site of infection, and infecting species, including a previously undescribed triad of trauma, cutaneo-articular localisations, and L. ramosa/M. circinelloides. Diagnostic contribution of Polymerase Chain Reaction (PCR) increased from 16% (4/25) in 2012 to 91% (61/67) in 2022, with more than 50% of diagnoses relying solely on PCR in 2022. We also found seasonal variations with relatively more cases in autumn. Ninety-day mortality was 55.8% (276/495). Independent prognostic factors were age, diagnosis in Intensive Care Unit (ICU), and HM while diagnosis after 2015 (i.e. large implementation of PCR) and surgery were associated with reduced mortality. Interpretation This study reveals major mucormycosis epidemiological changes in France, with a large predominance of HM patients, and a parallel between PCR multicentre implementation and improved prognosis. We also evidence new associations between species, localisations and risk factors, as well as seasonal variations. Funding Recurrent financial support from Santé Publique France and Institut Pasteur.

Background The Great Mekong Subregion has attained a major decline in malaria cases and fatalities over the last years, but residual transmission hotspots remain, supposedly fueled by forest workers and migrant populations. This study aimed to: (i) characterize the fine-scale mobility of forest-goers and understand links between their daily movement patterns and malaria transmission, using parasites detection via real time polymerase chain reaction (RT PCR) and the individual exposure to Anopheles bites by quantification of anti- Anopheles saliva antibodies via enzyme-linked immunosorbent assay; (ii) assess the concordance of questionnaires and Global Positioning System (GPS) data loggers for measuring mobility. Methods Two 28 day follow-ups during dry and rainy seasons, including a GPS tracking, questionnaires and health examinations, were performed on male forest goers representing the population at highest risk of infection. Their time spent in different land use categories and demographic data were analyzed in order to understand the risk factors driving malaria in the study area. Results Malaria risk varied with village forest cover and at a resolution of only a few kilometers: participants from villages outside the forest had the highest malaria prevalence compared to participants from forest fringe’s villages. The time spent in a specific environment did not modulate the risk of malaria, in particular the time spent in forest was not associated with a higher probability to detect malaria among forest-goers. The levels of antibody response to Anopheles salivary peptide among participants were significantly higher during the rainy season, in accordance with Anopheles mosquito density variation, but was not affected by sociodemographic and mobility factors. The agreement between GPS and self-reported data was only 61.9% in reporting each kind of visited environment. Conclusions In a context of residual malaria transmission which was mainly depicted by P. vivax asymptomatic infections, the implementation of questionnaires, GPS data-loggers and quantification of anti-saliva Anopheles antibodies on the high-risk group were not powerful enough to detect malaria risk factors associated with different mobility behaviours or time spent in various environments. The joint implementation of GPS trackers and questionnaires allowed to highlight the limitations of both methodologies and the benefits of using them together. New detection and follow-up strategies are still called for.

Background Over the last decades, the number of malaria cases has drastically reduced in Cambodia. As the overall prevalence of malaria in Cambodia declines, residual malaria transmission becomes increasingly fragmented over smaller remote regions. The aim of this study was to get an insight into the burden and epidemiological parameters of Plasmodium infections on the forest-fringe of Cambodia. Methods 950 participants were recruited in the province of Mondulkiri in Cambodia and followed up from 2018 to 2020. Whole-blood samples were processed for Plasmodium spp . identification by PCR as well as for a serological immunoassay. A risk factor analysis was conducted for Plasmodium vivax PCR-detected infections throughout the study, and for P. vivax seropositivity at baseline. To evaluate the predictive effect of seropositivity at baseline on subsequent PCR-positivity, an analysis of P. vivax infection-free survival time stratified by serological status at baseline was performed. Results Living inside the forest significantly increased the odds of P. vivax PCR-positivity by a factor of 18.3 (95% C.I. 7.7–43.5). Being a male adult was also a significant predictor of PCR-positivity. Similar risk profiles were identified for P. vivax seropositivity. The survival analysis showed that serological status at baseline significantly correlated with subsequent infection. Serology is most informative outside of the forest, where 94.0% (95% C.I. 90.7–97.4%) of seronegative individuals survived infection-free, compared to 32.4% (95% C.I.: 22.6–46.6%) of seropositive individuals. Conclusion This study justifies the need for serological diagnostic assays to target interventions in this region, particularly in demographic groups where a lot of risk heterogeneity persists, such as outside of the forest.

Introduction Les fongémies à levures (FL) sont une cause importante de morbi- mortalité chez les patients atteints d'hémopathies malignes. Leur épidémiologie a beaucoup évolué ces dernières années et la plupart des données dont nous disposons sont des données adultes. L'objectif de notre étude était de décrire l'épidémiologie des FL chez les enfants atteints d'hémopathies malignes durant les 20 dernières années et de la comparer à celle des adultes. Matériels et méthodes Un programme prospectif multicentrique de surveillance hospitalière des patients développant une FL a été mené entre octobre 2002 et décembre 2022 en région parisienne (Observatoire des levures) par le Centre National de Référence des Mycoses Invasives et Antifongiques (CNRMA). A partir de cette base, nous avons analysé les données des premiers épisodes de FL chez les enfants âgés de 6 mois à 16 ans atteints d'hémopathies malignes et les avons comparées à celles de la population adulte recueillies sur la même période. Résultats Au cours de la période, 928 épisodes de fongémies ont été enregistrés chez 82 enfants et 798 adultes atteints d'hémopathies malignes. L'âge médian au moment du premier épisode était de 8.1 ans (IQR: 3-13,2) dans la population pédiatrique et de 55,3 ans (IQR: 38,5-72) dans la population adulte. Au moment de l'épisode, 11% des enfants vs 35% des adultes étaient en réanimation (p<0,001). Dans la majorité des épisodes (n=906) une seule espèce était responsable de la fongémie. Vingt-deux épisodes (21 dans la population adulte et 1 dans la population pédiatrique) étaient dus à 2 espèces de levures, une seule espèce de levures était retrouvée au cours des autres épisodes. La distribution des espèces était statistiquement différente dans les deux populations (p=0,006) avec une prévalence plus faible de C. albicans et de C. glabrata et une prévalence plus élevée de C. kefyr et de T. asahii chez les enfants par rapport aux adultes. Au moment de la positivation de l'hémoculture, l'antifongique le plus souvent prescrit après les échinocandines était l'amphotéricine B en pédiatrie alors que les azolés étaient préférés dans la population adulte (p<0,001). Le taux de mortalité à 30 jours était significativement plus bas en pédiatrie (11% vs 38%, p<0,001). Conclusion L'épidémiologie des fongémies à levures chez les patients atteints d'hémopathies malignes en pédiatrie est différente de différente de celle des adultes. Ces résultats renforcent l'importance de recommandations spécifiques pédiatriques pour améliorer leur prise en charge.Aucun lien d'intérêt

Primaquine for radical cure of Plasmodium vivax malaria poses a potentially life-threatening risk of haemolysis in G6PD-deficient patients. Herein, we review five events of acute haemolytic anaemia following the administration of primaquine in four malaria trials from Indonesia, the Solomon Islands, and Vietnam. Five males aged 9 to 48 years were improperly classified as G6PD-normal by various screening procedures and included as subjects in trials of anti-relapse therapy with daily primaquine. Routine safety monitoring by physical examination, urine inspection, and blood haemoglobin (Hb) assessment were performed in all those trials. Early signs of acute haemolysis, i.e., dark urine and haemoglobin drop >20%, occurred only after day 3 and as late as day 8 of primaquine dosing. All patients were hospitalized and fully recovered, all but one following blood transfusion rescue. Hb nadir was 4.7 to 7.9 g/dL. Hospitalization was for 1 to 7 days. Hb levels returned to baseline values 3 to 10 days after transfusion. Failed G6PD screening procedures in these trials led G6PD-deficient patients to suffer harmful exposures to primaquine. The safe application of primaquine anti-relapse therapy requires G6PD screening and anticipation of its failure with a means of prompt detection and rescue from the typically abrupt haemolytic crisis.