Nosocomial Malaria Transmissions Resolved by Genomic Analyses-A Retrospective Case Report Study in France: 2007-2021.

BACKGROUND: Exposure of blood to malaria parasites can lead to infection even in the absence of the mosquito vector. During a stay in a healthcare facility, accidental inoculation of the skin with blood from a malaria patient might occur, referred to as nosocomial malaria. METHODS: Between 2007 and 2021, we identified 6 autochthonous malaria cases that occurred in different French hospitals, originating from nosocomial transmission and imported malaria cases being the infection source. Four cases were observed during the coronavirus disease 2019 pandemic. The genetic relatedness between source and nosocomial infections was evaluated by genome-wide short tandem repeats (STRs) and single-nucleotide polymorphisms (SNPs). RESULTS: None of the patients with autochthonous malaria had travel history to an endemic area nor had been transfused. For each case, both the source and recipient patients stayed a few hours in the same ward. After diagnosis, autochthonous cases were treated with antimalarials and all recovered except 1. Genetically, each pair of matched source/nosocomial parasite infections showed <1% of different STRs and <6.9% (<1.5% for monoclonal infections) of different SNPs. Similar levels of genetic differences were obtained for parasite DNA samples that were independently sequenced twice as references of identical infections. Parasite phylogenomics were consistent with travel information reported by the source patients. CONCLUSIONS: Our study demonstrates that genomics analyses may resolve nosocomial malaria transmissions, despite the uncertainty regarding the modes of contamination. Nosocomial transmission of potentially life-threatening parasites should be taken into consideration in settings or occasions where compliance with universal precautions is not rigorous.

Impact of Chemoprophylaxis on Plasmodium vivax and Plasmodium ovale Infection Among Civilian Travelers: A Nested Case-Control Study With a Counterfactual Approach on 862 Patients.

BACKGROUND: The impact of chemoprophylaxis targeting Plasmodium falciparum on Plasmodium vivax and Plasmodium ovale, which may remain quiescent as hypnozoites in the liver, is debated. METHODS: We conducted a nested case-control analysis of the outcomes of P. vivax and P. ovale infections in imported malaria cases in France among civilian travelers from 1 January 2006, to 31 December 2017. Using adjusted logistic regression, we assessed the effect of chemoprophylaxis on the incubation period, time from symptoms to diagnosis, management, blood results, symptoms, and hospitalization duration. We analyzed the effect of blood-stage drugs (doxycycline, mefloquine, chloroquine, chloroquine-proguanil) or atovaquone-proguanil on the incubation period. We used a counterfactual approach to ascertain the causal effect of chemoprophylaxis on postinfection characteristics. RESULTS: Among 247 P. vivax- and 615 P. ovale-infected travelers, 30% and 47%, respectively, used chemoprophylaxis, and 7 (3%) and 8 (1%) were severe cases. Chemoprophylaxis users had a greater risk of presenting symptoms >2 months after returning for both species (P. vivax odds ratio [OR], 2.91 [95% confidence interval {CI}, 1.22-6.95], P = .02; P. ovale OR, 2.28 [95% CI, 1.47-3.53], P < .001). Using drugs only acting on the blood stage was associated with delayed symptom onset after 60 days, while using atovaquone-proguanil was not. CONCLUSIONS: Civilian travelers infected with P. vivax or P. ovale reporting chemoprophylaxis use, especially of blood-stage agents, had a greater risk of delayed onset of illness. The impact of chemoprophylaxis on the outcomes of infection with relapse-causing species calls for new chemoprophylaxis acting against erythrocytic and liver stages.

Investigating the Joint Amplitude and Phase Imaging of Stained Samples in Automatic Diagnosis.

The diagnosis of many diseases relies, at least on first intention, on an analysis of blood smears acquired with a microscope. However, image quality is often insufficient for the automation of such processing. A promising improvement concerns the acquisition of enriched information on samples. In particular, Quantitative Phase Imaging (QPI) techniques, which allow the digitization of the phase in complement to the intensity, are attracting growing interest. Such imaging allows the exploration of transparent objects not visible in the intensity image using the phase image only. Another direction proposes using stained images to reveal some characteristics of the cells in the intensity image; in this case, the phase information is not exploited. In this paper, we question the interest of using the bi-modal information brought by intensity and phase in a QPI acquisition when the samples are stained. We consider the problem of detecting parasitized red blood cells for diagnosing malaria from stained blood smears using a Deep Neural Network (DNN). Fourier Ptychographic Microscopy (FPM) is used as the computational microscopy framework to produce QPI images. We show that the bi-modal information enhances the detection performance by 4% compared to the intensity image only when the convolution in the DNN is implemented through a complex-based formalism. This proves that the DNN can benefit from the bi-modal enhanced information. We conjecture that these results should extend to other applications processed through QPI acquisition.

Intravenous Artesunate for the Treatment of Severe Imported Malaria: Implementation, Efficacy, and Safety in 1391 Patients.

BACKGROUND: Intravenous artesunate is the World Health Organization-recommended first-line treatment for severe malaria worldwide, but it is still not fully licensed in Europe. Observational studies documenting its safety and efficacy in imported malaria are thus essential. METHODS: We prospectively collected clinical and epidemiological features of 1391 artesunate-treated patients among 110 participant centers during the first 7 years (2011-2017) of a national program implemented by the French Drug Agency. RESULTS: Artesunate became the most frequent treatment for severe malaria in France, rising from 9.9% in 2011 to 71.4% in 2017. Mortality was estimated at 4.1%. Treatment failure was recorded in 27 patients, but mutations in the Kelch-13 gene were not observed. Main reported adverse events (AEs) were anemia (136 cases), cardiac events (24, including 20 episodes of conduction disorders and/or arrhythmia), and liver enzyme elevation (23). Mortality and AEs were similar in the general population and in people with human immunodeficiency virus, who were overweight, or were pregnant, but the only pregnant woman treated in the first trimester experimented a hemorrhagic miscarriage. The incidence of post-artesunate-delayed hemolysis (PADH) was 42.8% when specifically assessed in a 98-patient subgroup, but was not associated with fatal outcomes or sequelae. PADH was twice as frequent in patients of European compared with African origin. CONCLUSIONS: Artesunate was rapidly deployed and displayed a robust clinical benefit in patients with severe imported malaria, despite a high frequency of mild to moderate PADH. Further explorations in the context of importation should assess outcomes during the first trimester of pregnancy and collect rare but potentially severe cardiac AEs.

Plasmodium ovale wallikeri and P. ovale curtisi Infections and Diagnostic Approaches to Imported Malaria, France, 2013-2018.

We retrospectively analyzed epidemiologic, clinical, and biologic characteristics of 368 Plasmodium ovale wallikeri and 309 P. ovale curtisi infections treated in France during January 2013­December 2018. P. ovale wallikeri infections displayed deeper thrombocytopenia and shorter latency periods. Despite similar clinical manifestations, P. ovale wallikeri­infected patients were more frequently treated with artemisinin-based combination therapy. Although the difference was not statistically significant, P. ovale wallikeri­infected patients were 5 times more frequently hospitalized in intensive care or intermediate care and had a higher proportion of severe thrombocytopenia than P. ovale curtisi­infected patients. Rapid diagnostic tests that detect aldolase were more efficient than those detecting Plasmodium lactate dehydrogenase. Sequence analysis of the potra gene from 90 P. ovale isolates reveals an insufficient polymorphism for relapse typing.

Microsporidiosis after liver transplantation: A French nationwide retrospective study.

BACKGROUND: Microsporidiosis has been largely reported in patients with acquired immunodeficiency syndrome, but emerged as a cause of persistent diarrhea in solid organ transplant patients. METHODS: Through the French Microsporidiosis Network and the Groupe français de recherche en greffe de foie, we collected all microsporidiosis cases identified in liver transplant patients between 1995 and 2020 in France. RESULTS: We identified 24 liver transplant recipients with microsporidiosis. Sex ratio was balanced and median age was 58.8 (3.5-83.5) years (there were 4 children). Microsporidiosis occurred at a median time of 3.9 (0.1-18.9) years post-transplant. Median duration of diarrhea before diagnosis was 22 days (12-45). Therapeutic care included immunosuppressive therapy changes in 20 patients, as follows: stop cyclosporine or tacrolimus (n = 2), dose reduction of cyclosporine or tacrolimus (n = 12), stop MMF (n = 5), and dose reduction of corticosteroids (n = 1). In addition, 15 patients received specific therapy against microsporidiosis: fumagillin (n = 11) or albendazole (n = 4). Median duration of treatment was 14 days (8-45 days). Finally, 7 patients had immunosuppressive treatment tapering only. Microsporidiosis was complicated by renal failure in 15 patients, requiring dialysis in one case. Two patients had infection relapse. No patient presented proven rejection within the 3 months after microsporidiosis. None of the patients died within the 3 months after microsporidiosis. CONCLUSIONS: Microsporidiosis is a very rare infection after liver transplantation but can induce severe dehydration and renal failure. Therefore, it must be systematically sought in any case of persistent diarrhea after first line screening of frequent infectious causes.

Propensity Score Analysis of Artesunate Versus Quinine for Severe Imported Plasmodium falciparum Malaria in France.

BACKGROUND: Little is known on the use of artesunate compared with quinine for the treatment of imported malaria cases in nonendemic countries with a high level of care. Therefore, we compared the 2 treatments in terms of mortality and hospital and intensive care unit (ICU) discharge rates. METHODS: We analyzed the cohort of all severe imported malaria patients reported to the French National Reference Center from 2011 to 2017. After controlling for differences between quinine- and artesunate-treated individuals using the inverse probability of treatment weighting method, 28-day mortality rate was compared between the groups as well as hospital and ICU discharge rates using Kaplan-Meier estimation and weighted Cox proportional hazard models. RESULTS: Overall, 1544 patients were enrolled. Fifty patients died, 18 in the quinine group (n = 460) and 32 in the artesunate group (n = 1084), corresponding to death rates of 3.9% and 2.9%, respectively. No difference was evident between quinine and artesunate either in mortality or in hospital discharge rate, with hazard ratios (HRs) of 1.03 (95% confidence interval [CI], 0.47-2.25) and 1.12 (95% CI, 0.94-1.34), respectively. Artesunate was associated with a faster ICU discharge rate (HR, 1.18. 95% CI, 1.02-1.36). CONCLUSIONS: In a country with a high level of care, artesunate was associated with a shorter length of stay in the ICU, which supports the actual therapeutic transition; however, no difference was found in terms of mortality or in hospital discharge rates between artesunate- and quinine-treated patients.

Fatal Invasive Aspergillosis and Coronavirus Disease in an Immunocompetent Patient.

Invasive pulmonary aspergillosis is a complication in critically ill patients with acute respiratory distress syndrome, especially those with severe influenza pneumonia. We report a fatal case of invasive pulmonary aspergillosis in an immunocompetent patient in France who had severe coronavirus disease-associated pneumonia.

Mortality from malaria in France, 2005 to 2014.

IntroductionMalaria is a notifiable disease in all European Union and European Economic Area countries except Belgium and France, where only autochthonous malaria is notifiable. Although morbidity caused by malaria has been assessed, little is known about mortality incidence.ObjectiveOur aim was to estimate the number of imported malaria-related deaths in hospital in metropolitan France.MethodsWe matched individual deaths reported between 1 January 2005 and 31 December 2014 to the French National Reference Centre for malaria (FNRCm) with malaria-related deaths from two other sources: the French National Registry on medical causes of death and the French national hospital discharge database. A capture-recapture method with log-linear modelling was used. Age, sex and place of death stratification were applied to remove heterogeneity.ResultsThe estimated malaria-related deaths in metropolitan France during the study period were 205 (95% confidence interval (CI): 191-219). The annual mean number of malaria-related deaths was estimated at 21 (95% CI: 19-22). The FNRCm malaria-related deaths surveillance had a 38% sensitivity (95% CI: 32-44). Among 161 in-hospital individual malaria-related deaths reported from three data sources, the sex ratio (male to female) was 2.6. Median age of the patients was 57 years, ranging from 1 to 89 years.ConclusionThe pertinent finding of this report is that malaria-related death records were significantly less complete [corrected] than case records. Therefore, data comparison of imported malaria morbidity and mortality between countries should imperatively be assessed using standard indicators weighted according to the completeness of health surveillance systems.

Plasmodium falciparum Clearance Is Pitting-Dependent With Artemisinin-Based Drugs but Pitting-Independent With Atovaquone-Proguanil or Mefloquine.

Pitting, the removal of dead parasites from their host erythrocyte, has been studied in patients with severe malaria treated parenterally with quinine or artesunate, and was recently shown to contribute to delayed hemolysis, a frequent adverse event of artesunate. We quantified pitting in 81 travelers treated with oral antimalarial therapy. Pitting rate was high (55.8%) with artemisinin-based combinations, but <10% with the nonartemisinin drugs quinine, mefloquine, and atovaquone-proguanil. This may, in part, explain the slower parasite clearance in patients treated with antimalarial drugs lacking an artemisinin component, as well as the absence of posttreatment hemolysis with these drugs.