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This article examines the historical and ongoing efforts to fight malaria, a parasitic disease caused by Plasmodium species and transmitted by Anopheles mosquitoes. Despite over a century of control efforts, malaria remains a major global health issue. In 2022, there were an estimated 249 million cases across 85 countries, leading to approximately 600,000 deaths. In the recently published Global Technical Strategy for Malaria 2016–2030, the World Health Organization (WHO) has prioritized malaria eradication. The main goals are to reduce malaria incidence and mortality by 90% by 2030 compared to 2015 levels. However, as of 2022, progress has been limited, with only a 2% reduction in incidence and a 6% reduction in mortality. This review traces the historical context of malaria, highlighting its ancient origins and the pivotal scientific discoveries in the late 19th century that paved the way for modern control measures. The Global Malaria Eradication Programme launched by the WHO in 1955 initially showed promise, largely due to the insecticide DDT, but ultimately failed to achieve its goals mainly due to logistical problems, vector resistance to DDT, and inadequate funding. Despite significant advances in the early 21st century, including the Roll Back Malaria initiative and increased international funding, malaria eradication remains a distant goal. Persistent challenges, such as weak healthcare systems, parasite and vector resistance to drugs and insecticides, and inadequate funding, continue to hamper global efforts. Therefore, this article underscores the need for a deeper understanding of malaria's history and recent evolution to inform future strategies for eradication. [ABSTRACT FROM AUTHOR]

Malaria is a deadly disease that is transmitted through mosquito bites. Microscopists use a microscope to examine thin blood smears at high magnification (1000x) to identify parasites in red blood cells (RBCs). Estimating parasitemia is essential in determining the severity of the Plasmodium falciparum infection and guiding treatment. However, this process is time-consuming, labor-intensive, and subject to variation, which can directly affect patient outcomes. In this retrospective study, we compared three methods for measuring parasitemia from a collection of anonymized thin blood smears of patients with Plasmodium falciparum obtained from the Clinical Department of Parasitology-Mycology, National Reference Center (NRC) for Malaria in Paris, France. We first analyzed the impact of the number of field images on parasitemia count using our framework, MALARIS, which features a top-classifier convolutional neural network (CNN). Additionally, we studied the variation between different microscopists using two manual techniques to demonstrate the need for a reliable and reproducible automated system. Finally, we included thin blood smear images from an additional 102 patients to compare the performance and correlation of our system with manual microscopy and flow cytometry. Our results showed strong correlations between the three methods, with a coefficient of determination between 0.87 and 0.92. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Amoebic infection (colitis, extra-intestinal abscesses) due to Entamoeba histolytica (Eh) is usually transmitted by the fecal-oral route. • It can also be transmitted sexually, particularly among men who have sex with men (MSM) when they are asymptomatic carriers. • Genotypic analysis allowed us to understand the sequence of events in this case of sexually-transmitted ameboma without recent travel. [ABSTRACT FROM AUTHOR]

BackgroundIn European France, the bulk of malaria cases are travel-related, and only locally acquired cases are notifiable to assess any risk of re-emergence.AimsWe aimed to contribute to assessing the health impact of locally acquired malaria and the potential of malaria re-emergence in European France by documenting modes of transmission of locally acquired malaria, the Plasmodium species involved and their incidence trends.MethodsWe retrospectively analysed surveillance and case investigation data on locally acquired malaria from 1995 to 2022. We classified cases by most likely mode of transmission using a classification derived from the European Centre for Disease Prevention and Control. A descriptive analysis was conducted to identify spatial and temporal patterns of cases.ResultsFrom 1995 to 2022, European France reported 117 locally acquired malaria cases, mostly due to Plasmodium falciparum (88%) and reported in Île-de-France (54%), Paris Region. Cases were classified as Odyssean malaria (n = 51), induced malaria (n = 36), cryptic malaria (n = 27) and introduced malaria (n = 3). Among the 117 patients, 102 (93%) were hospitalised, 24 (22%) had severe malaria and seven (7%) died.ConclusionLocally acquired malaria remains infrequent in European France, with four reported cases per year since 1995. However, with the recent increasing trend in Odyssean malaria and climate change, the risk of re-emergence in non-endemic countries should be monitored, particularly in areas with autochthonous competent vectors. The vital risk of delayed diagnosis should make physicians consider locally acquired malaria in all patients with unexplained fever, especially when thrombocytopenia is present, even without travel history.

Background: Given the altered responses to both artemisinins and lumefantrine in Eastern Africa, monitoring antimalarial drug resistance in all African countries is paramount. Methods: We measured the susceptibility to six antimalarials using ex vivo growth inhibition assays (IC 50 ) for a total of 805 Plasmodium falciparum isolates obtained from travelers returning to France (2016-2023), mainly from West and Central Africa. Isolates were sequenced using molecular inversion probes (MIPs) targeting fourteen drug resistance genes across the parasite genome. Findings: Ex vivo susceptibility to several drugs has significantly decreased in 2019-2023 versus 2016-2018 parasite samples: lumefantrine (median IC 50 : 23·0 nM [IQR: 14·4-35·1] in 2019-2023 versus 13·9 nM [8·42-21·7] in 2016-2018, p<0·0001), monodesethylamodiaquine (35·4 [21·2-51·1] versus 20·3 nM [15·4-33·1], p<0·0001), and marginally piperaquine (20·5 [16·5-26·2] versus 18.0 [14·2-22·4] nM, p<0·0001). Only four isolates carried a validated pfkelch13 mutation. Multiple mutations in pfcrt and one in pfmdr1 (N86Y) were significantly associated with altered susceptibility to multiple drugs. The susceptibility to lumefantrine was altered by pfcrt and pfmdr1 mutations in an additive manner, with the wild-type haplotype ( pfcrt K76- pfmdr1 N86) exhibiting the least susceptibility. Interpretation: Our study on P. falciparum isolates from West and Central Africa indicates a low prevalence of molecular markers of artemisinin resistance but a significant decrease in susceptibility to the partner drugs that have been the most widely used since a decade -lumefantrine and amodiaquine. These phenotypic changes likely mark parasite adaptation to sustained drug pressure and call for intensifying the monitoring of antimalarial drug resistance in Africa.

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., Competing Interests: Potential conflicts of interest. M. L. G. reports support for attending meetings and/or travel from the European Congress of Clinical Microbiology and Infectious Diseases. M. T. reports payment or honoraria as a speaker at the Colloque Experts Praticiens Infectiologie on 4 February 2022 in Paris for Pfizer. S. J. reports payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from Alfa Sigma expert board; participation on a data and safety monitoring board or advisory board for Artesunate; and data safety surveillance on behalf of the French National Agency for the Safety of Medicines and Health Products. All other authors report no conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: An electronic surveillance system was released to monitor morbidity and mortality incidence of imported malaria cases, investigate autochthonous cases, and assess chemosensitivity of Plasmodium isolates among travelers to and from endemic areas. The aim of this study is to evaluate the use of an electronic surveillance system for imported malaria in France., Materials and Methods: Three main indicators were used to assess the online malaria web-based surveillance system: (1) the quality of the surveillance system; (2) the capacity of the online system to early warning in case of particular events of public health; (3) the knowledge, attitude, and practice of online electronic system by practitioners of malaria network in France., Results: Overall, the median time onset a case is reported to the system decrease by 99%, ranging from 227 days (144-309) to 2 days (1-6) in 2006 and 2020, respectively., Conclusion: The online malaria surveillance system in France has demonstrated its effectiveness and can therefore be extended to carry out numerous investigations linked to research on malaria., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

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., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)