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Background: Procalcitonin (PCT) has been proposed as a marker for malaria severity in adults, with a threshold of 10 ng/ml for severe falciparum disease. Whether PCT is useful in children is debated., Patients & Methods: A retrospective case-control study was conducted to compare initial PCT levels in children with uncomplicated malaria and a control group, and between children with uncomplicated and severe malaria., Results: Results showed significantly higher PCT levels in malaria cases compared to the control group and in malaria severe cases compared to uncomplicated cases. A Receiving Operator Characteristic curve established a PCT threshold of 0.65 ng/ml with a negative predictive value of 98.8 % based on a prevalence of 10 %. Analyzing the pooled results of five studies suggested a threshold of 6.17 ng/ml for differentiating uncomplicated and severe malaria., Conclusion: PCT might be a useful tool to help rule out malaria and predict potential disease severity in returning travelers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Sorbonne Université. Published by Elsevier Ltd.. All rights reserved.)

Background: In endemic foci, the use of an aquaphilic cream containing paromomycin with/without gentamicin to treat cutaneous leishmaniasis (CL) is safe, painless and cures 78-82% of patients with New and Old World CL. Self-application in travelers requires evaluation., Methods: Travelers with 1-10 lesions of confirmed CL were prospectively treated with the paromomycin-gentamicin formulation (WR279396, 2012-2017, Group 1) and carefully follow up, or treated with a locally produced paromomycin-only cream (2018-2022, Group 2). The cream was applied once under supervision, then self-applied daily for 20-30 days. A cured lesion was defined as 100% re-epithelialization at day 42 without relapse at three months., Results: Medical features were similar in Group 1 (17 patients), and Group 2 (23 patients). Patients were infected with either Leishmania major, L. infantum, L. killicki, L. guyanensis, L. braziliensis, or L. naiffi. Intention-to-treat and per-protocol cure rates were 82% (95% confidence interval (CI) [64.23;100.00]) and 87% (95% CI [71,29;100.00]) in Group 1, and 69% (95% CI [50.76; 88.37]) and 76% (95% CI [57.97; 94.41]) in Group 2. In the pooled Group 1&2, 75% (95% CI [61.58;88.42]) (30/40) and 81% (95% CI [68,46;93.6]) (30/37) of patients were cured in intention-to-treat and per-protocol, respectively. There were no significant differences observed in the success rates between Old World and New World CL (83.3% vs. 60%, p = 0.14). Prospective observations in Group 1 showed that adverse events were mainly pruritus (24%) and pain (18%) on lesions (all mild or moderate). No mucosal involvement was observed in either group., Discussion: In this representative population of travelers who acquired CL either in the Old or New World, the 81% per-protocol cure rate of a self-applied aminoglycoside cream was similar to that observed in clinical trials., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests : PB is member of the scientific advisory committee of Drugs for Neglected Diseases initiative., (Copyright: © 2023 Mouri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In acute malaria, the bulk of erythrocyte loss occurs after therapy, with a nadir of hemoglobin generally observed 3-7 days after treatment. The fine mechanisms leading to this early post-treatment anemia are still elusive. We explored pathological changes in RBC subpopulations by quantifying biochemical and mechanical alterations during severe malaria treated with artemisinin derivatives, a drug family that induce "pitting" in the spleen. In this study, the hemoglobin concentration dropped by 1.93 G/dl during therapy. During the same period, iRBC accounting for 6.12% of all RBC before therapy (BT) were replaced by pitted-RBC, accounting for 5.33% of RBC after therapy (AT). RBC loss was thus of 15.9%, of which only a minor part was due to the loss of iRBC or pitted-RBC. When comparing RBC BT and AT to normal controls, lipidomics revealed an increase in the cholesterol/phosphatidylethanolamine ratio (0.17 versus 0.24, p < 0.001) and cholesterol/phosphatidylinositol ratio (0.36 versus 0.67, p = 0.001). Using ektacytometry, we observed a reduced deformability of circulating RBC, similar BT and AT, compared to health control donors. The mean Elongation Index at 1.69Pa was 0.24 BT and 0.23 AT vs. 0.28 in controls ( p < 0.0001). At 30Pa EI was 0.56 BT and 0.56 AT vs. 0.60 in controls ( p < 0.001). The retention rate (rr) of RBC subpopulations in spleen-mimetic microsphere layers was higher for iRBC (rr = 20% p = 0.0033) and pitted-RBC (rr = 19%, p = 0.0031) than for healthy RBC (0.12%). Somewhat surprisingly, the post-treatment anemia in malaria results from the elimination of RBC that were never infected., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chambrion, Depond, Angella, Mouri, Kendjo, Fricot-Monsinjon, Roussel, Biligui, Tantaoui, Taieb, Argy, Houzé, Piarroux, Siriez, Jaureguiberry, Larréché, Théllier, Cenac, Buffet and Ndour.)

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.)

At the emergency department of the Robert-Debré children's hospital in Paris, France, artenimol/piperaquine (AP) has been the first-line antimalarial treatment since September 2012. Most children receive the first dose at the hospital and return home if, after 1 hour's observation, there have been no episodes of vomiting. Here we report the case of two children, aged 11 years and 5 years, respectively, in whom the entire cumulative 3 days' treatment course combined was accidentally administered instead of just the first-day treatment dose. Serum piperaquine levels were measured between Hour 40 (H40) and Day 29 (D29) post-ingestion for the first patient, and between H17 and D7 for the second patient. Corrected QT (QTc) values were measured between H12 and D20 for the first patient and between H17 and H64 for the second patient. Despite reports of adverse electrophysiological events, AP overdose occurred without consequence on the QTc interval or clinical cardiac state in these two children., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Since the 2007 French guidelines on imported Falciparum malaria, the epidemiology, treatment, and prevention of malaria have changed considerably requiring guidelines for all Plasmodium species to be updated. Over the past decade, the incidence of imported malaria has decreased in all age groups, reflecting the decrease in the incidence of malaria in endemic areas. The rates of severe pediatric cases have increased as in adults, but fatalities are rare. The parasitological diagnosis requires a thick blood smear (or a rapid immunochromatographic test) and a thin blood film. Alternatively, a rapid antigen detection test can be paired with a thin blood film. Thrombocytopenia in children presenting with fever is highly predictive of malaria following travel to a malaria-endemic area and, when detected, malaria should be strongly considered. The first-line treatment of uncomplicated P. falciparum malaria is now an artemisinin-based combination therapy (ACT), either artemether-lumefantrine or artenimol-piperaquine, as recommended by the World Health Organization in endemic areas. Uncomplicated presentations of non-falciparum malaria should be treated either with chloroquine or ACT. The first-line treatment of severe malaria is now intravenous artesunate which is more effective than quinine in endemic areas. Quinine is restricted to cases where artesunate is contraindicated or unavailable. Prevention of malaria in pediatric travelers consists of nocturnal personal protection against mosquitoes (especially insecticide-treated nets) combined with chemoprophylaxis according to the risk level., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: Although malaria remains one of the major public health threats in inter-tropical areas, there is limited understanding of imported malaria in children by paediatricians and emergency practitioners in non-endemic countries, often resulting in misdiagnosis and inadequate treatment. Moreover, classical treatments (atovaquone-proguanil, quinine, mefloquine) are limited either by lengthy treatment courses or by side effects. Since 2010, the World Health Organization (WHO) has recommended the use of oral artemisinin-based combination therapy for the treatment of uncomplicated Plasmodium falciparum malaria worldwide. The benefits of artenimol-piperaquine in children have been validated in endemic countries but experience remains limited in cases of imported malaria., Methods: This prospective observational study in routine paediatric care took place at the Emergency Department, Robert-Debré Hospital (Paris, France) from September 2012 to December 2014. Tolerance and efficacy of artenimol-piperaquine in children presenting with the following inclusion criteria were assessed: P. falciparum positive on thin or thick blood smear; and the absence of WHO-defined features of severity., Results: Among 83 children included in this study, treatment with artenimol-piperaquine was successful in 82 children (98.8%). None of the adverse events were severe and all were considered mild with no significant clinical impact. This also applied to cardiological adverse events despite a significant increase of the mean post-treatment QTc interval., Conclusion: Artenimol-piperaquine displays a satisfying efficacy and tolerance profile as a first-line treatment for children with imported uncomplicated falciparum malaria and only necessitates three once-daily oral intakes of the medication. Comparative studies versus artemether-lumefantrine or atovaquone-proguanil would be useful to confirm the results of this study.

Post-malaria neurologic syndrome (PMNS) is a rare complication following a Plasmodium falciparum infection and its pathophysiology remains unclear. This is the first report of a pediatric PMNS following an infection acquired in Africa and the fourth description of pediatric PMNS overall. Neither intrathecal synthesis of Immunoglobin G nor specific P. falciparum antibodies were found in the cerebrospinal fluid.

We report on 4 patients (1 immunocompetent, 3 immunosuppressed) in whom visceral leishmaniasis had become unresponsive to (or had relapsed after) treatment with appropriate doses of liposomal amphotericin B. Under close follow-up, full courses of pentavalent antimony were administered without life-threatening adverse events and resulted in rapid and sustained clinical and parasitological cure.

Quinine was the main treatment for malaria between 1630 and the beginning of the XXth century. In the 1940s, the synthesis of chloroquine gave rise to the hope of eliminating this plague. Falciparum resistance to chloroquine, first observed in Asia then in sub-Saharan Africa, lead researchers to discover halofantrine, mefloquine, atovaquone-proguanil and artemisinin combined therapies. There is no ideal treatment for uncomplicated imported malaria in children. Medical teams have to develop a protocol according to available drugs and their personal experience, with a special attention to follow-up at days 3-4 and day 28. From now on, severe malaria must be treated with intravenous artesunate, a more effective therapy than quinine., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Background: Chloroquine (CQ) was the main malaria therapy worldwide from the 1940s until the 1990s. Following the emergence of CQ-resistant Plasmodium falciparum, most African countries discontinued the use of CQ, and now promote artemisinin-based combination therapy as the first-line treatment. This change was generally initiated during the last decade in West and Central Africa. The aim of this study is to describe the changes in CQ susceptibility in this African region, using travellers returning from this region as a sentinel system., Methods: The study was conducted by the Malaria National Reference Centre, France. The database collated the pfcrtK76T molecular marker for CQ susceptibility and the in vitro response to CQ of parasites from travellers' isolates returning from Senegal, Mali, Ivory Coast or Cameroon. As a proxy of drug pressure, data regarding CQ intake in febrile children were collated for the study period. Logistic regression models were used to detect trends in the proportions of CQ resistant isolates., Results: A total of 2874 parasite isolates were genotyped between 2000-2011. The prevalence of the pfcrt76T mutant genotype significantly decreased for Senegal (from 78% to 47%), Ivory Coast (from 63% to 37%), Cameroon (from 90% to 59%) and remained stable for Mali. The geometric mean of the 50% inhibitory concentration (IC50) of CQ in vitro susceptibility and the proportion of resistant isolates (defining resistance as an IC50 value > 100 nM) significantly decreased for Senegal (from 86 nM (59%) to 39 nM (25%)), Mali (from 84 nM (50%) to 51 nM (31%)), Ivory Coast (from 75 nM (59%) to 29 nM (16%)) and Cameroon (from 181 nM (75%) to 51 nM (37%)). Both analyses (molecular and in vitro susceptibility) were performed for the 2004-2011 period, after the four countries had officially discontinued CQ and showed an accelerated decline of the resistant isolates for the four countries. Meanwhile, CQ use among children significantly deceased in this region (fixed effects slope = -0.3, p < 10-3)., Conclusions: An increase in CQ susceptibility following official withdrawal of the drug was observed in travellers returning from West and Central African countries. The same trends were observed for molecular and in vitro analysis between 2004-2011 and they correlated to the decrease of the drug pressure.

Febrile exanthema is a common symptom in returning travelers. In addition to cosmopolitan diseases, etiologies specific to the visited country must be considered. As an accurate diagnosis is important, clinical suspicion should be confirmed by laboratory tests. The case reports of three brothers returning from Indonesia highlight the possibility of misdiagnosis due to the clinical similarity and serological cross reactivity of dengue fever and measles., (© 2012 International Society of Travel Medicine.)

In order to assess cardiac tolerance of halofantrine in children, we studied, retrospectively, 15 non complicated falciparum malaria cases treated with halofantrine, and focused on the effect on ventricular repolarisation. Our data showed that halofantrine can produce a moderate QTc prolongation without any life-threatening arrhythmia. As long as contraindications of the drug are respected, this treatment should be considered as a therapeutical option in young children presenting with non complicated falciparum malaria.

Introduction: The influenza A (H1N1) 2009 outbreak caused death and a disruption of public health services. Rapid influenza diagnostic tests (RIDT) could be helpful to ease the triage of patients and prevent an overload of emergency and laboratory facilities., Objectives: To compare the sensitivity and specificity of the Clearview Exact Influenza A&B test and real-time reverse transcription(RT)-PCR to detect influenza A (H1N1) 2009 in a paediatric emergency department of a paediatric teaching hospital in Paris, France., Methods: 76 children with an influenza-like illness and either severe symptoms or an underlying medical condition were prospectively recruited between July 2009 and October 2009. RIDT and RT-PCR were simultaneously performed and compared., Results: Among 39 influenza A (H1N1) 2009 RT-PCR-positive children (median age 5&emsp14;years), 23 Clearview Exact Influenza A&B tests were positive. Sensitivity was 59% (95% CI 42.2 to 74) and specificity was 94.6% (95% CI 80.5 to 99.1)., Conclusions: This study shows a sensitivity of RIDT of 59%, in agreement with other prospective studies, which could be useful in clinical practice for diagnosis influenza A (H1N1) 2009 in children. In outbreaks of a high prevalence, such as the 2009 outbreak, this test can help to prevent an overload of public health services.

Staff at the paediatric A&E department of Robert-Debré Hospital in Paris are regularly confronted with difficulties in understanding families most of whom are migrants. Adapted communication tools have been created by the team as part of a collaborative project.

Whether the high variable incubation period of cutaneous larva migrans depends on the parasite or other host factors remains unknown. Two brothers were contaminated simultaneously, but had 15- and 165-day incubation periods, respectively, suggesting a possible influence of host factors. A long incubation period does not rule out cutaneous larva migrans in patients with creeping eruption.

Congenital malaria is uncommon in France. The purpose of this report is to describe a case involving a six-week-old infant who was hospitalized with fever, hepatosplenomegaly, anemia and thrombopenia. Thick and thin blood smears were positive for Plasmodium malariae. The infant responded favorably to chloroquine. Based on this experience, we performed a search of the literature to find case reports on congenital malaria in France and compare clinical and epidemiologic data with series reported in the United States and from endemic areas. The placenta appears to provide an effective barrier against Plasmodium since infection is much more common than disease. The delay for onset of clinical symptoms is longer in temperate zones than in endemic areas. The type of parasite could account for this difference since African congenital malaria are due to Plasmodium falciparum while most cases described in the United States are due to Plasmodium vivax. We also discuss the possible implications of coinfection by HIV in the mother.