Self-application of aminoglycoside-based creams to treat cutaneous leishmaniasis in travelers.

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.

Altered Subpopulations of Red Blood Cells and Post-treatment Anemia in Malaria.

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.

Unintentional artenimol/piperaquine overdose in two children occurring without evidence of subsequent cardiotoxicity.

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.

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.

Artenimol-piperaquine in children with uncomplicated imported falciparum malaria: experience from a prospective cohort.

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: A Rare Pediatric Case Report.

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.

Antimony to Cure Visceral Leishmaniasis Unresponsive to Liposomal Amphotericin B.

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.

Effect of halofantrine on QT interval in children.

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.

Differential diagnosis of dengue fever: beware of measles!

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.

[Improving the care of migrant populations in Emergency Department]. / Améliorer la prise en charge des populations migrantes aux urgences.

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.

Individual variability of the cutaneous larva migrans (CLM) incubation period.

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.