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.
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.
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.
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.
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.
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,
< 0.001) and cholesterol/phosphatidylinositol ratio (0.36 versus 0.67,
= 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 (
< 0.0001). At 30Pa EI was 0.56 BT and 0.56 AT vs. 0.60 in controls (
< 0.001). The retention rate (rr) of RBC subpopulations in spleen-mimetic microsphere layers was higher for iRBC (rr = 20%
= 0.0033) and pitted-RBC (rr = 19%,
= 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.
Autochthonous leishmaniasis caused by Leishmania martiniquensis cases in Thailand have dramatically increased in the recent years. L. martiniquensis infection primarily occurs in immunocompromised ...patients, especially AIDS patients. In Thailand, amphotericin B is the only drug available for leishmaniasis treatment, and some patients relapse after amphotericin B therapy. Moreover, the efficacy of anti-leishmanial drugs against L. martiniquensis has not been evaluated to date. In this study, we determined the efficacy of various anti-leishmanial drugs against the promastigote and intracellular amastigote stages of L. martiniquensis using a colorimetric assay. Two strains (CU1 and CU1R1) were isolated from leishmaniasis HIV co-infected patient from Songkhla province, southern Thailand. The CU1 strain was isolated from the patient in 2011, and CU1R1 was isolated from the same patient in 2013, when he was diagnosed as relapse leishmaniasis. The third strain (LSCM1) used in this study has been isolated from immunocompetent patient from Lamphun province, northern Thailand. All strains were identified as L. martiniquensis by sequencing of ribosomal RNA ITS-1 and large subunit of RNA polymerase II gene. Bioassays have been conducted both with promastigote and intracellular amastigote stages of the parasite. All L. martiniquensis strains have been tested against amphotericin B, miltefosine and pentamidine to determine the efficacy of the drugs against the parasite by using a PrestoBlue. The efficacy of miltefosine and pentamidine exhibit no significant difference between each stage of L. martiniquensis among all strains. Surprisingly, the promastigote and intracellular amastigote of the CU1R1 isolate, which was isolated from a relapsed patient after amphotericin B treatment, exhibited a two-fold increased inhibitory concentration (IC50) against amphotericin B compared with other strains, and the difference was statistically significant (p < 0.05). Moreover, intracellular amastigotes isolated from CU1R1 exhibited slightly increased susceptibility to amphotericin B compared with the promastigote (p < 0.05). The result of this experiment is a scientific evident to support that in case of relapsed leishmaniasis caused by L. martiniquensis, increasing dosage of amphotericin B is essential. Moreover, this study also determined efficacy of other anti-leishmanial drugs for treatment the leishmaniasis in Thailand in case of these drugs are available in the country and the clinicians should have alternative drugs for treatment leishmaniasis in Thailand apart from amphotericin B.
Cutaneous leishmaniasis is caused by several Leishmania species that are associated with variable outcomes before and after therapy. Optimal treatment decision is based on an accurate identification ...of the infecting species but current methods to type Leishmania isolates are relatively complex and/or slow. Therefore, the initial treatment decision is generally presumptive, the infecting species being suspected on epidemiological and clinical grounds. A simple method to type cultured isolates would facilitate disease management.
We analyzed MALDI-TOF spectra of promastigote pellets from 46 strains cultured in monophasic medium, including 20 short-term cultured isolates from French travelers (19 with CL, 1 with VL). As per routine procedure, clinical isolates were analyzed in parallel with Multilocus Sequence Typing (MLST) at the National Reference Center for Leishmania.
Automatic dendrogram analysis generated a classification of isolates consistent with reference determination of species based on MLST or hsp70 sequencing. A minute analysis of spectra based on a very simple, database-independent analysis of spectra based on the algorithm showed that the mutually exclusive presence of two pairs of peaks discriminated isolates considered by reference methods to belong either to the Viannia or Leishmania subgenus, and that within each subgenus presence or absence of a few peaks allowed discrimination to species complexes level.
Analysis of cultured Leishmania isolates using mass spectrometry allows a rapid and simple classification to the species complex level consistent with reference methods, a potentially useful method to guide treatment decision in patients with cutaneous leishmaniasis.
Determining specific immune status against Toxoplasma gondii is essential for assessing the risk of reactivation in immunocompromised patients or defining serological monitoring and appropriate ...prophylactic measures during pregnancy. In France, toxoplasmosis serological screening requires systematic testing for IgM and IgG antibodies. The Platelia Toxo IgG and IgM test (Bio-Rad) is one of the most widely used tests for anti-toxoplasmic antibody detection. We performed a study on 384 sera, including 123 IgG negative (<6 IU/mL) and 261 IgG equivocal (6–9 IU/mL) sera tested with Platelia Toxo IgG and collected during routine screening at Pitié-Salpêtrière Hospital, Paris, France to determine the best-performing IgG titer cut-off value. Out of these 383 sera, 298 were IgM negative by Platelia Toxo IgM and 86 were IgM positive. All sera were also tested against Toxo IgG II LD BIO western blot test as confirmation. Our results indicated that an IgG titer cut-off value of ≥4.4 IU/mL for the Platelia Toxo IgG met the definition of positivity, a value significantly lower than that indicated by the manufacturers. In the presence of IgM antibodies, the IgG titer cut-off decreased significantly to a value ≥0.2 IU/mL. This latter cut-off also allowed adequate diagnosis of proven toxoplasmosis seroconversion in 76.7% of cases (33/43). Our findings may improve toxoplasmosis care by reducing therapeutic intervention time and eliminating the need for further serological monitoring.
La détermination du statut immunitaire spécifique contre Toxoplasma gondii est essentielle pour évaluer le risque de réactivation chez les patients immunodéprimés ou définir la surveillance sérologique et les mesures prophylactiques appropriées pendant la grossesse. En France, le dépistage sérologique de la toxoplasmose repose sur la mise en évidence des IgG et IgM antitoxoplasmiques. La technique Platelia Toxo IgG (Bio-Rad) est l’un des tests les plus couramment utilisés pour la détection des anticorps anti-toxoplasmose. Nous avons réalisé une étude sur 384 sérums dont 123 étaient IgG négatifs (< 6 UI/mL) et 261 étaient douteux (6–9 UI/mL) avec la technique Platelia Toxo IgG, collectés dans le cadre de l’activité de routine des Hôpitaux Pitié Salpêtrière à Paris, France, afin de déterminer la valeur la plus discriminante du seuil de positivité pour le titre des IgG. Parmi les 384 sérums, 298 étaient IgM négatifs et 86 étaient IgM positifs avec la technique Platelia Toxo IgM. Tous les sérums ont été systématiquement testés en Western Blot avec la trousse LD BIO Toxo IgG II LDBIO utilisée comme test de référence. Nos résultats montrent qu’un titre d’IgG ≥ 4.4 UI/mL pour le Platelia Toxo IgG définit le seuil de positivité de la technique, une valeur nettement inférieure à celle recommandé par le fabricant (9 UI/mL). En présence d’IgM, le seuil de positivité du titre des IgG baisse de manière significative à ≥ 0.2 UI/mL. Ce dernier seuil a permis le diagnostic de 76.7 % (33/43) des séroconversions toxoplasmiques avérées. Nos résultats peuvent améliorer le soin de la toxoplasmose en réduisant la durée des interventions thérapeutiques et en éliminant le besoin de surveillance sérologique supplémentaire.
Patients with severe malaria treated with artesunate sometimes experience a delayed hemolytic episode. Artesunate (AS) induces pitting, a splenic process whereby dead parasites are expelled from ...their host erythrocytes. These once-infected erythrocytes then return to the circulation. We analyzed hematologic parameters in 123 travelers treated with AS for severe malaria. Among 60 nontransfused patients observed for more than 8 days, 13 (22%) had delayed hemolysis. The peak concentration of circulating once-infected erythrocytes was measured during the first week in 21 patients and was significantly higher in 9 patients with delayed hemolysis than in 12 with other patterns of anemia (0.30 vs 0.07; P = .0001). The threshold of 180 million once-infected erythrocytes per liter discriminated patients with delayed hemolysis with 89% sensitivity and 83% specificity. Once-infected erythrocyte morphology analyzed by using ImageStream in 4 patients showed an 8.9% reduction in their projected area, an alteration likely contributing to their shorter lifespan. Delayed clearance of infected erythrocytes spared by pitting during AS treatment is an original mechanism of hemolytic anemia. Our findings consolidate a disease framework for posttreatment anemia in malaria in which delayed hemolysis is a new entity. The early concentration of once-infected erythrocytes is a solid candidate marker to predict post-AS delayed hemolysis
•After being killed by artesunate, malaria parasites are expelled from red cells and then these pitted red cells reenter the circulation.•When many pitted red cells are produced during therapy, their delayed clearance a few weeks later triggers hemolytic episodes.
Prognostic factors of coronavirus disease 2019 (COVID-19) patients among European population are lacking. Our objective was to identify early prognostic factors upon admission to optimize the ...management of COVID-19 patients hospitalized in a medical ward. This French single-center prospective cohort study evaluated 152 patients with positive severe acute respiratory syndrome coronavirus 2 real-time reverse transcriptase-polymerase chain reaction assay, hospitalized in the Internal Medicine and Clinical Immunology Department, at Pitié-Salpêtrière's Hospital, in Paris, France, a tertiary care university hospital. Predictive factors of intensive care unit (ICU) transfer or death at day 14 (D14), of being discharge alive and severe status at D14 (remaining with ventilation, or death) were evaluated in multivariable logistic regression models; models' performances, including discrimination and calibration, were assessed (C-index, calibration curve, R2, Brier score). A validation was performed on an external sample of 132 patients hospitalized in a French hospital close to Paris, in Aulnay-sous-Bois, Île-de-France. The probability of ICU transfer or death was 32% (47/147) (95% CI 25-40). Older age (OR 2.61, 95% CI 0.96-7.10), poorer respiratory presentation (OR 4.04 per 1-point increment on World Health Organization (WHO) clinical scale, 95% CI 1.76-9.25), higher CRP-level (OR 1.63 per 100mg/L increment, 95% CI 0.98-2.71) and lower lymphocytes count (OR 0.36 per 1000/mm3 increment, 95% CI 0.13-0.99) were associated with an increased risk of ICU requirement or death. A 9-point ordinal scale scoring system defined low (score 0-2), moderate (score 3-5), and high (score 6-8) risk patients, with predicted respectively 2%, 25% and 81% risk of ICU transfer or death at D14. Therefore, in this prospective cohort study of laboratory-confirmed COVID-19 patients hospitalized in a medical ward in France, a simplified scoring system at admission predicted the outcome at D14.
Loiasis is a vector-borne parasitic disease caused by the filarial Loa loa (L. loa). Definitive diagnosis can be done by identifying and counting microfilariae in the peripheral blood by microscopy ...and with L.loa–specific PCR. An additional diagnostic method is the detection of L.loa–specific antibodies. Accurate methods are needed to automate quantification of microfilaria (mf) in peripheral blood. Indeed, the treatment procedure depends on the microfilarial L. loa load in blood. We report the first documented use of flow cytometry as a new method to count microfilaraemia in peripheral blood from a patient with L. loa infection. The diagnosis of loiasis was strongly suspected based on clinical presentation and rapidly confirmed by identifying typical features of L. loa in the peripheral blood. This diagnosis was achieved by flow cytometry using a specific fluorescence pattern for microfilaraemia count. The current report highlights the potential of flow cytometry to assess microfilarial L. loa load from a patient with loiasis infection.
Abstract
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.
From 2011, artesunate was deployed in France through a specific program streamlined by prepositioning in hospital pharmacies to treat severe imported malaria. Robust clinical benefit was confirmed in 1391 patients, as in several subgroups. Anemia was the commonest adverse event.
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