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Objectives: Cutaneous leishmaniasis (CL) in Asia, Northern, and Sub-Saharan Africa is mainly caused by Leishmania major and Leishmania tropica. We describe and evaluate the treatment outcome of CL among travelers and migrants in Europe., Methods: We conducted a retrospective study of parasitological confirmed CL cases caused by L. major and L. tropica during 2013-2019 in Europe. Data were collected from medical records and databases within the LeishMan network., Results: Of 206 included cases of CL, 75 were identified as L. major and 131 as L. tropica. Of patients with L. tropica infection, 80% were migrants, whereas 53% of patients with L. major infection had been visiting friends and relatives. Among patients with L. tropica, 48% were younger than 15 years. Pentavalent antimony cured 73% (L. major) and 78% (L. tropica) of patients. The cure rate for intralesional administration was 86% and 67% for systemic, on L. tropica. Liposomal amphotericin B had a cure rate of 44-63%., Conclusion: L. major infections were mostly found in individuals visiting friends and relatives, whereas L. tropica were mainly identified in migrants. No patients with L. major relapsed. Pentavalent antimony, liposomal amphotericin B, and cryotherapy had cure rates in accordance with previous studies., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Patients treated for adult T-Cell leukemia/lymphoma (ATL) have a poor prognosis and are prone to infectious complications which are poorly described. As the French reference center for ATL, we retrospectively analyzed 47 consecutive ATL (acute, n = 23; lymphoma, n = 14; chronic, n = 8; smoldering, n = 2) patients between 2006 and 2016 (median age 51 years, 96% Afro-Caribbean origin). The 3-year overall survival (OS) was 15.8%, 11.3%, and 85.7% for acute, lymphoma, and indolent (chronic and smoldering) forms respectively. Among aggressive subtypes, 20 patients received, as frontline therapy, high dose of zidovudine and interferon alfa (AZT-IFN⍺) resulting in an overall response rate (ORR) of 39% (complete response [CR] 33%) and 17 chemotherapy resulting of an ORR of 59% (CR 50%). Ninety-five infections occurred in 38 patients, most of whom had an acute subtype (n = 73/95; 77%). During their follow-up, patients receiving frontline chemotherapy or frontline AZT-IFNα developed infections in 74% (n = 14/19) and 89% (n = 24/27) of the cases respectively. Sixty-four (67%) of infections were microbiologically documented. Among them, invasive fungal infections (IFI, n = 11) included 2 Pneumocystis jirovecii pneumonia, 5 invasive aspergillosis, and 4 yeast fungemia. IFI exclusively occurred in patients with acute subtype mostly exposed to AZT-IFNα (n = 10/11) and experiencing prolonged (> 10 days) grade 4 neutropenia. Patients with aggressive subtype experiencing IFI had a lower OS than those who did not (median OS 5.4 months versus 18.4 months, p = 0.0048). ATL patients have a poor prognosis even in the modern era. Moreover, the high rate of infections impacts their management especially those exposed to AZT-IFNα., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Cutaneous leishmaniasis (CL) is frequent in travellers and can involve oro-nasal mucosae. Clinical presentation impacts therapeutic management., Methodology: Demographic and clinical data from 459 travellers infected in 47 different countries were collected by members of the European LeishMan consortium. The infecting Leishmania species was identified in 198 patients., Principal Findings: Compared to Old World CL, New World CL was more frequently ulcerative (75% vs 47%), larger (3 vs 2cm), less frequently facial (17% vs 38%) and less frequently associated with mucosal involvement (2.7% vs 5.3%). Patients with mucosal lesions were older (58 vs 30 years) and more frequently immunocompromised (37% vs 3.5%) compared to patients with only skin lesions. Young adults infected in Latin America with L. braziliensis or L. guyanensis complex typically had an ulcer of the lower limbs with mucosal involvement in 5.8% of cases. Typically, infections with L. major and L. tropica acquired in Africa or the Middle East were not associated with mucosal lesions, while infections with L. infantum, acquired in Southern Europe resulted in slowly evolving facial lesions with mucosal involvement in 22% of cases. Local or systemic treatments were used in patients with different clinical presentations but resulted in similarly high cure rates (89% vs 86%)., Conclusion/significance: CL acquired in L. infantum-endemic European and Mediterranean areas displays unexpected high rates of mucosal involvement comparable to those of CL acquired in Latin America, especially in immunocompromised patients. When used as per recommendations, local therapy is associated with high cure rates., Competing Interests: The authors have declared that no competing interests exist.

We report a case of chronic hepatosplenic aspergillosis following immune reconstitution complicating colic aspergillosis in an AIDS patient with multicentric Castleman disease. Symptoms mimicked the clinical presentation of chronic disseminated candidiasis and responded to corticosteroid. This emerging entity enlarges the spectrum of fungal immune reconstitution inflammatory syndrome in the HIV setting., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Systemic use of voriconazole (VCZ) might be restricted by adverse events, such as hepatotoxicity and neurotoxicity, or drug-drug interactions. Topical VCZ application to skin may help to treat local infection more effectively and limit unwanted whole-body exposure. Topical VCZ cream was stable for 90 days when refrigerated. A patient with cutaneous Fusarium solani infection on his right forearm was successfully treated with topical 1% VCZ cream after failure of oral VCZ treatment., (Copyright © 2020 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Cryptococcal meningitis is a severe cause of central nervous system infections among immunocompromised solid organ transplant (SOT) patients. While new diagnostic methods as multiplex meningitis/encephalitis (ME) NAT (nucleic acid test) are increasingly used as a first-line tool in hospital practice, data in HIV-negative patients including SOT remain scarce. We report here false-negative results of multiplex NAT among SOT patients with proven cryptococcal meningitis., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

P. aeruginosa bloodstream infection (BSI) is associated with high hospital mortality. Empirical combination therapy is commonly used, but its benefit remains debated. The purpose of this study was to describe in a paediatric population, demographical characteristics and outcome of children treated for P. aeruginosa BSI receiving either a combined or single antibacterial therapy. We performed a retrospective, single-centre, cohort study of hospitalized children with P. aeruginosa BSI from 2007 to 2015. A total of 118 bloodstream infections (BSI) were analysed (102 (86.4%) hospital-acquired, including 52 (44.1%) hospitalized in intensive care unit). In immunocompromised children, 52% of BSI episodes were recorded. Recent medical history revealed that 68% were hospitalized, 31% underwent surgery and 67% had a prior antibiotic therapy within the last 3 months. In-hospital mortality was similar for patients receiving single or combined anti-Pseudomonas therapy (p = 0.78). In multivariate analysis, independent risk factors for in-hospital mortality were neutropenia (OR = 6.23 [1.94-20.01], hospitalization in ICU (OR = 5.24 [2.04-13.49]) and urinary tract infection (OR = 4.40 [1.02-19.25]).Conclusion: P. aeruginosa BSI mainly occurred in immunocompromised children. Most infections were hospital-acquired and associated with high mortality. Combination therapy did not improve survival. What is Known: • P. aeruginosa bloodstream infection (BSI) is associated with high hospital mortality. Empirical combination therapy is commonly used but its benefit remains debated. What is New: • This is the largest cohort of Pseudomonas aeruginosa bacteraemia in children ever published. P. aeruginosa Bloodstream mainly occurred in immunocompromised children. Most infections were hospital-acquired and associated with high mortality. Combination therapy did not improve survival.

Immune deficiency of diverse etiology, including human immunodeficiency virus (HIV), antineoplastic agents, immunosuppressive agents used in solid organ recipients, immunomodulatory therapy, and other biologics, all promote invasive fungal infections. Subsequent voluntary or unintended immune recovery may induce an exaggerated inflammatory response defining immune reconstitution inflammatory syndrome (IRIS), which causes significant mortality and morbidity. Fungal-associated IRIS raises several diagnostic and management issues. Mostly studied with Cryptococcus , it has also been described with other major fungi implicated in human invasive fungal infections, such as Pneumocystis , Aspergillus , Candida , and Histoplasma . Furthermore, the understanding of IRIS pathogenesis remains in its infancy. This review summarizes current knowledge regarding the clinical characteristics of IRIS depending on fungal species and existing strategies to predict, prevent, and treat IRIS in this patient population, and tries to propose a common immunological background to fungal IRIS.

Background: Non-typhoidal salmonellosis (NTS) often occurs in children with sickle-cell disease (SCD) and remains a significant cause of mortality in developing countries. However, there is lack of reports on the clinical presentation, outcome and complications of NTS in adults with SCD., Methods: We performed a chart review between 2006 and 2016 of adults SCD diagnosed with NTS in 3 referral centers monitoring approximately 3500 SCD adults., Results: Twenty-three episodes of NTS were diagnosed among 22 SCD adults. Diagnosis was challenging: 65% (n = 15/23) of patients presented with vaso-occlusive crisis (VOC) and 30% had no fever. Isolated serotypes were: ser. Enteritidis (n = 8), ser. Typhimurium (n = 6), others (n = 3). We identified two patterns of infections: (1) bacteremic NTS (n = 15) with (n = 9) or without secondary foci of infections (n = 6); (2) non-bacteremic NTS with extra-intestinal foci of infection (n = 8), including primary bones/joints infections (n = 5). Half of patients with osteo-articular localization (n = 6/13) had a previous history of osteonecrosis (n = 2) or osteomyelitis (n = 4) at the same site. Morbidity was high, 6 patients (26%) were admitted to the intensive care unit, 14 patients (61%) required RBC transfusion for VOC. Half of the episodes (n = 12) required surgery (n = 10) or interventional radiology (n = 2) to control the infection. One patient presented a relapse of NTS bacteraemia one year after the first episode., Conclusions: Besides bloodstream infections, clinical presentation of NTS in adults with SCD is non-specific at admission. A triad including bacteraemia, secondary focis of infection and bone localizations was observed in 30% of cases.

Heterozygosity for human signal transducer and activator of transcription 3 ( STAT3 ) dominant-negative (DN) mutations underlies an autosomal dominant form of hyper-immunoglobulin E syndrome (HIES). We describe patients with an autosomal recessive form of HIES due to loss-of-function mutations of a previously uncharacterized gene, ZNF341 ZNF341 is a transcription factor that resides in the nucleus, where it binds a specific DNA motif present in various genes, including the STAT3 promoter. The patients' cells have low basal levels of STAT3 mRNA and protein. The autoinduction of STAT3 production, activation, and function by STAT3-activating cytokines is strongly impaired. Like patients with STAT3 DN mutations, ZNF341-deficient patients lack T helper 17 (T H 17) cells, have an excess of T H 2 cells, and have low memory B cells due to the tight dependence of STAT3 activity on ZNF341 in lymphocytes. Their milder extra-hematopoietic manifestations and stronger inflammatory responses reflect the lower ZNF341 dependence of STAT3 activity in other cell types. Human ZNF341 is essential for the STAT3 transcription-dependent autoinduction and sustained activity of STAT3., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: Complex cutaneous and muco-cutaneous leishmaniasis (CL and MCL) often requires systemic therapy. Liposomal amphotericin B (L-AmB) has a strong potential for a solid clinical benefit in this indication., Methods: We conducted a retrospective analysis of data from a French centralized referral treatment program and from the "LeishMan" European consortium database. All patients with parasitologically proven CL or MCL who received at least one dose of L-AmB were included. Positive outcome was based on ulcer closure as per recent WHO workshop guidelines., Results: From 2008 through 2016, 43 travelers returning from 18 countries (Old World n = 28; New World n = 15) were analyzed with a median follow-up duration of 79 days [range 28-803]. Main clinical forms were: localized CL with one or multiple lesions (n = 32; 74%) and MCL (n = 8; 19%). As per published criteria 19 of 41 patients (46%) were cured 90 days after one course of L-AmB. When the following items -improvement before day 90 but no subsequent follow-up, delayed healing (>3 months) and healing after a second course of L-AmB- were included in the definition of cure, 27 of 43 patients (63%) had a positive outcome. Five patients (MCL = 1; CL = 4) experienced a relapse after a median duration of 6 months [range 3-27] post treatment and 53% of patients (23/43) experienced at least one adverse event including severe hypokalaemia and acute cardiac failure (one patient each). In multivariate analysis, tegumentary infection with L. infantum was associated with complete healing after L-AmB therapy (OR 5.8 IC 95% [1.03-32]) while infection with other species had no impact on outcome., Conclusion: In conditions close to current medical practice, the therapeutic window of L-AmB was narrow in travellers with CL or MCL, with the possible exception of those infected with L. infantum. Strict follow-up is warranted when using L-AmB in patients with mild disease.