Christelle Pomares

Toxoplasmosis has long been recognized as a serious complication in immunocompromised host, particularly those with advanced HIV/AIDS, hematopoietic stem‐cell transplantation (HSCT), solid‐organ transplant (SOT), and hematological malignancies. The rapid expansion of targeted immunomodulators, including chimeric antigen receptor T‐cell (CAR‐T) therapies, monoclonal antibodies, and small‐molecule inhibitors, is creating new at‐risk populations beyond traditional transplant settings. We present a 9‐year‐old boy with high‐risk B‐cell acute lymphoblastic leukemia (B‐ALL), who developed prolonged fever and macrophage activation syndrome (MAS). After an extensive unrevealing workup, disseminated acute toxoplasmosis was identified incidentally on bone marrow aspirate via morphologic identification of tachyzoites and confirmed by Toxoplasma gondii PCR. This case exemplifies the emerging threat of toxoplasmosis in non‐transplant immunomodulated hosts and supports three core mitigation strategies. First, baseline Toxoplasma IgG and IgM serology should be obtained in all patients initiating targeted immunotherapy, recognizing that B‐cell depletion or hypogammaglobulinemia may render IgG unreliable, and that IgM may be falsely negative, delayed, or persistently positive in immunocompromised individuals. Second, targeted PCR from clinically relevant compartments or metagenomic next‐generation sequencing when conventional diagnostics is unrevealing should be applied early. Third, prevention requires a bundled approach: baseline screening, patient education for seronegative individuals, and trimethoprim‐sulfamethoxazole prophylaxis with or without serial qPCR monitoring for seropositive patients. Toxoplasmosis is no longer a transplant‐exclusive concern. As targeted immunomodulators reshape practice across rheumatology, oncology, neurology, and autoimmune disease, infectious diseases specialists must lead efforts to raise cross‐specialty awareness, establish guidelines, and build registries to define the true burden of toxoplasmosis in these growing populations.

La leishmaniose à Leishmania infantum est une zoonose transmise de mammifère à mammifère par la piqûre d'un insecte vecteur, le phlébotome femelle. S'il est classiquement décrit la leishmaniose viscérale avec la triade classique fièvre, pâleur et splénomégalie, de nombreuses formes cliniques peuvent être associées à ce parasite. Le portage asymptomatique est la forme la plus fréquente et la plus répandue dans l'Ancien Monde ou le Nouveau Monde. Entre la leishmaniose viscérale et le portage asymptomatique, plusieurs formes cliniques sont présentes. Ainsi certains sujets vont exprimer la leishmaniose sous forme d'adénopathies isolées. Ces formes sont intermédiaires entre une expression pauci symptomatique et une leishmaniose viscérale larvée. Alors que L. infantum n'est pas classiquement retrouvé dans des formes muqueuses, des cas ont été récemment décrits. Ces formes muqueuses isolées ne sont pas rares puisque sur les 3 CHU Marseille, Montpellier et Nice, entre 1997 et 2009, 10 cas de leishmaniose muqueuse à L. infantum ont été diagnostiquées principalement chez des sujets immunodéprimés. Il est important de faire le diagnostic de ces formes cliniques particulières puisqu'elles ont pour diagnostic différentiel des néoplasies (lymphome pour la première et néoplasie de la sphère ORL pour la seconde). Afin d'appréhender le rôle du parasite dans l'expression clinique, il a été réalisé le typage par les microsatellites de neuf souches isolées de sujets porteurs asymptomatiques. Il s'avère que ces neuf souches sont très peu polymorphes et que sept d'entre elles possèdent un génotype unique.

La fréquence de la schistosomiase importée par les migrants mineurs non accompagnés (MNA) est mal connue en France. Nous avons recherché, entre décembre 2023 et février 2024, une schistosomiase chez les MNA en plus du dépistage de la tuberculose dans notre Centre de lutte antituberculeuse des Alpes-Maritimes. Un dépistage sérologique (Western Blot) a été proposé à tous les MNA originaires d’Afrique subsaharienne (ASS). En cas de positivité, un examen parasitologique des urines et des selles a été proposé. Au cours de ces trois mois, 187 MNA d’ASS ont été dépistés. La sérologie était positive pour 116 (62 %) d’entre eux. L’âge médian était de 16 ans et le sex-ratio (H/F) de 6,9. Des examens parasitologiques ont pu être réalisés pour 58 (50 %) des 116 MNA ayant une sérologie positive. Des œufs de schistosome ont été trouvés chez 24 d’entre eux. Il y avait des œufs de Schistosoma mansoni dans les selles de 14 MNA, des œufs de S. haematobium dans les urines de 9 MNA et la présence à la fois de S. mansoni et de S. haematobium chez 1 MNA. Cinq MNA présentaient une hématurie (avec S. haematobium) au moment de l’étude. La prévalence de la schistosomiase était d’au moins 12,5 % (24/187). La schistosomiase est fréquente chez les MNA et les formes asymptomatiques sont les plus nombreuses.

: Leishmaniasis caused by Leishmania infantum is endemic in the south of France. Here, we report a case of isolated pulmonary leishmaniasis in a patient with chronic obstructive pulmonary disease. In November 2023, the patient underwent a transbronchial biopsy, which resulted in a histopathological diagnosis of leishmaniasis. This finding was confirmed by polymerase chain reaction (PCR) testing targeting Leishmania species on the biopsy tissue and positive serology, although the results of PCR testing on peripheral blood were negative. These results supported a diagnosis of isolated pulmonary leishmaniasis. Additionally, no clinical or biological indicators of visceral leishmaniasis were identified. Atypical forms of leishmaniasis are rare and often lead to delayed diagnosis. In cases with unusual clinical presentations and a history of exposure in an endemic area, evaluation for leishmaniasis should include a comprehensive assessment of all potentially affected organs, regardless of the patient’s immune status.

Leishmaniases are vector-borne parasitic diseases that pose a threat to over 1 billion people worldwide. The parasites target cells of the reticulohistiocytic system, such as macrophages, where they replicate. The disease manifests in various forms, ranging from localized cutaneous leishmaniasis to life-threatening visceral forms, which are fatal in 95% of cases without treatment. Current treatments rely on the invasive administration of toxic and expensive drugs that are increasingly encountering resistance. Therefore, finding alternative treatments for this disease is imperative. This literature review focuses on recent advancements in alternative treatments and aims to present the various strategies designed to address current limitations, including cost, toxicity, off-target effects, administration routes, and the emergence of drug resistance. Starting with an overview of the existing approved treatments and their specific limitations, we categorize treatment development strategies into five key sections: (i) combination therapies using existing approved treatments to enhance efficacy and reduce resistance; (ii) nanoparticle formulations, which enable targeted delivery to infected organs and improved therapeutic efficiency; (iii) drug repositioning, a strategy that has already contributed to the approval of over half of current therapeutic compounds; (iv) immunomodulation, used in conjunction with standard chemotherapies to enhance treatment efficacy and lower relapse rates; and (v) ethnobotanicals, which have demonstrated promising in vitro results by combining low toxicity, immunomodulatory properties, and potent anti-parasitic effects. In summary, this review outlines current strategies in treatment development, emphasizing their advantages over conventional therapies while acknowledging their limitations.

The prevalence of asymptomatic leishmaniasis in dogs and their owners in the main endemic areas of France has not been studied to date. The objective of this study was to quantify asymptomatic Leishmania infantum infection in southeast France in healthy people and their dogs using molecular and serological screening techniques. We examined the presence of parasitic DNA using specific PCR targeting kinetoplast DNA (kDNA) and specific antibodies by serology (ELISA for dogs and Western blot for humans) among immunocompetent residents and their dogs in the Alpes-Maritimes. Results from 343 humans and 607 dogs were included. 46.9% (n = 161/343) of humans and 18.3% (n = 111/607) of dogs were PCR positive; 40.2% of humans (n = 138/343) and 9.9% of dogs (n = 60/607) were serology positive. Altogether, 66.2% of humans (n = 227) and 25.7% of dogs (n = 156) had positive serologies and/or positive PCR test results. Short-haired dogs were more frequently infected (71.8%, n = 112) than long-haired dogs (12.2%, n = 19) (p = 0.043). Dogs seemed to be more susceptible to asymptomatic infection according to their breed types (higher infection rates in scenthounds, gun dogs and herding dogs) (p = 0.04). The highest proportion of dogs and human asymptomatic infections was found in the Vence Region, corresponding to 28.2% (n = 20/71) of dogs and 70.5% (n = 31/44) of humans (4.5/100,000 people). In conclusion, the percentage of infections in asymptomatic humans is higher than in asymptomatic dogs in the studied endemic area. It is questionable whether asymptomatic infection in humans constitutes a risk factor for dogs.

Dysregulated immune response is the key factor leading to unfavorable coronavirus disease 2019 (COVID-19) outcome. Depending on the pathogen-associated molecular pattern, the NLRP3 inflammasome can play a crucial role during innate immunity activation. To date, studies describing the NLRP3 response during severe acute respiratory syndrome coronavirus 2 infection in patients are lacking. We prospectively monitored caspase-1 activation levels in peripheral myeloid cells from healthy donors and patients with mild to critical COVID-19. The caspase-1 activation potential in response to NLRP3 inflammasome stimulation was opposed between nonclassical monocytes and CD66b+CD16dim granulocytes in severe and critical COVID-19 patients. Unexpectedly, the CD66b+CD16dim granulocytes had decreased nigericin-triggered caspase-1 activation potential associated with an increased percentage of NLRP3 inflammasome impaired immature neutrophils and a loss of eosinophils in the blood. In patients who recovered from COVID-19, nigericin-triggered caspase-1 activation potential in CD66b+CD16dim cells was restored and the proportion of immature neutrophils was similar to control. Here, we reveal that NLRP3 inflammasome activation potential differs among myeloid cells and could be used as a biomarker of a COVID-19 patient’s evolution. This assay could be a useful tool to predict patient outcome. This trial was registered at www.clinicaltrials.gov as #NCT04385017.

Leishmaniases are a group of parasitic diseases transmitted through the bite of female phlebotomine sandflies. Depending on the Leishmania species, the reservoirs can be humans (anthroponosis) or different animals (zoonosis). Zoonotic leishmaniasis present several clinical forms in function of the species involved: visceral leishmaniasis (VL), cutaneous leishmaniasis (CL), and muco-cutaneous leishmaniasis (MCL). The biological diagnosis is of utmost importance because the clinical features are not specific. In addition to parasitological and molecular biology (polymerase chain reaction, PCR) assays, serology is routinely used for the diagnosis of leishmaniasis. Indeed, although PCR is more sensitive than serological assays, its implementation is limited to referral laboratories and research centers. Therefore, serology is still a key element for their diagnosis. Here, we discuss the different serological assays available for the diagnosis of zoonotic leishmaniasis. We will review the enzyme-linked immunosorbent assay, immunofluorescence antibody test, immunochromatography test (ICT), direct agglutination test, and western blot as well as the different diagnostic strategies in function of the clinical form (VL, CL, and MCL). We will also discuss the place of serology for detecting asymptomatic carriers and for the follow-up of VL. Depending on the laboratory, different assays can be used, from ICT, which is appropriate for field testing, to a combination of serological tests to improve the sensitivity.

Background: Primary infection byToxoplasma gondiiin pregnant women can result in serious outcomes for the foetus. A false-positive IgG result during pregnancy can lead to a misdiagnosis of past infection and to stopping preventive measures. We collected 189 sera with positive Architect^®Toxo IgG assay (Abbott Laboratories) and negative IgG results with at least two other serological tests, in order to find an explanation for the suspected false-positive IgG results. We used therecomLine Toxoplasma IgG^®immunoblot (Mikrogen Diagnostik) to search for specific antigenic reactivities of the sera, and the LDBio Toxo II IgG^®immunoblot (LDBio Diagnostics) as a confirmatory test.Results: The bands GRA8 and/or GRA7 were positive for 148 samples (78.3%). GRA8 was the most frequent band, appearing in 133 patterns (70.4%), whereas GRA7 was present for 49 samples (25.9%). Of the 81 samples tested with LDBio^®, 23 (28.4%) turned out to be positive. Of the 58 negative LDBio^®tests (71.6%) (real false-positive Architect^®IgG), 23 samples (39.6%) did not show either a GRA8 or p30 band byrecomLine^®. Their false positivity with Architect^®remains unexplained since Abbott uses these two recombinant antigens for their assay.Conclusions: The Architect^®IgG false positivity forT. gondiiseems to be due to reactivity against GRA8 for the majority of the sera and GRA7 to a lesser extent. The hypothesis of past contact with parasites genetically close toT. gondiisuch asHammondia hammondiorNeospora caninumseems promising and should be assessed further.