Candida haemulonii complex, an emerging threat from tropical regions?

BACKGROUND: Candida haemulonii complex-related species are pathogenic yeasts closely related to Candida auris with intrinsic antifungal resistance, but few epidemiological data are available. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed clinical and demographic characteristics of patients with fungemia due to C. haemulonii complex and related species (C. pseudohaemulonii, C. vulturna) reported in France during 2002-2021, and compared them to data of C. parapsilosis fungemia, as they all can be commensal of the skin. We also conducted a study on adult inpatients and outpatients colonized by C. haemulonii complex, managed at the University Hospital of Martinique during 2014-2020. Finally, we performed a literature review of fungemia due to C. haemulonii complex and related species reported in Medline (1962-2022). In total, we identified 28 fungemia due to C. haemulonii complex in France. These episodes were frequently associated with bacterial infection (38%) and high mortality rate (44%), and differed from C. parapsilosis fungemia by their tropical origin, mainly from Caribbean and Latin America. All isolates showed decreased in vitro susceptibility to amphotericin B and fluconazole. In Martinique, we found that skin colonization was frequent in the community population, while colonization was strongly associated with the presence of foreign devices in ICU patients. The literature review identified 274 fungemia episodes, of which 56 were individually described. As in our national series, published cases originated mainly from tropical regions and exhibited high crude mortality. CONCLUSIONS/SIGNIFICANCE: Multidrug-resistant C. haemulonii complex-related species are responsible for fungemia and colonization in community and hospital settings, especially in tropical regions, warranting closer epidemiological surveillance to prevent a potential C. auris-like threat.

Pregnancy in primary immunodeficiency diseases: The PREPI study.

BACKGROUND: Primary immunodeficiencies (PID) are a heterogeneous group of rare inborn immunity defects. As management has greatly improved, morbidity and mortality are reduced in this population, while our knowledge on pregnancy's unfolding and outcome remains scarce. OBJECTIVE: We conducted a retrospective monocentric study to study pregnancy outcomes in women with PID. METHODS: The study cohort consisted of women over 18 included in the national registry for PID (CEREDIH), living in the greater Paris area, reporting ≥1 pregnancy. Data were collected through a standardized questionnaire and medical records. We analyzed PID features, pregnancy course and outcome, and neonatal features (NCT04581460). RESULTS: We studied 93 women with PID (27 combined immunodeficiencies, 51 predominantly antibody deficiencies, and 15 innate immunodeficiencies) and their 222 pregnancies (67, 119, and 36 in each group, respectively). One hundred fifty-four (69%) of 222 pregnancies led to 157 live births, including 4 severe preterm births (3%), in the range of pregnancy outcome in the French general population. In a multivariate model, poor obstetrical outcome (fetal loss or pregnancy termination) was associated with history of severe infection (adjusted odds ratio 0.28, 95% confidence interval 0.11-0.67, P = .005). Only 59% pregnancies were led with optimal anti-infective prophylaxis; severe infections were reported in only 2 pregnancies (1%). One infant died during the neonatal period. CONCLUSION: Pregnancy is achievable in women with a wide group of PID. Prematurity is increased and history of severe infection is associated with significant increase of fetal loss/pregnancy termination. Adjustment of care during pregnancy needs to be better delivered.

Development of a case fatality prognostic score for HIV-associated histoplasmosis.

OBJECTIVES: The burden of histoplasmosis is as great as that of tuberculosis in Latin America and the attributable mortality is even higher. A better assessment of severity could help reduce mortality. METHODS: From the French Guiana HIV-histoplasmosis database, we attempted to identify factors associated with 30-day death after antifungal drug initiation and constructed a prognostic score. We evaluated its discrimination performance using several resampling methods. RESULTS: Of the 415 patients included, 56 (13.5%) died within 30 days of treatment. The fatality-associated factors were performance status ≥3, altered mental status, dyspnea, C-reactive protein ≥75 mg/l, hemoglobin <9 g/dl and/or a platelet <100000/ml, and an interstitial lung pattern on chest X-ray. We constructed a 12-point prognostic score. A threshold ≥5 classified patients as alive or dead at 30 days with a sensitivity of 84%, a specificity of 81%, a positive predicted value of 40%, and a negative predicted value of 97%. The area under the curve of the receiver operating characteristic curves from the different resamples were stable between 0.88 and 0.93. CONCLUSION: The histoplasmosis case fatality score, which is easy and inexpensive to perform, is a good tool for assessing severity and helping in the choice of induction therapy. An external validation remains necessary to generalize these results.

Establishing the proportion of severe/moderately severe vs mild cases of progressive disseminated histoplasmosis in patients with HIV.

BACKGROUND: Progressive disseminated histoplasmosis remains a major but neglected cause of death among patients with advanced HIV. Recently, aiming to reduce avoidable deaths, the Pan American Health Organization issued the first diagnosis and treatment guidelines for HIV-associated histoplasmosis. But what proportion of progressive disseminated histoplasmosis in HIV-infected patients is severe is currently not known. Because this proportion influences treatment needs, we aimed to estimate this in a cohort of 416 patients in French Guiana. METHODS: We used the definition in the recent PAHO/WHO guidelines for severity. We used regression modelling to predict the impact of CD4 count on the proportion of severe cases. In a territory where treatment cost is not a limiting factor and where histoplasmosis is well known, we assumed that clinicians' initial treatment reflected their perception about the severity of the case and therefore, the needs for different treatments. RESULTS: Using these definitions, since the beginning, there were 274 (65.9%) severe/moderately severe cases and 142 (34.1%) mild cases. In practice 186 cases were treated with deoxycholate or liposomal amphotericin B (44.7%) and 230 (55.3%) cases treated with itraconazole as first line treatment. The Kappa concordance measure between the guideline definition and the actual treatment given was 0.22. There was a 9% risk difference for death within 30 days of antifungal treatment initiation between severe/moderately severe and mild cases. Over threequarters (77%) of early deaths were attributed to severe/moderately severe cases. CONCLUSIONS: This is the only rigorous estimate of the proportion of severe/moderately severe cases of progressive disseminated histoplasmosis in symptomatic HIV patients on the largest published cohort. These numbers may help defend budget needs for rapid diagnostic tests and liposomal amphotericin B.