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Background: Nirmatrelvir/ritonavir (NMV/r) and three-day course remdesivir (3RDV) have been approved as early treatments for COVID-19 outpatients not requiring supplemental oxygen. Real-life data on the efficacy of antivirals among immunocompromised patients or directly comparing their effectiveness in preventing hospitalization and/or death are scarce. Methods: Prospective, observational study conducted in a tertiary care hospital, from 1 January 2022 until 15 March 2023, during the prevalence of the Omicron variant. Inverse probability of treatment weighting (IPTW) was used to account for differences between treatment groups. Results: We included 521, mainly immunocompromised (56%), patients in our analysis; 356 (68.3%) received 3RDV and 165 (31.7%) NMV/r. Overall, 15/521 (2.9%) patients met the primary end-point of hospitalization at 30 days (3RDV arm: 10/356, 2.8% vs. NMV/r arm: 5/165, 3%, p = 1). On IPTW-adjusted univariable analysis, the choice of treatment did not affect outcomes. In multivariable logistic regression analysis, we found that one (OR 0.26, 95%CI 0.07–0.99, p = 0.049) or two (OR 0.06, 95%CI 0.01–0.55, p = 0.014) vaccine booster shots reduced the risk for adverse outcomes. Conclusion: In our patient population of high-risk, mainly immunocompromised, vaccinated patients during the prevalence of the Omicron variant, NMV/r and 3RDV were equally effective early treatments for the prevention of hospitalization and/or death.

Background The tick-borne bacterium, Neoehrlichia mikurensis (N. mikurensis) can cause severe febrile illness and thromboembolic complications in immunocompromised individuals. We investigated the presence of N. mikurensis DNA in retrospectively collected plasma from a well-characterized cohort of Danish immunocompromised patients. Methods Plasma samples from 239 patients with immune dysfunction related to hematological or rheumatological disease or due to immunosuppressive therapy, were retrieved from a transdisciplinary biobank (PERSIMUNE) at Rigshospitalet, Copenhagen, Denmark. Serving as immunocompetent controls, plasma samples from 192 blood donors were included. All samples were collected between 2015 and 2019. Real-time PCR targeting the groEL gene was used to detect N. mikurensis DNA. Sequencing was used for confirmation. Borrelia burgdorferi sensu lato IgG antibodies were detected by ELISA as a proxy of tick exposure. Prevalence was compared using Fisher’s exact test. Results Neoehrlichia mikurensis DNA was detected in 3/239 (1.3%, 95% confidence interval (CI): 0.3 – 3.6%) patients, all of whom primarily had a hematological disease. Follow-up samples of these patients were negative. N. mikurensis DNA was not detected in any of the blood donor samples. IgG antibodies against B. burgdorferi s.l. were detected with similar prevalence in immunocompromised patients and blood donors, i.e., 18/239 (7.5%, 95% CI: 4.8–11.5%) and 11/192 (5.7%, 95%: CI 3.2–10.0%). Conclusion In this study, patients with N. mikurensis were not identified by clinical indication and N. mikurensis may therefore be underdiagnosed in Danish patients. Further investigations are needed to explore the clinical significance and implications of this infection.

BackgroundThe use of steroid therapy in potentially life-threatening neuroinvasive forms of West Nile infection (WNND) is controversial. The aim of this study is to assess the efficacy of steroid therapy in reducing intrahospital mortality, length of stay, and neurological sequelae at discharge.MethodsThis was a multicenter, retrospective, observational study conducted in 5 hospitals in Northern Italy, headed by the Fondazione IRCSS Policlinico San Matteo (Pavia). We extracted all patient data with WNND diagnoses, comparing patients who received steroid treatment with patients who did not receive steroid treatment between January 2014 and January 2022. Comparisons between the 2 groups were performed using chi-square tests for categorical variables and Mann-Whitney tests for non-normal continuous data, and a generalized linear model for the binomial family was carried out.ResultsData from 65 WNND patients were extracted. Among these patients, 33 (50.7%) received steroid therapy at any point during their hospitalization. Receiving steroid therapy did not significantly reduce intrahospital mortality (odds ratio [OR], 1.70; 95% CI, 0.3–13.8; P = .89) or neurological sequelae at discharge (OR, 0.53; 95% CI, 0.16–1.76; P = .47).ConclusionsSteroid treatment is currently used on a single-case basis in severe WNND. More prospective data are needed to demonstrate a protective effect on mortality and neurological sequelae.

IntroductionImmunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines.MethodsHere we compared the B-cell, T-cell and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus after the fourth dose of mRNA COVID-19 vaccines in patients with hematological malignancies (HM, n=71), solid tumors (ST, n=39) and immune-rheumatological (IR, n=25) diseases. The humoral and T-cell responses to SARS-CoV-2 vaccination were analyzed by quantifying the anti-RBD antibodies, their neutralization activity and the IFN-γ released after spike specific stimulation.ResultsWe show that the T-cell response is similarly boosted by the fourth dose across the different subgroups, while the antibody response is improved only in patients not receiving B-cell targeted therapies, independent on the pathology. However, 9% of patients with anti-RBD antibodies did not have neutralizing antibodies to either virus variants, while an additional 5.7% did not have neutralizing antibodies to Omicron BA.2, making these patients particularly vulnerable to SARS-CoV-2 infection. The increment of neutralizing antibodies was very similar towards Omicron BA.2 and WT virus after the third or fourth dose of vaccine, suggesting that there is no preferential skewing towards either virus variant with the booster dose. The only limited step is the amount of antibodies that are elicited after vaccination, thus increasing the probability of developing neutralizing antibodies to both variants of virus.DiscussionThese data support the recommendation of additional booster doses in frail patients to enhance the development of a B-cell response directed against Omicron and/or to enhance the T-cell response in patients treated with anti-CD20.

1. In healthy young adults, pre-exposure immunisation against rabies can most likely be accomplished with only a single injection, irrespective of intramuscular or intradermal route.2. Intradermal injection of a fractional dose of conjugated meningococcal vaccine is safe and likely elicits an antibody response comparable to intramuscular injection with a standard dose.3. A single subcutaneous vaccination with yellow fever vaccine provides a duration of protection well in excess of 10 years.4. Oral vaccination against cholera solicits an antibody response in most kidney transplant patients, but this response is clearly stratified by immunosuppressive regime.

1. In healthy young adults, pre-exposure immunisation against rabies can most likely be accomplished with only a single injection, irrespective of intramuscular or intradermal route.2. Intradermal injection of a fractional dose of conjugated meningococcal vaccine is safe and likely elicits an antibody response comparable to intramuscular injection with a standard dose.3. A single subcutaneous vaccination with yellow fever vaccine provides a duration of protection well in excess of 10 years.4. Oral vaccination against cholera solicits an antibody response in most kidney transplant patients, but this response is clearly stratified by immunosuppressive regime.

COVID-19 infection; Hematological malignances; Immunocompromised patients Infecció per COVID-19; Neoplasies hematològiques; Pacients immunodeprimits Infección por COVID-19; Neoplasias hematológicas; Pacientes inmunodeprimidos Background: The outcome of COVID-19 in allogeneic hematopoietic stem cell transplantation (HSCT) recipients is almost uniformely considered poor. The aim of present study was to retrospectively analyse the outcome and risk factors for mortality in a large series of patients who developed COVID-19 infection after an allogeneic HSCT. Methods: This multicenter retrospective study promoted by the European Hematology Association – Infections in Hematology Study Working Group, included 326 adult HSCT patients who had COVID-19 between January 2020 and March 2022. Results: The median time from HSCT to the diagnosis of COVID-19 was 268 days (IQR 86-713; range 0-185 days). COVID-19 severity was mild in 21% of the patients, severe in 39% and critical in 16% of the patients. In multivariable analysis factors associated with a higher risk of mortality were, age above 50 years, presence of 3 or more comorbidities, active hematologic disease at time of COVID-19 infection, development of COVID-19 within 12 months of HSCT, and severe/critical infections. Overall mortality rate was 21% (n=68): COVID-19 was the main or secondary cause of death in 16% of the patients (n=53). Conclusions: Mortality in HSCT recipients who develop COVID-19 is high and largely dependent on age, comorbidities, active hematologic disease, timing from transplant and severity of the infection. EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223). The funder of the study had no role in study design, data analysis, interpretation, or writing of the report. All authors had full access to the data and had final responsibility for the decision to submit for publication.

Candida spp. is one among the major causes of nosocomial infection, with candidemia gaining increasing prevalence worldwide in parallel with mortality rates ranging from 10-49%. Epidemiology and predisposing factors of candidemia have changed since the number of patients receiving transplants and immunosuppressive therapy, the use of broadspectrum antimicrobials, and the number of AIDS patients have increased. Candidemia is more common among patients with subcutaneous and cutaneous candida infections, through percutaneous inoculation. Major predisposing factors for invasive candidiasis includes neutropenia, haematological malignancies, bone marrow transplantation, total parenteral nutrition, chemotherapy, invasive procedures, and immune-suppressive agents. This study analyses the risk factors of immunocompromised patients with candidemia and antibiogram of Candida spp. isolated from ICU patients. To evaluate the prevalence, distribution and antibiogram of Candida spp., associated risk factors, and outcome in candidemia patients. Blood samples received from patients with clinically suspected fungal infections were subjected to gram staining, culture, sugar assimilation & fermentation, Candida Chrome agar (CCA) & Corn meal agar for identification and speciation. Antifungal susceptibility tests were performed by disk-diffusion tests. Among a total of 337 samples received, 22 (6.5%) samples were positive for candida infections, of which Candida tropicalis 9 (41%) was the predominant isolate followed by C. albicans 5 (23%), Candida glabrata 4 (18%), Candida parapsilosis 2 (9%) and Candida krusei 2 (9%). Male patients had a higher prevalence of candidemia 15 (68.2%). Among the age group of 51-70 years, uncontrolled DM(Diabetes mellitus) and CKD (chronic kidney disease) were found to be the predominant co-morbidities with candidemia.

Xuequn Guo,1 Donghao Guo2 1Department of Respiratory Medicine, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, People’s Republic of China; 2Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People’s Republic of ChinaCorrespondence: Donghao GuoDepartment of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong Special Administrative Region, People’s Republic of ChinaEmail guodonghao@link.cuhk.edu.hkBackground: The existing comorbidity indexes, like Charlson Comorbidity Index (CCI) and the Elixhauser Comorbidity Index (ECI), do not take infection factors into account for critically ill patients with immunocompromise, bringing about a decrease of prediction accuracy. Therefore, we attempted to incorporate infection location into the analysis to construct a rapid comorbidity scoring system independent of laboratory tests.Methods: Data were extracted from the Multiparameter Intelligent Monitoring in Intensive Care III database. A total of 3904 critically ill patients with immunocompromise admitted to ICU were enrolled and assigned into training or validation sets according to the date of ICU admission. The predictive nomogram was constructed in the training set based on logistic regression analysis and then undergone validation in the validation set in comparison with SOFA, CCI and ECI.Results: Factors eligible for the nomogram included patient’s age, gender, ethnicity, underlying disease of immunocompromise like metastatic cancer and leukemia, possible infection on admission including pulmonary infection, urinary tract infection and blood infection, and one comorbidity, coagulopathy. The nomogram we developed exhibited better discrimination than SOFA, CCI and ECI with an area under the receiver operating characteristic curve (AUC) of 0.739 (95% CI 0.707– 0.771) and 0.746 (95% CI 0.713– 0.779) in the training and validation sets, respectively. Combining the nomogram and SOFA could bring a new prediction model with a superior predictive effect in both sets (training set AUC = 0.803 95% CI 0.777– 0.828, validation set AUC = 0.818 95% CI 0.783– 0.854). The calibration curve exhibited coherence between the nomogram and ideal observation for two cohorts (p> 0.05). Decision curve analysis revealed the clinical usefulness of the nomogram in both sets.Conclusion: We established a nomogram that could provide an accurate assessment of 30 days ICU mortality in critically ill patients with immunocompromise, which can be employed to evaluate the short-term prognosis of those patients and bring more clinical benefits without dependence on laboratory tests.Keywords: immunocompromised patients, intensive care unit, large observational database, 30 days ICU mortality, nomogram

Aims Immunocompromised patients have been excluded from studies of SARS-CoV-2 messenger RNA vaccines. The immune response to vaccines against other infectious agents has been shown to be blunted in such patients. We aimed to analyse the humoral and cellular response to prime-boost vaccination with the BNT162b2 vaccine (Pfizer-BioNTech) in cardiothoracic transplant recipients. Methods and results A total of 50 transplant patients [1–3 years post heart (42), lung (7), or heart–lung (1) transplant, mean age 55 ± 10 years] and a control group of 50 healthy staff members were included. Blood samples were analysed 21 days after the prime and the boosting dose, respectively, to quantify anti-SARS-CoV-2 spike protein (S) immunoglobulin titres (tested by Abbott, Euroimmun and RocheElecsys Immunoassays, each) and the functional inhibitory capacity of neutralizing antibodies (Genscript). To test for a specific T-cell response, heparinized whole blood was stimulated with SARS-CoV-2 specific peptides, covering domains of the viral spike, nucleocapsid and membrane protein, and the interferon-γ release was measured (QuantiFERON Monitor ELISA, Qiagen). The vast majority of transplant patients (90%) showed neither a detectable humoral nor a T-cell response three weeks after the completed two-dose BNT162b2 vaccination; these results are in sharp contrast to the robust immunogenicity seen in the control group: 98% exhibited seroconversion after the prime dose already, with a further significant increase of IgG titres after the booster dose (average > tenfold increase), a more than 90% inhibition capability of neutralizing antibodies as well as evidence of a T-cell responsiveness. Conclusions The findings of poor immune responses to a two-dose BNT162b2 vaccination in cardiothoracic transplant patients have a significant impact for organ transplant recipients specifically and possibly for immunocompromised patients in general. It urges for a review of future vaccine strategies in these patients.

Background: Immunocompromised patients with coronavirus disease 2019 (COVID-19) have prolonged infectious viral shedding for more than 20 days. A test-based approach is suggested for de-isolation of these patients. Methods: The strategy was evaluated by comparing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load (cycle threshold (Ct) values) and viral culture at the time of hospital discharge in a series of 13 COVID-19 patients: six immunocompetent and seven immunocompromised (five solid organ transplant patients, one lymphoma patient, and one hepatocellular carcinoma patient). Results: Three of the 13 (23%) patients had positive viral cultures: one patient with lymphoma (on day 16) and two immunocompetent patients (on day 7 and day 11). Eighty percent of the patients had negative viral cultures and had a mean Ct value of 20.5. None of the solid organ transplant recipients had positive viral cultures. Conclusions: The mean Ct value for negative viral cultures was 20.5 in this case series of immunocompromised patients. Unlike those with hematological malignancies, none of the solid organ transplant patients had positive viral cultures. Adopting the test-based approach for all immunocompromised patients may lead to prolonged quarantine. Large-scale studies in disease-specific populations are needed to determine whether a test-based approach versus a symptom-based approach or a combination is applicable for the de-isolation of various immunocompromised patients.

Immunocompromised patients experience reduced vaccine effectiveness and are at higher risk for coronavirus disease 19 (COVID-19) death. Pre-exposure prophylaxis (PrEP) aims to protect these patients. So far, only tixagevimab/cilgavimab is authorized for use as PrEP. This paper aims to provide real-world data on the use of tixagevimab/cilgavimab and sotrovimab as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PrEP in immunocompromised patients, comparing the evolution of antibody levels and reporting the incidence of breakthrough infections. A retrospective, single-center analysis was conducted including 132 immunocompromised patients with inadequate vaccine response, who received COVID-PrEP at our clinic between January and June 2022. Initially, 95 patients received sotrovimab while 37 patients received tixagevimab/cilgavimab. Antibody levels after first PrEP with sotrovimab remain high for several months after infusion (median 10,058 and 7235 BAU/mL after 1 and 3 months, respectively), with higher titers than after tixagevimab/cilgavimab injection even 3 months later (7235 vs. 1647 BAU/mL, p = 0.0007). Overall, breakthrough infections were rare (13/132, 10%) when compared to overall infection rates during this period (over 30% of the Austrian population), with mild disease course and rapid viral clearance (median 10 days). Sotrovimab may be an additional option for SARS-CoV-2 PrEP.

This study, which used a cross-sectional correlational design, aimed to assess the levels of fear and health anxiety and to investigate their predictors during the current outbreak of COVID-19 in immunocompromised and chronic disease patients in Saudi Arabia. Sociodemographic and clinical data, fear of COVID-19, and health anxiety measurements were collected by online surveys. Univariate and multiple linear regression analysis was used to identify predictors.

Background : Non-invasive positive pressure ventilation （NPPV） is highly recommended for immunocompromised patients with acute respiratory failure. In this population it remains uncertain, however, whether high flow nasal canula（HFNC）is as beneficial as NPPV. Methods : We retrospectively studied immunocompromised patients with acute respiratory failure admitted to our ICU from ２０１１ to ２０１８. The background and clinical outcomes of patients initially treated with HFNC and NPPV were compared. Results : Upon admission, １２ patients were treated with HFNC and １０ with NPPV. While the length of ICU stay was significantly shorter in HFNC group （HFNC４．６days vs. NPPV１３．８days, p=０．０２）, no intergroup difference was seen in ICU mortality （１６．７％ vs.３０．０％, p=０．４６）or intubation rate（３３．３％ vs.５０．０％, p=０．４３）. Conclusions : For immunocompromised patients with acute respiratory failure, HFNC may be an alternative to NPPV. Further prospective investigation is warranted.

Rhizomucor pusillus is an opportunistic fungus that causes infections (mucormycosis) in patients with a predisposing disease, such as diabetes mellitus and immunodeficiency. Classic manifestations are sinus, pulmonary, and skin infections. Skin lesions consist of tender, erythematous, indurated, and necrotic plaques. The diagnosis is made by identification of the organisms by histopathological analysis of the lesion, showing nonseptate fungal hyphae in the dermis and invasion of the vessel walls, or by means of cultures. Amphotericin B and surgery are the treatments of choice.

Objectives: We aimed to assess the short-term effectiveness of COVID-19 vaccines among immunocompromised patients to prevent laboratory-confirmed symptomatic COVID-19 infection. Methods: Systematic review and meta-analysis. We calculated the pooled diagnostic odds ratio [DOR] (95% CI) for COVID-19 infection between immunocompromised patients and healthy people or those with stable chronic medical conditions. VE was estimated as 100% x (1-DOR). We also investigated the rates of developing anti-SARS-CoV-2 spike protein IgG between the 2 groups. Results: Twenty studies evaluating COVID-19 vaccine response, and four studies evaluating VE were included in the meta-analysis. The pooled DOR for symptomatic COVID-19 infection in immunocompromised patients was 0.296 (95% CI: 0.108-0.811) with an estimated VE of 70.4% (95% CI: 18.9%- 89.2%). When stratified by diagnosis, IgG antibody levels were much higher in the control group compared to immunocompromised patients with solid organ transplant (pOR 232.3; 95% Cl: 66.98-806.03), malignant diseases (pOR 42.0, 95% Cl: 11.68-151.03), and inflammatory rheumatic diseases (pOR 19.06; 95% Cl: 5.00-72.62). Conclusions: We found COVID-19 mRNA vaccines were effective against symptomatic COVID-19 among the immunocompromised patients but had lower VE compared to the controls. Further research is needed to understand the discordance between antibody production and protection against symptomatic COVID-19 infection.

The availability of multiple versions of vaccines designed to help prevent COVID-19 has offered an opportunity to at least control the current pandemic, and possibly to quickly eradicate this disease fully, along with the implementation of other preventive measures. In order to accomplish this feat more effectively, as many people as possible need to be vaccinated, especially for high-risk groups having co-morbid conditions such as diabetes, obesity and old age, and possibly those with various forms of immunodeficiencies, such as HIV/AIDS. This chapter focuses primarily on some of the basic biomedical aspects on vaccine design and use, and any possible concerns that need to be considered in getting people in the high-risk category vaccinated and monitored thereafter for their continuous health and well-being.

Prior studies of antibody response after full SARS-CoV-2 vaccination in hematological patients have confirmed lower antibody levels compared to the general population. Serological response in hematological patients varies widely according to the disease type and its status, and the treatment given and its timing with respect to vaccination. Through probabilistic machine learning graphical models, we estimated the conditional probabilities of having detectable anti-SARS-CoV-2 antibodies at 3–6 weeks after SARS-CoV-2 vaccination in a large cohort of patients with several hematological diseases (n= 1166). Most patients received mRNA-based vaccines (97%), mainly Moderna® mRNA-1273 (74%) followed by Pfizer-BioNTech® BNT162b2 (23%). The overall antibody detection rate at 3 to 6 weeks after full vaccination for the entire cohort was 79%. Variables such as type of disease, timing of anti-CD20 monoclonal antibody therapy, age, corticosteroids therapy, vaccine type, disease status, or prior infection with SARS-CoV-2 are among the most relevant conditions influencing SARS-CoV-2-IgG-reactive antibody detection. A lower probability of having detectable antibodies was observed in patients with B-cell non-Hodgkin’s lymphoma treated with anti-CD20 monoclonal antibodies within 6 months before vaccination (29.32%), whereas the highest probability was observed in younger patients with chronic myeloproliferative neoplasms (99.53%). The Moderna® mRNA-1273 compound provided higher probabilities of antibody detection in all scenarios. This study depicts conditional probabilities of having detectable antibodies in the whole cohort and in specific scenarios such as B cell NHL, CLL, MM, and cMPN that may impact humoral responses. These results could be useful to focus on additional preventive and/or monitoring interventions in these highly immunosuppressed hematological patients., REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research. We thank the Spanish Society of Hematology (SEHH) for its support on the study. We sincerely want to thanks the invaluable aid of microbiology services for their commitment in SARS-CoV-2-reactive IgG antibody monitoring in these highly immunosuppressed patients from all participating centers. Finally, we also want to thank the patients, nurses, and study coordinators for their foremost contributions in this study.

Infections occurring in immunocompromised patients after intensive chemotherapy are often difficult to eradicate and are capable of even being fatal. New emergent and dangerous drug-resistant micro-organisms are likely to appear in these specific scenarios. Clinical features mainly include progressive pneumonia, bacteriemia/fungemia, or extrapulmonary dissemination among infections. The treatment of these microorganisms is still an open challenge since there is a lack of clear treatment guidelines. Indeed, infections from these microorganisms can lead to a rapidly fatal clinical course in immunocompromised patients, especially those who have acute leukemia. We describe the case of a young patient with acute myeloid leukemia who contracted an infection from Saprochaete capitata during post-chemotherapy aplasia.

Cryptosporidium is a protozoan that infects a wide variety of vertebrates, including humans, causing acute gastroenteritis. The disease manifests with abdominal pain and diarrhea similar to that of choleric infection. In the immunocompromised hosts, the parasite causes prolonged infections that can also be fatal. For this reason, cryptosporidiosis is considered one of riskiest opportunistic infections for patients with acquired immunodeficiency syndrome. The best way to control the infection in these patients is setting up sensitive and specific diagnostic tests for epidemiological surveillance and morbidity reduction. Here, we summarized the general aspects of Cryptosporidium infection focusing on available diagnostic tools used for the diagnosis of cryptosporidiosis. Molecular methods currently available for its detection and progress in the development of new diagnostics for cryptosporidiosis are also discussed.

BackgroundCutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer whose incidence is growing parallel to the lengthening of the average lifespan. Cemiplimab, an antiPD-1 monoclonal antibody, is the first approved immunotherapy for patients with locally advanced CSCC (laCSCC) or metastatic CSCC (mCSCC) thanks to phase I and II studies showing high antitumor activity and good tolerability. Nevertheless, at present, very few data are available regarding cemiplimab in real-life experience and in frail, elderly, and immunosuppressed patients as well as regarding biomarkers able to predict response so as to guide therapeutic choices.Patients and MethodsWe built a retroprospective cohort study including 30 non-selected patients with laCSCC (25) and mCSCC (five) treated with cemiplimab from August 2019 to November 2020. Clinical outcomes, toxicity profile, and correlations with disease, patients, and peripheral blood parameters are explored.ResultsThe median age was 81 years (range, 36–95), with 24 males and five patients having an immunosuppressive condition, while the frailty prevalence was 83% based on index derived from age, Eastern Cooperative Oncology Group performance status, and Charlson Comorbidity Index. We reported 23 responses (76.7%) with nine complete responses (30%). A statistically significant higher response rate was observed in head and neck primary tumors and in patients with hemoglobin level >12 g/dl. No difference was observed with respect to frailty, median age, sex, and body mass index. The baseline low neuthophil/lymphocyte ratio and low platelet/lymphocyte ratio resulted to be also correlated with a better response. Moreover, lymphocyte, neutrophil, and monocyte behaviors had an opposite trend in responders and non-responders. An overall response was reported in four of five immunosuppressed patients. Seventeen patients (57.6%) have an ongoing response and are still alive. Six responders had interrupted treatment (two for toxicity and four for personal choice) but maintained their response. The treatment was well tolerated by the majority of patients. The most common adverse events were fatigue in seven patients (23.3%) and skin toxicity in 10 patients (33.3%), including pruritus in six patients, rash in three patients, and bullous erythema in one patient.ConclusionsIn our real-life experience, cemiplimab showed a high antitumor activity with acceptable safety profile similar to those in trials with selected patients. Moreover, its antitumor activity resulted to be not impaired in very elderly patients and in those with immunocompromised status.

Xuequn Guo,1 Donghao Guo2 1Department of Respiratory Medicine, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, People’s Republic of China; 2Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People’s Republic of ChinaCorrespondence: Donghao GuoDepartment of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong Special Administrative Region, People’s Republic of ChinaEmail guodonghao@link.cuhk.edu.hkBackground: The existing comorbidity indexes, like Charlson Comorbidity Index (CCI) and the Elixhauser Comorbidity Index (ECI), do not take infection factors into account for critically ill patients with immunocompromise, bringing about a decrease of prediction accuracy. Therefore, we attempted to incorporate infection location into the analysis to construct a rapid comorbidity scoring system independent of laboratory tests.Methods: Data were extracted from the Multiparameter Intelligent Monitoring in Intensive Care III database. A total of 3904 critically ill patients with immunocompromise admitted to ICU were enrolled and assigned into training or validation sets according to the date of ICU admission. The predictive nomogram was constructed in the training set based on logistic regression analysis and then undergone validation in the validation set in comparison with SOFA, CCI and ECI.Results: Factors eligible for the nomogram included patient’s age, gender, ethnicity, underlying disease of immunocompromise like metastatic cancer and leukemia, possible infection on admission including pulmonary infection, urinary tract infection and blood infection, and one comorbidity, coagulopathy. The nomogram we developed exhibited better discrimination than SOFA, CCI and ECI with an area under the receiver operating characteristic curve (AUC) of 0.739 (95% CI 0.707– 0.771) and 0.746 (95% CI 0.713– 0.779) in the training and validation sets, respectively. Combining the nomogram and SOFA could bring a new prediction model with a superior predictive effect in both sets (training set AUC = 0.803 95% CI 0.777– 0.828, validation set AUC = 0.818 95% CI 0.783– 0.854). The calibration curve exhibited coherence between the nomogram and ideal observation for two cohorts (p> 0.05). Decision curve analysis revealed the clinical usefulness of the nomogram in both sets.Conclusion: We established a nomogram that could provide an accurate assessment of 30 days ICU mortality in critically ill patients with immunocompromise, which can be employed to evaluate the short-term prognosis of those patients and bring more clinical benefits without dependence on laboratory tests.Keywords: immunocompromised patients, intensive care unit, large observational database, 30 days ICU mortality, nomogram

BK polyomavirus (BKPyV) persists lifelong in renal and urothelial cells with asymptomatic urinary shedding in healthy individuals. In some immunocompromised persons after transplantation of hematopoietic stem cells (HSCT), the BKPyV high-rate replication is associated with haemorrhagic cystitis (HC). We tested whether the status of BKPyV immunity prior to HSCT could provide evidence for the BKPyV tendency to reactivate. We have shown that measurement of pretransplant anti-BKPyV 1 and 4 IgG levels can be used to evaluate the HC risk. Patients with anti-BKPyV IgG in the range of the 1st–2nd quartile of positive values and with positive clinical risk markers have a significantly increased HC risk, in comparison to the reference group of patients with “non-reactive” anti-BKPyV IgG levels and with low clinical risk (LCR) (p = 0.0009). The predictive value of pretransplant BKPyV-specific IgG was confirmed by determination of genotypes of the shed virus. A positive predictive value was also found for pretransplant T-cell immunity to the BKPyV antigen VP1 because the magnitude of IFN-γ T-cell response inversely correlated with posttransplant DNAuria and with HC. Our novel data suggest that specific T-cells control BKPyV latency before HSCT, and in this way may influence BKPyV reactivation after HSCT. Our study has shown that prediction using a combination of clinical and immunological pretransplant risk factors can help early identification of HSCT recipients at high risk of BKPyV disease.

BackgroundAn immunodiagnostic assay that sensitively detects a cell-mediated immune response to SARS-CoV-2 is needed for epidemiological investigation and for clinical assessment of T cell-mediated immune response to vaccines, particularly in the context of emerging variants that might escape antibody responses.MethodsThe performance of a whole blood interferon-gamma (IFN-γ) release assay (IGRA) for the detection of SARS-CoV-2 antigen-specific CD4 and CD8 T cells was evaluated in COVID-19 convalescents tested serially up to 10 months post-infection and in healthy blood donors. SARS-CoV-2 IGRA was applied in contacts of households with index cases. Freshly collected blood in the lithium heparin tube was left unstimulated, stimulated with a SARS-CoV-2 peptide pool, and stimulated with mitogen.ResultsThe overall sensitivity and specificity of IGRA were 84.5% (153/181; 95% confidence interval [CI] 79.0-89.0) and 86.6% (123/142; 95% CI;80.0-91.2), respectively. The sensitivity declined from 100% (16/16; 95% CI 80.6-100) at 0.5-month post-infection to 79.5% (31/39; 95% CI 64.4-89.2) at 10 months post-infection (PConclusionsThe SARS-CoV-2 IGRA is a useful clinical diagnostic tool for assessing cell-mediated immune response to SARS-CoV-2.Key pointsSARS-CoV-2 immunodiagnostics are needed to identify infected individuals in order to understand the transmission dynamics of emerging variants and to assess vaccine response. Interferon-gamma release assay maintains sensitivity 10 months post-infection in convalescents and detects more household contacts than IgG.

BackgroundPatients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate the safety and efficacy after two doses of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls.Methods539 study subjects (449 patients and 90 controls) were included in the clinical trial. The patients had either primary (n=90), or secondary immunodeficiency disorders due to human immunodeficiency virus infection (n=90), allogeneic hematopoietic stem cell transplantation/chimeric antigen receptor T cell therapy (n=90), solid organ transplantation (SOT) (n=89), or chronic lymphocytic leukemia (CLL) (n=90). The primary endpoint was seroconversion rate two weeks after the second dose. The secondary endpoints were safety and documented SARS-CoV-2 infection.FindingsAdverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred. 72·2% of the immunocompromised patients seroconverted compared to 100% of the controls (p=0.004). Lowest seroconversion rates were found in the SOT (43·4%) and CLL (63·3%) patient groups with observed negative impact of treatment with mycophenolate mofetil and ibrutinib, respectively.InterpretationThe results showed that the mRNA BNT162b2 vaccine was safe in immunocompromised patients. The rate of seroconversion was substantially lower than in healthy controls, with a wide range of rates and antibody titres among predefined patient groups and subgroups. This clinical trial highlights the need for additional vaccine doses in certain immunocompromised patient groups and/or subgroups to improve immunity.FundingKnut and Alice Wallenberg Foundation, Nordstjernan AB, Region Stockholm, Swedish Research Council, Karolinska Institutet, and organizations for PID/CLL-patients in Sweden.

Mycoplasma hominis is a rarely identified cause of respiratory infection that can cause significant morbidity and mortality in immunocompromised patients. It is often missed due to the difficult detection of the organism with routine laboratory methods. We present the case of a 63-year-old male with a history of lymphoma who was transferred to our hospital with recurrent right-sided empyema and lung abscess in the right lower lobe. Advanced microbiological analysis finally revealed infection with M hominis. Despite appropriate antibiotic treatment, prolonged drainage as well as repeated surgery, which eventually resulted in right lower bilobectomy, were necessary for clinical improvement of our patient. Infection with M hominis may be more prevalent than previously indicated and can cause severe morbidity and mortality in thoracic surgery patients. Due to the diagnostic challenge, the appropriate antimicrobial treatment is often delayed. Inherent resistance to macrolides and inactivity of cell wall-active agents potentially complicate empiric antibiotic therapy. A review of the currently available literature enables a better understanding of the diagnostic difficulties and importance of this infection.

Pneumocystis jirovecii pneumonia (PJP) has emerged as a main issue in non Human Immunodeficiency Virus (HIV) immunocompromised hosts, exposing patients to high mortality rates, especially when the diagnosis is delayed. Since microbiological confirmation is often unfeasible or difficult to obtain, High-resolution Computed Tomography (HRCT) represents a main tool for guiding the diagnosis in the appropriate clinical scenario. Nevertheless, radiologists must be aware that PJP at HRCT is a multifaceted process, with a variety of common and less frequent findings, along with a broad spectrum of infectious (e.g., viral and certain fungal and bacterial pneumonias) and non-infectious (e.g., pulmonary oedema, diffuse alveolar haemorrhage, and drug toxicity) differential diagnoses. In this review we resume background clinical information on PJP in non-HIV immunocompromised patients, illustrate both typical and less frequent HRCT findings, and present the spectrum of infectious and non-infectious mimickers at HRCT, highlighting the similarities with PJP and providing clues for the differential diagnosis.

This paper presents three cases of immunocompromised patients for whom therapeutic drug monitoring (TDM) of ganciclovir in combination with cytomegalovirus (CMV) viral load measurement was used to guide treatment. The first patient is diagnosed with Thymoma A, the second is a heart transplant recipient and the third is an HIV positive patient. These patients were all diagnosed with CMV and treated with ganciclovir. Our case studies illustrate how TDM guided dosing can be helpful in the management of these complex cases.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Life-threatening, invasive fungal infections (IFIs) cause over 1.5 million deaths worldwide and are a major public health concern with high mortality rates even with medical treatment. Infections with the opportunistic fungal pathogen, Aspergillus fumigatus are among the most common. Despite the growing clinical need, there are no licensed vaccines for IFIs. Here we evaluated the immunogenicity and protective efficacy of an A. fumigatus recombinant protein vaccine candidate, AF.KEX1, in experimental murine models of drug-induced immunosuppression. Immunization of healthy mice with AF.KEX1 and adjuvant induced a robust immune response. Following AF.KEX1 or sham immunization, mice were immunosuppressed by treatment with either cortisone acetate or hydrocortisone and the calcineurin inhibitor, tacrolimus. To test vaccine efficacy, immunosuppressed mice were intranasally challenged with A. fumigatus conidia (Af293) and weight and body temperature were monitored for 10 days. At study termination, organism burden in the lungs was evaluated by quantitative PCR and Gomori’s methanamine silver staining. In both models of immunosuppression, AF.KEX1 vaccinated mice experienced decreased rates of mortality and significantly lower lung organism burden compared to non-vaccinated controls. The lung fungal burden was inversely correlated with the peak anti-AF.KEX1 IgG titer achieved following vaccination. These studies provide the basis for further evaluation of a novel vaccine strategy to protect individuals at risk of invasive aspergillosis due to immunosuppressive treatments.

Immunocompromised patients, including HSCT recipients, may have a poor prognosis after contracting COVID-19 due to the absence of a pathogen-specific adaptive immune response. One of the possible options for severe COVID-19 treatment may be the transfusion of hyperimmune SARS-CoV-2 convalescent plasma. A 9-month-old girl with juvenile myelomonocytic leukemia received an HSCT from a haploidentical donor. On day +99, during routine virologic monitoring, SARS-CoV-2 was detected without any clinical symptoms. On day +144, the child developed a polysegmental bilateral viral pneumonia with 60 % damage to the lung tissue and confirm a positive SARS-Cov-2 results in throat swab. The patient was treated with tocilizumab and three doses of fresh frozen plasma obtained from a SARS-CoV-2 convalescent patient. Therapy with tocilizumab and three doses of fresh frozen plasma was well tolerated. In spite of full resolution of the lung lesions, complete elimination of SARS-CoV-2 has not been achieved 4 months after the first detection, which is due to persistence of secondary immunodeficiency after HSCT and the lack of reconstitution of the adaptive immune response. This case represents a demonstration of an atypical course of COVID-19 and the delayed development of lung lesions, which was most likely associated with the features of the patient's immune status after HSCT. SARS-CoV-2 convalescent plasma in combination with other therapeutic approaches is one of the possible curative options for this clinical situation.

Microsporidiosis is an emerging opportunistic infection causing severe digestive disorders in immunocompromised patients. The aim of this study was to investigate the prevalence of intestinal microsporidia carriage among immunocompromised patients hospitalized at a major hospital complex in the Tunis capital area, Tunisia (North Africa), and perform molecular epidemiology and population structure analyses of Enterocytozoon bieneusi, which is an emerging fungal pathogen. We screened 250 stool samples for the presence of intestinal microsporidia from 171 patients, including 81 organ transplant recipients, 73 Human Immunodeficiency Virus (HIV)-positive patients, and 17 patients with unspecified immunodeficiency. Using a nested PCR-based diagnostic approach for the detection of E. bieneusi and Encephalitozoon spp., we identified 18 microsporidia-positive patients out of 171 (10.5%), among which 17 were infected with E. bieneusi. Microsporidia-positive cases displayed chronic diarrhea (17 out of 18), which was associated more with HIV rather than with immunosuppression other than HIV (12 out of 73 versus 6 out of 98, respectively, p = 0.02) and correlated with extended hospital stays compared to microsporidia-negative cases (60 versus 19 days on average, respectively, p = 0.001). Strikingly, internal transcribed spacer (ITS)-based genotyping of E. bieneusi strains revealed high-frequency occurrence of ITS sequences that were identical (n = 10) or similar (with one single polymorphic site, n = 3) to rare genotype WL12. Minimum-spanning tree analyses segregated the 17 E. bieneusi infection cases into four distinct genotypic clusters and confirmed the high prevalence of genotype WL12 in our patient population. Phylogenetic analyses allowed the mapping of all 17 E. bieneusi strains to zoonotic group 1 (subgroups 1a and 1b/1c), indicating loose host specificity and raising public health concern. Our study suggests a probable common source of E. bieneusi genotype WL12 transmission and prompts the implementation of a wider epidemiological investigation.

International audience; Herpes simplex virus (HSV) infections remain an important cause of morbidity among immunocompromised patients, such as transplant recipients and human immunodeficiency virus [HIV]-infected individuals. Only few antiviral drugs are available to treat HSV infections: (val)acyclovir, foscarnet, and cidofovir. Prophylactic and curative antiviral treatments administered during prolonged periods among patients with altered T-cell immunity may lead to the emergence of HSV resistance to antivirals, contributing to a challenging therapeutic management of viral infection. The persistence of herpetic lesions after 10 days of well-conducted antiviral therapy is suggestive of viral resistance. Resistance to antivirals can be detected using genotypic methods (identifications of antiviral resistance-associated mutations by sequencing genes encoding viral proteins involved in the mechanism of action of antivirals) or phenotypic methods (measure of antiviral drug concentration inhibiting 50% of viral replication in cell culture). The prevalence of HSV resistance to acyclovir is below 1% in immunocompetent individuals, except those with herpetic keratitis for whom prevalence can reach 7%, and varies from 3.5% to 11% in immunocompromised patients. Adverse effects and the absence of eradication of viral latent infection constitute other limits to the use of antiviral drugs. New antiviral compounds undergoing clinical trials and novel potential viral targets seem very promising to enlarge the panel of efficient compounds to treat HSV infections.; Les infections par les virus herpes simplex (HSV) constituent une cause majeure de morbidité chez les patients immunodéprimés tels que les receveurs de greffe ou les individus infectés par le virus de l’immunodéficience humaine (HIV). Les molécules antivirales utilisées pour le traitement de ces infections sont actuellement peu nombreuses : (val)aciclovir, foscarnet et cidofovir. L’instauration de traitements antiviraux préventifs ou curatifs, souvent durant des périodes prolongées, chez des patients dont l’immunité cellulaire est altérée, peut conduire à l’émergence de résistance des HSV aux antiviraux, compliquant alors la prise en charge thérapeutique de l’infection virale. La persistance de lésions herpétiques après 10 jours de traitement antiviral bien conduit doit faire suspecter une résistance virologique. Il est possible de détecter cette résistance par des méthodes génotypiques (identification de mutations associées à la résistance aux antiviraux par séquençage des gènes codant les protéines virales directement impliquées dans le mécanisme d’action des antiviraux) ou par des méthodes phénotypiques (mesure de la concentration d’un antiviral inhibant 50 % de la multiplication virale en culture de cellules). La prévalence de la résistance des HSV à l’aciclovir est inférieure à 1 % chez les individus immunocompétents, hormis ceux souffrant de kératite herpétique pour qui elle est de l’ordre de 7 %, et elle varie de 2,5 % à 11 % chez les individus immunodéprimés. De plus, il existe d’autres limitations à l’utilisation de ces antiviraux, comme leurs effets indésirables ou l’impossibilité d’éradiquer les infections virales latentes. À ce jour, de nouveaux composés en cours d’essais cliniques et de nouvelles cibles virales potentielles semblent très prometteuses pour agrandir le panel de molécules efficaces pour traiter les infections dues aux HSV.

Made available in DSpace on 2021-06-25T15:38:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-09-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundacao de Apoio ao Desenvolvimento do Ensino, Ciencia e Tecnologia do Estado de Mato Grosso do Sul (FUNDECT/MS) Objectives: Visceral leishmaniasis (VL) is a progressive disease that, left untreated, is typically fatal. The purpose of this investigation was to detect Leishmania sp. infection in hemodialysis patients who had received multiple blood transfusions at a private clinic in Campo Grande, Mato Grosso do Sul state, Midwest Brazil. Methods: Fifty randomly selected volunteers were interviewed for collection of demographic, socioeconomic, and epidemiological data. Indirect immunofluorescence (titers positive when >= 1:40) and rK39 immunochromatographic tests were employed for serological investigation. Results: Males predominated (60%). Age ranged from 20 to 77 years. Most subjects reported being on hemodialysis for at least one year (94%) and 84% were candidates for kidney transplantation, 67% of whom were on the waiting list. Leishmania sp. infection was detected in 32%. Contact with infected dogs was the only variable associated with infection. Conclusions: Under immunocompromised conditions, VL is opportunistic and potentially fatal. Despite existing risks, screening for VL is not performed in asymptomatic donors and recipients. The detection of anti-Leishmania antibodies in these patients reinforces the need for infection screening before immunosuppressive treatment is initiated to reduce not only the risks of VL development and severity, but also mortality rates in cases of reactivation of latent infection. (C) 2020 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. Univ Fed Mato Grosso do Sul, Lab Clin Parasitol, Grad Program Infect & Parasit Dis, Campo Grande, MS, Brazil Univ Fed Mato Grosso do Sul, Undergrad Program Med, Campo Grande, MS, Brazil Univ Estadual Paulista, Botucatu Sch Med, Botucatu, SP, Brazil Univ Estadual Paulista, Botucatu Sch Med, Botucatu, SP, Brazil CAPES: 001 Fundacao de Apoio ao Desenvolvimento do Ensino, Ciencia e Tecnologia do Estado de Mato Grosso do Sul (FUNDECT/MS): 114/2014 Fundacao de Apoio ao Desenvolvimento do Ensino, Ciencia e Tecnologia do Estado de Mato Grosso do Sul (FUNDECT/MS): SIAFEM 023,670 Fundacao de Apoio ao Desenvolvimento do Ensino, Ciencia e Tecnologia do Estado de Mato Grosso do Sul (FUNDECT/MS): 23/200.262/2014

Background: The emergence of influenza viruses resistant to anti-influenza drugs is a threat to public health. The Korea Centers for Disease Control and Prevention operates the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS) to monitor epidemic of influenza and Severe Acute Respiratory Infection (SARI) to identify mutated influenza viruses affecting drug resistance, pathogenesis, and transmission. Methods: Oropharyngeal swab samples were collected from KINRESS and SARI during the 2018-2019 season. The specimens confirmed influenza virus using real-time RT-PCR on inoculated MDCK cells. HA and NA sequences of the influenza viruses were analyzed for phylogeny and mutations. Neuraminidase inhibition and hemagglutination inhibition assays were utilized to characterize the isolates. Results: Two A(H1N1)pdm09 isolates harboring an H275Y substitution in the neuraminidase sequence were detected in patients with acute hematologic cancer. They had prolonged respiratory symptoms, with the virus present in the respiratory tract despite oseltamivir and peramivir treatment. Through the neuraminidase inhibition assay, both the viruses were found to be resistant to oseltamivir and peramivir, but not to zanamivir. Although hemagglutinin and neuraminidase phylogenetic analyses suggested that the two A(H1N1)pdm09 isolates were not identical, their antigenicity was similar to that of the 2018-19 influenza vaccine virus. Conclusions: Our data indicate the utility of monitoring influenza-infected immunocompromised patients in general hospitals for the early detection of emerging neuraminidase inhibitor-resistant viruses and maintaining continuous laboratory surveillance of patients with influenza-like illness in sentinel clinics to monitor the spread of such new variants. Finally, characterization of the virus can inform the assessment of risk for future epidemics and pandemics caused by drug-resistant influenza viruses.

Background: The purpose of this study was to determine the prevalence and genotype of Cryptosporidium spp. in different groups of immunocompromised patients admitted to the referral hospitals in center of Iran during 2015–2016. Methods: This cross-sectional study was conducted on 346 immunocompromised patients (HIV+/AIDS, Lymphoma, Leukemia and organ transplants) in referred hospitals from central parts of Iran including Isfahan, Markazi, Yazd and Chaharmahale Bakhtiari provinces. Stool samples were analyzed for Cryptosporidium species, modified Ziehl–Neelsen staining techniques followed by the semi-nested PCR and DNA sequencing methods. Results: The total rate of Cryptosporidium spp. was 3.46% (12/346) in the patients, however, the prevalence of the parasite, was 4.6% (4/87) in HIV+/AIDS patients, 3.6% (6/168) in patients with blood malignancy and 2.1% (2/91) in organ transplant recipients. The SSU rRNA gene of Cryptosporidium spp. in all microscopic-positive samples was effectively amplified by the semi-nested PCR and DNA sequences, exposed the existence of two Cryptosporidium species, including C. hominis 91.6% (11/12) and C. parvum 8.3% (1/12). Conclusion: The predominance of C. hominis in the present study may be certifies the importance of anthroponotic transmission of cryptosporidiosis in center of Iran.

Since oncologic patients have been considered an important risk group for parasitic infections, it is fundamental to find out what they know about intestinal parasites. This study aimed at evaluating knowledge that the adult oncologic patients undergoing chemotherapy in the main centers of treatment for cancer in the city of Pelotas, Brazil, has about intestinal parasites. A semi-structured questionnaire was used for collecting data from two hundred oncologic patients who were undergoing chemotherapy. Results showed that 69.5% know what intestinal parasites are and cited Ascaris lumbricoides and Taenia sp. as being the most known ones. The statistical comparison between the group that knows intestinal parasites and the one that does not know about them – associated with socioeconomic variables –, showed that factors that significantly influenced their knowledge were their place of residence, schooling and household income (p≤0.05). Only 36% stated that they know when they are infected with parasites and misdescribed some signs and symptoms. Regarding prevention, 52% mentioned that they do not know how to avoid parasitism. The population under study showed that there are some gaps in its knowledge of the theme under investigation. Therefore, it is important to implement socioeducational measures in hospitals and clinics that treat cancer patients. Resumo Pacientes oncológicos são considerados um importante grupo de risco para infecções parasitárias, logo, é fundamental conhecer o que sabem sobre parasitos intestinais. O objetivo deste estudo foi avaliar os conhecimentos de indivíduos oncológicos adultos submetidos à quimioterapia nos principais centros de tratamento para o câncer no município de Pelotas, RS, sobre as enteroparasitoses. O instrumento utilizado para coleta dos dados foi um questionário semiestruturado. Foram incluídos nesta pesquisa 200 pacientes oncológicos submetidos à quimioterapia. Destes, 69,5% sabem o que são parasitos intestinais, citando Ascaris lumbricoides e Taenia sp. como os mais conhecidos. Quando realizada a comparação estatística do grupo que conhece parasitos intestinais/vermes com o grupo dos que desconhecem o tema, associadas com variáveis socioeconômicas, foi verificado que a zona em que residiam, a escolaridade e a renda familiar são fatores que influenciam no conhecimento dos indivíduos de forma significativa (p≤0,05). Apenas 36% dos indivíduos afirmaram saber quando estão parasitados, relatando alguns sinais e sintomas equivocadamente. Relacionado à prevenção, 52% mencionaram não saber como evitar o parasitismo. A população estudada possui lacunas no conhecimento sobre o tema abordado e, por isso, é importante a realização de ações socioeducativas junto aos hospitais e clínicas de tratamento dos pacientes com câncer.

Résumé Le tractus gastro-intestinal est fréquemment le siège de manifestations infectieuses chez les patients immunocompromis. Les symptômes les plus fréquemment rencontrés sont l'odynophagie, la dysphagie et les diarrhées. Ces affections sont plus souvent observées chez les patients HIV. Ces affections gastro-intestinales sont de différents types: soit liées au virus HIV lui-même (entérite liée au HIV, œsophagite ulcérée idiopathique), soit liées à des germes également responsables d'infections chez les patients immunocompétents (Salmonellose, shigellose, …), soit des infections opportunistes (CMV, Mucormycose,Cryptosporidium, Mycobactéries,Isospora belli, …). La prévalence, la pathogenèse, les manifestations cliniques, les aspects macroscopique et microscopique sont discutés pour chaque entité.

Background Cutaneous phaeohyphomycosis is an emerging disease in immunocompromised patients, being Alternaria one of the most common genera reported as a causative agent. Species identification is not carried out mainly due to the complexity of the genus. Analysis of the ITS barcode has become standard for fungal identification, but in Alternaria it is only able to discriminate among species-groups or sections. Methods We present three cases of cutaneous infection caused by Alternaria isolates morphologically identified as belonging to section Infectoriae. They have been morphologically characterised and phylogenetically delineated with five molecular markers (ITS, ATPase, gapdh, rpb2 and tef1). Results Mycotic infections have been diagnosed by repeated cultures and histopathological examination in two of the cases. The polyphasic approach has allowed to delineate three new species of Alternaria section Infectoriae, that is A anthropophila, A atrobrunnea and A guarroi. ATPase has been the only locus able to discriminate most of the species (29 out of 31) currently sequenced in this section, including A infectoria the commonest reported species causing alternariosis. Susceptibility test showed different antifungal patterns for the three species, although terbinafine was the most active in vitro drug against these fungi. Conclusions The ATPase gene is recommended as an alternative barcode locus to identify Alternaria clinical isolates in section Infectoriae. Our results reinforce the relevance of identification of Alternaria isolates at the species level and the necessity to carry out antifungal susceptibility testing to determine the most adequate drug for treatment.

Cytomegalovirus (CMV) infection is a major complication in immunocompromised patients, including those with autoimmune diseases. Here, we describe the first case of granulomatosis with polyangiitis treated with steroids and cyclophosphamide, complicated by a multid-rug-resistant (MDR) CMV infection in presence of weak antiviral cellular immunity. Since reports regarding CMV infection in rheumatological patients are rarely described and no guidelines on its management exist, the described case contributes to identify potential strategies to predict the risk of CMV disease and developing of MDR-CMV in these patients, through virological and immunological surveillance.

Background: Respiratory complications of solid organ transplant (SOT) are a diagnostic and therapeutic challenge when requiring intensive care unit (ICU) admission. We aimed at describing this challenge in a prospective cohort of SOT recipients admitted in the ICU. Methods: In this post hoc analysis of an international cohort of immunocompromised patients admitted in the ICU for an acute respiratory failure, we analyzed all SOT recipients and compared their severity, etiologic diagnosis, prognosis, and outcome according to the performance of an invasive diagnostic strategy (encompassing a fiber-optic bronchoscopy and bronchoalveolar lavage), the type of transplanted organ, and the need of invasive ventilation at day 1. Results: Among 1611 patients included in the primary study, 142 were SOT recipients (kidney, n = 73; 51.4%; lung, n = 33; 23.2%; liver, n = 29; 20.4%; heart, n = 7; 4.9%). Lung transplant recipients were younger than other SOT recipients, and severity did not differ across type of received organ. An invasive diagnostic strategy was more frequently performed in lung transplant recipients with a trend toward a higher rate of bacterial etiology in lung than kidney transplant recipients. Overall ICU survival of SOT recipients was 75.4%. Invasive diagnostic strategy, type of transplanted organ, and need of invasive mechanical ventilation at day 1 did not affect ICU prognosis. Conclusions: ICU management of hypoxemic acute respiratory failure in SOT recipients translated into a low ICU mortality rate, whatever the transplanted organ or the acute respiratory failure cause. The post-ICU burden of acute respiratory failure SOT recipients remains to be investigated., SCOPUS: ar.j, info:eu-repo/semantics/published

Stenotrophomonas maltophilia has emerged as an important opportunistic pathogen in the last decade. Increased resistance to sulfamethoxazole/trimethoprim (SMX/TMP) has been reported in S. maltophilia strains in the past few years, leading to few therapeutic options. We conducted a prospective multicenter study at two Brazilian teaching hospitals that identified S. maltophilia isolates and evaluated their antimicrobial susceptibility profile, SMX/TMP resistance genes and their clonality profile. A total of 106 non-repeated clinical samples of S. maltophilia were evaluated. Resistance to SMX/TMP was identified in 21.6% of the samples, and previous use of SMX/TMP occurred in 19 (82.6%). PCR detected the sul1 gene in 14 of 106 strains (13.2%). Of these isolates, nine displayed resistance to SMX/TMP. The resistant strains presented a polyclonal profile. This opportunistic pathogen has emerged in immunocompromised hosts, with few therapeutic options, which is aggravated by the description of emerging resistance mechanisms, although with a polyclonal distribution profile.

Background Despite the widespread availability of pneumococcal vaccines, rates of pneumococcal disease are disproportionately high in adults with chronic and immunocompromising conditions. This study investigated pneumococcal disease rates and associated resource utilization and costs in this group. Methods A retrospective, observational study was conducted using the Truven Health MarketScan® Commercial Claims and Encounters database. The study population was adults aged 19–64 years with continuous health plan enrollment for at least one year before and at least one day after January 1st 2012, 2013 and/or 2014. Medical conditions were identified using ICD-9-CM diagnosis codes and grouped into at-risk (chronic) and high-risk (immunocompromising) conditions. Pneumococcal disease was stratified into all-cause pneumonia (ACP) and invasive pneumococcal disease (IPD). Results Thirty-six million adults aged 19–64 years were included in the study. 17% had a condition that put them at increased risk for pneumococcal disease. Rates of ACP and IPD in adults with at-risk conditions were 3.6 and 4.6 times the rate in healthy adults, respectively, and 5.3 and 10.5 for adults with high-risk conditions. Risk was particularly high in adults with ≥2 medical conditions: rates of ACP and IPD were 8.1 and 10.6 times higher in adults with at-risk conditions than healthy adults and 6.3 and 13.4 times higher in adults with high-risk conditions, respectively. Resource use and costs were substantially higher per episode of ACP in at-risk and high-risk adults, with costs reaching $6,534 and $9,168, compared to $4,725 for healthy adults. Conclusions Pneumococcal disease rates in at-risk and high-risk adults are significantly higher than healthy adults leading to substantial economic burden. Electronic supplementary material The online version of this article (10.1186/s12879-018-3326-z) contains supplementary material, which is available to authorized users.

International audience; Cryptosporidium spp. are a major cause of gastrointestinal diseases in humans worldwide. While a single subtype of Cryptosporidium hominis has been shown to be responsible for several large outbreaks related to water contamination in developed countries, little is known about the epidemiology of C. hominis in developing countries. This study reports the first genetic characterization of C. hominis at the subtype level in several human populations in Tunisia using the gp60 gene. Eighteen isolates were identified as C. hominis by a restriction fragment length polymorphism (RFLP) analysis. The prevalence of this species in different human populations ranges from 1.53% to 13.04% with a high prevalence being reported in immunocompromised children (13.04%) followed by patients with malignent myeloma (5.5%) and HIV-infected patients (4.59%). The gp60 analysis on C. hominis isolates, performed in 14 cases, showed the presence of a single subtype family: "Ia". Different subtypes were identified within this family (A11G1R1, A12R3, A23G1R1, A26G1R1, A27G1R1, A28G1R1). The IaA26G1R1 subtype was the most dominant subtype described in this area (50%). Despite the high genetic diversity of Cryptosporidium spp, a low heterogeneity at the subtype level was observed within C. hominis circulating in Tunisia. This distribution is an indicator for intensive and stable anthroponotic cryptosporidiosis in this region. Besides, the presence of a unique genotype in 5 HIV-infected patients attending the same hospital ward suggests the possible occurrence of hospital-acquired infection and underlines the need to implement preventive measures to avoid nosocomial transmission.

Summary Objectives The results of the T-SPOT.TB (T-SPOT) assay are reduced in immunocompromised patients with active tuberculosis (ATB), and it is difficult using T-SPOT results to distinguish ATB from latent tuberculosis infection (LTBI) in this condition. The aim of this study was to determine the performance of the TBAg/PHA ratio in T-SPOT assay in the diagnosis of ATB in immunocompromised patients. Methods One hundred and forty three immunocompromised ATB patients and 124 LTBI individuals were diagnosed according to conventional tests and T-SPOT assay. Results The results of T-SPOT assay are of no value in the diagnosis of ATB in immunocompromised patients. However, the number of phytohaemagglutinin (PHA) spot-forming cells (sfc) in T-SPOT assay was substantially decreased in immunocompromised ATB patients compared with that in LTBI individuals. Receiver operating characteristic (ROC) analysis revealed that a further calculation of the TBAg/PHA ratio (the larger of the ESAT-6/PHA and CFP-10/PHA) showed a better performance in distinguishing these two diseases. Using the threshold value of 0.316, the sensitivity and specificity for distinguishing immunocompromised ATB patients from LTBI individuals were respectively 79.21 and 94.05%. Conclusions Our findings suggest that the TBAg/PHA ratio might have some significance for the diagnosis of TB disease in immunocompromised patients.

Background and Purpose: Gastroenteritis and the clinical profile caused by Microsporidia, an opportunistic pathogen, may be severe in immunocompromised individuals, especially in AIDS patients. Conventionally, it is necessary to detect the small infective spores in stained smears. However, due to the limitations of the microscopy-based methods, several DNA-based methods such as polymerase chain reaction (PCR) have recently been developed to enhance diagnosis sensitivity. Therefore,we sought to evaluate the rate of infection in immunocompromised patients as compared with immunocompetent patients in Kerman, Iran. Materials and Methods: We collected stool samples of 199 human subjects (116 males and 83 females), aged 1 to 69 years old. They were divided into immunocompromised (i.e., AIDS [n=72] and cancer-positive patients [n=59]) and immunocompetent (n=68) groups. We comparatively examined the fecal materials using the microscopy and PCR methods. Results: The overall prevalence rate of Microsporidia infection was 10.05% (20/199). Entrocytozoon bieneusi was the only species within the Microsporidia genus that was identified in 14.5% (19/131) of the immunocompromised patients and 1.47% (1/68) of the immunocompetent individuals. Conclusion: Considering the higher prevalence rate of microsporidiosis in patients with immunodeficiency (10.03%), we suggest performing sensitive and specific techniques such as PCR for the detection of these parasites in immunocompromised patients.

Introduction: Respiratory viruses (influenza, parainfluenza, respiratory syncytial virus, coronavirus, human metapneumovirus, and rhinovirus) represent the most common causes of respiratory viral infections in immunocompromised patients. Also, these infections may be more severe in immunocompromised patients than in the general population. Early diagnosis and treatment of viral infections continue to be of paramount importance in immunocompromised patients; because once viral replication and invasive infections are evident, prognosis can be grave. Areas covered: The purpose of this review is to provide an overview of the main antiviral agents used for the treatment of respiratory viral infections in immunocompromised patients and review of the new agents in the pipeline. Expert commentary: Over the past decade, important diagnostic advances, specifically, the use of rapid molecular testing has helped close the gap between clinical scenarios and pathogen identification and enhanced early diagnosis of viral infections and understanding of the role of prolonged shedding and viral loads. Advancements in novel antiviral therapeutics with high resistance thresholds and effective immunization for preventable infections in immunocompromised patients are needed.

Background: Viruses and atypical pathogens can cause significant respiratory illness in immunocompromised patients. Multiplex polymerase chain reaction (MPCR) has improved the diagnostic yield of pathogens, and it is easier to identify the co-infections also. The present study was done to evaluate the performance of MPCR on bronchoalveolar lavage (BAL) samples in immunocompromised patients. Methods: Atotal of 177 BAL specimens collected over a 19 months period from immunocompromised patients with respiratory illness were analyzed with the MPCR and aerobic culture. Patients were divided into four according to the pathogens. Category V (only viral), Category NV (nonviral, i.e., bacteria and atypical), Category M (mixed, i.e., both viral and nonviral pathogen), and Category UK (unknown etiology). Results: MPCR identified the causative pathogen in 59.3% of patients while culture could identify only in 37.8% of patients. Most frequent etiological agent was Klebsiella pneumoniae (32%), followed by cytomegalovirus (21%), and Pneumocystis jirovecii (10%). Numbers of patients in each category were Category V (9.6%), Category NV (43.5%), Category M (19.8%), and Category UK (27.1%). Mortality was significantly higher in patients of Category M having mixed infections. Conclusion: MPCR is highly sensitive and rapid tool which can be considered in the routine diagnostic algorithm of respiratory illness in immunocompromised patients.

Background and Purpose: Gastroenteritis and the clinical profile caused by Microsporidia, an opportunistic pathogen, may be severe in immunocompromised individuals, especially in AIDS patients. Conventionally, it is necessary to detect the small infective spores in stained smears. However, due to the limitations of the microscopy-based methods, several DNA-based methods such as polymerase chain reaction (PCR) have recently been developed to enhance diagnosis sensitivity. Therefore, we sought to evaluate the rate of infection in immunocompromised patients as compared with immunocompetent patients in Kerman, Iran. Materials and Methods: We collected stool samples of 199 human subjects (116 males and 83 females), aged 1 to 69 years old. They were divided into immunocompromised (i.e., AIDS [n=72] and cancer-positive patients [n=59]) and immunocompetent (n=68) groups. We comparatively examined the fecal materials using the microscopy and PCR methods. Results: The overall prevalence rate of Microsporidia infection was 10.05% (20/199). Entrocytozoon bieneusi was the only species within the Microsporidia genus that was identified in 14.5% (19/131) of the immunocompromised patients and 1.47% (1/68) of the immunocompetent individuals. Conclusion: Considering the higher prevalence rate of microsporidiosis in patients with immunodeficiency (10.03%), we suggest performing sensitive and specific techniques such as PCR for the detection of these parasites in immunocompromised patients.