Foreword: Preventing COVID-19 Among the Immunocompromised Population.

The COVID-19 pandemic represented 1 of the more significant and unique public health challenges facing the global community, particularly afflicting those with compromised immune systems. These immunocompromised individuals were readily recognized as a group at high risk of infection by SARS-CoV-2 and the associated severe outcomes of COVID-19. Although preventive strategies such as vaccination are important, initial clinical vaccine trials did not enroll immunocompromised individuals; in-depth evaluations of the safety, immunogenicity, and real-world outcomes associated with these vaccines were conducted in this population thereafter. As immunogenicity data of COVID-19 vaccination among this disparate group of individuals emerged, vaccination strategies were adapted to address outstanding challenges and further protect the entirety of this population. This 8-part journal supplement characterizes in-depth the mRNA-based COVID-19 vaccination strategies across the spectrum of immunocompromised individuals, focusing on the ongoing approaches to challenges facing this group as the pandemic continues to evolve.

Genomic and phylogenetic characterization of Elizabethkingia anophelis strains: The first two cases of life-threatening infection in Japan.

OBJECTIVE: Elizabethkingia anophelis causes meningitis, bloodstream infections, and respiratory infections in immunocompromised individuals. We examined two E. anophelis strains isolated from the first life-threatening cases caused by this species in Japan to determine the phylogenetic origin and genomic features of them. METHODS: We performed whole genome-based analysis to clarify the genetic relationship for the two strains (EK0004 and EK0079) and Elizabethkingia sp. strains isolated from worldwide and to characterize the genomic features such as the prevalence of virulence- and antimicrobial resistance (AMR)-related genes. PATIENTS: A 29-year-old man with hepatosplenic T-cell lymphoma and a 52-year-old man with systemic lupus erythematosus developed fatal bacteremia and meningitis due to E. anophelis, respectively. RESULTS: Two strains, EK0004 and EK0079, were genetically different but most closely related to the strains isolated from the largest outbreak in Wisconsin, USA from 2015 to 2016, and the strain isolated from cerebrospinal fluid of a patient in Florida, USA in 1982, respectively. The two strains contained AMR-related genes such as those encoding for an extended-spectrum ß-lactamase and multiple metallo-ß-lactamases and several virulence-related genes such as capsular polysaccharide synthesis gene clusters. CONCLUSIONS: Although further functional analyses are required to understand the virulence of these clones, these finding suggests that enough caution of E. anophelis infection in immunocompromised patients is required since the number of infections by this species is increasing outside Japan.

Immunogenic multi-epitope-based vaccine development to combat cyclosporiasis of immunocompromised patients applying computational biology method.

Cyclospora cayetanensis infections, also known as cyclosporiasis, persist to be the prevalent emerging protozoan parasite and an opportunist that causes digestive illness in immunocompromised individuals. In contrast, this causal agent can affect people of all ages, with children and foreigners being the most susceptible populations. For most immunocompetent patients, the disease is self-limiting; in extreme circumstances, this illness can manifest as severe or persistent diarrhea as well as colonize on secondary digestive organs leading to death. According to recent reports, worldwide 3.55% of people are infected by this pathogen, with Asia and Africa being more prevalent. For the treatment, trimethoprim-sulfamethoxazole is the only licensed drug and does not appear to work as well in some patient populations. Therefore, the much more effective strategy to avoid this illness is immunization through the vaccine. This present study uses immunoinformatics for identifying a computational multi-epitope-based peptide vaccine candidate for Cyclospora cayetanensis. Following the review of the literature, a highly efficient, secure, and vaccine complex based on multi-epitopes was designed by utilizing the identified proteins. These selected proteins were then used to predict non-toxic and antigenic HTL-epitopes, B-cell-epitopes, and CTL-epitopes. Ultimately, both a few linkers and an adjuvant were combined to create a vaccine candidate with superior immunological epitopes. Then, to establish the vaccine-TLR complex binding constancy, the TLR receptor and vaccine candidates were placed into the FireDock, PatchDock, and ClusPro servers for molecular docking and iMODS server for molecular-dynamic simulation. Finally, this selected vaccine construct was cloned into Escherichia coli strain-K12; thus, the constructed vaccines against Cyclospora cayetanensiscould improve the host immune response and can be produced experimentally.

Oral mycotic infection caused by a rare Verticillium species - a case report.

BACKGROUND: Deep-seated fungal infections of the oral cavity present a diagnostic challenge as the clinical presentation is usually aggressive leading to misdiagnosis of malignancy. Nevertheless, the species of fungi responsible for such diseases in immunocompromised individuals are varied thus, further complicating the diagnosis. CASE PRESENTATION: Presented below is a case regarding the diagnosis and management of deep mycotic infection of the oral cavity caused by a fungus that very rarely causes disease in humans, the Verticillium species. CONCLUSIONS: The case highlights the fact that rare pathogens should also be considered in the differential diagnosis, especially in patients with debilitating conditions like uncontrolled diabetes. Likewise, histopathological evaluation and microbiological investigations are of paramount importance and remain the gold standard to reach a definitive diagnosis.

Brain Abscess Caused by Listeria monocytogenes: A Rare Case of Supratentorial Neurolisteriosis.

Listeria monocytogenes is a Gram-positive bacillus that presents a tropism for the central nervous system (CNS). In fact, CNS involvement occurs in over two-thirds of infections caused by this agent. Meningitis is the most common manifestation, while brain abscess is rare. We present the case of a 77-year-old male patient on corticosteroid treatment for bronchiolitis obliterans organizing pneumonia with a history of unpasteurized cheese consumption, who presented with fever and altered mental status. Brain computerized tomography scan revealed left frontal cortico-subcortical hypodensity mimicking an ischemic stroke. Subsequent magnetic resonance imaging revealed a brain abscess, and blood cultures yielded Listeria monocytogenes. A good clinical outcome was achieved after appropriate antimicrobial therapy and abscess drainage. This case underscores the importance of considering Listeria monocytogenes in CNS infections, especially in immunocompromised individuals over 65 years of age. The atypical supratentorial involvement challenges the more common rhombencephalitis presentation. Maintaining a high level of suspicion in relevant populations is crucial for timely diagnosis and intervention, especially in patients with comorbidities, who present particularly high mortality rates.

Global research landscape of health care-associated infections among immunocompromised people before and after the start of the COVID-19 pandemic.

Health care-associated infections (HCAIs) pose a substantial threat to immunocompromised individuals and represent a frequent adverse event in health care delivery. The aim of this study was to evaluate the global research landscape of HCAIs among immunocompromised populations before and during the COVID-19 pandemic. A systematic search of articles published between 2013 and 2022 in the Web of Science Core Collection database was conducted, and content analytics and integrated science mapping were used for data analysis and interpretation. The review identified 1,473 articles. Only 633 articles authored by 4,151 individuals and published in 366 journals were included. The average citation rate was 14.27 per document, and research production grew annually by 9.07% peaking in 2021 during the COVID-19 pandemic but declining in 2022. The United States emerged as the most productive country, with 743 publication appearances and 2,485 citations. Keywords such as "epidemiology," "infection," "mortality," and "risk factors" were frequently encountered in the analyzed literature. The main research themes, including "mortality," "sepsis," "immunosuppression," "expression," and "pneumonia," underscored the focal points of importance within this domain. This study highlighted the growing interest regarding HCAIs in immunocompromised populations, especially during the COVID-19 pandemic. The study findings underscore the need to advance research efforts to understand different immunocompromised states, develop tailored infection prevention measures, and address health care disparities to mitigate the burden of HCAIs among immunocompromised individuals.

An Atypical Presentation of an Uncommon Malignancy: Plasmablastic Lymphoma Presenting As Recurrent Scrotal Abscesses.

Plasmablastic lymphoma (PBL) is a rare and extremely diagnostically challenging entity. We report a unique case of PBL in an adult male with a history of recurrent scrotal abscesses who presented with progressively worsening scrotal pain, swelling, and drainage. Pelvic CT demonstrated a large scrotal abscess with external draining tracts with foci of air. Surgical debridement revealed necrotic tissue throughout the abscess cavity, abscess wall, and scrotal skin. Immunohistochemical analysis of the scrotal skin specimen uncovered diffuse proliferation of plasmacytoid cells with immunoblastic features that stained positive for CD138, CD38, IRF4/MUM1, CD45, lambda restriction, and Epstein-Barr encoded RNA in situ hybridization (EBER-ISH) with high Ki-67 proliferation index greater than 90%. Taken together, these findings confirmed a diagnosis of PBL. Treatment with six cycles of infusional etoposide, prednisolone, vincristine, cyclophosphamide, and hydroxydaunorubicin (EPOCH-like regimen) was administered with subsequent positron emission tomography (PET)/CT confirmation of complete response. There was no clinical evidence of lymphoma recurrence at the time of follow-up six months later. Our case exemplifies the growing diversity of ways in which PBL may manifest and underscores the importance of a clinician's familiarity with this entity and its well-defined risk factor of immunosuppression.

Progressive disseminated histoplasmosis in idiopathic CD4 lymphocytopenia an underdiagnosed combination - a case report.

Progressive disseminated histoplasmosis (PDH) usually presents as fever, anemia, leukopenia, hepatosplenomegaly, lymphadenopathy and pulmonary symptoms. There are few reports on the association of idiopathic CD4 lymphocytopenia (ICL) with histoplasmosis. We describe a 65-year-old female presented with a history of fever, papulo-nodular rash and significant weight loss and diagnosed as progressive disseminated histoplasmosis. All immunocompromised conditions were ruled out. In addition, her 2 consecutive CD4 counts were below 300. The patient was diagnosed with PDH associated with ICL. The patient showed significant improvement with liposomal amphotericin B and itraconazole. Absolute CD4 counts should be done in all cases of progressive disseminated histoplasmosis even in HIV negative individuals to rule out associated ICL.

Mycobacterium abscessus Pneumonia in Severe Alcoholism.

Non-tuberculous mycobacterial infections (mycobacterium other than Mycobacterium tuberculosis and Mycobacterium leprae) are organisms that are commonly found in the environment such as water, soil, and dust. They may form difficult to eliminate biofilms and have been reported to cause significant infections in humans, especially in immunocompromised hosts. This article describes an interesting case of Mycobacterium abscessus in the lung.

Immune Response to COVID-19 and mRNA Vaccination in Immunocompromised Individuals: A Narrative Review.

Immunocompromised individuals are at high risk of poor coronavirus disease 2019 (COVID-19) outcomes and demonstrate a lower immune response to COVID-19 vaccines, including to the novel mRNA vaccines that have been shown to elicit high neutralizing antibody levels. This review synthesized available data on the immune response to COVID-19 and critically assessed mRNA COVID-19 vaccine immunogenicity in this vulnerable subpopulation. Patients with various immunocompromising conditions exhibit diverse responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 severity and mortality, and available vaccines elicit lower immune responses, particularly in solid organ transplant recipients. Strategies to improve vaccine responses in immunocompromised individuals are being implemented in vaccine recommendations, including the use of a third and fourth vaccine dose beyond the two-dose series. Additional doses may enhance vaccine effectiveness and help provide broad coverage against emerging SARS-CoV-2 variants. Continued investigation of vaccines and dosing regimens will help refine approaches to help protect this vulnerable subpopulation from COVID-19.

Characteristics and mechanisms to control a COVID-19 outbreak on a leukemia and stem cell transplantation unit.

Immunosuppressed patients like patients with leukemia or lymphoma, but also patients after autologous or allogeneic stem cell transplantation are at particular risk for an infection with COVID-19. We describe a COVID-19 outbreak on our leukemia and stem cell transplantation unit (LSCT-Unit) originating from a patient with newly diagnosed acute myeloid leukemia. The patient was treated with intensive induction chemotherapy and we characterize the subsequent outbreak of COVID-19 on a LSCT-Unit. We describe the characteristics of the 36 contacts among the medical team, the results of their PCR and antibody tests and clinical aspects and features of infected employees. Of these 36 close contacts, 9 employees of the LSCT-Unit were infected and were tested positive by PCR and/or antibody-testing. 8/9 of them were symptomatic, 3/9 with severe, 5/9 with mild symptoms, and one person without symptoms. Due to stringent hygiene measures, the outbreak did not lead to infections of other patients despite ongoing clinical work. Moreover, we demonstrate that incubation period and clinical course of a COVID-19 infection in an immunosuppressed patient could be unusual compared to that of immunocompetent patients. Consistent PCR and antibody testing are helpful to understand, control, and prevent outbreaks. For the safety of health-care workers and patients alike, all employees wore FFP2 masks and were trained to adhere to several further safety guidelines. The implementation of rigorous hygiene measures is the key to controlling an outbreak and preventing infections of other patients.

Exploring antifungal activities of acetone extract of selected Indian medicinal plants against human dermal fungal pathogens.

A broad spectrum of medicinal plants was used as traditional remedies for various infectious diseases. Fungal infectious diseases have a significant impact on public health. Fungi cause more prevalent infections in immunocompromised individuals mainly patients undergoing transplantation related therapies, and malignant cancer treatments. The present study aimed to investigate the in vitro antifungal effects of the traditional medicinal plants used in India against the fungal pathogens associated with dermal infections. Indian medicinal plants (Acalypha indica, Lawsonia inermis Allium sativum and Citrus limon) extract (acetone/crude) were tested for their antifungal effects against five fungal species isolated from skin scrapings of fungal infected patients were identified as including Alternaria spp., Curvularia spp., Fusarium spp., Trichophyton spp. and Geotrichum spp. using well diffusion test and the broth micro dilution method. All plant extracts have shown to have antifungal efficacy against dermal pathogens. Particularly, Allium sativum extract revealed a strong antifungal effect against all fungal isolates with the minimum fungicidal concentration (MFC) of 50-100 µg/mL. Strong antifungal activity against Curvularia spp., Trichophyton spp., and Geotrichum spp. was also observed for the extracts of Acalypha indica, and Lawsonia inermis with MFCs of 50-800 µg/mL respectively. The extracts of Citrus limon showed an effective antifungal activity against most of the fungal strains tested with the MFCs of 50-800 µg/mL. Our research demonstrated the strong evidence of conventional plants extracts against clinical fungal pathogens with the most promising option of employing natural-drugs for the treatment of skin infections. Furthermore, in-depth analysis of identifying the compounds responsible for the antifungal activity that could offer alternatives way to develop new natural antifungal therapeutics for combating resistant recurrent infections.

Humoral response to a 13-valent pneumococcal conjugate vaccine in kidney transplant recipients.

BACKGROUND: Vaccination against S. pneumoniae is recommended by national guidelines. Moderate immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13) has been reported in adult kidney transplant recipients (KTR). This study further defines the immunogenicity of PCV13 in this cohort. METHODS: 49 KTR were immunized with PCV13. A validated opsonophagocytic killing assay (OPA), a global anti-pneumococcal capsular polysaccharide (anti-PCP) IgG, IgG2, IgM and IgA ELISA, and - for selected patients - a serotype specific anti-PCP WHO reference ELISA were performed pre-vaccination and at month 1 and 12 post-vaccination. RESULTS: Geometric mean OPA titers increased significantly for 13/13 serotypes at month 1 and for 10/13 serotypes at month 12 post-vaccination. Vaccine response defined as an OPA titer ≥1:8 was reached in 9/13 serotypes (median). 53% reached the vaccine response criteria at month 1 and 45% at month 12. At month 1 after vaccination, the median OPA titer in an age-group matched healthy reference population was 5- to 10-fold higher than in KTR. OPA titers correlated strongly with results to the global and serotype specific anti-PCP IgG ELISA. Lower OPA titers significantly (p < 0.05) correlated with albuminuria, an interval between vaccination and transplantation <12 months, age and treatment with mycophenolate mofetil. Global IgG, IgG2, IgM and IgA, as well as serotype specific anti-PCP antibody concentrations (12/13 serotypes) increased significantly at month 1 and 12 post-vaccination. CONCLUSIONS: Kidney transplant recipients show a significant humoral response after vaccination with PCV13. Functional antibody response exists, but is not as vigorous as in healthy adults.

Prevalence of Pneumocystis jirovecii among immunocompromised patients in hospitals of Tehran city, Iran.

Pneumocystis jirovecii is an opportunistic organism that can cause extreme complications such as Pneumocystis pneumonia in immunocompromised individuals. There is no comprehensive study was conducted Iran to determine the prevalence of this infection in susceptible individuals. In the present study, 160 sera samples were collected from immunocompromised patients, including acquired immunodeficiency syndrome (AIDS) patients, diabetic patients, Hodgkin lymphoma patients and non-Hodgkin lymphoma patients. The specimens were collected from Imam Khomeini and army's 501 hospitals. The specimens were examined using indirect fluorescent antibody test. The results of the study showed that 39.30% specimens were found positive, with different rates in different groups, including 20, 22.50, 37.50, and 77.50% of diabetic patients, non-Hodgkin patients, Hodgkin lymphoma patients, and AIDS patients, respectively. This occurrence is relatively high and can be a potential life-threatening hazard to infected patients in studied groups, on the other hand the organism can be transmitted from infected people to other susceptible individuals.

Manipulación de la inmunosenescencia / Immunosenescence manipulation

En la actualidad existe un aumento del envejecimiento poblacional en Cuba y a nivel mundial, consecuencia del éxito de las políticas de salud pública y del desarrollo socioeconómico. Con el incremento progresivo de la edad se evidencian cambios en el sistema inmunológico que contribuyen a una susceptibilidad incrementada a las enfermedades infecciosas, condiciones patológicas relacionadas con la inflamación, enfermedades autoinmunes, el cáncer y se manifiesta una respuesta reducida ante la vacunación. La manipulación de la inmunosenescencia a través de diferentes terapéuticas se espera que contribuya al rejuvenecimiento del sistema inmune y por consiguiente a la restauración de la inmunidad en individuos inmunocomprometidos, al control del cáncer y al incremento de la eficacia de la vacunación en ancianos(AU)

There is an increase of population aging in Cuba and globally, as a result of the success of public health policies and socio-economic development. With the progressive increase in age, there are changes in the immune system that contribute to an increased susceptibility to infectious diseases, pathological conditions related to inflammation, autoimmune diseases, cancer and a reduced response to vaccination. The manipulation of immunosenescence through different therapies has been studied. It is expected to possibly contribute to the 'rejuvenation' of the immune system and consequently, to the restoration of immunity in immunocompromised individuals, the improvement of the effectiveness of vaccination in the elderly and the control of cancer(AU)