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Candida albicans is an "opportunistic fungal agent" in cancer patients that can become colonized in both mucosal and deep tissues and cause severe infections. Most evidence has shown that C. albicans can enhance the progress of different cancers by several mechanisms such as generating virulence factors, participation in endogenous production of pro-inflammatory mediators, and stimulating a wide range of immune cells in the host. The main idea of this review is to describe a range of Candida-used mechanisms that are important in candidiasis-associated malignant processes and cancer development, particularly breast cancer. This review intends to provide a detailed discussion on different regulatory mechanisms of C. albicans that undoubtedly help to open new therapeutic horizons of cancer therapy in patients with fungal infection. The current therapeutic approach is not fully effective in immunocompromised and cancer patients, and further studies are required to find new products with effective antifungal properties and minimal side effects to increase the susceptibility of opportunistic fungal infections to conventional antifungal agents. So, in this situation, a special therapy should be considered to control the infection and simultaneously have the most therapeutic index on tumor patients. [ABSTRACT FROM AUTHOR]

The purpose of this study was to establish a porcine model of urinary tract infection (UTI) with gram‐positive uropathogens. Ten female domestic pigs were experimentally inoculated with human UTI isolates of Enterococcus faecalis (n = 3), Staphylococcus saprophyticus (n = 3), or Staphylococcus aureus (n = 4) and followed with regular urine samples. Bladders and kidneys were aseptically removed at termination (5–7 days post infection) and assessed by gross pathology and bacterial enumeration. Enterococcus faecalis (n = 3 of 3) and S. aureus (n = 2 of 4) successfully colonized the pig bladders. Inoculation with S. saprophyticus never resulted in detectable bacteriuria. All infected pigs had cleared the infection spontaneously before termination. Surprisingly, three (of four) pigs inoculated with S. aureus led to spontaneous infection with opportunistic pathogens. Also, one pig colonized with E. faecalis resulted in spontaneous infection with E. coli. In conlusion, the pig supports experimental UTI with E. faecalis for up to 24 h but not prolonged infection. S. aureus and S. saprophyticus fails to cause UTI in pigs and other animals should be considered for studying these pathogens. [ABSTRACT FROM AUTHOR]

Introduction: Cytomegalovirus (CMV) is a common opportunistic infection after solid organ transplantation, with significant impact on morbidity and long-term survival. Despite advances in diagnostics and therapeutics, the management of CMV remains very challenging. Areas Covered: This article reviews emerging data on the clinical utility of laboratory assays that quantify cell-mediated immune responses to CMV. Observational studies have consistently demonstrated that a deficiency in pathogen-specific cell-mediated immunity is correlated with a heightened risk of primary, reactivation or recurrent CMV after transplantation. A limited number of interventional studies have recently investigated cell-mediated immune assays in guiding the prevention and treatment of CMV infection after solid organ transplantation. Expert Opinion: The pathogenesis and outcome of CMV after solid organ transplantion reflect the interplay between viral replication and CMV-specific immune reconstitution. Research in CMV-specific cell-mediated immunity paved way for the development of several laboratory assays that may assist clinicians in predicting the risk of CMV after transplantation, individualize the approach to CMV disease prevention, guide the need and duration of treatment of CMV infection, and predict the risk of relapse after treatment. More interventional studies are needed to further solidify the role of cell-mediated immune assays in various clinical situations after transplantation. [ABSTRACT FROM AUTHOR]

Introduction: HIV replication leads to a change in lymphocyte phenotypes that impairs immune protection against opportunistic infections. We examined current HIV replication as an independent risk factor for tuberculosis (TB). Methods: We included people living with HIV from 25 European cohorts 1983–2015. Individuals <16 years or with previous TB were excluded. Person-time was calculated from enrolment (baseline) to the date of TB diagnosis or last follow-up information. We used adjusted Poisson regression and general additive regression models. Results: We included 272,548 people with a median follow-up of 5.9 years (interquartile range [IQR] 2.3–10.9). At baseline, the median CD4 cell count was 355 cells/μL (IQR 193–540) and the median HIV-RNA level 22,000 copies/mL (IQR 1,300–103,000). During 1,923,441 person-years of follow-up, 5,956 (2.2%) people developed TB. Overall, TB incidence was 3.1 per 1,000 person-years (95% confidence interval [CI] 3.02–3.18) and was four times higher in patients with HIV-RNA levels of 10,000 compared with levels <400 copies/mL in any CD4 stratum. CD4 and HIV-RNA time-updated analyses showed that the association between HIV-RNA and TB incidence was independent of CD4. The TB incidence rate ratio for people born in TB-endemic countries compared with those born in Europe was 1.8 (95% CI 1.5–2.2). Conclusions: Our results indicate that ongoing HIV replication (suboptimal HIV control) is an important risk factor for TB, independent of CD4 count. Those at highest risk of TB are people from TB-endemic countries. Close monitoring and TB preventive therapy for people with suboptimal HIV control is important. [ABSTRACT FROM AUTHOR]

Purpose: A causal role of type-I interferons (IFN-I) in autoinflammatory type-I interferonopathies such as SAVI (STING–associated vasculopathy with onset in infancy) and CANDLE (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures) is suggested by elevated expression of IFN-I stimulated genes (ISGs). Hitherto, the lack of specific inhibitors of IFN-I signaling has prevented the verification of a causal role for IFN-I in these conditions. Commonly used inhibitors of the JAK/STAT pathway exert broad effects on multiple signaling pathways leading to more general immunosuppression beyond IFN-I signaling. Methods: Here we show in four patients with SAVI and one patient with CANDLE syndrome that blockade of the IFNAR1 receptor (Anifrolumab) exerts an additive effect over JAK-inhibitor alone. In two patients with SAVI, monotherapy with Anifrolumab is sufficient to retain a suppressed IFN-I signature and clinical improvement. Results: Anifrolumab normalizes IFN-I signature genes and relieves symptoms beyond what is typically achieved by a JAK-inhibitor (Baricitinib) alone in patients with type-I interferonopathies. In two patients Anifrolumab was used successfully as monotherapy. Addition of Anifrolumab enabled steroid tapering and cessation with reduced overall immunosuppression and lower risks of opportunistic infections and improved metabolic states and growth which is highly beneficial in these young patients. Conclusion: These results verify a causal role of IFN-I signaling in type-I Interferonopathies SAVI and CANDLE and suggests Anifrolumab as an important new treatment option in autoinflammatory diseases with elevated IFN-I induced gene expression. Genia Kretzschmar, Laura Piñero Páez, and Ziyang Tan are shared-first authors. Sara Alehashemi, AnnaCarin Horne, and Petter Brodin are co-senior author. [ABSTRACT FROM AUTHOR]

Background: Cryptococcus is an opportunistic infection acquired through inhalation from the environment, primarily affecting individuals with compromised immune systems. It typically leads to pneumonia upon passing through lung tissue. The infection can disseminate to various organs via the bloodstream, resulting in meningitis or encephalitis in the central nervous system. Disseminated Cryptococcus has been reported to involve the skin, liver, eyes, lymph nodes, bone marrow, spleen, kidneys, and intestines, significantly increasing morbidity and mortality. However, pancreatic involvement in Cryptococcus is relatively rare, and a few case reports have highlighted severe organ damage and high mortality rates. Case presentation: In this case report, we present the case of a 36-year-old Asian man who presented with a 2-week history of headaches and blurred vision in his right eye. Brain magnetic resonance imaging revealed multiple brain masses, along with a mass in the lower left lung field and a tumor in the pancreatic tail, as detected by chest computed tomography. Endoscopic ultrasound-guided fine needle biopsy and computed tomography-guided lung biopsy confirmed the diagnosis of disseminated cryptococcal infection involving the pancreas, lung, and brain. The patient's clinical condition improved following antifungal therapy. Additionally, we identified anti-granulocyte–macrophage colony-stimulating factor antibody as a risk factor for disseminated cryptococcal infection in this patient. Conclusion: Disseminated cryptococcosis can be a potentially lethal condition, as highlighted by previous literature. However, early diagnosis using contrast-enhanced harmonic endoscopic ultrasound and endoscopic ultrasound-guided biopsies, as well as prompt treatment as demonstrated in our case, can improve outcomes and prevent mortality. [ABSTRACT FROM AUTHOR]

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BACKGROUND Kidney transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV is an emerging practice. It has been performed since 2016 under the U.S. congressional HIV Organ Policy Equity Act and is currently approved for research Only. The Department of Health and Human Services is considering expanding the procedure to clinical practice, but data are limited to small case series that did not include donors without HIV as controls. METHODS In an observational study conducted at 26 U.S. centers, we compared transplantation of kidneys from deceased donors with HIV and donors without HIV to recipients with HIV. The primary outcome was a safety event (a composite of death from any cause, graft loss, serious adverse event, HIV breakthrough infection, persistent failure of HIV treatment, or opportunistic infection), assessed for noninferiority (margin for the upper bound of the 95 % confidence interval, 3.00). Secondary outcomes included overall survival, survival without graft loss, rejection, infection, cancer, and HIV superinfection. RESULTS We enrolled 408 transplantation candidates, of whom 198 received a kidney from deceased donor; 99 received a kidney from a donor with HIV and 99 from a donor without HIV. The adjusted hazard ratio for the composite primary outcome was 1.00 (95% confidence interval ICI], 0.73 to 1.38), which showed noninferiority. The following secondary outcomes were similar whether the donor had HIV or not: overall survival at 1 year (94% vs. 9596) and 3 years (85% vs. 87%), survival without graft loss at 1 year (93% vs. 9096) and 3 years (84% vs. 81%), and rejection at 1 year (13% vs. 21°/0) and 3 years (21% vs. 2496). The incidence of serious adverse events, infections, surgical or vascular complications, and cancer was similar in the groups. The incidence of HIV breakthrough infection was higher among recipients of kidneys from donors with HIV (incidence rate ratio, 3.14; 95°/0, CI, 1.02 to 9.63), with one potential HIV superinfection among the 58 recipients in this group with sequence data and no persistent failures of HIV treatment. CONCLUSIONS In this observational study of kidney transplantation in persons with HIV, transplantation from donors with HIV appeared to be noninferior to that from donors without HIV. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT03500315.). [ABSTRACT FROM AUTHOR]

Background: Immune reconstitution inflammatory syndrome (IRIS) is an inflammatory reaction that occurs in HIV/AIDS patients after antiretroviral therapy (ART) initiation. Along with immune system recovery, IRIS can overreact to existing infections or latent pathogens, causing symptoms that mimic those infections. Few studies elucidated the clinical features and prognosis of Talaromycosis marneffei (TSM)-associated IRIS in HIV/AIDS patients. The aim of our study was to evaluate the incidence, clinical characteristics, and prognosis of TSM-associated IRIS by retrospectively analyzing the clinical data of HIV/AIDS patients with TSM. Methodology/Principal findings: A total of 224 HIV/AIDS inpatients with TSM were enrolled, aged between 19 and 81 years. Among them, 86.6% were male and 13.4% were female, of which 24 (10.7%) patients developed IRIS. In IRIS group, the median time from ART initiation to IRIS occurrence was 9.0 days (IQR, 5.0–16.8 days), with 87.5% (21/24) occurring within 2 weeks. Primary clinical manifestations included recurrent fever and exacerbation of pulmonary infection. At the onset of IRIS, 54.2% (13/24) patients were treated with intravenous dexamethasone, and 12.5% (5/24) patients were treated with oral prednisone for 1–3 weeks. No significant differences in baseline characteristics or ART regimens were observed between IRIS and non-IRIS groups; however, patients in IRIS group had higher levels of CRP, CD4+ count, and CD4+/CD8+ ratio than non-IRIS group (equivalent time point: 1–2 weeks after ART initiation) at IRIS onset. The IRIS group exhibited longer hospital stays and higher readmission rates, but equivalent mortality rates compared with non-IRIS group. Conclusions/Significance: IRIS is a common complication in HIV/AIDS patients with TSM, often occurring within 2 weeks after ART initiation and exhibiting more pronounced immune reconstitution. The occurrence of IRIS significantly extended the hospitalization duration and increased the rate of readmission but had no influence on the mortality rate. Author summary: Immune reconstitution inflammatory syndrome (IRIS) is an inflammatory reaction that occurs in HIV/AIDS patients after antiretroviral therapy (ART) initiation. Along with immune system recovery, IRIS can overreact to existing infections or latent pathogens, causing symptoms that mimic those infections. The clinical characteristics of IRIS depend on the causative pathogen. Talaromycosis marneffei (TSM) is one of the common opportunistic infections in HIV/AIDS patients, and often presents a disseminated form of infection, affecting multiple organs throughout the body. However, few reports on TSM-associated IRIS lead to challenges in clinical management. In this study, we carried out a retrospective analysis of TSM-associated IRIS, elucidated the occurrence and clinical features of TSM-associated IRIS, and compared the laboratory examination data and outcomes in TSM patients with or without IRIS. This study aims to review clinical data from HIV/AIDS patients with TSM to assess the frequency, features, and outcomes of TSM-associated IRIS, to improve understanding of the condition, and to facilitate clinical treatment effectively. [ABSTRACT FROM AUTHOR]

Objective: Systemic lupus erythematosus (SLE) patients receiving immunosuppressive therapy are at risk for opportunistic infections (OIs), particularly Pneumocystis pneumonia (PCP). This study aimed to evaluate the effectiveness of trimethoprim/sulfamethoxazole (TMP/SMX) as primary prophylaxis against OIs and its adverse effects in SLE patients receiving low-level immunosuppressive treatment in a real-world setting. Methods: This open-label randomized controlled trial enrolled SLE patients receiving low-level immunosuppressive treatment at Ramathibodi Hospital between May 2021 and December 2022. Patient demographics and relevant clinical data were collected. Participants were randomized 1:1 to receive TMP/SMX or no prophylaxis, with dose adjustments according to renal function. The incidences of TMP/SMX-sensitive OIs and adverse events were monitored for 12 months post-enrollment. Results: The trial was terminated early due to a high rate of adverse drug reactions (ADRs) associated with TMP/SMX. In total, 138 SLE patients receiving low-level immunosuppressive treatment were enrolled. Most patients (98.4%) were in disease remission. No TMP/SMX-sensitive OIs were observed in either group during the 12-month follow-up period. Among individuals receiving TMP/SMX, 10/70 (14.3%) developed ADRs. Of these 10 patients, eight experienced grade 1 ADRs, and two had grade 3 ADRs; all declined to resume prophylaxis. There were no deaths in the study. Conclusions: During the 12-month follow-up period, no TMP/SMX-sensitive OIs occurred in SLE patients receiving low-level immunosuppressive therapy, suggesting that primary prophylaxis with TMP/SMX may not significantly benefit this population. The high rate of ADRs observed underscores the need for clinicians to carefully consider the risks and benefits of TMP/SMX prophylaxis in these patients. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion A substantial percentage of people with HIV are still admitted for care at advanced disease stages. Here, we investigate the availability of the supplies and infrastructure required to provide care for this population in healthcare facilities and explore correlations with local demand.AIDS Healthcare Foundation's partner facilities were invited to respond to a survey addressing the availability of services to support clients with advanced HIV. We present results per continent and according to gross national income per capita using frequencies and percentages. We generated country‐level scores taking the average percentage of facilities with available resources on 10 key items and used Spearman's correlation to investigate relationships between country scores and local demand, depicted by the percentages of people with HIV newly enrolled in care with a CD4 T‐cell count <200/mm3 in 2022.A total of 643 facilities from 37 countries responded to the survey between September and December 2021. Overall, services requiring more costly equipment and/or supplies were less frequently available. Facilities in Africa, Asia, and Latin America/Caribbean and those with lower gross national income had a somewhat lower availability of diagnostic and therapeutic resources. Availability of services was not correlated with local demand: 14 countries (42%) had scores below the 50% percentile despite having >20% of newly enrolled people with HIV with a CD4 T‐cell count <200/mm3.Appropriate care can mitigate the morbidity and mortality associated with advanced HIV. We found that the healthcare services recommended by the World Health Organization as essential to support clients with advanced HIV are often unavailable in facilities providing HIV care, despite high local demand. [ABSTRACT FROM AUTHOR]

Corticosteroids can reduce the mortality rate among patients with severe COVID-19 pneumonia. However, opportunistic infections such as Mycobacterium tuberculosis are of concern, especially among those on high doses of corticosteroids. It is unknown whether the risk of developing subsequent TB infection is high or not among COVID-19 patients on high doses of corticosteroids. Hence, this study was conducted to address this gap of knowledge. We conducted a retrospective, cross-sectional study at the King Chulalongkorn Memorial Hospital from October 12, 2022 to June 30, 2023. Two hundred forty-three participants with documented COVID-19 diagnosis on high dose corticosteroids were enrolled into the study. Baseline characteristics and risk factors of developing TB were collected. The prevalence of TB was significantly different among participants with chronic kidney disease (CKD) stages 2–4 and chronic lung diseases. The incidence of TB post 1-year diagnosis of COVID-19 was 4 out of 243 patients (1.6%) or 1,646 cases per 100,000 person-year. The mortality rate among subsequent TB group was significantly much higher than the non-TB group (50% vs 0.4%; p-value = 0.001). COVID-19 participants on high doses of corticosteroids also were co-infected with other infections such as bacteria (37.1%), fungi (5.3%), and Pneumocystis jirovecii (PJP) (1.2%). We found that the incidence of TB in participants with COVID-19 on high doses of corticosteroids was 11 times higher than the general population. Therefore, we recommend screening for latent TB among these patients to prevent/early diagnose TB disease. [ABSTRACT FROM AUTHOR]

BACKGROUND. Most humans have been infected with cytomegalovirus (CMV) by midlife without clinical signs of disease. However, in settings in which the immune system is undeveloped or compromised, the virus is not adequately controlled and consequently presents a major infectious cause of both congenital disease during pregnancy as well as opportunistic infection in children and adults. With clear evidence that risk to the fetus varies with gestational age at the time of primary maternal infection, further research on humoral responses to primary CMV infection during pregnancy is needed. METHODS. Here, systems serology tools were applied to characterize antibody responses to CMV infection in pregnant and nonpregnant women experiencing either primary or chronic infection. RESULTS. Whereas strikingly different antibody profiles were observed depending on infection status, limited differences were associated with pregnancy status. Beyond known differences in IgM responses used clinically for identification of primary infection, distinctions observed in IgA and FcγR-binding antibodies and among antigen specificities accurately predicted infection status. Machine learning was used to define the transition from primary to chronic states and predict time since infection with high accuracy. Humoral responses diverged over time in an antigen-specific manner, with IgG3 responses toward tegument decreasing over time as typical of viral infections, while those directed to pentamer and glycoprotein B were lower during acute and greatest during chronic infection. CONCLUSION. In sum, this work provides insights into the antibody response associated with CMV infection status in the context of pregnancy, revealing aspects of humoral immunity that have the potential to improve CMV diagnostics. FUNDING. CYMAF consortium and NIH NIAID. [ABSTRACT FROM AUTHOR]

Background: Pneumocystis jirovecii pneumonia (PcP) is an opportunistic infection associated with immunocompromised patients. The development of novel immunotherapies has promoted the incidence of PcP. This study describes the clinical course and outcome of PcP in chimeric antigen receptor (CAR) T cell recipients with hematological malignancies. Methods: This is a retrospective case series of CAR-T recipients diagnosed with PcP in our center. The cases were all confirmed by metagenomic next-generation sequencing of clinical samples. The demographic, clinical, and outcome data were retrieved from the patients' medical charts and electronic medical record system. Results: In total, 8 cases of PcP were identified. The underlying malignancies included T-acute lymphoblastic leukemia (ALL) (n = 1), diffuse large B cell lymphoma (DLBCL) (n = 4), and B-ALL (n = 3). One patient received short-term sulfamethoxazole-trimethoprim (SMZ-TMP) while the others had no prophylaxis. Four patients had neutropenia/lymphopenia at the diagnosis of PcP, and two patients had immunosuppressants within one month before PcP manifestation. The median time from CAR-T infusion to PcP diagnosis was 98.5 days (range 52–251). Seven patients recovered from PcP after proper management while one died of septic shock. Conclusion: PcP can occur after different CAR-T product, and the long-term depletion of immune cells seems to be related to PcP. SMZ-TMP is effective in this setting. More real-world experience of CAR-T therapy is required to assess the incidence and outcome of PcP in this population. [ABSTRACT FROM AUTHOR]

Background: Opportunistic infections (OIs) pose a significant threat to children infected with HIV. Despite advancements in antiretroviral therapy (ART), these infections continue to be a public health concern. However, there is limited evidence regarding the incidence and predictors of OIs among HIV-infected children in Ethiopia, particularly in the study area. Therefore, the objective of this study was to assess the incidence and predictors of OIs among HIV-infected children on ART at public health facilities of Southwest Ethiopia People Regional State. Methods: The study employed an institution-based retrospective cohort design, conducted from July 1, 2018 to July 31, 2023, among HIV-infected children aged less than 15 years. Data were extracted using the national ART intake and follow-up forms. KoboCollect version 2023.2.4 and STATA version 14.0 were used for data collection and analysis, respectively. The Kaplan-Meier survival curve was used to estimate the probability of OI-free survival time. Variables with P-value < 0.25 in the bivariable Cox proportional hazard model were selected as candidates. In multivariable analysis, P-value < 0.05 and adjusted hazard ratio (AHR) with 95% confidence interval (CI) were used to declare statistically significant predictors. Results: Of the total 409 HIV infected children, 122(29.8%) developed at least one OI, contributing to 954.95 person-years of risk. The overall incidence rate was 12.8 (95% CI: 10.7, 15.2) per 100 person-years. The OI-free survival probability at the end of the follow-up period was 0.277(95% CI: 0.139, 0.434). The commonest OI was pulmonary tuberculosis, 30.33% (95% CI: 22.7, 39.2). Non-disclosing HIV status (AHR: 2.56, 95% CI: 1.42, 4.63), children aged 10–14 years (AHR: 2.34, 95% CI: 1.10, 4.95), no history of prevention of mother-to-child transmission of HIV (AHR: 2.33, 95% CI: 1.48, 3.66), hemoglobin level < 10 mg/dL (AHR: 2.26, 95% CI: 1.37, 3.75), fair or poor adherence to ART (AHR: 1.74, 95% CI: 1.09, 2.79), and having past history of OIs (AHR: 1.61, 95% CI: 1.03, 2.55) were statistically significant predictors of OIs. Conclusion and recommendations: The incidence of OIs was high in the study area. Hence, health facilities need to regularly monitor hemoglobin, enhance ART adherence, provide OI prophylaxis for at-risk children, reinforce PMTCT programs for early OI detection and management, and encourage timely and age-appropriate HIV status disclosure. Caregivers of HIV-infected children are also required to oversee and assist their children in adhering to the ART. [ABSTRACT FROM AUTHOR]

Background: Candida species have emerged as a significant cause of opportunistic infections. Alongside the expression of various virulence factors, the rise of antifungal resistance among Candida species presents a considerable clinical challenge. Aim: This study aimed to identify different Candida species isolated from clinical specimens, evaluate their antifungal sensitivity patterns, identify key genes regulating virulence mechanisms using multiplex PCR and to assess any correlation between their virulence profiles and antifungal resistance patterns. Method: A total of 100 Candida spp. was isolated from 630 different clinical specimens and identified to the species level. Their antifungal susceptibility was phenotypically evaluated in accordance with CLSI guidelines using the Vitek-2 Compact System. Virulence markers, including biofilm formation capacity, protease production, melanin production, coagulase production and hemolysin production, were also phenotypically detected. The genetic determinants for biofilm formation and extracellular hydrolytic enzymes were assessed using a multiplex PCR assay. Results: The prevalence of Candida spp. was 15.9%, with C. albicans (48%) and C. glabrata (16%) being the most common. C. albicans showed the highest virulence, with strong biofilm formation, and high proteinase and melanin production. Multiplex PCR revealed Hlp in 22.0%, Hwp in 80.0%, Als in 56.0%, and Sap genes in 56.0% of isolates. Virulence genes were more common in C. albicans than in non-albicans Candida (NAC). Resistance patterns significantly correlated with virulence profiles, with notable associations between flucytosine resistance and the presence of Hlp and Hwp genes. Conclusion: The significant correlation between virulent markers such as germination, coagulase, hemolysin production and resistance patterns among different Candida isolates is crucial for predicting the severity and outcomes of Candida infections. This understanding aids in guiding tailored treatment strategies. [ABSTRACT FROM AUTHOR]

Evolving evidence suggests that Janus Kinase Inhibitors (JAKi) may predispose to certain infections, including tuberculosis and human herpes viruses. This review aimed to compare the infection risk in patients on a systemic JAKi for a dermatologic indication to a placebo. A systematic review was carried out from inception to June 2023, using the EMBASE, Medline, SCOPUS, and Cochrane Library of Registered Trials databases. Eligible studies included placebo‐controlled randomized trials that investigated the incidence of infection in patients with a dermatologic indication. Primary outcomes included the most commonly reported infections pertaining to serious and opportunistic infections, upper respiratory tract infections, nasopharyngitis, herpes simplex, varicella zoster, tuberculosis, neutropenia, and lymphopenia. A meta‐analysis of incidence ratios was conducted to determine odds ratios (OR), with a 95% confidence interval (CI) analysis. The meta‐analysis found no increased risk of serious (OR: 0.92, 95% CI: 0.61–1.43, P = 0.74) or opportunistic infections (OR: 0.65, 95% CI: 0.32–1.31, P = 0.23). The incidence of varicella‐zoster infections was significantly higher in the JAKi cohort (OR: 1.72, 95% CI: 1.08–2.72, P = 0.022). From 25 studies, there was no overall increased risk of herpes simplex infections (OR: 1.43, 95% CI: 0.93–2.23, P = 0.102) to placebo; however, a significantly higher risk in those with atopic dermatitis to alopecia areata was demonstrated (OR: 1.73, 95% CI: 1.13–2.69, P = 0.013). The results of this analysis do not suggest an increased risk of serious and opportunistic infections in those on JAKi compared to placebo. However, they support an increased risk of varicella‐zoster infections and a higher risk of herpes simplex infections in those with atopic dermatitis to alopecia areata. The results of this report support these agents' short‐term safety but signal that vigilance should be practiced in patients at risk for serious or recurrent herpes virus infections. [ABSTRACT FROM AUTHOR]

Background: Pneumocystis jirovecii infection is an opportunistic infection that mostly affects patients with immunosuppressive conditions like human immunodeficiency virus (HIV) infection or medications, like corticosteroids. This study reports a rare case of Pneumocystis Jiroveci infection in a relatively immunocompetent patient which presented with uncommon radiological findings. Case presentation: A 46-year-old man with a malnourished appearance and a history of opium dependence presented with dry cough, dyspnea, and weight loss to the hospital. There was no evidence of an immunocompromised condition or use of any immunosuppressive medication in the history of the patient. A lung high-resolution computed tomography (HRCT) scan revealed a crazy-paving appearance and localized infiltration. Methenamine silver staining and the histopathological findings in the transbronchial lung biopsy confirmed the diagnosis of PJP. Antibiotics and bronchodilators were administrated and the patient was discharged after 6 days of hospitalization. HIV testing and immunoglobulin levels were normal in the hospital course as well as his follow-up visits. After a 2-month follow-up, the patient was in good condition despite of mild remaining infiltration in his lung. Conclusions: PJP typically affects HIV-infected patients, but due to excessive use of immunosuppressive medications, its prevalence is increasing in non-HIV-infected patients. Malnutrition may predispose the patients to PJP, even in the absence of immunosuppressive conditions. [ABSTRACT FROM AUTHOR]

Invasive pulmonary mucormycosis (IPM) is a deadly opportunistic mold infection in patients with hematological malignancies (HM). Radiologic imaging is essential for its timely diagnosis. Here, we compared IPM lesions visualized by chest computed tomography (CCT) and chest X-ray (CXR) and determined the prognostic significance of discordant imaging. Therefore, we reviewed 44 consecutive HM patients with probable/proven IPM at MD Anderson Cancer Center in 2000–2020 who had concurrent CCT and CXR studies performed. All 44 patients had abnormal CCTs and 39 (89%) had anormal CXR findings at IPM diagnosis. However, only 26 patients (59%) showed CCT-matching IPM-suspicious lesions on CXR. Acute Physiology and Chronic Health Evaluation II score > 18 at IPM diagnosis and breakthrough infection to Mucorales-active antifungals were the only independent risk factors for 42-day and/or 84-day mortality. Absence of neutropenia at IPM diagnosis, neutrophil recovery in neutropenic patients, and surgical revision of mucormycosis lesions were protective factors. Although not reaching significance on multivariable analysis, visualization of CCT-matching lesions on CXR was associated with significantly increased 84-day mortality (log-rank test, p = 0.033), possibly as a surrogate of extensive lesions and tissue necrosis. This observation supports the exploration of radiologic lesion kinetics as a prognostic staging tool in IPM patients. [ABSTRACT FROM AUTHOR]

The Caribbean continues to have high HIV prevalence globally with concurrently high mortality rates due to opportunistic Infections. This study addresses the prevalence of histoplasmosis and cryptococcosis among patients living with advanced HIV disease (AHD) in Trinidad and Tobago, focusing on the implementation of antigen-based diagnostic assays. Conducted as a cross-sectional survey across five HIV treatment sites, 199 participants with advanced HIV disease were enrolled between July 2022 and September 2023. Diagnostic testing was performed using the Clarus Histoplasma Galactomannan Enzyme Immunoassay (EIA), and the Immy CrAg® LFA Cryptococcal Antigen Lateral Flow Assay on urine and blood samples, respectively. Results revealed that 14.6% of participants were found to be co-infected with either histoplasmosis or cryptococcosis, with histoplasmosis being more prevalent (10.5%) than cryptococcosis (4.0%). The study found no significant demographic differences between newly diagnosed and previously diagnosed participants. However, a lower median CD4 count was associated with a higher risk of fungal opportunistic infections. The findings underscore the critical role of systematic use of fungal antigen-based diagnostic assays among patients with AHD to improve the timely diagnosis and treatment of fungal infections among people living with HIV in resource-limited settings and to improve patient outcomes and survival. [ABSTRACT FROM AUTHOR]

Yellow nail syndrome (YNS) is a rare clinical syndrome characterized by nail bed changes, pulmonary involvement, and lymphatic drainage disorders. Pulmonary involvement usually manifests as bronchiectasis, bronchiolitis, and pleural effusion. There are few studies on yellow nail syndrome combined with opportunistic infection. Here, we report a case of clinically diagnosed YNS combined with Nocardia cyriacigeorgica infection and the course of treatment used, which can provide some useful information for clinicians to better understand this rare illness. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Early initiation of anti‐retroviral treatment and prompt management of heart failure in a AIDS patient is crucial. If resources available endomyocardial biopsy can guide the future management. HIV‐associated cardiomyopathy (HIVAC) is a serious complication of HIV with poorly understood pathology. Systolic dysfunction was a common characteristic of HIVAC which is now replaced as diastolic dysfunction due to the availability of ART. There are various etiologies of HIVAC depending on the degree of viral replication, immune response, availability of ART, and also the disparity between high and low‐income countries. We present the case report of a 65‐year‐old male with a past medical history of untreated HIV who came to the hospital with hemodynamic instability and was diagnosed with HIVAC with pulmonary TB, where the cause of HIVAC was poor immune response and opportunistic infection. Therefore, early cardiac monitoring is essential in HIV patients to prevent its advancement. [ABSTRACT FROM AUTHOR]

Background: In kidney transplantation, concerns have been raised regarding increased incidence of viral opportunistic infections in hepatitis C virus (HCV) nucleic acid test (NAT)‐negative (‐) recipients who received HCV NAT‐positive (+) donor kidneys, specifically BK polyomavirus (BKPyV), cytomegalovirus (CMV), and Epstein‐Barr virus (EBV). The purpose of this study was to determine the incidence of these three viral opportunistic infections in HCV NAT‐ recipients who have undergone kidney transplantation with HCV NAT+ donor kidneys at our institution. Methods: This was an Institutional Review Board‐approved, single‐center, retrospective case‐control study of HCV NAT‐ kidney transplant recipients with HCV NAT+ donors from 2018 to 2021. The primary outcome was the cumulative incidence of viral infections of BKPyV, CMV, and/or EBV within 1 year following kidney transplantation. Results: A total of 231 patients were included, 77 in the exposed (donor HCV NAT+) group and 154 in the control (donor HCV NAT‐) group. The adjusted cumulative incidence of viremia within 1 year did not statistically differ between groups (77% exposed group versus 66% for the control group, hazard ratio 1.34, 95% confidence interval 0.95–1.89). In addition, no statistically significant differences were observed for secondary outcomes with the exception of CMV viremia (62% exposed versus 49% control, p = 0.021). However, there were more patients in the exposed group at high risk for CMV viremia based on serostatus (CMV Donor+/Recipient‐, D+/R‐). Conclusion: Among patients who received HCV NAT+ donor kidneys, no clear association was observed between exposure to HCV NAT+ donor kidneys and viral infections of BKPyV, CMV, or EBV. [ABSTRACT FROM AUTHOR]

Background: While a penicillin allergy label has been linked to various negative clinical outcomes, limited studies have specifically characterized the implication of sulfonamide allergy labels (SAL) on clinical outcomes. We examined the impact of SAL on clinical outcomes of solid organ transplant recipients. Methods: In this retrospective matched cohort study, we utilized the TriNetX US collaborative Network, a multicenter de‐identified US database, and identified solid organ transplant recipients with and without SAL. The 1‐year probability of developing Pneumocystis jirovecii pneumonia (PJP), toxoplasmosis, and nocardiosis was estimated and contrasted between the two study groups. The hazard ratio (HR) and the 95% confidence interval (CI) quantified the strength and direction of the association between SAL and these outcomes. Results: When comparing 1571 solid organ transplant recipients with SAL to an equal number of matched controls, patients with SAL had a higher probability of developing nocardiosis (HR 3.85; 95% CI, 1.44–10.30; p =.004; corrected p =.04), and toxoplasmosis (HR, 1.87; 95% CI, 1.10–3.17; p =.019; corrected p =.19), but no difference in the risk of developing PJP (HR, 1.64; 95% CI, 0.68–3.95; p =.27). There was no mortality difference (HR, 1.31; 95% CI, 0.99–1.75; p =.061; corrected p =.6). SAL influenced antibiotic prescription with overutilization of dapsone, atovaquone, and pentamidine and underutilization of trimethoprim and sulfamethoxazole. Conclusion: SAL is associated with an increased risk of opportunistic infections following solid organ transplantation. Measures to evaluate and de‐label sulfonamide allergy prior to transplantation or desensitizing shortly after transplantation are advisable. [ABSTRACT FROM AUTHOR]

The article discusses the impact of sulfonamide allergy labels on the risk of opportunistic infections after solid organ transplantation (SOT). SOT recipients with a sulfonamide allergy label were found to have an increased risk of Toxoplasma and Nocardia infections compared to those without the label. The study highlights the importance of reassessing sulfonamide allergy labels in SOT recipients to optimize prophylactic treatment and reduce the risk of opportunistic infections. Efforts should be made to identify safe delabeling strategies and promote the use of trimethoprim/sulfamethoxazole (TMP‐SMX) in eligible SOT recipients. [Extracted from the article]

Pulmonary infections are an important consideration in the management of patients with rheumatological diseases, especially in those with associated lung disease. Underlying altered immune status and administration of immunomodulatory drugs are thought to be the primary drivers of increased susceptibility to infection. Multiple studies have suggested that rheumatic patients, especially those taking biologic agents such as tumor necrosis factor-alpha (TNF-a) inhibitors, are at an increased risk of infection. Clinicians can attenuate the risk of serious infections by ensuring appropriate vaccination and by screening patients carefully for opportunistic infections prior to initiating therapy with biologic agents. Any signs or symptoms of pulmonary infection should be taken seriously, and both common and uncommon pathogens must be considered in the differential diagnosis. The management of pulmonary infections in rheumatic patients can be challenging, sometimes requiring cessation of immunomodulatory therapy and consultation with infectious diseases specialists andshould be tailored to the individual patient. [ABSTRACT FROM AUTHOR]

Background: Marmosets (Callithrix sp.), including black‐tuffed marmosets (C. penicillata), are neotropical primates that can be highly adapted to urban environments, especially parks and forested areas near cities. Staphylococcus spp. are part of the microbiota of many different hosts and lead to opportunistic severe infection. Isolates from wild animals can be resistant to antimicrobial drugs. However, there are a few studies that evaluated Staphylococcus spp. in neotropical primates. The goal of this study was to evaluate Staphylococcus spp. isolated from free‐ranging black‐tuffed marmosets. Methods: Marmosets were captured in six urban parks. After sedation, skin and rectal swabs and feces were sampled. Staphylococcus spp. isolates were identified by MALDI‐ToF and their antimicrobial susceptibility was determined. Results: Over 30% of captured individuals were positive for Staphylococcus spp., and S. aureus was the most isolated species followed by Mammaliicoccus (Staphylococcus) sciuri. With the exception of the marmoset subjected to necropsy, none of the other had lesions, which supports that notion that Staphylococcus spp. are members of the microbiota, but also opportunistic pathogens. Most isolates were susceptible to all antimicrobials tested; however, one isolate of S. epidermidis was resistant to multiple antimicrobials (penicillin, cefoxitin, ciprofloxacin, clindamycin, and erythromycin). We considered S. aureus as the main staphylococci to colonize black‐tuffed marmosets. Conclusions: Black‐tuffed marmosets can be colonized by several Staphylococcus species, most frequently by S. aureus, and the majority of isolates were sensible to the antimicrobials tested. One S. epidermidis isolate was considered multidrug resistant. [ABSTRACT FROM AUTHOR]

Background: Adverse drug reaction is one of the emerging challenges in antiretroviral treatment. Determining the incidence rate and predictors among children on antiretroviral treatment (ART) is essential to improve treatment outcomes and minimize harm. And also, evidence regarding the time to major adverse drug reactions and its predictors among children on antiretroviral treatment is limited in Ethiopia. Objective: This study aimed to assess the time to major adverse drug reaction and its predictors among children on antiretroviral treatment at selected public hospitals in Northwest Amhara, Ethiopia, 2023. Method: A retrospective cohort study was conducted among 380 children on antiretroviral treatment who enrolled from June 27, 2017, to May 31, 2022. Data was collected using a structured data extraction checklist. Data were entered into Epidata 4.6 and analyzed using STATA 14. The incidence rate of major adverse drug reactions was determined per person/months. The Cox proportional hazards regression model was used to identify predictors of major adverse drug responses. A p-value less than 0.05 with a 95% CI was used to declare statistical significance. Result: The minimum and maximum follow-up time was 6 and 59 months, respectively. The study participants were followed for a total of 9916 person-months. The incidence rate of major adverse drug reactions was 3.5 /1000 person–months. Advanced clinical stages of HIV/AIDS (III and IV) [adjusted hazard ratio = 7.3, 95% CI: 2.74–19.60)], poor treatment adherence [adjusted hazard ratio = 0.33, 95% CI: 0.21–0.42], taking antiretroviral treatment twice and more [adjusted hazard ratio = 3.43, 955 CI: (1.26–9.33)] and not taking opportunistic infection prophylaxis [adjusted hazard ratio = 0.35, 95% CI: 0.23–0.52)] were predictors of major adverse drug reactions. Conclusion: The incidence rate of major adverse drug reactions among children on antiretroviral treatment was congruent with studies in Ethiopia. Advanced clinical stages of HIV/AIDS, poor treatment adherence, taking antiretroviral treatment medications twice or more, and not taking opportunistic infection prophylaxis were predictors of major adverse drug reactions. [ABSTRACT FROM AUTHOR]

Inflammatory myopathies, such as polymyositis and dermatomyositis, are systemic inflammatory disorders that affect skeletal muscles and internal organs. The treatment of inflammatory myopathies usually involves long-term use of high doses of steroids and/or immunosuppressants, making patients susceptible to opportunistic infections. Unfortunately, infections are a leading cause of morbidity and mortality in patients with inflammatory myopathies. Musculoskeletal nontuberculous mycobacterial infections are rare. Nontuberculous mycobacterial infections are easily overlooked owing to their rarity, leading to delayed diagnosis and treatment, indolent clinical course, and difficulty isolating the pathogen. Nontuberculous mycobacterial infections are a growing health concern because of their increasing incidence and the need for prolonged treatment. In patients with connective tissue diseases, immunosuppressant use may lead to an increased risk of nontuberculous mycobacterial infection with a poor prognosis, which highlights the need for early diagnosis and treatment. Herein, we report the case of a 59-year-old man diagnosed with dermatomyositis, who had prolonged use of immunosuppressants and developed a disseminated soft tissue infection in both thighs caused by Mycobacterium abscessus. Multimodal images were obtained using magnetic resonance imaging, ultrasonography, and computed tomography. A strong suspicion of possible combined opportunistic infections and appropriate staining is essential in diagnosing nontuberculous mycobacterial myositis. [ABSTRACT FROM AUTHOR]

In recent decades, the risk of developing opportunistic infections has increased in parallel with the ever-increasing number of people suffering from chronic immunosuppressive diseases or undergoing prosthetic surgery. Staphylococcus warneri is a Gram-positive and coagulase-negative bacterium. Usually found as a component of the healthy human and animal microbiota of the skin and mucosae, it can take on the role of an opportunistic pathogen capable of causing a variety of infections, ranging from mild to life-threatening, not only in immunocompromised patients but even, although rarely, in healthy people. Here, in addition to a concise discussion of the identification and distinguishing features of S. warneri compared to other staphylococcal species, a systematic overview of the findings from case reports and clinical studies is provided. The paper highlights the virulence and antibiotic resistance profiles of S. warneri, the different clinical contexts in which it has proven to be a serious pathogen, emphasizing its ability to colonize artificial prosthetic materials and its tropism for musculoskeletal and cardiovascular tissues. Some original data on orthopedic implant infections by S. warneri complement the discussion. Finally, from a different perspective, the paper addresses the possibilities of industrial exploitation of this bacterium. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is a life-threatening genetic disease characterised by chronic lung infections sustained by opportunistic pathogens such as Pseudomonas aeruginosa. During the chronic long-lasting lung infections, P. aeruginosa adapts to the host environment. Hypermutability, mainly due to defects in the DNA repair system, resulting in an increased spontaneous mutation rate, represents a way to boost the rapid adaptation frequently encountered in CF P. aeruginosa isolates. We selected 609 isolates from 51 patients with CF chronically colonised by P. aeruginosa to study, by full-length genome sequencing, the longitudinal evolution of the bacterium. We recovered at least one hypermutable (mutator) isolate in 57% of patients. By combining genomic information and phenotypic analyses, we followed the evolutionary pathways of the P. aeruginosa mutator strains, identifying their contribution to multi-drug resistance and the emergence of new sub-lineages. By implementing patient clinical data, we observed that mutators preferentially follow a specific evolutionary trajectory in patients with a negative clinical outcome and that maintenance antibiotic polytherapy, based on alternating molecules, apparently reduces the occurrence of hypermutability. Finally, we draw attention to the possibility that modulator-induced changes in the pulmonary environment may be associated with the onset of hypermutability. [ABSTRACT FROM AUTHOR]

Background: Idiopathic CD4 lymphocytopenia (ICL) is an underdiagnosed immunodeficiency syndrome characterised by persistent low CD4 counts in the absence of HIV and other causes of lymphocytopenia. ICL patients are susceptible to opportunistic infections, with human papillomavirus, cryptococcal, and tuberculosis being the most common infections reported. Nocardiosis is rarely reported in patient with ICL. Case Presentation: We herein discuss a 46-year-old female presented with complaints of weight loss, low grade fever and cough with expectoration from last four months. The patient was diagnosed with pulmonary nocardiosis and aspergillosis co-infection four years back; in addition she also had ICL. Subsequently, the patient was lost in follow-up and readmitted four years later. Bronchoalveolar lavage sample shows the presence of acid-fast bacilli in modified gram stain, which later identified as Nocardia otitidiscaviarum by metagenomic next-generation sequencing. Her CD4 counts were still found low (298 cells/mm3). After an initial improvement with trimethoprim-sulfamethoxazole (TMP-SMX), she was commenced on indefinite secondary prophylaxis. Conclusions: Nocardiosis without usual risk factors should be evaluated for ICL. This case emphasize the importance of periodic follow-up with CD4 count monitoring and secondary prophylaxis therapy to prevent recurrence or the emergence of new infections in ICL. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Background: The performance and availability of invasive and non-invasive investigations for the diagnosis of Pneumocystis jirovecii pneumonia (PCP) vary across clinical settings. Estimating the pre-test probability of PCP is essential to the optimal selection and interpretation of diagnostic tests, such as the 1,3-β-D-glucan assay (BDG), for the prioritization of bronchoscopy, and to guide empiric treatment decisions. We aimed to develop a multivariable risk score to estimate the pre-test probability of PCP. Methods: The score was developed from a cohort of 626 individuals who underwent bronchoscopy for the purposes of identifying PCP in a Canadian tertiary-care centre, between 2015 and 2018. We conducted a nested case-control study of 57 cases and 228 unmatched controls. Demographic, clinical, laboratory, and radiological data were included in a multivariable logistic regression model to estimate adjusted odds ratios for PCP diagnosis. A clinical risk score was derived from the multivariable model and discrimination was assessed by estimating the score's receiver operating characteristic curve. Results: Participants had a median age of 60 years (interquartile range [IQR] 49–68) and 115 (40%) were female; 40 (14%) had HIV and 49 (17%) had a solid organ transplant (SOT). The risk score included prior SOT or HIV with CD4 ≤ 200/µL (+ 2), serum lactate dehydrogenase ≥ 265.5 IU/mL (+ 2), radiological pattern typical of PCP on chest x-ray (+ 2) or CT scan (+ 2.5), and PCP prophylaxis with trimethoprim-sulfamethoxazole (-3) or other antimicrobials (-2). The median score was 4 points (IQR, 2-4.5) corresponding to a 28% probability of PCP. The risk prediction model had good discrimination with a c-statistic of 0.79 (0.71–0.84). Given the operating characteristics of the BDG assay, scores ≤ 3 in patients without HIV, and ≤ 5.5 in those with HIV, paired with a negative BDG, would be expected to rule out PCP with 95% certainty. Conclusion: We propose the PCP Score to estimate pre-test probability of PCP. Once validated, it should help clinicians determine which patients to refer for invasive investigations, when to rely on serological testing, and in whom to consider pre-emptive treatment. [ABSTRACT FROM AUTHOR]

Tuberculosis is the most common opportunistic infection in individuals with HIV, and rifampicin is crucial in the treatment of tuberculosis. Drug–drug interactions complicate the use of DTG in HIV/TB co‐infection, which makes drug administration more difficult. This study aimed to develop the population pharmacokinetic model of DTG when co‐administered with rifampicin. The developed model was further used to investigate different dosing regimens. Forty HIV/TB‐co‐infected participants receiving DTG 50 mg once daily (OD) with food or DTG 50 mg twice daily (b.i.d.) without food were included in the analysis. Intensive pharmacokinetic samples were collected. The data were analyzed using a nonlinear mixed‐effects modeling approach. A total of 332 DTG concentrations from 40 PLWH were analyzed. The pharmacokinetics of DTG co‐administered with rifampicin can be best described by a one‐compartment model with first‐order absorption (incorporating lag time) and elimination. Total bilirubin was the only covariate that significantly affected CL/F. DTG 50 mg b.i.d. results in the highest proportion of individuals achieving in vitro IC90 of 0.064 mg/L and in vivo EC90 of 0.3 mg/L, while more than 90% of individuals receiving DTG 100 mg OD would achieve the in vitro IC90 target. Therefore, DTG 100 mg OD could serve as an alternative regimen by minimizing the difficulty of drug administration. However, its clinical efficacy requires additional evaluation. [ABSTRACT FROM AUTHOR]

This article explores the use of nitazoxanide as a potential treatment for Enterocytozoon bieneusi intestinal microsporidiosis in immunocompromised patients. The authors present two cases of heart transplant recipients who were successfully treated with nitazoxanide, highlighting the limited availability and potential toxicities of the current first-line therapy, oral fumagillin. While nitazoxanide improved symptoms, the infection was not completely cleared. The article also provides a summary of existing literature on nitazoxanide treatment for microsporidiosis. Overall, more research is needed to determine effective second-line treatment options for this infection. [Extracted from the article]

Background: Antiretroviral therapy has reduced the incidence and mortality of AIDS‐defining malignancies (ADM); however, non–AIDS‐defining malignancies (NADM) are a major cause of death among people living with HIV (PLWH) today. Though current guidelines suggest that PLWH should receive the same treatment as the general population, there are limited studies focused on how HIV status affects the prognosis of cancers. The present study aimed to investigate the characteristics and prognosis of malignant diseases among PLWH in Japan. Methods: Patients with HIV diagnosed with malignant diseases at our institution between 2011 and 2021 were retrospectively reviewed. Results: There were 205 patients who were diagnosed with malignancies. Of these, 87 (42.4%) were diagnosed with ADM and 118 (57.6%) were diagnosed with NADM. Among 69 patients who received chemotherapy for ADM, 24 (34.8%) developed AIDS‐defining opportunistic infections during treatment. In contrast, only one (1.8%) of the 56 patients administered chemotherapy for NADM developed AIDS‐defining opportunistic infections. Complications of opportunistic infections at diagnosis of malignancies, low CD4+ T‐cell count, positive HIV RNA, and nonadministration of antiretroviral therapy were associated with 5‐year overall survival among patients with malignant lymphomas. However, the variables associated with HIV did not affect NADM prognosis. Conclusions: In this analysis, HIV status had a small impact on the prognosis of malignant diseases in PLWH. Few patients with NADM developed AIDS‐defining opportunistic infections after receiving chemotherapy. This retrospective study reports the characteristics and prognosis of malignancies among people living with HIV in Japan. The impact of HIV status at the time of malignant diseases diagnosis was relatively small among patients with non–AIDS‐defining solid tumors, whereas uncontrolled HIV status was associated with poor outcomes among patients with malignant lymphoma. [ABSTRACT FROM AUTHOR]

Nocardia is widely distributed in the natural environment and typically cause opportunistic infections. However, it is important to note that the pathogenicity of different Nocardia species may vary significantly. Here we reported the first case of brain abscess caused by Nocardia beijingensis (N. beijingensis) infection in China. A 70-year-old male immunocompetent individual came to our hospital for treatment due to headache. After examination, it was found that he had a brain abscess caused by N. beijingensis. By utilizing a combination of surgical intervention and antibiotic therapy, the patient ultimately achieved full recovery. In addition, we isolated this strain and displayed its ultrastructure through scanning electron microscopy. The phylogenetic tree was analyzed by 16 S rRNA sequence. A literature review of N. beijingensis infections in all immunocompetent and immunocompromised patients was presented. It highlighted that abscess formation appears to be a common manifestation of N. beijingensis infection, and N. beijingensis has become an emerging pathogen in immunocompetent individuals. [ABSTRACT FROM AUTHOR]

The Conference on Retroviruses and Opportunistic Infections (CROI) is usually the most significant HIV conference of the year in terms of basic and clinical scientific output. CROI 2024 in Denver, USA, felt very much back to ‘business as usual’ following COVID‐19 disruptions that had impacted preceding years, but also felt more global and outward‐ facing. The British HIV Association supports a working group to attend CROI annually and deliver feedback in the UK. This article summarizes the highlights from that meeting. [ABSTRACT FROM AUTHOR]

Today, the rise of opportunistic infections and their resistance to current antifungal drugs has led to the inevitable need to produce effective antimicrobials at a reasonable cost. This study aimed at producing a calcium carbonate/cobalt oxide nanocomposite with the most excellent antifungal activity against Candida albicans (C. albicans). Thus, nine experimental designs using the Taguchi technique were utilized to discover the greatest combination of parameters for antifungal activity. The colony‐forming unit (CFU) method was used to test the produced nanocomposites' antifungal properties against C. albicans. The results indicated that the synthesized nanocomposite in optimal conditions (20 mg/mL of calcium carbonate, 3 mg/mL of cobalt oxide, and 90 min of stirring time) could inhibit the growth of C. albicans by more than 74%. Various analyses were applied to determine the structural properties of the calcium carbonate/cobalt oxide nanocomposite, and its constituents revealed the fabricated nanocomposite's desirable properties. In the study, the nanocomposite was an efficient antifungal agent that might be employed in various fields, including medicine, dentistry, and life sciences. [ABSTRACT FROM AUTHOR]

Talaromycosis is a fungal infection caused by an opportunistic dimorphic fungus Talaromyces marneffei. During infection, T. marneffei resides inside phagosomes of human host macrophages where the fungus encounters nutrient scarcities and host-derived oxidative stressors. Previously, we showed that the deletion of acuK, a gene encoding Zn(2)Cys(6) transcription factor, caused a decreased ability for T. marneffei to defend against macrophages, as well as a growth impairment in T. marneffei on both low iron-containing medium and gluconeogenic substrate-containing medium. In this study, a paralogous gene acuM was deleted and characterized. The ΔacuM mutant showed similar defects with the ΔacuK mutant, suggesting their common role in gluconeogenesis and iron homeostasis. Unlike the pathogenic mold Aspergillus fumigatus, the ΔacuK and ΔacuM mutants unexpectedly exhibited normal siderophore production and did not show lower expression levels of genes involved in iron uptake and siderophore synthesis. To identify additional target genes of AcuK and AcuM, RNA-sequencing analysis was performed in the ΔacuK and ΔacuM strains growing in a synthetic dextrose medium with 1% glucose at 25 °C for 36 hours. Downregulated genes in both mutants participated in iron-consuming processes, especially in mitochondrial metabolism and anti-oxidative stress. Importantly, the ΔacuM mutant was sensitive to the oxidative stressors menadione and hydrogen peroxide while the ΔacuK mutant was sensitive to only hydrogen peroxide. The yeast form of both mutants demonstrated a more severe defect in antioxidant properties than the mold form. Moreover, ribosomal and ribosomal biogenesis genes were expressed at significantly lower levels in both mutants, suggesting that AcuK and AcuM could affect the protein translation process in T. marneffei. Our study highlighted the role of AcuK and AcuM as global regulators that control multiple cellular adaptations under various harsh environmental conditions during host infection. These transcription factors could be potentially exploited as therapeutic targets for the treatment of this neglected infectious disease. Author summary: Talaromyces marneffei invades host macrophages to establish infection. Major stressors inside the macrophage compartments are nutrient deprivation and oxidative substances. Here, we demonstrated that AcuK and AcuM transcription factors are necessary for T. marneffei to grow under iron and glucose limitation, and to survive oxidative stress and macrophage killing. AcuK and AcuM regulate non-glucose carbon utilization via the transcriptional control of gluconeogenic genes. For iron homeostasis, the two proteins regulate the expression of genes involved in iron-utilization pathways. Lastly, the AcuK and AcuM play a role in oxidative stress response likely by regulating the expression of genes encoding antioxidant enzymes and alternative respiration enzymes. Thus, AcuK and AcuM control multiple cellular adaptations that allow T. marneffei to cope with major stressors occurring during macrophage infection. Since AcuK and AcuM are critical for cellular metabolism and macrophage engulfment, this new information could lead to a better understanding of host-pathogen interaction and could be ultimately developed into fungal-specific diagnostic tools and therapeutic agents. [ABSTRACT FROM AUTHOR]

Molecular chaperons stabilize protein folding and play a vital role in maintaining tissue homeostasis. To this intent, mitochondrial molecular chaperons may be involved in the regulation of oxidative phosphorylation and apoptosis during stress events such as infections. However, specific human infectious diseases relatable to defects in molecular chaperons have yet to be identified. To this end, we performed whole exome sequencing and functional immune assessment in a previously healthy Asian female, who experienced severe respiratory failure due to Pneumocystis jiroveci pneumonia and non-HIV-related CD4 lymphocytopenia. This revealed that a chaperon, the mitochondrial paralog of HSP90, TRAP1, may have been involved in the patient’s susceptibility to an opportunistic infection. Two rare heterozygous variants in TRAP1, E93Q, and A64T were detected. The patient’s peripheral blood mononuclear cells displayed diminished TRAP1 expression, but had increased active, cleaved caspase-3, caspase-7, and elevated IL-1β production. Transfection of A64T and E93Q variants in cell lines yielded decreased TRAP1 compared to transfected wildtype TRAP1 and re-capitulated the immunotypic phenotype of enhanced caspase-3 and caspase-7 activity. When infected with live P. jiroveci, the E93Q or A64T TRAP1 mutant expressing cells also exhibited reduced viability. Patient cells and cell lines transfected with the TRAP1 E93Q/A64T mutants had impaired respiration, glycolysis, and increased ROS production. Of note, co-expression of E93Q/A64T double mutants caused more functional aberration than either mutant singly. Taken together, our study uncovered a previously unrecognized role of TRAP1 in CD4+ lymphocytopenia, conferring susceptibility to opportunistic infections. [ABSTRACT FROM AUTHOR]

Background: Patients who were infected by the Human Immunodeficiency Virus (HIV) could have weakened immunity that is complicated by opportunistic infections, especially for Mycobacterium tuberculosis (MTB). Notably, the HIV-MTB co-infection will accelerate the course of disease progress and greatly increase the mortality of patients. Since the traditional diagnostic methods are time-consuming and have low sensitivity, we aim to investigate the performance of mNGS (metagenomic Next-Generation Sequencing) and mNPS (metagenomic NanoPore Sequencing) for the rapid diagnosis of tuberculosis in HIV-infected patients. Methods: The 122 HIV-infected patients were enrolled for the retrospective analysis. All of the patients underwent traditional microbiological tests, mNGS, and (or) mNPS tests. The clinical comprehensive diagnosis was used as the reference standard to compare the diagnostic performance of culture, mNGS, and mNPS on tuberculosis. We also investigate the diagnostic value of mNGS and mNPS on mixed-infection. Furthermore, the treatment adjustment directed by mNGS and mNPS was analyzed. Results: Compared with the composite reference standard, the culture showed 42.6% clinical sensitivity and 100% specificity, and the OMT(other microbiological testing) had 38.9% sensitivity and 100% specificity. The mNGS had 58.6% clinical sensitivity and 96.8% specificity, and the mNPS had 68.0% clinical sensitivity and 100% specificity. The proportion of mixed-infection cases (88.9%) in the TB group was higher than those in the non-TB group (54.8%) and the mNGS and mNPS are more competitive on mixed-infection diagnosis compared with the traditional methods. Furthermore, there are 63 patients (69.2%) and 36 patients (63.2%) achieved effective treatment after receiving the detection of mNPS and mNGS, respectively. Conclusion: Our study indicated that mNPS and mNGS have high sensitivity and specificity for TB diagnosis compared with the traditional methods, and mNPS seems to have better diagnostic performance than mNGS. Moreover, mNGS and mNPS showed apparent advantages in detecting mixed infection. The mNPS and mNGS-directed medication adjustment have effective treatment outcomes for HIV-infected patients who have lower immunity. [ABSTRACT FROM AUTHOR]

Background Human immunodeficiency virus (HIV) infection in children is a significant public health concern, increasing the risk of infant mortality. Immunodeficiency caused by HIV favors the development of opportunistic infections (OIs), which are responsible for over 90% of HIV-related deaths. This study seeks to determine the primary OIs in children with HIV followed at the Hassan II Regional Hospital Center in Sous Massa, during the period from 2012 to 2023. Materials and Methods This retrospective study is the first in Morocco to investigate OIs among HIV-infected children. It analyzed 76 complete medical records, using a data collection form designed based on existing literature. Results This study revealed that 37% of participants were suffering from OIs, mainly diarrhea (11%), tuberculosis (9%) and pneumonia (7%).There was a significant correlation between OIs and HIV clinical stage (P=0.001), age (P=0.007), and anemia (P=0.001). Despite progress in management, the presence of OIs remains a risk factor for infant morbidity and mortality. Conclusion The study highlights the importance of early detection, prevention, and adherence to treatment in reducing this burden. Management of anemia is essential. [ABSTRACT FROM AUTHOR]

Background: Pneumocystis jirovecii is a fungal pathogen that can present as an opportunistic cause of pneumonia and can occur in Individuals with various causes of immunosuppression, including malignancy and treatments form malignancy that confer increased risk. Although the guidelines for use of Pneumocystis prophylaxis in certain populations are clear, the rapid development of novel cancer therapies elicits the need to accurately assess the degree of immunosuppression conferred by these regimens and to deter- mine if patients receiving these therapies warrant Pneumocystis prophylaxis. Case Series: We present 2 cases of Pneumocystis jirovecii pneumonia in patients with invasive ductal carcinoma of the breast treated with a dose-dense chemotherapy regimen consisting of doxorubicin, cyclophosphamide, and paclitaxel. Conclusion: The use of a dose-dense regimen, in which the interval between doses is shortened compared to a standard regimen, has become a common therapy for patients diagnosed with early breast cancer. Although this approach leads to improved disease-free and overall survival, it has also been associated with an increased risk of developing Pneumocystis jirovecii pneumonia. Further research involving patients receiving dose-dense chemotherapy regimens is needed to determine their risk of developing opportunistic infections and whether that risk warrants changes in clinical management. [ABSTRACT FROM AUTHOR]

Infections remain a major concern following bispecific antibody therapy but are not well described in pivotal trials. We present the first well-documented case of a classic but rare opportunistic infection, disseminated Mycobacterium avium complex, in a patient receiving bispecific antibody therapy. [ABSTRACT FROM AUTHOR]