Search

BACKGROUND: During the early stages of the coronavirus disease 2019 (COVID-19) pandemic, those with severe COVID-19 infection were at risk for a number of opportunistic infections including COVID-19-associated pulmonary aspergillosis (CAPA). We initiated a randomized clinical trial to evaluate whether isavuconazole, a triazole antifungal, could prevent CAPA and improve survival in patients admitted to the ICU with severe COVID-19 infection. METHODS: We designed a phase III/IV randomized, double-blind, two-arm, placebo-controlled trial evaluating standard of care (SOC) plus isavuconazole versus SOC plus placebo and were to enroll participants admitted to the ICU with severe COVID-19 infection at three medical centers in California, United States. The projected sample size was 162 participants. RESULTS: Due to poor enrollment and the declining number of COVID-19 cases over time, the study was terminated after 7 participants were enrolled, all enrolled at one study site (UC San Diego Health). CAPA was suspected in two participants and they were started on open-label isavuconazole. One was withdrawn due to possible isavuconazole-related adverse side effects. CONCLUSION: Enrollment was slower-than-expected due to multiple factors, including competing COVID-19-related studies and hesitancy from potential study participants or their families to join the study. Our experience highlights some of the difficulties in planning and running a clinical trial focused on fungal superinfections involving severely ill patients during the height of the COVID-19 pandemic. Lessons learned from this study will help in the design of proposed studies examining antifungal prophylaxis against aspergillosis following other severe respiratory viral infections.

Liver cirrhosis is a chronic condition that is associated with a variety of complications across organ systems. Patients with cirrhosis also suffer from immune dysfunction, which may predispose them to catastrophic bacterial and fungal infections. Bacterial infections in liver cirrhosis have been well-documented, however, data remains scarce regarding fungal infections. Candida and Aspergillus have been reported as the most common pathogens among patients with cirrhosis, causing both invasive and non-invasive infections. However, other pathogens such as Coccidioides, Pneumocystis, Cryptococcus, and Rhizopus have been increasing in incidence. Diagnosis of fungal infection is often difficult, particularly in regards to distinguishing colonization from invasive infection. Serum markers such as beta-D-glucan (BDG) and galactomannan are beneficial diagnostic tools in conjunction with fungal cultures and imaging modalities. Bronchoscopy with bronchoalveolar lavage (BAL) or lung biopsy can be useful adjuncts as well. Liver transplantation is another important consideration as invasive fungal infection (IFI) is a contraindication to transplant surgery. Additionally, patients are at increased risk for infection due to immunosuppression in the post-transplant period. We aim to discuss the mechanisms responsible for immune dysfunction in advanced liver disease, the epidemiology of fungal infections in this population, as well as presentations and management considerations pertaining to specific pathogens and antifungal regimens.

Hematopoietic stem cell transplant (HSCT) is now recognized as a standard treatment option for people with HIV (PWH) who develop high-risk hematologic malignancies. However, the involved polypharmacy can lead to complications from drug interactions and toxicities, affecting the efficacy and safety of chemotherapy and antiretroviral therapy (ART). Managing these patients requires a personalized approach, including the careful selection of ART based on previous therapies and potential interactions, alongside risk assessment for infections. This discussion will address the history of HSCT in PWH and management considerations for this group. [ABSTRACT FROM AUTHOR]

Nocardia species primarily affect the lungs of immunocompromised individuals. The clinical presentation may mimic pulmonary tuberculosis. Accurate identification and high clinical suspicion are crucial for correct diagnosis and treatment, especially in tuberculosis-endemic regions. A prolonged antibiotic regimen with two or more drugs is needed, and non adherence to the treatment protocol can lead to potentially fatal outcomes. A 37-year-old man with systemic hypertension and chronic kidney disease, who also underwent live-related renal transplantation, presented with fever, cough, and weight loss. No other significant complaints were noted. Physical examination revealed elevated body temperature and bilateral basal crepitations. Baseline investigations showed anaemia, leukopenia and elevated renal parameters. A chest X-ray indicated right lower zone opacity. A provisional diagnosis of pulmonary tuberculosis or mycosis was considered. Video bronchoscopy revealed thick mucoid secretions that were collected for staining, culture, and sensitivity testing. Gram stain and modified Acid-Fast Bacilli (AFB) stain showed microscopic features suggestive of Nocardia species, while the colonies that grew on culture were identified as N. cyriacigeorgica. Treatment was initiated with oral cotrimoxazole and intravenous imipenem. After 14 days, he was discharged with a continuation plan but did not adhere to the regimen. The patient eventually presented again 10 days later with seizures and altered sensorium, leading to a diagnosis of cerebral nocardiosis. Despite treatment, he progressed to septic shock and died. Effective treatment of nocardiosis requires a multidrug regimen, typically consisting of cotrimoxazole, amikacin, or imipenem, tailored to the severity of the infection. Early diagnosis, prompt treatment, and strict adherence to protocols are mandatory for successful treatment, as delays or non compliance can lead to fatal outcomes.

Background & Aims: Mucormycosis, commonly known as "Black Fungus," is an angio-invasive fungus and has become a significant concern during the Coronavirus disease 2019 (COVID-19) pandemic. This study aimed to determine the prevalence rate of mucormycosis and related risk factors among COVID-19 patients, making an essential contribution to further understanding this opportunistic disease. Methods & Materials: This descriptive-analytical cross-sectional study was carried out among 276 patients. Patients were divided into two groups according to the presence of mucormycosis. The diagnosis of mucormycosis was established through a combination of clinical symptoms, imaging findings, and microbiological confirmation. The study examined demographic and clinical characteristics of the patients, including age, gender, duration of hospitalization, and laboratory results, such as C-reactive protein (CRP) and blood sugar levels. The statistical analysis was performed using the SPSS Statistics software package (version 26). Statistical significance was set at a P-value of 0.05. Results: The mean age of patients participating in the study was 59±16 years. Among them, 158 patients (57.2%) were male, and 20 (7.2%) were diagnosed with mucormycosis. The analysis revealed a significant association between mucormycosis presence and various demographic and clinical variables, notably impacting hospitalization duration, blood sugar level, and serum CRP level. Conclusion: Findings from our study indicate that elevated CRP and blood sugar levels, as well as prolonged hospitalization, are significant risk factors for mucormycosis in the patients.

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]

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]

Aim: Clostridium difficile (C. diff.) infection (CDI) is the major contributor of nosocomial infection globally. The current review aims to provide a comprehensive understanding of the mechanisms behind the critical role of intestinal 3Ms (i.e., microbiota, metabolome, and metabolism) in the pathogenesis and prophylaxis of recurrent CDI. Material and methods: Primarily centering around the mechanisms related to gut microbiota-dependent risk factors, we have discussed why gut microbial diversity and abundance are critical determinants of infection risk. Additionally, emphasis has been given on the intestine-specific molecular mechanisms related to the modulation of the global metabolome and signaling processes which trigger disease susceptibility. Key findings: Patients with CDI harbor altered gut microbial phenotype compared to healthy individuals and asymptomatic careers. Clinical and experimental (germ-free mice, mono-strain interactions, longitudinal trails) evidences indicate that alterations of the gut microbiota due to antibiotic exposure, advanced age, immunocompromised conditions and prolonged hospitalization could lead to gastrointestinal colonization of C. diff. Further, the gut microbiota mediated modulation of the mucosal signaling (farnesoid X receptor, aryl hydrocarbon receptor, conserved nuclear receptors, immunological signaling) and the luminal metabolomic signatures play critical role in the disease susceptibility and progression. The use of live biotherapeutics and fecal microbiota transplantation are currently the most suitable prophylactic strategy against recurrent CDI. Significance: The current review highlights the host-microbiota interaction which dictates the intestinal signaling responsible for the pathogenesis of recurrent CDI.

Polymicrobial infections are the leading causes of complications incurred from injuries that burn patients develop. Such patients admitted to the hospital have a high risk of developing hospital-acquired infections, with longer patient stays leading to increased chances of acquiring such drug-resistant infections. Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis are the most common multidrug-resistant (MDR) Gram-negative bacteria identified in burn wound infections (BWIs). BWIs caused by viruses, like herpes simplex and varicella zoster, and fungi-like Candida species appear to occur occasionally. However, the preponderance of infection by opportunistic pathogens is very high in burn patients. Variations in the causative agents of BWIs are due to differences in geographic location and infection control measures. Overall, burn injuries are characterized by elevated serum cytokine levels, systemic immune response, and immunosuppression. Hence, early detection and treatment can accelerate the wound-healing process and reduce the risk of further infections at the site of injury. A multidisciplinary collaboration between burn surgeons and infectious disease specialists is also needed to properly monitor antibiotic resistance in BWI pathogens, help check the super-spread of MDR pathogens, and improve treatment outcomes as a result.

Background: Young farm animals are susceptible to the opportunistic infections which may cause economic losses due to mortality and poor weight gain. Development of antimicrobial resistance and desire to improve therapy efficacy and safety are the reasons to seek for new antibacterial drugs ensuring rapid recovery with minimum adverse events. Aim: To estimate the efficacy of DOKSI AVZ 500 in respiratory pathologies in young pigs. Methods: The study was conducted in 65–70-day old Yorkshire piglets with the signs of bacterial respiratory pathologies. The animals were treated with the test drug for 3 or 5 days. The reference group received TETRAMAX 500 which is similar to the test drug in terms of chemical structure, mechanism of action and spectrum. The animal status was assessed using clinical examination, CBC and bacteriological tests. Results: Both test and reference drugs were well tolerated and ensured the animal recovery within about 4 days. The recovery was accompanied with normalization of hematological parameters and flora composition. The bacteria associated with the disease development, Streptococcus suis, was virtually completely eliminated in all groups. No adverse events were noted. After the treatment, all the animals readily gained the weight and live market quality. Conclusion: DOKSI AVZ 500 was a highly efficient therapy for respiratory pathologies caused by the resident opportunistic flora in piglets. It also has shown noninferiority vs. TETRAMAX 500 in terms of all the health-related parameters and thus can be recommended for introduction in veterinary practice in pig farms. [Open Vet J 2024; 14(5.000): 1098-1102]

Xixia Chen,1 Sang Lin,2 Qiwen Jin,1 Lu Zhang,3 Wei Jiang,3 Xin Lu,3 Guochun Wang,1,3 Yongpeng Ge3 1Peking University China-Japan Friendship School of Clinical Medicine, Beijing, People’s Republic of China; 2Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Rheumatology, Key Myositis Laboratories, China-Japan Friendship Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yongpeng Ge, Department of Rheumatology, China-Japan Friendship Hospital, Yinghua East Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86 13716106183, Email gyp2016@163.comObjective: To investigate the prevalence, risk factors and prognosis of invasive pulmonary aspergillosis (IPA) in patients with anti-melanoma differentiation-associated gene 5 positive dermatomyositis (anti-MDA5+ DM).Methods: A retrospective analysis was conducted in anti-MDA5+ DM patients diagnosed between January 2016 and March 2023. Patients with lower respiratory tract specimens were categorized into IPA+ and IPA- groups based on the presence of IPA and their clinical characteristics and prognoses then compared.Results: Of the 415 patients diagnosed with anti-MDA5+ DM, 28 cases had IPA (prevalence rate of 6.7%) with Aspergillus fumigatus being the most common species. The patients were categorized into IPA+ (n=28) and IPA- (n=98) groups, with no significant age or gender-related differences (P> 0.05). The IPA+ group had a lower lymphocyte count, particularly the CD4+ T-cell count, and reduced serum albumin and higher serum ferritin levels (P all< 0.05). An elevated bronchoalveolar lavage fluid (BALF) galactomannan level was found to be the sole independent risk factor for the occurrence of IPA (adjusted OR=2.191, P=0.029) with a cut-off value of 0.585 and area under the curve of 0.779. The mortality rate in the IPA+ group was 25%. Compared to survivors, non-survivors in this group exhibited a higher incidence of rapidly progressive interstitial lung disease, lower lymphocyte counts, and increased co-infection with Pneumocystis jirovecii (P all< 0.05).Conclusion: IPA was not rare in patients with anti-MDA5+ DM, with elevated BALF galactomannan levels being an independent risk factor for IPA occurrence. Clinicians must exercise vigilance to identify patients exhibiting the aforementioned risk factors.Keywords: invasive pulmonary aspergillosis, opportunistic infection, anti-MDA5+ dermatomyositis, prevalence, risk factors, prognosis

IntroductionAn unusual cluster of myoclonic epilepsy was observed in a Romanian pediatric HIV cohort concurrent with measles outbreaks. We describe this particular form of subacute measles encephalitis (SME) in a group of HIV-infected children and adolescents with severe immunosuppression.MethodsThis is a single-center study, starting in 1997 and covering 4 measles outbreaks in Romania. The presumptive diagnosis of subacute myoclonic measles encephalitis (SMME) was based on: (1) epidemiological data, previous measles episode or presumed contact with measles virus (MV), (2) clinical presentation with initial localized myoclonic jerks with rapid extension and subsequent motor deficit with preserved mental status, and (3) neuroimaging studies revealing cortical gray matter lesions. Definitive diagnosis was based on a neuropathological exam and immunohistochemistry of brain tissues, and measles RNA detection in the cerebrospinal fluid (CSF).ResultsThirty-six patients were diagnosed with a particular form of SME during consecutive measles outbreaks in Romania: 1996-1998 (22); 2005-2008 (12); 2010-2011 (1) and 2016-2018 (1). Most children were born in the late 80s and had parenterally acquired HIV infection in early childhood. Before the episode of SMME, 11 patients had confirmed measles, while the rest, without typical rash, had a respiratory tract infection and/or presumed previous measles contact. In all patients, the clinical onset was sudden, with unilateral myoclonus. MRI findings revealed mainly focal cortical gray matter lesions. Neurologic symptoms progressed rapidly to coma and death in most patients. Three patients survived SMME, they had higher CD4 count at onset, slower progression of neurological symptoms, and benefit of immune recovery with cART. Immunocytochemistry studies revealed MV in the brain with a pattern suggesting an ascending viral neural infection. MV was isolated from CSF in 7 out of 8 patients. Sequence analysis of MV RNA from both nasopharyngeal swabs and CSF was available for one patient with similar N-450 strain characteristics.ConclusionDuring an outbreak of measles, neurological manifestations, especially myoclonus in immunosuppressed patients, can be related to measles even in the absence of an acute episode. This particular form of subacute myoclonic measles encephalitis is an opportunistic fatal disease. Immune recovery due to effective antiretroviral treatment might increase survival.

Solid organ transplant recipients (SOTRs) are at an increased risk of nocardiosis, a rare but life-threatening opportunistic infection. Universal PCP prophylaxis with trimethoprim–sulfamethoxazole (TMP-SMX) is used at our center, which is active in vitro against most species of the Nocardia genus and may have a role in preventing early infections. This is a single-center retrospective cohort study of nocardiosis in adult SOTRs at a large transplant center between January 2012 and June 2022, with comprehensive review of literature. Out of 6179 consecutive cases, 13 (0.2%) were diagnosed with nocardiosis. The patients were predominantly male (76.9%) and kidney transplant recipients (62%). Infection was diagnosed at median of 8.8 months (range, 3.7–98) after transplant. Patients were followed for a median of 457 days (range 8–3367). Overall mortality within one year after diagnosis was 46% (6/13), of which 17% (1/6) of deaths was attributable to Nocardia infection. No recurrence was reported. Nocardia infections were noted in a small proportion of our SOTRs and carried significant morbidity and mortality. TMP-SMX prophylaxis may be protective in some cases given low incidence of cases. [ABSTRACT FROM AUTHOR]

Background: Young farm animals are susceptible to opportunistic infections which may cause economic losses due to mortality and poor weight gain. The development of antimicrobial resistance and the desire to improve therapy efficacy and safety are the reasons to seek for new antibacterial drugs ensuring rapid recovery with minimum adverse events. Aim: To estimate the efficacy of DOKSI AVZ 500 in respiratory pathologies in young pigs. Methods: The study was conducted in 65-70-day-old Yorkshire piglets with signs of bacterial respiratory pathologies. The animals were treated with the test drug for 3 or 5 days. The reference group received TETRAMAX 500 which is similar to the test drug in terms of chemical structure, mechanism of action, and activity spectrum. The animal's status was assessed using clinical examination, clinical blood count, and bacteriological tests. Results: Both test and reference drugs were well tolerated and ensured the animal recovery within about 4 days. The recovery was accompanied by normalization of hematological parameters and flora composition. The bacterium associated with the disease development, Streptococcus suis, was virtually completely eliminated in all groups. No adverse events were noted. After the treatment, all the animals readily gained weight and live market quality. Conclusion: DOKSI AVZ 500 was a highly efficient therapy for respiratory pathologies caused by the resident opportunistic flora in piglets. It has also shown noninferiority vs. TETRAMAX 500 in terms of all the health-related parameters and thus can be recommended for introduction in veterinary practice in pig farms. [ABSTRACT FROM AUTHOR]

Polymicrobial infections are the leading causes of complications incurred from injuries that burn patients develop. Such patients admitted to the hospital have a high risk of developing hospital-acquired infections, with longer patient stays leading to increased chances of acquiring such drug-resistant infections. Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis are the most common multidrug-resistant (MDR) Gram-negative bacteria identified in burn wound infections (BWIs). BWIs caused by viruses, like herpes simplex and varicella zoster, and fungi-like Candida species appear to occur occasionally. However, the preponderance of infection by opportunistic pathogens is very high in burn patients. Variations in the causative agents of BWIs are due to differences in geographic location and infection control measures. Overall, burn injuries are characterized by elevated serum cytokine levels, systemic immune response, and immunosuppression. Hence, early detection and treatment can accelerate the wound-healing process and reduce the risk of further infections at the site of injury. A multidisciplinary collaboration between burn surgeons and infectious disease specialists is also needed to properly monitor antibiotic resistance in BWI pathogens, help check the super-spread of MDR pathogens, and improve treatment outcomes as a result. Key Words: burn wound infections; biofilm; epidermis; hospital; opportunistic infection [ABSTRACT FROM AUTHOR]

Assessing immune responses to cytomegalovirus (CMV) after liver transplant in patients on immunosuppressive therapy remains challenging. In this study, employing ELISPOT assays, 52 liver-transplant recipients were evaluated for antiviral T-cell activity in peripheral blood mononuclear cells (PBMCs), measuring interferon-γ (IFN-γ) secretion upon stimulation with CMV-specific peptides (CMV peptide pool, CMV IE-1, and pp65 antigens). Parameters such as stimulation index, mean spot size, and mean spot count were measured. The study found that heightened immunosuppression, especially with prednisolone in triple therapy, significantly dampened CMV-specific immune responses. This was demonstrated by decreased IFN-γ production by CMV-specific T-cells (CMV peptide pool: p = 0.036; OR = 0.065 [95% CI: 0.005–0.840], pp65 antigen: p = 0.026; OR = 0.048 [95% CI: 0.003–0.699]). Increased immunosuppression correlated with reduced IFN-γ secretion per cell, reflected in smaller mean spot sizes for the CMV peptide pool (p = 0.019). Notably, shorter post-transplant intervals correlated with diminished antiviral T-cell IFN-γ release at two years (CMV peptide pool: p = 0.019; IE antigen: p = 0.010) and five years (CMV peptide pool: p = 0.0001; IE antigen: p = 0.002; pp65 antigen: p = 0.047), as did advancing age (pp65 antigen: p = 0.016, OR = 0.932, 95% CI: 0.881–0.987). Patients with undetectable CMV antigens had a notably higher risk of CMV reactivation within six months from blood collection, closely linked with triple immunosuppression and prednisolone use. These findings highlight the intricate interplay between immunosuppression, immune response dynamics, and CMV reactivation risk, emphasizing the necessity for tailored immunosuppressive strategies to mitigate CMV reactivation in liver-transplant recipients. It can be concluded that, particularly in the early months post-transplantation, the use of prednisolone as a third immunosuppressant should be critically reconsidered. Additionally, the use of prophylactic antiviral therapy effective against CMV in this context holds significant importance. [ABSTRACT FROM AUTHOR]

This study aims to screen for IgG antibodies against Toxoplasma gondii (T. gondii) in the sera of 155 newly diagnosed Human Immunodeficiency Virus (HIV) positive patients under surveillance in Greek Infectious Disease Units. Additionally, risk factors based on patient demographics were examined, and a comparative evaluation of commercially available serological methods was conducted. Three methods were employed to detect IgG antibodies against T. gondii: Enzyme-Linked Immunosorbent Assay (ELISA), Indirect Immunofluorescence Antibody Test (IFAT), and Western Blot (WB), which was used as a reference here. Forty-nine sera samples were true-positive for IgG antibodies against T. gondii, resulting in a 31.61% positivity rate, and the immunoassay test statistical reliability analysis resulted in higher IFAT accuracy (90.97%) compared to ELISA (76.26%). Furthermore, statistical analysis of demographic and immunological data included in the study placed female and foreign/non-Greek individuals at 2.24 (p = 0.0009) and 2.34 (p = 0.0006) times higher risk of positive T. gondii IgG testing compared to their male and Greek counterparts, respectively. Our findings on positivity rates and comparative serology underscore the importance of early and suitable screening measures for newly diagnosed HIV+ patients to mitigate the life-threatening outcomes that may arise from a potential subsequent T. gondii activation. [ABSTRACT FROM AUTHOR]

ObjectiveSARS-CoV-2 transmission has become a serious worldwide public health concern. However, there is currently insufficient data to determine whether SARS-CoV-2 infection would affect opportunistic infections in inflammatory bowel disease (IBD) patients.MethodsA retrospective study included 451 IBD patients (294 UC and 157 CD). The IBD patients were divided into two groups: before SARS-CoV-2 infection and after SARS-CoV-2 infection, and outcomes were measured for these groups. The primary outcome was the presence and distribution of opportunistic infections. The secondary outcomes included factors associated with opportunistic infections, based on which a nomogram prediction model was developed and validated.ResultsAfter SARS-CoV-2 infection, the proportion of IBD patients with opportunistic infections by Clostridium difficile (21.31% vs. 14.01%, p = 0.044) and Epstein–Barr virus (13.93% vs. 4.35%, p = 0.001) was significantly higher compared to that before. Conversely, the proportion of patients with hepatitis B virus (3.69% vs. 10.14%, p = 0.006) and herpes simplex virus type I (1.23% vs. 4.35%, p = 0.04) infections was significantly lower after the infection. Additionally, pre-SARS-CoV-2 infection factors associated with opportunistic infections in IBD include duration of illness, red blood cell count, the presence of comorbid chronic illnesses, and alcohol consumption, while post-SARS-CoV-2 infection, the primary risk factors involve corticosteroid use, red blood cell count, protein level, and high-sensitivity C-reactive protein.ConclusionAfter the SARS-CoV-2 infection, there has been a shift in the occurrence of opportunistic infections among IBD patients. It might be attributed to the use of corticosteroids and also the strengthening of containment measures, heightened public health awareness, and widespread vaccination.

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.

Background & aim: Opportunistic fungal infections following COVID-19 is problematic. Antifungal medications are as well used to treat people who have fungal infections. The aim of the present study was to evaluate the prevalence of fungal infections and the usage of antifungal medications before and after the COVID-19 pandemic. Methods: The present descriptive, analytical, and retrospective study was conducted in 2021.The records of patients who were hospitalized in Abadan hospitals in the year before or the first two years of the COVID-19 pandemic and received at least one of the antifungal medication’s fluconazole, caspofungin, or amphotericin B were extracted and assessed for the present study. Demographic information of patients, type of ward, and type of fungal infection, history of previous infection with covid-19 and severity of disease were extracted from patient files. Descriptive analysis, chi-square, and ANOVA statistics were used to analysis the data. Results: The results indicated that the mucormycosis and aspergillus fungal infections had dramatically increased in the two years since the COVID-19 pandemic initiated. Although it was not statistically significant, the usage of antifungal medications rose in the two years following the beginning of COVID-19 compared to the prior two years. The mucormycosis fungus was the most prevalent fungal infection. The lung was the most commonly infected organ. All patients with fungal infection had a history of severe COVID-19 following the COVID-19 pandemic. The most often used medication was amphotericin B. This difference was substantial (P< 0.001) when aspergillosis patients received capsofungin, mucormycosis patients received amphotericin B, and candida patients received fluconazole. Conclusion: The present indicated that aspergillosis and mucormycosis fungal infections were more common during the COVID-19 pandemic, and as a result, antifungal medication use has increased as well. Additionally, all three medications (fluconazole, caspofungin, and amphotericin B) were administrated according guidelines.

Background: The incidence of HIV/AIDS-related opportunistic infections should have decreased significantly in recent times due to antiretroviral therapy (ART). However, several factors such as patients diagnosed in the late stage of HIV infection, not starting and continuing ART, or ineffective ART will increase the incidence of opportunistic infections in PLWHA (people living with HIV/AIDS). Knowing about opportunistic infections in PLWHA can provide information about the types of opportunistic infections that occur most often and their epidemiology. Objectives: To identify opportunistic infections in PLWHA at RSUD Dr. Pirngadi Medan in 2018-2022. Methods: This study used analytical retrospective quantitative research using the Spearman correlation test by observing secondary data in the form of medical records with total sampling technique. Result: There were 253 PLWHA with opportunistic infections in 2018-2022 with the majority of male gender (82.6%), age group 25-32 years (37.5%), CD4 count

People living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), referred to as PLWHA, have a high rate of mortality and morbidity due to opportunistic central nervous system infections. The infections are attributed to the immune deficiency caused by HIV exposure to the immune system's cluster of differentiation 4 (CD4) cells. This allows the central nervous system, the most vital body system, to acquire an opportunistic infection. The purpose of this study was to determine the existence and magnitude of a risk by examining the correlation between CD4 count and the incidence of central nervous system infection among HIV/AIDS patients. This analytical cross-sectional study utilized a simple random sampling technique on the population of HIV/AIDS patients, which consisted of 80 medical records from January 2020 to December 2022. This study was conducted at Gatot Soebroto Presidential Hospital, also known as Gatot Soebroto Central Army Hospital, in Jakarta, Indonesia. The data analysis was performed using Fisher's exact test (p<0.05) and the prevalence odds ratio (POR). The results showed that 16.3% of the patients suffered a central nervous system infection, which consisted of cerebral toxoplasmosis (76.9%) and brain abscess (23.1%). The bivariate analysis suggested a significant correlation between CD4 count and the incidence of central nervous system infection, with an 11.5-fold increased risk for HIV/AIDS patients who had a CD4 count of <200 cells/mm³ (p=0.000; OR=11.5; 95% CI=2.9-43.8). This study concludes that CD4 count is correlated with the incidence of central nervous system infection, indicating a higher risk for HIV/AIDS patients with a low CD4 count. [ABSTRACT FROM AUTHOR]

Primary immune regulatory disorders (PIRDs) constitute a spectrum of inborn errors of immunity (IEIs) that are primarily characterized by autoimmunity, lymphoproliferation, atopy, and malignancy. In PIRDs, infections are infrequent compared to other IEIs. While susceptibility to infection primarily stems from antibody deficiency, it is sometimes associated with additional innate immune and T or NK cell defects. The use of immunotherapy and chemotherapy further complicates the immune landscape, increasing the risk of diverse infections. Recurrent sinopulmonary infections, particularly bacterial infections such as those associated with staphylococcal and streptococcal organisms, are the most reported infectious manifestations. Predisposition to viral infections, especially Epstein–Barr virus (EBV)-inducing lymphoproliferation and malignancy, is also seen. Notably, mycobacterial and invasive fungal infections are rarely documented in these disorders. Knowledge about the spectrum of infections in these disorders would prevent diagnostic delays and prevent organ damage. This review delves into the infection profile specific to autoimmune lymphoproliferative syndrome (ALPS), Tregopathies, and syndromes with autoimmunity within the broader context of PIRD. Despite the critical importance of understanding the infectious aspects of these disorders, there remains a scarcity of comprehensive reports on this subject. [ABSTRACT FROM AUTHOR]

We present a case of a 43-year-old immunocompromised female patient diagnosed with disseminated histoplasmosis on bone marrow examination, at clinical laboratory of Kasturba Hospital, Manipal, Karnataka, India. The patient, presenting with symptoms like weight loss, appetite loss, and pancytopenia, underwent bone marrow aspiration and biopsy. The bone marrow studies revealed HIV-associated changes and the yeast form of Histoplasma capsulatum, confirming disseminated histoplasmosis. Bone marrow examination is highlighted as a diagnostic tool with significant sensitivity in such cases. The report stresses on the importance of awareness and early diagnosis of histoplasmosis in immunocompromised patients, given its potential lethality and the need for timely therapeutic intervention for better prognosis. [ABSTRACT FROM AUTHOR]

Background: Human immunodeficiency virus (HIV) management guidelines have evolved from initiating therapy at CD4 counts of < 200 cells/m3 to implementing universal test and treat (UTT). This study aimed to assess whether in clinical practice, patients are presenting with higher baseline CD4 counts, describe the incidence of opportunistic infections and the proportion that achieved viral suppression. Methods: A retrospective cohort design with convenience sampling was conducted. Cohort 1 included patients initiated on antiretroviral therapy (ART) between 01 January 2014 and 31 December 2014, when criteria were set at CD4 count ≤ 350 cells/mm³. Cohort 2 included patients initiated on ART between 01 January 2019 and 31 December 2019, during the UTT era. Results: At ART initiation, the median CD4 cell was 170 cells/mm³ (interquartile range [IQR]: 85.5-287) in Cohort 1 cells/mm³ and 243 cells/mm³ (IQR: 120-411) in Cohort 2. Tuberculosis was the predominant OI in the group with CD4 cell count ≤ 200 cells/m³ in both Cohort 1 (26.8%) and Cohort 2 (27.9%), p = 0.039. At 1 year, virological suppression was achieved in only 77.7% and 84.7% of Cohorts 1 and 2 patients. Conclusion: A notable portion of patients at King Edward VIII Hospital's HIV clinic commenced ART with CD4 counts significantly below the recommended guideline thresholds. Contribution: The research revealed a delay in initiating ART. A comprehensive reevaluation is essential to pinpoint the factors contributing to this delay and to devise customised interventions. [ABSTRACT FROM AUTHOR]

Infection with BK polyomavirus (BKPyV) is a common opportunistic infection after kidney transplantation (KT) and may affect graft function. We aimed to determine the incidence, risk factors, and clinical outcomes of BKPyV DNAemia in a prospective cohort of 601 KT recipients transplanted from 2012 to 2020. BKPyV PCR on plasma was performed at days 60, 90, 180, 270, and 360 post-KT. Any BKPyV DNAemia was defined as a single BKPyV DNA of ≥1000 copies/mL. Severe BKPyV DNAemia was defined as two consecutive BKPyV DNA of ≥10,000 copies/mL. Cumulative incidences were investigated using the Aalen–Johansen estimator, and the risk factors were investigated in Cox proportional hazard models. The incidence of any BKPyV DNAemia and severe BKPyV DNAemia was 21% (18–25) and 13% (10–16) at one year post-KT, respectively. Recipient age > 50 years (aHR, 1.72; 95% CI 1.00–2.94; p = 0.049), male sex (aHR, 1.96; 95% CI 1.17–3.29; p = 0.011), living donors (aHR, 1.65; 95% CI 1.03–2.74; p = 0.045), and >3 HLA-ABDR mismatches (aHR, 1.72; 95% CI 1.01–2.94; p = 0.046) increased the risk of severe BKPyV DNAemia. Any BKPyV DNAemia was associated with an increased risk of graft function decline (aHR, 2.26; 95% CI 1.00–5.12; p = 0.049), and severe BKPyV DNAemia was associated with an increased risk of graft loss (aHR, 3.18; 95% CI 1.06–9.58; p = 0.039). These findings highlight the importance of BKPyV monitoring post-KT. [ABSTRACT FROM AUTHOR]

Background: Despite the use of antiviral prophylaxis, cytomegalovirus (CMV) remains a common opportunistic infection following heart transplantation. This study analyzes the rates, risk factors, and outcomes of CMV among heart transplant recipients. Methods: A retrospective cohort study was conducted of adults who underwent heart transplantation between January 1, 2011, and March 31, 2019. The primary outcome was clinically significant CMV infection (csCMVi), defined as CMV disease or asymptomatic infection requiring pre-emptive therapy. The secondary outcome was all-cause mortality. Patients received valganciclovir prophylaxis up to 6 months, depending on CMV donor/recipient serostatus. Kaplan-Meier curve and multivariable Cox regression were used for outcome analysis. Results: Among 553 heart transplant recipients, 101 (18.3%) experienced csCMVi, including 35 (6.3%) with CMV disease. csCMVi was uncommon during prophylaxis. In multivariable analysis, CMV D+/R– status hazard ratio (HR 12.88, 95% CI 6.76-24.56; p

Late onset combined immunodeficiency (LOCID) is a rare variant of common variable immunodeficiency (CVID), typically affecting adult patients who present with opportunistic infections (OI) and/or low CD4+ T lymphocytes. Diagnostic delay is common due to the rareness of this entity, increasing morbidity and mortality. We report on a 66-year-old male who developed a severe gastrointestinal cytomegalovirus (CMV) infection, refractory to antiviral treatment and anti-cytomegalovirus specific human immunoglobulin administration, with a fatal outcome due to an undiagnosed LOCID.

Abstract Background Aspergillus spp. are among the fungal pathogens that can cause life-threatening infections in patients with a history of COVID-19. Case presentation We present the case of a 58-year-old Iranian woman with post-COVID-19 Aspergillus fumigatus endocarditis complicated by numerous thromboembolisms. She underwent mitral valve replacement surgery and multiple lower extremity embolectomies and was treated with voriconazole, which led to her final recovery. Conclusions Aspergillus endocarditis should be considered in any patient with suspected endocarditis who has a history of COVID-19 infection and does not respond to routine antibiotic and antifungal therapy, as COVID-19 interferes with proper immune function, and lack of underlying cardiac conditions and immunodeficiencies does not preclude the diagnosis. Culture and histopathological evaluation of vegetations and emboli, as well as PCR, can confirm the diagnosis. Early initiation of antifungal therapy and surgical removal of infected valves and emboli can improve prognosis in patients with Aspergillus endocarditis.

The non-neoformans Cryptococci are increasingly causing opportunistic infections in both immunocompetent and immunocompromised individuals worldwide. Non. neoformans Cryptococci are skin and mucous membrane colonizers as well as environmental fungi. Cryptococcus laurentii and Cryptococcus albidus cause more than 80% of non-neoformans Cryptococcal infections are gaining recognition as human pathogens because of the advancements in diagnostic techniques. Here, we report 2 cases of C. laurentii fungaemia in an immunocompetent adult and a preterm neonate in Nigeria. The first case was a 51-year-old man with 31% second-degree mixed-thickness burns. He fully recovered with the addition of fluconazole early in its treatment. The second case was a preterm neonate in whom fungaemia was diagnosed after a fatal outcome had occurred. These two cases highlight that the new identification and susceptibility diagnostic techniques allow for earlier diagnosis and better treatment of unusual fungal infections. However, the timely and early commencement of empirical antifungal drugs improves patient outcomes.

Visceral leishmaniasis (VL) is an opportunistic infectious disease in people living with HIV. We report VL's diagnosis and treatment process in a patient admitted to the hospital due to high fever during the first week of antiretroviral therapy. Leishmania indirect fluorescent antibody test titers were positive, and amastigotes were observed in the biopsy specimen. The patient's condition improved following liposomal amphotericin B (LA-B) treatment. VL is endemic in Türkiye, and there is also an increase in HIV-positive cases. VL should be included in the differential diagnosis in HIV-positive cases alongside other opportunistic infections. [ABSTRACT FROM AUTHOR]

Shewanella putrefaciens is an opportunistic pathogen rarely responsible for human infection. However, it has been reported that it causes skin and soft tissue infections and bacteremia in immune-compromised patients, such as cellulitis, abscesses, bacteremia, and wound infection. It is an oxidase and catalase-positive non-fermenter gram-negative rod that produces hydrogen sulfide. We report the case of a 90-year-old woman, who presented an invasive infectious burn wound associated with Shewanella putrefaciens bacteremia. She was admitted into the burn center of the military hospital M.S Nekkache of Algiers, suffering from 40% TBSA with a history of diabetes. After one week of admission, the patient complained of a high fever. Microbiological culture of the catheter tip was positive and showed pale colonies on the MacConkey agar, non-lactose fermenting plate. Nutritive agar medium culture showed red pale tan colonies with a concentration >10° CFU. Identification and antibiotic susceptibility were obtained by the Phoenix system (Becton-Dickinson, USA) as Shewanella putrefaciens. This was confirmed by standards and semi-automated microbiological techniques. Gram stain showed Gram-negative bacilli with positive oxidase and catalase reactions. Production of hydrogen sulfide was confirmed by the semi-automated API 20NE method (biomerieux, France). The isolate was resistant to gentamicin, amikacin, ceftazidime, aztreonam, amoxicillin-clavulanic acid, cefepime, trimethoprim/sulfamethoxazole, and nitrofurantoin. In our case, S. putrefaciens was found in a mixed culture with Klebsiella pneumoniae. No earlier exposure of the patient to marine water had been noticed. Blood culture indicated colonies growth of Acinetobacter baumannii. No further isolation of this bacteria was noticed after treatment. The patient was given imipenem, vancomycin and colistin. Despite our best efforts, the patient could not be saved because of sepsis and renal function failure. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cell transplant (HSCT) is now recognized as a standard treatment option for people with HIV (PWH) who develop high-risk hematologic malignancies. However, the involved polypharmacy can lead to complications from drug interactions and toxicities, affecting the efficacy and safety of chemotherapy and antiretroviral therapy (ART). Managing these patients requires a personalized approach, including the careful selection of ART based on previous therapies and potential interactions, alongside risk assessment for infections. This discussion will address the history of HSCT in PWH and management considerations for this group.

Retno Dewi Prisusanti, Untung Slamet Suhariyono, Chanif Mahdi Medical Record and Health Information Department, ITSK RS DR Soepraoen Malang, Kota Malang, Jawa Timur, IndonesiaCorrespondence: Retno Dewi Prisusanti, ITSK RS DR Soepraoen Malang, Kota Malang, Jawa Timur, Indonesia, Email retnodewi@itsk-soepraoen.ac.id

We present a case of a 43-year-old immunocompromised female patient diagnosed with disseminated histoplasmosis on bone marrow examination, at clinical laboratory of Kasturba Hospital, Manipal, Karnataka, India. The patient, presenting with symptoms like weight loss, appetite loss, and pancytopenia, underwent bone marrow aspiration and biopsy. The bone marrow studies revealed HIV-associated changes and the yeast form of Histoplasma capsulatum, confirming disseminated histoplasmosis. Bone marrow examination is highlighted as a diagnostic tool with significant sensitivity in such cases. The report stresses on the importance of awareness and early diagnosis of histoplasmosis in immunocompromised patients, given its potential lethality and the need for timely therapeutic intervention for better prognosis.

Immunotherapies can lead to an immune compromised state that can allow for opportunistic pathogens such as Rhodococcus to flourish. The vast majority of Rhodococcus infections occur in immunocompromised hosts. Here we describe disseminated Rhodococcus equi infection in a patient with diffuse large B-cell lymphoma treated with immunotherapy. Infection with Rhodococcus can be diagnosed with the aid of cytomorphology and histochemical findings and the organism confirmed by sequencing. In conclusion, Rhodococcus should be considered in the differential of granulomatous inflammation in immunocompromised individuals treated with immunotherapies.

Background: Human immunodeficiency virus (HIV) management guidelines have evolved from initiating therapy at CD4 counts of ≤ 200 cells/m3 to implementing universal test and treat (UTT). This study aimed to assess whether in clinical practice, patients are presenting with higher baseline CD4 counts, describe the incidence of opportunistic infections and the proportion that achieved viral suppression. Methods: A retrospective cohort design with convenience sampling was conducted. Cohort 1 included patients initiated on antiretroviral therapy (ART) between 01 January 2014 and 31 December 2014, when criteria were set at CD4 count ≤ 350 cells/mm3. Cohort 2 included patients initiated on ART between 01 January 2019 and 31 December 2019, during the UTT era. Results: At ART initiation, the median CD4 cell was 170 cells/mm3 (interquartile range [IQR]: 85.5–287) in Cohort 1 cells/mm3 and 243 cells/mm3 (IQR: 120–411) in Cohort 2. Tuberculosis was the predominant OI in the group with CD4 cell count ≤ 200 cells/m3 in both Cohort 1 (26.8%) and Cohort 2 (27.9%), p = 0.039. At 1 year, virological suppression was achieved in only 77.7% and 84.7% of Cohorts 1 and 2 patients. Conclusion: A notable portion of patients at King Edward VIII Hospital’s HIV clinic commenced ART with CD4 counts significantly below the recommended guideline thresholds. Contribution: The research revealed a delay in initiating ART. A comprehensive reevaluation is essential to pinpoint the factors contributing to this delay and to devise customised interventions.

Background: Aspergillus spp. are among the fungal pathogens that can cause life-threatening infections in patients with a history of COVID-19. Case presentation: We present the case of a 58-year-old Iranian woman with post-COVID-19 Aspergillus fumigatus endocarditis complicated by numerous thromboembolisms. She underwent mitral valve replacement surgery and multiple lower extremity embolectomies and was treated with voriconazole, which led to her final recovery. Conclusions: Aspergillus endocarditis should be considered in any patient with suspected endocarditis who has a history of COVID-19 infection and does not respond to routine antibiotic and antifungal therapy, as COVID-19 interferes with proper immune function, and lack of underlying cardiac conditions and immunodeficiencies does not preclude the diagnosis. Culture and histopathological evaluation of vegetations and emboli, as well as PCR, can confirm the diagnosis. Early initiation of antifungal therapy and surgical removal of infected valves and emboli can improve prognosis in patients with Aspergillus endocarditis. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a quintessential systemic autoimmune disease with multiorgan involvement. Although its pathology has been elucidated and therapeutic advances are being made, infections remain the leading cause of death in SLE. In addition to immune abnormalities caused by SLE itself, the use of nonspecific glucocorticoids and immunosuppressants during treatment induces a state of immune suppression, increasing the risk of infection. Bacterial infections are the most common, but impaired cell-mediated immunity may also lead to the development of opportunistic infections, as well as viral and fungal infections. When treating SLE, caution is required for the development of infectious complications, such as latent tuberculosis, de novo hepatitis B, Pneumocystis jiroveci pneumonia (PJP), herpes zoster, and cytomegalovirus infection. Vaccination is recommended for vaccine-preventable diseases for appropriate management of infections. For other infectious diseases, such as tuberculosis, PJP, and disseminated herpes zoster, adequate treatment is necessary. [ABSTRACT FROM AUTHOR]

Medicinal and recreational uses of Cannabis sativa, commonly known as cannabis or hemp, has increased following its legalization in certain regions of the world. Cannabis and hemp plants interact with a community of microbes (i.e., the phytobiome), which can influence various aspects of the host plant. The fungal composition of the C. sativa phytobiome (i.e., mycobiome) currently consists of over 100 species of fungi, which includes phytopathogens, epiphytes, and endophytes, This mycobiome has often been understudied in research aimed at evaluating the safety of cannabis products for humans. Medical research has historically focused instead on substance use and medicinal uses of the plant. Because several components of the mycobiome are reported to produce toxic secondary metabolites (i.e., mycotoxins) that can potentially affect the health of humans and animals and initiate opportunistic infections in immunocompromised patients, there is a need to determine the potential health risks that these contaminants could pose for consumers. This review discusses the mycobiome of cannabis and hemp flowers with a focus on plant-infecting and toxigenic fungi that are most commonly found and are of potential concern (e.g., Aspergillus, Penicillium, Fusarium, and Mucor spp.). We review current regulations for molds and mycotoxins worldwide and review assessment methods including culture-based assays, liquid chromatography, immuno-based technologies, and emerging technologies for these contaminants. We also discuss approaches to reduce fungal contaminants on cannabis and hemp and identify future research needs for contaminant detection, data dissemination, and management approaches. These approaches are designed to yield safer products for all consumers. [ABSTRACT FROM AUTHOR]

The non-neoformans Cryptococci are increasingly causing opportunistic infections in both immunocompetent and immunocompromised individuals worldwide. Non. neoformans Cryptococci are skin and mucous membrane colonizers as well as environmental fungi. Cryptococcus laurentii and Cryptococcus albidus cause more than 80% of non-neoformans Cryptococcal infections are gaining recognition as human pathogens because of the advancements in diagnostic techniques. Here, we report 2 cases of C. laurentii fungaemia in an immunocompetent adult and a preterm neonate in Nigeria. The first case was a 51-year-old man with 31% second-degree mixed-thickness burns. He fully recovered with the addition of fluconazole early in its treatment. The second case was a preterm neonate in whom fungaemia was diagnosed after a fatal outcome had occurred. These two cases highlight that the new identification and susceptibility diagnostic techniques allow for earlier diagnosis and better treatment of unusual fungal infections. However, the timely and early commencement of empirical antifungal drugs improves patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Toxoplasma gondii is an opportunistic protozoan parasite that causes a life-threatening disease -- toxoplasmosis -- in immunocompromised individuals, including patients with cancer. This prospective cross-sectional study set out to determine the prevalence of toxoplasmosis in patients with cancer compared with that of healthy individuals. Methods: A prospective cross-sectional study was conducted in Sulaimani City of Iraq from November 2019 to May 2020. Anti-T. gondii IgG and IgM antibodies were measured in the blood samples of 113 patients with cancer (80 with solid organ tumors and 33 with haematological malignancies) entered to Hiwa Cancer Hospital and 82 healthy controls, who were referred to the Directorate of Blood Transfusion for blood donation, using chemiluminescence microparticle immunoassay (CMIA). Results: The prevalence of anti-T. gondii IgG was 39.8% in the patient group and 24.4% in the control group, which amounted to a significant difference (P = 0.024). Only one case of anti-T. gondii IgM positivity was observed in the patient group, and no IgM seropositivity was reported in the control group. Moreover, the seroprevalence of anti-T. gondii IgG was non-significantly higher (P = 0.102) in the patients with haematological malignancies (51.5%) than in those with solid organ tumors (35%). Occupation was the only risk factor which had a significant association with T gondii infection (odds ratio [OR]: 1.3, 95% confidence interval [CI]: 0.6746163 - 2.4282788, P = 0.029). Conclusion: The prevalence of T. gondii infection is higher in patients with cancer than in healthy individuals. Therefore, T. gondii screening in patients with cancer is recommended. [ABSTRACT FROM AUTHOR]

The objective of this article is to review the current status of the bacteria-virus interplay in Kaposi's sarcoma-associated herpesvirus (KSHV) infection and KSHV-driven cancers. KSHV is the etiological agent of several cancers, including Kaposi's sarcoma (KS) and primary effusion lymphoma. Due to immunosuppression, patients with KSHV are at an increased risk for bacterial infections. Moreover, among patients coinfected by HIV and KSHV, patients with KS have distinct oral microbiota compared to non-KS patients. Bacterial biomarkers associated with KSHV-driven cancers can provide insights in discerning the mechanisms of KSHV-induced oncogenesis. For example, pathogen-associated molecular patterns and bacterial products of certain bacterial species can regulate the expression of KSHV lytic and latent genes, thereby affecting viral replication and dissemination. In addition, infection with distinct opportunistic bacterial species have been associated with increased cell proliferation and tumorigenesis in KSHV-induced cancers through activation of pro-survival and -mitogenic cell signaling pathways. By elucidating the various mechanisms in which bacteria affect KSHV-associated pathogenesis, we will be able to pinpoint therapeutic targets for KSHV infection and KSHV-related cancers.

Abstract Background Opportunistic infections associated with immunosuppressive treatments for inflammatory bowel disease pose an important safety concern. Here we report the case of a patient with active ulcerative colitis and cryptococcal pneumonia who was treated with vedolizumab combined with fluconazole. Case presentation A 56-year-old Japanese man with ulcerative colitis and a history of Sweet’s syndrome who was taking prednisolone and azathioprine presented with a moderate exacerbation of ulcerative colitis, abdominal pain, diarrhea, and bloody stools along with cytomegalovirus infection. Increasing the prednisolone dose without using antiviral drugs improved cytomegalovirus infection; however, ulcerative colitis did not improve, and cryptococcal pneumonia occurred. Thus, treatment with fluconazole followed by vedolizumab was initiated for ulcerative colitis. The patient gradually recovered and achieved clinical remission without the exacerbation of pneumonia. Conclusions We reported the first case of a patient with ulcerative colitis who was treated with vedolizumab and concomitant fluconazole for active cryptococcal pneumonia. Vedolizumab constitutes a high-potential treatment regimen owing to its safety in inflammatory bowel disease associated with opportunistic infections.

Solid organ transplant recipients (SOTRs) are at an increased risk of nocardiosis, a rare but life-threatening opportunistic infection. Universal PCP prophylaxis with trimethoprim–sulfamethoxazole (TMP-SMX) is used at our center, which is active in vitro against most species of the Nocardia genus and may have a role in preventing early infections. This is a single-center retrospective cohort study of nocardiosis in adult SOTRs at a large transplant center between January 2012 and June 2022, with comprehensive review of literature. Out of 6179 consecutive cases, 13 (0.2%) were diagnosed with nocardiosis. The patients were predominantly male (76.9%) and kidney transplant recipients (62%). Infection was diagnosed at median of 8.8 months (range, 3.7–98) after transplant. Patients were followed for a median of 457 days (range 8–3367). Overall mortality within one year after diagnosis was 46% (6/13), of which 17% (1/6) of deaths was attributable to Nocardia infection. No recurrence was reported. Nocardia infections were noted in a small proportion of our SOTRs and carried significant morbidity and mortality. TMP-SMX prophylaxis may be protective in some cases given low incidence of cases.

This study aims to screen for IgG antibodies against Toxoplasma gondii (T. gondii) in the sera of 155 newly diagnosed Human Immunodeficiency Virus (HIV) positive patients under surveillance in Greek Infectious Disease Units. Additionally, risk factors based on patient demographics were examined, and a comparative evaluation of commercially available serological methods was conducted. Three methods were employed to detect IgG antibodies against T. gondii: Enzyme-Linked Immunosorbent Assay (ELISA), Indirect Immunofluorescence Antibody Test (IFAT), and Western Blot (WB), which was used as a reference here. Forty-nine sera samples were true-positive for IgG antibodies against T. gondii, resulting in a 31.61% positivity rate, and the immunoassay test statistical reliability analysis resulted in higher IFAT accuracy (90.97%) compared to ELISA (76.26%). Furthermore, statistical analysis of demographic and immunological data included in the study placed female and foreign/non-Greek individuals at 2.24 (p = 0.0009) and 2.34 (p = 0.0006) times higher risk of positive T. gondii IgG testing compared to their male and Greek counterparts, respectively. Our findings on positivity rates and comparative serology underscore the importance of early and suitable screening measures for newly diagnosed HIV+ patients to mitigate the life-threatening outcomes that may arise from a potential subsequent T. gondii activation.

Assessing immune responses to cytomegalovirus (CMV) after liver transplant in patients on immunosuppressive therapy remains challenging. In this study, employing ELISPOT assays, 52 liver-transplant recipients were evaluated for antiviral T-cell activity in peripheral blood mononuclear cells (PBMCs), measuring interferon-γ (IFN-γ) secretion upon stimulation with CMV-specific peptides (CMV peptide pool, CMV IE-1, and pp65 antigens). Parameters such as stimulation index, mean spot size, and mean spot count were measured. The study found that heightened immunosuppression, especially with prednisolone in triple therapy, significantly dampened CMV-specific immune responses. This was demonstrated by decreased IFN-γ production by CMV-specific T-cells (CMV peptide pool: p = 0.036; OR = 0.065 [95% CI: 0.005–0.840], pp65 antigen: p = 0.026; OR = 0.048 [95% CI: 0.003–0.699]). Increased immunosuppression correlated with reduced IFN-γ secretion per cell, reflected in smaller mean spot sizes for the CMV peptide pool (p = 0.019). Notably, shorter post-transplant intervals correlated with diminished antiviral T-cell IFN-γ release at two years (CMV peptide pool: p = 0.019; IE antigen: p = 0.010) and five years (CMV peptide pool: p = 0.0001; IE antigen: p = 0.002; pp65 antigen: p = 0.047), as did advancing age (pp65 antigen: p = 0.016, OR = 0.932, 95% CI: 0.881–0.987). Patients with undetectable CMV antigens had a notably higher risk of CMV reactivation within six months from blood collection, closely linked with triple immunosuppression and prednisolone use. These findings highlight the intricate interplay between immunosuppression, immune response dynamics, and CMV reactivation risk, emphasizing the necessity for tailored immunosuppressive strategies to mitigate CMV reactivation in liver-transplant recipients. It can be concluded that, particularly in the early months post-transplantation, the use of prednisolone as a third immunosuppressant should be critically reconsidered. Additionally, the use of prophylactic antiviral therapy effective against CMV in this context holds significant importance.

Tuberculosis (TB) is an opportunistic infection caused by Mycobacterium TB, and it has plagued mankind since ages, posing a major health concern in developing countries. Pulmonary TB is the most common form, but extrapulmonary TB is also not uncommon, with an incidence of 8-14%. Cutaneous manifestations of TB, known as lupus vulgaris, are extremely rare, constituting less than 1% of cases worldwide. Diagnosing a cutaneous lesion of TB poses a challenge for clinicians, as it requires both absolute and relative criteria. In the present case report, the author presents the case of a 15-year-old male from a low socio-economic background who presented with painless oedema over the penis for one and a half months. The patient had a history of dry cough and tested positive for Coronavirus Disease-2019 (COVID-19). Systemic examination was normal, and vital signs were stable. Local examination revealed oedema, redness, and phimosis over the penile shaft, along with non tender ulcerative lesions and deep cracks in the groin crease. A skin biopsy revealed lymphocytic infiltration with Langhanstype giant cells and epithelioid cell granulomas, suggesting TB of the skin overlying the penis. Laboratory investigations revealed a positive Mantoux test and an elevated Erythrocyte Sedimentation Rate (ESR) of 42. The patient was initiated on antitubercular therapy, comprising isoniazid, rifampicin, pyrazinamide, and ethambutol (HRZE). After one month of treatment, the oedema subsided, and the penile ulcers and groin skin cracks healed. Penile skin involvement in TB is rare, and the clinical appearance of such involvement may vary.

We report a patient with anorexia nervosa without bronchiectasis and cystic fibrosis who developed acute pneumonia caused by Exophiala dermatitidis (E. dermatitidis). The black fungus found in multiple sputum cultures was determined to be E. dermatitidis using mass spectrometry and identified using genetic analysis. Although the initiation of antifungal therapy was late, the pneumonia gradually improved with long-term treatment. This case highlights the need for early diagnosis and effective long-term treatment of the fungal etiologic agent.

Introduction: Toxoplasma gondii is an opportunistic protozoan parasite that causes a life-threatening disease – toxoplasmosis – in immunocompromised individuals, including patients with cancer. This prospective cross-sectional study set out to determine the prevalence of toxoplasmosis in patients with cancer compared with that of healthy individuals. Materials & Methods: Anti-T.gondii IgG and IgM antibodies were measured in the blood samples of 113 patients with cancer (80 with solid organ tumours and 33 with haematological malignancies) and 82 healthy controls, using chemiluminescence microparticle immunoassay (CMIA). Results: The prevalence of anti-T.gondii IgG was 39.8% in the patient group and 24.4% in the control group, which amounted to a significant difference (p = 0.024). Only one case of anti-T.gondii IgM positivity was observed in the patient group, and no IgM seropositivity was reported in the control group. Moreover, the seroprevalence of anti-T.gondii IgG was non-significantly higher (p = 0.102) in the patients with haematological malignancies (51.5%) than in those with solid organ tumours (35%). Conclusion: These results demonstrate that the prevalence of T. gondii infection is higher in patients with cancer than in healthy individuals. Therefore, T. gondii screening in patients with cancer is recommended.