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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 One was withdrawn due to possible isavuconazole-related adverse side effects.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.

Ulcerative colitis (UC) is a chronic non-specific colitis disease. In recent years, fecal microbiota transplantation (FMT), including improved washed microbiota transplantation (WMT), and biological agents have helped improve the prognosis of patients with UC. However, a significant number of patients with moderate to severe UC do not get relief from glucocorticoids, immunosuppressants, and TNF-α antagonists. Patients with severe UC are frequently burdened with opportunistic infections and subsequent surgical interventions. Combined treatment modalities are crucial for patients with severe UC and opportunistic infections. Herein, we reported a case of a 25-year-old female with refractory severe UC complicated with recurrent Clostridioides difficile infection and recurrent cytomegalovirus infection for six years. Surgical removal of the affected bowel segment was almost unavoidable. She showed endoscopic and histological recovery after comprehensive WMT and Vedolizumab treatment. The following are our learnings from the case: 1. A combination of WMT and biological agents can potentially obviate the necessity for surgical treatment in patients with refractory severe UC and promote histological remission. 2. Personalized comprehensive treatment and chronic disease management models for patients with UC should be emphasized. 3. WMT can help treat opportunistic infections, which may also strengthen the treatment with gut-targeted biological agents when traditional TNF-α antagonists show poor efficacy. [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. [ABSTRACT FROM AUTHOR]

Botryomycosis is a rare granulomatous response to chronic bacterial infection most frequently associated with Staphylococcus aureus. This disease, which predominantly affects immunocompromised patients, may present with cutaneous, visceral, or soft tissue manifestations. Soft tissue involvement typically has an aggressive mass-like appearance on imaging which can be concerning for malignancy. In immunocompromised patients, botryomycosis can resemble fungal infection both clinically and histologically; therefore, definitive diagnosis requires tissue sampling along with histological and microbiological analysis. Presented here is a 25-year-old man with an enlarging intramuscular soft tissue mass of the right forearm as his first presentation of undiagnosed acquired immunodeficiency syndrome (AIDS). MR imaging showed a mildly T2 hyperintense and enhancing mass with infiltrative margins extending through tissue planes. Biopsy of the mass revealed Staphylococcus aureus–associated botryomycosis, which improved with nonsurgical treatment employing antibiotics. Unfortunately, the patient subsequently expired from other manifestations of his new AIDS diagnosis. This case describes the MR and PET-CT appearance of botryomycosis and also underscores that infection can mimic sarcoma, particularly in the setting of immunodeficiency. [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]

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]

RHOH, an atypical small GTPase predominantly expressed in hematopoietic cells, plays a vital role in immune function. A deficiency in RHOH has been linked to epidermodysplasia verruciformis, lung disease, Burkitt lymphoma and T cell defects. Here, we report a novel germline homozygous RHOH c.245G > A (p.Cys82Tyr) variant in a 21-year-old male suffering from recurrent, invasive, opportunistic infections affecting the lungs, eyes, and brain. His sister also succumbed to a lung infection during early adulthood. The patient exhibited a persistent decrease in CD4+ T, B, and NK cell counts, and hypoimmunoglobulinemia. The patient’s T cell showed impaired activation upon in vitro TCR stimulation. In Jurkat T cells transduced with RHOHC82Y, a similar reduction in activation marker CD69 up-regulation was observed. Furthermore, the C82Y variant showed reduced RHOH protein expression and impaired interaction with the TCR signaling molecule ZAP70. Together, these data suggest that the newly identified autosomal-recessive RHOH variant is associated with T cell dysfunction and recurrent opportunistic infections, functioning as a hypomorph by disrupting ZAP70-mediated TCR signaling. [ABSTRACT FROM AUTHOR]

Talaromyces marneffei is a thermally dimorphic fungus which causes opportunistic infections in immunocompromised individuals. The diagnosis of T. marneffei infection rests on the microscopic demonstration of the fungus in the tissues and/or isolation of the fungus from clinical specimens. In this report, we discuss a case involving a 23-year-old man who presented with a history of intermittent fever, cough and constitutional symptoms. Clinically, the patient exhibited pallor, jaundice, generalized seborrhoeic dermatitis, hepatomegaly, and small palpable cervical lymph nodes. A computed tomography (CT) scan of the abdomen showed homogenous hypodense lesions in both liver lobes. HIV screening result was reactive. Microscopic examination of the bone marrow aspirate smear and trephine biopsy identified fungal bodies, and culture of the marrow aspirate confirmed the presence of T. marneffei. Notably, the liver biopsy revealed Burkitt lymphoma alongside fungal bodies. He was treated with intravenous Amphotericin B but ultimately succumbed to the illness due to severe metabolic acidosis and multiorgan failure. This case underscores the importance of presumptive diagnosis through morphological or histological examination of bone marrow samples, as microbiologic culture methods can be time-consuming. Timely diagnosis and aggressive treatment are critical in managing patients with T. marneffei infection. [ABSTRACT FROM AUTHOR]

Abtract: Digestive symptoms in HIV patients are frequent and little-known. Their management varies from symptomatic treatment to specialised care by the gastroenterologist. Our aim is to determine these manifestations in HIV patients through a retrospective study including all HIV-positive patients followed at the University Hospital of Fez. These manifestations were essentially liquid diarrhoea in 62 patients (27%), epigastralgia in 40 patients (17.5%), chronic abdominal pain in 10 patients (5%), apyretic hepatic colic in six patients and defecatory rectorrhagia (n = 4, 2.8%). Complications such as post-viral B cirrhosis with ascitic decompensation occurred in one patient (0.4%) and an association with IBD was found in three patients. Complications such as liver abscesses and lymphoma were also reported. Our study is the first large-scale study in Morocco to focus solely on digestive manifestations in HIV patients, and provides a gastroenterologist's perspective on the management of this complex pathology. [ABSTRACT FROM AUTHOR]

Candida lusitaniae fungemia is a serious infection that is rarely reported in children. The aim of this study is to describe a case series of C. lusitaniae fungemia and review previous publications regarding this rare pathogen. This is a multicenter case series of children diagnosed with C. lusitaniae fungemia. A total of 18 cases that occurred over a 15-year period in five tertiary hospitals were included. Additionally, a review of the literature regarding C. lusitaniae fungemia in children was performed. A total of 18 cases were enrolled; 11/18 (61%) were males, with a mean age of 2.3 years. All patients had severe underlying diseases and risk factors for opportunistic infection, most commonly prematurity and malignancies. More than one-third of cases occurred during the last 2 years of the study period. All isolates were susceptible to all tested antifungals. The survival rate following the acute infection was 94%, whereas the survival rate of 14 previously published cases was 71%, with the most common underlying diseases being CGD and malignancies. Candida lusitaniae fungemia is not a common event in the pediatric population, occurring exclusively in children with severe underlying diseases and significant risk factors. This cohort revealed better clinical outcomes than previously reported. All tested isolates were susceptible to all antifungal agents; variability in susceptibility as previously reported was not found in this study. The allegedly higher rate of infection in recent years is in need of further investigation in larger prospective studies in order to conclude if a real trend is at play. [ABSTRACT FROM AUTHOR]

Immunosuppressed patients can present with opportunistic infections resulting from an intrinsic systemic disease, which easily evolves into more aggressive and less common conditions. This work reports a clinical case of a female patient with histoplasmosis lesions in the nasal and oral mucosa, including pulmonary, hematological, and hepatic impairment, which led to the diagnosis of HIV seropositivity. In the presence of severe immunosuppression, morbidity is increased due to deep fungal infections and their unusual clinical characteristics can make diagnosis difficult. Therefore, it can be very helpful to recognize these clinical characteristics in order to determine early diagnostic interventions. It is important to recognize mucocutaneous manifestations of histoplasmosis because the biopsy of these lesions, and subsequent histopathological analysis, is one of the quickest, safest, and cheapest methods of diagnosis. [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

Cutaneous pseudolymphomas are a wide group of diseases mimicking cutaneous lymphoma. They comprise several skin conditions with different etiopathogenesis, clinical–pathological features, and prognosis, which may occur in the absence of an identifiable trigger factor or after administration of medications or vaccinations, tattoos, infections, or arthropod bites. They present with different manifestations: from solitary to regionally clustered lesions, up to generalized distribution and, in rare cases, erythroderma. They persist variably, from weeks to years, and resolve spontaneously or after antibiotics, but may recur in some cases. CD30+ T‐cell pseudolymphomas are characterized by the presence of large, activated lymphoid cells, generally in response to viral infections, arthropod assault reactions, and drug eruptions. Stenotrophomonas maltophilia is a ubiquitous Gram‐negative bacillus responsible for opportunistic infections in immunocompromised patients. Infection of intact skin in immunocompetent patients is particularly rare. Here, we report a case of a man presenting an isolated nodule histopathologically mimicking a primary cutaneous CD30+ T‐cell lymphoproliferative disorder. [ABSTRACT FROM AUTHOR]

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]

Fungal infections in HIV-positive patients present a major challenge, despite advances in antiviral treatments. With an incidence of around 37%, these infections go beyond simple benign mycoses to include serious and potentially fatal forms. The management of these infections requires an individualised approach, taking into account the severity of the infection, drug sensitivity, co-morbidities and drug interactions, as these patients are often on a combination of antibacterial, antifungal and antiviral treatments. Candidiasis, particularly of the oropharynx, is the most common. Initial treatment involves local antifungal agents such as nystatin, followed by systemic treatments such as fluconazole in the event of resistance. Oesophageal candidiasis requires a broad-spectrum antifungal agent, principally fluconazole. Vaginal candidiasis is treated locally with imidazoles. Cryptococcosis, caused by Cryptococcus neoformans, is treated in three phases with a combination of amphotericin B, flucytosine and fluconazole, with close monitoring of the patient's response. Histoplasmosis, caused by Histoplasma capsulatum, can affect various organs. Initial treatment is with liposomal amphotericin B, followed by itraconazole if there is improvement, with particular attention to plasma levels due to variable absorption. Aspergillosis, although rare, has a high mortality rate. Voriconazole is the treatment of choice, requiring rigorous monitoring of plasma concentrations to avoid drug interactions. In summary, the management of fungal infections in HIV-positive patients requires a strategic approach, combining local and systemic treatments, with close monitoring to adjust therapies according to the patient's individual response. [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]

Background Currently, there is no effective treatment for adult-onset immunodeficiency (AOID) syndrome with anti-interferon-gamma autoantibodies (anti-IFN-γ-auto-Abs). This study aimed to investigate the effectiveness of bortezomib (BTZ) for decreasing anti-IFN-γ-auto-Abs. Methods A pre- and post-intervention study was conducted from February 2017 through June 2019 at Siriraj Hospital (Bangkok, Thailand). Five patients were invited to receive once-weekly BTZ (1.3 mg/m2 body surface area) subcutaneously for 8 weeks followed by oral cyclophosphamide (1 mg/kg/d) for 4 months. The primary outcomes were the difference in antibody level at 8 and 48 weeks compared with baseline and the incidence of serious adverse events (AEs). The secondary outcome was the occurrence of opportunistic infections (OIs) during the 72 weeks after starting BTZ. Results The median patient age was 46 years (range, 34–53). All patients had 3–5 OIs prior to enrollment. All patients were receiving antimycobacterial agents for treatment of nontuberculous mycobacterial infection at enrollment. There was no significant difference in the mean optical density of auto-Abs at 8 weeks (3.73 ± 0.72) or 48 weeks (3.74 ± 0.53) compared with baseline (3.84 ± 0.49; P =.336 and P =.555, respectively). However, after serum dilution, the antibody titer nonsignificantly decreased 8–16 weeks after BTZ initiation (P =.345). Ten OIs were observed 24–72 weeks after BTZ initiation. Conclusions Treatment with BTZ followed by cyclophosphamide yielded no significant decrease in antibody titer levels, and 10 OIs were observed during 24–72 weeks of BTZ treatment. No serious AEs were observed. Combining rituximab with BTZ is likely necessary to prevent generation of new autoantibody-producing plasma cells. Clinical Trials Registration. NCT03103555. [ABSTRACT FROM AUTHOR]

Introduction: Dimorphic fungi cause infection following the inhalation of spores into the pulmonary system. In the lower respiratory tract, the conidia transform into yeasts, which are engulfed by alveolar macrophages and may be destroyed without disease manifestation. However, in some immunocompromised individuals, they may persist and cause active fungal disease characterized by formation of granulomas in the infected tissues, which may mimic Mycobacterium tuberculosis (MTB). Objective: To determine the prevalence of pulmonary dimorphic fungal infections among HIV/AIDS patients with non‐TB chronic cough at Mulago National Referral and Teaching Hospital in Kampala, Uganda. Methods: Sputum samples were collected from 175 consented HIV/AIDS patients attending the immuno‐suppression syndrome (ISS) clinic at the hospital. Upon Xpert MTB/RIF sputum testing, 21 patients tested positive for MTB, and these were excluded from further analysis. The other 154 sputum negative samples were then subjected to PCR for dimorphic fungi at MBN Clinical Laboratories. Singleplex PCR was used to detect the target sequences in selected respective genes of each dimorphic fungal species of interest. DNA amplicons were detected based on gel electrophoresis. Results: Dimorphic fungi were detected in 16.2% (25/154) of the studied population. Of these 9.1% (14/154) had Blastomyces dermatitidis and 7.1% (11/154) had Talaromyces marneffei. The remaining 84% of the studied participants had no dimorphic fungi. Histoplasma capsulatum, Coccidioides immitis and Paracoccidioides brasiliensis were not detected in any of the participants. Conclusion: Dimorphic fungi (B. dermatitidis and T. marneffei) were found in 16.2% of the HIV/AIDS patients with non‐TB chronic cough in Kampala, Uganda. We recommend routine testing for these pathogens among HIV/AIDS patients with chronic cough. [ABSTRACT FROM AUTHOR]

Background While opportunistic infections are a frequent and challenging problem in kidney transplant recipients, their long-term epidemiology remains hardly known. Methods Opportunistic infections were recorded in 1144 recipients transplanted in our center between 2004 and 2015. Incidence rates and baseline risk factors were determined using joint frailty models. Results After a median follow-up of 5.6 years, 544 opportunistic infections occurred in 373/1144 (33%) patients, dominated by viral infections (396/544, 72%), especially cytomegalovirus (CMV) syndromes and diseases (213/544, 39%). One-third of the infected patients experienced at least two opportunistic infections. The incidence of opportunistic infections was 10 times higher during the first year post-transplantation than after that (34.7 infections for 100 patient-years vs 3.64). Opportunistic infections associated with the age of the donor (P  = .032), the age of the recipient (P  = .049), the CMV serostatus (P  < 10−6), a higher class II HLA mismatch (P  = .032) and an induction treatment including rabbit anti-thymocyte globulins (P  = .026). Repeated opportunistic infections associated with each other (P  < 10−6) and with renal death (P  < 10−6). Conclusion Opportunistic infections occur with a two-period incidence pattern and many susceptible patients suffer from repeated episodes. This knowledge may help tailor new prevention and follow-up strategies to reduce the burden of opportunistic infections and their impact on transplantation outcome. [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

This article discusses a case study of a 64-year-old female kidney transplant recipient who developed a lung mass. The patient had received immunosuppressive medications and prophylactic antibiotics following the transplant. After presenting with weight loss, fever, and cough, the patient was diagnosed with Nocardia nova infection. Treatment with antibiotics led to significant improvement in the patient's condition. The article emphasizes the importance of considering Nocardia infection in immunocompromised patients and highlights the role of CT imaging in diagnosing and managing the condition. [Extracted from the article]

Introduction: Pneumocystis jirovecii pneumonia (PJP) is a rare complication of hematopoietic stem cell transplantation (HSCT). Primary prophylaxis for 6–12 months post‐HSCT is the standard approach. However, there is no consensus regarding the optimal duration of prophylaxis. Methods: We identified patients who developed PJP more than 1‐year post‐HSCT. All patients had previously received 12 months of PJP prophylaxis. PJP was diagnosed based on clinical findings and the detection of P. jirovecii in bronchoalveolar lavage (BAL) using polymerase chain reaction (PCR). The CD4+ T‐cell percentage was determined using flow cytometry. Data expressed as median (interquartile range). Results: Ten patients developed PJP at 17.5 months (16–24 months) post‐HSCT. PJP diagnosis occurred 5.5 months (3–15 months) after discontinuing prophylaxis. Eight patients received anti‐thymocyte globulin (ATG) as graft versus host disease (GVHD) prophylaxis. At diagnosis, only one patient had lymphopenia; all patients had CD4+ T‐lymphocyte counts ≥0.2 × 109/L (median 0.337 × 109/L). Three patients had concomitant bacterial infections. The clinical presentation was mild; only three required hospitalization, none of them required intensive care and there were no deaths. Conclusion: There is a need to develop risk‐adapted prophylactic strategies in the contemporary era using ATG‐based GVHD prophylaxis. [ABSTRACT FROM AUTHOR]

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]

A 16‐month‐old, male, entire beagle presented for suspected relapse of steroid‐responsive meningitis‐arteritis 12 months after diagnosis. Following improvement with immunosuppressive treatment, the dog developed lethargy and right pelvic limb lameness. Neuroanatomical localisation was to the L4–S3 spinal cord segments/associated peripheral nerves. Magnetic resonance imaging revealed peripherally contrast‐enhancing, fluid‐isointense, cavitary lesions within the right and left great adductor, gracilis muscles and right semimembranosus, internal and external obturator, superficial glutaeal and coccygeal muscles. Culture and sensitivity of muscle fine‐needle aspiration revealed Corynebacterium species without antibiotic resistance. Clinical signs resolved on amoxicillin‐clavulanate (25 mg/kg/12 h) and clindamycin (20 mg/kg/12 h), but relapsed after 6 weeks. Addition of marbofloxacin (2 mg/kg/24 h) achieved clinical resolution. After 2 weeks, the dog relapsed and the owner elected euthanasia. Postmortem biopsies of the gracilis and semitendinosus muscles revealed pyogranulomatous polymyositis. Corynebacterium species should be considered a differential diagnosis for pyogranulomatous polymyositis in dogs. Lack of response to appropriate antibiotic treatment in immunosuppressed dogs may carry a poor prognosis. [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]

• CF airways are prone to opportunistic infections that can drive local inflammation. • Prevalence changes were studied from 2001-2019 for 7 CF bacterial opportunists. • Overall opportunist prevalence generally fell as population health improved. • Year-to-year prevalence change rates differed across organisms and birth cohorts. • More people changed infection status yearly than was suggested by prevalence change. Opportunistic bacterial infection is a hallmark of cystic fibrosis (CF) lung disease and early mortality. Poorly characterized prevalence changes have accompanied two decades of health improvements, with CFTR modulators likely to further affect infection epidemiology. Bacterial prevalence change trends across birth cohorts were assessed with linear regression using 2001–2019 US CF Foundation Patient Registry data. Informative missingness was assessed, as was age-to-age infection status. Bacterial prevalence constantly changed from 2001 to 2019, with changes differing across birth cohorts. Informative censoring affected prevalence change for some organisms. Age-to-age infection status changes were greater than net changes in bacterial prevalence and varied by age. CF infection epidemiology changed over two decades and will continue to do so. Understanding how modulators affect infection epidemiology will require creative designs for longitudinal prevalence change studies emphasizing prevalence changes independent of effects on lung biology. [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.

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