Search

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]

• 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]

Liver transplant recipients are prone to both short-term and long-term complications and may present to any emergency department. This narrative review summarized key aspects of liver transplantation and reviewed the major complications that may result in emergency department presentation. Liver transplantation is the only curative therapy for end-stage liver disease and the liver is the second most commonly transplanted solid organ. With nearly 100,000 living liver transplant recipients in the United States, these patients no longer present exclusively to transplantation centers. Critical complications may manifest with a variety of subtle signs and symptoms that must be considered by the emergency physician. Appropriate evaluation often includes laboratory analysis and imaging. Treatment may be time-sensitive and is variable depending on the specific complication. Emergency physicians in all settings must be prepared to evaluate and treat liver transplant recipients who present with potential graft- and life-threatening complications. [ABSTRACT FROM AUTHOR]

We report for the first time a case of disseminated infection caused by Peziza ostracoderma , a mold not previously associated with invasive infections in humans. P. ostracoderma occurs in natural and sterilized soil and may cause hypersensitivity pneumonitis in greenhouse workers. The immunocompromised patient presented with neutropenic fever that did not respond to broad-spectrum antibiotics and developed multiple skin and lung lesions. A skin biopsy demonstrated an angioinvasive mold, identified as Peziza ostracoderma by culture and DNA sequencing. Minimum inhibitory concentration (MIC) for amphotericin B was 0.125 mg/L, for isavuconazole 0.125 mg/L, for voriconazole 0.06 mg/L, and for posaconazole 0.03 mg/L. The skin lesions have resolved completely, and the lung lesions have decreased significantly in size after 14 months of mold-active antifungal therapy, mostly isavuconazole. In conclusion, Peziza species can be opportunistic pathogens causing considerable morbidity in immunocompromised hosts. The infection may be successfully treated with mold-active antifungal drugs. • Peziza ostracoderma may cause angioinvasive infection in immunocompromised hosts. • Genomic methods are useful in the diagnostics of fungal infections of unknown origin. • Peziza ostracoderma may be treated with mold-active azoles or amphotericin B. [ABSTRACT FROM AUTHOR]

This study aimed to examine the factors associated with cytomegalovirus (CMV) antigenemia and the time of onset of CMV antigenemia among patients with rheumatic diseases. A single-center, retrospective, observational study was conducted in our institution from January 2009 to December 2017. This study included patients with rheumatic diseases who had at least one CMV antigen measurement. Multivariate analysis and receiver operating characteristic analysis was performed. A total of 249 patients underwent CMV antigenemia assay, and 84 (33.7%) patients tested positive. When the association between CMV antigenemia and possible associated factors was investigated, multivariate analysis showed that daily steroid dose increased the odds of having CMV [odds ratio 16.25, 95% confidence interval (CI), 5.360–49.253]. In this study, the cutoff value of daily steroid dose found in this study (0.45 mg/kg/day) was reasonable in clinical practice, and the area under the curve of the steroid dose was 0.838 [95% CI 0.781–0.882], which was the largest of the known indicators. Moreover, the median time from the start of immunosuppressive therapy to the onset of CMV antigenemia was 30 (interquartile range, 21–44) days, and most of the daily steroid users (85.7%) developed CMV antigenemia within 60 days. The daily steroid dose is the most important factor associated with CMV antigenemia. Therefore, monitoring and treatment strategies based on the steroid dose, especially in the initial 2 months, are important. [ABSTRACT FROM AUTHOR]

Globally, many hospitalized COVID-19 patients can experience an unexpected acute change in status, prompting rapid and expert clinical assessment. Superimposed infections can be a significant cause of clinical and radiologic deviations in this patient population, further worsening clinical outcome and muddling the differential diagnosis. As thrombotic, inflammatory, and medication-induced complications can also trigger an acute change in COVID-19 patient status, imaging early and often plays a vital role in distinguishing the cause of patient decline and monitoring patient outcome. While the common radiologic findings of COVID-19 infection are now widely reported, little is known about the clinical manifestations and imaging findings of superimposed infection. By discussing case studies of patients who developed bacterial, fungal, parasitic, and viral co-infections and identifying the most frequently reported imaging findings of superimposed infections, physicians will be more familiar with common infectious presentations and initiate a directed workup sooner. Ultimately, any abrupt changes in the expected COVID-19 imaging presentation, such as the presence of new consolidations or cavitation, should prompt further workup to exclude superimposed opportunistic infection. • Any radiologic changes in a COVID-19 patient should prompt further workup to exclude superimposed opportunistic infection. • Accurate diagnosis and optimal treatment of co-infections in COVID-19 patients is a challenging task. • Common infections should be considered in the differential diagnosis to avoid missing a highly preventable disease. [ABSTRACT FROM AUTHOR]

De la primo-infection au stade du syndrome d'immunodéficience humaine acquise en passant par la phase asymptomatique, le polymorphisme de la symptomatologie de l'infection par le virus de l'immunodéficience humaine exige un large recours au dépistage, afin d'enrailler la transmission du virus, et la mise en place précoce d'un traitement. La prise en charge des patients s'intègre dans une démarche pluridisciplinaire, associant un suivi spécialisé par un infectiologue pour adapter la stratégie thérapeutique et un suivi spécifique au profil de chaque individu. From the primary infection to the acquired human immunodeficiency syndrome stage, including the asymptomatic phase, the polymorphism of the symptomatology of human immunodeficiency virus infection requires extensive screening in order to stop the transmission of the virus and the early implementation of treatment. The management of patients is part of a multidisciplinary approach, combining specialized follow-up by an infectious disease specialist to adapt the therapeutic strategy and specific follow-up to each individual's profile. [ABSTRACT FROM AUTHOR]

Eye disease is common among kidney transplant recipients, and their management is challenging. Chronic kidney disease is associated with ocular complications, both independently and in the context of various systemic disorders. In addition, chronic immunosuppression predisposes kidney transplant recipients to an array of long-term ocular issues. This may be broadly categorized into infections, malignancies, and other immunosuppression-specific side effects. The interdependence of kidney disease, transplant pharmacotherapy, and ocular health, therefore, requires a multispecialty approach. Although the kidney transplant population has grown along with the burden of associated oculopathies, systematic guidelines targeting this patient group are lacking. This evidenced-based narrative review summarizes the pertinent issues that may present in the ophthalmic and optometric clinical settings, with emphasis on collaborative management and directions for future research. [ABSTRACT FROM AUTHOR]

Fusarium species manifests as an opportunistic infection with intrinsic resistance to most antifungals. We present a case of a 63-year-old male with myelodysplasia who received allogeneic stem cell transplantation and presented with endophthalmitis as the initial manifestation of invasive fusariosis that progressed to a fatal outcome despite combined intravitreal and systemic antifungal therapies. We urge clinicians to consider this complication of fusarium infection especially with the widespread use of antifungal prophylaxis that may incur selection of more resistant, invasive fungal species. • Prognosis of invasive fusariosis is generally poor with a median survival of six days. • Clinical signs of dissemination prompt confirmatory diagnosis followed by initiation of early aggressive therapy. • Antifungal prophylaxis may incur selection of resistant, invasive fungal species. [ABSTRACT FROM AUTHOR]

A healthy microbiome plays an important role in the prevention of illness and maintenance of overall health, including reproductive health. Although the therapeutic advantages of probiotics have been shown to run across multiple organ systems, their role in pregnancy is not well explored. The aim of this review is to highlight the potential advantages and adverse effects of probiotics in pregnancy. Data were collected from the literature over the past decade using PubMed, Medline, Google Scholar, Ovid, Scopus, and Science Direct. A total of 40 articles were utilized in this review. Collected data indicated that prenatal and post-natal supplementation with lactobacilli alone or lactobacilli with Bifidobacterium spp. seems to be protective. Probiotics may improve insulin resistance and consequently reduce the risk of gestational diabetes. Probiotics may also reduce anxiety and depression by influencing brain activity. Additionally, they interfere with vaginal flora to make it friendlier to beneficial bacteria, and enhance anti-inflammatory or reduce pro-inflammatory cytokines. They may also decrease eczema in breastfed infants and prevent allergic reactions by downregulating Th2 responses to specific allergens from mid to late gestation. Leveraging the cervicovaginal microbiota could promote a number of positive pregnancy-related health outcomes. Caution should be exercised in the selection, dosing, and monitoring of probiotics administration. More comprehensive randomized clinical trials are needed to reach a more meaningful evidence-based clinical knowledge. [ABSTRACT FROM AUTHOR]

Objectives: No current academic data is available with respect to the optimal timing to initiate antiretroviral therapy (ART) in HIV-positive patients with talaromycosis. Our study aimed to evaluate the optimal timing of ART initiation for patients presenting with AIDS-related talaromycosis.Methods: In this prospective, randomized, open-label multicenter trial, 228 patients from 15 hospitals in China were randomly assigned to an early ART group (initiation of ART within 2 weeks after randomization) and a deferred ART group (initiation of ART 2 weeks after randomization). The primary endpoint was all-cause mortality during the 48 weeks after randomization.Results: We observed a significant difference in mortality between the early ART group and the deferred ART group (2.2% vs. 8.9%, 95%CI: -0.15 to 14.05, p = 0.049). The composite outcome of AIDS-defining events or death in the early ART group was found to be lower than that in the deferred ART group (3.3% vs. 14.9%; 95%CI: 2.93 to 19.23, p = 0.008).Conclusions: The prognosis of HIV-infected patients with talaromycosis in the early ART group was more favorable than that of patients in the deferred ART group. These results demonstrate that early ART initiation should be considered in HIV-infected patients with talaromycosis . [ABSTRACT FROM AUTHOR]

Scedosporium apiospermum is an opportunistic mold that is an emerging disease in humans and animals. This report describes a case of S. apiospermum infection inciting a mural urinary bladder mass and focal peritonitis in a dog that had a history of multiple traumatic events several years prior. For diagnosis, culture followed by MALDI-ToF, PCR, and sequencing was performed to accurately identify the species. Susceptibility testing was also performed due to the inherent resistance of S. apiospermum to numerous antifungal agents. [ABSTRACT FROM AUTHOR]

• TGF-β levels are higher in liver and kidney recipients than healthy individuals. • TGF-β levels are higher in liver and kidney recipients with opportunistic infection. • ELISA of TGF-β from cultured supernatant can be a novel marker of infection. Transforming growth factor-β (TGF-β) has been associated with numerous human infections, but its role in the occurrence of opportunistic infection (OI) after solid organ transplantation remains unexplored. This study aimed to assess the utility of the TGF-β following in vitro stimulation of whole peripheral blood (WPB) as a surrogate biomarker of post-transplant OI in a cohort of liver and kidney recipients. Thirty liver and thirty-one kidney transplant recipients were recruited to be prospectively monitored for one-year post-transplantation. Enzyme-linked immunosorbent assay (ELISA) was performed to calculate IFN-γ, IL-17, IL-10 and TGF-β concentration in the supernatant from the activated WPB. Recipients showed higher TGF-β concentrations compared to IFN-γ, IL-17, IL-10 at baseline, although these differences were not significant between INF and NoINF. However, recipients who developed an OI within the first sixth months had a higher concentration of TGF-β than those without OI. A concentration of TGF-β > 363.25 pg/ml in liver and TGF-β > 808.51 pg/ml in kidney recipients were able to stratify patients at high risk of OI with a sensitivity and specificity above 70% in both types of solid organ transplantations. TGF-β could provide valuable information for the management of liver and kidney recipients at risk of post-transplant infection. [ABSTRACT FROM AUTHOR]

India is going through an epidemiologic and demographic transition made possible by increased investment in health sector and sustained development. The country has more than 2 million people infected with human immunodeficiency virus (HIV). Information on cost-effectiveness of competing interventions is a useful contributor to decisions concerning allocation and prioritization of healthcare resources. This paper aims to study the cost, health outcomes as measured by disability-adjusted life-years (DALYs), and cost-effectiveness per DALY averted of prophylaxis for tuberculosis, diarrhea, and mouth ulcers in HIV-infected adults. Data were analyzed on 375 HIV-infected persons enrolled at the ART Centre in New Delhi between April 2004 and April 2006. Using estimates of the age of onset of HIV infection, cost of medicines, and antiretroviral regimen followed, we used standard methods to calculate the cost per DALY as a measure of cost-effectiveness. Sensitivity analysis was conducted to determine the robustness of cost-effectiveness results by making reasonable changes in underlying assumptions. The results revealed that the incremental cost-effectiveness ratio for tuberculosis prophylaxis was ₹4821.48 ($78.86) per DALY averted compared with no prophylaxis, followed by diarrhea (₹8299.08, $135.74) and mouth ulcers (₹20 058.14, $328.07). The estimates are less than the per capita gross domestic product of India, indicating that the current treatments are highly cost-effective. This will help policymakers understand the best opportunities to improve population health and help researchers to develop more standardized methods in the area, thus improving quality and comparability across cost per DALY studies. [ABSTRACT FROM AUTHOR]

Les patients atteints de lupus érythémateux systémique (LES) sont à risque de développer une infection à cytomégalovirus (CMV), à cause de la maladie elle-même ou à cause du traitement immunosuppresseur. Le CMV serait par ailleurs susceptible de déclencher des poussées lupiques. Dans cette étude rétrospective monocentrique, nous avons rapporté une série de patients atteints de LES hospitalisés et présentant une infection à CMV documentée. L'objectif était de décrire leurs caractéristiques, l'évolution de l'infection à CMV, les complications éventuelles en termes de poussée lupique et d'infections secondaires, et de synthétiser la littérature sur le sujet. Nous décrivons, à partir d'une cohorte de 400 patients avec LES, 12 cas d'infection à CMV. Les manifestations sévères du CMV (atteinte spécifique d'organe) étaient rencontrées chez 7 des 10 patients sous traitement immunosuppresseur, et chez 1 des 2 patients naïfs de traitement. Le diagnostic d'infection à CMV a été porté de manière concomitante à celui de LES dans 3 cas. L'infection à CMV a été compliquée d'événements infectieux intercurrents dans 6 cas. Nous avons noté la survenue de poussée lupique dans les 3 mois dans 3 cas. L'évolution de l'infection à CMV était favorable pour les 12 patients. L'infection à CMV survient plus fréquemment chez les patients lupiques traités par immunosuppresseurs, mais se voit également chez des patients naïfs de traitement avec parfois des tableaux cliniques graves. La sévérité potentielle d'une infection à CMV au cours du LES et ses complications suggèrent l'utilité d'un traitement antiviral rapide. Patients with systemic lupus erythematosus (SLE) are at risk of cytomegalovirus (CMV) infection, due to the disease itself or to drug-induced immunosuppression. Also, active CMV infection may trigger or worsen SLE flare-up. In this retrospective single-centre cohort study, we reported all adult inpatients with a diagnosis of SLE, presenting with active and confirmed CMV infection. The goal was to describe their characteristics and outcomes (evolution of CMV infection, secondary infections and SLE flare-up), and to review the existing literature. We identified 400 patients with confirmed SLE, including 12 who presented with active CMV infection. Severe CMV manifestations were present in 7 patients treated with immunosuppressive regimen out of 10, and in one patient out of two without immunosuppressive therapy. Six patients developed other infections, and 3 showed characterised SLE flare-up over the 3-month follow-up. All patients were alive at end of follow-up. Among patients with SLE, CMV infection affected more frequently those treated with immunosuppressive drugs, but treatment-free patients were sometimes severely affected. CMV infection was associated with an increased incidence of SLE flare-up and infectious complications. Our results suggest that early anti-viral chemotherapy may be beneficial in these patients. [ABSTRACT FROM AUTHOR]

• Nocardiosis mainly affects elderly patients with chronic respiratory conditions and those under corticosteroid treatment. • Infections in HIV and solid organ transplantation patients have practically disappeared. • Nocardiosis most commonly affects the lungs. • Nocardiosis caused by N. farcinica is apparently a risk factor for poor clinical outcome. To analyse relevant changes in incidence, clinical and microbiological characteristics of nocardiosis over the last 24 years at the current institution. The clinical records of patients with nocardiosis (2006–2018) were reviewed and then compared with a previous cohort (1995–2006). Nocardia isolates were identified by 5'-end-16S-rRNA-gene-PCR targeting the first 500 bp of the gene and sequencing. Susceptibility tests were determined by broth microdilution (CLSI guidelines). Forty-two patients (64.3% male) with nocardiosis were evaluated in the recent cohort: 51.2% had COPD, 43.9% were on corticosteroid therapy and 31.7% had cancer. The incidence of nocardiosis varied from 6.3 to 7.1/100,000 admissions (p = 0.62). There was a decrease in HIV patients (27% vs. 4.9%, p = 0.01) and solid organ transplantation (SOT) recipients (18.9% vs. 2.4%, p = 0.01). Cases with pulmonary involvement had increased (70.3% vs. 90.5%, p = 0.04). Nocardia species were similar but the most common were N. cyriacigeorgica (32.4% vs. 40.5%, p = 0.49) and N. farcinica (24.3% vs. 14.3%, p = 0.39). Antibiotic resistance remained stable: cotrimoxazole (10.8% vs. 5.7%, p = 0.68), imipenem (5.4% vs. 5.6%, p = 1.0); amikacin and linezolid were 100% active. No differences were found in breakthrough nocardiosis (21.6% vs. 9.8%, p = 0.21) or related mortality (21.6% vs. 21.4%, p = 1.0). The multivariate analysis confirmed that nocardiosis caused by N. farcinica is a risk factor for poor outcome (p = 0.045). Nocardiosis incidence has remained stable. It mainly affected elderly patients with chronic respiratory conditions and those on corticosteroid treatment. Infections in HIV and SOT patients have practically disappeared. Pulmonary involvement remains the most common area to be affected. Nocardiosis caused by N. farcinica is apparently a risk factor for poor clinical outcome. [ABSTRACT FROM AUTHOR]

Corticosteroids have been used for the treatment of a great variety of diseases. Therefore, the relationship between high doses of cortisol and infections has been widely known and prophylactic therapy has been established. Adrenocortical carcinoma is a rare malignancy with poor prognosis, so little is known about how to deal with the complications resulting from hormone excess such as Cushing's syndrome. Here we report a case of an 82-year-old woman who presented with a 1-day history of dyspnea and was finally diagnosed as disseminated cryptococcosis at autopsy. The patient had received a diagnosis of metastatic adrenocortical carcinoma and Cushing's syndrome three months earlier. The findings of this study indicate the relation between severe hypercortisolemia due to adrenocortical carcinoma and opportunistic infections. In the setting of adrenocortical carcinoma with Cushing's syndrome, clinicians should maintain a high index of suspicion for opportunistic infections including cryptococcosis, which are potentially treatable by early detection and prompt intervention. [ABSTRACT FROM AUTHOR]

This review will concentrate on commonly encountered infectious diseases in biopsy practice and will consider three scenarios: Firstly, the most frequent, where the biopsy arrives with the infectious disease stated on the request form. Secondly, where the patient has a risk factor placing infectious diseases high in the differential diagnosis and, thirdly, where infection is one of several possible aetiologies when a liver biopsy shows a particular pattern of inflammation. [ABSTRACT FROM AUTHOR]

• Improved adherence to ART increased annual baseline costs in HIV-infected patients. • Having ADIs significantly increased annual costs up to 99% (i.e., cryptococcosis). • ADIs occurred less frequently in years with improved adherence to ART. • Economic burden of ADIs was attenuated in years with improved adherence to ART. We assessed the economic burden of AIDS-defining illnesses (ADIs), which was further stratified by adherence to antiretroviral therapy (ART). A nationwide longitudinal cohort of 18,234 incident cases with HIV followed for 11 years was utilized. Adherence to ART was measured by medication possession ratio (MPR). Generalized estimating equations modeling was used to estimate the cost impact of ADIs. Having opportunistic infections increased the annual cost by 9% (varicella-zoster virus infection) to 98% (cytomegalovirus disease), while the annual costs increased by 26% (Kaposi's sarcoma) to 95% (non-Hodgkin's lymphoma) in the year when AIDS-related cancer occurred. ADIs occurred more frequently in the years with low adherence for ART compared to the high-adherence years (e.g., 0.1 ≤ MPR < 0.8 vs. MPR ≥ 0.8, event rate of cytomegalovirus disease 4.03% vs. 0.51%). The annual baseline costs in the years with MPR < 0.1, 0.1 ≤ MPR < 0.8, and MPR ≥ 0.8 were $250, $4,752, and $8,990 (in 2018 USD), respectively. The economic impact of ADIs in the years with low adherence (MPR < 0.1) was larger than that in the high-adherence years (MPR ≥ 0.8) (e.g., MPR < 0.1 vs. MPR ≥ 0.8, annual cost increased by 244% vs. 9% when candidiasis occurred). Adherence to ART may increase the baseline medical costs but mitigate the incidence and economic burden of ADIs. [ABSTRACT FROM AUTHOR]

Human monkeypox (mpox) is usually self-limited infection; however, rising data show a worse outcome in patients with impaired immune status, particularly those co-infected with HIV [Mitjà O, Alemany A, Marks M, Lezama Mora JI, Rodríguez-Aldama JC, Torres Silva MS et al. Mpox in people with advanced HIV infection: A global case series. Lancet. 2023; 401:939–49. DOI: https://doi.org/10.1016/S0140-6736(23)00273-8 ] [Govind A, Lazarte SM, Kitchell E, Chow JY, Estelle CD, Fixsen E et al. Severe mpox infections in people with uncontrolled human immunodeficiency virus (HIV). Clin Infect Dis. 2023; 76:1843–6. DOI: https://doi.org/10.1093/cid/ciad052 ]. We report the clinical, pathological, and molecular study of a patient with mpox infection and a late HIV diagnosis, with fatal outcome. Necropsy revealed visceral spread of mpox. Mpox virus was sequenced twice during the admission, uncovering an emerging mutation near a genomic region where mutations associated with tecovirimat resistance have been documented. Monkeypox can manifest as an opportunistic infection in individuals with advanced HIV-associated immunosuppression. [Display omitted] [ABSTRACT FROM AUTHOR]

Magnusiomyces clavatus is a rare yeast-like fungus that can cause opportunistic infections in immunocompromised patients. Here, we present a 14-year-old patient who was followed up with the diagnosis of acute lymphoblastic leukemia, developed skin rashes, and Magnusiomyces clavatus infection detected. The patient died shortly after the infection was diagnosed. [ABSTRACT FROM AUTHOR]

Phaeohyphomycosis is a fungal infection common in immunocompromised patients such as those with hematologic malignancies, transplant recipients or under prolonged corticosteroid use. Here we describe a rare case of phaeohyphomycosis due to Biatriospora mackinnonii in a kidney transplant patient. We confirmed B. mackinnonii identity by sequencing of the internal transcribed spaces (ITS) region of ribosomal DNA (rDNA) and achieved a satisfactory therapeutic response with itraconazole administration. [ABSTRACT FROM AUTHOR]

Nocardia affects immunocompromised human host exhibiting an altered cell-mediated immunity. Infectious risk after allogeneic hematopoietic cell transplantation (AHCT) is significantly correlated to the recovery status of donor-derived immune system, especially CD4+ T-cells reconstitution and thymopoiesis. The purpose of this paper is to highlight a lack of cell-mediated immunity recovery for patients presenting a nocardiosis compared to a control cohort. This is a case control retrospective monocentric study. We retrospectively analyzed a monocentric cohort of 15 cases of nocardiosis after AHCT and we explored the degree of patients' immunosuppression by phenotyping circulating lymphoid subpopulations, including NK cells, CD8+ T-cells, CD4+ T-cells and CD19+ B-cells. We focused on CD4+ T-cell subsets to appreciate thymic output, especially on naive CD4+ T-cells (NTE, CD45RA+/RO− CD4+ T-cells) and recent thymic emigrants (RTE, CD4+CD45RA+/RO−/CD31+). Infected patients were paired with a control cohort of patients with identical transplantation characteristics screened on hematological disease, AHCT conditioning, primary graft- versus -host disease (GHVD) prophylaxis, graft type, sex, age, and season at the AHCT and data concerning immunological reconstitution were compared. At onset of nocardiosis, circulating lymphocytes and CD4+ T-cells means count were respectively 730/μL and 162/μL. CD8+ T-cells, CD56+ NK cells and CD19+ B-cells means count were respectively 362/μL, 160/μL, 112/μL. CD4+ T-cells subpopulations, naïve CD4+ T-cells production was impaired with NTE and RTE means count at 26/μL and 11/μL respectively. Comparison between nocardiosis cohort and control cohort over time highlight significant lower cellular count for lymphocytes, CD4+ T-cells, NTE and RTE with p = 0.001, p < 0.001, p < 0.001, p < 0.001 respectively. Immune recovery monitoring follow-up after AHCT is of particular importance to identify patients susceptible to develop Nocardiosis. Efficient microbiological investigations toward Nocardia such PCR should be used in case of compatible clinical presentation. [ABSTRACT FROM AUTHOR]

Following a fatal case of Cryptococcus neoformans meningitis in a child with X-linked hyper-immunoglobulin M syndrome (XHIGM), we evaluated the fungal isolate in an experimental infection in a mouse model with respect to microbiology, epidemiology, virulence and response to therapy. The minimum inhibitory concentrations for antifungals in the susceptibility test were 0.5 mg/L for amphotericin B, 4.0 mg/L for fluconazole and 0.12 mg/L for voriconazole. Evaluation of pathogenicity by means of an experimental infection in BALB/c mice showed that fungus isolated from the blood and cerebrospinal fluid of the child was able to disseminate, reaching the spleen, lungs and brain, where it caused significant macroscopic alterations in the size and texture of each organ. Treatment of infected mice with amphotericin B reduced the fungal load in the spleen and lungs, but not in the brain. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Cytomegalovirus (CMV) infection is associated with relapse and exacerbation of ulcerative colitis (UC), especially in immunosuppressed patients. Objectives The aim of this study was to identify risk factors for CMV colitis and to develop a predictive risk score to estimate the probability of CMV colitis in UC patients supporting clinical decision making. Study design A cohort of 239 UC-patients was retrospectively analyzed. Univariate and multivariate regression analysis identified several independent risk factors for CMV colitis and a predictive risk score was established using ROC analysis. Results CMV colitis is common in patients with severe ulcerative colitis. Clinical UC activity, disease duration and extent as well as the use of steroids and anti-TNF-α agents were identified as risk factors (p < 0.05 each). Based on five predictive parameters, a web-based risk score was developed. A strong correlation between the predicted and actual rates of CMV colitis was found (AUC: 0.855; 95% CI 0.79-0.92; p < 0.0001). Conclusions Our study supports the pathogenic relevance of CMV in UC. The predictive risk score estimates the risk of CMV colitis and might aid in clinical decision making, especially when timely modifications of therapeutic regimens are needed and reliable diagnostic tools are not readily available. [ABSTRACT FROM AUTHOR]

Introduction Rituximab is commonly used for the treatment of hematological malignancies and autoimmune diseases. Despite a reputation for good tolerance, case-series and registries reported rituximab-related infections of variable severity including opportunistic infections. We aimed at describing the natural history of infectious events (IE) after treatment by rituximab providing clinical and microbiological features and outcome. Patients and methods We retrospectively analyzed the medical records of patients treated with rituximab in an internal medicine department of a tertiary hospital between 2007 and 2015, and identified all IE after this therapy. Events' severity was assessed using the Common Terminological Criteria of Adverse Events (version 4.3) definitions. Results Among 101 patients treated with rituximab, we identified 228 IE in 74 (73.3%) of these patients (median follow-up 30.4 months). Indication for rituximab was either autoimmune disease (AID) (52.5% of patients), or monoclonal hematological disease (MHD) (47.5%). Patients received an overall median number of 5 rituximab infusions [interquartile range: 4–8], representing a cumulative dose of 4340 mg [2620–6160]. After last rituximab infusion, IE occurred after 3.1 months [0.7–9.4]. Respectively, IE were severe in 28.1% of cases in patients treated for AID vs 58.0% in patients treated for MHD (p < 0.001), due to opportunistic pathogens in 7.8% vs 11.0% (p = 0.49) and fatal in 4.7% vs 13.0% (p = 0.044). Factor associated with mortality were polymicrobial infection (p < 0.001), monoclonal hematological disease (p = 0.035), use of steroids over 10 mg/d within the last two weeks (p = 0.003), and rituximab cumulative dose (p < 0.001). We identified a group of 10 patients (9.9%) showing life-threatening, polymicrobial, and opportunistic infections constituting a ‘catastrophic infectious syndrome’, which was lethal in 7 cases. Conclusion IE after treatment by rituximab can be extremely severe, especially in patients immunocompromised by several other drugs. Further studies should focus on the group with life-threatening polymicrobial infections. [ABSTRACT FROM AUTHOR]

This review will concentrate on commonly encountered infectious diseases in biopsy practice and will consider three scenarios: Firstly, the most frequent, where the biopsy arrives with the infectious disease stated on the request form. Secondly where the patient has a risk factor placing infectious diseases high in the differential diagnosis and, thirdly, where infection is one of several possible aetiologies when a liver biopsy shows a particular pattern of inflammation. [ABSTRACT FROM AUTHOR]

Summary Background Nocardiosis is a rare disease with polymorphic presentations. The epidemiology and clinical presentation could change with the increasing number of immunocompromised patients. Methods The medical records and microbiological data of patients affected by nocardiosis and treated at the university hospitals of Marseille between 2004 and 2014 were analyzed retrospectively. Results The cases of 34 patients infected by Nocardia spp during this period were analyzed. The main underlying conditions were transplantation ( n = 15), malignancy ( n = 9), cystic fibrosis ( n = 4), and immune disease ( n = 3); no immunodeficiency condition was observed for three patients. No case of AIDS was observed. At diagnosis, 61.8% had received steroids for over 3 months. Four clinical presentations were identified, depending on the underlying condition: the disseminated form (50.0%) and the visceral isolated form (26.5%) in severely immunocompromised patients, the bronchial form (14.7%) in patients with chronic lung disease, and the cutaneous isolated form (8.8%) in immunocompetent patients. Nocardia farcinica was the main species identified (26.5%). Trimethoprim–sulfamethoxazole was prescribed in 68.0% of patients, and 38.0% underwent surgery. Mortality was 11.7%, and the patients who died had disseminated or visceral nocardiosis. Conclusions The clinical presentation and outcome of nocardiosis depend on the patient’s initial immune status and underlying pulmonary condition. Severe forms were all iatrogenic, occurring after treatments altering the immune system. [ABSTRACT FROM AUTHOR]

• JAKis have transformed management of RA; however, associated OIs have been reported. • This structured review summarizes 105 publications of OIs associated with JAKi in RA. • Highest exposure-adjusted incidence rates were for HZ, any OI and TB (limited data). • Lack of head-to-head trials and trial differences preclude direct comparison across JAKis. • Higher OI rates were seen in Asian/Australian populations and with increasing JAKi dose. The availability of Janus kinase (JAK) inhibitors has transformed the management of rheumatoid arthritis (RA), helping patients achieve clinical remission. However, the emergence of opportunistic infections (OIs) associated with the use of JAK inhibitors has been reported. This structured literature review was conducted to summarize reports of OIs associated with JAK inhibitor treatment for RA in clinical trials. Structured searches were performed in MEDLINE® and Embase® to identify relevant clinical trial data through March 2021. Bibliographic searches of recent reviews were also conducted, and gray literature searches were used to supplement key gap areas. Publications were screened, extracted, and quality assessed. Data were narratively synthesized. Following screening, 105 publications describing 62 unique clinical trials reporting the rates of OIs in RA patients treated with JAK inhibitors were included. Overall, the highest exposure-adjusted incidence rate was reported for herpes zoster (HZ) infection (any form), followed by OI (any) and tuberculosis based on limited data from clinical trials with approved doses of JAK inhibitors. Lack of head-to-head trials and differences in trial design preclude direct comparison across JAK inhibitors. Higher rates of OIs were noted in the Asian and Australian populations compared with the global population. Higher rates of OIs were also noted with increasing dose of JAK inhibitors in most clinical trial data. HZ was the most common OI reported among RA patients using all currently approved JAK inhibitors in clinical trials, although tuberculosis and other OIs were also reported. More long-term safety studies in the real-world setting are needed to compare the risk of OIs between various JAK inhibitors. [Display omitted] [ABSTRACT FROM AUTHOR]

Summary Pharmacists have demonstrated a positive impact on the care of patients with human immunodeficiency virus/acquired immunodeficiency syndrome through enhancing patient outcomes associated with antiretroviral therapy. This pre- and postintervention study assessed the impact of pharmacist intervention on improving the use of prophylactic medications for opportunistic infections (OI). Of the 139 patients screened, 42 patients were included in the prospective intervention group. A total of 27 interventions were made on 15 patients, and 24 recommendations (89%) were accepted by providers. Compared with the retrospective control group, prescribing of OI prophylaxis increased from 58% to 93% ( P <0.001) with the addition of pharmacist intervention. [ABSTRACT FROM AUTHOR]

Kidney transplant recipients are at increased risk of developing clinical disease due to uncommon opportunistic viral pathogens. Refractory anemia is classically associated with parvovirus B19 infection. West Nile virus has the propensity to cause fever and neurologic symptoms, while spastic paresis and lymphoma can be triggered by human T cell lymphotrophic virus. In this review article, the epidemiology, clinical manifestations, diagnosis and treatment of less common viruses are discussed in the setting of kidney transplantation. [ABSTRACT FROM AUTHOR]

Peri-implantitis has emerged in the last few years as a complication difficult to resolve. The etiopathogenesis consensus is mainly attributed to bacteria. Following the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines, a PubMed/Medline literature search was performed using the US National Library of Medicine database up to 2015 to analyze available scientific data on the rationale and risk of superinfection associated to systemic antimicrobials in human peri-implant disease. A hand search was also conducted on relevant medical and microbiology journals. The methodological index for non-randomized studies (MINORS) was independently assessed for quality on the selected papers. Proposed combined therapies use broad-spectrum antibiotics to halt the disease progression. A major associated risk, particularly when prescribed empirically without microbiological follow-up, is the undetected development of superinfections and overgrowth of opportunistic pathogens difficult to eradicate. Peri-implant superinfections with opportunistic bacteria, yeast and viruses, are plausible risks associated to the use of systemic antibiotics in immunocompetent individuals. Lack of microbiological follow-up and antibiotic susceptibility testing may lead to ongoing microbial challenges that exacerbate the disease progression. The increased proliferation of antimicrobial resistance, modern implant surface topography and indiscriminative empiric antibiotic regimens may promote the escalation of peri-implant disease in years to come. A personalized 3-month supportive therapy may help prevent risks by sustaining a normal ecological balance, decreasing specific pathogen proportions and maintaining ideal plaque control. [ABSTRACT FROM AUTHOR]

Thymomas with immunodeficiency (formerly Good's syndrome) are a rare acquired disease of combined T- and B-cell immunodeficiency accompanying a thymoma. Recurrent opportunistic infections associated with disorders of both humoral and cell-mediated immunity frequently accompany this rare primary, adult-onset immunodeficiency. This is a report of a case of a thymoma with immunodeficiency in a 65-year-old male patient who developed recurrent oral herpetic infections. He consulted us about recurrent vesiculo-ulcerative lesions on his tongue, lower lip, and buccal mucosa. Results of laboratory examinations indicated hypogammaglobulinemia accompanied by diminished B cells in the peripheral blood, which is consistent with the characteristic features of a thymoma with immunodeficiency. After a diagnosis confirming herpes simplex virus infection, systemic antiviral therapy was administered, which was effective for his vesiculo-ulcerative lesions at follow-up. When an intractable infection accompanied by a thymoma is encountered, increased awareness about the clinical and immunological profiles of this primary immunodeficiency may help in its early diagnosis, thereby preventing mortality. [ABSTRACT FROM AUTHOR]

Aims: This manuscript aims to explain the relationship between mucositis caused by 5-FU over gut bacterial species and susceptibility to opportunistic infection caused by P. aeruginosa. Main methods: BALB/c mice were intraperitoneally treated with PBS or 5-FU. Bodyweight and faecal consistency were checked daily. Mice faecal DNA was extracted, and bacterial phylogenetic groups were analysed using qPCR or high-throughput sequencing. Immunofluorescence was used to evaluate BMDM activation by mice-treated faecal content. Mice were challenged intratracheally with virulent P. aeruginosa , and the CFU and histology were analysed. Faecal microbiota were transplanted to evaluate the gut microbiota and resistance to pulmonary P. aeruginosa recovery. Key findings: The animals treated with 5-FU presented mucositis with great weight loss, altered faecal consistency, bacterial gut dysbiosis and histological changes in the intestinal mucosa. Mice under 5-FU treatment were more susceptible to lung infection by the bacteria P. aeruginosa and had more extensive tissue damage during their lung infection with greater pro-inflammatory gene expression. It was observed that the mucositis remained in the groups with 5-FU even with the FMT. The results caused by mucositis in animals that received allogeneic FMT were reversed, however, with a decrease in P. aeruginosa susceptibility in animals treated with 5-FU and allogeneic FMT compared to animals treated with 5-FU and autologous FMT. Significance: Treatment with 5-FU in a murine model makes it more susceptible to pulmonary infection by the bacterium P. aeruginosa , FMT offers an opportunity to protect against this susceptibility to infection. [Display omitted] [ABSTRACT FROM AUTHOR]

In our earlier studies, we observed that when mice are treated with cyclophosphamide and fragmented exogenous dsDNA (18–30 h post cytostatic treatment), they develop a very characteristic set of symptoms and 80–90% of such animals succumb within 6–25 days. This was called “delayed death” phenomenon, and the gap between cyclophosphamide and DNA injections required for such phenotype to develop was termed “death window”. We established that mice succumbed to multi-organ failure, which was caused by systemic inflammation and sepsis. These processes unfolded along with accidental involution of lymphoid organs, which resulted from the failure of CD34 + hematopoietic stem cells to differentiate into lymphoid lineage progenitors. Here we compare SPF and non-SPF animals, and demonstrate that the major cause of systemic inflammation and sepsis observed upon such treatments is activation of an opportunistic infection. Mice of the same strain (CBA) housed under SPF conditions do not develop the characteristic symptoms, nor do they become moribund. Yet, regardless of the breeding conditions, upon synergistic action of cyclophosphamide and dsDNA, CD34 + hematopoietic stem cells consistently fail to give rise to lymphoid lineage progenitors. We demonstrate that this differentiation defect is reversible and that population of lymphoid progenitors is restored by day 29 after cyclophosphamide injection. [ABSTRACT FROM AUTHOR]

Background Cytomegalovirus (CMV) infection is a major complication of immunosuppression after heart transplant. Recent studies suggest the actual immunosuppressive regimen may affect the risk of CMV infection. Objectives To evaluate incidence, risk factors and clinical consequences of CMV infection and assess the possible differential effect of distinct immunosuppressive protocols. Study design Single centre, prospective cohort study of 378 consecutive heart transplant recipients undergoing CMV monitoring. Preemptive treatment was the standard of care. Patients were grouped as follows: group A, without any CMV infection; group B, with CMV infection not requiring pre-emptive treatment; group C, treated for CMV infection or disease. Results Most recipients never required antiviral therapy because of no CMV infection/disease (group A, 31%) or CMV levels below the cut-off for pre-emptive treatment (group B, 28%). Group C recipients (41%) were significantly older than group A patients (49.1 ± 13.2 vs. 44.8 ± 15.1 years; p = 0.028). Most cases occurred within the second month post-transplant. CMV viremia was detected in 77% and 62% of patients primed with thymoglobulin or ATG Fresenius, respectively, (OR 2.06, 95% C.I. 1.27–3.34; p = 0.0034). Use of everolimus was associated with a significantly lower rate of CMV infection compared to azathioprine or mycophenolate (OR 0.19, 95% C.I. 0.09–0.39; p < 0.0001). Major opportunistic infections were significantly more common in groups B and C. Conclusion In a large and homogeneous cohort of heart transplant recipients, we observed a strong relationship between the immune suppressive regimen and CMV infection, as well as an increased incidence of other opportunistic infections in recipients with CMV infection/disease. [ABSTRACT FROM AUTHOR]

Screening HIV-positive migrants for neglected tropical diseases having potential for life-threatening reactivation, such as Chagas disease and strongyloidiasis is not widely implemented. We evaluated the prevalence of these infections among a large cohort of HIV-infected migrants from Latin America living in Italy. Cross-sectional study evaluating the prevalence of Trypanosoma cruzi and Strongyloides stercoralis infections in HIV-infected migrants from Latin America enrolled in the Italian Cohort of Antiretroviral-Naïve patients (ICONA) between 1997 and 2018, based on serology performed on sera stored in the ICONA Foundation biobank. Screening for Chagas disease was performed using two commercial ELISA complemented by commercial Immunoblot and CLIA if discordant. Strongyloidiasis was evaluated using a commercial ELISA. 389 patients were analysed. Fifteen (3.86%) had at least one positive Chagas ELISA test. Prevalence of Chagas disease was 0.5% or 1.29% depending on the confirmatory technique. Serology for strongyloidiasis was positive in 16 (4.11%) patients. Only Nadir CD4+ T cell count was associated with discordant serology for Chagas disease (p = 0.046). The accuracy of seroassays for Chagas disease and strongyloidiasis in HIV-positive patients is unclear. To avoid missing potentially life-threatening infections, we suggest implementing additional diagnostic strategies in at-risk patients with inconclusive serology results. [ABSTRACT FROM AUTHOR]

Mucormycosis is an opportunistic mycosis common in poorly-controlled insulin dependent diabetic patients particularly with ketoacidosis. Fungal osteomyelitis is a life-threatening condition affectation of the nose and paranasal sinuses within the orofacial region. We present a 63-year-old diabetic male patient with maxillary mucormycotic osteomyelitis threatening his better seeing eye and review the clinical symptoms, relevant imaging, and management. We highlight a rare pattern of craniofacial fungal bone infection with maxillary and orbital involvement that ultimately spared the optic nerve. This case report offers the clinician a review of important clinical and diagnostic findings that can help direct the need for orbital exenteration. Maxillary mucormycotic osteomyelitis is an aggressive infection that needs to be addressed promptly to prevent fatal consequences. • Fungal maxillary osteomyelitis must be addressed immediately to avoid compromise of cranial nerves and loss of vision. • An understanding of MRI findings suggesting Mucor orbital involvement is essential to monitoring osteomyelitis progression. • Sparing the orbit near the better-seeing eye is critical to post-recovery quality of life. [ABSTRACT FROM AUTHOR]

Résumé L’aspergillose invasive de localisation cérébrale est une infection rare mais grave. La mortalité reste élevée malgré un traitement adapté. Nous rapportons le cas d’une patiente transplantée hépatique dans un contexte de cirrhose alcoolique et retransplantée sept ans plus tard pour une cholangite ischémique. Dans les suites d’une infection virale active acquise à VHC et traitée par bithérapie antivirale, la patiente a présenté, six mois après cette seconde intervention, une aspergillose cérébrale. La présentation était pseudotumorale, avec une évolution rapidement défavorable avec un tableau d’hypertension intracrânienne. Si la prise en charge thérapeutique est bien établie, le diagnostic reste difficile. Cette observation permet de discuter les différents critères diagnostiques de l’aspergillose cérébrale. Summary Cerebral invasive aspergillosis is a rare but serious infection. Mortality is still high despite appropriate treatment. We report the case of a patient with liver transplantation in the context of alcoholic cirrhosis and transplanted back seven years later consequently to an ischemic cholangitis. Following an acquired active viral infection by HCV and treated by antiviral combination therapy the patient presented six months after this second operation a cerebral aspergillosis of tumour-like presentation. It rapidly evolved to an unfavourable outcome with intracranial hypertension state. If the therapeutic management is well established, the diagnosis is difficult. This observation allows us to discuss the various diagnostic criteria of cerebral aspergillosis. [ABSTRACT FROM AUTHOR]

Summary Objectives To describe the clinical features, treatments, outcomes, and subtype prevalence of cryptococcosis in Singapore. Methods All patients with laboratory confirmed cryptococcal infections admitted from 1999 to 2007 to a teaching hospital in Singapore were reviewed retrospectively. Identification and molecular types of Cryptococcus neoformans variants and Cryptococcus gattii were determined by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Serotypes were inferred with a multiplex PCR method. Results Of 62 patients with cryptococcosis, C. neoformans var. grubii was the predominant subtype (in 95%), affecting mainly immunocompromised hosts (91%) with HIV infection (80%). Patients with HIV were younger (median age 36.5 vs. 49.5 years, p = 0.006) and less likely to present with an altered mental status (14% vs. 50%, p = 0.013). In contrast, delayed treatment (median 7 days vs. 2 days, p = 0.03), pulmonary involvement (58% vs. 14%, p = 0.03), and initial treatment with fluconazole (25% vs. 2%, p = 0.02) were more common in HIV-negative patients. C. gattii was uncommon, affecting only three patients, all of whom were immunocompetent and had disseminated disease with pulmonary and neurological involvement. All C. gattii were RFLP type VG II, serotype B and all C. neoformans var. grubii were RFLP type VN I, serotype A, except for one that was RFLP type VN II. Conclusion C. neoformans var. grubii , subtype VN I, was the predominant subtype in Singapore, infecting younger, mainly immunocompromised hosts with HIV. C. gattii was uncommon, causing pulmonary manifestations in older, immunocompetent patients and were RFLP type VG II. [ABSTRACT FROM AUTHOR]

Background Opportunistic infections (OIs) can be defined as infections in immunosuppressed patients that are more frequent or severe because of immunosuppression. The literature on OIs in pemphigus is sparse. Objective We assessed the incidence, risk factors, and characteristics of OIs in patients with pemphigus. Methods This was a historical prospective study following a cohort of 172 patients with newly diagnosed pemphigus for the development of OIs. Results Fourteen patients developed OIs at a mean of 4 months from the time of diagnosis while taking a mean dose of 0.8 mg/kg/day of prednisone, 5 in conjunction with azathioprine. The risk of developing an OI in the first year after the diagnosis of pemphigus was 9.3%, subsequently dropping to 0. Advanced age and possibly diabetes were found to be risk factors for OI development. Infectious agents included Nocardia, cytomegalovirus, Legionella, and Listeria. Two patients died within 2 months of OI diagnosis, and 2 more had neurologic impairment. Limitations Limitations include the extraction of historical data and the cohort originating from a single geographic region. Conclusion OIs present in a significant number of patients with pemphigus during the first year after the diagnosis of pemphigus, with potential deleterious effects. Older and possibly diabetic patients are at increased risk. Physician vigilance and patient education on limiting pathogen exposure is recommended. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To describe the spectrum of central nervous system (CNS) disorders and the contribution of neurological immune reconstitution inflammatory syndrome (IRIS) in hospitalized HIV/AIDS patients in You'an Hospital, Beijing China. Study design & methods: A retrospective observational study conducted over a 24-month period in You'an Hospial, a public sector referral hospital in Beijing, China. This study enrolled HIV seropositive patients who were admitted for developing new or recurrent neurological and (or) psychiatric symptoms from September 2009 to August 2011. Medical records were reviewed, demographic and clinical data were collected. Patients with peripheral neuropathy and those in delirium were excluded from this study. Results: Of the total 620 HIV/AIDS hospital admissions from September 2009 to August 2011, 60 patients (9.7%) were hospitalized for CNS complications. The diagnosis of HIV infection was made after hospital admission in 16 of the 60 patients (26.7%), and 34 of them (56.7%) were already on antiretroviral therapy (ART) at the point of admission. The median CD4 cell count in these subjects was 39 (21–133) cells/mm3, and 93.3% (56/60) of these patients belonged to stage IV HIV disease according to World Health Organization (WHO) classification. The most frequent diagnosis in these subjects included cryptococcal meningitis (CM, n=13, 22%), cerebral toxoplasmosis (n=10, 17%), and CNS tuberculosis (n=7, 11.7%). The overall mortality was 13% (8/60) and the case-fatality rates were: cryptococcal meningitis 7.7% (1/13), cerebral toxoplasmosis 20% (2/10) and tuberculous meningitis 28.6% (2/7). Of the 34 patients who were on ART, paradoxical neurological IRIS (the conditions of their existing CNS disorders get paradoxically worse after ART because of an exuberant inflammatory response directed towards opportunistic pathogens) was diagnosed in 4 patients (11.8%), 2 of whom related to TB infection (out of 5TB patients, 40%), and the other 2 related to CM (out of 8 patients, 25%). Conclusion: Opportunistic infections, such as cryptococcal meningitis, cerebral toxoplasmosis and CNS tuberculosis were the most frequent diagnosis of CNS disease in hospitalized HIV/AIDS patients in You'an Hospital, Beijing, China. About 10% patients on ART were diagnosed as neurological IRIS in such a group of patients. [Copyright &y& Elsevier]

Highlights: [•] Demonstrated intranasal immunization with a non-adjuvanted MP3. [•] The MP3 could have an ability to bind the ECM in vitro and in vivo. [•] MP3-specific antibody titers exhibited 9 (log2) with 3 or 4 doses in immunized mice. [•] Multiple doses in immunized mice could prevent opportunistic infection. [ABSTRACT FROM AUTHOR]

Abstract: The 3-dimensional quantitative structure–activity relationship (3D-QSAR) molecular modeling technique or comparative molecular field analysis (CoMFA) has been used to design analogs of the natural product cryptolepine (1). Twenty-three compounds with their in vitro biological activities (IC50 values) against Crytococcus neoformans were used to generate the training set database of compounds for the CoMFA studies. The cross-validated q 2, noncross-validated r 2, and partial least squares (PLS) analysis results were used to predict the biological activity of 11 newly designed test set compounds. The best CoMFA model produced a q 2 of 0.815 and an r 2 of 0.976 indicating high statistical significance as a predictive model. The steric and electrostatic contributions from the contour map were interpreted from the color-coded contour plots generated from the PLS model and the active structural components for potency against C. neoformans were determined and validated in the test set compounds. The 3-substituted benzylthio quinolinium salts (4) that make up the test set were synthesized and evaluated based on the predicted activity from the CoMFA model and the results produced a good correlation between the predicted and experimental activity (R =0.82). Thus, CoMFA has served as an effective tool to aid the design of new analogs and in this case, it has aided the identification of compounds equipotent with amphotericin B, the gold standard in antifungal drug design. [Copyright &y& Elsevier]

Abstract: Background: Human cytomegalovirus (HCMV) is an important pathogen in HIV exposed infants with pneumonia. However, the diagnosis of HCMV pneumonia in this setting is challenging due to limited access to bronchoscopy, lung biopsy and direct sampling of the lower respiratory tract. HCMV viraemia is more accessible, but their diagnostic performance in this context has not been studied. Objective: To describe the prevalence of HCMV viraemia and evaluate its clinical utility in HIV exposed infants. Study design: In this cross-sectional study, we performed qualitative and quantitative PCR to detect HCMV viraemia in HIV exposed asymptomatic infants and in infants with severe pneumonia in the Western Cape province of South Africa. Results: 283 asymptomatic HIV exposed infants and 142 HIV exposed infants with severe pneumonia were studied. Infants with pneumonia had a higher prevalence of HCMV viraemia compared to asymptomatic infants (68% vs 24% OR 6.7, 95% CI 4.2–10.8). This increased prevalence remained significant (OR 4.3 95% CI 2.6–7.0) after adjusting for HIV infection. Of the infants with pneumonia, the level of HCMV viraemia was significantly higher in a subset of infants diagnosed with HCMV pneumonia (median HCMV viral load 4.6 vs 2.5 log copies/ml p <0.001). Receiver operator characteristic (ROC) analysis showed the area under the curve was 0.78 (95% CI 0.71–0.86) and a threshold of 4.1 log copies/ml was able to correctly identify 70% of HCMV pneumonia cases. Conclusion: Prevalence and level of HCMV viraemia in sub-Saharan HIV-exposed and infected infants peaks at 3–4 months of age. Quantitative HCMV PCR may be useful in diagnosing HCMV pneumonia. [Copyright &y& Elsevier]

Highlights: [•] HIV-patients with low CD4+ cells may differ in clinical presentation (AIDS/non-AIDS). [•] Non-AIDS patient NK cells show increased expression of NKp46 and NKp30. [•] NK immune activation persists in cART treated patients, both AIDS and non-AIDS. [•] CD4+ T cells in non-AIDS patients have higher potential of interaction with NK cells. [•] Increased activating NK cell receptor–ligand interaction may protect from OI. [Copyright &y& Elsevier]

Abstract: This review will concentrate on commonly encountered infectious diseases in biopsy practice and will consider three scenarios: Firstly, the most frequent, where the biopsy arrives with the infectious disease stated on the request form. Secondly where the patient has a risk factor placing infectious diseases high in the differential diagnosis and, thirdly, where infection is one of several possible aetiologies when a liver biopsy shows a particular pattern of inflammation. [Copyright &y& Elsevier]

Abstract: Background: Myelitis is a rare complication of varicella zoster virus (VZV) infection and is more prevalent in immunocompromised individuals. Clinical features, outcomes, and presentations vary. The aim of the current study was to compare the clinical presentations of our patients with those reported in the literature, and to evaluate the differences in clinical features between immunocompromised and immunocompetent patients. Methods: A review of the literature on VZV myelitis was carried out by searching PUBMED from 1980 to 2012. Clinical features of our cases and those in the literature were compared. Results: There were 5 cases at our hospital and 26 were reported in the literature. Seventeen patients were immunocompromised (54.8%), and most had acquired immune deficiency syndrome (AIDS). Typical presentations (skin lesions followed by myelopathy at the corresponding level) were observed in 14 patients (45.2%). The immunocompromised patients were prone to atypical presentations (p<0.05). Outcomes were good in immunocompetent patients and relatively poor in immunocompromised patients (p<0.05). Anti-herpetic agents had no statistically significant effect on outcomes in immunocompromised patients (p=0.280), but could reduce mortality rate in AIDS patients (p<0.05). Conclusion: Immunocompromised individuals are susceptible to this disease, and prone to atypical presentations and poorer outcomes. Timely recognition and anti-herpes therapy may be beneficial to the outcomes. In the AIDS patients, anti-herpes therapy can reduce mortality effectively. [Copyright &y& Elsevier]

Abstract: Mucormycosis is a fungal infection commonly affecting structures in the head and neck, such as air sinuses, orbit and brain. Common predisposing factors includes diabetes mellitus and immunosuppression, but rarely seen in apparently normal individuals. The infection commonly begins in the nose and paranasal sinuses, and can spread to orbital and intracranial structures either by direct invasion or through the blood vessels. We report a case of primary paranasal mucormycosis in a healthy adult with emphasis on the importance of early recognition and aggressive treatment to reduce the mortality and morbidity. [Copyright &y& Elsevier]