Background. Alemtuzumab is being increasingly used for the prevention and/or treatment of acute allograft rejection in organ transplant recipients. We assessed the risks of infection in, to our ...knowledge, the largest cohort and broadest range of organ transplant recipients yet reported to have received alemtuzumab. Methods. All patients who received alemtuzumab from September 2002 through March 2004, either as induction therapy at the time of transplantation or for the treatment of rejection, were evaluated for the development of an opportunistic infection (OI) until death or for 12 months after receipt of the last dose of alemtuzumab. Results. A total of 547 recipients were included, 65% of whom received alemtuzumab for induction therapy only. Overall, 56 recipients (10%) developed 62 OIs, including cytomegalovirus disease (n = 16), BK virus infection (n = 12), posttransplantation lymphoproliferative disease (n = 5), human herpesvirus 6 infection (n = 1), parvovirus infection (n = 1), esophageal candidiasis (n = 12), cryptococcosis (n = 2), invasive mold infection (n = 4), Nocardia infection (n = 4), mycobacterial infection (n = 3), Balamuthia mandrillaris infection (n = 1), and toxoplasmosis (n = 1). Patients who received alemtuzumab for induction therapy were significantly less likely to develop an OI, compared with patients who received alemtuzumab for rejection therapy (4.5% vs. 21%; P < .001). Independent predictors of the development of an OI were administration of alemtuzumab for rejection therapy (odds ratio OR, 3.5; 95% confidence interval CI, 1.8–6.8; P < .001), allograft failure (OR, 2.1; 95% CI, 1.1–4.4; P = .04), and receipt of a lung transplant (OR, 3.7; 95% CI, 1.7–8.0; P = .001) or an intestinal transplant (OR, 8.3; 95% CI, 3.5–19.5; P < .001). Conclusions. Patients who received alemtuzumab for the treatment of allograft rejection were significantly more likely to develop an OI, compared with patients who received alemtuzumab for induction therapy only. Such data have implications for new antimicrobial prophylactic strategies.
September 2012 marked the beginning of the largest reported outbreak of infections associated with epidural and intra-articular injections. Contamination of methylprednisolone acetate with the black ...mold, Exserohilum rostratum, was the primary cause of the outbreak, with >13,000 persons exposed to the potentially contaminated drug, 741 confirmed drug-related infections, and 55 deaths. Fatal meningitis and localized epidural, paraspinal, and peripheral joint infections occurred. Tissues from 40 laboratory-confirmed cases representing these various clinical entities were evaluated by histopathological analysis, special stains, and IHC to characterize the pathological features and investigate the pathogenesis of infection, and to evaluate methods for detection of Exserohilum in formalin-fixed, paraffin-embedded (FFPE) tissues. Fatal cases had necrosuppurative to granulomatous meningitis and vasculitis, with thrombi and abundant angioinvasive fungi, with extensive involvement of the basilar arterial circulation of the brain. IHC was a highly sensitive method for detection of fungus in FFPE tissues, demonstrating both hyphal forms and granular fungal antigens, and PCR identified Exserohilum in FFPE and fresh tissues. Our findings suggest a pathogenesis for meningitis involving fungal penetration into the cerebrospinal fluid at the injection site, with transport through cerebrospinal fluid to the basal cisterns and subsequent invasion of the basilar arteries. Further studies are needed to characterize Exserohilum and investigate the potential effects of underlying host factors and steroid administration on the pathogenesis of infection.
Summary Several countries have seen rising frequencies of mucormycosis among patients with haematological disorders, malignancies, or diabetes mellitus, and among transplant recipients. Growing ...numbers of immunocompromised hosts, widespread use of antifungal agents inactive against mucormycosis, or other unidentified factors, could be contributing to this situation. The predominant clinical manifestations of mucormycosis vary from host to host. Additionally, risk factors specific to different subgroups have been identified, such as leukaemia, allogeneic haemopoietic stem-cell transplant, voriconazole prophylaxis, diabetes, and malnutrition. We summarise the current state of knowledge of characteristics and risk factors and discuss topical developments in therapeutic methods and strategies in the management of mucormycosis.
Basidiobolomycosis of the colon is a very rare fungal infection disease. We report here primary colonic Basidiobolomycosis as the first female case in Iraq. A 48 years old Insulin dependent diabetic ...patient presented with abdominal pain , right side abdominal mass and weight loss for few months duration. CT scan revealed caecal wall thickening without intestinal obstruction. Colonoscopy revealed large fungative ulcerated mass in caecum but the mucosal biopsy was negative for malignancy and in favour of chronic inflammation .Laparotomy with right hemicolectomy and ilio-transverse anastomosis done. Histopathological examination of the excised specimen prove Basidiobolomycosis of colon for which she received 6 months course of oral Itraconazole . She recovered well from the disease with no sequela or recurrence .
Fungal infections remain a significant global health problem in humans. Fungi infect millions of people worldwide and cause from acute superficial infections to life-threatening systemic disease to ...chronic illnesses. Trying to decipher the complex innate and adaptive immune mechanisms that protect humans from pathogenic fungi is therefore a key research goal that may lead to immune-based therapeutic strategies and improved patient outcomes. In this review, we summarize how the cells and molecules of the innate immune system activate the adaptive immune system to elicit long-term immunity to fungi. We present current knowledge and exciting new advances in the context of organ-specific immunity, outlining the tissue-specific tropisms for the major pathogenic fungi of humans, the antifungal functions of tissue-resident myeloid cells, and the adaptive immune responses required to protect specific organs from fungal challenge.
Summary
Antifungal prophylaxis during treatment for haematological malignancies has been studied for 50 years, yet it has not been wholly effective even when using antifungal drugs that exhibit ...potent activity in vitro against a broad range of fungal pathogens. Trials have demonstrated that it can reduce the incidence of invasive fungal diseases (IFD) and fungal deaths, but only two studies have had an impact on overall mortality. Furthermore, it has not significantly reduced the need for empirical antifungal therapy. Posaconazole was effective in preventing invasive aspergillosis in two studies of high‐risk patients, and consensus guidelines grade it as a suitable choice for antifungal prophylaxis of invasive mould disease; however, its bioavailability was compromised by vomiting or diarrhoea so that an alternative parenteral antifungal drug was required. A recent trial of voriconazole prophylaxis after allogeneic stem cell transplantation failed to show superiority over fluconazole. With more accurate definitions of IFD, that utilize fungal biomarkers, such as galactomannan, together with computerized tomographic imaging, there is growing interest in a diagnostic‐driven strategy, which could prove to be a more efficacious approach.
Immune response to fungal infections Blanco, Jose L.; Garcia, Marta E.
Veterinary immunology and immunopathology,
09/2008, Letnik:
125, Številka:
1
Journal Article
Recenzirano
The immune mechanisms of defence against fungal infections are numerous, and range from protective mechanisms that were present early in evolution (innate immunity) to sophisticated adaptive ...mechanisms that are induced specifically during infection and disease (adaptive immunity). The first-line innate mechanism is the presence of physical barriers in the form of skin and mucous membranes, which is complemented by cell membranes, cellular receptors and humoral factors. There has been a debate about the relative contribution of humoral and cellular immunity to host defence against fungal infections. For a long time it was considered that cell-mediated immunity (CMI) was important, but humoral immunity had little or no role. However, it is accepted now that CMI is the main mechanism of defence, but that certain types of antibody response are protective. In general, Th1-type CMI is required for clearance of a fungal infection, while Th2 immunity usually results in susceptibility to infection. Aspergillosis, which is a disease caused by the fungus
Aspergillus, has been the subject of many studies, including details of the immune response. Attempts to relate aspergillosis to some form of immunosuppression in animals, as is the case with humans, have not been successful to date. The defence against
Aspergillus is based on recognition of the pathogen, a rapidly deployed and highly effective innate effector phase, and a delayed but robust adaptive effector phase.
Candida albicans, part of the normal microbial flora associated with mucous surfaces, can be present as congenital candidiasis or as acquired defects of cell-mediated immunity. Resistance to this yeast is associated with Th1 CMI, whereas Th2 immunity is associated with susceptibility to systemic infection. Dermatophytes produce skin alterations in humans and other animals, and the essential role of the CMI response is to destroy the fungi and produce an immunoprotective status against re-infection. The resolution of the disease is associated with a delayed hypersensitive response. There are many effective veterinary vaccines against dermatophytoses.
Malassezia pachydermatis is an opportunistic yeast that needs predisposing factors to cause disease, often related to an atopic status in the animal. Two species can be differentiated within the genus
Cryptococcus with immunologic consequences:
C. neoformans infects predominantly immunocompromised hosts, and
C. gattii infects non-immunocompromised hosts.
Pneumocystis is a fungus that infects only immunosupressed individuals, inducing a host defence mechanism similar to that induced by other fungal pathogens, such as
Aspergillus.
Smooth newts (Lissotriton vulgaris) established recently in Melbourne, Australia. Previously, the population's disease status was unknown. Samples from 34 adults and 78 larvae, collected 2011–16, ...were tested for two pathogens driving the global amphibian extinction crisis. The fungus Batrachochytrium dendrobatidis was identified (6.3% quantitative PCR positive); ranaviruses were not detected.
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