Pneumocystis jirovecii has gained attention during the last decade in the context of the AIDS epidemic and the increasing use of cytotoxic and immunosuppressive therapies. This article summarizes ...current knowledge on biology, pathophysiology, epidemiology, diagnosis, prevention, and treatment of pulmonary P jirovecii infection, with a particular focus on the evolving pathophysiology and epidemiology. Pneumocystis pneumonia still remains a severe opportunistic infection, associated with a high mortality rate.
Legionnaire's Disease in Compromised Hosts Lanternier, Fanny; Ader, Florence; Pilmis, Benoit ...
Infectious disease clinics of North America,
03/2017, Letnik:
31, Številka:
1
Journal Article
Recenzirano
Legionnaire's disease (LD) is mainly reported in apparently immunocompetent patients. Among them, risk factors include chronic lung disease and smoking. However, LD is also well reported among ...immunocompromised patients, particularly those treated with anti-tumor necrosis factor alpha therapy, patients with hematological malignancy, and transplant patients. This article discusses the available data on immunity against Legionella spp, epidemiology, clinical presentation, diagnosis, and treatment of LD in immunocompromised patients.
Background Ataxia-telangiectasia (A-T) is a rare genetic disease caused by germline biallelic mutations in the ataxia-telangiectasia mutated gene (ATM) that result in partial or complete loss of ATM ...expression or activity. The course of the disease is characterized by neurologic manifestations, infections, and cancers. Objective We studied A-T progression and investigated whether manifestations were associated with the ATM genotype. Methods We performed a retrospective cohort study in France of 240 patients with A-T born from 1954 to 2005 and analyzed ATM mutations in 184 patients, along with neurologic manifestations, infections, and cancers. Results Among patients with A-T, the Kaplan-Meier 20-year survival rate was 53.4%; the prognosis for these patients has not changed since 1954. Life expectancy was lower among patients with mutations in ATM that caused total loss of expression or function of the gene product (null mutations) compared with that seen in patients with hypomorphic mutations because of earlier onset of cancer (mainly hematologic malignancies). Cancer (hazard ratio, 2.7; 95% CI, 1.6-4.5) and respiratory tract infections (hazard ratio, 2.3; 95% CI, 1.4-3.8) were independently associated with mortality. Cancer (hazard ratio, 5.8; 95% CI, 2.9-11.6) was a major risk factor for mortality among patients with null mutations, whereas respiratory tract infections (hazard ratio, 4.1; 95% CI, 1.8-9.1) were the leading cause of death among patients with hypomorphic mutations. Conclusion Morbidity and mortality among patients with A-T are associated with ATM genotype. This information could improve our prognostic ability and lead to adapted therapeutic strategies.
Background Mastocytosis is a heterogeneous disease characterized by mast cell accumulation in 1 or more organs. Gastrointestinal manifestations of systemic mastocytosis have been previously studied ...in small cohorts of patients, and no specific histologic description is available. Objective We sought to assess the clinical and pathologic features of gastrointestinal manifestations in patients with mastocytosis. Methods Medical history and gastrointestinal symptoms of patients with mastocytosis (n = 83) were compared with those of matched healthy subjects (n = 83) by means of patient questionnaire. Data were analyzed for epidemiologic, clinical, biological, and genetic factors associated with gastrointestinal symptoms for patients with mastocytosis. A comparative analysis of gastrointestinal histology from patients with mastocytosis (n = 23), control subjects with inflammatory bowel disease (n = 17), and healthy subjects (n = 19) was performed. Results The following gastrointestinal symptoms occurred more frequently and were more severe in patients with mastocytosis than in healthy subjects: bloating (33% vs 7.2%, P < .0001), abdominal pain (27.3% vs 4.8%, P < .0001), nausea (23% vs 8.4%, P = .02), and diarrhea (33.85% vs 1.2%, P < .0001). Patients with mastocytosis had a significantly higher incidence of personal history of duodenal ulcer ( P = .02). Wild-type (WT) c-Kit was associated with diarrhea ( P = .03). Specific histologic lesions were present in patients with mastocytosis but were not correlated with clinical symptoms. Conclusion Gastrointestinal manifestations in patients with mastocytosis are highly prevalent and often severe. Clinical symptoms do not correspond to histologic findings, are nonspecific, and can simulate irritable bowel syndrome.
Objective Our objective was to describe the incidence and risk factors of legionellosis associated with tumor necrosis factor (TNF)-α antagonist use. Methods From February 1, 2004, to January 31, ...2007, we prospectively collected all cases of legionellosis among French patients receiving TNF-α antagonists in the Research Axed on Tolerance of Biotherapies (RATIO) national registry. We conducted an incidence study with the French population as a reference and a case-control analysis with four control subjects receiving TNF-α antagonists per case of legionellosis. Results Twenty-seven cases of legionellosis were reported. The overall annual incidence rate of legionellosis for patients receiving TNF-α antagonists, adjusted for age and sex, was 46.7 (95% CI, 0.0-125.7) per 100,000 patient-years. The overall standardized incidence ratio (SIR) was 13.1 (95% CI, 9.0-19.1; P < .0001) and was higher for patients receiving infliximab (SIR, 15.3 95% CI, 8.5-27.6; P < .0001) or adalimumab (SIR, 37.7 95% CI, 21.9-64.9; P < .0001) than etanercept (SIR, 3.0 95% CI, 1.00-9.2; P = .06). In the case-control analysis, exposure to adalimumab (OR, 8.7 95% CI, 2.1-35.1) or infliximab (OR, 9.2 95% CI, 1.9-45.4) vs etanercept was an independent risk factor for legionellosis. Conclusions The incidence rate of legionellosis for patients receiving TNF-α antagonists is high, and the risk is higher for patients receiving anti-TNF-α monoclonal antibodies than soluble TNF-receptor therapy. In case of pneumonia occurring during TNF-α antagonist therapy, specific urine antigen detection should be performed and antibiotic therapy should cover legionellosis. Trial registry ClinicalTrials.gov ; No.: NCT00224562 ; URL: www.clinicaltrials.gov
Background Primary immunoglobulin deficiencies lead to recurrent bacterial infections of the respiratory tract and bronchiectasis, even with adequate immunoglobulin replacement therapy. It is not ...known whether patients able to secrete IgM (eg, those with hyper-IgM HIgM syndrome) are as susceptible to these infections as patients who lack IgM production (eg, those with panhypogammaglobulinemia PHG). Objective This study is aimed at identifying specific microbiological and clinical (infections) characteristics that distinguish immunoglobulin-substituted patients with PHG from patients with HIgM syndrome. Methods A cohort of patients with HIgM syndrome (n = 25) and a cohort of patients with PHG (n = 86) were monitored prospectively for 2 years while receiving similar polyvalent immunoglobulin replacement therapies. Regular bacterial analyses of nasal swabs and sputum were performed, and clinical events were recorded. In parallel, serum and saliva IgM antibody concentrations were measured. Results When compared with patients with PHG, patients with HIgM syndrome were found to have a significantly lower risk of nontypeable Haemophilus influenzae carriage in particular (relative risk, 0.39; 95% CI, 0.21-0.63). Moreover, patients with HIgM syndrome (including those unable to generate somatic hypermutations of immunoglobulin genes) displayed anti–nontypeable H influenzae IgM antibodies in their serum and saliva. Also, patients with HIgM syndrome had a lower incidence of acute respiratory tract infections. Conclusions IgM antibodies appear to be microbiologically and clinically protective and might thus attenuate the infectious consequences of a lack of production of other immunoglobulin isotypes in patients with HIgM syndrome. Polyvalent IgG replacement therapy might not fully compensate for IgM deficiency. It might thus be worth adapting long-term antimicrobial prophylactic regimens according to the underlying B-cell immunodeficiency phenotype.
We sought to determine whether invasive aspergillosis (IA) during the first year after lung transplantation increased the risk of chronic lung allograft dysfunction (CLAD).
We retrospectively ...reviewed the records of 191 patients who underwent lung transplantation at our institution between January 2013 and December 2017. Screening for
was with bronchial aspirates, bronchoalveolar lavage if indicated or during surveillance bronchoscopy, radiography, and computed tomography. We used Fine and Gray multivariable regression to identify potential risk factors for CLAD.
During the first posttransplant year, 72 patients had at least 1 deep-airway sample positive for
; 63 were classified as having IA and were included in the study. Median number of endoscopies per patient during the first year was 9 (range, 1-44). Median time from transplantation to first
-positive sample was 121 d. Bronchial aspirate samples and bronchoalveolar lavage fluid were positive in 71 and 44 patients, respectively.
(n = 36, 50%) predominated; bacterial samples were also positive in 22 (31%) patients. IA within 4 mo after transplantation was independently associated with CLAD development (subdistribution hazard ratio, 3.75; 95% confidence interval CI, 1.61-8.73;
< 0.01) by regression analysis. Survival at 3 and 5 y conditional on 1-y CLAD-free survival was 37% (95% CI, 24%-58%), and 24% (95% CI, 11%-52%) in the IA <4 mo group compared to 65% (95% CI, 57%-73%) and 54% (95% CI, 43%-66%) in the non-IA group and to 69% (95% CI, 58%-83%) and 54% (95% CI, 35%-82%) in the IA ≥4 mo group, respectively (
< 0.01, logrank test).
Our evaluation of de novo IA showed that this infection was most strongly associated with CLAD when found within 4 mo after transplantation.
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