No consensus has previously been formed regarding the types and presentations of infectious pathogens to be considered as 'opportunistic infections' (OIs) within the setting of biologic therapy. We ...systematically reviewed published literature reporting OIs in the setting of biologic therapy for inflammatory diseases. The review sought to describe the OI definitions used within these studies and the types of OIs reported. These findings informed a consensus committee (infectious diseases and rheumatology specialists) in deliberations regarding the development of a candidate list of infections that should be considered as OIs in the setting of biologic therapy. We reviewed 368 clinical trials (randomised controlled/long-term extension), 195 observational studies and numerous case reports/series. Only 11 observational studies defined OIs within their methods; no consistent OI definition was identified across studies. Across all study formats, the most numerous OIs reported were granulomatous infections. The consensus group developed a working definition for OIs as 'indicator' infections, defined as specific pathogens or presentations of pathogens that 'indicate' the likelihood of an alteration in host immunity in the setting of biologic therapy. Using this framework, consensus was reached upon a list of OIs and case-definitions for their reporting during clinical trials and other studies. Prior studies of OIs in the setting of biologic therapy have used inconsistent definitions. The consensus committee reached agreement upon an OI definition, developed case definitions for reporting of each pathogen, and recommended these be used in future studies to facilitate comparison of infection risk between biologic therapies.
Anti-tumour necrosis factor (TNF) monoclonal antibodies or soluble TNF receptors have become an invaluable treatment against chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory ...bowel disease and psoriasis. Individuals who are treated with TNF antagonists are at an increased risk of reactivating latent infections, especially tuberculosis (TB). Following TNF antagonist therapy, the relative risk for TB is increased up to 25 times, depending on the clinical setting and the TNF antagonist used. Interferon-γ release assays or, as an alternative in individuals without a history of bacille Calmette-Guérin vaccination, tuberculin skin testing is recommended to screen all adult candidates for TNF antagonist treatment for the presence of latent infection with Mycobacterium tuberculosis. Moreover, paediatric practice suggests concomitant use of both the tuberculin skin test and an interferon-γ release assay, as there are insufficient data in children to recommend one test over the other. Consequently, targeted preventive chemotherapy is highly recommended for all individuals with persistent M. tuberculosis-specific immune responses undergoing TNF antagonist therapy as it significantly reduces the risk of progression to TB. This TBNET consensus statement summarises current knowledge and expert opinions and provides evidence-based recommendations to reduce the TB risk among candidates for TNF antagonist therapy.
Screening for active tuberculosis (TB) and latent TB infection (LTBI) is mandatory prior to the initiation of tumour necrosis factor-alpha inhibitor therapy. However, no agreement exists on the best ...strategy for detecting LTBI in this population. The aim of the present study was to analyse the performance of the tuberculin skin test (TST) and QuantiFERON-TB Gold in-tube (QFT-GIT) on LTBI detection in subjects with immunomediated inflammatory diseases (IMID). The TST and QFT-GIT were prospectively performed in 398 consecutive IMID subjects, 310 (78%) on immunosuppressive therapy and only 16 (4%) had been bacillus Calmette-Guérin (BCG) vaccinated. Indeterminate results to QFT-GIT were found in five (1.2%) subjects. Overall, 74 (19%) out of 393 subjects were TST-positive and 52 (13%) were QFT-GIT-positive. Concordance between TST and QFT-GIT results was good (87.7%): 13 were QFT-GIT-positive/TST-negative and 35 QFT-GIT-negative/TST-positive. By multivariate analysis both tests were significantly associated with older age. Only the TST was associated with BCG vaccination and radiological lesions of past TB. Use of immunosuppressive drugs differently modulated QFT-GIT or TST scoring. Use of the QuantiFERON-TB Gold in-tube, as a screening tool for latent tuberculosis among immunomediated inflammatory disease subjects, is feasible. Until further data will elucidate discordant tuberculin skin test/QuantiFERON-TB Gold in-tube results, a strategy of simultaneous tuberculin skin and QuantiFERON-TB Gold in-tube testing in a low prevalence bacillus Calmette-Guérin vaccinated population, should maximise potentials of latent tuberculosis diagnosis.
Tuberculous peritonitis is an uncommon disease in countries with low tuberculosis (TB) incidence, most often affecting non-white race, foreign-born individuals. We describe a case of TB with ...peritoneal involvement in a 32-year-old man immigrated to Italy from Burkina Faso, who presented with a history of fever, malaise, abdominal pain and abdominal swelling. Due to its nonspecific clinical presentation and paucibacillary nature, diagnosis of tuberculous peritonitis can be challenging, and requires a high index of suspicion. This report highlights the diagnostic challenges posed by tuberculous peritonitis and emphasizes the importance of imaging (computed tomography, CT) in identifying typical findings, and the value of histological examination of tissue specimens from peritoneum or any site of suspected TB as a tool for diagnosis confirmation.
The use of biological agents has grown exponentially in immune-mediated inflammatory diseases (IMID), often achieving a good control of disease progression and improving patients' quality of life. ...However, their use resulted in an increased risk of adverse events, including reactivation of chronic/latent infectious diseases. As for the risk of Cytomegalovirus (CMV) reactivation, very few data are available. We reviewed the literature reporting cases of CMV infection in IMID patients during biological therapy. Although the risk of CMV reactivation cannot be excluded, we concluded that there is no evidence to warrant CMV screening before starting a biological agent.
Previous studies on commensal Escherichia coli from healthy children in the Bolivian Chaco have shown remarkable resistance rates to the old antibiotics since the early 1990s, and the emergence of ...resistance to newer drugs (fluoroquinolones and expanded-spectrum cephalosporins) in the 2000s. Here we report the results of a new survey conducted in 2011 in the same setting. Rectal swabs were obtained from 482 healthy children (aged 6-72months) from three urban areas of the Bolivian Chaco. Screening for antibiotic-resistant E. coli was performed by a direct plating method, as in the previous studies. The blaCTX-M genes were investigated by PCR/sequencing, and CTX-M-producing isolates were subjected to genotyping and detection of several plasmid-mediated quinolone resistance mechanisms. Results showed high rates of resistance to nalidixic acid (76%), ciprofloxacin (44%) and expanded-spectrum cephalosporins (12.4%), demonstrating a relentless increase of resistance to those drugs over the past two decades. CTX-M-type extended-spectrum beta-lactamases were found to be widespread (12%, 97% of extended-spectrum beta-lactamase producers). Compared with the previous studies, CTX-M-producing E. coli underwent a dramatic dissemination (120-fold increase since early 2000s) and a radical change of dominant CTX-M groups (CTX-M-1 and CTX-M-9 groups versus CTX-M-2 group). Most CTX-M producers were not susceptible to quinolones (91%), and 55% carried plasmid-mediated quinolone resistance genes (different combinations of aac(6')-Ib-cr, qnrB and qepA). This study shows the rapid and remarkable increasing trend for resistance to fluoroquinolones and expanded-spectrum cephalosporins in one of the poorest regions of Latin America, and underscores the need for urgent control strategies aimed at preserving the efficacy of those drugs in similar settings.
The diseases caused by non-tuberculous mycobacteria (NTM), in both AIDS and non-AIDS populations, are increasingly recognized worldwide. Although the American Thoracic Society published the ...guidelines for diagnosis of NTM pulmonary disease (NTM-PD), the diagnosis is still difficult. In the first part of the study, we collected data on NTM isolates in the Mycobacteriology Laboratory of Careggi Hospital (Florence, Italy) and analysed the epidemiological data of NTM isolates. Then, to analyse the risk factors associated to NTM-PD, we studied the presence of ATS/IDSA criteria for NTM-PD in patients who had at least one positive respiratory sample for NTM and were admitted to the Infectious Disease Unit and the Section of Respiratory Medicine. We selected 88 patients with available full clinical data and, according to ATS/IDSA criteria, classified 15 patients (17%) as NTM-PD cases and 73 as colonized patients (83%). When comparing colonized and NTM-PD patients we did not find significant differences of age, gender and comorbidity. We observed that Mycobacterium avium and M. intracellulare were statistically associated with NTM-PD (P = 0·001) whereas M. xenopi was statistically associated with colonization. Although the number of studied patients is limited, our study did not identify risk factors for NTM-PD that could help clinicians to discriminate between colonization and disease. We underline the need of close monitoring of NTM-infected patients until the diagnosis is reasonably excluded. Further larger prospective studies and new biological markers are needed to identify new useful tools for the diagnosis of NTM-PD.
The use of biological agents in the treatment of rheumatic diseases has been widely associated with an increased risk of reactivation of several latent infections. National and international ...guidelines recommend screening for infectious diseases before starting these drugs. In Western countries screening is limited to latent tuberculosis infection, HIV and viral hepatitis. However, the increasing globalisation and the remarkable number of migrating and travelling people worldwide make this approach no longer adequate. The Italian and Spanish Societies of Rheumatology and Tropical Medicine wish to issue a warning about the need to improve awareness of doctors about the risk of reactivation of infectious tropical diseases in migrant or travelling patients who undergo biological therapy. Thus, the Italian and Spanish Societies are now planning to issue specific recommendations, based on a multidisciplinary contribution and a systematic review of the literature, for screening and follow-up of active and latent chronic infections in candidate patients for biological agents, taking into account the patient's area of origin and risk of infectious diseases.
Chagas disease, a neglected tropical disease that due to population movements is no longer limited to Latin America, threatens a wide spectrum of people(travellers, migrants, blood or organ ...recipients,newborns, adoptees) also in non-endemic countries where it is generally underdiagnosed. In Italy, the available epidemiological data about Chagas disease have been very limited up to now, although the country is second in Europe only to Spain in the number of residents from Latin American. Among 867 at-risk subjectsscreened between 1998 and 2010, the Centre for Tropical Diseases in Negrar (Verona) and the Infectious and Tropical Diseases Unit, University of Florence found 4.2% patients with positive serology for Chagas disease (83.4% of them migrants, 13.8% adoptees).No cases of Chagas disease were identified in blood donors or HIV-positive patients of Latin American origin. Among 214 Latin American pregnant women,three were infected (resulting in abortion in one case).In 2005 a case of acute Chagas disease was recorded in an Italian traveller. Based on our observations, we believe that a wider assessment of the epidemiological situation is urgently required in our country and public health measures preventing transmission and improving access to diagnosis and treatment should be implemented.
To describe the health-seeking behaviour and use of antibiotics in the urban community of Yurimaguas in the Amazonian area of Peru. Cross-sectional survey of caregivers of 798 children aged 6-72 ...months by interview using a semi-structured questionnaire. Reported symptoms were classified as illnesses where antibiotics would or would not be recommended based on principles of the integrated management of childhood illnesses algorithm. Forty-one per cent of consultations were with health care professionals; 71% of antibiotics were obtained through the formal public health sector and prescribed mainly by medical doctors. All prescribed antibiotics were on the Peruvian essential drugs list. When prescribing, doctors and nurses hardly discriminated between illnesses where antibiotic treatment was or was not indicated; there was no significant difference in antibiotic prescribing rates between the two (doctors, P = 0.24; nurses, P = 0.32). Not all caregivers sought help for children with severe symptoms. Although most of the antibiotics were prescribed by doctors and nurses, they were commonly prescribed for illnesses where they were not indicated. The use of antibiotics needs to be rationalized, and barriers to health care must be overcome.
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