Cândida Abreu

Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease

The treatment of inflammatory bowel disease (IBD) has been revolutionised over the past decade by the increasing use of immunomodulators, mainly azathioprine (AZA)/6-mercaptopurine (6-MP) and methotrexate (MTX), together with the advent of biological therapy. Immunomodulators are being used more often and earlier in the course of the disease.1 The introduction of biologic agents, especially inhibitors of the key proinflammatory cytokine, tumor necrosis factor alpha (TNF-α) initiated a new therapeutic era, whose use has grown continuously since their introduction in 1998.2 With such immunomodulation, the potential for opportunistic infection is a key safety concern for patients with IBD. Opportunistic infections pose particular problems for the clinician: they are often difficult to recognise and are associated with appreciable morbidity or mortality, because they are potentially serious and hard to treat effectively. Enhancing awareness and improving the knowledge of gastroenterologists about opportunistic infections are important elements to optimise patient outcomes through the development of preventive or early diagnostic strategies. A long list of opportunistic infections has been described in patients with IBD. Many questions remain unanswered, not only concerning the need for screening, preventive measures or the best diagnostic approach, but also on appropriate treatment and management of immunomodulator therapy once infection occurs. This led the European Crohns and Colitis Organisation (ECCO) to establish a Consensus meeting on opportunistic infections in IBD. The formal process of a Consensus meeting has been described,3 but the purpose is to quantify expert opinion in the context of a systematic review of existing evidence. To organise the work, infections were classified into six major topics (see plan). Specific questions were asked for each infectious agent. The different topics were distributed to working groups that comprised junior and senior gastroenterologists with infectious disease experts. Each group performed a systematic review of the literature and answered …

Severe imported malaria in an intensive care unit: a review of 59 cases

BackgroundIn view of the close relationship of Portugal with African countries, particularly former Portuguese colonies, the diagnosis of malaria is not a rare thing. When a traveller returns ill from endemic areas, malaria should be the number one suspect. World Health Organization treatment guidelines recommend that adults with severe malaria should be admitted to an intensive care unit (ICU).MethodsSevere cases of malaria in patients admitted to an ICU were reviewed retrospectively (1990-2011) and identification of variables associated with in-ICU mortality performed. Malaria prediction score (MPS), malaria score for adults (MSA), simplified acute physiology score (SAPSII) and a score based on WHOs malaria severe criteria were applied. Statistical analysis was performed using StataV12.ResultsFifty nine patients were included in the study, all but three were adults; 47 (79,6%) were male; parasitaemia on admission, quantified in 48/59 (81.3%) patients, was equal or greater than 2% in 47 of them (97.9%); the most common complications were thrombocytopaenia in 54 (91.5%) patients, associated with disseminated intravascular coagulation (DIC) in seven (11.8%), renal failure in 31 (52.5%) patients, 18 of which (30.5%) oliguric, shock in 29 (49.1%) patients, liver dysfunction in 27 (45.7%) patients, acidaemia in 23 (38.9%) patients, cerebral dysfunction in 22 (37.2%) patients, 11 of whom with unrousable coma, pulmonary oedema/ARDS in 22 (37.2%) patients, hypoglycaemia in 18 (30.5%) patients; 29 (49.1%) patients presented five or more dysfunctions. The case fatality rate was 15.2%. Comparing the four scores, the SAPS II and the WHO score were the most sensitive to death prediction. In the univariate analysis, death was associated with the SAPS II score, cerebral malaria, acute renal and respiratory failure, DIC, spontaneous bleeding, acidosis and hypoglycaemia. Age, partial immunity to malaria, delay in malaria diagnosis and the level of parasitaemia were not associated with death in this cohort.ConclusionSevere malaria cases should be continued monitored in the ICUs. SAPS II and the WHO score are good predictors of mortality in malaria patients, but other specific scores deserve to be studied prospectively.

Tuberculosis in anti-TNF-α treated patients remains a problem in countries with an intermediate incidence: Analysis of 25 patients matched with a control population

BACKGROUND AND AIMS An increased incidence of tuberculosis (TB) in patients under anti-TNF-α therapy has been reported, but outcome compared with TB in the general population are unknown. METHODS Patients who had active tuberculosis while taking anti-TNF-α drugs were studied and compared with a control group of community-acquired TB matched for sex, age and data of TB. RESULTS Twenty-five cases of TB were reported from a cohort of 765 patients under anti-TNF-α from 2001 to 2012. The incidence of TB per 100,000 patient-years was estimated to be 1337, 792 and 405 respectively for those on infliximab, adalimumab and etanercept. Twelve patients had inflammatory bowel disease, ten had rheumatologic diseases and three had psoriasis. From the 17 patients screened for latent TB before anti-TNF-α, three were treated with isoniazid. TB was diagnosed 1-108 months after starting anti-TNF-α, being the median time six, seven and 89 months respectively for those on infliximab, adalimumab and etanercept. Sixty per cent of the cases had extra-pulmonary TB. No deaths occurred in the case groups, while two died in control TB patients. Patients on anti-TNF-α drugs had more frequent extra-pulmonary TB, fever on presentation, higher mean C-reactive protein and lower positive rate of acid-fast bacilli. CONCLUSIONS TB may still occur in those with negative testing, some of them probably representing new infections instead of reactivations. Three out of 25 patients had TB in spite of previously treated LTB, although, the outcome of TB was not worse than in the general population.

Listeria infection in patients on anti-TNF treatment: Report of two cases and review of the literature

Listeria monocytogenes is an aerobic gram positive intracellular bacillus, predominantly affecting pregnant women, immunocompromised patients and old individuals. Invasive listeriosis, meningitis and meningoencephalitis, bacteraemia with or without joint, eye or heart focalization are clinical manifestations of the disease. Anti-TNF-α drugs blocking the hosts response against various microorganisms, particularly intracellular agents like Listeria monocytogenes, increase the risk of disease. We report two cases of L. monocytogenes meningitis in ulcerative colitis patients under infliximab plus steroids. One patient is HIV-1 infected. A review of reported invasive listeriosis cases under anti-TNF drugs is also showed.

Nocardia infections among immunomodulated inflammatory bowel disease patients: A review

Human nocardiosis, caused by Nocardia spp., an ubiquitous soil-borne bacteria, is a rare granulomatous disease close related to immune dysfunctions. Clinically can occur as an acute life-threatening disease, with lung, brain and skin being commonly affected. The infection was classically diagnosed in HIV infected persons, organ transplanted recipients and long term corticosteroid treated patients. Currently the widespread use of immunomodulators and immunossupressors in the treatment of inflammatory diseases changed this scenario. Our purpose is to review all published cases of nocardiosis in immunomodulated patients due to inflammatory diseases and describe clinical and laboratory findings. We reviewed the literature concerning human cases of nocardiosis published between 1980 and 2014 in peer reviewed journals. Eleven cases of nocardiosis associated with anti-tumor necrosis factor (TNF) prescription (9 related with infliximab and 2 with adalimumab) were identified; 7 patients had inflammatory bowel disease (IBD), 4 had rheumatological conditions; nocardia infection presented as cutaneous involvement in 3 patients, lung disease in 4 patients, hepatic in one and disseminated disease in 3 patients. From the 10 cases described in IBD patients 7 were associated with anti-TNF and 3 with steroids and azathioprine. In conclusion, nocardiosis requires high levels of clinical suspicion and experience of laboratory staff, in order to establish a timely diagnosis and by doing so avoid worst outcomes. Treatment for long periods tailored by the susceptibility of the isolated species whenever possible is essential. The safety of restarting immunomodulators or anti-TNF after the disease or the value of prophylaxis with cotrimoxazole is still debated.

Disseminated cutaneous herpes simplex infection in a patient with Crohn's disease under azathioprine and steroids: First case report and literature review

Immunosuppressive treatments used in the management of Inflammatory Bowel Disease, namely steroids, thiopurines and anti-TNF drugs, raise the risk of acquiring opportunistic infections. However, most of these infections are mild and self-limited, not requiring specific therapy or suspension of the immunosuppressors. We report a case of disseminated cutaneous herpes simplex infection in a patient with Crohns disease under steroids and azathioprine.

Angola's 2013 dengue outbreak: clinical, laboratory and molecular analyses of cases from four Portuguese institutions.

INTRODUCTION Dengue virus (DENV) is the arbovirus with the widest impact on human health. In Africa in general, and in Angola in particular, the epidemiology and public health impact of DENV is far from clear. However, rapid population growth, unplanned urbanization, increased international travel, and the presence of virus major vector (Aedes aegypti) in the country suggest that DENV transmission may occur. METHODOLOGY In parallel to the occurrence of a dengue outbreak affecting the capital of Angola, between March and July 2013 four Portuguese institutions diagnosed dengue infection in 146 individuals returning to Portugal. Clinical presentation, laboratory findings, and molecular analyses of partial viral genomic segments were performed. RESULTS The mean age of the individuals included in this study was 42 years old, the majority being men of Portuguese nationality, reporting various lengths of stay in Angola. Fever was the most reported clinical sign, being frequently associated (61.0%) with myalgia and headache. Hematological values, including hematocrit, white-blood cell and platelets counts, correlated with the absence of severe or complicated cases, or coagulation disorders. No deaths were observed. Viral NS1 was detected in 56.2% of the samples, and all NS1 negative cases had anti-dengue IgM antibodies. RT-PCR indicated the presence of DENV1, which was confirmed by phylogenetic analysis of 25 partial NS5 viral sequences. CONCLUSION The DENV cases analyzed conformed to classical and uncomplicated dengue, caused by the suggested exclusive circulation of a genetically homogeneous DENV1 of genotype III, apparently with a single origin.

Immunisations in Crohn's disease: Who? Why? What? When?

Immunosuppression induced by drugs increase the risk of infections in Crohns disease (CD) patients. The vaccination rate in CD patients is usually low due to inaccurate information concerning the safety and efficacy of vaccines. Vaccines and immunoglobulins, are artificial ways of protection from common infectious diseases and they have had a major effect on mortality. Herein we detail the need of protection induced by vaccines of measles, varicella, Zoster, papillomavirus, shingles, pneumococcal invasive disease, influenza, hepatitis A and B in CD at diagnosis and during the course of the disease even during immunosuppression periods but with different singularities. Vaccination in CD travellers and the matters related to immunization of household healthy members of immunosuppressed patients are also discussed.

Serial Tuberculosis Screening in Inflammatory Bowel Disease Patients Receiving Anti-TNFα Therapy

Background and Aims One of the adverse effects of the tumour necrosis factor alpha [[TNFα] monoclonal antibodies for the treatment of immune-mediated inflammatory diseases is a higher propensity for tuberculosis development. The aim of this study was to explore the utility and sensitivity of serial tuberculosis screening during anti-TNFα treatment. Methods A cohort of 46 inflammatory bowel disease patients receiving infliximab was prospectively recruited and followed for 26 months. During this period of time, a tuberculosis skin test and two different interferon ϒ release assays [QFT-GIT and T-SPOT.TB] were applied at 4-6-month intervals. Results Overall, 16 patients were diagnosed with latent tuberculosis infection after having at least one test conversion: 12 patients had a positive tuberculosis skin test, seven patients had a positive T-SPOT.TB, and two patients had a positive QFT-GIT. Active tuberculosis was excluded in all; 15 were treated with isoniazid. A comparison between tests showed a moderate accuracy [72% to 85%] but low kappa values [0.063 to 0.377]. Concerning association with demographic and clinical characteristics, test conversion was more common among the male gender and those with a longer disease duration. Conclusions Tuberculosis tests conversions were common in inflammatory bowel disease patients treated with infliximab alone or in association with immunomodulators. In these immunosuppressed individuals, the classical tuberculosis skin test seems to have a higher sensitivity than the modern tests based on the release of interferonϒ.

Reintroduction of Anti-TNFα Therapy After (or even During) Anti-TNFα-associated Tuberculosis in Immune-mediated Diseases.

Dear Editor There is no consensus on whether it is safe to undertake retreatment with anti-tumour necrosis factor α (TNFα) drugs in patients in whom active tuberculosis (TB) has been associated with this therapy. Only a few cases of readministration of TNFα inhibitor after TB have been reported so far, and there are still no reports concerning other, more recent biological drugs, such as ustekinumab. The American College of Rheumatology guidelines state that TNFα inhibitors could be resumed for rheumatoid arthritis management after completion of anti-TB treatment if clinically relevant, though with a low level of …