Epidemiology and reporting of candidaemia in Belgium: a multi-centre study.

The primary aim of this study was to collect national epidemiological data on candidaemia and to determine the reporting time of species identification and antifungal susceptibility in clinical practice. During a 1-year period (March 2013 until February 2014), every first Candida isolate from each episode of candidaemia was included prospectively from 30 Belgian hospitals. Identification and susceptibility testing were performed according to local procedures and isolates were sent to the National Reference Center for Mycosis. Species identification was checked by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) and internal transcribed spacer (ITS) sequencing in case no reliable identification was obtained by MALDI-TOF MS. Antifungal susceptibility testing was performed according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) methodology. A total of 355 isolates were retrieved from 338 patients. The mean incidence rate of candidaemia was 0.44 (range: 0.07 to 1.43) per 1000 admissions or 0.65 (range: 0.11 to 2.00) per 10,000 patient days. Candida albicans was most frequently found (50.4 %), followed by C. glabrata (27.3 %) and C. parapsilosis sensu lato (9.8 %). The overall resistance to fluconazole was 7.6 %, ranging from 3.9 % in C. albicans to 20.0 % in C. tropicalis. Only one C. glabrata isolate was resistant to the echinocandins. Four days after blood culture positivity, 99.7 % of the identifications and 90.3 % of the antifungal profiles were reported to the treating clinician. Candidaemia incidence rates differed up to 20-fold among Belgian hospitals; no clear factors explaining this difference were identified. The overall antifungal resistance rates were low but high azole resistance rates were recorded in C. tropicalis.

Evaluation of different confirmatory algorithms using seven treponemal tests on Architect Syphilis TP-positive/RPR-negative sera.

The Architect Syphilis TP is considered to be a suitable screening test due to its high sensitivity and full automation. According to the International Union against Sexually Transmitted Infections (IUSTI) 2014 guidelines, however, positive screening tests need confirmation with Treponema pallidum particle agglutination (TP.PA). Among Architect-positive results, samples with a negative non-treponemal test present the major diagnostic challenge. In this multicenter study, we investigated if other, preferable less labor-intensive treponemal tests could replace TP.PA. A total of 178 rapid plasma reagin (RPR)-negative sera with an Architect value between 1 and 15 S/CO were prospectively selected in three centers. These sera were analyzed with TP.PA and six alternative treponemal tests: three immunoblots and three tests on random-access analyzers. The diagnostic performance of the treponemal tests differed substantially, with the overall agreement between the six alternative tests ranging from 44.6 to 82.0%. Based on TP.PA as the gold standard, the INNO-LIA IgG blot, the BioPlex 2200 IgG, and the Syphilis TPA showed a high sensitivity, while the EUROLINE-WB IgG blot, recomLine Treponema IgG blot, and the Chorus Syphilis screen showed a high specificity. However, an Architect cut-off of 5.6 S/CO can serve as an alternative for these confirmatory treponemal tests in case of an RPR-negative result. Treponemal tests show poor agreement in this challenging group of Architect-positive/RPR-negative sera. The most optimal algorithm is obtained by assigning sera with an Architect value >5.6 S/CO as true-positives and sera with a value between 1 and 5.6 S/CO as undetermined, requiring further testing with TP.PA.

Management of pregnant women infected with Ebola virus in a treatment centre in Guinea, June 2014.

We report two cases of confirmed Ebola virus disease in pregnant women, who presented at the Médecins Sans Frontières Ebola treatment centre in Guéckédou. Despite the very high risk of death, both pregnant women survived. In both cases the critical decision was made to induce vaginal delivery. We raise a number of considerations regarding the management of Ebola virus-infected pregnant women, including the place of amniocentesis and induced delivery, and whether certain invasive medical acts are justified.

Early infection of hip joint prosthesis by Clostridium difficile in an HIV-1 infected patient.

Anaerobes are less frequently described as causative pathogen of prosthetic joint infection (PJI). We report the first case of early PJI after hip arthroplasty due to Clostridium difficile in a diabetic and HIV-1 infected patient with bacteremia. Our patient was successfully treated through surgical debridement and prosthesis retention combined with targeted antibiotic therapy.

Novel Tropheryma species in a lung biopsy sample from a kidney transplant recipient.

OBJECTIVES: A kidney transplant recipient with recurrent pleuritis underwent an open lung biopsy, the results of which revealed multiple nodular infiltrates. Grocott and periodic acid-Schiff staining were positive. Fungal and Tropheryma whipplei PCR were, however, negative. Further identification was needed. METHODS: Formalin-fixed, paraffin-embedded (FFPE) extraction was performed using an FFPE extraction kit. T. whipplei was searched for using a real-time PCR targeting the noncoding repeat specific for T. whipplei. Identification of the bacteria in the extract was done using 16S rDNA and 23S rDNA sequencing and BLAST analysis. Internal transcribed spacer PCR was used for fungal DNA identification. RESULTS: The FFPE extract was negative for fungi and T. whipplei. 16S rDNA sequence analysis of a 1375 bp fragment gave T. whipplei as the best match with 26 mismatches, resulting in only 98% agreement. Sequence analysis of the 23S rDNA gene again gave T. whipplei as the best match, but with only 91% agreement. A pan-Tropheryma 16S rDNA real-time PCR was developed, and both the biopsy sample and a respiratory sample of the patient were strongly positive. The patient received antimicrobial treatment targeting T. whipplei with good clinical outcome. CONCLUSIONS: 16S and 23S rDNA sequencing gave T. whipplei as the best hit, although with limited agreement. These findings suggest that a novel Tropheryma species that lacks the noncoding repeat, most frequently used for molecular detection of Whipple disease, might be the cause of the pulmonary disease. Adaptation of current PCR protocols is warranted in order to detect all Tropheryma species.

Effects of two Ca2+ modulators in normal and albumin-sensitized guinea-pig trachea.

The voltage-dependent Ca2+ channel blocker, verapamil, and the calmodulin antagonist, trifluoperazine, each reduced resting tone and attenuated constriction induced by acetylcholine or vagal stimulation in normal guinea-pig trachea. Attenuation of vagal responses involved both pre- and post-junctional effects on cholinergic neurotransmission. In albumin-sensitized trachea both drugs caused small increases in resting tone. Vagally mediated constrictor responses were resistant to attenuation by verapamil in sensitized trachea. Trifluoperazine was less effective against acetylcholine-induced tone in sensitized, as compared to untreated, trachea. The results indicate that Ca2+ handling is altered in airway smooth muscle in this animal model of bronchial asthma. Abnormal Ca2+ handling, therefore, may underlie the hyperresponsiveness to vagal input exhibited in sensitized trachea and could contribute to the generalised airway hyperreactivity characteristic of asthma.

Late presentation for human immunodeficiency virus HIV diagnosis results of a Belgian single centre.

BACKGROUND: Antiretroviral therapy reduces mortality and morbidity in HIVinfected individuals, most markedly when initiated early, before advanced immunodeficiency has developed. Although the international guidelines recommend starting antiretroviral therapy ART with a high CD4 cell count level, in the practice, this is particularly challenging to achieve, especially in late presentation of HIV diagnosis. The aim of this study was to determine the frequency and the demographic features associated with late presentation for HIV diagnosis in our Centre. METHODS: All newly diagnosed patients with HIV between January 2007 and December 2011 in our AIDS Reference Centre, were included. Late presenter patient was defined as patient with CD4 count 350/mm(3) at the time of diagnosis. Demographic age, sex, ethnicity, migration and clinical characteristics transmission mode, CD4 cell count, viral load were collected. We also collected data on outcome median day of hospitalization, mortality, virological response to ART and lost to followup LTFU. LTFU was defined as patient without any medical contact and viral load measurements during two consecutive years in our centre. RESULTS: From 2007 to 2011, 154 429 out of 359 patients newly diagnosed with HIV were late presenters. According to univariate analysis, age 50, female gender, migrant from subSaharan Africa and heterosexual contact were associated with late presentation for HIV diagnosis. In the multivariate analysis, age 50, heterosexual contact and migrant status particularly women were the only independent risk factors for late presentation. Late presenters tend to have a worse outcome than nonlate presenters. CONCLUSION: A considerable proportion of patients continue to be diagnosed with advanced HIV disease, despite the fact that risk factors for late presentation have been clearly identified. Despite high testing rate for HIV in Belgium, highrisk population like migrant, heterosexual contact, remain under tested. In order to be able to detect and treat all patients with high CD4 cell count as recommended by all international guidelines, we recommend developing testing policies specifically focused on these categories at high risk for late presentation.

Relapsing visceral leishmaniasis in a HIV-1 infected patient with advanced disease.

Leishmaniasis, an intracellular protozoal infection in which tissue macrophages are targeted, is transmitted by female sandfly bite and occurs in 98 countries. Visceral leishmaniasis (VL) is the clinical form of leishmaniasis most frequently associated with HIV, especially in Europe. Both diseases have a synergistic detrimental effect on the cellular immune response. Treatment of VL in patients with underlying HIV-infection is associated with lower cure rates, higher rates of drug toxicity, higher relapse rates and greater mortality than treatment of VL in immunocompetent patients. We report the case of a HIV-1 infected patient with advanced disease who presented VL with multiple relapses. This case highlights the difficulties of treating VL in patients with HIV co-infection.

Imported malaria in a tertiary hospital in Belgium: epidemiological and clinical analysis.

BACKGROUND AND OBJECTIVE: There has been a marked increase in tourism, immigration, and business travel to malaria-endemic areas. Non-immune individuals (western travellers) or immigrants living for more than one year in non-endemic areas who visit friends and relatives (VFR) are particularly susceptible to developing severe malaria when travelling to areas with high levels of transmission. In this study, epidemiological, clinical and biological features of malaria in travellers returning from endemic areas were analysed. This may help clinicians unfamiliar with malaria not to overlook this disease in its early stage, and to initiate prompt treatment. PATIENTS AND METHODS: We retrospectively analysed all cases of patients who presented with malaria in our institution between 2003 and 2008. RESULTS: Eighty patients were included. Most patients visited Africa (93.6%). Accordingly, P. falciparum was the main species identified (67/77 patients i.e. 87%). Sixty-five patients (65/78 i.e. 83.3%) had not taken any prophylaxis and 13 (16.7%) had taken it inadequately. Common clinical features were fever (80/80, 100%), influenza-like symptoms (16/80, 20.1%), respiratory symptoms (5/80, 6.3%), neurological symptoms (2/80, 2.5%) or digestive symptoms (15/80, 18.8%). Digestive symptoms were predominant in children < 16 y.o. (60% of these patients). CONCLUSION: Imported malaria cases are mostly related to the lack of adequate use of chemoprophylaxis. Plasmodium falciparum is the main species responsible for imported cases of malaria in our institution. Clinical features vary, but fever is universally present at presentation. As such, all cases of fever upon return from a malaria-endemic area must be considered as malaria until proven otherwise, at least during the first three months after the return.

Tigecycline-induced acute pancreatitis: about two cases and review of the literature.

Tigecycline (formerly CAR-936, Tygacyl) is the first glycylcycline antibiotic available for clinical use. It has an expanded broad-spectrum antibiotic activity. Phase III studies have identified gastrointestinal side-effects, especially nausea and vomiting, as the most common adverse events. Few cases of acute pancreatitis (AP) have been described in the literature. We report two new cases of mild tigecycline-induced pancreatitis. Tigecycline was given for soft-tissue infection in both cases. Symptoms such as nausea, vomiting and mostly abdominal pain occurred within 5 days after starting Tigecycline. Pancreatic enzymes elevation occurred five to six days after initiation of treatment, and resolved within a week after drug-discontinuation. Diagnosis of mild pancreatitis was confirmed after performing CT-Scan of the abdomen in both cases. We take this opportunity to review the literature about this potentially serious side-effect induced by tigecycline.

Neuroarthropathy secondary to transthyretin amyloidosis (ATTR V30M).

In this article we report the case of a 46-years-old Portuguese woman admitted in our orthopaedic ward with right knee pain. Radiological findings were consistent with neuroarthropathy. After exclusion of the most common causes of polyneuropathy, Familial amyloid polyneuropathy (FAP) was diagnosed by the discovery of a mutation V30M on chromosome 18 by polymerase chain reaction on a fibroblast culture of her skin biopsy. FAP is one of many aetiologies of polyneuropathy. Although a rare disease, genetic screening in selected populations makes early diagnosis and prompt treatment of asymptomatic family members readily available.

High FDG uptake on FDG-PET scan in HIV-1 infected patient with advanced disease.

UNLABELLED: We report the case of a 48-year-old Caucasian male positive for HIV-1 who was admitted in our clinic for a fever of unknown origin with weight loss. The CD4 cell count was 99/mm3 and the viral load (VL) was 836500 copies/ml. A first FDG-PET-CT showed abnormal hypermetabolism of multiple lymp nodes, of the bone marrow and of the spleen. Tuberculosis and lymphoma were excluded by a lymph node biopsy and a culture. Six months after the start of a highly active anti-retroviral therapy (HAART) containing lamuvidine, tenofovir, atazanavir boosted by ritonavir, a new FDG-PET-CT showed a complete normalisation of the metabolism in the regions previously described as having a high FDG uptake. The VL was < 37 copies/ml and his CD4 cell count was 399/mm3. IN CONCLUSION: in patients with advanced HIV infections presenting with FUO, high uptake in 18FDG-PET-CT can be the marker of advanced disease reflecting the areas of viral replication.

HIV-associated multicentric Castleman disease: a report of 4 cases and review of the literature.

BACKGROUND: Multicentric Castleman's disease (MCD) is a rare, non-clonal lymphoproliferative disorder characterized by constitutional symptoms, anaemia and generalised lymphadenopathy. Its incidence among the HIV-positive population seems to have increased during the past decades. AIM: The present study intends to compare demographic features, clinical presentation, laboratory studies, imaging results as well as treatment regimens and outcome in our MCD patients to those of larger reported series. METHOD: We reviewed the files of 920 HIV-1-infected patients from our AIDS Reference Centre. Data was collected from the operating software for the patients' medical records of our institution (Medical Explorer v3r3, Cliniques St Luc, 2008). RESULTS: We report a series of four cases of MCD among our HIV/AIDS patients' cohort. Three were of African origin. They were diagnosed after 2003, after a mean duration of 54 months of HIV-seropositivity (ranging from 7 to 120 months) All presented with characteristic clinical features and laboratory findings, and were started on HAART a few months before or upon MCD diagnosis. Three patients were treated with chemotherapy (ABV), and one with HAART only. One patient who was given ABV is in continuous remission after 3 years of follow-up. The remaining three are alive, with good symptom control, regardless of the treatment they received. CONCLUSION: MCD is a rare, but rising issue among HIV-infected patients. The clinical and paraclinical features of our series of four patients are in keeping with those of larger reported series. Currently, treatment is mainly chemotherapy-based, but a wide variety of protocols have been used, mainly because of the lack of available evidence. New approaches such as anti-CD 20 antibodies seem highly effective, and the role of HHV-8 needs to be further investigated, as it might be an important target for future treatment. In light of this review, we are looking forward to offer these opportunities to our patients, despite unhelpful regulations.

Prospective clinical evaluation of Amplicor Mycobacterium tuberculosis PCR test as a screening method in a low-prevalence population.

Of 656 respiratory samples analyzed for Mycobacterium tuberculosis by microscopy, culture, and the Amplicor PCR method, 25 were positive by culture, 12 were positive by microscopy, and 17 were positive by the Amplicor PCR method; 16 samples were Amplicor PCR positive and culture negative. No patient except one with culture-negative, Amplicor PCR-positive samples had clinical indications of tuberculosis. The sensitivity and specificity of the Amplicor PCR compared with those of culture were 68 and 97.4%, respectively. For culture-positive, smear-negative samples, the sensitivity of the Amplicor PCR was 46%.