Disseminated histoplasmosis in a kidney liver transplant patient from a non-endemic area: A diagnostic challenge.

Disseminated histoplasmosis is a rare opportunistic infection in non-endemic areas, where the disease is often diagnosed late. The spectrum of clinical manifestations is broad and life-threatening complications occur. We present a detailed case of a kidney liver transplant patient with disseminated histoplasmosis in a non-endemic area. Our case highlights the wide range of pathogens to consider in the immunocompromised patient, the delayed diagnosis of Histoplasmosis Capsulatum in non-endemic areas and the possibility of severe gastrointestinal disease. We also briefly review diagnostic tests and treatment options.

Community-acquired bacterial meningitis in adults: emergency department management protocol.

Acute bacterial meningitis (ABM) is a rare but disabling infectious condition that requires a performant multidisciplinary management approach. Between 70 and 90 adult patients are diagnosed with community-acquired ABM in Belgium annually, and reported case fatality rates range from 17 to 40%. The currently available guidelines provide evidence-based guidance on how to manage this disease. However, these guidelines do not translate the evidence to the daily practice at the emergency department in a Belgian healthcare context. We created a taskforce in University Hospitals Leuven consisting of experts with complementary expertise in managing this disease: neurology, neurosurgery, intensive care medicine, microbiology and infectious diseases. The taskforce agreed upon a flowchart containing seven management steps encompassing all relevant phases in emergency ABM management. In addition to the focus on timely and adequate initiation of antimicrobial treatment, the flowchart and protocol also provide guidance on practical hurdles such as how to assess the safety of performing a lumbar puncture and when to refer patients to the intensive care department. This protocol was implemented in University Hospitals Leuven and fosters inter-disciplinary coordination of ABM care.

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.

Mycobacterium genavense infection in a solid organ recipient: a diagnostic and therapeutic challenge.

Renal transplant recipients are highly susceptible to infections caused by uncommon pathogens because of their immunocompromised state. We report a case of disseminated Mycobacterium genavense infection in a patient with a combined renal and cardiac transplant. Diagnosing M. genavense infections remains a challenge because of the absence of specific clinical symptoms in combination with the difficulties of culturing the organism using standard mycobacterial culture procedures. This clinical case demonstrates the importance of molecular techniques as part of the initial work-up in order to rapidly establish the diagnosis.

Late presentation to HIV testing is overestimated when based on the consensus definition.

OBJECTIVES: In 2011, a consensus was reached defining "late presenters" (LPs) as individuals presenting for care with a CD4 count < 350 cells/µL or with an AIDS-defining event, regardless of CD4 count. However, a transient low CD4 count is not uncommon in recent infections. The objective of this study was to investigate how measurements of late presentation change if the clinical stage at the time of diagnosis is taken into account. METHODS: Case surveillance data for newly diagnosed patients in Belgium in 1998-2012 were analysed, including CD4 count at diagnosis, the presence of AIDS-defining events, and recent infections (< 6 months) as reported by clinicians in the case of acute illness or a recent negative test. First, proportions of LPs were calculated according to the consensus definition. Secondly, LPs were reclassified as "nonlate" if infections were reported as recent. RESULTS: A total of 7949 HIV diagnoses were included in the study. Recent infections were increasingly reported over time, accounting for 8.2% of new infections in 1998 and 37.5% in 2012. The consideration of clinical stage significantly modified the proportion of LPs: 18.2% of men who have sex with men (MSM) diagnosed in 2012 would be classified as LPs instead of 30.9% using the consensus definition (P < 0.001). The proportion of patients misclassified as LPs increased significantly over time: 5% in MSM in 1998 vs. 41% in 2012. CONCLUSIONS: This study suggests that low CD4 counts in recent infections may lead to overestimation of late presentation when applying the consensus definition. The impact of transient CD4 count on late presentation estimates should be assessed and, if relevant, the introduction of clinical stage in the definition of late presentation should be considered.

Laboratory diagnosis of schistosomiasis and Katayama syndrome in returning travellers.

The gold standard for laboratory diagnosis of schistosomiasis is the presence of typical eggs in stool or urine. The laboratory diagnosis of schistosomiasis and Katayama syndrome in returning travellers is difficult because the number of excreted eggs is often very limited. In early infections and in patients with only a few contacts with contaminated water, the total number of parasites, migrating larvae or schistosomulae, and adult worms, is very low. Eggs can only be found in faeces or urine when there is at least one pair of adult worms at the final location. The number of parasites increases as a function of the number of contacts with infected water. The exact latency between contamination and egg production is unknown. It is estimated that excretion of eggs starts after 40-50 days. The specific diagnosis of early schistosomiasis and Katayama fever relies essentially on serologic tests or preferably on PCR (if available). These assays are much more sensitive (up to four times) in the early phase of schistosomiasis than microscopic examination for typical eggs. Eosinophilia (sometimes exceeding 50%) is often present in patients with acute schistosomiasis (Katayama fever), but may be limited or absent in late fibrotic manifestations of the disease.

Fever in HIV-infected patients: less frequent but still complex.

Fever was a common symptom in patients with Human Immunodeficiency Virus (HIV) infection in the early phases of the epidemic. Fever of Unknown Origin (FUO) was frequent in HIV-patients and conditions causing FUO were often opportunistic conditions. The HIV-epidemic continues to expand, but access to effective antiretroviral therapy is also expanding, resulting in a growing number of HIV-infected patients less likely to be severely immunocompromised and less likely to present opportunistic conditions. Yet part of newly diagnosed patients continue to present with advanced HIV-infection and are still at high risk of opportunistic conditions. This epidemiological evolution strongly influences the spectrum of conditions causing fever and FUO in HIV-patients. While some patients with HIV-associated fever and FUO may still be suffering from opportunistic conditions classically associated with HIV-related FUO, many others will have causes of fever that are similar to the non-HIV-infected population or to classical FUO. Strategies for diagnosis and treatment of fever and its causes in HIV-infected patients need to take into account this evolution.

Significance of the isolation of Candida species from airway samples in critically ill patients: a prospective, autopsy study.

PURPOSE: Recovery of Candida from the respiratory tract is common. Large series on the incidence of histologically proven Candida pneumonia in intensive care unit (ICU) patients are lacking. METHODS: A two-year prospective study of all autopsies performed on patients who died in the ICU was conducted. For autopsy-proven cases of Candida pneumonia, we required microscopic demonstration of yeast invasion in lung autopsy specimens that showed inflammation. We looked for differences in incidence in patients with and without respiratory samples positive for Candida species pre-mortem. RESULTS: Of 1,587 patients admitted to the ICU, 301 (19%) died of whom 232 (77%) were autopsied. Of those, 135 patients (58%) had histopathological evidence of pneumonia. A total of 77 cases (57%) with pneumonia at autopsy had positive tracheal aspirate and/or BAL cultures for Candida spp. performed during the preceding two weeks. No cases of Candida pneumonia were identified amongst those 77 cases. In the other 58 patients with autopsy-proven pneumonia and no Candida isolation pre-mortem, no Candida pneumonia was observed either. CONCLUSIONS: Despite frequent isolation of Candida spp. from the airways, over a two-year period no single case of Candida pneumonia was found among the patients with evidence of pneumonia on autopsy. This study indicates that Candida pneumonia is an extremely rare occurrence in ICU patients and provides further evidence against the common use of antifungal therapy triggered by a microbiology report of Candida isolation from the respiratory tract.

Mediterranean spotted fever, a diagnostic challenge in travellers.

Mediterranean spotted fever or boutonneuse fever is caused by Rickettsia conorii and transmitted by the brown dog tick. The commonest symptoms are pyrexia, a maculopapular rash, lymphadenopathies and an inoculation eschar. Increasingly, it is recognised as a cause of serious illness in southern Europe. Rickettsial infections of the spotted fever group are rarely reported in Belgium. We report the case of a 20-year-old traveller returning from Morocco who presented with fever and a markedly swollen inguinal lymph node. Our case report illustrates the challenges rickettsioses can pose to physicians facing febrile travellers. Awareness of the epidemiology and the spectrum of clinical manifestations of this acute zoonosis can help physicians to promptly start appropriate empiric antibiotic therapy.

Disorders of glucose metabolism in human immunodeficiency virus-infected patients.

Over the past 10 years, the development of highly active antiretroviral therapy (HAART) has dramatically improved morbidity and mortality in human immunodeficiency virus (HIV)-infected patients. Since the introduction of HAART however, unexpected metabolic abnormalities, including lipodystrophy, dyslipidaemia and dysregulation of glucose metabolism, are reported with increasing frequency in HIV-infected persons. Such metabolic disorders, if not treated, may be associated with an increased risk of cardiovascular disease in HIV-infected patients. In this paper, the prevalence, mechanisms and therapeutic strategies for the disorders of glucose metabolism in the context of HIV-infection are discussed.

Infective endocarditis.

The diagnosis of infective endocarditis remains difficult. The complication rate is very high. Serious complications may occur and the overall mortality is still 20-25%. The sooner the treatment is started, the better the final result. Antibiotic therapy is essential but cardiac surgery is frequently necessary. Early surgery improves outcome. A multidisciplinary approach by internal medicine, cardiology and cardiac surgery facilitates the efficiency of diagnosis and treatment.

Fungemia at a tertiary care hospital: incidence, therapy, and distribution and antifungal susceptibility of causative species.

The aim of this study was to review fungal bloodstream infections at a large tertiary care hospital to evaluate the incidence of fungemia and the distribution of causative species during the period 2001-2005. Another aim was to assess the extent of antifungal resistance. A review of all episodes of fungemia at the University Hospitals of Leuven (Belgium) was conducted between January 2001 and December 2005. For the first yeast isolate collected from each non-mould fungemic episode during a 1-year period (June 2004-June 2005), susceptibility to seven antifungal agents was determined using Sensititre YeastOne plates (Trek Diagnostic Systems, East Grinstead, UK), and the antifungal therapy was reviewed. The annual incidence of fungemia ranged between 1.30 and 1.68 episodes per 10,000 patient-days (on a total of 2,680,932 patient-days), with a decreasing trend observed over the 5-year study period. The most common species were Candida albicans (59%), Candida glabrata (22%), Candida parapsilosis (10%), and Candida tropicalis (4%). Overall, fluconazole resistance was rare (1.6%) and was detected only in C. glabrata and C. krusei. Voriconazole and caspofungin inhibited 100% of the isolates at a concentration of

Simultaneous determination of 8 HIV protease inhibitors in human plasma by isocratic high-performance liquid chromatography with combined use of UV and fluorescence detection: amprenavir, indinavir, atazanavir, ritonavir, lopinavir, saquinavir, nelfinavir and M8-nelfinavir metabolite.

A simple, accurate and fast method was developed for determination of the commonly used HIV protease inhibitors (PIs) amprenavir, indinavir, atazanavir, ritonavir, lopinavir, nelfinavir, M8-nelfinavir metabolite and saquinavir in human plasma. Liquid-liquid extraction was used with hexane/ethylacetate from buffered plasma samples with a borate buffer pH 9.0. Isocratic chromatographic separation of all components was performed on an Allsphere hexyl HPLC column with combined UV and fluorescence detection. Calibration curves were constructed in the range of 0.025-10 mg/l. Accuracy and precision of the standards were all below 15% and the lowest limit of quantitation was 0.025 mg/l. Stability of quality control samples at different temperature conditions was found to be below 20% of nominal values. The advantages of this method are: (1) inclusion and determination of the newly approved atazanavir, (2) simultaneous isocratic HPLC separation of all compounds and (3) increased specificity and sensitivity for amprenavir by using fluorescence detection. This method can be used for therapeutic drug monitoring of all PIs currently commercialised and is now part of current clinical practice.

Three cases of destructive native valve endocarditis caused by Staphylococcus lugdunensis.

Described here are three cases of acute native valve endocarditis due to the coagulase-negative pathogen Staphylococcus lugdunensis with serious complications. Two of the three patients died despite optimal antibiotic therapy and cardiovascular surgery. These cases demonstrate the aggressive nature of S. lugdunensis and emphasize the importance of identifying coagulase-negative staphylococci to the species level and not considering the isolation of S. lugdunensis from normally sterile body fluids as contamination. On the contrary, when this organism is found in patients with endocarditis, early surgery should be considered. The possibility that this organism could be misidentified as S. aureus because of "autocoagulation" and that commercial identification systems may misidentify it as S. haemolyticus, S. hominis or S. warneri should also be remembered.

Families affected by HIV: parents' and children's characteristics and disclosure to the children.

The reduced risk of mother-to-child transmission due to improved HIV treatment has resulted in an increasing number of healthy children born to mothers living with HIV. The study's objective was to identify the number of parents or caregivers in a sample of persons living with HIV in Flanders, the number of HIV-affected children as well as specific family-related characteristics. Using a structured survey quantitative data were assessed on a total of 628 patients at three Flemish Aids reference centres. Qualitative data were collected in a small sub-sample of African caregivers living in Flanders. Twenty-seven per cent of the overall sample had children younger than 18 years, totalling 165 HIV-affected families with 279 children. Parents from developing countries had significantly more children than European parents. One hundred and eighty-two (68%) of all children were HIV-negative, while the HIV status of 75 (28%) was unknown. Disclosure rate was low: 26 (10%) children were aware of the parental HIV disease. The study shows that HIV-affected families have to deal with complex psychosocial issues such as migration, family illness, family secrecy around HIV and disclosure. Service implications are discussed.

Treatment of acute diarrhoea: update of guidelines based on a critical interuniversity assessment of medications and current practices.

Further to a thorough analysis of the problem of acute diarrhoea and the therapeutic options, recommendations were defined following a multidisciplinary approach. These guidelines take into account the reality of frequent self-medication. They further differ as a function of age (children, primarily treated by ORS and for whom self-medication is not advised versus adults who can self-medicate), symptoms (uncomplicated diarrhoea versus dysentery) and location where the diarrhoea is contracted (at home or when travelling).