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.

HIV-1 proviral resistance mutations: usefulness in clinical practice.

OBJECTIVES: Transmitted HIV strains may harbour drug resistance mutations. HIV-1 drug resistance mutations are currently detected in plasma viral RNA. HIV-1 proviral DNA could be an alternative marker, as it persists in infected cells. METHODS: This was a prospective study assessing the prevalence and persistence of HIV-1 drug resistance mutations in DNA from CD4 cells before and after protease inhibitor (PI)- or nonnucleoside reverse transcriptase inhibitor (NNRTI)-based therapy initiation in 69 drug-naïve patients. RESULTS: Before therapy, 90 and 66% of detected mutations were present in CD4 cells and plasma, respectively. We detected seven key mutations, and four of these (M184M/V, M184M/I, K103K/N and M46M/I) were only found in the cells. When treatment was started, 40 patients were followed; the mutations detected at the naïve stage remained present for at least 1 year. Under successful treatment, new key mutations emerged in CD4 cells (M184I, M184M/I and Y188Y/H). CONCLUSIONS: The proportion of mutations detected in the DNA was statistically significantly higher than that detected in standard RNA genotyping, and these mutations persisted for at least 1 year irrespective of therapy. The pre-existence of resistance mutations did not jeopardise treatment outcome when the drug concerned was not included in the regimen. Analysis of HIV-1 DNA could be useful in chronic infections or when switching therapy in patients with undetectable viraemia.

[Tarsal osteoarthritis: a rare localisation of tuberculosis]. / Ostéoarthrite tarsienne: une localisation rare de la tuberculose.

We report the case of a 39-year-old woman with an uneventful medical history who presented an inflammatory left foot with no notion of trauma or fever. The plain x-ray and magnetic resonance imaging demonstrated talonavicular and subtalar osteoarthritis. A surgical biopsy with excision of inflammatory and necrotic tissue and removal of a fistular tract was performed. Histology revealed the presence of granulomas with caseous central necrosis suggesting tuberculosis of the bone. The diagnosis was confirmed when bacteriology samples grew Mycobacterium tuberculosis. Antituberculosis drugs were administered for twelve months. At 24 months, the patient presents a painful stiff rear foot after the development of secondary talonavicular degeneration. This case illustrates a particular clinical presentation of tuberculosis. This diagnosis should be considered in the presence of atypical bony lesions with a chronic course. Early diagnosis enables proper therapeutic management. Useful diagnostic imaging techniques include plain x-rays, computed tomography, and magnetic resonance imaging. Certain diagnosis is based on bacteriological and histological examinations.

Breast prosthesis infection and pets: A case report and review of the literature.

INTRODUCTION: Pets are not always the human's best friends, particularly in the presence of comorbidities such as wounds. The following case report describes a Pasteurella multocida infection of a reconstructive breast implant due to a close contact between a cat and its owner. PRESENTATION OF CASE: A 33-year-old woman developed a breast implant infection 13 days after an immediate breast reconstruction following a mastectomy for a multifocal ductal carcinoma. The wound was explored surgically and the implant removed. Culture extracted from fluid around the prosthesis evidenced the presence of P. multocida, a Gram-negative coccobacillus which is present in the oral commensal flora of cats and dogs. CONCLUSION: In the case of breast infection, surgical revision - with or without removal of the implant - is required in order to carry out a meticulous intraoperative cleaning. Antibiotherapy is always necessary in such cases. Particularly when patients presenting comorbidities are concerned, the focus must be put on avoiding close contact of the wound with pets.

Key pharmacokinetic parameters of isepamicin in febrile neutropenic cancer patients and in women with acute pelvic inflammatory disease.

The pharmacokinetics (PK) of isepamicin were studied in 8 febrile neutropenic patients with hematologic malignancy and in 20 young women with acute pelvic inflammatory disease (PID). Isepamicin was given as a slow intravenous infusion over 30 min at a dose of 15 mg/kg once daily (OD). Serum levels of isepamicin were determined by fluorescence polarization immunoassay, and PK analyses were obtained based on a one-compartment open model after 24 hours (steady state) and after 7 days. On day 1, the volume of distribution (Vd) of isepamicin, for both populations, appeared about 30% higher than classically reported in healthy individuals: 0.31 and 0.36 L/kg for neutropenic and PID patients respectively. However on day 7, Vd displayed significant reduction (0.28 and 0.27 L/kg, respectively for neutropenic and PID patients). A reduction of isepamicin clearance was also observed between day 1 and day 7 (137 vs 120 mL/min and 130 vs 101 mL/min for neutropenic and PID populations, respectively). Such changes are consistent with a significant increase in the Cmax concentrations (45 vs 50 mg/L, and 38 vs 49 mg/L) and in the AUC (136 vs 158 and 137 vs 162 mg/L.h) observed after a week of treatment in neutropenic and PID patients, respectively. In conclusion, taking into account the importance of reaching early active concentrations, we recommend the use of higher loading dose of isepamicin (>15 mg/kg) in neutropenic cancer patients and in women with PID, particularly in case of a combination with a possibly ineffective antibacterial agent, in case of infection with bacteria at upper limit of susceptibility, in the presence of high infectious inoculum or in the presence of sequestered sites of infection.

Vaccinations for adult solid organ transplant recipient: current recommendations.

The need for immunization in solid organ transplant recipient can arise from three factors: immune deficit owing to underlying disease, rejection of the organ graft, and immunosuppressive therapy given after transplantation. As a general rule, primary immunizations should be given as early as possible before transplantation because the immune response to vaccines is decreased in patients with end-stage organ disease. There are three categories of vaccines: Live vaccines--oral polio, vaccinia, bacillus Calmette-Guerin, live oral typhoïd, and intranasal influenza vaccines--are contraindicated in solid organ transplant recipients. The use of varicella vaccine remains controversial. The use of rubella vaccine is recommended in young women of childbearing age. Of the killed vaccines or genetically engineered vaccines, the following are recommended: pneumococcal vaccine, influenza vaccine, hepatitis A vaccine, hepatitis B vaccine, diphtheria, and tetanus vaccine. Vaccination of household contacts and health care workers in transplant centers is recommended. However, live vaccine (with the exception of varicella vaccine) should be avoided in these contacts.

Clinical features and outcome of typhoid fever and invasive non-typhoidal salmonellosis in a tertiary hospital in Belgium: analysis and review of the literature.

OBJECTIVES: Typhoid fever (TF) occurs rarely in industrialized countries because of advances in health care and improvement of drinking water. Conversely, non-typhoid salmonellosis (NTS) remains widespread, because of food contamination or asymptomatic carriage. Non-typhoid salmonellosis can be severe when becoming invasive non-typhoid salmonellosis (iNTS). Although established prognostic indicators of the two pathologies are different, direct comparisons between iNTS and TF in the literature remain scarce. The purpose of this study was to analyse and compare demographic, clinical features and outcome of hospitalized patients with TF and iNTS. METHODS: Demographic, clinical features and outcome were retrospectively analysed in a series of patients hospitalized between 2007 and 2012. RESULTS: A total of 33 patients were enrolled, including 13 with established TF and 20 with iNTS. No differences between TF and iNTS patients were observed in incidence of fever, abdominal cramps, diarrhoea, headache, nausea and vomiting and duration of antibiotic therapy (≤ 7 days in both groups). Although the clinical outcome of TF patients was identical to that of iNTS patients, including incidence of complications, length of hospitalization and mortality (1/13 (7.7%) vs 2/20 (10%), P = 0.43), comorbidities were less frequent in the TF group than in the iNTS group (2/13 vs 15/20, P = 0.003). CONCLUSION: The clinical profile and outcome of TF patients are similar to those with iNTS. Although comorbidities are more often associated with iNTS, the results of our study suggest that clinical management of these two diseases should remain similar.

Nocardia prosthetic knee infection successfully treated by one-stage exchange: case report and review.

A 64-year-old man with a history of sarcoidosis on corticosteroids and azathioprine was admitted to our hospital with complaints of worsening left knee pain and swelling for the past 3 weeks. His past medical history is also significant for severe osteoarthritis requiring a cemented total left knee arthroplasty 1 year ago. Diagnostic investigation during his hospital admission eventually led to the diagnosis of Nocardia nova knee prosthetic joint infection in the setting of a disseminated nocardiosis. He was successful treated by one-stage complete hardware exchange in conjunction with an adapted antibiotic therapy regimen (meropenem and doxycycline followed by ceftriaxone and doxycycline). Two years later, his recovery was deemed excellent.

Ritonavir/saquinavir plus one nucleoside reverse transcriptase inhibitor (NRTI) versus indinavir plus two NRTIs in protease inhibitor-naive HIV-1-infected adults (IRIS study).

OBJECTIVES: To compare the efficacy, tolerability and safety of a ritonavir 400 mg/saquinavir hard gel fomulation 400 mg twice daily versus an indinavir 800 mg once every 8 h containing first-line protease inhibitor (PI) treatment regimen. METHODS: Open, randomized, multicentre clinical trial. PI-naive patients received either ritonavir/saquinavir and one nucleoside reverse transcriptase inhibitor (NRTI) or indinavir and two NRTIs. Intention-to-treat (ITT) and on-treatment (OT) analyses were performed. RESULTS: The baseline characteristics of the study participants were similar in both arms, 67 patients (37%) were naive to antiretroviral treatment. The proportion of patients who achieved a plasma viral load below the level of detection of 400 copies/ml at week 48 was 43% (39/90) in the ritonavir/saquinavir arm and 63% (57/90) in the indinavir arm (P=0.005, I

Elevation of serum thyroxine-binding globulin (but not of cortisol-binding globulin and sex hormone-binding globulin) associated with the progression of human immunodeficiency virus infection.

PURPOSE: In order to assess the relation of thyroid function tests to human immunodeficiency virus (HIV) infection, we determined the levels of serum thyroid hormones, serum binding proteins [thyroxine-binding globulin (TBG), cortisol-binding globulin (CBG), and sex hormone-binding globulin (SHBG)], and serum tumor necrosis factor (TNF) in HIV-seropositive subjects at different clinical stages. PATIENTS AND METHODS: Thirty-seven HIV-seropositive patients were studied: 7 at stage II, 13 at stage III, and 17 at stage IV (eight ambulatory and nine hospitalized) according to the Centers for Disease Control's criteria. RESULTS: As compared with stage II and stage III patients, stage IV patients had significantly higher mean TBG and total thyroxine (TT4) values, similar and normal total triiodothyronine (TT3) levels, and similar and abnormally low reverse triiodothyronine (rT3) concentrations. However, stage IV hospitalized patients had significantly lower TT3 values than stage IV ambulatory patients. In contrast to TBG, mean levels of CBG and SHBG were comparable in the three groups and within normal limits. For the whole population of HIV patients, there was a highly significant correlation between the CD4 lymphocyte count and TBG (r = -0.529, p less than 0.001) but not with CBG and SHBG levels. Finally, TNF values higher than 10 pg/mL were detected in six of the 17 stage IV patients and in only one of the 13 stage III patients (p = 0.059); elevated TNF levels correlated with a lower CD4 count (p less than 0.01) but not with serum TBG levels. CONCLUSION: The progression of HIV infection is associated with an elevation of serum TNF and TBG, but not of CBG or SHBG. HIV-infected patients have an unexpectedly normal TT3-low rT3 state.

Molecular characterization of femA from Staphylococcus hominis and Staphylococcus saprophyticus, and femA-based discrimination of staphylococcal species.

The femA gene encodes a protein precursor which plays a role in peptidoglycan biosynthesis in Staphylococcus aureus and is also considered as a factor influencing the level of methicillin resistance. A femA homologous gene was recently characterized in S. epidermidis, entailing the possibility of femA phylogenetic conservation in staphylococcal species. Accordingly, we assessed the presence of femA homologous genes in S. hominis and S. saprophyticus. Strategy for identification relied upon alignment of S. aureus and D. epidermidis femA sequences and upon identification of potentially conserved regions. Amplifications of portions of the femA genes were performed under permissive annealing conditions, by using several sets of primers designed to match the consensus regions. DNA sequencing of overlapping PCR fragments led to the characterization of the entire femA genes of S. hominis and S. saprophyticus, and provided more precise information on the femA start codon for all five species. The genomic organization of all these femA genes appeared highly conserved, with alternance of homologous and variable regions. On this basis, a consensus sequence of the femA gene was defined and interspecies variations were exploited to design strategies for staphylococci species-specific identification, including multiplex PCR amplification and a reverse hybridization assay.

HIV-1 detection by nested PCR and viral culture in fresh or cryopreserved postmortem skin: potential implications for skin handling and allografting.

AIMS: To date, the risk relating to the handling or allografting of human immunodeficiency virus type 1 (HIV-1) infected postmortem skin remains hypothetical. While blood screening for HIV antibodies is still the key safety procedure to detect HIV infected cadavers, false negative results are a concern. Conversely, false positive results may hamper the collection of skin allografts. Accordingly, viral culture was used to clarify skin infectivity and the nested polymerase chain reaction (PCR) was used to assess the reliability of skin PCR testing. METHODS: Viral culture and nested PCR performed with gag and pol specific primers were investigated in cadaveric skin and blood from 12 HIV-1 infected patients. Samples were collected repeatedly between one and five days in seven patients. In most cases, analyses were performed on triplicate skin samples: fresh (n = 26); cryopreserved in 5% dimethylsulphoxide (n = 21), or cryopreserved in 30% glycerol (n = 26). RESULTS: HIV was isolated in two of 26 cultures of fresh skin specimens (8%), seven of 47 cryopreserved skin specimens (15%), and eight of 26 blood specimens (31%). The nested PCR detected HIV-1 in all skin samples (n = 73), regardless of the postmortem interval or cryopreservation. In blood, a positive signal was found in eight of 12 patients but two of them had discordant results on successive samples. CONCLUSIONS: These data suggest that nested PCR on postmortem skin samples can detect HIV more reliably than on blood. They also demonstrate the potential viral infectivity of fresh or stored skin postmortem samples in HIV infected patients. They underscore the need for caution during the handling of skin tissue from HIV infected cadavers and confirm the potential risk related to accidental allografting of HIV contaminated skin.

Cytogenetic observations after meglumine antimoniate therapy for visceral leishmaniasis.

Few data are available concerning the genotoxic effects of antimonial salts therapy in humans. A patient suffering from visceral leishmaniasis was treated for 15 days with a cumulative dose meglumine antimoniate 42.5 g. Peripheral blood lymphocytes sampled before treatment, 7 days later, and at the end of therapy (day 15) were examined for the presence of structural chromosome aberrations, sister chromatid exchanges (SCEs), and micronuclei in binucleated cells. The treatment resulted in an increase of binucleated cells carrying micronuclei, with no changes in chromosome structural aberrations or in mean SCE frequency. On the basis of these observations and of experimental results reported in the literature, we conclude that therapy with meglumine antimoniate apparently does not represent a mutagenic or carcinogenic risk to humans.

Community-acquired Serratia marcescens meningitis.

Serratia marcescens is an unusual cause of community-acquired meningitis in adults. We report a case of S. marcescens meningitis occurring 29 years after a head injury and preceded by 3 years of intermittent nasal discharge of cerebrospinal fluid (CSF). One month before admission, the patient had received treatment with cefadroxil. This case illustrates the risk of Gram-negative bacillary meningitis in patients with a CSF leak when they are treated with antibiotics. When patients have a chronic clear nasal discharge, one should look for a past medical history of head injury before prescribing antibiotics. In the presence of a fistula, any antibiotherapy may lead to the selection of resistant organisms which may be difficult to treat. Due to the high risk of meningitis and the fact that spontaneous closure in delayed CSF rhinorrhoea is unlikely, surgical repair of any associated fistulae is mandatory.

Fluconazole orally dispersible tablets for the treatment of patients with oropharyngeal candidiasis.

The efficacy and tolerability of fluconazole orally dispersible tablets (ODT) in the treatment of oropharyngeal candidiasis was evaluated in this multicentre non-comparative study. A total of 89 adults with signs and symptoms of oropharyngeal candidiasis were enrolled; 70 of whom completed therapy with fluconazole ODT 100 mg once daily for 7 - 14 days. Acquired immunodeficiency syndrome (AIDS)/ AIDS-related complex was an underlying illness in 69% of patients (61). An antimicrobial and corticosteroid therapy was given in 52% (46) and 20% (18) of patients, respectively. Of the 60 patients who had baseline signs and symptoms of infection and a culture positive for Candida albicans, 90% (54) were cured or had improved at the end of therapy, and the fungal pathogen was eradicated in 19/57 (33%) patients. At the 4-week posttreatment follow-up, signs and symptoms of oropharyngeal candidiasis were absent in 73% (27/37) patients. The adverse events and laboratory abnormalities recorded during the study period were attributable to underlying illnesses rather than to fluconazole therapy. These results indicate that this novel dosage form of fluconazole is effective and well tolerated in the treatment of oropharyngeal candidiasis.

[Aids and chorioretinal opportunistic infections]. / SIDA et infections opportunistes de la choriorétine.

Retrospective study of 19 cases of opportunistic infections of the chorioretina in patients with the Acquired Immunodeficiency Syndrome. We observed 14 cases of CMV retinitis, 2 cases of toxoplasmic chorioretinitis, 1 case of cryptococcal choroiditis and 2 cases of herpes zoster retinitis. Review of the clinical, angiographical and histopathological aspects of these infections. Review of the vital and visual prognosis after treatment.

[Nonketotic hyperglycemic coma induced by somatostatin in an AIDS patient]. / Coma hyperglycémique non cétosique induit par la somatostatine chez un patient atteint du SIDA.

A 33-year-old woman with AIDS was treated with somatostatin (continuous infusion 6 mg/day) for intractable diarrhoea. Improvement was insufficient and the dose was increased to 12 mg/day 5 days later. Hyperosmolar non-ketotic coma occurred two days later (blood glucose 53 mmol/l, bicarbonate 8 mmol/l, pH of arterial blood 7.2). Search for urinary ketones was negative. Klebsiella pneumonia was isolated in the urine sample. Somatostatin was withdrawn and the patient improved with parenteral nutrition and intravenous insulin. Glucose tolerance was verified after recovery and was normal. Somatostatin is known to impair glucose tolerance and as shown in this case should also be recognized as a cause of hyperosmolar non-ketotic coma. Increasing use of somatostatin, particularly in HIV patients often given other hyperglycaemia inducing drugs such as didanosine, pentamidine, dapsone, and phenytoin should be accompanied with careful monitoring of blood glucose levels.

[Streptococcus milleri subacute spinal cord abscess. Apropos of a case]. / Abcès médullaire subaigu à Streptococcus milleri. A propos d'un cas.

Since 1830, more than eighty cases of spinal cord abscesses have been reported. In half of these cases, it was unfortunately a post-mortem diagnosis. Magnetic resonance imaging (MRI) now gives new possibilities in the diagnosis and treatment of this rare pathology. We report here a case of cervical spinal cord abscess due to Streptococcus milleri. The clinical and laboratory findings, the MRI features, the pathogenicity of the offending pathogen and the surgical approach are discussed and compared with the data from the literature. The functional course was unexpectedly favourable in this patient. MRI allows prompt diagnosis and a precise localisation of the suspected abscess. Rapid surgical drainage is a critical prognostic factor for effective management of spinal cord abscess.

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.

Pneumococcal septic arthritis in adults: clinical analysis and review.

BACKGROUND: Septic arthritis (SA) is a rheumatological emergency that can lead to rapid joint destruction and irreversible loss of function. The most common pathogen causing SA is Staphylococcus aureus which is responsible for 37-65% of cases. Streptococcus pneumoniae is traditionally described as an uncommon cause of SA of a native joint. The objective of our study was to analyse clinical characteristics, treatment, and outcome of all cases of pneumococcal septic arthritis treated in our institution, and to compare them with other series published in the literature. MATERIALS AND METHODS: We conducted a retrospective study of pneumococcal SA identified among all cases of SA diagnosed in a teaching hospital of one thousand beds between 2004 and 2009. Diagnosis was based on culture of joint liquid or by the presence of pneumococcal bacteraemia and purulent (more than 50 000/mm(3) white blood cells with more than 90% neutrophils) joint fluid aspiration. RESULTS: Among 266 cases of SA, nine patients (3·3%) were diagnosed as having pneumococcal SA. The median age was 75 years. The main affected joint was the knee (7/9). No patient had more than one joint involved. Four patients suffered from concomitant pneumonia. Joint culture and blood cultures were positive in 7/9 and 5/9, respectively. Median (range) length of stay was 18 days (3-47 days). One patient with associated pneumococcal bacteraemia died 19 days after admission. Seven patients recovered completely. CONCLUSIONS: Streptococcus pneumoniae is now being increasingly recognized as a common agent of SA. This organism is frequently associated with pneumococcal pneumonia or bacteraemia, particularly in patients with advanced age and comorbidities. Direct inoculation of joint fluid into blood culture medium BACTEC system increases the probability of microbiological diagnosis. The prognosis is usually favourable if the disease is promptly recognized and treated (antibiotic therapy combined with joint drainage).