Antibiotic Therapy for 6 or 12 Weeks for Prosthetic Joint Infection.

BACKGROUND: The management of prosthetic joint infection usually consists of a combination of surgery and antimicrobial therapy. The appropriate duration of antimicrobial therapy for this indication remains unclear. METHODS: We performed an open-label, randomized, controlled, noninferiority trial to compare 6 weeks with 12 weeks of antibiotic therapy in patients with microbiologically confirmed prosthetic joint infection that had been managed with an appropriate surgical procedure. The primary outcome was persistent infection (defined as the persistence or recurrence of infection with the initial causative bacteria, with an antibiotic susceptibility pattern that was phenotypically indistinguishable from that at enrollment) within 2 years after the completion of antibiotic therapy. Noninferiority of 6 weeks of therapy to 12 weeks of therapy would be shown if the upper boundary of the 95% confidence interval for the absolute between-group difference (the value in the 6-week group minus the value in the 12-week group) in the percentage of patients with persistent infection within 2 years was not greater than 10 percentage points. RESULTS: A total of 410 patients from 28 French centers were randomly assigned to receive antibiotic therapy for 6 weeks (205 patients) or for 12 weeks (205 patients). Six patients who withdrew consent were not included in the analysis. In the main analysis, 20 patients who died during follow-up were excluded, and missing outcomes for 6 patients who were lost to follow-up were considered to be persistent infection. Persistent infection occurred in 35 of 193 patients (18.1%) in the 6-week group and in 18 of 191 patients (9.4%) in the 12-week group (risk difference, 8.7 percentage points; 95% confidence interval, 1.8 to 15.6); thus, noninferiority was not shown. Noninferiority was also not shown in the per-protocol and sensitivity analyses. We found no evidence of between-group differences in the percentage of patients with treatment failure due to a new infection, probable treatment failure, or serious adverse events. CONCLUSIONS: Among patients with microbiologically confirmed prosthetic joint infections that were managed with standard surgical procedures, antibiotic therapy for 6 weeks was not shown to be noninferior to antibiotic therapy for 12 weeks and resulted in a higher percentage of patients with unfavorable outcomes. (Funded by Programme Hospitalier de Recherche Clinique, French Ministry of Health; DATIPO ClinicalTrials.gov number, NCT01816009.).

Trypanosoma brucei gambiense excreted/secreted factors impair lipopolysaccharide-induced maturation and activation of human monocyte-derived dendritic cells.

Trypanosoma brucei gambiense, an extracellular eukaryotic flagellate parasite, is the main etiological agent of human African trypanosomiasis (HAT) or sleeping sickness. Dendritic cells (DCs) play a pivotal role at the interface between innate and adaptive immune response and are implicated during HAT. In this study, we investigated the effects of T gambiense and its excreted/secreted factors (ESF) on the phenotype of human monocyte-derived DCs (Mo-DCs). Mo-DCs were cultured with trypanosomes, lipopolysaccharide (LPS), ESF derived from T gambiense bloodstream strain Biyamina (MHOM/SD/82), or both ESF and LPS. Importantly, ESF reduced the expression of the maturation markers HLA-DR and CD83, as well as the secretion of IL-12, TNF-alpha and IL-10, in LPS-stimulated Mo-DCs. During mixed-leucocyte reactions, LPS- plus ESF-exposed DCs induced a non-significant decrease in the IFN-gamma/IL-10 ratio of CD4 + T-cell cytokines. Based on the results presented here, we raise the hypothesis that T gambiense has developed an immune escape strategy through the secretion of paracrine mediators in order to limit maturation and activation of human DCs. The identification of the factor(s) in the T gambiense ESF and of the DCs signalling pathway(s) involved may be important in the development of new therapeutic targets.

Trypanosoma musculi Infection in Mice Critically Relies on Mannose Receptor-Mediated Arginase Induction by a TbKHC1 Kinesin H Chain Homolog.

Arginase activity induction in macrophages is an escape mechanism developed by parasites to cope with the host's immune defense and benefit from increased host-derived growth factor production. We report that arginase expression and activity were induced in macrophages during mouse infection by Trypanosoma musculi, a natural parasite of this host. This induction was reproduced in vitro by excreted/secreted factors of the parasite. A mAb directed to TbKHC1, an orphan kinesin H chain from Trypanosoma brucei, inhibited T. musculi excreted/secreted factor-mediated arginase induction. Anti-TbKHC1 Ab also inhibited T. musculi growth, both in vitro and in vivo. Induction of arginase activity and parasite growth involved C-type lectin receptors, because mannose injection decreased arginase activity induction and parasite load in vitro and in vivo. Accordingly, the parasite load was reduced in mice lacking mannose receptor C-type 1. The T. musculi KHC1 homolog showed high similarity with TbKHC1. Bioinformatics analysis revealed the presence of homologs of this gene in other trypanosomes, including pathogens for humans and animals. Host metabolism dysregulation represents an effective parasite mechanism to hamper the host immune response and modify host molecule production to favor parasite invasion and growth. Thus, this orphan kinesin plays an important role in promoting trypanosome infection, and its neutralization or the lock of its partner host molecules offers promising approaches to increasing resistance to infection and new developments in vaccination against trypanosomiasis.

Prognostic factors of calcaneal osteomyelitis.

BACKGROUND: Calcaneal osteomyelitis is difficult to manage and requires a multidisciplinary approach. The aim of this study was to describe the characteristics and outcomes of calcaneal osteomyelitis, and to determine prognostic factors. METHODS: This was an observational and retrospective study including all patients presenting with calcaneal osteomyelitis referred to a tertiary referral centre between January 2005 and December 2010. RESULTS: Forty-two patients (mean age 50.7 y, range 22-89 y) were included. Fifteen were female. The mean duration of follow-up was 20 months (range 12-48 months). Twenty-six (62%) were post-traumatic osteomyelitis and 16 (38%) were secondary to neurological damage (sensitivity or motor impairment). All patients underwent surgical management with bone curettage and appropriate antibiotic therapy. Staphylococcus aureus was the most commonly isolated bacterium and was found in 29 patients. Polymicrobial samples were observed in 29 patients. Pseudomonas aeruginosa was associated with calcaneal osteomyelitis secondary to neurological damage (n = 7; 44% p = 0.045). Twenty-eight patients (66.7%) healed without the need to resort to amputation. The mean time to healing was 29 weeks with a range of 4-144 weeks. Relapse of bone infection occurred in 17 patients (40.5%). Seven patients (16.7%) required amputations. Favourable prognostic factors for healing without amputation were an American Society of Anesthesiologists (ASA) score < 2 (p < 10(-4)), post-traumatic calcaneal osteomyelitis (p = 0.001), age < 65 y (p = 0.02), absence of neuropathy (p = 0.005), and absence of diabetes mellitus (p = 0.02). CONCLUSIONS: Calcaneal osteomyelitis is characterized by frequent relapse with delayed wound healing. Clinicians should take into account the impact of older age, as well as co-morbidities such as diabetes mellitus or the presence of neuropathy, during the routine management of patients with this difficult-to-treat bone infection.

Assessment of the impact of telehealth intervention in patients with bone and joint infection.

OBJECTIVES: Patients with bone and joint infections (BJI) are involved in a complex care pathway and require prolonged antimicrobial treatment. Some studies have suggested that a pharmacist-led telehealth intervention (TI) could help to ensure better follow-up of chronic diseases. To our knowledge, there are no data on the effects of pharmacist-led TI on patients with BJI. The aim of this study is to assess the impact of a TI on patients treated for BJIs at three weeks after hospital discharge. PATIENTS AND METHODS: Patients encountered during hospitalization and receiving standardized care including TI were included in the study. All adverse events (AE) reported by patients during TI were evaluated. Impact of pharmaceutical interventions (PIs) provided by a clinical pharmacist following TI was evaluated by CLEO© (CLinical, Economic and Organizational) scale. Patient satisfaction concerning TI was assessed by an anonymous questionnaire following medical consultation at the end of antimicrobial treatment. RESULTS: Over a 4-month period, 36 patients received TI. Fifty-two AEs were identified in 21 patients (58%). Two patients were hospitalized due to an AE. Clinical pharmacists provided 34 pharmaceutical interventions (PIs) for 23 patients (64%). According to CLEO scale, 11 PIs had a major clinical impact (32%), 6 PIs (18%) had a favorable impact on the direct cost of treatment and 27 PIs (79%) had positive organizational impact. Concerning TI process, patients were satisfied or very satisfied, with an average score of 9.6/10. CONCLUSION: TI led to a high number of pharmaceutical interventions (PIs), with a meaningful clinical, organizational, and economic impact. Patients were also highly satisfied with this intervention.

Clinical features and treatment outcomes of bone and joint nontuberculous mycobacterial infections according to immune status: a 9-year retrospective observational cohort.

OBJECTIVES: Nontuberculous mycobacteria (NTM) bone and joint infections (BJIs) are uncommon. We evaluated the characteristics of BJIs and identified differences according to immune status. METHODS: We performed a multicenter retrospective study in France involving patients with documented NTM BJI over a 9-year period. We collected the clinical and microbiological characteristics, management, and clinical outcomes of the patients. RESULTS: Overall, 95 patients were included, of whom 50.5% (48/95) were immunosuppressed. Tenosynovitis was more frequent in the immunocompetent group, and native arthritis more common in the immunosuppressed group. Mycobacerium marinum and M. abscessus complex were significantly more frequent in the immunocompetent group, and M. avium and M. xenopi were significantly more frequent in the immunosuppressed group. The combination of antibiotherapy with surgery tended to be more frequent in the immunocompetent than the immunosuppressed group (63.8% (30/47) vs 47.8% (22/46), respectively); of the latter, 45.7% (21/46) received antimicrobial therapy alone, a higher frequency than in the immunocompetent group (23.4%, 11/47). The median duration of antimicrobial treatment was similar in the two groups (11 months). Mortality was significantly higher in the immunosuppressed group. CONCLUSIONS: Although the clinical presentations and the NTM species involved in BJI differed according to immune status, most recovered completely after treatment.

Characteristics of prosthetic joint infections leading to bacteremia: a case-control study.

The possible systemic infectious consequences of prosthetic joint infections (PJI) are poorly documented in the literature. We assessed the frequency of postoperative prosthetic hip and knee infections leading to bacteremia and investigated their associated factors among patients treated between 2005 and 2009. Among 633 patients with PJI, 62 (9.8%) also had positive blood cultures (95% confidence interval (CI) 7.5-12.1). After complete investigations, the prosthesis was considered as the direct cause of bacteremia in 14 cases (2.2%; 95% CI 1.1-3.4). In the conditional logistic regression analysis, PJI leading to bacteremia was more frequently observed in cases of relapses of a prior PJI (adjusted odds ratio (aOR) 7.3, p = 0.07) and in patients with a C-reactive protein value upon admission ≥ 180 mg/l (aOR 4.5, p = 0.04). None of the 8 bacteremic patients treated with surgical debridement and prosthetic retention were cured from joint infection. These preliminary results raise concerns about the fact that debridement with prosthetic retention may not be an appropriate option in the context of PJI leading to bacteremia, contrary to PJI resulting from hematogenous seeding.

Ultrasonography performed by an infectiologist in hip and knee prosthetic joint and native joint infections.

INTRODUCTION: Clinical ultrasonography (US) by infectiologists has only recently been developing, and as now there is little literature on the subject. Our study focuses on the conditions and diagnostic performance of clinical ultrasound imaging by infectiologists in cases of hip and knee prosthetic and native joint infection. METHODS: A retrospective study carried out between June 1st 2019 and March 31st 2021 in the University Hospital of Bordeaux, South-Western France. We measured US sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV), combined or not with the analysis of articular fluid, compared to the MusculoSketetal Infection Society (MSIS) score in prosthetic joints, or to expert diagnosis in native joints. RESULTS: Fifty-four patients underwent US by an infectiologist in an infectious disease ward, including 11 (20.4%) for native joint and 43 (79.6%) for prosthetic joint. Joint effusion and/or periarticular collection were highlighted in 47 (87%) patients, and US led to 44 punctures. In all patients (n = 54), Se, Sp, PPV and NPV of US alone were 91%, 19%, 64% and 57%, respectively. When US was combined with fluid analysis, Se, Sp, PPV, NPV were 68%, 100%, 100%, 64% in all patients (n = 54), 86%, 100%, 100%, 60% in acute arthritis (n = 17) and 50%, 100%, 100% and 65% respectively in non-acute arthritis (n = 37). CONCLUSION: These results suggest that US by infectiologists effectively diagnoses osteoarticular infections (OAIs). This approach has many applications in infectiology routines. Consequently, it would be interesting to define the contents of a first level of infectiologist competence in US clinical practice.

Preoperative and perioperative risk factors, and risk score development for prosthetic joint infection due to Staphylococcus aureus: a multinational matched case-control study.

OBJECTIVES: We aim to identify the preoperative and perioperative risk factors associated with post-surgical Staphylococcus aureus prosthetic joint infections (PJI) and to develop and validate risk-scoring systems, to allow a better identification of high-risk patients for more efficient targeted interventions. METHODS: We performed a multicenter matched case-control study of patients who underwent a primary hip and knee arthroplasty from 2014 to 2016. Two multivariable models by logistic regression were performed, one for the preoperative and one for perioperative variables; predictive scores also were developed and validated in an external cohort. RESULTS: In total, 130 cases and 386 controls were included. The variables independently associated with S. aureus-PJI in the preoperative period were (adjusted OR; 95% CI): body mass index >30 kg/m2 (3.0; 1.9 to 4.8), resident in a long-term care facility (2.8; 1.05 to 7.5), fracture as reason for arthroplasty (2.7; 1.4 to 5.03), skin disorders (2.5; 0.9 to 7.04), previous surgery in the index joint (2.4; 1.3 to 4.4), male sex (1.9; 1.2 to 2.9) and American Society of Anesthesiologists index score 3 to 4 (1.8; 1.2 to 2.9). The area under the receiver operating characteristic curve was 0.73 (95% CI 0.68 to 0.78). In perioperative model, the risk factors were the previous ones plus surgical antibiotic prophylaxis administered out of the first 60 minutes before incision (5.9; 2.1 to 16.2), wound drainage for >72 hours after arthroplasty (4.5; 1.9 to 19.4) and use of metal bearing material versus ceramic (1.9; 1.1 to 3.3). The area under the receiver operating characteristic curve was 0.78 (95% CI 0.72 to 0.83). The predictive scores developed were validated in the external cohort. DISCUSSION: Predictive scores for S. aureus-PJI were developed and validated; this information would be useful for implementation of specific preventive measures.

Rates and Predictors of Treatment Failure in Staphylococcus aureus Prosthetic Joint Infections According to Different Management Strategies: A Multinational Cohort Study-The ARTHR-IS Study Group.

INTRODUCTION: Guidelines have improved the management of prosthetic joint infections (PJI). However, it is necessary to reassess the incidence and risk factors for treatment failure (TF) of Staphylococcus aureus PJI (SA-PJI) including functional loss, which has so far been neglected as an outcome. METHODS: A retrospective cohort study of SA-PJI was performed in 19 European hospitals between 2014 and 2016. The outcome variable was TF, including related mortality, clinical failure and functional loss both after the initial surgical procedure and after all procedures at 18 months. Predictors of TF were identified by logistic regression. Landmark analysis was used to avoid immortal time bias with rifampicin when debridement, antibiotics and implant retention (DAIR) was performed. RESULTS: One hundred twenty cases of SA-PJI were included. TF rates after the first and all surgical procedures performed were 32.8% and 24.2%, respectively. After all procedures, functional loss was 6.0% for DAIR and 17.2% for prosthesis removal. Variables independently associated with TF for the first procedure were Charlson ≥ 2, haemoglobin < 10 g/dL, bacteraemia, polymicrobial infection and additional debridement(s). For DAIR, TF was also associated with a body mass index (BMI) > 30 kg/m2 and delay of DAIR, while rifampicin use was protective. For all procedures, the variables associated with TF were haemoglobin < 10 g/dL, hip fracture and additional joint surgery not related to persistent infection. CONCLUSIONS: TF remains common in SA-PJI. Functional loss accounted for a substantial proportion of treatment failures, particularly after prosthesis removal. Use of rifampicin after DAIR was associated with a protective effect. Among the risk factors identified, anaemia and obesity have not frequently been reported in previous studies. TRIAL REGISTRATION: This study is registered at clinicaltrials.gov, registration no. NCT03826108.

Staphylococcus aureus is one of the most virulent bacteria and frequently causes prosthetic joint infections.Knowledge of the treatment of this type of infection has advanced in recent years, and treatment guidelines have led to improved management. Typically, the successful treatment of these infections has been determined by clinical cure, that is, the symptoms of infection have disappeared, but has not taken into account loss of function (such as significant difficulties walking), which is critical for the patient's quality of life. Our aim in this study was to evaluate the success of current management strategies for S. aureus prosthetic joint infection, including recovery of functionality, and the factors that predict why some of these infections are not cured, to identify areas for improvement.In a multinational cohort of 128 patients with S. aureus prosthetic joint infection, rates of treatment failure were found to be high, with significant rates of loss of function, especially when the prosthesis needed to be removed. Loss of function was less frequent when the infection was initially treated with surgical cleaning without removal of the prosthesis, even when this procedure failed at first. We found that anaemia and obesity were associated with lower treatment success, and that the probability of treatment success increased when surgical cleaning without prosthesis removal was performed early, and when the antibiotic rifampicin was used in combination with another antibiotic.

Increased risk of abnormal proximal renal tubular function with HIV infection and antiretroviral therapy.

Abnormal kidney function is common in the course of human immunodeficiency virus (HIV) infection. Here, we performed a cross-sectional analysis using 399 patients within the Aquitaine cohort (a hospital-based cohort of HIV-1-infected patients receiving routine clinical management) to estimate the prevalence of proximal renal tubular dysfunction (PRTD) associated with HIV infection. These patients did not differ statistically by sociodemographics, median age, years since HIV diagnosis, AIDS stage, or median CD4 cell count from the entire 3080 patient cohort. Antiretroviral therapy was received by 352 patients, with 256 given tenofovir (TDF); 325 had undetectable HIV plasma viral load, and 26 were diagnosed with PRTD. In multivariate analysis, significant independent associations were found between PRTD and age (odds ratio (OR) 1.28 per 5-year increase), atazanavir (OR 1.28 per year of exposure), and TDF (OR 1.23 per year) treatment. Among patients having received TDF-containing regimens over a 5-year period, PRTD remained significantly associated with TDF exposure when treatment was ongoing (OR 5.22) or had been discontinued (OR 11.49). Thus, cumulative exposure to TDF and/or atazanavir was associated with an increased risk of PRTD, with concern about its reversibility in patients with HIV.

Management of Chronic Osteomyelitis by an Orthoplastic Team: 7-Year Experience of a University Hospital.

BACKGROUND: Treating chronic osteomyelitis of the lower extremities is challenging. The treatment of acute lower limb trauma by orthoplastic teams has shown good results over the past few decades. This study aimed to characterize surgical outcomes of leg and heel chronic osteomyelitis by an orthoplastic team. METHODS: The cases of 113 consecutive leg and heel chronic osteomyelitis patients undergoing soft-tissue reconstruction with an orthopedic procedure were reviewed in this retrospective single-center observational study. The main objective was to assess surgical outcomes of skin healing and gait recovery at the 1-year follow-up. The secondary objective was to evaluate the global success rate at the last follow-up. RESULTS: The median follow-up was 19.7 months. A free flap was performed for 33 patients (29.2 percent) and a locoregional flap was used in 79 patients (69.9 percent). Seventy-two patients (63.7 percent) had chronic osteomyelitis on continuous bone. The others had a septic pseudarthrosis with a mean bone defect length of 42.9 mm. Forty-four patients (38.9 percent) underwent curettage only, eight (7.1 percent) underwent curettage and cement, 20 (17.7 percent) underwent curettage and bone fixation, and 39 (34.5 percent) underwent the Masquelet technique. At the 1-year follow-up, 72 patients (63.7 percent) had achieved skin healing and had recovered their gait. The success rate at all follow-up time points was 82.3 percent. The median time to achieve skin healing was 6.5 months and that to bone union in cases of septic pseudarthrosis was 7.9 months. CONCLUSION: Orthoplastic management of leg and heel chronic osteomyelitis patients with combined soft-tissue reconstruction using an orthopedic procedure was a viable strategy that offered good results even though the time to complete healing was long. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Impact on the Gut Microbiota of Intensive and Prolonged Antimicrobial Therapy in Patients With Bone and Joint Infection.

There is a growing interest in the potentially deleterious impact of antibiotics on gut microbiota. Patients with bone and joint infection (BJI) require prolonged treatment that may impact significantly the gut microbiota. We collected samples from patients with BJI at baseline, end of antibiotics (EOT), and 2 weeks after antibiotic withdrawal (follow-up, FU) in a multicenter prospective cohort in France. Microbiota composition was determined by shotgun metagenomic sequencing. Fecal markers of gut permeability and inflammation as well as multi-drug-resistant bacteria (MDRB) and Clostridioides difficile carriage were assessed at each time point. Sixty-two patients were enrolled: 27 native BJI, 14 osteosynthesis-related BJI, and 21 prosthetic joint infections (PJI). At EOT, there was a significant loss of alpha-diversity that recovered at FU in patients with native BJI and PJI, but not in patients with osteosynthesis-related BJI. At EOT, we observed an increase of Proteobacteria and Bacteroidetes that partially recovered at FU. The principal component analysis (PCoA) of the Bray-Curtis distance showed a significant change of the gut microbiota at the end of treatment compared to baseline that only partially recover at FU. Microbiota composition at FU does not differ significantly at the genus level when comparing patients treated for 6 weeks vs. those treated for 12 weeks. The use of fluoroquinolones was not associated with a lower Shannon index at the end of treatment; however, the PCoA of the Bray-Curtis distance showed a significant change at EOT, compared to baseline, that fully recovered at FU. Levels of fecal neopterin were negatively correlated with the Shannon index along with the follow-up (r 2 = 0.17; p < 0.0001). The PCoA analysis of the Bray-Curtis distance shows that patients with an elevated plasma level of C-reactive protein (≥5 mg/L) at EOT had a distinct gut microbial composition compared to others. MDRB and C. difficile acquisition at EOT and FU represented 20% (7/35) and 37.1% (13/35) of all MDRB/C. difficile-free patients at the beginning of the study, respectively. In patients with BJI, antibiotics altered the gut microbiota diversity and composition with only partial recovery, mucosal inflammation, and permeability and acquisition of MDRB carriage. Microbiome interventions should be explored in patients with BJI to address these issues.

Variable-number tandem-repeat markers for typing Mycobacterium intracellulare strains isolated in humans.

BACKGROUND: Mycobacterium intracellulare, a species of the Mycobacterium avium complex, may be the cause of severe lung, lymphatic node, skin and bone/joint infections, as well as bacteriemia. The goal of this work was to identify Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeat (MIRU-VNTR) markers and to study their variability in a collection of isolates of M. intracellulare collected in humans. We studied 61 isolates collected in humans between 2001 and 2008, as well as the reference strain, M. intracellulare ATCC 13950. RESULTS: We identified 45 MIRU-VNTR candidates, of which 17 corresponded to the MIRU-VNTR identified in the genome of M. intracellulare ATCC 13950. Among the 45 potential MIRU-VNTR, seven were selected for use in a MIRU-VNTR assay applied to our collection of isolates. Forty-four patterns were found by MIRU-VNTR typing and the discriminatory power of the assay was high with a Hunter-Gaston diversity index of 0.98. We do not have evidence of a particular distribution of MIRU-VNTR polymorphism according to clinical situation. CONCLUSIONS: Our results suggest that MIRU-VNTR typing could be used for molecular epidemiological studies applied to M. intracellulare.

Association between psoas abscess and prosthetic hip infection: a case-control study.

BACKGROUND AND PURPOSE: The relationship between prosthetic hip infection and a psoas abscess is poorly documented. We determined the frequency of prosthetic hip infections associated with psoas abscesses and identified their determinants. METHODS: We conducted a 2-year observational study. Data from patients with psoas abscesses that were associated with prosthetic hip infections were examined in a case-control study. RESULTS: Of 106 patients admitted to the Infectious Diseases Department with prosthetic hip infection, 13 also had a psoas abscess (12%; 95% CI: 6-19). By conditional logistic regression analysis, psoas abscesses were observed more frequently in cases of hematogenous prosthetic infections (OR = 93, p = 0.06) and in patients with a history of neoplasm (OR = 20, p = 0.03). INTERPRETATION: Our results suggest that the presence of psoas abscesses is a frequent but under-diagnosed complication of prosthetic hip infection. We recommend that an abdominal CT scan be performed on patients with hematogenous prosthetic hip infection or with a history of neoplasm.

Purification of Extracellular Trypanosomes, Including African, from Blood by Anion-Exchangers (Diethylaminoethyl-cellulose Columns).

This method allows the separation of trypanosomes, parasites responsible for animal and human African trypanosomiasis (HAT), from infected blood. This is the best method for diagnosis of first stage HAT and furthermore this parasite purification method permits serological and research investigations. HAT is caused by Tsetse fly transmitted Trypanosoma brucei gambiense and T. b. rhodesiense. Related trypanosomes are the causative agents of animal trypanosomiasis. Trypanosome detection is essential for HAT diagnosis, treatment and follow-up. The technique described here is the most sensitive parasite detection technique, adapted to field conditions for the diagnosis of T. b. gambiense HAT and can be completed within one hour. Blood is layered onto an anion-exchanger column (DEAE cellulose) previously adjusted to pH 8, and elution buffer is added. Highly negatively charged blood cells are adsorbed onto the column whereas the less negatively charged trypanosomes pass through. Collected trypanosomes are pelleted by centrifugation and observed by microscopy. Moreover, parasites are prepared without cellular damage whilst maintaining their infectivity. Purified trypanosomes are required for immunological testing; they are used in the trypanolysis assay, the gold standard in HAT serology. Stained parasites are utilized in the card agglutination test (CATT) for field serology. Antigens from purified trypanosomes, such as variant surface glycoprotein, exoantigens, are also used in various immunoassays. The procedure described here is designed for African trypanosomes; consequently, chromatography conditions have to be adapted to each trypanosome strain, and more generally, to the blood of each species of host mammal. These fascinating pathogens are easily purified and available to use in biochemical, molecular and cell biology studies including co-culture with host cells to investigate host-parasite relationships at the level of membrane receptors, signaling, and gene expression; drug testing in vitro; investigation of gene deletion, mutation, or overexpression on metabolic processes, cytoskeletal biogenesis and parasite survival.

Added value of [18F]fluorodeoxyglucose positron emission tomography/computed tomography for the diagnosis of post-operative instrumented spine infection.

PURPOSE: Post-operative instrumented spine infection (PISI) is an infrequent complication. Diagnosis of spinal implant infection can be difficult, especially in case of chronic infection. METHODS: This retrospective study attempts to evaluate the diagnostic performance of [18F]fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in PISI. Imagings were performed between April 2010 and June 2018 among patients referred for suspected chronic spinal implant infection. PET/CT were performed more than 12 weeks after surgery. PET/CT images were re-interpreted independently by two nuclear medicine physicians without knowledge of the patient's conditions. PET/CT data were analyzed both visually and semi-quantitatively (SUVmax). MRI results were collected from medical records. The final diagnosis of infection was based on bacteriological cultures or a twelve-month follow-up. RESULTS: Forty-nine PET/CT were performed in 44 patients (22 women, median age 65.0 years). Twenty-two patients had a diagnosis of infection during follow-up. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for PET/CT were 86.4%, 81.5%, 79.2%, and 88.0%. Sensitivity, specificity, PPV and NPV were 66.7%, 75.0%, 66.0%, 75.0% respectively for MRI and 50.0%, 92.6%, 84.6% and 69.4% for serum C-reactive protein (CRP). Although these values were higher for PET/CT than for MRI or CRP, the differences were not statistically significant. In this setting, false positives with PET/CT can be observed in case of previous spine infection or adjacent segments disc disease. False negatives can result of extensive instrumented arthrodesis or infection with low virulence bacteria. CONCLUSION: PET/CT is useful for the diagnosis of PISI. These results should be evaluated in further prospective study.

Trypanosomatid Infections: How Do Parasites and Their Excreted-Secreted Factors Modulate the Inducible Metabolism of l-Arginine in Macrophages?

Mononuclear phagocytes (monocytes, dendritic cells, and macrophages) are among the first host cells to face intra- and extracellular protozoan parasites such as trypanosomatids, and significant expansion of macrophages has been observed in infected hosts. They play essential roles in the outcome of infections caused by trypanosomatids, as they can not only exert a powerful antimicrobial activity but also promote parasite proliferation. These varied functions, linked to their phenotypic and metabolic plasticity, are exerted via distinct activation states, in which l-arginine metabolism plays a pivotal role. Depending on the environmental factors and immune response elements, l-arginine metabolites contribute to parasite elimination, mainly through nitric oxide (NO) synthesis, or to parasite proliferation, through l-ornithine and polyamine production. To survive and adapt to their hosts, parasites such as trypanosomatids developed mechanisms of interaction to modulate macrophage activation in their favor, by manipulating several cellular metabolic pathways. Recent reports emphasize that some excreted-secreted (ES) molecules from parasites and sugar-binding host receptors play a major role in this dialog, particularly in the modulation of the macrophage's inducible l-arginine metabolism. Preventing l-arginine dysregulation by drugs or by immunization against trypanosomatid ES molecules or by blocking partner host molecules may control early infection and is a promising way to tackle neglected diseases including Chagas disease, leishmaniases, and African trypanosomiases. The present review summarizes recent knowledge on trypanosomatids and their ES factors with regard to their influence on macrophage activation pathways, mainly the NO synthase/arginase balance. The review ends with prospects for the use of biological knowledge to develop new strategies of interference in the infectious processes used by trypanosomatids, in particular for the development of vaccines or immunotherapeutic approaches.