Olivier Epaulard

African Tick Bite Fever in Elderly Patients: 8 Cases in French Tourists Returning from South Africa

BACKGROUND African tick-bite fever, a tickborne disease caused by Rickettsia africae, is endemic in rural areas of sub-Saharan Africa and in the French West Indies. Most cases reported in the literature occurred in middle-aged, otherwise-healthy persons and corresponded to benign diseases. The course of African tick bite fever in elderly people is less well documented. METHODS The medical records of 8 elderly patients infected with R. africae during a trip to South Africa in 2005 are presented to summarize the epidemiologic, clinical, microbiological, treatment, and disease course characteristics. RESULTS Eight patients, aged 63-75 years, developed African tick bite fever symptoms after a trip to South Africa. R. africae was grown from cutaneous eschar biopsy specimens obtained from 4 patients, confirming African tick bite fever. We observed unusual findings in this elderly population. Rash was frequent (present in 87.5% of patients), vesicular (in 100% of patients with rash), and often associated with an enanthema (in 50% of patients with rash). Severe clinical manifestations occurred: lymphangitis and myocarditis in 1 patient and suspected brain involvement in 2 patients. We observed severe and long-lasting general symptoms, including fever (in 75% of patients), chills (87.5%), asthenia (50%), anorexia (50%), and weight loss (12.5%). With doxycycline therapy, the outcome was favorable in all cases, but complete recovery was slow. CONCLUSION Ecotourism to sub-Saharan Africa is expanding, and people of advanced age, often with underlying chronic diseases, account for an increasing proportion of travelers. African tick bite fever appears to be more symptomatic in this population. Recommendations advising personal prophylactic measures to prevent tick bites in travelers to regions of endemicity may be particularly important for elderly individuals.

Quantitative real‐time PCR tests for diagnostic and prognostic purposes in cases of legionellosis

The usefulness of two quantitative real-time PCR assays (qrt-PCRmip targeting Legionella pneumophila, and qrt-PCR16S targeting all Legionella species) performed on lower respiratory tract (LRT) samples for diagnostic and prognostic purposes in 311 patients hospitalized for community-acquired pneumonia (CAP) in Rhône-Alpes (France) was evaluated. The Now Legionella urinary antigen test (UAT) from Binax (Portland, ME, USA) was used as a reference test. Samples were divided into two groups. Group A included 255 CAP patients admitted to Chambery hospital in 2005 and 2006. The Now Legionella UAT was positive in 14 patients. Sensitivities, specificities, positive predictive and negative predictive values for both qrt-PCR tests were 63.6, 98.7, 77.7 and 97.4%, respectively. Group B included 56 consecutive legionellosis patients diagnosed during a 4-year period (2003-2006) at the Grenoble University Hospital. The qrt-PCR16S and qrt-PCRmip displayed a sensitivity of 82.14 and 80.4%, respectively. Among the 70 legionellosis cases, L. pneumophila serogroup 1 was isolated in 15; qrt-PCRmip was positive in another 36, suggesting L. pneumophila infection, whereas the Legionella species involved could not be determined in the remaining 19 cases. The Legionella burden in LRT samples at the time of admission was determined in 46 patients using qrt-PCR16S tests, 44 for qrt-PCR mip groups A and B patients. It varied from 1.9 to 8.35 log(10) DNA copies/mL of LRT sample for qrt-PCR16S and from 1.9 to 8.11 log(10) DNA copies/mL of sample for qrt-PCRmip. High bacterial loads in LRT samples at hospital admission were significantly associated with higher Fine classes, the need for hospitalization in an intensive care unit and for prolonged hospitalization.

Active Tuberculosis and Venous Thromboembolism: Association According to International Classification of Diseases, Ninth Revision Hospital Discharge Diagnosis Codes

BACKGROUND Infections are risk factors for venous thromboembolism (VTE), especially if severe and acute. The role of chronic infections such as active tuberculosis is ill defined, although several case reports and small series have suggested an association between tuberculosis and VTE. METHODS Using data from the Premier Perspective database (27 659 947 admissions), we performed a multivariate analysis to assess the specific VTE risk associated with tuberculosis. The analysis was adjusted on classic risk factors for VTE. RESULTS The prevalence of VTE among patients with active tuberculosis was 2.07% (95% confidence interval [CI], 1.62%-2.59%). In a multivariate analysis model, adults with active tuberculosis had a greater risk of VTE than those without (odds ratio, 1.55 [95% CI, 1.23-1.97], P < .001), close to the previously reported risk associated with neoplasia. No particular link was found between pulmonary tuberculosis and pulmonary embolism, or between extrapulmonary tuberculosis and deep vein thrombosis. This may suggest the preponderant role of a systemic hypercoagulable state over an intrathoracic venous compression mechanism. In-hospital mortality of patients with both active tuberculosis and VTE (11/72 [15%]) was higher than mortality of patients with only active tuberculosis (92/3413 [2.7%]) or only VTE (5062/199 480 [2.5%]) (P < .001). Pulmonary embolism was more frequent in black patients, suggesting that this population, which is also more likely to suffer from tuberculosis, should be followed carefully. CONCLUSIONS Tuberculosis must be considered as a pertinent risk factor for VTE and should be included in thromboembolism risk evaluation similar to any acute and severe infection.

Kawasaki disease in adults: Observations in France and literature review.

OBJECTIVE Kawasaki disease (KD) is a vasculitis that mostly occurs in young children and rarely in adults. We analyzed the characteristics of adult-onset KD (AKD) in France. METHODS We collected retrospective and prospective data for patients with a diagnosis of KD occurring after the age of 18 years. Cases were obtained via various French medical networks and identified from the international literature. RESULTS We included 43 patients of AKD at 26 institution from 1992 to 2015, with mean (SD) age 30 (11) years (range 18-68) and sex ratio (M/F) 1.2; 34 patients met the American Heart Association criteria and 9 were incomplete AKD. The median time to diagnosis was 13 days (interquartile range 8-21). The main symptoms were fever (100%), exanthema (98%), changes in the extremities (91%), conjunctivitis (77%), oral cavity changes (89%), cervical adenitis (55%) and cardiac abnormalities (45%). Overall, 35% of patients showed large-vessel vasculitis: coronary vasculitis (26%) and coronary aneurysm (19%). Treatment was mostly intravenous immunoglobulins (79%) and aspirin (81%). Four patients showed myocardial infarction due to coronary vasculitis, but none were treated with IVIg because of late diagnosis. After a median follow-up of 5 months (range 1-117), persistent aneurysm was noted in 9% of cases. Damage was significantly lower with early treatment than late or no treatment (p=0.01). CONCLUSION Given the high frequency of cardiac involvement and complications in this series of AKD, diagnosis and treatment should not be delayed, and early IVIg treatment seems to improve the outcome.

Fatal adenoviral and enteroviral infections and an Epstein-Barr virus positive large B-cell lymphoma after alemtuzumab treatment in a patient with refractory Sézary syndrome

Alemtuzumab is an antibody binding to CD52, an antigen expressed on lymphocytes. This immunotherapy has been tested as potential therapy in haematological malignancies. We report adenoviral and enteroviral infections and an EBV positive B-cell lymphoma after alemtuzumab therapy. These fatal opportunistic complications have been rarely, if ever, reported before.

Imported pulmonary histoplasmosis in three French cavers after a trip to Cuba.

Pulmonary histoplasmosis is a rare disease in France, where all cases are imported. Diagnosis is difficult in nonendemic areas, often based on travel history and observation of epidemic in a group. We report three cases of pulmonary histoplasmosis that occurred in a group of 12 French cavers traveling to Cuba.

Multicenter evaluation of whole-blood Epstein-Barr viral load standardization using the WHO international standard

ABSTRACT The first WHO international standard for Epstein-Barr virus (EBV) (WHO EBV standard) for nucleic acid amplification technology (NAT)-based assays was commercialized in January 2012 by the National Institute for Biological Standards and Control. In the study reported here, we compared whole-blood EBV DNA load (EDL) results from 12 French laboratories for seven samples (Quality Controls for Molecular Diagnostics 2013 proficiency panel) in order to determine whether expression in international units reduces interlaboratory variability in whole-blood EDLs. Each testing laboratory used a conversion factor to convert EDL results from copies per milliliter to international units per milliliter. This conversion factor was calculated from the WHO EBV standard according to the protocol described in this study (nine laboratories) or the recommendations of the PCR kit suppliers (three laboratories). The interlaboratory variability in whole-blood EDL results was reduced after standardization of the results using the WHO EBV standard. For the seven samples tested, standard deviations (SD) ranged from 0.41 to 0.55 when the results were expressed in log copies per milliliter, whereas the SD ranged from 0.17 to 0.32 when results were given in log international units per milliliter. Comparing the variance data (F test), we showed that the dispersion of whole-blood EDL results was significantly lower when they were expressed in log international units per milliliter (P < 0.001 for six of seven samples and P < 0.05 for one sample with a low mean EDL of 2.62 log IU/ml). This study showed that the use of the WHO EBV standard could improve the homogeneity of whole-blood EDL results between laboratories as well as the monitoring of patients at high risk of posttransplant lymphoproliferative disorders or other EBV-associated diseases.

Infective endocarditis-related stroke: Diagnostic delay and prognostic factors

Infective endocarditis is frequently revealed by complications such as stroke, but the diagnostic delay between stroke and infective endocarditis may be long. We retrospectively reviewed all cases of infective endocarditis-associated stroke referred to our institution from 2000 to 2007, with special attention to diagnostic delay and survival. Most (26) of the 34 studied patients presented with stroke before diagnosis of infective endocarditis. The median delay before infective endocarditis diagnosis was 8 d (0–40 d), and was longer in cases with negative blood cultures. Diagnostic delay had no influence upon survival. When diagnosis of infective endocarditis occurred first, stroke developed in 3 patients during the first week of antibiotic therapy; in 3 patients, stroke occurred after valvular surgery. Overall survival was 67.6%; a small vegetation and non-staphylococcal aetiology were associated with a better outcome. In conclusion, infective endocarditis diagnosis is frequently delayed in patients presenting with stroke, particularly if blood cultures are sterile. The risk of delayed stroke after valvular surgery must be considered.

Evolution of EBV seroprevalence and primary infection age in a French hospital and a city laboratory network, 2000–2016

Background According to rare studies, the age at EBV primary infection (PI) has recently risen in some developed countries. A later age at infection is generally considered a risk factor for severe EBV PI, although few studies exist on this subject. Our investigation aimed to determine whether EBV seroprevalence and EBV PI epidemiology have evolved in France, and to what extent age and infection intensity (regarding biological parameters) are correlated. Methods and findings We conducted a retrospective study of the following EBV serological tests databases: tests carried out at Grenoble University Hospital (2000–2016) (n = 53,553); and tests carried out by a network of city laboratories in Grenoble area (2008–2015) (n = 27,485). The hospital population showed a continuous, significant decrease in EBV seroprevalence over the studied period for patients aged 20 and over (p<0.01). The seroprevalence also decreased for different age classes (<10, 15–19, 20–30, and 30–40 years old) over the periods 2001–2005, 2006–2010, and 2011–2015. Consistently, the age at PI was significantly higher in the years 2008–2015 than in the years 2001–2007 (15.6±12.0 vs. 13.7±11.0; p = 0.03). The city laboratory population showed the same trend of decreasing seroprevalence (p = 0.06); no significant variations in age at PI were observed. The age at PI was positively correlated with ASAT, ALAT, γGT, and bilirubin blood levels (p<0.01) and negatively correlated with platelet counts (p<0.05). Conclusion In the last 15 years, the age at EBV PI has increased, whereas seroprevalence has decreased. Moreover, our findings confirm the positive correlation between age and biological abnormalities. Taken together, these results suggest that the incidence of severe EBV PI will increase in the future.

Dynamics of Epstein‐Barr viral load after hematopoietic stem cell transplantation and effect of preemptive rituximab therapy

Epstein‐Barr virus (EBV) displays oncogenic properties, particularly in the immunocompromised host. Notably, hematopoietic stem cell transplantation (HSCT) recipients with a detectable blood EBV viral load (BEBVL) are considered at higher risk of post‐transplant lymphoproliferative diseases (PTLD). Therefore, BEBVL is monitored after HSCT, and preemptive rituximab may be used in patients with high values. However, little is known about post‐HSCT BEBVL dynamics, and the threshold that should lead to anti‐CD20 therapy is poorly defined.