Epidemiology and risk factors for extension of necrotizing otitis externa.

PURPOSE: Necrotizing otitis externa (OEN) is an aggressive and morbid infection of the external acoustic meatus. What are the risk factors for OEN extension? METHODS: French monocentric retrospective study (2004-2021), including patients with OEN defined by the association of an inflamed EAM, a positive nuclear imaging, the presence of a bacteriological sample and the failure of a well-followed local and/or general antibiotic treatment. OEN was extensive if it was associated with vascular or neurological deficits, if nuclear imaging fixation and/or bone lysis extended beyond the tympanic bone. RESULTS: Our population (n = 39) was male (74%), type 2 diabetic (72%), aged 75.2 years and pseudomonas aeruginosa was found in 88% of cases. Complications for 43% of patients were extensive fixation on nuclear imaging, for 21% of them the presence of extensive bone lysis, for 13% the appearance of facial palsy, for 5.3% the presence hypoglossal nerve palsy and for 2.5% the presence of thrombophlebitis or other nerves palsies. 59% of our population had extensive OEN. The diagnosis of the extensive OEN was made 22 days later (p = 0.04). The clinical presentation was falsely reassuring due to easier identification of the tympanic membrane (70% vs 46%, p = 0.17) but associated with periauricular oedema (42% vs 0%), bone exposure (16% vs 0%) and a temporomandibular joint pain (41% vs 12%). CONCLUSION: Delayed treatment of OEN, identification of clinical bone lysis, especially when the tympanic membrane is easily visualized, and the presence of unbalanced diabetes are potential risk factors for extension of OEN.

Prevalence of geophagy and knowledge about its health effects among native Sub-Saharan Africa, Caribbean and South America healthy adults living in France.

Geophagy is widespread among women from Sub-Saharan Africa, South America and the Caribbean and may persist in western countries. This practice may be associated with adverse effects such as anaemia, constipation or intestinal occlusion. We aimed to determine the prevalence of geophagy and the level of knowledge about its health effects among healthy adults originating from these countries and attending a travel medicine and international vaccination consultation in France. Among 101 travellers enrolled in the study, 83 (82.1%) were born in Sub-Saharan Africa and 13 (12.8%) in South America or the Caribbean. The mean duration of residence in France was 15.6 ± 10.4 years. Previous or current geophagy was present in 42 travellers [previous geophagy in 31 (30.7%) and current consumption in 11 (10.9%)]; 38 (90.5%) were women. The rate of awareness of harmful effects of geophagy as the risk of iron-deficient anaemia (18.8%) and soil-transmitted intestinal parasitic infections (11.9%) was low overall. Women with previous or current geophagy more often had history of iron therapy compared to those who never consumed, both during pregnancy (50.0 versus 14.3%; p = 0.0009) and outside pregnancy (47.4 versus 2.8%; p < 0.0001). Despite a long period of residence in France, geophagy was still a current practice among 10.9% of Sub-Saharan, South American and Caribbean travellers, who are poorly informed of its harmful effects. Therefore, specific information tailored to Sub-Saharan, South American and Caribbean about the risks of geophagy should be implemented in western countries.Level of evidence Level V, descriptive cross-sectional survey.

Factors Associated with Geophagy and Knowledge About Its Harmful Effects Among Native Sub-Saharan African, Caribbean and French Guiana HIV Patients Living in Northern France.

Geophagy, or the ingestion of earth or clay, is widespread among women of Sub-Saharan African, Caribbean or French Guiana origin. Little is known about this practice among HIV patients native of these countries and who are followed-up in France. The aims of this study were to determine (i) the prevalence and factors associated with geophagy among HIV patients native of these countries, (ii) patients' knowledge about the harmful effects of geophagy, and (iii) the association of geophagy with iron deficiency, or a history of anemia or constipation. Among the 119 included patients, current geophagy and previous geophagy were present in 11/119 (9%) and 47/119 (40%) patients, respectively. Female gender was the only factor associated with consumption (OR 5.37; 95% CI 2.07-15.92 p = 0.001). Awareness about the risk of iron-deficient anemia was low (24%). Preventive education should be integrated into the care of HIV adults from countries in which geophagy is a culture and widely accepted practice.

Major Persistent 5' Terminally Deleted Coxsackievirus B3 Populations in Human Endomyocardial Tissues.

We performed deep sequencing analysis of the enterovirus 5' noncoding region in cardiac biopsies from a patient with dilated cardiomyopathy. Results displayed a mix of deleted and full-length coxsackievirus B3, characterized by a low viral RNA load (8.10(2) copies/µg of nucleic acids) and a low viral RNA positive-sense to RNA negative-sense ratio of 4.8.

Virus detection and semiquantitation in explanted heart tissues of idiopathic dilated cardiomyopathy adult patients by use of PCR coupled with mass spectrometry analysis.

Viral detection in heart tissues has become a central issue for the diagnosis and exploration of the pathogenesis of idiopathic dilated cardiomyopathy (IDCM). In the present study, common cardiotropic viruses in 67 explanted heart samples of 31 IDCM adult patients were detected and semiquantified by using for the first time a new technology based on PCR assay coupled to electrospray ionization-time of flight mass spectrometry analysis (PCR-MS), with comparison to reference quantitative real-time PCR (RT-qPCR) assay. PCR-MS identified single or mixed enterovirus (EV) and parvovirus B19 (PVB19) infections in 27 (40.2%) of 67 samples, corresponding to 15 (48.3%) of the 31 patients, whereas RT-qPCR identified viral infections in 26 (38.8%) samples, corresponding to 16 (51.6%) of the patients. The PCR-MS results correlated well with EV and PVB19 detection by RT-qPCR (kappa = 0.85 [95% confidence interval {CI}, 0.72 to 1.00] and kappa = 0.82 [95% CI, 0.66 to 0.99], respectively). The levels of EV RNA (median, 550 [range, 178 to 3,200] copies/µg of total extracted nucleic acids) and of PVB19 DNA (median, 486 [range, 80 to 1,157] copies/µg of total extracted nucleic acids) were measured using PCR-MS and correlated with those obtained by RT-qPCR (r(2) = 0.57, P = 0.002 and r(2) = 0.64, P < 0.001 for EV and PVB19, respectively). No viruses other than EV and PVB19 strains were detected using the new PCR-MS technology, which is capable of simultaneously identifying 84 known human viruses in one assay. In conclusion, we identified single or mixed EV and PVB19 cardiac infections as potential causes of IDCM. The PCR-MS analysis appeared to be a valuable tool to rapidly detect and semiquantify common viruses in cardiac tissues and may be of major interest to better understand the role of viruses in unexplained cardiomyopathies.

Virological diagnosis and management of two cases of congenital measles.

Measles is a highly contagious viral infection causing congenital infections with a risk of neurological complications in the newborn. Two cases of measles, which occurred in pregnant women within 14 days before the delivery, are described. Mother-to-child transmission of the virus was documented in the newborns either by RT-PCR in saliva or by IgM detection in blood. The measles strains evidenced in saliva samples were genotyped and belonged to the D4 Genotype. An early viral RT-PCR detection allowed successful immunoglobulin prophylaxis in one newborn taking into account that the duration between the onset of the skin rash in the mother and the delivery was less than 6 days. Twenty-four months later, none of the newborns developed classical or neurological clinical signs of measles infection. Measles RT-PCR assay in salivary samples can be used before symptoms develop in the infant to confirm early mother-to-child transmission, therefore permitting the use of an immunoglobulin prophylaxis in the newborn.

Frequent occurrence of parvovirus B19 DNAemia in the first year after kidney transplantation.

Described for the first time in 1986, Parvovirus B19 (B19V) infection in kidney transplant recipients remains little-known and probably underestimated. The aims of this study were to establish B19V infection frequency during the first year after kidney transplant and to determine predisposing factors and manifestations of the infection in renal transplant recipients. Sixty consecutive adult patients, transplanted less than a year before, were included in this study. B19V and other opportunistic viral infections were detected retrospectively in plasma samples collected every 15 days during the first 3 months and every month from 3 months to 1 year following the kidney transplant. Demographic characteristics, immunosuppressive treatment and biological findings were recorded on each sampling date. Six patients (10%) presented B19V viremia, while eight CMV (13.3%), seven EBV (11.7%), five HHV-6 (8.3%), five BKV (8.3%), and two adenovirus (3.3%) infections were detected. The mean value of B19V viral load was 149 UI/ml. B19V infections were either reactivation or reinfection due to genotype two in five cases, while one case of primary infection with genotype 1 was observed. Neither risk factors nor biological consequences of B19V infection have been identified. These results rank B19V third among opportunistic viral infections occurring during the first year after a kidney transplant. With regard to this high incidence, and even if the risk factors and biological consequences of the infection should be assessed in larger studies, the question of systematic screening and follow-up of B19V infection in kidney transplant recipients is relevant.

Quantitative genomic and antigenomic enterovirus RNA detection in explanted heart tissue samples from patients with end-stage idiopathic dilated cardiomyopathy.

Standardized one-step real-time RT-PCR assay detected enterovirus RNA in cardiac biopsy samples from 4 of 20 patients suffering from idiopathic dilated cardiomyopathy (IDCM). The median viral load was 287 copies per microgram of total extracted nucleic acids, with positive- to negative-strand RNA ratios ranging from 2 to 20. These results demonstrate enterovirus persistence in the heart of IDCM patients, characterized by low viral loads and low positive- to negative-RNA ratios.

Broad respiratory virus detection in infants hospitalized for bronchiolitis by use of a multiplex RT-PCR DNA microarray system.

Newly available molecular tools allow a sensitive detection of a broad panel of viruses in respiratory tract specimens. In the present study, the application of a multiplex RT-PCR DNA microarray in diagnosis and epidemiological survey of viral infections in infants hospitalized for bronchiolitis was assessed. One hundred and thirty-eight nasopharyngeal aspirates collected from October 2007 to September 2008 were tested by direct immunofluorescence and viral culture, a combination of referenced RT-PCRs and the DNA microarray. One or more viruses were detected in 96, 126 and 126 of the specimens by direct immunofluorescence and viral culture, RT-PCRs and DNA microarray, respectively (70 vs. 91 vs. 91%, P < 10(-3)). The RT-PCRs and the DNA microarray yielded concordant results for 99% of specimens and identified mixed viral infections in 85 (62%). The most common associations were: human bocavirus and respiratory syncytial virus (32%), adenovirus and respiratory syncytial virus (30%), and parainfluenza virus type 3 and respiratory syncytial virus (23%). None of the bronchiolitis severity parameters including intensive care unit admission, O(2) supply, O(2) saturation percentage, O(2) length and length of stay at the hospital appeared to be significantly increased in multiple viral infections compared to single viral infections (P > 0.1). In conclusion, the use of this DNA microarray in clinical virology practice allows rapid and accurate identification of common and uncommon viral respiratory pathogens in infants hospitalized for bronchiolitis. It should improve the clinical management, the epidemiological survey, and the prevention of the nosocomial transmission of respiratory viruses in pediatric wards.

Structures and Functions of Viral 5' Non-Coding Genomic RNA Domain-I in Group-B Enterovirus Infections.

Group-B enteroviruses (EV-B) are ubiquitous naked single-stranded positive RNA viral pathogens that are responsible for common acute or persistent human infections. Their genome is composed in the 5' end by a non-coding region, which is crucial for the initiation of the viral replication and translation processes. RNA domain-I secondary structures can interact with viral or cellular proteins to form viral ribonucleoprotein (RNP) complexes regulating viral genomic replication, whereas RNA domains-II to -VII (internal ribosome entry site, IRES) are known to interact with cellular ribosomal subunits to initiate the viral translation process. Natural 5' terminally deleted viral forms lacking some genomic RNA domain-I secondary structures have been described in EV-B induced murine or human infections. Recent in vitro studies have evidenced that the loss of some viral RNP complexes in the RNA domain-I can modulate the viral replication and infectivity levels in EV-B infections. Moreover, the disruption of secondary structures of RNA domain-I could impair viral RNA sensing by RIG-I (Retinoic acid inducible gene I) or MDA5 (melanoma differentiation-associated protein 5) receptors, a way to overcome antiviral innate immune response. Overall, natural 5' terminally deleted viral genomes resulting in the loss of various structures in the RNA domain-I could be major key players of host-cell interactions driving the development of acute or persistent EV-B infections.

Pulmonary adverse events related to idelalisib therapy: A single centre experience.

Idelalisib is a potent and selective inhibitor of the PI3Kδ approved since September 2014 for the treatment of several types of B cell malignancies. Pulmonary adverse events related to idelalisib are an emerging serious adverse event. We report here a single centre cohort of 16 patients who initiated idelalisib as routine treatment. Five of them experienced severe pulmonary adverse events related to idelalisib therapy. Comparison of the 5 patients with severe pulmonary events versus the 11 patients without identified no predisposing factors. Severe pulmonary adverse events were related to infectious pneumonia and/or to a drug-induced pneumonitis. The mechanisms of idelalisib-associated pneumonitis are unknown but consistent with the drug-induced pneumonitis described with mTOR inhibitors. Indeed, by inhibiting PI3Kδ, idelalisib also inhibits the mTOR pathway. Clinicians should be aware that any idelalisib-treated patient who presents with pulmonary symptoms should be evaluated for pneumonitis. Corticosteroids should be considered in addition to anti-infective therapy in case of severe pneumonitis or persistent pulmonary symptoms despite adequate antibiotic therapy.

Early neuropsychological adverse events after switching from PI/r to dolutegravir could be related to hyperthyroidism in patients under levothyroxine.

We report two patients who had taken levothyroxine at the same dose for several years and who had stable thyroid stimulating hormone (TSH) levels, and who developed clinical and biological hyperthyroidism following switch from ritonavir-boosted protease inhibitors (PIs) to dolutegravir-based HAART. Levothyroxine is metabolized by deiodination and glucuronidation and the induction of glucuronidation by ritonavir leads to an increased elimination of levothyroxine and a necessity of higher daily doses. Patients who switch from ritonavir-boosted PIs to antiretroviral drugs-based HAART with minimal drug-interaction such as dolutegravir, may require an adjustment in their dose of levothyroxine in order to prevent hyperthyroidism due to impaired elimination of levothyroxine without ritonavir.

Severe apoptotic enteropathy caused by methotrexate treatment for rheumatoid arthritis.

The folic acid antagonist methotrexate is a cornerstone treatment of rheumatoid arthritis. Its use is limited chiefly by gastrointestinal toxicity, which is among the main reasons for methotrexate discontinuation. Here, we report the case of a 40-year-old man on chronic methotrexate therapy in whom life-threatening apoptotic enteropathy with watery diarrhea and hypovolemic shock developed after he was switched from the oral to the intramuscular route, with no change in dosage. Colonic biopsies suggested drug-induced colitis, showing a nonspecific, mildly inflammatory infiltrate of lymphocytes and plasma cells, dilated damaged crypts, and a marked increase in basal crypt apoptosis (>20 apoptotic bodies/100 crypts). Clinicians should be aware that methotrexate can cause life-threatening apoptotic enteropathy. Increased basal crypt apoptosis in colonic biopsies with more than 5 apoptotic bodies/100 crypts should routinely suggest drug-induced enteropathy.

Portal hypertension with extensive fibrosis and plasma cell infiltration in multiple myeloma.

Plasma cell infiltration of the liver has been described in about 45% of patient with multiple myeloma in autopsy review; however, it is usually not associated with significant liver dysfunction. Indeed, only rare cases of massive plasma cell infiltration leading to non-obstructive cholestasis and hepatic failure have been described. Here, we report a case with a history of 8 years of MM with extensive liver fibrosis and portal hypertension with no other evidence aetiology unless massive plasma cell infiltration who presented a significant regression of both biological liver abnormalities and liver stiffness after ten months of chemotherapy concomitantly to a significant decrease of the IgG serum monoclonal band.

High prevalence of measles seronegativity in adults with HIV infection born in the era of measles vaccination in Northern France.

We investigated measles humoral immunity levels in a cohort of HIV-infected adult patients in France and attempted to identify risk factors for antimeasles antibodies seronegativity. Being born after 1983 [odds ratio (OR) 4.40; 95% confidence interval (95% CI) 1.26-14.09; P = 0.0013] and a nadir CD4⁺ cell count below 100 cells/µl (OR 4.79; 95% CI 1.61-14.82; P = 0.0048) were the two factors independently associated with measles seronegativity. Systematic measles antibody screening should be performed in HIV-infected individuals born in the era of measles vaccination (after 1983 in France).

Continuous free access to HAART could be one of the potential factors impacting on loss to follow-up in HAART-eligible patients living in a resource-limited setting: N'djamena, Chad.

BACKGROUND: Retention of HAART-eligible HIV-infected patients in clinical follow-up systems are now becoming an important issue in sub-Saharan African countries. METHODS: In this retrospective study (April 2008 to November 2011), we assessed the attrition rate variations in a cohort of 509 HAART-eligible patients in Chad. RESULTS: Decrease in levels of loss to follow-up were observed during the implementation of continuous free access to HAART (72.5 vs 10%; p<0.001) and was independent of gender, age, WHO clinical stage and CD4+ T cell count at inclusion and of the time delay to initiate HAART (p>0.48). CONCLUSIONS: These data suggest that the implementation of free access to HAART without any interruption of supply, from autumn 2009, could be the factor that potentially changed the HIV patient attrition rate in this resource-limited setting.

Post-mortem diagnosis, of cytomegalovirus and varicella zoster virus co-infection by combined histology and tissue molecular biology, in a sudden unexplained infant death.

BACKGROUND: An autopsy case of a two-month-old male infant who suddenly and unexpectedly died during his sleep, eight days after the onset of benign varicella. OBJECTIVES: To describe post-mortem combined histological and tissue molecular biological techniques for the diagnosis of cytomegalovirus and varicella zoster virus co-infection as a cause of death. STUDY DESIGN: Real-time quantitative PCR and RT-PCR assays for Herpesviruses, respiratory viruses, Adenovirus, Enterovirus and Parvovirus B19 were performed on multi-organ frozen samples and paraffin-embedded tissues in combination with histology. RESULTS: Cytomegalovirus and varicella zoster virus were detected by molecular biology with highest viral loads detected in the lungs (4.6×10(7) and 1.9×10(5) genome copies per million of cells, respectively). Pulmonary extensive necrotizing inflammation and immunohistochemistry correlated to virological data. Virological molecular biology was negative on paraffin-embedded tissues. CONCLUSIONS: This case shows that thorough quantitative virological investigations on frozen tissues must be performed in combination with histology and immunohistochemistry for the determination of the cause of a sudden unexplained infant death.

Is total community viral load a robust predictive marker of the efficacy of the TasP strategy?

A mild but significant association between a decrease in the total community viral load (CVL) and a decrease in the number of new HIV diagnoses was observed between 2005 and 2010 in the population of northern and eastern France. This result suggests that CVL could be used as robust marker of the efficacy of the "Treatment as Prevention" strategy, and it may even be stronger if a large number of undiagnosed patients and early HIV infection cases indicated by extend screening are included in the CVL measurement.