The Extent of Aspergillosis in Critically Ill Patients With Severe Influenza Pneumonia: A Multicenter Cohort Study.

OBJECTIVES: To determine the frequency and prognosis of invasive pulmonary aspergillosis in critically ill patients with severe influenza pneumonia. DESIGN: Retrospective multicenter cohort study. SETTING: Five French ICUs. PATIENTS: Patients with influenza admitted to ICU between 2009 and 2018. MEASUREMENTS AND MAIN RESULTS: Of the 524 patients admitted for severe influenza diagnosed with a positive airway reverse-transcriptase polymerase chain reaction test, 450 (86%) required mechanical ventilation. A lower respiratory tract sample yielded with Aspergillus (Asp+) in 28 patients (5.3%). Ten patients (1.9%) were diagnosed with putative or proven invasive pulmonary aspergillosis, based on the validated AspICU algorithm. A multivariate model was built to identify independent risk factors for Aspergillus-positive pulmonary culture. Factors independently associated with Aspergillus-positive culture were liver cirrhosis (odds ratio = 6.7 [2.1-19.4]; p < 0.01), hematologic malignancy (odds ratio = 3.3 [1.2-8.5]; p = 0.02), Influenza A(H1N1)pdm09 subtype (odds ratio = 3.9 [1.6-9.1]; p < 0.01), and vasopressor requirement (odds ratio = 4.1 [1.6-12.7]; p < 0.01). In-hospital mortality of Asp+ patients was 36% versus 21% in patients without Aspergillus-positive pulmonary culture (p = 0.09). CONCLUSIONS: In this large retrospective multicenter cohort of critically ill patients, putative invasive pulmonary aspergillosis according to AspICU algorithm was a relatively rare complication of influenza. Patients at higher risk of Aspergillus pulmonary colonization included those with liver cirrhosis, hematologic malignancy, H1N1pdm09 influenza A virus, and requiring vasopressors. Our results provide additional data on the controversial association between severe influenza and invasive pulmonary aspergillosis. Reaching a consensual definition of invasive pulmonary aspergillosis becomes mandatory and confers further prospective research.

Sputum versus nasopharyngeal samples for the molecular diagnosis of respiratory viral infection in cystic fibrosis: A pilot study.

Viruses are important agents in lung function deterioration in Cystic Fibrosis (CF). To date, no standard operating procedures (SOPs) have been established to determine which sampling method is the most effective for an optimal virological diagnosis of respiratory viral infections in CF. Here we investigated the performances of two sampling sites, sputum samples versus nasopharyngeal (NP) swabs, for thirty participants from three CF centres presenting an acute respiratory infection. Sputum and NP samples were simultaneously collected and multiplex PCR targeting 16 to 18 viruses were performed. Viruses were detected for 18/30 patients (60%). A high concordance between the sputum and NP samples was observed in 25 (83%) paired samples of which 13 tested positive and 12 tested negative. These results highlighted the relevance of sputum sampling for diagnostic of respiratory viruses in CF, which is less invasive and better accepted by CF patients than NP, and allows accurate bacterial detection.

Pneumocystis primary infection in infancy: Additional French data and review of the literature.

Data on features of Pneumocystis primary infection in infancy are still fragmented. To study Pneumocystis primary infection, 192 infants who were monitored for acute pulmonary disease or fever over a 40-month period were retrospectively investigated. P. jirovecii detection on archival nasopharyngeal aspirates was performed using a qPCR assay. Factors associated with P. jirovecii were assessed using univariate and multivariate analyses. P. jirovecii genotypes in infants and a control group of adults contemporaneously diagnosed with Pneumocystis pneumonia were identified using unilocus, bilocus, and multilocus sequence typing (MLST). P. jirovecii was detected in 35 infants (18.2%). The univariate analysis pointed out four factors: viral infection (P = .035, OR [IC 95], 2.2 [1.1-4.7]), lower respiratory tract infection (P = .032, OR [IC 95], 2.5 [1.1-5.9]), absence of hospital discharge after birth (P = .003, OR (IC 95), 0.1 (0.02-0.5]), and the 63-189-day group (P < .001, OR [IC 95], 42.2 [5.4-332]). The multivariate analysis confirmed these two latter factors (P = .02, OR [IC 95], 0.1 [0.02-0.72]; P = .005, OR [IC 95], 11.5 [2.1-63.5]). Thus, P. jirovecii acquisition mostly takes place in the community. A comparison of these data with those of previously published studies showed that median and interquartile range of positive-infant ages were close to those observed in Chile, Denmark, and Peru, highlighting similar characteristics. Common unilocus or bilocus genotypes were identified in infants and adults, whereas no MLST genotypes were shared. Therefore, a common reservoir made up of infected infants and adults is still hypothetical. Finally, primary infection is a worldwide phenomenon occurring at the same time in childhood regardless of geographical location, rather than an incidental event.

Impact of rotavirus vaccination on hospitalizations for rotavirus diarrhea: the IVANHOE study.

The aim of the IVANHOE study was to determine the real-world impact of the rotavirus vaccine, controlling for epidemic-to-epidemic variation in disease burden. A population-based prospective cohort study was conducted in Brest City and 7 suburban districts (CUB area), North-western Brittany, France (210,000 inhabitants; 5500 births per year). The vaccination program started in May 2007 for a 2-year period for all infants born in the Brest birth zone through pediatricians, public outpatient clinics and general practitioners. To determine vaccine impact we monitored trends in hospitalizations for rotavirus-specific diarrhea using an active hospital-based surveillance system initiated 5 years before vaccine introduction. The number of hospitalizations for rotavirus-specific diarrhea during the 2008/2009 epidemic in infants less than 2 years of age whose parents lived within the CUB area was modelled as a function of (1) the number of hospitalizations in infants 2-5 years of age to control for epidemic-to-epidemic variation and (2) vaccine introduction. A total of 4684 infants received at least one dose. Of these, 2635 lived within the CUB area. Vaccine coverage for a complete schedule in the CUB area was 47.1%. Poisson modelling revealed a reduction by a factor of 2.04 (1.56-2.66) in the number of hospitalizations during the last epidemic season (2008/2009), the number of observed cases being equal to 30, against an expected number of 61. Relative risk reduction for hospitalizations for rotavirus diarrhea was 98% (95% CI: 83-100%). We observed a noticeable impact of vaccination on rotavirus diarrhea hospitalizations within 2 years of vaccine introduction integrating for the first time rotavirus epidemics variation. The trial is registered with ClinicalTrials.gov, number, NCT00740935.

Molecular and clinical characterization of rotavirus from diarrheal infants admitted to pediatric emergency units in france.

BACKGROUND: rotaviruses are the major cause of acute gastroenteritis in young children worldwide, and require careful surveillance, especially in the context of vaccination programs. Prospective surveillance is required to monitor and characterize rotavirus infections, including viral and clinical data, and to detect the emergence of potentially epidemic strains. METHODS: between 2006 and 2009, stool samples and clinical records were collected from 2044 children with acute diarrhea admitted to the pediatric emergency units of 13 French university hospitals. Rotaviruses were detected in stools, then genotyped by reverse transcription-polymerase chain reaction with regard to their outer capsid proteins VP4 and VP7. RESULTS: the genotyping of 1947 rotaviruses showed that G1 (61.7%) and G9 (27.4%) strains were predominant and stable, followed by G2 (6.5%), G3 (4.0%), and G4 (2.5%) strains. Most strains were associated with P[8] (92.9%). Overall, 31 uncommon strains and possible zoonotic reassortants were detected including G12 and G8 strains, some being closely related to bovine strains. No difference in clinical presentation and severity was found among genotypes. CONCLUSIONS: the relative stability of rotavirus genotypes currently cocirculating in France may ensure vaccine effectiveness in the short and medium term. However, the likely emergence of G12 and G8 strains should be monitored during ongoing and future vaccination programs, especially as all genotypes can cause severe infections. Special attention should be paid to the emergence of new rotavirus reassortants not included in current rotavirus vaccines.

Prevalence of rotavirus, adenovirus, norovirus, and astrovirus infections and coinfections among hospitalized children in northern France.

From January to December 2007, 973 stool specimens were prospectively collected from children hospitalized for gastroenteritis signs or from neonates and premature cases who were born in two French hospital settings in the north of France. They were tested by rapid enzyme immunoassay (EIA) analyses for rotavirus and adenovirus and by two commercially available ELISA tests for the detection of norovirus and astrovirus. The overall rates of prevalence for rotavirus, norovirus, adenovirus, and astrovirus were 21, 13, 5, and 1.8%, respectively, and they did not significantly differ between the two hospital settings (P=0.12). Mixed virus infections were detected in 32 (3.3%) of the 973 study children and were associated with norovirus in 21 (66%) infants, including 5 premature cases. From fall to spring, norovirus infections accounted for 52% of documented gastroenteritidis viral infections at a time when rotavirus was epidemic, resulting in mixed norovirus and rotavirus gastrointestinal tract infections. Of the 367 documented viral gastroenteritis cases, 15 (4.1%) were identified as nosocomial infections, 5 of which occurred in premature cases. These findings highlight the need to implement norovirus and astrovirus ELISA detection assays in association with rapid EIA rotavirus and adenovirus detection assays for the clinical diagnosis and the nosocomial prevention of gastroenteritis viral infections in pediatric departments.

Human papillomavirus quantification in urine and cervical samples by using the Mx4000 and LightCycler general real-time PCR systems.

During the last decade, growing efforts have focused on human papillomavirus (HPV) detection using liquid hybridization, conventional PCR, and real-time PCR-based methods to increase the overall proportion of patients participating in cervical cancer screening procedures. We proposed a new general HPV DNA real-time PCR on the Mx4000 (Stratagene) and LightCycler (Roche Diagnostics) systems usable for both cervical scrape specimens and urine samples. A linear range was obtained from 5 DNA copies to 8 log(10) DNA copies/ml, and intra- and interassay variations were between 1.8 and 4%. Cervical carcinoma and HPV DNA screening was performed in 333 individual women referred for gynecological examination at the university hospitals of Angers and Brest and enrolled in the PapU study. Among cervical specimens (n = 333), 45% were positive for HPV DNA, with a mean viral load at 5.00 log/ml (+/- 1.73). Among urine samples (n = 177), 37% were positive with a significant 50-fold-lower mean viral load (3.77 +/- 1.32 log/ml; P < 0.0001). Kappa agreement for HPV DNA between cervical and urine specimens was excellent (93%). Thus, we developed a highly sensitive and quantitative general HPV DNA real-time PCR method that allows mass screening of patients with HPV infection. The ongoing longitudinal and prospective multicenter PapU study should give us the opportunity to validate this method adapted to HPV DNA screening in urine samples in a larger population.