A European multicentre evaluation of detection and typing methods for human enteroviruses and parechoviruses using RNA transcripts.

Polymerase chain reaction (PCR) detection has become the gold standard for diagnosis and typing of enterovirus (EV) and human parechovirus (HPeV) infections. Its effectiveness depends critically on using the appropriate sample types and high assay sensitivity as viral loads in cerebrospinal fluid samples from meningitis and sepsis clinical presentation can be extremely low. This study evaluated the sensitivity and specificity of currently used commercial and in-house diagnostic and typing assays. Accurately quantified RNA transcript controls were distributed to 27 diagnostic and 12 reference laboratories in 17 European countries for blinded testing. Transcripts represented the four human EV species (EV-A71, echovirus 30, coxsackie A virus 21, and EV-D68), HPeV3, and specificity controls. Reported results from 48 in-house and 15 commercial assays showed 98% detection frequencies of high copy (1000 RNA copies/5 µL) transcripts. In-house assays showed significantly greater detection frequencies of the low copy (10 copies/5 µL) EV and HPeV transcripts (81% and 86%, respectively) compared with commercial assays (56%, 50%; P = 7 × 10-5 ). EV-specific PCRs showed low cross-reactivity with human rhinovirus C (3 of 42 tests) and infrequent positivity in the negative control (2 of 63 tests). Most or all high copy EV and HPeV controls were successfully typed (88%, 100%) by reference laboratories, but showed reduced effectiveness for low copy controls (41%, 67%). Stabilized RNA transcripts provide an effective, logistically simple and inexpensive reagent for evaluation of diagnostic assay performance. The study provides reassurance of the performance of the many in-house assay formats used across Europe. However, it identified often substantially reduced sensitivities of commercial assays often used as point-of-care tests.

Emerging resistance mutations in PI-naive patients failing an atazanavir-based regimen (ANRS multicentre observational study).

Background: Atazanavir is a PI widely used as a third agent in combination ART. We aimed to determine the prevalence and the patterns of resistance in PI-naive patients failing on an atazanavir-based regimen. Methods: We analysed patients failing on an atazanavir-containing regimen used as a first line of PI therapy. We compared the sequences of reverse transcriptase and protease before the introduction of atazanavir and at failure [two consecutive viral loads (VLs) >50 copies/mL]. Resistance was defined according to the 2014 Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) algorithm. Results: Among the 113 patients, atazanavir was used in the first regimen in 71 (62.8%) patients and in the first line of a PI-based regimen in 42 (37.2%). Atazanavir was boosted with ritonavir in 95 (84.1%) patients and combined with tenofovir/emtricitabine or lamivudine (n = 81) and abacavir/lamivudine or emtricitabine (n = 22). At failure, median VL was 3.05 log10 copies/mL and the median CD4+ T cell count was 436 cells/mm3. The median time on atazanavir was 21.2 months. At failure, viruses were considered resistant to atazanavir in four patients (3.5%) with the selection of the following major atazanavir-associated mutations: I50L (n = 1), I84V (n = 2) and N88S (n = 1). Other emergent PI mutations were L10V, G16E, K20I/R, L33F, M36I/L, M46I/L, G48V, F53L, I54L, D60E, I62V, A71T/V, V82I/T, L90M and I93L/M. Emergent NRTI substitutions were detected in 21 patients: M41L (n = 2), D67N (n = 3), K70R (n = 1), L74I/V (n = 3), M184V/I (n = 16), L210W (n = 1), T215Y/F (n = 3) and K219Q/E (n = 2). Conclusions: Resistance to atazanavir is rare in patients failing the first line of an atazanavir-based regimen according to the ANRS. Emergent NRTI resistance-associated mutations were reported in 18% of patients.

Prevalence of HIV-1 drug resistance in treated patients with viral load >50 copies/mL: a 2014 French nationwide study.

Background: Surveillance of HIV-1 resistance in treated patients with a detectable viral load (VL) is important to monitor, in order to assess the risk of spread of resistant viruses and to determine the proportion of patients who need new antiretroviral drugs with minimal cross-resistance. Methods: The HIV-1 protease and reverse transcriptase (RT) and integrase genes were sequenced in plasma samples from 782 consecutive patients on failing antiretroviral regimens, seen in 37 specialized centres in 2014. The genotyping results were interpreted using the ANRS v24 algorithm. Prevalence rates were compared with those obtained during a similar survey conducted in 2009. Results: The protease and RT sequences were obtained in 566 patients, and the integrase sequence in 382 patients. Sequencing was successful in 60%, 78%, 78% and 87% of patients with VLs of 51-200, 201-500, 501-1000 and >1000 copies/mL, respectively. Resistance to at least one antiretroviral drug was detected in 56.3% of samples. Respectively, 3.9%, 8.7%, 1.5% and 3.4% of patients harboured viruses that were resistant to any NRTI, NNRTI, PI and integrase inhibitor (INI). Resistance rates were lower in 2014 than in 2009. Resistance was detected in 48.5% of samples from patients with a VL between 51 and 200 copies/mL. Conclusion: In France in 2014, 90.0% of patients in AIDS care centres were receiving antiretroviral drugs and 12.0% of them had VLs >50 copies/mL. Therefore, this study suggests that 6.7% of treated patients in France might transmit resistant strains. Resistance testing may be warranted in all treated patients with VL > 50 copies/mL.

Acute flaccid paralysis following enterovirus D68 associated pneumonia, France, 2014.

Human enterovirus D68 (EV-D68) is known to be associated with mild to severe respiratory infections. Recent reports in the United States and Canada of acute flaccid paralysis (AFP) in children with detection of EV-D68 in respiratory samples have raised concerns about the aetiological role of this EV type in severe neurological disease. This case study is the first report of AFP following EV-D68 infection in Europe.

Phylogenetic evidence for a recent spread of two populations of human enterovirus 71 in European countries.

Human enterovirus 71 (EV-71) is a cause of seasonal epidemics of hand, foot and mouth disease, and of less common but severe neurological manifestations. Uncertainty persists regarding the circulation of virus populations in several geographical areas and the timescale of their dissemination. We determined EV-71 sequences at loci 1D (VP1 capsid protein) and 3CD (non-structural proteins) in 86 strains recovered in Austria, France and Germany and performed an evolutionary genetic study of extant virus populations. Phylogenetic analyses positioned 78 of the 86 sequences within two clades among subgenogroups C1 and C2. A minor sequence cluster was assigned to subgenogroup C4. Analyses incorporating the available sequences estimated the substitution rate in genogroup C at 3.66 x 10(-3) and 4.46 x 10(-3) substitutions per site year(-1) for loci 1D and 3CD, respectively, assuming a relaxed molecular-clock model for sequence evolution. Most of the 'European' strains belonged to clades C1b and C2b, which originated in 1994 [95 % confidence interval (CI), 1992.7-1995.8] and 2002 (95 % CI, 2001.6-2003.8), respectively. Estimates of divergence times for locus 3CD were consistent with those measured for locus 1D. Intertwining between clades representing EV-71 subgenogroups and clades corresponding to other enterovirus types (notably early coxsackievirus A prototype strains) in the 3CD phylogeny is highly indicative of ancestral recombination events. Incongruent phylogenetic patterns estimated for loci 1D and 3CD show that a single tree cannot model the epidemic history of circulating EV-71 populations. The evolutionary timescale of genogroup C estimated for both loci was measured only in decades, indicating recent dissemination.

[Enteroviral infections in adults treated with rituximab: A new case of chronic meningitis and myofasciitis and literature review]. / Infections à entérovirus de l'adulte traité par rituximab : un nouveau cas de méningite et myofasciite chronique et revue de la littérature.

INTRODUCTION: Chronic enterovirus infections can occur in primary immunodeficiency with hypogammaglobulinemia. They usually associate meningitis and myofasciitis. Such infections have also been described in adults with rituximab-induced hypogammaglobulinemia. CASE REPORT: We report the case of a 33-year-old woman who was given rituximab for immune thrombocytopenia and developed rituximab-induced hypogammaglobulinemia (IgG 4.4g/L). One year after the last rituximab infusion, she developed lower limbs myofasciitis, followed two months later by a chronic lymphocytic meningitis. PCR in the serum and the cerebrospinal fluid at the time of the meningitis and the myofasciitis were positive to the same enterovirus (echovirus 11) while it was negative in the fascia biopsy. Under treatment with intravenous immunoglobulins, all symptoms and laboratory abnormalities improved and enterovirus PCR became negative. CONCLUSION: We report a case of chronic enterovirus infection associating meningitis and myofasciitis in an adult with rituximab-induced hypogammaglobulinemia. Outcome was favorable under treatment with intravenous immunoglobulins.

Major 5'terminally deleted enterovirus populations modulate type I IFN response in acute myocarditis patients and in human cultured cardiomyocytes.

Major 5'terminally deleted (5'TD) group-B enterovirus (EV-B) populations were identified in heart biopsies of patients with fulminant myocarditis or dilated cardiomyopathy suggesting that these 5'TD forms are key drivers of host-cell interaction in EV cardiac infections. To date, early emergence of EV-B 5'TD forms and its impact on type 1 IFN response during acute myocarditis remains unknown. Using quantitative RACE-PCR assay, we identified major EV-B 5'TD RNA populations in plasma or heart samples of acute myocarditis cases. Deletions identified within the 5' non-coding region of EV-B populations only affected secondary-structural elements of genomic RNA domain I and were distinguished in two major groups based on the extent of RNA structural deletions. Proportions of these two respective EV-B 5'TD population groups were positively or negatively correlated with IFN-ß levels in plasma samples of myocarditis patients. Transfection of synthetic CVB3/28 RNAs harboring various 5'terminal full-length or deleted sequences into human cultured cardiomyocytes demonstrated that viral genomic RNA domain I possessed essential immunomodulatory secondary-structural elements responsible for IFN-ß pathway induction. Overall, our results highlight the early emergence of major EVB-TD populations which deletions affecting secondary-structures of RNA domain I can modulate innate immune sensing mechanisms in cardiomyocytes of patients with acute myocarditis.

Impact of rapid enterovirus molecular diagnosis on the management of infants, children, and adults with aseptic meningitis.

Enteroviruses (EV) are the main etiological agents of aseptic meningitis. Diagnosis is made by detecting the genome using RT-PCR. The aim of the study was to evaluate the impact of a positive diagnosis on the management of infants, children, and adults. During 2005, 442 patients were admitted to hospital with suspected meningitis. Clinical and laboratory data and initial treatment were recorded for all patients with enteroviral meningitis. The turnaround time of tests and the length of hospital stay were analyzed. The results showed that EV-PCR detected EV in 69 patients (16%), 23% (16/69) were adults. About 18% of CSF samples had no pleocytosis. After positive PCR results, 63% of children were discharged immediately (mean 2 hr 30 min) and 95% within 24 hr. Infants and adults were discharged later (after 1.8 and 2 days, respectively). The use of antibiotics was significantly lower in children than in infants and adults. The PCR results allowed discontinuation of antibiotics in 50-60% of all patients treated. Patients received acyclovir in 16% of cases (7% children vs. 50% adults) and 23% (11% vs. 69%) underwent a CT scan. Clinical data were compared between patients whose positive EV-PCR results were available within 24 hr (n = 32) and those whose results were available > 24 hr after collection of CSF (n = 14). Duration of antibiotic treatment (difference: 2.3 days; P = 0.05) was reduced between the two groups. No statistical difference in the length of stay was observed. The EV-PCR assay should be performed daily in hospital laboratory practice and considered as part of the initial management of meningitis.

[Genotyping and molecular epidemiology of non polyomyelitic enteroviruses]. / Génotypage et épidémiologie moléculaire des entérovirus non poliomyélitiques.

Nonpolio enteroviruses can be reliably identified with molecular and computer tools for taxonomic, diagnostic and epidemiologic purposes. Seroneutralization tests can efficiently be replaced by genotyping assays using the VP1 capsid protein encoding gene to identify enterovirus strains isolated in cell cultures. Genotyping showed the close genetic relatedness between human enterovirus serotypes and animal enteroviruses and also rhinoviruses currently classified in a separate genus within the Picornaviridae family. Enterovirus genotyping can be done prospectively within 2 to 5 days in a greater number of meningitis patients, using cerebrospinal fluid specimens and hence can help in providing a prompt response to health alert. In the molecular epidemiology of human enteroviruses, recent advances were made by investigating genetic diversity within individual serotypes (genotypes, lineages) and the patterns of circulation and transmission of virus variants involved in epidemics (echovirus 30, enterovirus 71). The observation of epidemiologic features such as the frequent viral immigration of strains from different geographical origins speaks in favour of developing molecular identification of enteroviruses. Recombinant enterovirus strains can also be identified by genotyping. Homologous recombination is a major contributor to the genetic diversity in enteroviruses. Molecular signatures of recombination events are observed in circulating strains, suggesting the occurrence of frequent co-infections during their circulation within the general population. The role of genetic recombination in the emergence of virus variants and its involvement in the epidemiology of human enteroviruses should be investigated.

Performance of genotypic algorithms for predicting tropism for HIV-1 CRF01_AE recombinant.

OBJECTIVES: There is no consensus about the performances of genotypic rules for predicting HIV-1 non-B subtype tropism. Three genotypic methods were compared for CRF01_AE HIV-1 tropism determination. METHODS: The V3 env region of 207 HIV-1 CRF01_AE and 178 B subtypes from 17 centers in France and 1 center in Switzerland was sequenced. Tropism was determined by Geno2Pheno algorithm with false positive rate (FPR) 5% or 10%, the 11/25 rule or the combined criteria of the 11/25, net charge rule and NXT/S mutations. RESULTS: Overall, 72.5%, 59.4%, 86.0%, 90.8% of the 207 HIV-1 CRF01_AE were R5-tropic viruses determined by Geno2pheno FPR5%, Geno2pheno FPR10%, the combined criteria and the 11/25 rule, respectively. A concordance of 82.6% was observed between Geno2pheno FPR5% and the combined criteria for CRF01_AE. The results were nearly similar for the comparison between Geno2pheno FPR5% and the 11/25 rule. More mismatches were observed when Geno2pheno was used with the FPR10%. Neither HIV viral load, nor current or nadir CD4 was associated with the discordance rate between the different algorithms. CONCLUSION: Geno2pheno predicted more X4-tropic viruses for this set of CRF01_AE sequences than the combined criteria or the 11/25 rule alone. For a conservative approach, Geno2pheno FPR5% seems to be a good compromise to predict CRF01_AE tropism.

[Clinical characteristics and course of hand, foot, and mouth disease]. / Symptomatologie et évolution de la maladie « pieds-mains-bouche ¼.

Hand, foot and mouth disease (HFMD) and herpangina (HA) are common childhood diseases mostly associated with human enteroviruses (EV). Although usually benign illnesses, neurological complications may be observed during large epidemics when enterovirus A71 (EV-A71) is involved, as observed in the Asia Pacific Region and in China since the late 1990s. The occurrence of these complications warrants reinforcing the surveillance of the emergence of EV-A71 infections in France and Europe. Monitoring EV infections associated with HFMD can be considered as an effective tool to detect an upsurge of EV-A71 infections in a timely manner. In 2014, a national sentinel surveillance system for HFMD/HA was set up in France through a network of volunteer pediatricians and coordinated by the National Reference Center for Enteroviruses and Parechoviruses. Although classical manifestations of HFMD/HA can be easily recognized, there are several atypical presentations of the disease that can be confused with other skin conditions. Delayed cutaneous manifestations, such as onychomadesis and acral desquamation, may also occur and should prompt consideration of HFMD in the preceding weeks. Severe complications following HFMD include neurological manifestations (mainly rhombencephalitis) or less frequently cardiopulmonary failure and can sometimes be fatal. In China, the case severity rate has been estimated at 1%, with a case fatality rate at 0.03%. EV-A71 was involved in more than 90% of the fatal cases. Diagnosis of EV infections associated with severe neurological manifestations is based on the molecular detection of the EV genome in vesicles, cerebrospinal fluid (CSF), throat and stool given that EV-A71 is rarely recovered from the CSF. Positive EV genome detection should be followed by EV genotyping to identify the type of the EV. In temperate-climate countries, outbreaks of HFMD occur mostly but not exclusively during summer and autumn months. Adults may also present with HFMD. In 2016, an upsurge of severe neurological manifestations was reported in France; EV-A71 accounted for 50% of the cases. No specific treatment is available, but two inactivated EV-A71 vaccines are currently available in China.

[Fatal case of enterovirus A71 hand, foot, and mouth disease infection]. / Décès d'un nourrisson dans un contexte de syndrome pieds-mains-bouche associé à l'entérovirus A71.

Hand, foot, and mouth disease associated with enterovirus (EV) infections is a common pediatric pathology that is usually considered as benign. However, neurological complications of varying severity, sometimes fatal, are possible, particularly when EV-A71 is involved. Several Asian countries are regularly affected by large-scale epidemics of EV infections with substantial morbidity and mortality, where early screening and appropriate therapeutic management are a public health challenge. In 2016, Europe experienced an epidemic of unusual magnitude, associated with increasing cases of severe neurological complications in Spain and France, mainly affecting children. Virological diagnosis is based on EV genome detection in peripheral clinical specimens (vesicles or oral ulcerations, throat, nasopharyngeal aspirate, stool) in addition to cerebrospinal fluid and blood. EV-A71 is rarely detected in cerebrospinal fluid, which renders the diagnosis of EV-A71-associated encephalitis challenging. We report the case of a 27-month-old child with hand, foot, and mouth disease turning into rapidly progressive and fatal cardiopulmonary failure associated with EV-A71 infection, in France in 2016. EV infections associated with hand, foot, and mouth disease warrant specific epidemiological surveillance outside the Asian region.

[Acute hemorrhagic edema of infancy associated with Coxsackie virus infection]. / Œdème aigu hémorragique du nourrisson associé à une infection à Coxsackie virus.

Acute hemorrhagic edema of infancy is a rare but benign vasculitis occurring in infants aged from 4 to 24 months. Skin lesions can take various forms, including extensive hemorrhagic purpura, and can therefore be mistaken for purpura fulminans if associated with fever, which leads to initiating broad-spectrum antibiotic treatment. In the present case, we describe a 7-month-old boy with acute hemorrhagic edema of infancy and rapidly extensive purpura lesions that led to intravenous cefotaxime and amikacin treatment. Diagnosis was made on the next day by a dermatologist, based on the typical aspect of skin lesions, hemodynamic stability, and negative bacteriological samples. Coxsackie virus B5, a pathogenic enterovirus, was found by specific PCR in cerebrospinal fluid. The outcome was spontaneously favorable after discontinuation of antibiotics on day 2. We discuss the imputability of the enterovirus in triggering this case of acute hemorrhagic edema of infancy.

Breast cancer is associated to impaired glucose/insulin homeostasis in premenopausal obese/overweight patients.

The association between breast cancer (BCa) presence and altered glucose/insulin metabolism is controversial likely due to an inaccurate insulin resistance (IR) assessment and inappropriate stratification of patients by body-mass index (BMI) and menopausal state. 148 women with suspect of sporadic BCa were stratified by BMI and menopause. Fasting levels of glucose, insulin, glycohemoglobin and selected IR-related and tumor-derived markers were measured. Glucose/insulin levels during OGTT were used to calculate insulin resistance/sensitivity indexes. Analysis of 77 BCa-bearing patients and 71 controls showed an association between BCa and IR as demonstrated by impaired glucose/insulin homeostasis (increased fasting- and OGTT-induced glucose levels) and deteriorated IR indexes, which was especially patent in premenopausal women. The association between BCa presence and IR was markedly influenced by BMI, being obese BCa patients significantly more insulin resistant than controls. BCa presence was associated to elevated levels of IR (glucose, triglycerides) and tumor-derived (VEGF) markers, especially in overweight/obese patients. BCa presence is associated to IR in overweight/obese premenopausal but not in premenopausal normal weight or postmenopausal women. Our data support a bidirectional relationship between dysregulated/imbalanced glucose/insulin metabolism and BCa, as tumor- and IR-markers are correlated with the impairment of glucose/insulin metabolism in overweight/obese premenopausal BCa patients.

[From prospective molecular diagnosis of enterovirus meningitis...to the prevention of antibiotic resistance]. / Du diagnostic moléculaire initial prospectif des méningites à entérovirus...à la lutte contre l'antibiorésistance.

Meningitis initially presents with intense manifestations that are not generally specific to a given etiology. The first major question for the physician is to decide whether to initiate a probabilistic treatment. Enteroviruses are a major cause of aseptic meningitis, which is benign in immunocompetent patients. Molecular diagnosis is now becoming the gold standard and its prospective use at the time of patient admission, on the sole basis of clinical suspicion of meningitis, has yielded more reliable data. Cytological and biochemical data from CSF analyses are of low predictive value to influence the initial decision to treat with antibiotics. In addition, cases of meningitis during winter are not uncommon. Adults are concerned in about 25% of cases. Thus, if molecular diagnostic tools are not rapidly available, patient management may be inconsistent, leading to unnecessary scans, laboratory investigations and treatment (including overconsumption of antibiotics). Current progress in the automation and practicability of viral genomic detection yields the result within a few hours after admission. Rapid molecular viral diagnosis of a benign disease that does not require treatment but which is initially worrying is of unquestionable advantage. It is of benefit to both the patient and the community because of its input on health economics, the needless consumption of drugs and, as a result, resistance to antibiotics. The diagnosis of meningitis can no longer remain a retrospective diagnosis after elimination of all the possible causes, since not prescribing unnecessary laboratory tests and not treating are true therapeutic decisions.

Lifetime drinking patterns of elders from a general population survey.

A telephone survey was conducted of 2325 residents of Erie County, New York, over age 59. Late-onset heavy drinking proved to be relatively rare. Most who were heavy drinkers when younger had attenuated their drinking. Drinking patterns from earlier in life were the best predictors of current drinking, with health-oriented lifestyle showing some effect. Stress was not related to drinking among older persons.

Drinking, problem drinking and life stressors in the elderly general population.

OBJECTIVE: Research shows that although heavy drinking in the United States is less prevalent among older persons, some maintain or increase heavy drinking. Late-onset heavy drinking is believed to be related to stressors of aging such as retirement or bereavement, particularly when coping resources or social supports are inadequate. This study investigated that relationship. METHOD: In 1990-91, a random-digit-dial telephone survey was conducted with 2,325 Erie County, New York, residents aged 60 or older. Heavy drinkers were oversampled. Questions included demographics, drinking quantity-frequency, alcohol dependence/problems, stressful life events, chronic stresses, coping resources and social supports. Analyses were conducted to examine the relationship between drinking and stress. RESULTS: There was no bivariate correlation between average alcohol consumption and acute or chronic stress. Logistic regressions with interaction terms show that stress has no relationship to heavy drinking (average alcohol consumption of 2+ drinks/day) regardless of coping style or social supports. Logistic regressions predicting late-onset heavy drinking also produced negative results. Chronic stress was, however, positively related to alcohol dependence and problems. CONCLUSIONS: Treatment and prevention programs for the elderly should not be based on the assumption that life stresses are a direct cause of drinking, although they may exacerbate consequences of drinking.

[What is the method of choice for hemodynamic monitoring in liver transplantation?]. / Quel monitorage hémodynamique lors des transplantations hépatiques?

Orthotopic liver transplantation requires close hemodynamic monitoring. Technological advances provide new possibilities of improving this monitoring. The most recent devices are the mixed venous oxygen saturation catheter, which gives continuous SVO2 values, and the right ejection fraction catheter used discontinuously. Our experience of 100 liver transplantations has enabled us to investigate the advantages of these catheters over the conventional Swan Ganz catheters.

A case of congenital Echovirus 11 infection acquired early in pregnancy.

Enterovirus (EV) maternal infection during pregnancy and its relation to fetal developmental pathology are seldomly described. When reported, the main manifestations of EV congenital infections are myocarditis or intra-uterine fetal demise (IUFD). No information on intrauterine Echovirus 11 infection or the effect of transplacental Echovirus 11 infection on development of the fetus has been described in literature up to date (excluding late-pregnancy infections). We report here a case of an extreme form of pulmonary hypoplasia in a neonate, characterized by total failure of development of terminal respiratory units. This pregnancy was marked by spontaneous demise of a co-twin at 14 weeks of gestation (WG), as well as by positive PCR for EV (Echovirus 11 serotype) in the amniotic fluid, performed for moderate pericardial effusion at 22WG. No signs of cardiac disease were further observed, but at 32WG a bilateral abnormal lung development was noticed After spontaneous delivery at 38WG, the child could not be resuscitated, and died at one hour after birth. Pulmonary hypoplasia is usually described following decrease intrapulmonary pressure due to oligohydramnios or compression due to intrathoracic mass of variable cause. However, rare cases of primary pulmonary hypoplasia are also described and usually of unknown etiology. The coexistence in our case of a congenital EV infection and a severe primary pulmonary hypoplasia with congenital acinar aplasia, challenges our understanding of the pathogenesis of this severe pulmonary growth arrest.

[Severe human parechovirus-3 sepsis in a 6-week-old infant]. / Infection sévère à paréchovirus de type 3 chez un nourrisson de 6semaines.

Febrile infants under 3 months of age are often treated with broad-spectrum intravenous antibiotics while awaiting culture results, to prevent mother-to-child bacterial infections. Human parechoviruses (HPeV) have recently been described as etiologic agents of meningitis and severe sepsis in neonates and young infants. They are rarely investigated and are therefore probably underestimated. They cause acute clinical symptoms that can incorrectly suggest a bacterial infection. In the present case, a 6-week-old infant infected with HPeV developed severe sepsis, complicated by hepatic cytolysis, meningitis, acute renal failure, and mild hemophagocytic lymphohistiocytosis. HPeV type 3 was found by routine specific RT-PCR in cerebrospinal fluid, stools, and plasma. The outcome was spontaneously favorable after 4 days. Early diagnosis of the HPeV infection by routine specific RT-PCR reduces unnecessary antibiotic use and extended hospitalization in febrile young infants.