Caractéristiques et évolution des enfants infectés par le VIH-1, porteurs de virus multirésistants

MONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUM (751062103) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Traitement de l'infection à VIH chez l'adolescent (quels sont les déterminants du succès thérapeutique?)

Introduction. Grâce aux progrès thérapeutiques, les enfants infectés par le VIH par transmission de la mère à l enfant (TME) atteignent l âge de l adolescence. Cette période, liée à des changements physiques, mentaux et sociaux, se caractérise par des difficultés de compliance. Matériel et méthodes. Nous avons recueilli des données dans les dossiers médicaux des adolescents âgés de 10 à 19 ans suivis et traités par traitement antirétroviral (ARV) pour une infection à VIH à l HEAR de Dakar. Résultats. Les 93 adolescents inclus dans notre étude ont été diagnostiqués à l âge de 8,1 +/- 3,4 ans, le plus souvent dans un contexte d infection symptomatique (64,8%), et le traitement a été débuté à 9,9 ans +/- 3,3. 58% des patients étaient encore traités au moment du recueil de données par l association initialement recommandée de 2 INRT et 1 INNRT. 41,9% des patients avaient reçu un génotypage de résistance et 30,8% des patients pouvaient bénéficier d une association à laquelle le virus était totalement sensible. Aux dernières nouvelles 22,6% des adolescents étaient encore en déficit immunitaire sévère. 32,2% avaient une charge virale indétectable. Les facteurs associés à un succès thérapeutique étaient le fait d'avoir au moins un parent vivant, une infection symptomatique au diagnostic, un taux de CD4 > 200/mm3 avant traitement et un âge > 10 ans à l'initiation du traitement. Discussion. Le diagnostic et la mise en routedu traitement tardifs sont grevés d'une plus grande morbi-mortalité, ce qui doit conduire à un renforcement de la prévention de la TME et du dépistage chez l'enfant. Les résultats immuno-virologiques peu satisfaisants de notre population sont le reflet d'une prise en charge tardive ne permettant pas toujours une reconstitution immunitaire satisfaisante et d'une mauvaise compliance dùe à la période difficile de l'adolescence. Celle-ci engendre l'apparition de mutations de résistance attestée par les génotypages; le manque de disponibilité des molécules et de nouvelles classes ARV dans les pays en voie de développement met parfois les patients en impasse thérapeutique.Introduction . Thanks to therapeutic progress, HIV-infected children through mother-to-child transmission grow up to become teenagers. This period is caracterized by a frequent lack of compliance . Materials and methods. We retrieved data from medical files including 10- to 19-year old teenagers followed up for an HIV infection and terated by highly active antiretroviral treatment (HAART) at Dakar's HEAR . Results. The 93 teenagers included in our study were diagnosed at the age of 8.1 + / - 3.4 years , most often after presenting with symptoms of the disease (64.8%) , and HAART was started at age 9.9 years + / - 3.3 . 58% of patients were treated at data collection by the initially recommended drug association . 30.8 % of patients who underwent a resistance genotype could be offered a treatment to which the virus was totally sensitive. At endpoint, 22.6 % of patients still presented with severe immunologic deficiency and 32.2% had an undetectable viral load. Factors associated with a good outcome were the fact of having at least one living parent, a symptomatic infection at time of diagnosis, CD4 count> 200/mm3 at beginning of HAART and age> 10 years at initiation of treatment. Discussion. Late diagnosis and HAART start in children are bound to a worse outcome, which should must lead to enforcement of mother-to-child transmission prevention and pediatric diagnosis. Poor immuno-virologic outcome is due to this late care, linking to dismal immunologic reconstitution, and to bad compliance because of the difficult time of adolescence. This results in viral reistance, attested by genotypes; weak drug disponibility in rising countries sometimes leads to therapeutic unsolvable situations.ST QUENTIN EN YVELINES-BU (782972101) / SudocSudocFranceF

Escherichia coli ST410 among humans and the environment in Southeast Asia

International audienceEscherichia coli ST410 (Ec-ST410) is an emerging, multidrug-resistant clone. Recent investigations of its global epidemiology and evolution have been based almost exclusively on isolates from Europe and North America. It is unclear whether Southeast Asian-origin Ec-ST410 (SEA-Ec-ST410) belong to these same clones or represent regionally disseminated variants. Antimicrobial resistance mechanisms among SEA-Ec-ST410 were characterised, and whether they belonged to regional variants was investigated by contextualising them within a global collection. Seven Ec-ST410 were identified among a recent collection of expanded-spectrum cephalosporin-resistant E. coli recovered from 91 healthy women (stool) and 26 infected patients (blood and urine) living in Phnom Penh, Cambodia. Nine additional Ec-ST410 genomes were identified from Thailand (n = 7) and Vietnam (n = 2) through EnteroBase and PubMed searches. The assembled genomes were characterised and a SNP-based phylogenetic tree was created comparing these 16 SEA-Ec-ST410 with a previously published Ec-ST410 collection, primarily sourced from Europe (97/128) and North America (24/128). SEA-Ec-ST410 belonged to several distinct branches within previously described clonal clades. SEA-Ec-ST410 within the B3/H24Rx sublineage encoded blaCTX-M-55 (8/12) and F18:A-:B1 plasmid replicons (6/12), neither of which were detected among other Ec-ST410 belonging to this clade. Three of four SEA-Ec-ST410 within the B4/H24RxC sublineage lacked both blaOXA-181 and an IncX3 plasmid replicon that were harboured by 97% and 100% of all other Ec-ST410 in this sublineage (n = 64), respectively. In conclusion, Ec-ST410 are present in Southeast Asia following multiple introductions. The unique pattern of antimicrobial resistance elements harboured by SEA-Ec-ST410 suggests independent circulation in the region

Real-Time PCR Measurement of Persistence of Bordetella pertussis DNA in Nasopharyngeal Secretions during Antibiotic Treatment of Young Children with Pertussis ▿

We used real-time PCR to examine the persistence of Bordetella pertussis DNA in serial nasopharyngeal aspirates from 22 children treated for pertussis. After 5 days of treatment, PCR was positive for all 21 assessable patients. After 14 and 21 days, PCR was still positive for 83% (10/12) and 66% (4/6) of assessable patients, respectively. One patient was tested 1 month after treatment initiation, and B. pertussis DNA was still detectable. Quantitative analysis showed that the DNA concentration diminished during treatment in all except one case. The PCR cycle threshold at which B. pertussis DNA became detectable increased by a mean of 1.7 cycles per day (range, 0.86 to 3.68 cycles per day). Real-time PCR can thus be used to diagnose pertussis in young children for up to 3 weeks after treatment initiation. Its potential value for assessing the treatment outcome remains to be determined

Meat and Fish as Sources of Extended-Spectrum β-Lactamase–Producing Escherichia coli , Cambodia

International audienceWe compared extended-spectrum β-lactamase-producing Escherichia coli isolates from meat and fish, gut-colonized women, and infected patients in Cambodia. Nearly half of isolates from women were phylogenetically related to food-origin isolates; a subset had identical multilocus sequence types, extended-spectrum β-lactamase types, and antimicrobial resistance patterns. Eating sun-dried poultry may be an exposure route

Klebsiella pneumoniae carriage in low-income countries: antimicrobial resistance, genomic diversity and risk factors

The genomic sequencing data were deposited in the NCBI/ENA/DDBJ databases and are accessible via the BioProject PRJEB29143International audienceKlebsiella pneumoniae (hereafter, Kp) is a major public health threat responsible for high levels of multidrug resistant (MDR) human infections. Besides, Kp also causes severe infections in the community, especially in Asia and Africa. Although most Kp infections are caused by endogenous intestinal carriage, little is known about the prevalence and microbiological characteristics of Kp in asymptomatic human carriage, and attached risk factors including environmental sources exposure. Here, 911 pregnant women from communities in Madagascar, Cambodia, and Senegal were screened for gut colonization by Kp. Characteristics of Kp strains (antimicrobial susceptibility, genomic diversity, virulence, and resistance genes) were defined, and associated risk factors were investigated.Kp carriage rate was 55.9%, and Kp populations were highly heterogeneous (6 phylogroups, 325 sequence types, Simpson index 99.6%). One third of Kp isolates had acquired antimicrobial resistance genes. MDR-Kp (11.7% to 39.7%) and extended spectrum beta-lactamase (ESBL)-producing Kp (0.7% to 14.7%) varied among countries. Isolates with virulence genes were detected (14.5%). Environmental exposure factors including food, animal contacts, or hospitalization of household members were associated with carriage of Kp, antimicrobial resistance and hypervirulence. However, risk factors were country-specific and Kp subpopulation-specific.This large-scale multicenter study uncovers the huge diversity of Kp in human gut carriage, demonstrates that antimicrobial resistance is widespread in communities of three low-income countries, and underlines the challenges posed by Kp colonization to the control of antimicrobia

Acquisition of extended spectrum beta-lactamase-producing enterobacteriaceae in neonates: A community based cohort in Madagascar

International audienceIn low and middle income countries (LMICs), where the burden of neonatal sepsis is the highest, the spread of extended spectrum beta-lactamase-producing enterobacteriaceae (ESBL-PE) in the community, potentially contributing to the neonatal mortality, is a public health concern. Data regarding the acquisition of ESBL-PE during the neonatal period are scarce. The routes of transmission are not well defined and particularly the possible key role played by pregnant women. This study aimed to understand the neonatal acquisition of ESBL-PE in the community in Madagascar. The study was conducted in urban and semi-rural areas. Newborns were included at birth and followed-up during their first month of life. Maternal stool samples at delivery and six stool samples in each infant were collected to screen for ESBL-PE. A Cox proportional hazards model was performed to identify factors associated with the first ESBL-PE acquisition. The incidence rate of ESBL-PE acquisition was 10.4 cases/1000 newborn-days [95% CI: 8.0-13.4 cases per 1000 newborn-days]. Of the 83 ESBL-PE isolates identified, Escherichia coli was the most frequent species (n = 28, 34.1%), followed by Klebsiella pneumoniae (n = 20, 24.4%). Cox multivariate analysis showed that independent risk factors for ESBL-PE acquisition were low birth weight (adjusted Hazard-ratio (aHR) = 2.7, 95% CI [1.2; 5.9]), cesarean-section, (aHR = 3.4, 95% CI [1.7; 7.1]) and maternal use of antibiotics at delivery (aHR = 2.2, 95% CI [1.1; 4.5]). Our results confirm that mothers play a significant role in the neonatal acquisition of ESBL-PE. In LMICs, public health interventions during pregnancy should be reinforced to avoid unnecessary caesarean section, unnecessary antibiotic use at delivery and low birth weight newborns

Stillbirths and neonatal mortality in LMICs: A community-based mother-infant cohort study

International audienceBackgroundThe exact timing, causes, and circumstances of stillbirth and neonatal mortality in low- and middle-income countries (LMICs) remain poorly described, especially for antenatal stillbirths and deaths occurring at home. We aimed to provide reliable estimates of the incidence of stillbirth and neonatal death in three LMICs (Madagascar, Cambodia and Senegal) and to identify their main causes and associated risk factors.MethodsThis study is based on data from an international, multicentric, prospective, longitudinal, community-based mother-infant cohort. We included pregnant mothers and prospectively followed up their children in the community. Stillbirths and deaths were systematically reported; information across healthcare settings was collected and verbal autopsies were performed to document the circumstances and timing of death.ResultsAmong the 4436 pregnancies and 4334 live births, the peripartum period and the first day of life were the key periods of mortality. The estimated incidence of stillbirth was 11 per 1000 total births in Cambodia, 15 per 1000 in Madagascar, and 12 per 1000 in Senegal. We estimated neonatal mortality at 18 per 1000 live births in Cambodia, 24 per 1000 in Madagascar, and 23 per 1000 in Senegal. Based on ultrasound biometric data, 16.1% of infants in Madagascar were born prematurely, where 42% of deliveries and 33% of deaths occurred outside healthcare facilities. Risk factors associated with neonatal death were mainly related to delivery or to events that newborns faced during the first week of life.ConclusionsThese findings underscore the immediate need to improve care for and monitoring of children at birth and during early life to decrease infant mortality. Surveillance of stillbirth and neonatal mortality and their causes should be improved to mitigate this burden in LMICs