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1.
Clin Infect Dis ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31665306

RESUMO

BACKGROUND: In women seronegative before pregnancy, cCMV related sequelae are exclusively seen in those infected in the first trimester of pregnancy. Up to 30% of infected neonates following maternal primary infection in the first trimester suffer long-term sequelae. Maternal parity is an established risk factor of cCMV in previously seronegative women. OBJECTIVE: to quantify the risk of cCMV and related sequelae following primary infection in the first trimester in subsequent pregnancies in a population of women seronegative at their first pregnancy. METHODS: 739 women seronegative at their first pregnancy had at least one of 971 subsequent pregnancies and deliveries managed at our institution. All women had CMV IgG and IgM testing at 11-14 weeks' of each pregnancy. RESULTS: 15.6% (115/739) of women seroconverted between 2 consecutive pregnancies. 29% (33/115) of seroconversions occurred in the periconceptional period or in the first trimester. The risks for cCMV and related sequelae (neurologic and/or hearing loss) following maternal infection in the first trimester were respectively 24 and 6-fold higher (RR [95%CI] =24 [10.8-62.3] and 6 [1.5-24]) than the general pregnant population. 88% (29/33) and 92% (11/12) of, respectively, all primary maternal infections and fetal infections in the 1st trimester occurred when the inter-pregnancy interval was ≤2 years. CONCLUSION: Women seronegative at their first pregnancy with a subsequent pregnancy within 2 years have the highest risk of delivering a child with cCMV-related sequelae. These women should be made aware of the risk and given the opportunity of serology screening in the first trimester.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31266724

RESUMO

INTRODUCTION: Hepatitis E virus (HEV) is a major cause of acute viral hepatitis worldwide, usually asymptomatic in children. However, a growing number of publications over the last decade have documented cases of chronic hepatitis related to HEV-genotype 3 infection, and progressing to cirrhosis in immuno-compromised patients, particularly in adult kidney transplant recipients. The aim of our study was to evaluate the prevalence and severity of HEV infection among pediatric liver transplant (PLT) recipients managed in our center. MATERIAL AND METHODS: Between November 1st 2014 and January 1st 2016, PLT recipients (less than 18 years-old) were screened for HEV infection [determined by HEV serology, HEV- immunoglobulin M (IgM) and immunoglobulin G (IgG), and HEV-ribonucleic acid (RNA) by reverse transcriptase polymerase chain reaction] at their annual follow-up visit. RESULTS: Eighty children were tested for HEV infection a mean of 5.4±5.3 years after liver transplantation (LT). The main indication for LT was biliary atresia (n=47, 59%). The prevalence of HEV-IgG was 8% (n=6; age range 1.3 to 14.2 years-old at the time of HEV testing). Prevalence increased to 30% when considering only the 20 children with a past history of an unexplained episode of elevated transaminases since LT. None had HEV IgM, serum HEV-RNA, or increased transaminases at the time of HEV testing. Among the six IgG seropositive children, two had received intravenous immunoglobulins prior to screening and four children had a negative control (seroreversion) 3 to 42 months after the first testing. CONCLUSION: The prevalence of HEV infection in our cohort is low and similar to other pediatric reports. We saw no cases of chronic hepatitis or fibrosis attributable to HEV. The lower immunosuppressive regimen used in PLT children compared to other solid organ transplant recipients may account for this good outcome.

6.
Clin Infect Dis ; 69(9): 1526-1532, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30596974

RESUMO

BACKGROUND: The known relationship between the gestational age at maternal primary infection an the outcome of congenital CMV is based on small, retrospective studies conducted between 1980 and 2011. They reported that 32% and 15% of cases had sequelae following a maternal primary infection in the first and second or the third trimester, respectively. We aimed to revisit this relationship prospectively between 2011 and 2017, using accurate virological tools. METHODS: We collected data on women with a primary infection and an infected child aged at least 1 year at the time of analysis. An accurate determination of the timing of the primary infection was based upon serial measurements of immunoglobulin (Ig) M and IgG and on IgG avidity in sera collected at each trimester. The case outcome was assessed according to a structured follow-up between birth and 48 months. RESULTS: We included 255 women and their 260 fetuses/neonates. The dating of the maternal infection was prospective in 86% of cases and retrospective in 14%. At a median follow-up of 24 months, the proportion of sensorineural hearing loss and/or neurologic sequelae were 32.4% (95% confidence interval [CI] 23.72-42.09) after a maternal primary infection in the first trimester, 0 (95% CI 0-6.49) after an infection in the second trimester, and 0 (95% CI 0-11.95) after an infection in the third trimester (P < .0001). CONCLUSIONS: These results suggest that a cytomegalovirus infection can be severe only when the virus hits the fetus in the embryonic or early fetal period. Recent guidelines recommend auditory follow-ups for at least 5 years for all infected children. This raises parental anxiety and generates significant costs. We suggest that auditory and specialized neurologic follow-ups may be recommended only in cases of a maternal infection in the first trimester.

7.
Brain Pathol ; 2018 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-30020561

RESUMO

BACKGROUND: The recent outbreak of Zika virus (ZIKV) infection and the associated increased prevalence of microcephaly in Brazil underline the impact of viral infections on embryo fetal development. The aim of the present study is to provide a detailed clinical and histopathological study of the fetal disruption caused by the ZIKV, with a special focus on the associated neuropathological findings. METHODS: A detailed feto-placental examination, as well as neuropathological and neurobiological studies were performed on three fetuses collected after pregnancy termination between 22 and 25 weeks of gestation (WG), because brain malformations associated with a maternal and fetal ZIKV infection was diagnosed. RESULTS: In all three cases, the maternal infection occurred during the first trimester of pregnancy. A small head was observed on the ultrasound examination of the second trimester of pregnancy and led to the diagnosis of ZIKV fetopathy and pregnancy termination. The fetal histopathological examination was unremarkable on the viscera but showed on the testis an interstitial lymphocytic infiltrate. The placenta contained a Hofbauer cells hyperplasia with signs of inflammation. Neuropathological findings included a meningoencephalitis and an ex vacuo hydrocephalus. Immunohistochemical studies showed the presence of T lymphocytic and histiocytic meningitis associated with an abundant cerebral astroglial and macrophagic reaction. In situ hybridization demonstrated, abundant ZIKV particles within the cerebral parenchyma mainly in the ventricular/subventricular zone and in the cortical plate. In addition massive cells death and endoplasmic reticulum damage were present. CONCLUSION: The present study reports on the clinical and histopathological findings observed in three fetuses infected by the ZIKV. It emphasizes the severity of brain damages and the minimal visceral and placental changes observed upon ZIKV infection. This confirms the selective neurotropism of ZIKV. Finally, it allows us to describe the cascade of multifactorial developmental defects leading to microcephaly.

8.
Sci Immunol ; 3(24)2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29907691

RESUMO

Heterozygosity for human signal transducer and activator of transcription 3 (STAT3) dominant-negative (DN) mutations underlies an autosomal dominant form of hyper-immunoglobulin E syndrome (HIES). We describe patients with an autosomal recessive form of HIES due to loss-of-function mutations of a previously uncharacterized gene, ZNF341 ZNF341 is a transcription factor that resides in the nucleus, where it binds a specific DNA motif present in various genes, including the STAT3 promoter. The patients' cells have low basal levels of STAT3 mRNA and protein. The autoinduction of STAT3 production, activation, and function by STAT3-activating cytokines is strongly impaired. Like patients with STAT3 DN mutations, ZNF341-deficient patients lack T helper 17 (TH17) cells, have an excess of TH2 cells, and have low memory B cells due to the tight dependence of STAT3 activity on ZNF341 in lymphocytes. Their milder extra-hematopoietic manifestations and stronger inflammatory responses reflect the lower ZNF341 dependence of STAT3 activity in other cell types. Human ZNF341 is essential for the STAT3 transcription-dependent autoinduction and sustained activity of STAT3.

9.
J Antimicrob Chemother ; 73(9): 2422-2429, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29860512

RESUMO

Objectives: To describe cidofovir pharmacokinetics and assess the link between concentration and safety/efficacy in children. Patients and methods: An observational study was conducted in 13 immunocompromised children receiving cidofovir for adenovirus and/or cytomegalovirus infection. A population pharmacokinetic model was built and AUC0-24 was derived for each patient. Virological success was defined as a decrease of the viraemia by ≥1 log10 copies/mL within 15 days of cidofovir initiation. The association between AUC0-24 and virological success was assessed using a Wilcoxon test. An AUC0-24 cut-off value was determined using a Fisher's exact test. Results: Overall, 86 blood samples were analysed. A two-compartment model with first-order absorption and elimination best described the cidofovir data. Virological success (VS) was reached in 6/8 children with adenovirus viraemia and in 1/4 children with cytomegalovirus viraemia. Patients with VS displayed a non-significant higher median AUC0-24 compared with patients with virological failure: 48.6 (range 8.9-72.6) versus 19.1 (6.9-22.7) mg·h/L. Adenovirus-viraemic patients with an AUC0-24 value below 19.1 mg·h/L had a higher probability of treatment failure (P = 0.03). Aviraemic children with stool and/or nasopharyngeal adenovirus carriage cleared the viral carriage within a month of cidofovir initiation. During treatment, 1/13 children developed a tubulopathy but none of them had an increase in creatininaemia. Conclusions: Cidofovir appears safe and reasonably well tolerated and seemed to have efficacy in a subset of patients with adenovirus/cytomegalovirus infection. Therapeutic drug monitoring may be useful in children receiving cidofovir and, in the case of adenovirus infection, targeting an AUC0-24 above 19.1 mg·h/L could be associated with higher probability of virological success.

10.
Transpl Infect Dis ; 20(2): e12846, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29360195

RESUMO

BACKGROUND: Donor (D)+/recipient (R)- serostatus is closely associated with a higher risk of cytomegalovirus (CMV) infection and disease. Antiviral prophylaxis is conventionally used in such patients, but late onset CMV infection/disease still occurs after the discontinuation of prophylaxis. METHODS: We retrospectively analyzed the data of 215 low immunological risk patients who received kidney transplantation in our center between 2011 and 2016. RESULTS: Ninety-seven patients received a combination of everolimus (EVL)/reduced doses of calcineurin inhibitors (CNI) (EVL group) de novo, and 118 received a combination of mycophenolic acid (MPA)/standard doses of CNI (MPA group) de novo. All patients received induction by basiliximab, steroids, and standardized antiviral prophylaxis depending on their CMV D/R serostatus. D+/R- recipients comprised 17% (n = 16) of the EVL group and 19% (n = 22) of the MPA group (P = .722). In the D+/R- subgroup, the 1-year incidence of late onset CMV primary disease after the withdrawal of prophylaxis was lower in the EVL group than in the MPA group (6% vs 41%, P = .025) while the rate of CMV disease in the D+/R+ group (8% vs 6%, P = 1) and the D-/R+ group (12% vs 9%, P = 1) were similar. Kaplan-Meier analysis of 1-year CMV primary disease-free survival in seronegative patients was significantly better in the EVL group (P = .029, log-rank test). CONCLUSIONS: Our data suggest that de novo use of EVL may reduce late onset CMV primary disease after the withdrawal of antiviral prophylaxis in kidney transplantation patients.


Assuntos
Antivirais/administração & dosagem , Infecções por Citomegalovirus/prevenção & controle , Everolimo/farmacologia , Transplante de Rim , Adulto , Idoso , Antivirais/uso terapêutico , Estudos de Coortes , Everolimo/administração & dosagem , Feminino , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Transplantados
11.
PLoS One ; 12(8): e0183376, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28813503

RESUMO

BACKGROUND: Whether spontaneous low levels of HIV-1 RNA in blood plasma correlate with low levels of HIV-1 RNA in seminal plasma has never been investigated in HIV controller (HIC) men so far. METHODS: HIC men enrolled in the ANRS CODEX cohort were eligible for the present study if they had no symptoms of sexually transmitted infections (STI). Two paired samples of blood and semen were collected four weeks apart. HIV-RNA was quantified in blood plasma (bpVL) and in seminal plasma (spVL), and cell-associated HIV-DNA was quantified in peripheral blood mononuclear cells (PBMC) and in non-sperm cells (NSC). Spearman rho tests were used to estimate correlations between bpVL and spVL. RESULTS: Ten men were enrolled. At Day 0 (D0), spVL was detectable in four patients: 458; 552; 256 copies/mL and PCR signal detectable below limit of quantification (LoQ, 40 copies/mL). At Day 28 (D28), spVL was detectable in the same four participants in whom spVL was detectable at D0 with 582; 802; 752 and 50 copies/mL, respectively. HIV-DNA was detectable below LoQ in NSC of one patient at D0 visit. No patient had detectable HIV-DNA in NSC at D28 visit. At D0, bpVL and spVL were highly positively correlated (Spearman rho: 0.94; p = 0.0001). Similar results were found at D28. CONCLUSION: We show that HIV-RNA can be detected in the semen of HIC men, with levels positively correlated with those measured concomitantly in blood plasma. HIC men should be aware of the risk of HIV genital shedding, especially if viral blips are reported.


Assuntos
Infecções por HIV/sangue , RNA Viral/sangue , RNA Viral/metabolismo , Sêmen/química , Adolescente , Adulto , Criança , Infecções por HIV/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Adulto Jovem
12.
Clin Infect Dis ; 65(3): 398-404, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28419213

RESUMO

Background: The design of diagnostic and preventive strategies have been prevented by gaps in knowledge of the epidemiology of congenital cytomegalovirus (cCMV) with the type of maternal infection as well as the lack of large-scale neonatal screening tools. Methods: In sum, 11715 consecutive newborns were screened for cCMV by polymerase chain reaction (PCR) in saliva. Prevalence, type of maternal infection, sociodemographic, obstetrical, and serological data were analyzed. Results: Positive predictive value of CMV PCR in saliva was 59%; false positive results were associated with lower viral loads (P < .001). Maternal seroprevalence was 61%, birth prevalence was 0.37%, resulting from primary and nonprimary infections in 52% and 47.7% of cases, respectively. The risk to deliver an infected baby after primary infection was increased in younger (OD = 7.9), parous (OD = 4.1) women born in high resources countries (OD = 5.2) and from higher income groups (P = .019). The only 2 risk factors to deliver an infected baby after nonprimary infection were to be young (OD = 4.6) and unemployed (OD = 5.8). The risk to deliver an infected baby was 4-fold higher in women seronegative before their pregnancy (P = .021). Conclusions: A positive CMV PCR in newborns' saliva should always be confirmed in a repeat-sample. Sociodemographic characteristics of women giving birth to an infected baby after primary and nonprimary infection are different. Seronegative, parous women represent the highest risk population for cCMV in countries with low to intermediate seroprevalence. Urgent action is needed to stop the cCMV's epidemic, particularly in this population easily identifiable by maternal serology and amenable to prevention messages. Clinical Trials Registration: NCT01923636.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , DNA Viral/análise , Triagem Neonatal , Complicações Infecciosas na Gravidez , Saliva/virologia , Adulto , Citomegalovirus/genética , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/virologia , DNA Viral/genética , Feminino , Humanos , Recém-Nascido , Reação em Cadeia da Polimerase , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Estudos Soroepidemiológicos , Carga Viral , Adulto Jovem
14.
Artigo em Inglês | MEDLINE | ID: mdl-27923540

RESUMO

Cytomegalovirus (CMV) congenital infection affects 0.7% of live births worldwide and is the leading cause of congenital neurological handicap of infectious origin. However, systematic screening for this infection has not been implemented in pregnancy or at birth in any country. This apparent paradox had been justified by persisting gaps in the knowledge of this congenital infection: uncertain epidemiological data, difficulty in the diagnosis of maternal infection, absence of validated prenatal prognostic markers, unavailability of an efficient vaccine and scarcity of data available on the treatment. However, in the last decade, new data have emerged towards better management of this congenital infection, including solid epidemiological data, good evidence for the accuracy of diagnosis of maternal CMV infection and good evidence for the feasibility of predicting the outcome of fetal infection by a combination of fetal imaging and fetal laboratory parameters. There is also some evidence that valaciclovir treatment of mothers carrying an infected fetus is feasible, safe and might be effective. This review provides an update on the evidence for diagnosis, prognosis and treatment of congenital infection in the antenatal period. These suggest a benefit to a proactive approach for prenatal congenital infections.


Assuntos
Infecções por Citomegalovirus/diagnóstico , Doenças Fetais/diagnóstico , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Complicações Infecciosas na Gravidez/diagnóstico , Aciclovir/análogos & derivados , Aciclovir/uso terapêutico , Líquido Amniótico/virologia , Anticorpos Antivirais/sangue , Antivirais/uso terapêutico , Ascite/diagnóstico por imagem , Ascite/etiologia , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/tratamento farmacológico , DNA Viral/análise , Feminino , Doenças Fetais/tratamento farmacológico , Humanos , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/etiologia , Hidropisia Fetal/diagnóstico por imagem , Hidropisia Fetal/etiologia , Imunização Passiva , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lisencefalia/diagnóstico por imagem , Lisencefalia/etiologia , Microcefalia/diagnóstico por imagem , Microcefalia/etiologia , Oligo-Hidrâmnio/diagnóstico por imagem , Oligo-Hidrâmnio/etiologia , Poli-Hidrâmnios/diagnóstico por imagem , Poli-Hidrâmnios/etiologia , Porencefalia/diagnóstico por imagem , Porencefalia/etiologia , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Soroconversão , Ultrassonografia Pré-Natal , Valaciclovir , Valina/análogos & derivados , Valina/uso terapêutico
15.
Euro Surveill ; 21(46)2016 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-27918268

RESUMO

We report 59 cases of severe paediatric conditions linked with enterovirus (EV)-A71 and EV-D68 in France between May and October 2016. Fifty-two children had severe neurological symptoms. EV sequence-based typing for 42 cases revealed EV-A71 in 21 (18 subgenotype C1, detected for the first time in France) and EV-D68 in eight. Clinicians should be encouraged to obtain stool and respiratory specimens from patients presenting with severe neurological disorders for EV detection and characterisation.


Assuntos
Coinfecção/virologia , Enterovirus Humano A/isolamento & purificação , Enterovirus Humano D/isolamento & purificação , Infecções por Enterovirus/epidemiologia , Tipagem Molecular , Doenças do Sistema Nervoso/virologia , Infecções Respiratórias/diagnóstico , Adolescente , Criança , Pré-Escolar , Coinfecção/epidemiologia , Enterovirus Humano A/genética , Enterovirus Humano D/genética , Infecções por Enterovirus/diagnóstico , Infecções por Enterovirus/virologia , Feminino , França/epidemiologia , Genótipo , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Masculino , Doenças do Sistema Nervoso/complicações , Filogenia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Vigilância de Evento Sentinela , Análise de Sequência de DNA , Índice de Gravidade de Doença
16.
J Exp Med ; 213(11): 2413-2435, 2016 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-27647349

RESUMO

Combined immunodeficiency (CID) refers to inborn errors of human T cells that also affect B cells because of the T cell deficit or an additional B cell-intrinsic deficit. In this study, we report six patients from three unrelated families with biallelic loss-of-function mutations in RLTPR, the mouse orthologue of which is essential for CD28 signaling. The patients have cutaneous and pulmonary allergy, as well as a variety of bacterial and fungal infectious diseases, including invasive tuberculosis and mucocutaneous candidiasis. Proportions of circulating regulatory T cells and memory CD4+ T cells are reduced. Their CD4+ T cells do not respond to CD28 stimulation. Their CD4+ T cells exhibit a "Th2" cell bias ex vivo and when cultured in vitro, contrasting with the paucity of "Th1," "Th17," and T follicular helper cells. The patients also display few memory B cells and poor antibody responses. This B cell phenotype does not result solely from the T cell deficiency, as the patients' B cells fail to activate NF-κB upon B cell receptor (BCR) stimulation. Human RLTPR deficiency is a CID affecting at least the CD28-responsive pathway in T cells and the BCR-responsive pathway in B cells.


Assuntos
Alelos , Linfócitos B/imunologia , Proteínas dos Microfilamentos/genética , Mutação/genética , Linfócitos T/imunologia , Adolescente , Adulto , Sequência de Bases , Antígenos CD28/metabolismo , Linfócitos T CD4-Positivos/imunologia , Diferenciação Celular/genética , Proliferação de Células/genética , Sobrevivência Celular/genética , Criança , Pré-Escolar , Dimerização , Feminino , Células HEK293 , Humanos , Memória Imunológica , Imunofenotipagem , Leucócitos/patologia , Masculino , NF-kappa B/metabolismo , Linhagem , Fenótipo , Receptores de Antígenos de Linfócitos B , Transdução de Sinais , Células Th17/imunologia , Células Th2/imunologia , Adulto Jovem
17.
J Antimicrob Chemother ; 71(11): 3202-3205, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27432601

RESUMO

OBJECTIVES: Intermittent seminal HIV-RNA detection can occur in MSM despite concomitant plasma virological control on combined ART (cART). We undertook the present study to determine if seminal HIV detection was associated with seminal cytomegalovirus (CMV) detection or detection of HIV-infected cells in semen. METHODS: Longitudinal semen samples from HIV-1-infected MSM on successful cART enrolled in the EVARIST ANRS EP 49 study were analysed. We first conducted a case-control analysis (ratio 1 : 3) to assess HIV-DNA detection in semen cells in the 20 patients with detectable HIV-RNA in seminal plasma (cases) matched with 60 participants with undetectable HIV-RNA (controls) based on total HIV-DNA load in blood cells. Second, we measured CMV-DNA in all seminal plasma samples. RESULTS: HIV-1-DNA in semen cells was detected on at least one sample visit in 12/20 cases and 11/60 controls. Detection of HIV-RNA in seminal plasma was associated significantly with the detection of HIV-DNA in semen cells [OR, 7.6 (95% CI, 2.1-28.4); P = 0.002] when adjusted on total HIV-DNA in blood cells. CMV-DNA was detected in 107/273 seminal plasma samples with a median value of 3.62 log10 copies/mL (IQR, 2.83-4.38), yielding a prevalence of 39.2%. Seminal CMV-DNA shedding [OR, 1.5 (95% CI, 0.6-3.6); P = 0.343] was not associated with the risk of detection of HIV-RNA in seminal plasma. CONCLUSIONS: The presence of HIV-DNA in semen cells was predictive of HIV-RNA detection, suggesting that viral particles arise through local HIV replication by infected semen cells. Despite virological control, compartmentalization of HIV in the genital tract might act in residual replication and transmission.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por Citomegalovirus/virologia , DNA Viral/análise , Infecções por HIV/virologia , HIV-1/isolamento & purificação , RNA Viral/análise , Sêmen/virologia , Estudos de Casos e Controles , Citomegalovirus/isolamento & purificação , Infecções por HIV/tratamento farmacológico , Homossexualidade Masculina , Humanos , Estudos Longitudinais , Masculino , Eliminação de Partículas Virais
18.
J Pediatr ; 175: 47-53.e3, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27339249

RESUMO

OBJECTIVE: To investigate the risk factors of empyema after acute viral infection and to clarify the hypothesized association(s) between empyema and some viruses and/or the use of nonsteroidal anti-inflammatory drugs (NSAIDs). STUDY DESIGN: A case-control study was conducted in 15 centers. Cases and controls were enrolled for a source population of children 3-15 years of age with acute viral infections between 2006 and 2009. RESULTS: Among 215 empyemas, 83 cases (children with empyema and acute viral infection within the 15 preceding days) were included, and 83 controls (children with acute viral infection) were matched to cases. Considering the intake of any drug within 72 hours after acute viral infection onset and at least 6 consecutive days of antibiotic use and at least 1 day of NSAIDs exposure, the multivariable analysis retained an increased risk of empyema associated with NSAIDs exposure (aOR 2.79, 95% CI 1.4-5.58, P = .004), and a decreased risk associated with antibiotic use (aOR 0.32, 95% CI 0.11-0.97, P = .04). The risk of empyema associated with NSAIDs exposure was greater for children not prescribed an antibiotic and antibiotic intake diminished that risk for children given NSAIDs. CONCLUSIONS: NSAIDs use during acute viral infection is associated with an increased risk of empyema in children, and antibiotics are associated with a decreased risk. The presence of antibiotic-NSAIDs interaction with this risk is suggested. These findings suggest that NSAIDs should not be recommended as a first-line antipyretic treatment during acute viral infections in children.


Assuntos
Antibacterianos/uso terapêutico , Anti-Inflamatórios não Esteroides/efeitos adversos , Empiema Pleural/etiologia , Viroses/tratamento farmacológico , Doença Aguda , Adolescente , Anti-Inflamatórios não Esteroides/uso terapêutico , Estudos de Casos e Controles , Criança , Pré-Escolar , Quimioterapia Combinada , Empiema Pleural/diagnóstico , Feminino , Humanos , Lactente , Modelos Logísticos , Masculino , Análise Multivariada , Fatores de Risco , Viroses/complicações , Viroses/diagnóstico
20.
Am J Obstet Gynecol ; 215(3): 342.e1-9, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27063062

RESUMO

BACKGROUND: Congenital cytomegalovirus infection occurs in 0.7% of live births with 15-20% of infected children developing long-term disability including hearing loss and cognitive deficit. Fetal cytomegalovirus infection is established by viral DNA amplification by polymerase chain reaction in amniotic fluid obtained by amniocentesis following maternal seroconversion or after the diagnosis of ultrasound features suggestive of fetal infection. Severe brain ultrasound anomalies are associated with a poor prognosis. The prognosis of an infected fetus showing either no ultrasound features or nonsevere ultrasound anomalies is difficult to establish up until late in the second or third trimester of pregnancy. OBJECTIVE: We sought to evaluate the prognostic value of fetal ultrasound, amniotic fluid, and fetal blood analysis at the time of prenatal diagnosis of fetal infection. STUDY DESIGN: We reviewed all cases of fetal cytomegalovirus infection with a sample of amniotic fluid positive for viral DNA and/or fetal blood analyzed in our laboratory from 2008 through 2013. Prenatal ultrasound features along with cytomegalovirus DNA loads in amniotic fluid and in fetal blood and fetal platelet counts were reviewed in relation to gestational age at maternal infection, neonatal examination, and postnatal follow-up or postmortem examination. RESULTS: In all, 82 fetuses were infected following maternal infection mainly in the first trimester. At the time of prenatal diagnosis at a median of 23 weeks, 19, 22, and 41 fetuses showed severe brain ultrasound abnormalities, nonsevere ultrasound features, and normal ultrasound examination, respectively. Nonsevere ultrasound features, higher DNA load in amniotic fluid, fetal platelet count ≤114,000/mm(3), and DNA load ≥4.93 log10 IU/mL in fetal blood were associated with a symptomatic status at birth in univariate analysis (P < .001, P = .001, and P = .018, respectively). Bivariate analysis combining ultrasound results and either adjusted viral load in amniotic fluid or fetal blood profile showed that these were independent prognostic factors of a symptomatic status at birth. Both fetal blood parameters were better predictors than amniotic fluid viral load. At the time of prenatal diagnosis, the ultrasound negative predictive value for symptoms at birth or at termination of pregnancy was 93%. The combined negative predictive values of ultrasound and viral load in amniotic fluid and that of ultrasound and fetal blood parameters were 95% and 100%, respectively. In fetuses presenting with nonsevere ultrasound features, the positive predictive values of ultrasound alone and in combination with amniotic fluid viral load or with fetal blood parameters were 60%, 78%, and 79%, respectively. CONCLUSION: Risk assessment of infected fetuses for being symptomatic at birth is possible as early as the time of diagnosis by using a combination of targeted ultrasound examination along with viral load in amniotic fluid and in fetal blood together with platelet count. The advantage of using amniotic fluid is that it is available at prenatal diagnosis. One may wonder if increasing the negative predictive value of the overall assessment of an infected fetus from 95-100% is worth the additional risk of cordocentesis for fetal blood sampling. This can only be an individual decision made by well-informed women and it seems therefore appropriate to use the figures presented here and their confidence intervals for counseling.


Assuntos
Líquido Amniótico/virologia , Encéfalo/diagnóstico por imagem , Infecções por Citomegalovirus/diagnóstico , Sangue Fetal/virologia , Diagnóstico Pré-Natal , Ultrassonografia Pré-Natal , Carga Viral , Amniocentese , Encéfalo/anormalidades , Citomegalovirus/genética , Infecções por Citomegalovirus/complicações , DNA Viral/análise , Deficiências do Desenvolvimento/virologia , Feminino , Doenças Fetais/diagnóstico , Perda Auditiva/virologia , Humanos , Recém-Nascido , Contagem de Plaquetas , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Prognóstico , Medição de Risco
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