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HIV暴露儿童和HIV感染儿童机会性感染的预防与治疗指南:美国疾病控制与预防中心、国立卫生研究院、美国传染病学会HIV医学协会、儿科传染病学会及美国儿科学会的建议

Guidelines for the Prevention and Treatment of Opportunistic Infections among HIV-exposed and HIV-infected children: recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics.

作者信息

Mofenson Lynne M, Brady Michael T, Danner Susie P, Dominguez Kenneth L, Hazra Rohan, Handelsman Edward, Havens Peter, Nesheim Steve, Read Jennifer S, Serchuck Leslie, Van Dyke Russell

机构信息

National Institutes of Health, Bethesda, Maryland, USA.

出版信息

MMWR Recomm Rep. 2009 Sep 4;58(RR-11):1-166.

Abstract

This report updates and combines into one document earlier versions of guidelines for preventing and treating opportunistic infections (OIs) among HIV-exposed and HIV-infected children, last published in 2002 and 2004, respectively. These guidelines are intended for use by clinicians and other health-care workers providing medical care for HIV-exposed and HIV-infected children in the United States. The guidelines discuss opportunistic pathogens that occur in the United States and one that might be acquired during international travel (i.e., malaria). Topic areas covered for each OI include a brief description of the epidemiology, clinical presentation, and diagnosis of the OI in children; prevention of exposure; prevention of disease by chemoprophylaxis and/or vaccination; discontinuation of primary prophylaxis after immune reconstitution; treatment of disease; monitoring for adverse effects during treatment; management of treatment failure; prevention of disease recurrence; and discontinuation of secondary prophylaxis after immune reconstitution. A separate document about preventing and treating of OIs among HIV-infected adults and postpubertal adolescents (Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents) was prepared by a working group of adult HIV and infectious disease specialists. The guidelines were developed by a panel of specialists in pediatric HIV infection and infectious diseases (the Pediatric Opportunistic Infections Working Group) from the U.S. government and academic institutions. For each OI, a pediatric specialist with content-matter expertise reviewed the literature for new information since the last guidelines were published; they then proposed revised recommendations at a meeting at the National Institutes of Health (NIH) in June 2007. After these presentations and discussions, the guidelines underwent further revision, with review and approval by the Working Group, and final endorsement by NIH, CDC, the HIV Medicine Association (HIVMA) of the Infectious Diseases Society of America (IDSA), the Pediatric Infectious Disease Society (PIDS), and the American Academy of Pediatrics (AAP). The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of the evidence supporting the recommendation so readers can ascertain how best to apply the recommendations in their practice environments. An important mode of acquisition of OIs, as well as HIV infection among children, is from their infected mother; HIV-infected women coinfected with opportunistic pathogens might be more likely than women without HIV infection to transmit these infections to their infants. In addition, HIV-infected women or HIV-infected family members coinfected with certain opportunistic pathogens might be more likely to transmit these infections horizontally to their children, resulting in increased likelihood of primary acquisition of such infections in the young child. Therefore, infections with opportunistic pathogens might affect not just HIV-infected infants but also HIV-exposed but uninfected infants who become infected by the pathogen because of transmission from HIV-infected mothers or family members with coinfections. These guidelines for treating OIs in children therefore consider treatment of infections among all children, both HIV-infected and uninfected, born to HIV-infected women. Additionally, HIV infection is increasingly seen among adolescents with perinatal infection now surviving into their teens and among youth with behaviorally acquired HIV infection. Although guidelines for postpubertal adolescents can be found in the adult OI guidelines, drug pharmacokinetics and response to treatment may differ for younger prepubertal or pubertal adolescents. Therefore, these guidelines also apply to treatment of HIV-infected youth who have not yet completed pubertal development. Major changes in the guidelines include 1) greater emphasis on the importance of antiretroviral therapy for preventing and treating OIs, especially those OIs for which no specific therapy exists; 2) information about the diagnosis and management of immune reconstitution inflammatory syndromes; 3) information about managing antiretroviral therapy in children with OIs, including potential drug--drug interactions; 4) new guidance on diagnosing of HIV infection and presumptively excluding HIV infection in infants that affect the need for initiation of prophylaxis to prevent Pneumocystis jirovecii pneumonia (PCP) in neonates; 5) updated immunization recommendations for HIV-exposed and HIV-infected children, including hepatitis A, human papillomavirus, meningococcal, and rotavirus vaccines; 6) addition of sections on aspergillosis; bartonella; human herpes virus-6, -7, and -8; malaria; and progressive multifocal leukodystrophy (PML); and 7) new recommendations on discontinuation of OI prophylaxis after immune reconstitution in children. The report includes six tables pertinent to preventing and treating OIs in children and two figures describing immunization recommendations for children aged 0--6 years and 7--18 years. Because treatment of OIs is an evolving science, and availability of new agents or clinical data on existing agents might change therapeutic options and preferences, these recommendations will be periodically updated and will be available at http://AIDSInfo.nih.gov.

摘要

本报告更新了2002年和2004年分别发布的关于预防和治疗暴露于HIV及感染HIV儿童机会性感染(OIs)的早期指南版本,并将其合并为一份文件。这些指南供美国为暴露于HIV及感染HIV儿童提供医疗服务的临床医生和其他医护人员使用。指南讨论了在美国出现的机会性病原体以及一种可能在国际旅行期间感染的病原体(即疟疾)。每个机会性感染所涵盖的主题领域包括儿童机会性感染的流行病学、临床表现和诊断的简要描述;暴露预防;通过化学预防和/或疫苗接种预防疾病;免疫重建后停止初级预防;疾病治疗;治疗期间不良反应的监测;治疗失败的管理;疾病复发的预防;以及免疫重建后停止二级预防。一份关于预防和治疗感染HIV的成人和青春期后青少年机会性感染的单独文件(《HIV感染成人和青少年机会性感染预防和治疗指南》)由成人HIV和传染病专家工作组编写。这些指南由来自美国政府和学术机构的儿科HIV感染和传染病专家小组(儿科机会性感染工作组)制定。对于每种机会性感染,自上次指南发布以来,具有相关专业知识的儿科专家查阅了文献以获取新信息;然后他们在2007年6月于美国国立卫生研究院(NIH)召开的一次会议上提出了修订建议。经过这些陈述和讨论后,指南经过进一步修订,由工作组审查和批准,并得到NIH、疾病控制与预防中心(CDC)、美国传染病学会(IDSA)的HIV医学协会(HIVMA)、儿科传染病学会(PIDS)和美国儿科学会(AAP)的最终认可。这些建议通过一个字母表示推荐强度,通过一个罗马数字表示支持该推荐的证据质量来进行评级,以便读者能够确定如何在其实际工作环境中最佳地应用这些建议。儿童获得机会性感染以及感染HIV的一个重要途径是通过其受感染的母亲;感染HIV且合并机会性病原体的女性可能比未感染HIV的女性更有可能将这些感染传播给她们的婴儿。此外,感染HIV的女性或感染HIV且合并某些机会性病原体的家庭成员可能更有可能将这些感染横向传播给她们的孩子,从而增加幼儿初次感染此类感染的可能性。因此,机会性病原体感染可能不仅影响感染HIV的婴儿,还影响因感染HIV的母亲或合并感染的家庭成员传播而感染病原体的暴露于HIV但未感染的婴儿。因此,这些儿童机会性感染治疗指南考虑对感染HIV的女性所生的所有儿童(无论感染HIV与否)中的感染进行治疗。此外,在围产期感染后存活至青少年期的青少年以及通过行为感染HIV的青年中,HIV感染越来越常见。尽管青春期后青少年的指南可在成人机会性感染指南中找到,但年龄较小的青春期前或青春期青少年的药物药代动力学和对治疗的反应可能有所不同。因此,这些指南也适用于尚未完成青春期发育的感染HIV的青年。指南中的主要变化包括:1)更加强调抗逆转录病毒疗法在预防和治疗机会性感染中的重要性,尤其是那些没有特定治疗方法的机会性感染;2)关于免疫重建炎症综合征的诊断和管理的信息;3)关于在患有机会性感染的儿童中管理抗逆转录病毒疗法的信息,包括潜在的药物相互作用;4)关于诊断HIV感染和推定排除影响新生儿预防耶氏肺孢子菌肺炎(PCP)所需预防性用药起始需求的婴儿HIV感染的新指南;5)针对暴露于HIV及感染HIV儿童的更新免疫接种建议,包括甲型肝炎、人乳头瘤病毒、脑膜炎球菌和轮状病毒疫苗;6)增加了关于曲霉病、巴尔通体、人疱疹病毒6型、7型和8型、疟疾以及进行性多灶性白质脑病(PML)的章节;7)关于儿童免疫重建后停止机会性感染预防的新建议。该报告包括六张与预防和治疗儿童机会性感染相关的表格以及两张描述0至6岁和7至18岁儿童免疫接种建议的图表。由于机会性感染的治疗是一门不断发展的科学,新药物的可用性或现有药物的临床数据可能会改变治疗选择和偏好,这些建议将定期更新,并可在http://AIDSInfo.nih.gov上获取。

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