Congenital CMV infection in the era of Option B in South Africa

 描述（由申请人提供）：先天性CMV感染（cCMV）是最常见的先天性感染，也是全球感音神经性听力损失的主要非遗传原因。cCMV的出生患病率与母体CMV血清阳性率水平成正比，在高血清阳性人群中观察到的患病率明显较高。在非洲人群中观察到cCMV感染率上升，有证据表明艾滋病毒等孕产妇合并感染在这些国家中发挥着关键作用，是cCMV的驱动因素。尽管撒哈拉以南非洲的艾滋病毒感染负担很高，但孕产妇艾滋病毒对宫内巨细胞病毒传播频率、出生时症状性感染和长期后遗症的影响尚未得到系统评价。我们最近在南非西开普省的HIV暴露新生儿中进行了第一项cCMV出生患病率研究，并证明了产前抗逆转录病毒预防时代的cCMV高患病率（2.93%; 95%CI 1.73-4.13）。婴儿巨细胞病毒感染与艾滋病毒疾病进展和死亡率的风险增加，以及对艾滋病毒暴露但未感染的赞比亚婴儿的生长，发育和总体发病率的不利影响广泛相关。这些发现表明，巨细胞病毒感染（宫内或产后获得）对未感染艾滋病毒的儿童的总体儿童发病率和死亡率有不利影响。我们假设母亲HIV感染增加了宫内CMV传播的风险，即使在选择B的时代，CMV感染的婴儿也容易出现不良结局。这项拟议的研究将提供可靠的估计出生流行率的先天性巨细胞病毒感染的艾滋病毒暴露和艾滋病毒未暴露的新生儿在撒哈拉以南非洲的背景下，在三联抗逆转录病毒治疗，以及初步数据的频率和时间出生后巨细胞病毒收购在婴儿期和巨细胞病毒感染的影响，在婴儿期收购儿童发病率。在这项研究中，我们将在Mshiyeni王子纪念医院筛查约4，200名新生儿，该医院是一家提供补贴医疗保健的地区医院，其中40%的孕妇感染艾滋病毒。新生儿CMV筛查将通过使用我们实验室开发的实时PCR方法检测干燥的唾液标本进行。将实施婴儿听力筛查和诊断听力学测试方案，以确定CMV相关听力损失的患病率。本研究的目的是：1）确定HIV暴露和未暴露新生儿中先天性CMV感染的出生患病率，2）确定先天性CMV感染的HIV暴露和未暴露新生儿中新生儿疾病和CMV相关后遗症的患病率，3）探索CMV感染（先天性和出生后）对儿童总体发病率和死亡率的影响。拟议的研究利用了具有相似兴趣和动机的调查小组的经验、专业知识和承诺，以确定母体HIV感染对CMV宫内传播、CMV相关听力损失的影响，以及婴儿早期获得的CMV感染是否影响儿童的总体发病率。

 DESCRIPTION (provided by applicant): Congenital CMV infection (cCMV) is the most common congenital infection and a leading non-genetic cause of sensorineural hearing loss worldwide. The birth prevalence of cCMV is directly proportional to maternal CMV seroprevalence levels, with substantially higher rates observed in highly seropositive populations. Increased rates of cCMV are observed in African populations, with evidence for a key role for maternal co-infections, such as HIV, as a driver of cCMV in these countries. Despite a high burden of HIV infection in sub-Saharan Africa, the impact of maternal HIV on the frequency of in utero CMV transmission, symptomatic infection at birth and long-term sequelae has not been systematically evaluated. We recently conducted the first study of cCMV birth prevalence among HIV-exposed newborns in the Western Cape, South Africa, and demonstrated a high rate of cCMV (2.93%; 95% CI 1.73-4.13) in the era of prenatal antiretroviral prophylaxis. Infant CMV infection has been widely associated with an increased risk of HIV disease progression and mortality, as well as an adverse impact on growth, development and overall morbidity in HIV-exposed but uninfected Zambian infants. These findings suggest that CMV infection (intrauterine or postnatal acquisition) has an adverse impact on overall childhood morbidity and mortality in children not infected with HIV. We hypothesize that maternal HIV infection increases the risk of intrauterine CMV transmission, and predisposes CMV-infected infants to adverse outcomes even in the era of option B. The proposed study will provide reliable estimates of the birth prevalence of congenital CMV infection in HIV-exposed and HIV-unexposed newborns in sub-Saharan Africa in the context of triple antiretroviral therapy, as well as preliminary data on the frequency and timing of postnatal CMV acquisition during infancy and the impact of CMV infection acquired in infancy on childhood morbidity. In this study, we will screen ~4,200 newborns at the Prince Mshiyeni Memorial Hospital, a regional hospital that provides subsidized health care where 40% of pregnant women are HIV-infected. Newborn CMV screening will be carried out by testing dried saliva specimens using a real-time PCR method developed in our laboratory. Hearing screening of infants and diagnostic audiology testing protocols will be implemented to determine the prevalence of CMV-associated hearing loss. The objectives of the study are: 1) To determine the birth prevalence of congenital CMV infection among HIV-exposed and HIV-unexposed newborns, 2) To determine the prevalence of newborn disease and CMV-associated sequelae in HIV-exposed and unexposed newborns with congenital CMV infection, and 3) To explore the impact of CMV infection (both congenital and postnatal) on overall childhood morbidity and mortality. The proposed studies take advantage of the experience, expertise and commitment of the investigative team with similar interests and motivation to determine the impact of maternal HIV infection on in utero transmission of CMV, CMV-associated hearing loss and whether CMV infection acquired in early infancy affects overall childhood morbidity.