Serologic evidence for Cryptococcus neoformans infection in early childhood
Serologic evidence for Cryptococcus neoformans infection in early childhood
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DOI：
10.1542/peds.107.5.e66
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发表时间：
2001-05-01
期刊：
影响因子：
8
通讯作者：
Casadevall, A
中科院分区：
文献类型：
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作者：
Goldman, DL;Khine, H;Casadevall, A
Objective.新生隐球菌是成人获得性免疫缺陷综合征（AIDS）中枢神经系统感染的重要原因，但在儿童AIDS中是一种罕见的疾病。这种与年龄有关的发病率差异的基础尚不清楚，但可能是由暴露或免疫反应的差异引起的。本研究的目的是确定隐球菌病在儿童中的低患病率是否与缺乏接触新型隐球菌有关。从185名年龄从1周至21岁的免疫功能正常的个体中获得血清，这些个体正在城市急诊科接受评估。通过免疫印迹法分析血清中新生念珠菌和白色念珠菌蛋白的抗体。免疫印迹模式进行了比较，从隐球菌病患者（n = 10）和工人的血清中的实验室致力于研究C新生。我们的研究结果的特异性得到了几种方法的证实，包括抗体吸收和阻断研究。同时采用酶联免疫吸附试验和乳胶凝集试验检测血清中隐球菌多糖的含量。1.1至2岁儿童的血清对新生隐球菌蛋白的反应性最低。相反，大多数2岁以上儿童的血清识别许多（大于或等于6）C neoformans蛋白。对于2.1至5岁的儿童，56%的血清（n = 25）与多种蛋白质反应，而对于>5岁的儿童（n = 120），70%的样品与多种蛋白质反应。通过用新型隐球菌提取物吸收血清或用实验感染的血清预孵育印迹，而不是对照大鼠的血清，反应性降低。对新生念珠菌蛋白的反应性与对白色念珠菌蛋白的反应性无关，白色念珠菌蛋白在1.1至2岁儿童的血清中很常见。在1名儿童的血清中检测到隐球菌多糖，滴度为1：16（类似于10 ng/mL），这名5.6岁的男孩因呕吐而到急诊室就诊。我们的研究结果提供了间接和直接的证据，新生隐球菌感染的免疫功能正常的儿童。我们的研究结果表明，C neoformans感染大多数儿童生活在布朗克斯后2岁。这些结果与以下几个观察结果一致：环境中C neoformans的普遍存在性，包括其与鸽子排泄物的关联;城市地区的鸽子数量众多;以及儿童一旦学会走路，环境暴露的可能性增加。免疫功能正常的儿童中与新型隐球菌感染相关的体征和症状仍有待确定。原发性肺隐球菌病可能无症状或产生与病毒感染混淆的症状，因此不被认为是真菌感染。我们的研究结果表明，艾滋病患儿隐球菌病的低发病率并不是缺乏接触新型隐球菌的结果。这些发现对新型隐球菌的发病机制和疫苗策略的发展具有重要意义。
Objective. Cryptococcus neoformans is an important cause of central nervous system infection in adults with acquired immunodeficiency syndrome (AIDS) but an unusual cause of disease in children with AIDS. The basis for this age-related difference in incidence is not known but may be caused by differences in exposure or immune response. The objective of this study was to determine whether the low prevalence of cryptococcal disease among children is related to a lack of exposure to C neoformans.Methods. Sera were obtained from 185 immunocompetent individuals ranging in age from 1 week to 21 years who were being evaluated in an urban emergency department. Sera were analyzed for antibodies to C neoformans and Candida albicans proteins by immunoblotting. Immunoblot patterns were compared with those obtained from sera of patients with cryptococcosis (n = 10) and workers in a laboratory devoted to the study of C neoformans. The specificity of our results was confirmed by several approaches, including antibody absorption and blocking studies. Sera were also analyzed for the presence of cryptococcal polysaccharide by both enzyme-linked immunosorbent assay and latex agglutination assays.Results. Sera from children 1.1 to 2 years old demonstrated minimal reactivity to C neoformans proteins. In contrast, the majority of sera from children >2 years old recognized many (greater than or equal to6) C neoformans proteins. For children between 2.1 and 5 years old, 56% of sera (n = 25) reacted with many proteins, whereas for children >5 years old (n = 120), 70% of samples reacted with many proteins. Reactivity was decreased by absorbing sera with C neoformans extracts or by preincubating blots with sera from experimentally infected but not from control rats. Reactivity to C neoformans proteins did not correlate with reactivity to C albicans proteins, which was common in sera from children between the ages of 1.1 and 2 years. Cryptococcal polysaccharide was detected at a titer of 1:16 (similar to 10 ng/mL) in the sera of 1 child, a 5.6-year-old boy who presented to the emergency department with vomiting.Conclusions. Our findings provide both indirect and direct evidence of C neoformans infection in immunocompetent children. Our results indicate that C neoformans infects a majority of children living in the Bronx after 2 years old. These results are consistent with several observations: the ubiquitous nature of C neoformans in the environment, including its association with pigeon excreta; the large number of pigeons in urban areas; and the increased likelihood of environmental exposure for children once they have learned to walk. The signs and symptoms associated with C neoformans infection in immunocompetent children remained to be determined. Primary pulmonary cryptococcosis may be asymptomatic or produce symptoms confused with viral infections and, therefore, not recognized as a fungal infection. Our results suggest that the low incidence of symptomatic cryptococcal disease in children with AIDS is not a result of lack of exposure to C neoformans. These findings have important implications for C neoformans pathogenesis and the development of vaccine strategies.