Accuracy of QuantiFERON-TB Gold-PLUS Test for the Diagnosis of Mycobacterium tuberculosis infection in Children.
QuantiFERON-TB Gold-PLUS 试验诊断儿童结核分枝杆菌感染的准确性。
- 作者列表："Buonsenso D","Delogu G","Perricone C","Grossi R","Careddu A","De Maio F","Palucci I","Sanguinetti M","Valentini P","Sali M
Background. Compared to its predecessor QuantiFERON-TB Gold in Tube (QFT-IT), QuantiFERON-TB Gold Plus (QFT-Plus) contains an additional antigen tube (TB2), stimulating both CD4+ and CD8+ T-cells. The ability to discriminate CD4+ and CD8+ responses is suggested to be useful in differentiating stages of M. tuberculosis infection. While QFT-Plus has already been evaluated in adults, there are not enough data in children evaluated for suspected active tuberculosis (TB) or latent TB infection (LTBI).Methods. A prospective cross-sectional study was conducted among children aged 0 to 17 years who were evaluated for suspected active TB or screened for LTBI. All children underwent QFT-Plus and further clinical, radiological, microbiological analyses according to clinical scenario.Results. Of the 198 children enrolled, 43 (21.7 %) were tested because of suspicion of active TB: 12/43 (27.9%) were diagnosed with active TB, and among these 10/12 (83.3%) had a positive QFT-Plus assay. Of the 155 children screened for LTBI 18 (11.6%) had a positive QFT-Plus and 5 (2.5%) had an indeterminate result. TB1 and TB2 quantitative responses were not able to discriminate active disease from latent infection. The percent agreement between TB1 and TB2 was 100%.Conclusions. QFT-Plus assay showed good sensitivity for active TB and was particularly useful for the evaluation of children with suspected LTBI, giving a low rate of indeterminate results in this group. More studies are needed to properly evaluate QFT-Plus ability in discriminating active disease from latent infection.
背景。与其前身 QuantiFERON-TB Gold in Tube (QFT-IT) 相比，QuantiFERON-TB Gold Plus (QFT-Plus) 含有额外的抗原管 (TB2),同时刺激 CD4 + 和 CD8 + T 细胞。区分 CD4 + 和 CD8 + 反应的能力被认为在鉴别结核分枝杆菌感染的阶段是有用的。虽然 QFT-Plus 已经在成人中进行了评估，但在儿童中评估疑似活动性结核病 (TB) 或潜伏性结核感染 (LTBI) 的数据不足。对 0 ~ 17 岁疑似活动性结核病或筛查 LTBI 的儿童进行前瞻性横断面研究。所有患儿均根据临床情况进行 QFT-Plus 和进一步的临床、放射学、微生物学分析。结果。在登记的 198 名儿童中，43 名 (21.7%) 因怀疑活动性结核病而接受检测: 12/43 名 (27.9%) 被诊断患有活动性结核病，其中 10/12 名 (83.3%) QFT-Plus 检测阳性。在筛查 LTBI 的 155 例儿童中，18 例 (11.6%) QFT-Plus 阳性，5 例 (2.5%) 结果不确定。TB1 和 TB2 定量反应不能区分活动性疾病和潜伏感染。TB1 和 TB2 之间的一致性百分比为 100%。结论。QFT-Plus 检测对活动性 TB 显示出良好的敏感性，对疑似 LTBI 患儿的评估特别有用，在该组中给出的不确定结果率较低。需要更多的研究来正确评价 QFT-Plus 区分活动性疾病和潜伏感染的能力。
METHODS:Novel interventions that do not rely on daily adherence to ART are needed to achieve sustained viral remission for perinatally infected children, who currently rely on lifelong ART. Considering the risks and expense associated with ART interruption trials, the identification of biomarkers of viral rebound will prioritize promising therapeutic intervention strategies, including anti-HIV Env protein therapeutics. However, comprehensive studies to identify those biomarkers are logistically challenging in human infants, demanding the need for relevant nonhuman primate models of HIV rebound. In this study, we developed an infant RM model of oral infection with simian-human immunodeficiency virus expressing clade C HIV Env and short-term ART followed by ATI, longitudinally characterizing the immune responses to viral infection during ART and after ATI. Additionally, we compared this infant RM model to an analogous adult RM rebound model and identified virologic and immunologic correlates of the time to viral rebound after ATI.To achieve long-term viral remission in human immunodeficiency virus (HIV)-infected children, novel strategies beyond early antiretroviral therapy (ART) will be necessary. Identifying clinical predictors of the time to viral rebound upon ART interruption will streamline the development of novel therapeutic strategies and accelerate their evaluation in clinical trials. However, identification of these biomarkers is logistically challenging in infants, due to sampling limitations and the potential risks of treatment interruption. To facilitate the identification of biomarkers predicting viral rebound, we have developed an infant rhesus macaque (RM) model of oral simian-human immunodeficiency virus (SHIV) SHIV.CH505.375H.dCT challenge and analytical treatment interruption (ATI) after short-term ART. We used this model to characterize SHIV replication kinetics and virus-specific immune responses during short-term ART or after ATI and demonstrated plasma viral rebound in 5 out of 6 (83%) infants. We observed a decline in humoral immune responses and partial dampening of systemic immune activation upon initiation of ART in these infants. Furthermore, we monitored SHIV replication and rebound kinetics in infant and adult RMs and found that both infants and adults demonstrated equally potent virus-specific humoral immune responses. Finally, we validated our models by confirming a well-established correlate of the time to viral rebound, namely, the pre-ART plasma viral load, as well as identified additional potential humoral immune correlates. Thus, this model of infant ART and viral rebound can be used and further optimized to define biomarkers of viral rebound following long-term ART as well as to preclinically assess novel therapies to achieve a pediatric HIV functional cure.
METHODS:There is a pressing need for next-generation influenza vaccine strategies that are better able to manage antigenic drift and the cocirculation of multiple drift variants and that consistently improve vaccine effectiveness. Influenza virus NA is a key target antigen as a component of a next-generation vaccine in the influenza field, with evidence for a role in protective immunity in humans. However, mechanisms of protection provided by antibodies directed to NA remain largely unexplored. Herein, we show that antibody Fc interaction with Fcγ receptors (FcγRs) expressed on effector cells contributes to viral control in a murine model of influenza. Importantly, a chimeric mouse-human IgG1 with no direct antiviral activity was demonstrated to solely rely on FcγRs to protect mice from disease. Therefore, antibodies without NA enzymatic inhibitory activity may also play a role in controlling influenza viruses and should be of consideration when designing NA-based vaccines and assessing immunogenicity.Influenza virus neuraminidase (NA) has been under intense study recently as a vaccine antigen, yet there remain unanswered questions regarding the immune response directed toward NA. Antibodies (Abs) that can inhibit NA activity have been shown to aid in the control of disease caused by influenza virus infection in humans and animal models, yet how and if interactions between the Fc portion of anti-NA Abs and Fcγ receptors (FcγR) contribute to protection has not yet been extensively studied. Herein, we show that poly- and monoclonal anti-NA IgG antibodies with NA inhibitory activity can control A(H1N1)pdm09 infection in the absence of FcγRs, but FcγR interaction aided in viral clearance from the lungs. In contrast, a mouse-human chimeric anti-NA IgG1 that was incapable of mediating NA inhibition (NI) solely relied on FcγR interaction to protect transgenic mice (with a humanized FcγR compartment) against A(H1N1)pdm09 infection. As such, this study suggests that NA-specific antibodies contribute to protection against influenza A virus infection even in the absence of NI activity and supports protection through multiple effector mechanisms.
METHODS:Maternal primary and non-primary cytomegalovirus (CMV) infection during pregnancy can result in in utero transmission to the developing fetus. Congenital CMV (cCMV) can result in significant morbidity, mortality or long-term sequelae, including sensorineural hearing loss, the most common sequela. As a leading cause of congenital infections worldwide, cCMV infection meets many of the criteria for screening. However, currently there are no universal programs that offer maternal or neonatal screening to identify infected mothers and infants, no vaccines to prevent infection, and no efficacious and safe therapies available for the treatment of maternal or fetal CMV infection. Data has shown that there are several maternal and neonatal screening strategies, and diagnostic methodologies, that allow the identification of those at risk of developing sequelae and adequately detect cCMV. Nevertheless, many questions remain unanswered in this field. Well-designed clinical trials to address several facets of CMV treatment (in pregnant women, CMV-infected fetuses and both symptomatic and asymptomatic neonates and children) are required. Prevention (vaccines), biology and transmission factors associated with non-primary CMV, and the cost-effectiveness of universal screening, all demand further exploration to fully realize the ultimate goal of preventing cCMV. In the meantime, prevention of primary infection during pregnancy should be championed to all by means of hygiene education.