Center for Infectious Diseases Research, American University of Beirut, Beirut, Lebanon.
Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
PLoS One. 2020 Sep 22;15(9):e0239258. doi: 10.1371/journal.pone.0239258. eCollection 2020.
Viral infections in children and adolescents with malignancy are commonly encountered and have a significant impact on morbidity and mortality. Studies and epidemiological data regarding viral infections in children with cancer in developing countries are lacking. This retrospective cohort study aims to assess the burden of viral infections in children and adolescents with cancer, by assessing prevalence, risk factors, as well as morbidity and mortality of common viruses over a period of 8 years.
Medical records of cancer patients treated at the Children Cancer Center of Lebanon were reviewed and 155 participants under the age of 21 were identified with at least one documented viral infection during the period from July 2009 to November 2017. This subset included 136 participants with active malignancy and 19 participants with a history of cancer who underwent hematopoietic stem cell transplantation [HSCT] and were in remission; the latter group was analyzed separately. Information regarding participant characteristics, hospital course, and complications were obtained. Associations between viral infections and certain factors were assessed. In the cohort, 64% were male, 81% were Lebanese. In participants with active malignancy, 90% received chemotherapy in the 6 months preceding the viral infection episode, 11% received radiotherapy. 51% of participants were neutropenic at the time of viral detection, and 77% were lymphopenic. 17% experienced a bacterial co-infection, and 3 experienced a viral co-infection. Among 162 viral infection episodes, clinically diagnosed skin infections, mainly herpes simplex virus type 1 and varicella-zoster virus, were the most common [44% of cases]. These were followed by laboratory-proven systemic herpes infections: cytomegalovirus [14%] and Epstein-Barr virus [6%]. Respiratory viruses: influenza and respiratory syncytial virus, accounted for 9% and 4%, respectively, whereas rotavirus represented 11% and BK virus represented 3% of cases. Acute lymphocytic leukemia was the most prevalent neoplasia [57%]. Fever was the most common presenting symptom [55%] and febrile neutropenia was the reason for admission in 24% of cases. The mean length of stay was significantly longer in participants with cytomegalovirus infections and significantly lower in rotavirus infection. Admission to the ICU occurred in 9%, complications in 8%, and mortality in 5%. Participants with viral infections post-HSCT were noted to have a significantly longer length of hospital stay compared to non-HSCT participants, with no other significant differences in clinical course and outcome. The study was limited by its retrospective nature and by the late introduction and underuse of multiplex PCR panels, which may have led to underdiagnosis of viral infections.
Viral infections were prevalent in our sample of cancer patients and may have contributed to morbidity and mortality. Newly available viral diagnostics are likely to vastly increase the number and scope of detectable viral infections in this population. Prospective studies using multiplex PCR technology with systematic testing of patients will be more helpful in defining the burden of viral infections. Furthermore, efforts at antimicrobial stewardship would benefit from the identification of viral causes of infection and limit the unnecessary use of antibiotics in the pediatric cancer population.
儿童和青少年恶性肿瘤患者常发生病毒感染，这对发病率和死亡率有重大影响。发展中国家儿童癌症患者病毒感染的研究和流行病学数据尚缺乏。本回顾性队列研究旨在评估 8 年间儿童癌症患者常见病毒的流行率、危险因素、发病率和死亡率。
对黎巴嫩儿童癌症中心治疗的癌症患者的病历进行了回顾，确定了 155 名年龄在 21 岁以下、2009 年 7 月至 2017 年 11 月期间至少有一次确诊病毒感染的参与者。这一组包括 136 名患有活动性恶性肿瘤的参与者和 19 名接受过造血干细胞移植[HSCT]并处于缓解期的癌症史参与者；后者组单独进行了分析。获取了参与者特征、住院过程和并发症的相关信息。评估了病毒感染与某些因素之间的关联。在该队列中，64%为男性，81%为黎巴嫩人。在患有活动性恶性肿瘤的参与者中，90%在病毒感染前 6 个月接受了化疗，11%接受了放疗。51%的参与者在病毒检测时出现中性粒细胞减少，77%的参与者出现淋巴细胞减少。17%的参与者发生了细菌合并感染，3 名参与者发生了病毒合并感染。在 162 例病毒感染中，临床诊断为皮肤感染，主要为单纯疱疹病毒 1 型和水痘-带状疱疹病毒，占 44%。其次是实验室确诊的全身性疱疹感染：巨细胞病毒[14%]和 EBV[6%]。呼吸道病毒：流感和呼吸道合胞病毒分别占 9%和 4%，而轮状病毒占 11%，BK 病毒占 3%。急性淋巴细胞白血病是最常见的肿瘤[57%]。发热是最常见的首发症状[55%]，发热性中性粒细胞减少症是 24%病例入院的原因。巨细胞病毒感染者的平均住院时间显著延长，轮状病毒感染者的平均住院时间显著缩短。入住 ICU 的比例为 9%，并发症为 8%，死亡率为 5%。与非 HSCT 参与者相比，接受过 HSCT 的参与者发生病毒感染后住院时间明显延长，但临床过程和结果无其他显著差异。该研究受到其回顾性和后期引入以及多重 PCR 板使用不足的限制，这可能导致病毒感染的诊断不足。
病毒感染在我们的癌症患者样本中很常见，可能导致发病率和死亡率升高。新出现的病毒诊断方法可能会大大增加该人群中可检测到的病毒感染数量和范围。使用多重 PCR 技术进行前瞻性研究，并对患者进行系统检测，将有助于更好地确定病毒感染的负担。此外，抗菌药物管理工作将受益于确定感染的病毒原因，并限制儿科癌症患者不必要地使用抗生素。
