BACKGROUND Human T-cell lymphotropic virus type 1 (HTLV-1) is a human retrovirus that causes a lifelong infection. Several diseases, including an aggressive form of leukaemia, have been designated as associated with HTLV-1, whereby having HTLV-1 is a necessary condition for diagnosis. Beyond these diseases, there is uncertainty about other health effects of HTLV-1. We aimed to synthesise evidence from epidemiological studies on associations between health outcomes and HTLV-1. METHODS For this systematic review and meta-analysis, we searched Embase, MEDLINE, MEDLINE In-Process, and Global Health for publications from their inception to July, 2018. We included cohort, case-control, and controlled cross-sectional studies that compared mortality or morbidity between people with and without HTLV-1. We excluded studies of psychiatric conditions, of symptoms or clinical findings only, of people who had undergone blood transfusion or organ transplant, and of population groups defined by a behavioural characteristic putting them at increased risk of co-infection with another virus. We extracted the risk estimates (relative risks [RRs] or odds ratios [ORs]) that reflected the greatest degree of control for potential confounders. We did a random-effects meta-analysis for groups of effect estimates where case ascertainment methods, age groups, and confounders were similar, presenting pooled estimates with 95% CIs and prediction intervals. FINDINGS Of the 3318 identified studies, 39 met the inclusion criteria, examining 42 clinical conditions between them. The adjusted risk of death due to any cause was higher in people with HTLV-1 when compared with HTLV-1-negative counterparts (RR 1·57, 95% CI 1·37-1·80). From meta-analysis, HTLV-1 was associated with increased odds of seborrheic dermatitis (OR 3·95, 95% CI 1·99-7·81), Sjogren's syndrome (3·25, 1·85-5·70), and, inversely, with lower relative risk of gastric cancer (RR 0·45, 0·28-0·71). There were a further 14 diseases with significant associations or substantially elevated risk with HTLV-1 from single studies (eczema [children]; bronchiectasis, bronchitis and bronchiolitis [analysed together]; asthma [males]; fibromyalgia; rheumatoid arthritis; arthritis; tuberculosis; kidney and bladder infections; dermatophytosis; community acquired pneumonia; strongyloides hyperinfection syndrome; liver cancer; lymphoma other than adult T-cell leukaemia-lymphoma; and cervical cancer). INTERPRETATION There is a broad range of diseases studied in association with HTLV-1. However, the elevated risk for death among people with HTLV-1 is not explained by available studies of morbidity. Many of the diseases shown to be associated with HTLV-1 are not fatal, and those that are (eg, leukaemia) occur too rarely to account for the observed mortality effect. There are substantial research gaps in relation to HTLV-1 and cardiovascular, cerebrovascular, and metabolic disease. The burden of disease associated with the virus might be broader than generally recognised. FUNDING Commonwealth Department of Health, Australia.

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HTLV-1感染与不良健康后果之间的关联：流行病学研究的系统回顾和荟萃分析。

背景技术人类T细胞淋巴病毒1型（HTLV-1）是引起终身感染的人类逆转录病毒。几种疾病，包括侵袭性白血病，已被指定与HTLV-1相关，因此具有HTLV-1是诊断的必要条件。除这些疾病外，HTLV-1的其他健康影响尚不确定。我们旨在从流行病学研究中得出关于健康结局与HTLV-1之间关联的证据。方法为了进行系统的回顾和荟萃分析，我们搜索了Embase，MEDLINE，MEDLINE In-Process和Global Health从成立到2018年7月的出版物。我们纳入了队列研究，病例对照研究和对照横断面研究，有和没有HTLV-1的人之间的死亡率或发病率。我们排除了对精神疾病的研究，仅症状或临床发现，接受过输血或器官移植的人以及行为特征所界定的人群，使他们面临与另一种病毒共同感染的风险增加。我们提取了风险估计值（相对风险[RRs]或优势比[ORs]），该估计值反映了对潜在混杂因素的最大控制程度。在病例确定方法，年龄组和混杂因素相似的情况下，我们对效果估算值组进行了随机效果荟萃分析，并提供了95％CI和预测间隔的汇总估算值。结果在确定的3318项研究中，有39项符合纳入标准，检查了其中的42种临床状况。与HTLV-1阴性患者相比，HTLV-1患者因任何原因导致的调整死亡风险更高（RR 1·57，95％CI 1·37-1·80）。根据荟萃分析，HTLV-1与脂溢性皮炎（OR 3·95，95％CI 1·99-7·81），干燥综合征（3·25、1·85-5·70）的发生率增加相关，相反，胃癌的相对危险性较低（RR 0·45、0·28-0·71）。单项研究还发现另外14种与HTLV-1有显着相关性或与HTLV-1风险显着升高的疾病（湿疹[儿童]；支气管扩张，支气管炎和细支气管炎[一起分析]；哮喘[男性]；纤维肌痛；类风湿性关节炎；关节炎；结核病；肾和膀胱感染；皮肤癣菌病；社区获得性肺炎；强一倍体过度感染综合征；肝癌；除成人T细胞白血病-淋巴瘤以外的淋巴瘤；以及子宫颈癌）。解释与HTLV-1相关的疾病研究范围很广。然而，现有的发病率研究并未解释HTLV-1患者死亡风险的升高。已显示许多与HTLV-1相关的疾病不是致命的，而那些（例如白血病）的疾病很少发生，无法解释观察到的死亡率影响。与HTLV-1和心血管，脑血管和代谢性疾病相关的研究差距很大。与该病毒有关的疾病负担可能比一般公认的更为广泛。资金澳大利亚联邦卫生部。与HTLV-1和心血管，脑血管和代谢性疾病相关的研究差距很大。与该病毒有关的疾病负担可能比一般公认的更为广泛。资金澳大利亚联邦卫生部。与HTLV-1和心血管，脑血管和代谢性疾病相关的研究差距很大。与该病毒有关的疾病负担可能比一般公认的更为广泛。资金澳大利亚联邦卫生部。