Sex Differences in Tuberculosis Burden and Notifications in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis

BackgroundTuberculosis (TB) case notification rates are usually higher in men than in women, but notification data are insufficient to measure sex differences in disease burden. This review set out to systematically investigate whether sex ratios in case notifications reflect differences in disease prevalence and to identify gaps in access to and/or utilisation of diagnostic services.Methods and FindingsIn accordance with the published protocol (CRD42015022163), TB prevalence surveys in nationally representative and sub-national adult populations (age ≥ 15 y) in low- and middle-income countries published between 1 January 1993 and 15 March 2016 were identified through searches of PubMed, Embase, Global Health, and the Cochrane Database of Systematic Reviews; review of abstracts; and correspondence with the World Health Organization. Random-effects meta-analyses examined male-to-female (M:F) ratios in TB prevalence and prevalence-to-notification (P:N) ratios for smear-positive TB. Meta-regression was done to identify factors associated with higher M:F ratios in prevalence and higher P:N ratios. Eighty-three publications describing 88 surveys with over 3.1 million participants in 28 countries were identified (36 surveys in Africa, three in the Americas, four in the Eastern Mediterranean, 28 in South-East Asia and 17 in the Western Pacific). Fifty-six surveys reported in 53 publications were included in quantitative analyses. Overall random-effects weighted M:F prevalence ratios were 2.21 (95% CI 1.92–2.54; 56 surveys) for bacteriologically positive TB and 2.51 (95% CI 2.07–3.04; 40 surveys) for smear-positive TB. M:F prevalence ratios were highest in South-East Asia and in surveys that did not require self-report of signs/symptoms in initial screening procedures. The summary random-effects weighted M:F ratio for P:N ratios was 1.55 (95% CI 1.25–1.91; 34 surveys). We intended to stratify the analyses by age, HIV status, and rural or urban setting; however, few studies reported such data.ConclusionsTB prevalence is significantly higher among men than women in low- and middle-income countries, with strong evidence that men are disadvantaged in seeking and/or accessing TB care in many settings. Global strategies and national TB programmes should recognise men as an underserved high-risk group and improve men’s access to diagnostic and screening services to reduce the overall burden of TB more effectively and ensure gender equity in TB care.

背景 结核病（Tuberculosis, TB）的病例报告率通常男性高于女性，但现有报告数据不足以衡量疾病负担的性别差异。本综述旨在系统探究病例报告中的性别比例是否能够反映疾病患病率的性别差异，并明确诊断服务获取和/或利用方面的缺口。
方法与结果 本研究遵循已发表的研究方案（CRD42015022163），通过检索PubMed、Embase、Global Health及Cochrane系统评价数据库，审阅相关摘要，并与世界卫生组织（World Health Organization）沟通，筛选了1993年1月1日至2016年3月15日期间发表的、针对低收入和中等收入国家具有全国及亚全国代表性的成人人群（年龄≥15岁）的结核病患病率调查研究。采用随机效应meta分析，评估结核病患病率的男女性别比（M:F）以及痰涂片阳性结核病的患病率-报告率比（P:N）。通过meta回归分析，明确与较高患病率性别比及较高患病率-报告率比相关的影响因素。最终筛选出28个国家的88项调查、共纳入超310万受试者的相关文献83篇（其中非洲36项、美洲3项、东地中海地区4项、东南亚28项、西太平洋地区17项）。其中53篇文献报道的56项调查被纳入定量分析。针对细菌学阳性结核病，所有纳入研究的随机效应加权男女性别患病率比为2.21（95%置信区间：1.92~2.54；共56项调查）；针对痰涂片阳性结核病，该比值为2.51（95%置信区间：2.07~3.04；共40项调查）。东南亚地区的男女性别患病率比最高，且在初始筛查环节无需自行报告体征与症状的调查中该比值同样偏高。患病率-报告率比的综合随机效应加权男女性别比为1.55（95%置信区间：1.25~1.91；共34项调查）。本研究计划按年龄、人类免疫缺陷病毒（Human Immunodeficiency Virus, HIV）感染状态以及城乡区域对分析进行分层，但仅有极少数研究报告了此类数据。
结论 低收入和中等收入国家中，男性的结核病患病率显著高于女性，且有充分证据表明，在诸多场景下男性在寻求和/或获取结核病诊疗服务方面处于不利地位。全球结核病防控策略及各国结核病防治项目应将男性视为服务不足的高风险人群，提升男性对诊断与筛查服务的可及性，从而更有效地降低结核病整体疾病负担，并保障结核病诊疗服务中的性别公平。