Can community-wide active case finding for tuberculosis and universal testing and treatment for HIV control the African tuberculosis epidemic?

社区范围内积极发现结核病病例以及普遍进行艾滋病毒检测和治疗能否控制非洲结核病流行？

• 批准号: MR/N020618/1
• 负责人: Lilanganee Telisinghe
• 金额: $ 28.21万
• 依托单位: London School of Hygiene & Tropical Medicine
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FN020618%2F1
• 关键词: community; wide; active; case; finding

Tuberculosis (TB) is an infectious disease, which is spread when the bacteria causing TB is released into the air by TB cases when they cough. Globally one third of the worlds population is infected with TB and 9 million new cases of disease, with 1.5 million deaths occurred in 2013.Only 1 in 10 individuals infected with TB goes on to develop disease but the risk is much higher in individuals who have a weakened immune system such as those infected with HIV. Because of the overlap between HIV and TB, sub-Saharan Africa has the highest rate of TB disease. But, with increasing globalisation and travel, this has also translated into increasing rates in other parts of the world such as the UK. Therefore preventing TB in sub-Saharan Africa helps countries devastated by this disease, and also decreases the risk of TB worldwide. To control TB a consistent decrease in the number of new cases and improved TB case outcomes (e.g. less deaths) are needed in the whole population.There is no effective vaccine against TB. However, if TB cases are identified earlier and started on effective treatment, before they normally present to healthcare, TB spread to others could be reduced. Active case finding for TB (ACF) involves systematically screening the whole population for TB disease and starting cases on treatment. This benefits the individual and should decrease the number of new cases by decreasing the spread of TB. Antiretroviral therapy (ART) improves a HIV-infected person's immune function and decreases their susceptibility to TB. Therefore if rolled-out widely to those who need it, ART should decrease the number of new TB cases. However to date, we don't have any strong evidence to show that ACF and ART can control TB in populations. HPTN071 is a large trial being conducted in 21 Zambian and South African communities, two countries devastated by TB and HIV, by the London School of Hygiene and Tropical Medicine in the UK, Zambart in Zambia and the Desmond Tutu TB Centre in South Africa. In this trial 14 intervention communities receive a HIV prevention package administered to the entire population and 7 control communities receive usual care. In the intervention communities, from 2014-2018, all adults and children are tested annually for HIV ("universal testing"). ART is started immediately in 7 communities ("universal treatment") and according to national guidelines in 7 communities. The trial will determine if new HIV infections can be decreased by this strategy of universal test and treat. To measure this, the study will follow 52500 adults aged 18-44 years for 3 years from all 21 communities, and compare the number of new HIV infections in the intervention and control communities. Given the TB problem in these communities, all individuals in the intervention communities are also asked about TB symptoms (e.g. cough, night sweats etc). If symptoms are reported, sputum is collected and tested for TB, with referral to local TB clinics for treatment. HPTN071 therefore combines community-wide ACF for TB and ART for HIV. It provides a unique opportunity to study if these interventions together can decrease the number of new TB cases and improve the clinical outcomes of TB cases. This proposed project will use information from the HPTN071 trial as well as the national TB records for these communities to see if the number of new TB cases have reduced in the intervention communities compared to the control communities, and also what the clinical outcomes for these patients are. A mathematical model will be used to better understand and tease out the effects of the two interventions. This project has the potential to change our approach to TB prevention in sub-Saharan Africa. It is an important study, which will make a major contribution in the fight against one of the most important diseases in the world.

结核病（TB）是一种传染病，当结核病患者咳嗽时将引起结核病的细菌释放到空气中时，结核病就会传播。全球三分之一的人口感染了结核病，2013年出现了900万新病例，其中150万人死亡。感染结核病的人中只有十分之一会继续发展成疾病，但在免疫系统较弱的个体中，如感染艾滋病毒的人，风险要高得多。由于艾滋病毒和结核病的重叠，撒哈拉以南非洲的结核病发病率最高。但是，随着全球化和旅游的增加，这也导致英国等世界其他地区的离婚率上升。因此，在撒哈拉以南非洲预防结核病有助于遭受这一疾病摧残的国家，并降低全球结核病的风险。为控制结核病，需要在整个人口中持续减少新发病例数并改善结核病病例结局（例如减少死亡）。目前还没有有效的结核病疫苗。然而，如果结核病病例在他们通常到卫生部门就诊之前及早发现并开始有效治疗，结核病向他人的传播就可以减少。主动发现结核病病例（ACF）涉及系统地筛查整个人群的结核病并开始对病例进行治疗。这对个人有益，并应通过减少结核病的传播来减少新病例的数量。抗逆转录病毒疗法（ART）可以改善艾滋病毒感染者的免疫功能，降低他们对结核病的易感性。因此，如果在需要的人群中广泛推广，抗逆转录病毒治疗应该会减少新发结核病病例的数量。然而，迄今为止，我们没有任何强有力的证据表明ACF和ART能够控制人群中的结核病。HPTN071是一项大型试验，由英国伦敦卫生和热带医学学院、赞比亚的Zambart和南非的Desmond Tutu结核病中心在赞比亚和南非的21个社区进行，这两个国家深受结核病和艾滋病毒的摧残。在这项试验中，14个干预社区接受了面向全体人口的艾滋病毒预防一揽子计划，7个对照社区接受了常规护理。在干预社区，从2014年至2018年，所有成人和儿童每年接受艾滋病毒检测（“普遍检测”）。在7个社区立即开始抗逆转录病毒治疗（“普遍治疗”），并根据国家指南在7个社区开展治疗。这项试验将确定这种普遍检测和治疗的策略是否能减少新的艾滋病毒感染。为了衡量这一点，该研究将对来自所有21个社区的52500名18-44岁的成年人进行为期3年的跟踪调查，并比较干预社区和控制社区的新艾滋病毒感染人数。鉴于这些社区的结核病问题，还向干预社区的所有个人询问结核病症状（如咳嗽、盗汗等）。如果报告出现症状，则收集痰液并进行结核病检测，并转诊到当地结核病诊所进行治疗。因此，HPTN071结合了社区范围的结核病ACF和艾滋病毒抗逆转录病毒治疗。它提供了一个独特的机会来研究这些干预措施是否能够共同减少结核病新发病例的数量并改善结核病病例的临床结果。这个拟议的项目将使用来自HPTN071试验的信息以及这些社区的国家结核病记录，以查看干预社区与对照社区相比，新发结核病病例的数量是否减少，以及这些患者的临床结果是什么。一个数学模型将被用来更好地理解和梳理出这两种干预措施的效果。这个项目有可能改变我们在撒哈拉以南非洲预防结核病的方法。这是一项重要的研究，将为抗击世界上最重要的疾病之一做出重大贡献。

项目成果

Diagnosing Pulmonary Tuberculosis in the Elderly

诊断老年人肺结核

• 发表时间: 2020
• 期刊: Curr Geri Rep
• 作者: Symes M.J.

Does tuberculosis screening improve individual outcomes? A systematic review.

• DOI: 10.1016/j.eclinm.2021.101127
• 发表时间: 2021-10
• 期刊: EClinicalMedicine
• 影响因子: 15.1
• 作者: Telisinghe L;Ruperez M;Amofa-Sekyi M;Mwenge L;Mainga T;Kumar R;Hassan M;Chaisson LH;Naufal F;Shapiro AE;Golub JE;Miller C;Corbett EL;Burke RM;MacPherson P;Hayes RJ;Bond V;Daneshvar C;Klinkenberg E;Ayles HM
• 通讯作者: Ayles HM

Community-based active case-finding interventions for tuberculosis: a systematic review.

• DOI: 10.1016/s2468-2667(21)00033-5
• 发表时间: 2021-05
• 期刊: The Lancet. Public health
• 作者: Burke RM;Nliwasa M;Feasey HRA;Chaisson LH;Golub JE;Naufal F;Shapiro AE;Ruperez M;Telisinghe L;Ayles H;Corbett EL;MacPherson P
• 通讯作者: MacPherson P

Interpretation of serial interferon-gamma test results to measure new tuberculosis infection among household contacts in Zambia and South Africa.

• DOI: 10.1186/s12879-020-05483-9
• 发表时间: 2020-10-15
• 期刊: BMC infectious diseases
• 影响因子: 3.7
• 作者: Sloot R;Shanaube K;Claassens M;Telisinghe L;Schaap A;Godfrey-Faussett P;Ayles H;Floyd S
• 通讯作者: Floyd S

THE SENSITIVITY OF QUANTIFERON®-TB GOLD PLUS IS NOT AFFECTED BY HIV-STATUS

QUANTIFERON®-TB GOLD PLUS 的敏感性不受 HIV 状态的影响

• 发表时间: 2017
• 作者: Telisinghe L