Male partner-assisted contact tracing for HIV and tuberculosis in Malawi: an adaptive multi-arm multi-stage randomised trial (mPATCH-TB)

在非洲，结核病和艾滋病毒(导致艾滋病的病毒)是主要的健康问题，每年都会影响数百万成年人。艾滋病毒会慢慢削弱免疫系统，使个人非常容易患上严重的结核病。尽管结核病和艾滋病毒都有有效的治疗方法，但许多需要治疗的人没有得到治疗，因为他们不知道自己感染了这种疾病，或者在获得诊所的检测和治疗方面遇到了困难。虽然他们没有接受治疗，但他们可以将感染传播给其家庭或社区中的其他人，并可能死于感染的后果。非洲男子在获得结核病和艾滋病毒检测和治疗方面尤其困难。我们之前在非洲的研究表明，在该社区中，未经治疗的结核病男性人数是女性的两倍。在获得艾滋病毒和结核病诊断方面，男性的延误时间比女性长得多(平均长达一年)。这是由一系列原因造成的，包括男性求医行为、与就业竞争的需求，以及认为保健中心不欢迎男性。此外，我们还表明，在非洲，高达2/3的新肺结核感染是由男性造成的。这意味着，改善男性结核病和艾滋病毒的及时诊断可以通过降低感染风险，对社区中的男子、妇女和儿童产生重要的健康益处。基于我们在撒哈拉以南非洲开展艾滋病毒和结核病研究的丰富经验，在这项研究中，我们的目标是严格确定能够提高男性结核病和艾滋病毒检测率的战略。妇女比男子更有可能去有结核病症状的保健中心就诊，因此是一个关键群体，通过这个群体可以接触到患有未确诊感染的男性伴侣。我们之前已经在最近的一项研究中成功地展示了这种方法，在这项研究中，前往诊所的孕妇被要求向她们的伴侣分发艾滋病毒自检试剂盒。在这项研究的第一阶段，我们将对男性、女性和医疗服务提供者进行详细的访谈，以确定和改进女性向其男性伴侣提供的干预措施可能是可行和可接受的。我们将以我们通过先前研究获得的测试经验为基础进行干预。干预措施类型包括：提供“对男性友好的快速通道诊所”；书面信息和提醒电话/短信；伴侣在家中收集痰；伴侣在家中进行艾滋病毒检测；以及不同程度的经济奖励。然后，我们将进行一项创新试验，以确定这些干预措施中哪些最有潜力在提高男性伴侣的结核病和艾滋病毒检测率方面有效、负担得起和安全。为此，我们将招募总共445名患有肺结核症状的妇女到布兰太尔的一家保健中心就诊。女性参与者将接受结核病和艾滋病毒检测，然后根据她们去诊所的日期随机分配到五个干预组中的一个。30天后，我们将评估每组中有多少男性伴侣完成了结核病和艾滋病毒的筛查。(为了确保公平的护理，所有家庭成员都将能够在诊所接受筛查，但主要重点将是男性伴侣，因为他们患病的风险很高)。我们将比较不同群体之间的检测率，没有达到高于护理标准的竞争性检测率的干预措施将被丢弃，只留下具有高公共卫生有效性潜力的干预措施。到研究完成时，我们将确定1-2项干预措施，可在一项更大的权威性试验中进行评估，该试验将调查公共卫生在减少未诊断结核病和艾滋病毒数量方面的有效性。

In Africa, tuberculosis and HIV (the virus that causes AIDS) are major health problems, and both affect millions of adults every year. HIV slowly weakens the immune system, and makes individuals very susceptible to developing severe tuberculosis. Although effective treatments are available for both tuberculosis and HIV, many individuals who need treatment don't receive it because they are unaware that they have the infection, or experience difficulties in accessing testing and treatment at clinics. Whilst they are not receiving treatment, they can transmit infection to others in their household or communities, and may die of the consequences of infection. Men in Africa experience particular difficulties in accessing testing and treatment for tuberculosis and HIV. Our previous research in Africa has shown that two-times as many men than women have untreated tuberculosis in the community. Men experience substantially longer delays than women in accessing diagnosis for HIV and TB (on average up to one year longer). This is for a number of reasons including masculine care-seeking behaviour, competing demands with employment, and perceptions that health centres are unwelcoming for men. We have additionally shown that men are responsible for up to 2/3rds of new tuberculosis infections in Africa. This means that improving timely diagnosis of TB and HIV among men could have important health benefits for men, women and children in the community by reducing infection risk. Building upon our substantial experience in undertaking HIV and tuberculosis research in sub-Saharan Africa, in this research we aim to rigorously identify strategies that could improve mens' rates of testing for tuberculosis and HIV. Women are substantially more likely than men to attend health centres with symptoms of tuberculosis, and are therefore a key group through which male partners with undiagnosed infection can be accessed. We have previously successfully demonstrated this approach in a recent study in which pregnant women attending clinics were asked to distribute HIV self-test kits to their partners. In the first stage of this research, we will conduct detailed interviews with men, women and health providers to identify and refine interventions that are likely to be feasible and acceptable when delivered by women to their male partners. We will base interventions upon those that we have experience of testing through previous studies. Types of interventions include: availability of a "male-friendly fast-track clinic"; written information and reminder phone-calls/text messages; home collection of sputum by partners; home HIV test delivery by partners; and varying levels of financial incentives. We will then conduct an innovative trial to identify which of these interventions has greatest potential to be effective, affordable and safe at increasing male partners' rates of TB and HIV testing. We will do this by recruiting a total of 445 women attending a health centre in Blantyre with symptoms of tuberculosis. Women participants will be tested for TB and HIV, and then randomly allocated to one of the five intervention groups according to the day they attend the clinic. After 30 days, we will assess how many male partners in each group have completed screening for tuberculosis and HIV. (To ensure equity of care, all household members will be able to access screening at the clinic, however the primary focus will be on male partners because of their high risk of disease). We will compare rates of testing between groups, and interventions that do not achieve rates of competing testing higher than the standard of care will be discarded, leaving only interventions with high potential for public health effectiveness. By the completion of the study, we will have identified 1-2 interventions that can be evaluated in a larger definitive trial that will investigate public health effectiveness in reducing the amount of undiagnosed TB and HIV.