控制結核病的新議程
http://www.thelancet.com / infection / Vol 23 / November 2023
結核病仍然是世界上最致命的傳染病之一，特別是在低收入和中等收入國家。據估計，到2021 年，全球共有1060 萬人患有這種疾病，並有160 萬人死於該病。耐多藥 (multidrug-resistant) 和廣泛耐藥結核病 (extensively drug-resistant) 的興起，加上新藥和疫苗開發緩慢，導致–與愛滋病毒共病感染、部分有效的疫苗和資金停滯等，均繼續阻礙與這種疾病的鬥爭。
卡介苗是唯一獲得許可的結核病疫苗，於 1921 年首次使用，但效果參差不齊，而且免疫力會隨著年齡的增長而減弱，導致青少年和成人的保護不足。最近，疫苗管道出現了一些新的活力，有幾種後期候選疫苗，其中最先進的是 M72。 M72 2b 期臨床試驗的最終分析顯示，經過 3 年的追蹤，在來自肯亞、南非和尚比亞的 3500 名 18-50 歲 IGRA 陽性、HIV 陰性成年人中，疫苗療效為 49·7% ，其中大多數人在嬰兒時期曾接種過卡介苗疫苗。 M72 的 3 期試驗將於 2024 年初開始。至少有 16 種不同的候選疫苗處於不同的臨床開發階段。在治療和診斷領域也看到了類似的希望之光，針對所有形式的結核病引入了優秀的短期預防方案，並發展了快速分子診斷。然而，所有這些進步都受到阻力、監管、基礎設施、資金和獲取上的障礙之挑戰。
COVID-19 對於結核病領域來說是一把雙面刃。一方面，它阻礙了結核病控制的實施，但另一方面也顯示，只要有足夠的資金，疫苗和治療方法就可以迅速開發。 COVID-19大流行凸顯了結核病的優先領域，例如持續監測、改進早期檢測、加速新疫苗和藥物試驗以及確定可靠的臨床生物標誌物，並提醒結核病界多學科科學的力量和政治善意。
9月22日，聯合國大會第二次結核病高級別會議為未來5年設定了崇高目標，例如讓90%的人獲得結核病預防和照護服務；使用世界衛生組織建議的快速檢測作為第一種診斷方法；向所有結核病患者提供一系列社會福利；許可至少一種新的結核病疫苗；並在2027 年之前縮小結核病實施和研究的資金缺口。結核病疫苗加速器委員會由世衛組織秘書長於9 月20 日成立。該委員會旨在透過創新的可持續融資、市場解決方案以促進新疫苗的開發、授權和使用，例如確保建立一個有利的生態系統，以便在疫苗可用時快速生產和公平分配疫苗，並透過七國集團、二十國集團和非洲聯盟等政治論壇進行宣傳。
2018年曾舉行類似會議；然而，幾乎所有當時設定的目標都沒有達成。 2018 年至 2022 年間，有 3,400 萬人接受了治療，而不是 4,000 萬人的目標，而且對該疾病的抗藥性形式的治療遠低於計劃的 150 萬人的目標。 2018 年會議僅實現了一項目標：為 600 萬名愛滋病毒感染者提供結核病的預防治療。
那麼這次可以採取哪些不同的做法呢？問責制、透明度和可近性對於確保結核病防治工作順利進行至關重要。民間社會、病患、利害關係人和倡議團體必須繼續敦促領導人和政府兌現這些承諾，特別是在衝突、氣候變遷和抗菌素抗藥性成為其未來議程的重要議題的情況下。社區、區域和國家各級的結核病服務必須完全透明，以確保資源得到充分利用。如果要實現這些目標，大型製藥公司可以發揮至關重要的作用，因為降低成本以及其他讓步將確保向最需要的人提供藥物、疫苗和診斷工具。如果我們要實現一個無結核病的世界，就必須盡一切可能從過去的錯誤中學習。
■刺胳針傳染病
A new agenda to control tuberculosis
http://www.thelancet.com/infection Vol 23 November 2023
Tuberculosis remains one of the deadliest infectious diseases in the world, particularly in low-income and middle-income countries. An estimated global total of 10·6 million people fell ill with the disease and 1·6 million succumbed to it in 2021. The rise of multidrug-resistant and extensively drug-resistant tuberculosis, together with slow development of new drugs and vaccines, co-infection with HIV, a partially effective vaccine, and stagnant funding, continue to impede the fight against this disease.
The only licensed vaccine for tuberculosis, BCG, was first used in 1921 but has variable effectiveness, and the immunity conferred wanes with age, leading to inadequate protection in adolescents and adults. Recently, there has been some reinvigoration of the vaccine pipeline with several late-stage vaccine candidates, of which the most advanced is M72. Final analysis of a phase 2b clinical trial of M72 showed that after 3 years of follow-up, vaccine efficacy was 49·7% in 3500 IGRA-positive, HIV-negative adults aged 18–50 years from Kenya, South Africa, and Zambia, the majority of whom had received BCG vaccination as infants. Phase 3 trials for M72 will commence in early 2024. There are at least 16 different vaccine candidates that are at different stages of clinical development. Similar glimmers of hope have been seen in therapeutics and diagnostics, with excellent short-course preventive regimens being introduced for all forms of tuberculosis and the development of rapid molecular diagnostics. However, all of these advances are challenged by resistance, and regulatory, infrastructure, funding, and access barriers.
COVID-19 served as a double-edged sword for the tuberculosis field. On one hand, it hampered the implementation of tuberculosis control, whereas on the other it showed that with adequate funding, vaccines and therapeutics can be developed rapidly. The COVID-19 pandemic highlighted priority areas in tuberculosis, such as continued surveillance, improvement of early detection, acceleration of new vaccine and drug trials, and identification of robust clinical biomarkers, and reminded the tuberculosis community of the power of multidisciplinary science and importance of political goodwill.
On Sept 22, the UN General Assembly second highlevel meeting on tuberculosis set lofty targets for the coming 5 years, such as reaching 90% of people with tuberculosis prevention and care services; using a WHO-recommended rapid test as the first method of diagnosis; providing social benefit packages to all people with tuberculosis; licensing at least one new tuberculosis vaccine; and closing funding gaps for tuberculosis implementation and research by 2027. The TB Vaccine Accelerator Council was established by the WHO Director General on Sept 20. The Council aims to facilitate the development, licensing, and use of new vaccines by innovative sustainable financing, market solutions, such as ensuring a favourable ecosystem is in place for the rapid manufacture and equitable distribution of vaccines when they become available, and advocacy through political forums, such as G7, G20, and the African Union.
A similar meeting was held in 2018; however, nearly all of the targets set then were not met. Between 2018 and 2022, 34 million people were treated instead of the target 40 million and treatment for the drugresistant forms of the disease fell way short of the planned 1·5 million target. Only one target from the 2018 meeting was achieved: providing tuberculosis preventive treatment for 6 million people with HIV.
So what can be done differently this time? Accountability, transparency, and accessibility are essential for ensuring that the fight against tuberculosis remains on track. Civil societies, patients, stakeholders, and advocacy groups will have to continue to press leaders and governments to deliver on these pledges, especially with conflicts, climate change, and antimicrobial resistance featuring highly on their future agendas. Tuberculosis services at the community, regional, and country levels will have to be fully transparent to ensure that resources are adequately used. Big pharmaceutical companies have a vital part to play if the targets are to be achieved as lowering costs, among other concessions, will ensure that drug, vaccines, and diagnostic tools are provided to those who need them the most. It is imperative to learn from past mistakes and do everything possible if we are to realise a tuberculosis-free world.
■ The Lancet Infectious Diseases