On this interview, we speak to Charles Wells, Head of Therapeutics Development on the Bill & Melinda Gates Medical Research Institute, about their current research into tuberculosis (TB) in addition to the recent updated guidelines for TB care.
Please could you introduce yourself and tell us what inspired your profession in tuberculosis (TB)?
I actually have the respect of serving because the Head of Therapeutics Development on the Bill & Melinda Gates Medical Research Institute. I joined the institute a bit over three years ago, following leadership roles within the pharmaceutical industry and on the CDC.
My profession has focused on infectious diseases, and I actually have spent a long time working on TB. My work on TB began after I left medical school, having “learned” that TB was a disease of the past. Nonetheless, after I moved to Atlanta in 1992 to begin my residency training in town’s extensive public hospital system, I saw that was removed from the case. In that urban setting, I cared for a lot of patients affected by TB, which was steadily increasing due largely to the growing HIV epidemic in town and the US more broadly.
I then trained in applied epidemiology within the Epidemic Intelligence Service (EIS) on the CDC within the mid-Nineteen Nineties, where I learned that TB remained one among the key infectious diseases killers worldwide, especially in low- and middle-income countries (LMICs). In my training, I focused on combatting the worldwide TB epidemic, and later as everlasting staff, I worked on global TB control projects as a part of a broader US Government response to the worldwide HIV and TB epidemics.
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TB is the second leading infectious killer after COVID-19, killing 1.5 million people in 2020 alone. Why is TB so prevalent worldwide, and what current treatment options can be found?
As much as 1 / 4 of the world’s population is regarded as latently infected with TB. In 2020 alone, an estimated 10 million people developed energetic TB— including 1.1 million children— and 1.5 million people died from TB, including an estimated 214,000 people living with HIV. The disease burden stays best in LMICs, which account for 98% of reported TB cases.
Prior to the appearance of the COVID-19 pandemic, TB was the leading explanation for death from a single infectious agent. The COVID-19 pandemic and the resulting strain on health service delivery has accentuated the TB burden, with access to care and case notifications decreasing sharply in 2020 and the variety of TB deaths increasing.
Currently, bacille Calmette-Guérin, referred to as BCG, is the one licensed TB vaccine. Nonetheless, it has limited impact on stopping Mtb infection and TB disease in adults. Treatment of TB disease is curative but lengthy, and compliance is usually incomplete. The worldwide prevalence of drug-resistant TB is substantial. Improved prevention tools and effective vaccines to stop the event of TB disease are urgently needed to speed up progress toward ending the TB epidemic. Nonetheless, for the reason that introduction of the BCG vaccine in 1921, only a few novel vaccine candidates have advanced into clinical efficacy trials.
Many individuals imagine TB is prior to now and don’t see this as a current global threat. Why is that this, and the way can we help address some misconceptions surrounding this disease?
TB is a disease of the poor, and unfortunately, TB research has experienced research funding shortfalls for a long time. As well as, the biology of TB is complex, and our understanding of the organism, TB pathogenesis, and immunology stays limited in support of vaccine design and development. These challenges should not easily overcome. Basic research must catch up.
The World Health Organization (WHO) has recently released recent guidelines in addition to a recent operational handbook on tuberculosis care and support. Please tell us more about these recent guidelines and what they mean for people living with TB?
The brand new guidelines on TB care and support are intended to enhance the standard of life and lead to higher outcomes for individuals with TB. They include implementation guidance on health education, counseling, and palliative care in addition to on social support, treatment administration options, and digital adherence technologies. The rules include recent 4-month (all oral) treatment regimens – the primary advance in shortening and improving treatment for drug-sensitive TB in a long time.
Recent clinical evidence informed the brand new guidelines, which permit for the programmatic implementation of treating just about all types of drug-resistant TB with either BPaLM (a mix of bedaquiline, pretomanid, linezolid, and moxifloxacin) or BPaL (bedaquiline, pretomanid, and linezolid).
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Why is it vital that individuals affected by TB receive adequate care and support?
As I discussed earlier, TB is a disease of the poor, and lots of LMICs shouldn’t have adequate infrastructure to support patients fully. Treatment of TB differs from the treatment of many other common diseases, which follow a pathway of diagnosis, a prescription for a course of treatment, and a follow-up visit. Within the case of TB, treatment takes a minimum of 6 months and requires ongoing patient engagement, including directly observed therapy for 5-6 days per week in a clinical setting, to support patient adherence and mitigate the chance of spreading the infection.
Treatment enablers reminiscent of transport to clinical facilities, taking the drugs with food, and other support is essential for TB patients and infrequently difficult to deliver in LMICs. Lastly, patients can sometimes feel higher after 3-5 weeks of treatment, resulting in poor compliance over the course of the required 6-month treatment period.
Despite recent guidelines being released, information normally shared is complex and difficult for most of the people to grasp. Why is it essential that these guidelines are also provided in easy language? How could governments, policymakers, and organizations make scientific information more digestible to the overall population?
The brand new guidelines are written to assist medical professionals and people working in public health. With these latest guidelines, the WHO did a superb job distilling the salient messages from the update and focused on what’s most meaningful and necessary in TB programs — delivering the treatment and care services to patients and the consequence for the patients.
This 2022 update is concise and easy regarding key points, improving further on the 2017 update, which some healthcare professionals perceived as heavy on technical details.
You’re currently the top of therapeutics development at Gates MRI. What are a few of the current projects underway at Gates MRI concerning TB?
The institute is supporting and investing in multiple vaccines and therapeutics programs. These include the event of novel vaccine interventions to stop TB and the establishment of worldwide clinical trial capabilities to support future novel approaches to TB control.
The institute’s TB vaccine program has a workstream focused on developing a candidate vaccine, M72/AS01E-4 (under an exclusive license with GSK), for stopping tuberculosis disease in adolescents and adults. In a phase 2b proof-of-concept clinical study (conducted by GSK with support from Aeras), the investigational vaccine demonstrated potential in stopping TB disease amongst Mtb infected individuals. The primary clinical trial Gates MRI has initiated with M72/AS01E-4 is a trial in South Africa to guage the security and immunogenicity of the vaccine candidate in people living with HIV, known as the MESA-TB trial (supported by each The Bill & Melinda Gates Foundation and The Wellcome Trust).
In anticipation of a phase 3 trial efficacy trial of the investigational vaccine, the institute is conducting a TB epidemiology study to document the prevalence of latent Mtb infection and the incidence of TB disease in populations with a high TB disease burden. The study also intends to construct the required clinical trial capability to support the investigational vaccine’s phase 3 trial evaluation.
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In addition to your current research into potential TB vaccines, Gates MRI is currently involved in revaccination efforts in low-and-middle-income countries. Please are you able to tell us more about these efforts and the importance of revaccination, especially in low-income countries?
One other of the institute’s current TB research programs, the BCG revaccination clinical trial, is underway in South Africa.
BCG vaccination is usually given to babies in the primary week of life, protecting children from TB for not less than ten years, but protection against TB in adolescents and adults is proscribed. The study has enrolled children and adolescents to evaluate whether a second dose of BCG vaccine at 10 to 18 years of age helps protect against Mtb. The study follows participants over 4 years, testing for Mtb infection every six months. If results are favorable, the goal is to implement policy change in countries with a high burden of TB. The study will even examine the immune response to Mtb infection and will help us understand mechanisms of protection and develop recent TB vaccines.
What do you think the longer term of TB looks like? Are you hopeful we are going to someday see TB eradicated with continued research, support, and funding?
TB may be preventable and curable with the appropriate investments and resources, and although there may be progress in the event of recent TB diagnostics, drugs, and vaccines, that is constrained by the general level of R&D investment. With continued investment, each monetary and scientific, I’m confident that a world without TB is attainable.
What’s next for you and your research at Gates MRI? Are you involved in any exciting upcoming projects?
The institute is a member of the Project to Speed up Latest Treatments for Tuberculosis (PAN-TB) collaboration (the collaboration comprises Evotec, GlaxoSmithKline, Janssen, Otsuka, TB Alliance, the Bill & Melinda Gates Medical Research Institute, and the Bill & Melinda Gates Foundation). This group of philanthropic, non-profit, and personal sector organizations is working together to expedite the event of a pan-TB regimen: a novel TB regimen able to treating nearly all TB patients, even those with drug-resistant forms, to enable a less complicated “test and treat” paradigm.
Inside the collaboration, Gates MRI is accountable for executing the Phase 2b/2c clinical trials intended to guage promising recent regimens constructed with TB drugs from the PAN-TB partners to discover the most effective regimen for subsequent Phase 3 evaluation in close coordination and joint governance with the partners.
A pan-TB regimen that is predicted to be significantly shorter than current standard TB treatments (2-3 months) would allow more TB patients to be cured, leading to less transmission of infection and a reduced burden on health systems that treat TB; this might permit more resources to be focused on finding the estimated 3 million cases of energetic TB which are often underreported and go undiagnosed and untreated every 12 months. All of those advancements would collectively end in greater global health impacts, with an accelerated decline in TB disease burden that ultimately paves the trail to eliminating TB.
Where can readers find more information?
Please visit the institute’s website at gatesmri.org and follow us on Twitter @GatesMRI and on LinkedIn at https://www.linkedin.com/company/bill-melinda-gates-medical-research-institute.
About Charles Wells
I actually have dedicated my profession to addressing global health issues and dealing to bring forward critically needed recent products and tools to handle unmet medical needs for TB, HIV, malaria, and other neglected infectious diseases.
My training and experience working in global health to combat the HIV and TB epidemics in low-and-middle-income countries (LMICs) for greater than a decade in my earlier profession have provided a vital and unique framework for my efforts to successfully develop business products for neglected infectious diseases.
Through the course of this work, I actually have led large and diverse mission-driven teams of local and international-based staff; managed complex partnerships, budgets and funding streams; mentored quite a few young professionals in infectious diseases, public health and pharmaceutical product development; and translated my experience and efforts into measurable impact on global health.