United Nations High-Level Meeting on Tuberculosis: Importance of drug quality

At the end of next month, the inaugural United Nations (UN) High-Level meeting on Tuberculosis (TB) will take place in New York to discuss the future of the bout against the devastating yet elusive disease. As TB remains the largest infectious disease torturer in today’s society taking the lives of 4500 humans each day, the theme of this occurrence is “United to end Tuberculosis: an urgent global response to a global panic”. This unparalleled step undertaken by governments throughout the world along with those allies engaged in ending Tuberculosis will address an assortment of issues at this meeting. Although the exact agenda has yet to be revealed, the resolution to host this single day meeting mentioned the following items could be discussed:

  • Adequate funding for novel diagnostic testing, medications, and vaccinations
  • Multi-Drug Resistant Tuberculosis (MDR-TB)
  • Responsibility for multisectoral collaboration within nation states, regions, and the globe
  • Universal health care coverage and ensuring tuberculosis coverage is included

Each of these items – ranging from the use of prophylactic low dose isoniazid therapy to equal distribution of the recently designed TB diagnostic test Xpert MTB/RIF – are crucial in accomplishing the END TB strategy laid out by the World Health Organization. However, after looking over these action items for the meeting, Tuberculosis drug quality seems to absent.

As health care professionals across the globe continue to treat TB on a patient specific basis, certain untreated cases occur that puzzle even those who have treated the disease for years. The reasoning behind treatment failure? Adherence to medication or drug resistance are often the first assumed thoughts those sharing their patient’s fate may have. Yet, the actual medicine with its various active and inactive ingredients is often not called into question.

Towards the end of last year, the World Health Organization released an alarming figure concerning drug quality in low to middle income countries. In the report released to the public, WHO stated that approximately 10% of medications are counterfeit in these areas of the world – which happen to be the areas where Tuberculosis and other infectious diseases take their largest toll. In addition, WHO added that this percentage is most likely only a small part of the number of humans truly affected by counterfeit medications. To provide clarification, WHO considers counterfeit medications to be unapproved by regulators, unable to meet quality standards, or purposefully misrepresented active or inactive ingredients in the medication. In addition to this report by WHO, the National Institutes of Health (NIH) published a report outlining in 2015 that 9% to 41% of anti-tuberculosis and other infectious disease medications failed to meet the standards sought in specific studies.

It is vital for the global health community to obtain an effective vaccine to prevent pulmonary tuberculosis, to have a rapid yet specific TB diagnostic test, to create a strategy for various sectors of a nation state to work together in ending TB, and novel agents to treat the most severe cases of MDR-TB. Individuals in rural Kampot, Cambodia, inmates in the Russian prison system, or those residing in the slums of Bangalore, India often can be restored to health through the means that have been available for the last half a century. The RIPE (rifampin, isoniazid, pyrazinamide, and ethambutol) regime has proven its success in treating non-resistant tuberculosis – so long as each of the medications are of appropriate quality. However, The Lancet released a report in January 2017 that found that 8.9% of Indian rifampicin products were of inadequate quality in a country that is burdened with the highest prevalence of tuberculosis across the globe. Moreover, WHO revealed that 28.3% of rifampicin containing medications found in the Russian Federation in 2011 failed to meet predetermined specifications for proper quality – a country known to have one of the highest MDR-TB burdens in the world. With the aforementioned statistics released by the WHO, The Lancet, and NIH, a renewed emphasis needs to be placed on ensuring the quality of each and every tuberculosis medication that reaches a human being. The possibility of one in ten (or more) TB medications being counterfeit will continue to lead to failed treatment regimes, inappropriate use of resources, and spread of MDR-TB even if innovative technology is developed.

In order to combat counterfeit medications on a global level, the World Health Organization developed a reporting system for the interconnectedness of the medication market. The Global Surveillance and Reporting System (GSRS), that all WHO members are eligible to contribute to, aims at collecting data on falsified medications, vaccines and other medical equipment to address real-time situations and prevent further harm. With this reporting arrangement in place, the WHO has reacted and thwarted mortality and morbidity associated with counterfeit medications – including the contaminated cough medication supply that led to 60 deaths in Pakistan and a number of individuals treated with an antidote in Paraguay in 2013. On top of the GSRS, WHO has implemented Good Manufacturing Practices (GMP) that each manufacturer should achieve in order to be certified by WHO; thus, providing a reliable source of medications that nation states can purchase from. Although these initiatives have brought about encouraging results along with halting global medication emergencies, there are still barriers that accompany these programs. The technical training, technology, and adequate staffing to properly identify and report through the GSRS is often difficult to obtain in the developing world while GMPs are often misapplied and have inadequate supervision. The root cause is the long-term development of countries’ public health systems – of which continuing problems with counterfeit medications remains deficiently addressed. A county’s public health care system is the vital organ to ensuring quality medications through these mechanisms that WHO has created and employed. An underutilized and under resourced public health care system leads a budding yet unregulated private market – unable to ensure proper treatment for those seeking it.

Since the United Nations declared this a high-level meeting, meaning all heads of member states are encouraged to participate in the highest level possible, this venue provides the ideal opportunity to recommit to guaranteeing TB drug quality. The sustained empowerment of the public health care systems for those countries tirelessly battling tuberculosis will be a step forward into truly ending this devastating disease. Each health care professional spanning the globe has a responsibility to accompany these governments, colleagues, and fellow humans by investing their time, resources, and talents to develop procedures and systems to ensure effective drug quality.

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Access to PrEP under NHS England: My trip to London

Pre-exposure prophylaxis (PrEP) is a way to prevent HIV infection for people who do not have HIV but who are at high risk of getting it by taking the pill everyday. When someone is exposed to HIV through sex or injection drug use, PrEP can work to keep the virus from establishing a permanent infection. Individuals who take 7 PrEP pills per week, have an estimated level of protection of 99%. It is a powerful prevention tool combined with condoms.

In the United States, PrEP became available in 2012 by the FDA and can be accessed in most clinics and hospitals and is free under most insurance plans. As of 2017, there are an estimated 136,000 people currently on the drug for HIV prevention. This is not the case in the United Kingdom. As a part of a research project for my MPH degree I traveled to London, England to meet with members from the LGBT community, advocates and public health professionals and to learn more about access to PrEP under the National Healthcare System (NHS) England. Currently, PrEP is not available under NHS England even though HIV continues to be a prevalent problem in England, namely among men who have sex with men (MSM) where approximately 54% of the total of MSM population were diagnosed in 2015. England is however enrolling 10,000 people over 3 years through the PrEP IMPACT trial.

Wales, Scotland, and Northern Ireland are also a component of the NHS. Wales has commenced their PrEPared Wales project, which provided information on where to access PrEP in the country. Scotland is currently the only country in the UK that offers a full PrEP provision through their NHS. Northern Ireland currently has no provision of PrEP.

The NHS is widely regarded as a remarkable system, allowing UK citizens to access certain free healthcare services. England has had some shortcomings however when it comes to preventing HIV and I was interested in learning more. I visited the Terrance Higgins Trust (THT), a British charity that campaigns on and provides services relating to HIV and sexual health. In particular, they aim to end the transmission of HIV in the UK, to support people living with HIV (PLWH), and decrease stigma around HIV. I met Greg Owen, the founder of iWantPrEPNow, a website that explains why it is important for HIV protection, who might consider PrEP, what you need to do before you start, where to buy it online, and how to take it. I also met with Will Nutland, who works alongside Greg and is the founder of Prepster, a guide and movement to safely buying PrEP. Both websites have experienced a lot of traffic since the IMPACT Trial began in October 2017. The trial seems like a step in the right direction when it comes to accessing PrEP, this is not the attitude for many and there continues to be a debate.  While there is significant evidence from other trials that demonstrates PrEP is an effective HIV prevention tool, many people believe that NHS will not endorse PrEP after the trial is complete.

I asked Liam Beattie, also a member of the THT team, why he believes NHS England did not endorse PrEP under its guidelines. He believed that it was because of 1. homophobia among the NHS and 2. the media. Liam was recently interviewed on BBC News. During the interview, PrEP was categorized as a “controversial drug,” which paints a negative light on the topic from the get-go.  While England is well-developed and progressive in so many ways, HIV is still known as the “middle-aged gay male virus.” THT and other organizations continue to develop new marketing tools and programs in order to target women, transgender persons, and people of color to visit a sexual health clinic and get tested. Taking PrEP is an advantage for not only the individuals health but the overall cost of healthcare. Many are hopeful that in the future, the NHS will work with organizations like THT to promote PrEP and other educational resources to prevent HIV.

The next big thing in global health innovation? A little less innovation, a little more implementation

A post like this should come with the qualification that I am no luddite when it comes to technology and innovation in global health. Quite the opposite actually. I have dedicated my entire career to championing ideas. Whether that was working in academic research evaluating new ways of helping people with chronic diseases live well or researching the technology and innovation pipeline to help healthcare organizations make decisions on what technologies and innovations to invest in; I have been and will continue to be a health technology and innovation advocate (and when I talk about innovation, I’m not just talking about clinical and biological technology or information and communication technology but more broadly about new programs, interventions, etc).

Five years ago I embarked on a new career path in global health which transformed the way I now think of innovation. One of my first projects was to help a local partner organization implement a logistics management information system to manage their post-rape care medication inventory. Since then, I have helped our partners through the process of implementing other technologies and in that short time, I learned the many pain points of implementing innovations.

When you have spent a good part of your career as I did working in controlled research environments where the protocol is often laid out months ahead of time with little room for deviance and with study participants who are often given incentives to participate, working on the last mile problem required a skill set refresh and a change in the way I viewed the innovation pathway. Whether it is learning how to integrate an innovation into a user’s workflow; getting users to trust you enough to tell you when something is just not working for them; finding out how to get innovations to stick; making mistakes and reiterating; using real-time data to enable feedback loops; understanding (and dealing with) organizational politics and leadership; mapping out relationships, etc. – graduate training in public health does very little to prepare you for the trial by error approach required for these undertakings. Researching and evaluating is very different from implementing. So many of us in this field spend much of our time working on research studies and programs based on the models and theories we’ve learned in school that we very rarely think closely about whether or not the studies or programs we work on are scalable, sustainable, or even ethical.

I recently attended a panel at Stanford consisting primarily of philanthropic organizations discussing how those of us working in the social sector and those of us supporting the work need to rethink innovation in terms of scale. One of the things that struck me during the discussion was that when it came to what metrics we use to define success we’re often talking about success on a small scale.  And too often they’re developed with the mindset of pleasing the donor or funder. When we think success metrics, we usually talk about some quantitative statistic that goes something like this: X% reduced morbidity or mortality in our sample size of N. At the end of the study or funding period, we leave the site, taking with us our intervention. We then go on to write a paper about it, submit it crossing our fingers it gets accepted in a high impact journal, we publish it, we present our ideas at conferences. We then call it a success and move onto our next grant.

While this is often the gold standard of success for academics and should still remain an important part of the innovation pathway, there are parts of this road to innovation success that are concerning, especially in the low-resource settings we work in. Firstly, is it ethical to put in an innovation into a site and then remove the intervention once the study period is over if we know it has helped them? Would the site be even able to afford the innovation once it passes the research phase? Secondly, is it enough to define the success of an innovation by saying the intervention did what we wanted it to do? After all, I’m pretty sure a company like Facebook didn’t call themselves a success after running a small study of 250 users that found that everyone liked the product and it changed their lives. They are successful because they have 1.94 billion daily active users worldwide (scale) and have been around for 14 years (sustainability) and they have changed the way we connect with others.

Dear global health colleagues, we have an enormous task at hand. One that requires us to roll up our sleeves and stop thinking small and start thinking big. Let’s end this epidemic of health technology pilotitis and start innovating in the implementation space. Let’s start thinking about ways of innovating outside of the academic space and in real-world settings with real-world obstacles. Implementing innovations demands collaboration so let’s also make sure that we influence those around us. We need to change the conversation on impact and start asking our colleagues and the organizations that support our work to start thinking about the long game. From there we need to make it easier to decide which technologies and innovations to adopt. Let’s also not forget about training our next generation of public health professionals to focus on creating true impact by teaching effective implementation in schools.

Implementation work is incredibly unsexy and a risky investment but needs to be the next big thing in global health as its value proposition is substantial. It is of notable importance when the future of funding for global health is becoming more uncertain. We need now more than ever to deliver long-lasting solutions, not just short-term fixes.

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A study looking at the proportion of children’s health grants funded by the US National Institutes of Health and the Bill and Melinda Gates Foundation found that 97% of grants were for developing new technologies and only 3% for improving delivery and use of existing technologies. Additionally, they found that new technologies would only reduce child mortality by 22% compared to 63% if existing technologies were fully utilized.

Although this study looked only at children’s health grants, the implementation gap can be found universally throughout global health. Learn more about how to bridge the “3/97” gap:

 

Progress toward #polio eradication is a much-needed reminder that global health is still winning

I always love spotlighting polio eradication. Along with Guinea worm, it is one of the few candidates to follow smallpox to the eternal (or so we all hope) halls of eradicated diseases. While the eradication effort has suffered its setbacks in recent years, public health workers have persisted, steadily marching onward. And frankly, there has been so much hand-wringing in global health in recent weeks that it is important to occasionally remember that there are still wins we can, and should, celebrate.

What makes this success possible in addition to trackable is the global network of polio surveillance systems, which was featured in CDC’s MMWR at the beginning of April:

The primary means of detecting poliovirus transmission is surveillance for acute flaccid paralysis (AFP) among children aged [less than] 15 years, combined with collection and testing of stool specimens from persons with AFP for detection of WPV and vaccine-derived polioviruses (VDPVs)…in WHO-accredited laboratories within the Global Polio Laboratory Network. AFP surveillance is supplemented by environmental surveillance for polioviruses in sewage from selected locations. Genomic sequencing of the VP1-coding region of isolated polioviruses enables mapping transmission by time and place, assessment of potential gaps in surveillance, and identification of the emergence of VDPVs. For public health nerds like me, all of MMWR’s polio reports can be found here.

Basically, a combination of syndromic and environmental surveillance allows public health systems to track polio where it pops up, and genetic sequencing helps to trace how the virus got to where it did to shed light on transmission patterns and find gaps in surveillance.

The WHO followed with two YouTube videos featuring the global polio surveillance system and polio vaccination, which is what will make eradication possible:



This is all pretty straightforward stuff – we all know generally that surveillance systems do, in fact, work when their infrastructure is properly supported and that children should be vaccinated against polio. But it’s important to not lose focus on our successes and global health progress, even when it is simple, straightforward, and sometimes slow.

Global Health in Conflict: A Weightier Commitment

It is important for early-career professionals interested in pursuing a career in global health to be aware of the realities of working internationally. Although stories of setting up vaccination clinics or fighting Ebola may stir up feelings of excitement, being a part of the action may require additional education and training in conflict resolution and institution building. This is especially true when it comes to conflict-affected areas and fragile states that are the most in need of health care/public health services as a result of the local health system infrastructure being weakened. A different kind of public health professional, one that is willing to risk their life and invest in the indigenous health system, is required in our world today.

I currently work as an epidemiologist at a regional health department in Texas. We serve two main roles for the 30 counties we cover. One of our roles is to function as a local health department and deliver a diverse range of services to 23 counties. The other main role is to serve as an extension of the state health department and provide surveillance/investigation guidance for the reportable conditions that health care providers, schools, and community members are mandated to report. This relationship is seen especially when we work with the 7 counties in our region that have their own local health departments. Before beginning this job, I actually worked at one of these local health departments and was on the receiving end of the interaction described above.

For most of my life, I’ve been interested in pursuing a career in global health or humanitarian work. When I was younger, I thought the only way I could pursue this dream was by being a physician (especially if I wanted to be able to support myself financially). I also believed this to be a great way to help communities that were dying from preventable illnesses. My introduction to public health helped me see that there were many other ways to help achieve the goal of combating deaths due to preventable illnesses. I focused in on epidemiology as a way to combine my science/laboratory background with my desire to serve and entered into an MPH program after completing my B.S. in Biology. Most of my MPH program was spent working hard to obtain tangible experiences in public health practice and deciding which skills would be most necessary for me to have before entering into the workforce. While pursuing my MPH from 2014-2015, some of the hot topics in public health were Ebola, antimicrobial resistance, bioterrorism, anti-vaccination movements, hospital-acquired infections, opioid abuse, tuberculosis trends related to travel, maternal and child health gaps, and continued efforts to end polio and AIDS, to name a few. Towards the end of my program, I began to hear more about the dangers of humanitarian work and global health as stories involving health care and humanitarian workers being targeted in conflict-affected areas/fragile states were highlighted in various media outlets. I also knew of at least one faculty member at the university I attended whose global health team was attacked shortly after the individual returned to the US (after working in the field for a number of years).

When I entered into the public health workforce in 2016, Zika was just becoming a hot topic in public health circles in the U.S. But there were other things for me to learn at my local health department. I received an introduction to the Immunization team and programs such as Texas Vaccines for Children which enable young people in Texas to receive affordable immunization coverage (there is an adult vaccine program too). I also received an introduction to the statewide ImmTrac system that stores vaccine records and learned about some of its strengths and challenges. Ultimately, I was able to see the importance of public health collaborating with healthcare providers, schools, and community members to ensure that a community has adequate herd immunity or, in the case of outbreaks, can deliver effective interventions in response to infectious disease threats. Something else I learned about was the role of immunization clinics or point of dispensing units (PODS) during natural disasters, such as floods, and other public health emergencies.

I’ve shared some of my experience working at the local level because it gave me a tangible picture of how public health functions in stable environments or areas that are not weakened by natural disasters. In conflict-affected areas or fragile states, public health efforts may be fragmented at best. For example, in August 2015 Nigeria was removed from the World Health Organization’s list of countries with endemic Wild Polio Virus (WPV). This was the result of global efforts aimed at eradicating polio through targeted immunization campaigns. Nigeria went two years without WPV cases before, in August 2016, two cases were reported in Borno-a conflict-affected state. Two additional cases were reported in September 2016. The cases were from inaccessible areas of the state with limited security and indicated that prolonged transmission had gone undetected as a result of armed conflict. Although the number of areas held by insurgents, and therefore without access to vaccines, eventually decreased, the conflict in Borno prevented timely vaccination campaigns and posed a risk to Nigeria as a whole. Specifically, migration between Internally Displaced People (IDPs) camps and refugee communities resulted in a higher potential for WPV cases to be reported in states not directly tied to the conflict. A similar trend was noticed with the Ebola outbreak that occurred in West Africa from 2014-2015. The disease posed an increased risk in fragile states and areas affected by conflict. For example, prior civil wars in Liberia and Sierra Leone severely weakened the countries’ infrastructure in the 1990s. The conflicts also affected surrounding countries and resulted in millions of displaced people. In some of instances, countries had the resources needed to respond to public health emergencies caused by conflict. However, groups of people or areas deemed to be inaccessible as a result of conflict continued to undermine the effectiveness of immunization clinics and infectious disease response efforts.

A comparative analysis conducted by Bourdeaux et al. in 2015 assessed the effect of conflict on health systems in Haiti, Kosovo, Afghanistan and Libya.  Health systems were defined as, “the organized network of institutions, resources and people that deliver health care to populations” and was based on the World Health Organization’s (WHO) Framework for Action (2007). The framework highlights financing, leadership/governance, information, medical products/vaccines/technologies, health workforce, and service delivery as essential components of effective health systems. When this organized network is destroyed as a result of armed conflict, high levels of morbidity and mortality occur and can have negative effects that persist even after the conflict is over. The analysis found that the building blocks most affected by conflict and security forces were “governance, information systems and indigenous health delivery organizations.”  In order to address these gaps, a suggestion provided by the authors is to deploy Health Security Teams comprised of individuals with training in public health and institution building to conflict-affected areas and fragile states. The teams would support indigenous health systems instead of creating parallel or temporary systems, and not be involved in serving military interests. Additionally, these teams would know how to guide security forces as they engage with health systems in diverse political climates.

At this point in time in my career, most of my work is done in an office on a phone or computer. When I started my journey in public health, I pictured something different. I still have the long-term goal to work internationally (or financially support myself while volunteering internationally). However, I am sobered by the fact that if I want to serve those who are truly in need (especially as it relates to conflicted-affected areas and fragile states) I will have to be at peace with laying my life on the line. I will also have to be prepared to navigate the challenges presented above. This includes learning as much as I can about conflict resolution and negotiating to protect health systems. In general, I feel that public health has much to do in terms of educating and re-assuring those we serve (both domestically and internationally). As a result, part of my journey in public health will include developing skills as a connector of people and someone that can see both sides of an issue. I think that all public health professionals interested in working in a global health or humanitarian worker capacity should consider this. At the same time, immigrants or refugees that have left their homes due to conflict or in search of better opportunities can also develop the skills needed to resolve conflict and rebuild institutions. The success of the suggested Health Security Teams could depend on this.

 

Photo: Diane Budd, M.D.

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