Repurposing Medications: Reimagining Treatment Options

Last month around the Chinese New Year holiday, a prominent Chinese scientist from Guangzhou Medical University made an announcement that stirred controversy both domestically and internationally while also highlighting a route to combat ailments that global academia and pharmaceutical industries have been attracted to for years. The scientist revealed that his team had been injecting patients with a malaria-causing parasite in order to cure a range of cancers – with two patients seeming to have no cancer cells remaining at the site of tumor and five additional patients having no disease progression out of ten total patients receiving this malarial therapy for at least a year. Although this type of treatment has been attempted in the past in an attempt to combat HIV in the 1990s, the Centers for Disease Control (CDC) and other health governing bodies determined that there was insufficient pre-clinical data to justify human trials during this time period. The controversy revolving around this announcement encompasses the aforementioned determination by CDC, the release of trial results before being published in a peer-reviewed journal, and, most importantly, the possibility of creating a malaria public health emergency for a country due to eradicate the communicable disease by 2020. Although the scientist who underwent this study clearly abdicated internationally conferred health principles, this avenue of repurposing – repositioning, re-profiling, re-tasking, etc – medications and therapy is becoming more appealing to those invested in novel treatment options for both established and emerging diseases.

Throughout the development lifecycle of new chemical entity (NCE), the process for regulatory approval could span over ten to fifteen years with an associated cost of over 2 billion dollars. This has led to an average of only 20 to 30 NCEs being approved by the Food & Drug Administration (FDA) each year. However, through repurposing medications, the development span can be cut to five to eight years at approximately 60% of the total NCE cost – in addition to higher approval rates from regulatory agencies. This repurposing process, as shown by the statistics, is enormously appealing for pharmaceutical companies/investors, but also provides targeted therapy for patient’s disease states at a theoretically lower price than an NCE. Even for rare genetic diseases, repurposing has become common due to only 400 medications being on the market to treat over 7000 genetic conditions. Repurposing is accomplished through the theory of translational research which takes a look at basic scientific discoveries and determining how a medication can be made to match this discovery – for example, examining the molecular pathway of diabetes and then matching it with a chemical entity that has an effect within the pathway like glucagon-like peptide 1 (GLP-1). The known chemical entities are commonly stored in giant databases within academia and the industry. Through big-data analytics, advanced modeling, and high throughput screening techniques, these chemical entities can then be extracted from the databases and determined if it has a possible role in a certain molecular pathway.

This method of establishing novel treatment options ought to be utilized more frequently and effectively, though there are medications over the years that have undergone this type of approval. The following are examples of already approved medications and others undergoing clinical trials:

Approved Repurposed Medications:

  1. Thalidomide, which was originally developed as a racemic mixture of enantiomers for the treatment of morning sickness but found to be teratogenic due to the effect of the (S)-isomer, was later successfully developed by Celgene as a single (R)-isomer product for the treatment of leprosy and multiple myeloma.
  2. Viagra (Pfizer’s sildenafil) was a drug that initially failed as an angina treatment in clinical studies; however, during these trials, its effect on erectile dysfunction was noted and then later approved for this indication.
  3. Celebrex, commonly used in osteoarthritis, works by inhibiting COX-2 receptors. Recently it has been shown that for patients that previously had colon cancer, taking this agent can reduce the risk of additional polyp formation without negative gastrointestinal effects associated with existing treatments.
  4. All-trans retinoic acid (ATRA), which is an acne medication, when combined with traditional chemotherapy, results in complete remission of acute promyelocytic leukemia in 90% of treated patients.
  5. Tamoxifen, a hormone therapy medication, treats metastatic breast cancers, or those that have spread to other parts of the body, in both women and men, and it was originally approved in 1977. Thirty years later, researchers discovered that it also helps people with bipolar disorder by blocking the enzyme PKC, which goes into overdrive during the manic phase of the disorder.
  6. Raloxifene was initially developed to treat osteoporosis, but has since been shown to reduce the risk of invasive breast cancer in postmenopausal women in 2007.
  7. Zidovudine (AZT) was initially developed to treat various types of cancer, but was determined to be ineffective. However, it was repurposed into the first approved HIV/AIDs medications in 1987 and has had a tremendous impact on the progression of the autoimmune disorder.

Repurposed Medications Undergoing Clinical Trials:

  1. The lipid soluble simvastatin is currently undergoing a trial in the UK to assess the efficacy of reducing the progression of Parkinson’s disease. The statin drug class is thought to prevent this ailment through its pleiotropic effects including reducing inflammation, reducing oxidative stress, reducing the formation of sticky bundles of alpha-synuclein, and increasing the production of neurotrophic factors. The results are expected to be released in 2020.
  2. Purdue University received a grant from the National Institutes of Health (NIH) to discover the effectiveness of Ebselen, a chemical entity, against methicillin-resistant Staphylococcus aureus (MRSA), and auranofin, which is FDA-approved for the treatment of unresponsive rheumatoid arthritis, against Clostridium difficile.
  3. Metformin, a first line agent for many diabetics, has been shown to reduce the risk of breast cancer in diabetes patients and is being investigated as a treatment for cancer in many different clinical trials

Although this is certainly not an exhaustible list of the impacts repurposing has had on healthcare, the majority of this repurposing stems from serendipitous observations rather than targeted interventions. Through these unanticipated occurrences, a range of disease states can now be more effectively treated ranging from communicable diseases like HIV/AIDS to mental health ailments including bipolar disorder and Parkinson’s disease to non-communicable diseases. As the rising cost of healthcare continues to devastate humanity and lead to health inequalities, heads of governments, pharmaceutical industries, academia, and nonprofits need to commit themselves into investing their time and resources into this repurposing method. The targeted repurposing interventions are more vital and should be devoted to in order to expand options for health disorders rather than the unexpected observed effects. The financial and health outcomes will lead to novel treatment options accessible to a majority of the world which will allow health care professionals to properly accompany their patients through their disease state.

The Future of HIV: Novel Treatment Options & A Possible Cure

As the medical community and those it serves welcomed in a new year, it brought with it the hope of scientific advancements that will alter the course of certain disease states. These advancements include the use of stem cells to treat to treat macular degeneration, novel microscopic techniques to capture images of the brain, the continued observed effectiveness of the experimental Ebola vaccine, and countless other interventions aimed at creating a healthier global society. Included in these optimisms for 2019 is the possibility for novel treatment options and a possible cure for one of the world’s leading causes of death, HIV. The stories of Timothy Brown – the only individual ever to be cured of HIV, the Mississippi baby and Clark Hawley – both having an extended period of time with undetectable HIV viral load with an interruption of Antiretroviral Therapy (ART), and the Boston patients/Mayo Clinic patient – all three having undetectable HIV viral loads for an extended period of time after a stem cell transplant, have brought much sanguinity to health care professionals and patients alike. However, these exciting results have been unable to be replicated in the majority of the population suffering from HIV and remain unique in their respective occurrences. Although ART has been vital to the HIV community in terms of longevity and quality life, there are still certain populations that are seeking other mechanisms to treat this infectious disease – and, of course, always coveting the idea of a cure. The following is a brief glimpse at the vast pipeline that awaits 2019 and the anticipations of the global healthcare community.  

Combination Approaches

  1. The AIDS Clinical Trial Group (ACTG) is currently exploring the option of combining vorinostat, a HDAC inhibitor along with tamoxifen, which is an FDA approved medication the treatment of breast cancer for postmenopausal women. Utilizing this approach is thought to prevent the reactivation of HIV in CD4+ cells that are latent in addition to increasing the latency-reversal effect of vorinostat through tamoxifen.
  2. Researchers from the USA, France, Germany, Italy, Spain, Switzerland, and the UK are collaborating for a trial testing the combination of two HIV vaccine candidates alongside a monoclonal antibody called vedolizumab. This method of treatment is thought to target a certain protein in the body, α4β7 integrin, that plays a role in transmission of HIV into CD4+ cells. In a macaque model, this combination has shown the control of SIV (HIV but in simians) after discontinuing ART.
  3. At the University of Minnesota, researchers are testing infusions of natural killer (NK) cells with the administration of cytokine interleukin-2 (IL-2). The researchers are hoping to add to the evidence of NK cells being able to exhaust HIV reservoirs and to control virus replication.
  4. In a version of the “kick & kill” method of curing HIV, researchers in Oxford and Barcelona are using a medication to active the latent HIV reservoir while boosting the immune response 1000 times stronger than the usual to rid the body of the virus. Preliminary results showed that 5/15 patients had undetectable viral loads for seven months without ART.

Immunotherapy Approaches

  1. Immunocore, a company founded in Oxford with heavy investment by Bill Gates, has designed T cell receptors that seek out and bind with the HIV virus. These receptors then instruct immune T cells to eliminate any HIV-infected cells, even when the levels happen to be extremely low. Since levels can be rather low in the reservoir of HIV virus that exists in an infected individual, this is a promising lead to completely remove this retrovirus from the body. This immunotherapy has shown to be effective in human tissue samples, but no results being tested in humans have been released.
  2. In France, a company known as InnaVirVax has established a vaccine, VAC-3S, that allows the body to stimulate a production of antibodies against the HIV protein 3S. This, in turn, causes T cells to attack the virus. This is considered a novel approach because it encourages the immune system to recover while equipping it with the tools to continue fighting off the virus. VAC-3S has completed Phase 2a trials, and is partnered with a DNA-based vaccine from FIT Biotech, a Finnish company, that both parties believe can lead to a functional cure.  
  3. In a recently initiated trial, IMPAACT 2008, held in the USA, Botswana, Brazil, and Zimbabwe, a broadly neutralizing antibody termed VRC01 is being investigated for its effectiveness in infants with HIV who are also started on ART within 12 weeks of birth. Although the study aims at establishing the safety profile for VRC01, it is also observing the difference in the HIV reservoir compared with only ART.

Novel Antiretroviral Agents

  1. The manufacturer, ABIVAX, believes it has developed a compound that may help the immune system recognize cells infected with HIV by allowing an increased presentation of HIV antigens on the cell’s service. This would lead to an augmented immune response to abolish these infected cells. This compound has been labelled ABX464 and targets the HIV protein Rev, which is responsible for the transcription of HIV RNA. Reductions of measured HIV DNA have been reported from 25% to 50% in eight of the fifteen patients participating in the study; however, no delay in viral load rebound was found when compared with placebo.
  2. Gilead has created a novel mechanism of targeting the HIV virus through the capsid inhibitors class. Capsids are involved in protecting HIV RNA and related proteins, and capsids also breaks down to release the viral contents into CD4 cells which enable reverse transcription to take place. The novel agent by Gilead, GS-CA1, blocks both the assembly and disassembly of capsids that create non-infectious and defective viruses.

Gene Therapy

  1. Chimeric antigen receptor (CAR) T therapy has been re-initiated in the first cure related clinical trial of this approach in people living with HIV who are on ART. CAR T cell therapy involves the modification of an individual’s T cells that can target antigens of interest. The specific cells modified by the initiative in China, called VC-CAR-T cells, have been modified to target HIV gp120. These modified cells were able to induce the destruction of HIV-infected cells, including latently infected cells exposed to latency-reversing agents, in the laboratory setting.  
  2. With the knowledge of knowing that about 1% of the world’s population is immune to HIV due to a genetic mutation on the gene that encodes for CCR5, US-based Sangamo has begun to edit DNA to introduce the aforementioned mutation. The CCR5 protein is attached to the surface of CD4 cells that allows HIV to enter and infect the cell; with the mutation, it would be impossible for HIV to enter cells. This company extracts patient’s CD4 cells in order to use zinc finger nucleases to edit patient’s DNA to make them resistant to HIV.
  3. Although a highly controversial topic amid the recent publication of the use of CRISPER in twin daughters in China, scientists believe that this tool can lead to a cure for HIV as it is believed to be a much easier, faster, and effective approach than other gene-editing methods. However, the majority of the global health community is in agreement that years of laboratory research and ethical standards need to be established before human trials are properly started.

With the HIV virus adapting and mutating to evade treatments almost as rapidly as the world is producing novel approaches to treating this infectious disease, the drive for continued research and testing should be relentless. These aforementioned examples of novel treatments and possible cures display the creative and diverse thought processes the medical community has put forth to tackle one of the most stigmatized diseases on this earth. However, the ethics behind these trials need to be sound and forthcoming for all of humanity. The trials that occur need to ensure an assortment of demographics including individuals from both developed and developing nations – a subtle form of medical colonialism has no place in the global health community. In addition, trials that enroll patients who willingly accept the benefits and risks associated with the experimental therapy have the moral obligation to supply lifetime treatment if it happens to be effective. The researchers and medical professionals who monitor these participants need to take extreme caution in ART interruptions/discontinuations and certify that the patients realize what complications could transpire due to them. Finally, and most importantly, the interventions that show promise of novel ways to approach HIV or even a cure have to be accessible, affordable, and available to all humans who suffer from HIV. The health inequalities that plague this fragile planet have already been clearly highlighted in this ailment throughout history; the global health community is in debt to humanity for a cure for all when discovered.  

With the global health community’s commitment, the future of the HIV virus continues to transition from infectious disease to chronic disease. While the step that will advance the chronic disease to a cure is still thought to be unknown, the excitement behind the aforementioned gene editing therapy is substantial. The ability to safely, effectively and ethically modify human cells to prevent the entry of the virus into the immune system is certainly the most promising option recently and possibly from this disease’s initial appearance; although, health care professionals haven’t quite figured out how to combine these aspects yet. A cure or even functional cure may be years away, but the global health community needs to continue to accompany those inflicted by this chronic infectious disease to meet the hopes and expectations of alleviating the burdens of HIV.

The Developing World & Non-Communicable Diseases: A Pandemic of Drug Shortages & Inequitable Access

Throughout the developing world, health demographics are rapidly shifting from communicable diseases to non-communicable diseases (NCDs) due to urbanization, lifestyle changes, and introduction of processed food. Although still retaining a significant portion of their communicable disease burden like tuberculosis and malaria, the prevalence of hypertension, diabetes, and cancer in developing countries has increased dramatically and is expected to cause every 7 out of 10 deaths by 2020. With the rise of these health ailments, the global health community has highlighted the importance and severity of these diseases through UN High-level meetings, incorporating relevant indicators in the Sustainable Development Goals (SDG’s), and forming interagency coalitions within countries to address the barriers of NCD prevention and treatment. However, NCD medication supplies have remained an underappreciated barrier that humans affected by global health inequalities confront each day. The complications of drug supplies range from common medications being out of stock to not having a vital class of medications available at the health facility. The medication shortages that plague developing nation states often have a more pronounced effect on underserved populations – essentially causing an impossible barrier to treating their chronic condition and preventing morbidity/mortality.

Last month on November 20thThe Lancet Diabetes & Endocrinology revealed predictions in the year 2030 regarding the world’s insulin supply that stunned health care professionals around the globe. From data gathered recently, the number of individuals diagnosed with Type 2 diabetes is estimated at 405 million people. Although some patients can be treated with oral or injectable diabetic medications like metformin or GLP1 inhibitors, there are approximately 63 million people on earth today that require the use of insulin to manage their diabetes. However, only 30 million individuals use insulin due to availability, affordability, and inequitable access to this essential class of medications. Although these numbers provide a clear indication of the necessity for change in regards to access to insulin globally, the scientists at Stanford that conducted the aforementioned study in The Lancet predicted that the number of individuals diagnosed with Type 2 diabetes will increase to 510 million in 2030 – 79 million of those will need insulin to proper manage their health disorder with only 38 million having equitable access to insulin. These statistics exhibit that, in 13 years, less than half of the people on this planet will be able to access insulin, a medication developed 97 years ago. Though over half of the world’s diagnosed Type 2 diabetics will reside in China, India, or the United States, the study continued and stated that the insulin supply shortage will distress those inhabiting Africa and Asia most significantly. The reasons formulated to explain this health disparity include the fact that three pharmaceutical industries control almost 100% of insulin being manufactured in the world, the complexity of insulin which is a hormone produced by living cells, and generic companies’ lack of interest in producing a biosimilar at an equitable price.   

Cardiovascular diseases (CVDs) pose an implausible health burden on the global society with 30% of all deaths worldwide being attributed to these ailments. Of this mortality caused by CVDs, it is estimated that 80% occurs in the developing world with projections suggesting a steady increase in this percentage. However, with equitable access to cardiovascular medications, approximately 75% of recurrent CVDs can be prevented causing a decrease in both mortality and morbidity for humanity. To determine the access to common cardiovascular medications like atenolol, captopril, hydrochlorothiazide, losartan, and nifedipine, the BMC Cardiovascular Disorders journal published findings in 2010 of a survey within 36 countries. The findings revealed that the drug shortages transcended more complex medications like insulin and affected the access of medications that are considered ubiquitous in the developed world. The analyzed data revealed that of the abovementioned medications in the 36 countries, only 26.3% was available in the public sector and 57.3% in the private sector. The study also stated that in several nations, the wages earned within one working day was insufficient to meet the cost of one day of purchasing treatment. When considering situations where monotherapy is inappropriate, this finding would disclose that treatment would be particularly unaffordable.

When considering access to NCD medications generally, wealth has been a substantial determinant of inequitable access to treatment of hypertension, asthma, cancer, and others classified as NCDs. In many low-income to middle-income countries (LMICs), a wealth gradient has even been observed. In order to gather information to disprove or support this theory, the BMJ Global Health Journal published a study conducted in Kenya in August 2018. The study administered surveys to patients prescribed hypertension, diabetes, and asthma medications and collected data on those medications available at their home, including location and cost of the service. When analyzing the data, the results clearly indicated a wealth gradient for each of the three diseases included in the study in terms of access. As household income increases, so does the likelihood that a family has an opportunity to obtain proper medication. In addition, the results showed that poorer patients had to travel further to obtain treatment than those with a higher income. Finally, and most meaningfully, poorer patients paid more for their medications than their fellow humans inhabiting other parts of the country.  

These global health inequalities are unjustifiable in a global society where the quantity and quality of medications on the market is incredible. The drug shortages and inequitable access differ between the developed world and developing world, but also by socioeconomic stratifications within countries themselves. In order to provide compassionate care to every human suffering from any of these ailments, governments need to begin initiatives to make insulin, losartan, albuterol, and every vital NCD medication available to every citizen in their country. Heads of states, pharmaceutical industries, ministries of health, and health care professionals need to accompany their citizens and patients with a health mindset moving away from health as a commodity to health as a right. Most urgently, universal health care coverage needs to be at the forefront of every national health agenda to properly address this pandemic of drug shortages and inequitable access.

Antibiotic Resistance: Hidden Rates in Rural Areas of the Developing World

When the age of antibiotics commenced in the 1950s, diseases and infections that typically would lead to humans being stigmatized by society, a permanent stay at a sanatorium, and then ultimately death were suddenly able to be treated quickly and efficiently. Penicillin and Streptomycin, not only improved a patient’s quality of life and longevity, but reshaped the very nature of treating infectious diseases. Health care professionals now possessed a cure to end the spread of the ailment and to eliminate the actual microorganism that created the suffering. However, these agents brought with them negative consequences that the global health community is still combating today – antibiotic resistance being one of the most significant issues. Antibiotic resistance is the predator’s (bacteria, virus, other microorganism) ability to resist an antibiotic that once was able to eliminate it. Although antibiotic resistance can occur naturally due to the cleverness of bacteria, fungi, and protozoa, the misuse of antibiotics in humans has tremendously accelerated the rate and severity of resistance. This inappropriate use of medicine and skills has led to difficult to treat infections like Extended-spectrum beta-lactamase (ESBL) producing strains of Enterobacteriaceae and even untreatable infections with no known drug on the market able to help an infected patient. The concept of antibiotic resistance often differs within the medical community when comparing the developed world, particularly urban areas, and the developing world, particularly rural areas. The amount of research, minds, and technology mobilized to address this unruly behavior by microorganisms varies drastically between the two sets.

In the urban developed world where physicians are equipped with the most innovative antibiotics known to man like daptomycin or the “Crispr” agents, antibiotic resistance is frequently a topic of discussion along with funding, human resources, and technology available to address it. Also, common ideology is that antibiotic resistance arises from the direct misuse of antibiotics rather than of natural causes. Contrasting the rural developing world, the aforementioned necessities to deter antibiotic resistance are often lacking due to health inequalities that unfortunately are ubiquitous throughout this fragile planet. More interesting though, health care professionals have formed an impression that antibiotic resistance more commonly stems from the dissemination of resistant organisms. With this mindset ingrained in world health leaders, the agenda has been to focus on prevention through this venue in the rural developing world – often lacking a call of funding to determine actual causes of antibiotic resistance and their associated rates in the rural developing world. While the dissemination of strains of Escherichia coli through feces and Multi-drug resistance Tuberculosis through poor air quality certainly needs to be addressed, the Centers for Disease Control and Prevention (CDC) released a report in 1999 encouraging health care professions to consider a range of socioeconomic and behavioral factors including misuse of antibiotics by physicians, unskilled practitioners, the public, counterfeit medications, inadequate surveillance, and political factors. To follow up with this theoretical account, the World Health Organization (WHO) conducted a survey across twelve (12) low to middle income countries across the world in 2015 to interview the population about their beliefs towards antibiotics and resistance. Some of the results are presented below:

  • In lower income countries, it was reported that antibiotic use is higher (42%) than in higher income countries (29%).
  • Across the countries, the range of patients obtaining their antibiotics with a physician’s prescription ranges from 56% to 93%.
  • The percentage of individuals believing they can use the same antibiotic as a family member did to treat a similar illness is 25% while 43% believe it is acceptable to buy the same antibiotic from a local pharmacy.
  • When patient’s start to feel better, 32% of the those interviewed believe they can stop the antibiotics and not follow through with full course.
  • When treating colds and viruses, 62% of respondents believe antibiotics could be used to treat these ailments.
  • Finally, 44% of those interviewed believe antibiotic resistance is only a problem for those regularly taking antibiotics.

These specific social results from patients in the developing world directly conflict with the thought of the major distributor of antibiotic resistance being through dissemination of the disease. The beliefs presented through these percentages seem to lead to a whole host of factors being involved similar to the developed world. In addition to these social results, PLOS Biology released data in 2018 that Escherichia coli was resistant to commonly prescribed antibiotics like ampicillin (92%), ceftazidime (90%), cefoxitin (88%), streptomycin (40%) and tetracycline (36%) in the rural areas of Sikkim, India in pre-school and school-going children. The Journal of the Pediatric Infectious Diseases Society reported similar rates among children in 2015 with Klebsiella pneumoniae having a median resistance to ampicillin with a rate of 94% in Asia and 100% in Africa, and cephalosporins having a rate of 84% in Asia and 50% in Africa. Also, The World Health Organization informed the global community that in Malawi in 2018, nearly 100% of Neisseria gonorrheae genital isolates were non-susceptible to ceftriaxone and roughly 15% were non-susceptible to azithromycin. When analyzing both the social and technical results from above, a renewed emphasis and novel perspective needs to be created in order to properly address antibiotic resistance in the rural developing world.

At the beginning of this year (January 2018), the World Health Organization released its initial reports utilizing an innovative reporting system for antibiotic resistance christened Global Antimicrobial Surveillance System (GLASS). This system was developed in order to preserve human and animal health throughout the globe in relation to antibiotics and their resistance. Although GLASS was officially launched in 2015, it is still in its early implementation period with only 22 countries reporting on actual resistance within their nation states and 40 countries reporting on their national surveillance program. However, GLASS aims at a variety of measures that will ensure antibiotic resistance is more appropriately addressed in the rural developing world by providing a standardized approach to collection, analysis, and dissemination of information to participating countries. GLASS will strengthen nation states antibiotic resistance surveillance systems and modify the data being studied from solely laboratory data to epidemiological, clinical, and population-level data. The preliminary results that were released by WHO revealed that across the 22 reporting countries, there were 500,000 individuals suffering from an infectious disease with antibiotic resistance. Although this data varies with completeness and accuracy across countries, the outcomes highlight the global emergency antibiotic resistance posses from the urban developed world to the rural developing world and everywhere in between – these mutated organisms will fail to respect national borders.

The global health bodies throughout the world have initiated programs and offered advice to nations that will serve the battle against antibiotic resistance well. However, the concealed rates of resistance in the rural developing world will need to be undertaken medically and socially in order to properly end this global emergency. Pipeline innovative antibiotics like relebactam, a novel beta-lactamase inhibitor and an educational emphasis on behavior habits will aid these parts of the world – but the health community will fall short unless the world changes its perception of antibiotic resistance in the countryside of Cambodia, the rice terraces of Vietnam, the jungles of Belize, and areas with similar socioeconomic status.

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.