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.

Three Observations from UN High Level Health Meetings

During the United Nations (UN) General Assembly, two historical High-Level meetings in the realm of health were held addressing ailments that afflict individuals from every corner of this fragile planet. The first UN High-Level meeting on Tuberculosis (TB), focusing on preventing and treating this elusive disease, was held on Wednesday, September 26th which finally put TB in a global spotlight. Additionally, the third UN High-Level Meeting on Non-Communicable Diseases (NCDs), under the theme “Scaling up multi‑stakeholder and multisectoral responses for the prevention and control of non‑communicable diseases in the context of the 2030 Agenda for Sustainable Development,” took place on Thursday, September 27th. World leaders and their ministers, non-government organizations (NGOs), and other stakeholders partook in these crucial meetings to curtail the suffering these various diseases cause. For each of these meetings, governments approved drafts of political declarations that commit countries to follow through with health policy, funding, and a multisector approach to these disorders. The following summarizes key points and commitments from each of the high-level meetings:

UN High-Level Meeting on Tuberculosis

  • A commitment to mobilize $13 billion for universal access to quality prevention, diagnosis and treatment
  • $2 billion for research and development of new drugs, diagnostics, vaccines, and other tools.
  • Commit to provide diagnosis and treatment with the aim of successfully treating 40 million people with tuberculosis from 2018 to 2022 (including 3.5 million children, and 1.5 million people with drug-resistant tuberculosis including 115,000 children with drug-resistant tuberculosis)
  • Pledge of 30 million people (including 4 million children under five years of age, 20 million other household contacts of people affected by tuberculosis, and 6 million people living with HIV and AIDS) to receive preventive TB treatment by 2022
  • Promise to overcome the global public health crisis of multidrug-resistant tuberculosis through actions for prevention, diagnosis, treatment and care, including compliance with stewardship programs to address the development of drug resistance
  • Oblige to consider how digital technologies could be integrated into existing health systems infrastructures and regulation for effective tuberculosis prevention, treatment and care
  • Commit to provide special attention to the poor, those who are vulnerable, including infants, young children and adolescents, as well as the elderly and communities especially at risk of and affected by tuberculosis.

UN High-Level Meeting on NCDs

  • Commitments to reduce NCD mortality by one third by 2030, and to scale-up funding and multi-stakeholder responses to treat and prevent NCDs
  • Health systems should be strengthened — and reoriented — towards the achievement of universal health coverage and improvement of health outcomes
  • Greater access to affordable, safe, effective and quality medicines and diagnostics
  • A commitment to ambitious multisectoral national responses, integrating action on prevention and control with promotion of mental health and well‑being
  • Increasing energies to reduce tobacco use, harmful alcohol use, unhealthy diets and physical inactivity through cost‑effective, evidence‑based interventions to halt obesity
  • To develop a national investment plan in order to raise awareness about the national public health burden caused by non‑communicable diseases and health inequities

While these are not all-inclusive of the commitments between nation states at these two meetings, they highlight the prominent concerns leaders in both the political and health dominion share. However, special attention should be brought to the dialogue held before and after the duration of the meetings. These discussions reveal the true apprehensions that world leaders fear affects their citizen’s health and well-being. The following are three observations from these two UN high-level meetings that may provide some significance in the future battle with TB and NCDs.

1. Is health trending towards being a right rather than a commodity among world leaders?

Before the UN high-level meeting on TB came to fruition, there was a highly controversial commitment in the declaration that concerned high-income countries like the United States. The commitment was centered around access to affordable medications, in particular, generic medications. The concerned countries had expressed reservations about language supporting UN member states’ rights to interpret and implement intellectual property rights in a way that defends public health and encourages access to medicines. Global health advocates believed this point as being essential to equitable access to medications across the world – treating health as a right rather than a product. In the end, health as a right was included into the declaration, through the leadership of South Africa and Médecins Sans Frontières (MSF), despite upsetting these powerful nation states. In addition, at the high-level meeting on NCDs, language was included that stated a similar commitment – to affirm the rights of UN member states to use intellectual property flexibilities to safeguard public health. Although the fight against these two devastating classes of diseases is certainly at the forefront of leaders’ minds, the seemingly endless interchange of health as a right and health as a commodity seems to be finally leaning towards the betterment for humanity – health as a right.

2. Technology and Policy – Finally Uniting to fight TB & NCDs

Throughout the UN General Assembly last week, several reports, policies and studies were released or highlighted that may prove to shape the future treatment of TB & NCDs. The following list are just a few of the major contributions that various sources released:

Health care professionals throughout the world realize that diseases need to be undertaken in a biosocial manner – utilizing both technology and policy. The outcomes that resulted from last week’s reports reaffirm that political leaders realize that the true way to overcome these burdens is to address them through this manner.

3. Multi-Sectoral Approaches – How should they be conducted?

One of the biggest initiatives in global health is the necessity to bring together all stakeholders in disease management in order to properly address the situation. With a vast array of input and ideas, different perspectives, and an atmosphere of collaboration, global health is trending rapidly in this manner – with a significant portion of the world partaking in multi-sectoral approaches already. However, the manner in which these are conducted can vary within countries and between NGOs and governments. Although these remarks may not apply to every country, the following statements made by world leaders may provide some insight into how a country could carry out these approaches:

  • A representative from the Netherlands state that including all stakeholders into the approach may cause conflict of interests – “The days are gone when the tobacco industry has a seat at the table” while also stating “multi-sectoral approaches are good, but governments should be in the lead” in reference to NCDs.
  • An NCD Alliance representative mentioned “it is for governments to determine their own priorities” and “civil society is ready to support, but governments must lead the way.” while simultaneously reaffirming her support for multi-sectoral approaches.
  • Finally, Gerda Verburg, coordinator of Scaling-Up Nutrition Movement explained that “Bigger companies are part of the problem, but we won’t succeed unless we make them part of the solution,” while also adding that she realizes that this is often difficult for civil society, and that “too often, they stand with their backs to the table where we need a critical dialogue with the private sector.” In addition, she supports the priority to “strengthen national systems.”

In a global society where the healthcare landscape is in constant motion, the ability to gather world leaders to commit to significant leaps of change is promising to all those who inhabit this planet. However, these commitments need to be followed up with action, funding, and the political will to properly solve the world’s number one killer and the deadliest infectious disease. The global health community should inspire and encourage their governments while correspondingly holding them accountable to adorn these commitments and continue to battle these overwhelming diseases.

 

World Rabies Day: Rabies Prevention Around the World

September 28th is World Rabies Day! This day of observance was created by the Global Alliance for Rabies Control (GARC) to spread awareness about the disease and educate others on how to prevent it. This year’s theme is Rabies “Share the message. Save a life.” 

Rabies is a preventable viral disease that affects only mammals and is transmitted through the saliva, cerebral spinal fluid or brain tissue of an infected host. If untreated, rabies is fatal. Most commonly, the disease is transmitted through a bite, but can also be transmitted if the infectious material gets directly into the eyes, nose, mouth or an open wound.  Rabies infects the central nervous system and causes a “disease of the brain.” Early symptoms of rabies can include fever, headache and fatigue – symptoms that are similar to many other illnesses such as the flu or common cold. However, as the disease develops, symptoms specific to rabies begin to appear: insomnia, paralysis, hallucinations, agitation, hypersalivation, difficulty swallowing and hydrophobia. The disease typically results in death within a few days after the onset of these rabies-specific symptoms.  

In the United States, reported rabies cases have shifted from mainly domestic animals to predominantly wildlife animal reports. Specifically, more than 90% of all rabies cases today are from wild animals. In addition, the number of rabies-related deaths in humans has decreased dramatically from 100 cases per year in the 1900’s to 1-2 per year. Our efforts to encourage prophylaxis after an exposure and the effectiveness of the vaccine have proven successful in decreasing rates of rabies in the United States.

However, rabies is found on every continent other than Antarctica and some continents struggle with the burden of rabies more than others. The overall death rate for rabies around the world is estimated at a staggering 59,000 people a year. Countries in Africa and Asia are affected by rabies disproportionately than the other continents and almost half of the victims of rabies in these countries are children younger than 15 years.

A main reason that such a young population affected is due to uncontrolled canine rabies in these countries. Canine rabies – which spreads from dog to dog – is actually the cause of 98% of human deaths globally. In the United States it has been eliminated because many people keep their animals vaccinated to prevent this type of rabies from re-entering our environment.  However, in many other countries, stray dogs roam around neighborhoods freely and when they contract rabies, they likely spread it to many people (primarily children) they come in contact with. Scientists predict that if 70% of dogs are vaccinated for rabies in an area, rabies can be controlled and human deaths will decrease.

Haiti has the highest number of human deaths by rabies – around 2 deaths per week. CDC and the Government of Haiti have started an animal rabies surveillance program (2013) to detect and have situational awareness of which regions of the country are greatly affected by rabies. In 2015, CDC also evaluated how many dogs were vaccinated in the country and found that only 45% of dogs received their shots. In addition, the total amount of dogs in the country was actually double the number they initially predicted. After these studies were done, the CDC helped train animal health workers to conduct large dog vaccination campaigns and continue rabies prevention efforts.  Many children started bringing their puppies to the events and were proud of their certificates ensuring their dogs had been vaccinated. It is CDC’s (along with the Government of Haiti) hope to reach a 70% vaccination rate among their dog population and sustain it for five years – long enough to create a ripple of effect among human deaths due to rabies.

CDC has helped establish similar campaigns in other countries. For example, they have trained animal control officers in Ethiopia to capture, vaccinate and release stray dogs as well as monitor human exposure cases and keep track of post-exposure prophylaxis (PEP) treatments.  In Vietnam, while there is not a high human death rate for rabies – 91 per year, the government spends an extraordinary amount of money on expensive PEP. It is much more feasible to vaccinate dogs than provide the costly post exposure treatment – $1.32 dollars vs one course of PEP at $153 dollars.  The CDC has helped support Vietnam in improving their rabies surveillance and coming up with new approaches to vaccinate their dogs and achieve the 70% canine vaccination goal.

The World Health Organization has been having meetings to discuss ways to eliminate rabies in Africa too. This past month, representatives from 24 countries in Africa met in Johannesburg to share information from a study they conducted regarding rabies.  The representatives pitched ideas for implementing the new recommendations for human rabies vaccines and how to improve surveillance dog vaccination campaigns. These meetings are exciting as they provide new insight for the global plan to achieve zero deaths from rabies.

Single countries like the Philippines, have proved to be great examples for national campaigns organized against rabies. The Philippines holds a nationwide World Rabies Day celebration as part of its educational outreach campaigns each year. The celebration has continued to grow yearly as more and more events are added to the agenda. It’s success emphasizes the importance of a program that is led and supported by their own national government and how the topic of rabies elimination is valued by the country’s leaders.

Overall, targeting the countries where rabies poses a significant risk and coming up with goals, campaigns and new tactics to eliminate rabies are substantial goals for the globe and many lives will be impacted by the CDC, the WHO and its many public health partners. But what can YOU do on a personal level that can also impact many lives? Here’s a quick checklist to follow:

  1. To start, you should always take your pet to the vet to get vaccinated for rabies regularly.
  2. Spaying or neutering your pet can also help with decreasing the amount of stray and potentially dangerous animals into your pet’s environment.  
  3. Always supervise your pet when they are outdoors. Wild high risk animals for rabies such as raccoons, coyotes or opossums can be in your backyard.
  4. Lastly, avoid contact with wild or unfamiliar animals (including dead animals). As tempting as it is to pet a stray cute kitten or dog, it is in your best interest to not feed or handle them.
  5. Continue sharing the message and saving lives!  Happy World Rabies Day!

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.