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.

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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.

Dengvaxia’s FDA Priority Review: Is the global health community settling on a Dengue vaccine?

The Food and Drug Administration (FDA) announced on October 30th that Dengvaxia’s, Sanofi Pasteur’s dengue vaccine, file has been accepted for priority review within the regulatory agency. With this announcement, the FDA will ensure that a decision will be declared on approval in the United States within six months for the world’s first licensed vaccine protecting against this flavivirus. While this declaration by the FDA displays an improved pragmatic approach to addressing neglected tropical diseases (NTDs), this vaccine has created controversy throughout the global health community. This vaccine is licensed in twenty countries to date and implemented into country wide vaccination programs. However, the concerns accompanying this recombinant, live, attenuated, tetravalent dengue vaccination have led to a discontinuation of this technology with a loss of confidence in several nation states. The Philippines, the first country to complement their vaccination program with this vaccine, has even instructed Sanofi to reimburse the $70 million the country spent to vaccinate 830,000 children. This has caused many global health experts to doubt the impact this vaccine can have throughout the world – causing many to wonder if the global health community is settling on a dengue vaccine.

The dengue virus is estimated to cause 400 million infections each year spanning each of the World Health Organization’s (WHO) regions. This arbovirus belongs to Flaviviridae family and is spread to humans through the bite of an infected female Aedes aegypti mosquito and to a lesser extent from the Aedes albopictus species. The dengue virus has four unique serotypes, DEN-1, DEN-2, DEN-3, and DEN-4, which has caused an effective vaccine to be eluded for centuries. When a person is infected with one certain serotype, the person gains life-long immunity to that serotype. However, if that person contracts a different serotype, it increases the risk of the person developing severe dengue. This phenomenon is called antibody-dependent enhancement (ADE) which allows the different serotype to enter cells more efficiently due to the previously created antibodies from the initial serotype. The symptoms that dengue causes depend on primary or secondary infection. Primary infection results in an acute febrile illness that is typically cleared by the immune system within seven days, while secondary infection can lead to dengue hemorrhagic fever or dengue shock syndrome causing serious morbidity and mortality. The dengue virus currently has no approved treatments – highlighting the importance of an effective and safe vaccine for children and adults alike.  

The significant setbacks for Dengvaxia first arose when Sanofi Pasteur released interim studies concerning children aged 2 to 16 receiving the vaccine who were seronegative. This information was released on November 29, 2017 and revealed that among dengue-seronegative participants, recipients had increased rates of hospitalization for virologically confirmed dengue (VCD) and severe VCD in the vaccine group than in the group not administered the vaccine. These risks were significantly elevated in patients who were aged 2 to 8 years of age and became evident earlier than those aged 9 to 16 years of age. When this data became available, it led to the Strategic Advisory Group of Experts on Immunization (SAGE) of the WHO to reconvene and update their guidance on Dengvaxia. On April 18, 2018, SAGE recommended that for countries considering implementing Dengvaxia, every individual should be screened to determine their serological status with only seropositive persons receiving the vaccine.

The flavivirus genus includes other NTDs including the Zika virus, Japanese Encephalitis, West Nile Fever and Yellow Fever in addition to the Dengue Virus. The symptoms of each these ailments can present almost identically, especially in their milder forms, seeming almost flu-like in nature. When considering these identical disease presentations and the WHO’s recommendation to prescreen individuals for Dengvaxia, health care professionals must turn to dengue serological testing to ensure best practice – if the vaccine is accidentally given to a person with, for example, the Zika virus with no previous case of dengue due to a misdiagnosis from medical history, this would increase the risk of morbidity and mortality if dengue was contracted subsequently. The gold standard for serological testing is isolation and characterization of the virus, like PCR; however, this typically takes six or more days to receive the results and can be burdensome with it’s cost on a public health care system. A more common approach is enzyme immunoassay (ELISA) which is cost effective and less time consuming. However, in areas where two or more of the aforementioned flaviviruses exist, there is IgG cross reactivity between the viruses causing false positives for the dengue virus when ELISA is used. This often rules out the use of ELISA due to a common vector, Aedes aegypti, being able to spread two or more of these viruses within the same zone. Since the dengue virus is endemic throughout the developing world, dedicated health care professionals in these areas often don’t have funds, technology, or training in order to utilize the gold standard, PCR, in dengue testing — further highlighting the health disparities that exist on this earth. This leaves a major barrier to giving proper care to a large portion of humanity including administering this vaccine safely.

With the addition of rapid, accurate dengue test for the serological status of individuals that is in the pipelines (although no estimate of how soon it will be developed has been released yet), this vaccine will certainly find its niche in the global health society. However, this niche will exclude an enormous percentage of humans that would benefit from a safe and effective dengue vaccine. Those individuals that are currently seronegative and those who don’t have access to well-funded public health care system will continue to be at risk for developing the fatal consequences of the dengue virus. Global health leaders need to continue to promote and demand a vaccine that will ensure protection for a greater majority of people. Although this vaccine will serve some well, health care professionals must not settle until the dengue virus and each neglected tropical disease is properly addressed.

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.

 

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.