Introduction
Emerging diseases are health problems that appear in geographic areas for the first time, or present unknown or undifferentiated clinical manifestations until that moment. From SARS to Zika, through Flu A H1N1 and Ebola, they have been able to cause panic in the world. Originally located in Asian or African countries, many times using animals as reservoirs, these viruses have had the ability to mutate and become pathogens for man, with different levels of aggressiveness, the ability to generate serious outbreaks and the characteristic of affecting countries with economies Developing.
Re-emerging ones are infectious diseases discovered in recent years or those already known, considered controlled, in a frank decline or almost disappeared, which re-emerged after not constituting a health problem and often appear to be taking on epidemic proportions. Within this group we have dengue, digestive diseases caused by enterohemorrhagic Escherichia coli (O157H7) and Clostridium difficile, cholera, yellow fever, etc.
The health impact of these diseases, whether emerging or re-emerging, is enormous, both socially and fundamentally economic. Both for Health Systems and for the countries themselves and their scale of growth. There is a complex interaction of factors that favor its appearance, both biological, social and economic, determined by the continuous and global growth of populations and rapid and disorderly urbanization, marginal urban overpopulation, lack of drinking water and poor hygiene, deforestation. and climate change and even the use of antimicrobials in agriculture and animal production. This creates the favorable conditions for the spread of these diseases and facilitates the circulation of pathogens and the transmission of infections and epidemics among various social groups.countries and regions. The situation is aggravated by the inefficiencies of the public health systems, the result of insufficient epidemiological surveillance, inadequate primary care and deficient prevention mechanisms and inadequate controls, among others.
Zika, like Ebola, represent two cases of implantation in a new species, - in this case man - of an infectious agent from another species, overcoming the so-called species barrier, often accompanied by rapid evolution and adaptation to the new one. Guest. In 2014, the devastating Ebola epidemic in western coastal African cities in countries such as Sierra Leone, Liberia and Guinea demonstrates the spread of the virus from its previous location in sub-Saharan Africa and raises awareness of the pandemic potential of the emergence of viral infections that in a short time can transform the apparent global health balance. The same has happened with the Zika virus, discovered in 1947 in Rhesus monkeys of the deep African jungle,and reappeared in the 21st century with particular virulence and the still uncertified possibility of generating brain and cranial malformations in humans that would imply a kind of apocalypse for the evolution of the world population. Obviously, the origin of these diseases in poor countries puts rich countries on alert, and when the alarms sound, they begin to search for the saving vaccine, an interesting incentive for the pharmaceutical industry.
Meanwhile, another sanitary time bomb runs deeper underground, but not without putting humanity at risk. Many bacteria by natural selection develop and will develop mutations that will make them increasingly resistant to specific drugs. There will be a great disaster, a great epidemic, when antibiotic resistance becomes widespread. Also from Zika to bacterial resistance, the health risks remain extremely and unacceptably unequal. Health efforts often conflict with powerful actors, which may be national or international, who have different interests, such as national security and sovereignty, or economic objectives. Between the search and development of new vaccines and new antibiotics, the former are winning the game.How much danger is there in health risks and economic costs? It will be necessary to calculate it and act accordingly.
The most important thing will be that the tree does not cover the forest.
Abstract
Emerging diseases are health problems appearing in new geographic areas for the first time, or have unknown or undifferentiated clinical affairs. From SARS to Zika, passing through Influenza A H1N1 and Ebola, have been able to cause panic in the world. Originally located in Asian and African countries, often using as reservoir animals, these viruses have the ability to mutate and become pathogenic to man, with different levels of aggressiveness, ability to generate serious outbreaks and property to affect economic developing countries.
The re-emerging infectious diseases are discovered in recent years or yet considered controlled, in decline or almost disappeared, resurfaced; after not constitute a health problem, often gaining epidemic proportions. Within this group we have dengue fever, digestive diseases caused by enterohemorrhagic Escherichia coli (O157H7) and
The particularity of the outbreak in Brazil coincided with a fourfold increase in the number of newborns with the incidence of microcephaly and multifocal calcifications in the brain, a situation that led to suspicion of a possible viral interaction with the nervous system in children of mothers infected during pregnancy. In 2015, Zika virus RNA was detected in the amniotic fluid of two fetuses, an indication that it would have crossed the placenta and be the cause of vertical transmission of the disease.
Analyzing the phenomenon of Brazil in particular, in the first place a definitive cause-effect relationship has not yet been proven. While in 2014 there were only 150 cases of microcephaly in Brazil, in 2015 there were 3,893 cases reported as of December, a situation that led to the definition of an international red alert by the WHO. Although 75 percent have no evidence of the Zika virus and the rest appear to have very limited effects, the world was once again at low risk of a pandemic. Most of the reported cases of microcephaly in the northwest of the country would probably be negative for the virus and related to malnutrition and poverty. There is no similar background to the Polynesian outbreak. Not without a certain spectacularity and little seriousness,An Australian scientist went to the press to venture on a genetic mutation that seems to threaten unpredictable and permanent consequences to human DNA, with the potential to provoke a dramatic regression in the intellectual evolution of man. Is not this an estimate not only premature, but rather risky, when there still seems to be a piece of the puzzle missing?
The official epidemiological bulletin of the Brazilian Ministry of Health indicated that between mid-2015 and January 2016 a total of 4,783 suspected cases of microcephaly were reported, including newborns and deaths. Of these, a total of 2,975 suspected cases of microcephaly related to Zika virus infection were notified to the SVS / MS, which were registered in 658 municipalities, with a special incidence (55%) in two states of the northeast region (Paraiba and Pernambuco). This implied an important quantitative leap with respect to the historical average of cases. (Figure 2)
Of the suspects, 1103 completed clinical, laboratory, and imaging tests and 404 (36.2%) were confirmed as microcephaly. Among these, the Zika virus was detected in 17 newborns, including two fetal deaths. The remaining 709 cases were ruled out, while 3,670 microcephaly suspects remain under investigation, with only six effectively linked to the virus.
Distribution of microcephaly cases in Brazil as of January 2016
It is worth considering that in December 2015, the Brazilian Ministry of Health revised the case definition for suspected microcephaly in newborns, and reduced the criteria for measuring head circumference in full-term babies from 33 cm to less than equal to 32 cm. In these cases of measurement readjustment, there is always a trade off between specificity and sensitivity. Although there is evidence of an increase in the number of microcephaly cases in the Brazilian territory, the number of suspected cases was based on a selection test with very low specificity. She therefore overestimated them, starting with the inclusion of mostly normal children with small heads.A singular fact is that the distribution of the number of suspected cases - according to the Brazilian Public Health Association - shows that those affected are the poorest members of society, who live facing dramatic socio-economic and environmental circumstances.
In no other country in the world has this association been registered. Of 3,177 pregnant women infected by the virus in Colombia, malformations linked to Zika were detected in none of the fetuses. Neither has Mexico, another of the countries with a high number of cases. A link between microcephaly and the use of a larvicide called pyriproxyfen, designed to combat the proliferation of the Aedes Aegypti mosquito, has been argued, also in a highly controversial way. The same question refers to Guillain Barre Syndrome and its specific connection with the virus, for now unknown. Theoretically, it could also be possible that the virus is completely innocent, and that the real culprit is another factor that appears in the same period of time that the outbreak of the disease occurs.Or that it is permanently present even beyond the disease itself.
Agent and vector have been associated in a complex definition between two problems: health and economic. Aedes is unmasking countries characterized by huge inequalities, a fragile public health system and a disgraceful lack of basic sanitation, where less than half the population has access to safe water and sewers. And Zika has become a global emergency, assuming this supposed threat to the brains of children in the richest countries. Between 1950 and 1970, the Americas were practically a dengue-free zone, due to the eradication of Aedes Aegypti in a vector control campaign carried out throughout the entire continent.The combination of the interruption of the campaign in the early 1970s and the acceleration of uncontrolled urbanization with its associated waste management problems in many Latin American cities, plus globalization, climate change, deforestation, and the increased frequency and interconnection of Air travel contributed both to the return of Aedes and to the faster circulation of the dengue virus and its biological cousins.
The classical theory of health always spoke of the agent - vector - host - environment relationship for these diseases. Precisely, the current health problem is that from the health authorities the discourse has focused on the citizen and his neglect as a possible factor responsible for an epidemic, which has only been able to acquire such proportions because the authorities proved incapable of going beyond palliative measures. It is thought that it is possible to fight this mosquito only by urging the population to wear repellent, pants and a long-sleeved shirt. And blaming the neighbor who leaves a small pot of water in the back of his house, which is as irresponsible as relativizing that the campaign against dengue is usually spasmodic and coincides with the jump from outbreak to epidemic.It is overlooked that the biggest challenge was changing the structure of the social and environmental determinants that allow the mosquito to exist. And that is the battle that is lost beforehand.
Regarding economics, an article by Shepard & Col. published in the American Journal of Tropical Medicine and Hygiene in 2011 pointed out that dengue in the Americas produced - between 2000 and 2007 - an average annual economic cost of more than US $ 2 trillions. When disaggregating this calculation on an annual basis, and projecting it, the figures range from a minimum of US $ 900 million to a maximum that could exceed US $ 4 billion at the current time when the largest number of dengue cases is registered, but if Chikungunya and Zika, his first cousins, are added, a situation that occurs in the present. With variations between countries, it is considered that of this cost, the weight of outpatient care represents 72.9%. 60% corresponds to indirect costs, including among them the reduction of labor productivity,of domestic services, loss of schooling and increased need for home caregivers among non-fatal cases.
A similar study, developed in Singapore between 2000-2009 and calculated in constant 2010 currency, translated into an average economic impact of between US $ 850 million and US $ 1.15 billion, of which the cost of vector control constituted 42% to 59%.. Similarly, the use of empirically derived disability weights allowed calculating an average annual disease burden of 9 to 14 DALYs per 100,000 population, a figure comparable to that of Hepatitis B infection.
Bacterial resistance. The silent emerging epidemic
While the epidemic of dengue and its partners occurs, and is dramatically presented with great titles catastrophe declaring the WHO the world health emergency, another enemy, more silent but no less important and lethal for public health seems to be not perceived or observed in its entire dimension. At least this is what happens in the field of health policy and management and health economics. It is the increasing resistance to antimicrobial drugs and the cost that this implies and will imply in the future for health systems. Experts warn of the possibility of a return to the pre-antibiotic era. There is talk of the existence of more than 20,000 potentially resistant genes on about 400 different types of bacteria,although the number of determinants of functional resistance existing in microbes may be much lower. Under this concept, the definition of "antibiotic" as first proposed by Waksman - the discoverer of streptomycin - may have been oversized. It is simply the description of a use, a laboratory effect, or an activity of a chemical molecule. The term does not define a type of compound or its natural function, but only its application. It is any class of organic molecule that inhibits or kills microbes by specific interactions with bacterial targets, regardless of the source of the compound or its particular class.It is simply the description of a use, a laboratory effect, or an activity of a chemical molecule. The term does not define a type of compound or its natural function, but only its application. It is any class of organic molecule that inhibits or kills microbes by specific interactions with bacterial targets, regardless of the source of the compound or its particular class.It is simply the description of a use, a laboratory effect, or an activity of a chemical molecule. The term does not define a type of compound or its natural function, but only its application. It is any class of organic molecule that inhibits or kills microbes by specific interactions with bacterial targets, regardless of the source of the compound or its particular class.
However. The need for these valuable drugs has also had a significant drawback. In the nearly 80 years since the introduction of the first effective antimicrobials, such as sulfonamides, in 1937, billions of tons of new antibiotics have been produced and used for a wide variety of purposes. Also, improvements in their production and the expiration of patents have provided increasingly less expensive compounds, which encourage their over-the-counter sale and use without prescription. Perhaps the cost of many generics has been more reduced to the packaging than to the active substance itself. The truth is that the world has become saturated with these drugs, which of course contributed significantly to the emergence of resistant strains.
Between 2000 and 2010, the consumption of antibiotics increased by 36%. The countries that make up the so-called BRICS (Brazil, Russia, India, China and South Africa) accounted for 76% of this increase. 50% of antibiotic use is known to be statistically and clinically inappropriate. In particular, an increase in the consumption of carbapenems (45%) and polymyxins (13%) has been observed. In this way, the development of generations of antibiotic-resistant microbes and their subsequent distribution throughout the planet is nothing more than the result of years of pressure from the pharmaceutical industry for their use in both humans and animals, as well as inadequate prescription and self-consumption, which have led to its overuse and misuse. Many of the bacterial pathogens associated with old epidemics, such as tuberculosis,they have become multidrug-resistant forms after the discontinuation of antibiotics. This 18th century pathogen became the new threat of the 21st century for both the most industrialized and developing nations. Therapeutic options are being reduced, as well as the times of attention and hospitalization are extended, in addition to becoming more expensive given its high virulence and transmissibility.as well as the times of attention and hospitalization are extended in addition to becoming more expensive given its high virulence and transmissibility.as well as the times of attention and hospitalization are extended in addition to becoming more expensive given its high virulence and transmissibility.
The term "superbugs" or superbugs refers to microbes with a higher generation of morbidity and mortality due to multiple mutations and high levels of resistance to antibiotics. This situation is not part of a natural but an artificial process, superimposed on the biological nature of the disease itself. Currently, two of the most notorious superbugs are Clostridium difficile and methicillin-resistant Staphylococcus aureus. The latter has become the main emergent of the intrahospital infection, moving out of the hospital to become one of the main pathogens in the community with the greatest virulence.
The World Health Organization itself estimates that humanity could be left unprotected against the onslaught of numerous diseases that are the result of the progressive resistance that bacteria develop against antibiotics. A study by Taylor & col, requested by RAND Europe at the request of the Independent Review of Antimicrobial Resistance estimates that if drastic actions are not considered, the increase in antibiotic-resistant infections could lead to a projection of 10 million deaths per year by 2050 and losses in economic production in the order of US $ 100 billion. Specifically, the reduction in population and the impact on morbidity would lead to an average reduction in the level of the world Gross Domestic Product of between 0.06% and 3.1%, ranging from 2,3% in the most developed countries to 10% in Sub-Saharan Africa, if there were a scenario of absolute resistance. Given that these GDP losses are annual, attentive to the time elapsed, the accumulated loss would range from US $ 2.1 billion to US $ 124.5 billion.
Given that the health and economic dangers of antimicrobial resistance are widely recognized, and perhaps greater than those of emerging viral epidemics, the question is why was not done or is more being done? One reason may be that antibiotic resistance has been skewed by evidence-based policies, which prioritize health problems because of economic burden. And perhaps from Health Economics the studies have not been so demonstrative in relation to the fact that resistance to antibiotics costs enough to be a health priority, when it is already a health priority. Or what to analyze the cost of resistance and what is the cost-effectiveness of interventions to reduce it,the conclusion is that the evidence regarding cost-effectiveness of the interventions was not significant. The other is that there are no new classes of antibiotics that have hit the market in the last 25 years.
The role of BigPharma and health dilemmas. Between interests, vaccines and antibiotics .
Something particular has happened at the beginning of this year. More than 80 Big Pharma and eight associations representing the pharmaceutical industry have asked the governments participating in the last Economic Forum in Davos, Switzerland, to work together in the fight against 'superbugs'. This is simply to deal in a peremptory and effective manner with infections resistant to a multitude of drugs that circulate in the world pharmaceutical market, given that in a few decades tens of millions of people around the world could “die” if they are not found. effective antibiotics to combat them.
The constant interaction between microorganisms and antibiotics allowed the progressive development of evasion mechanisms, which did not allow the efficient action of the latter. Such resistance mechanisms are encoded by genes that are transmitted from parent strains to their progeny (vertical transmission) and also between bacterial species.
(horizontal transmission). This sequence of events has favored infectious diseases to emerge as a dramatic factor in morbidity and mortality throughout the world. Precisely, the large pharmaceutical companies have highlighted the need for greater coordination among themselves and with the different countries, to significantly reduce the “unnecessary” use of antibiotics through strategies such as avoiding inappropriate prescribing and unnecessary self-medication. Or modify the prices of drugs to discourage their free consumption. This statement comes at a time when risk signals from increasing resistance to antibiotics are increasing, and shortly after China has warned that the gene called 'mcr-1' is what causes bacteria to be showing resistance to every known antibiotic.
What killed in the mid-twentieth century and was easily solved with an injection or a pill, today requires more and more powerful and scarce medicines. Bacterial resistance is thus a growing phenomenon, characterized by a partial or total refractoriness of the microorganisms to the effect of the drug, generated multifactorially. The problem is that it can affect any person, of any age or country in which they live with much greater severity than the diseases that today have put the world on alert, such as the now classic dengue, Zika and Chikungunya.
If epidemiology and health statistics are analyzed over time, the most dangerous emerging disease today seems to be resistance to antibacterial drugs in the “post-antibiotic era”, given the greater complexity assumed by infections caused by bacteria before. less offensive. In the same way, emerging health and economic circumstances arise from having to bear this cost and at the same time promote greater R&D in said therapeutic band, to have more effective alternatives. From the health systems, this phenomenon has enormous health, but also social and economic implications, given the increase in morbidity and mortality, the weight of the costs of new treatments, the long stays in Critical Units and the association with chronic diseases that weaken the immune system.It is a progressive problem, capable of worsening if quick action is not taken. In countries where antibiotics are available without a prescription, the emergence and spread of drug resistance has made matters worse. Similarly, in countries that lack protocols, professionals tend to prescribe them - and the general population to consume them - in excess.
The problem is that battles begin to be lost before finding more effective weapons, but the position of the pharmaceutical industry is not innocent. For many years, business strategies aimed at finding more profitable drugs, which were located in the band of chronic or high-cost diseases, were privileged, assigning low priority to R&D in antibiotics, or directly eliminating it. Added to this was some difficulty in demonstrating significant differences in effectiveness and safety for new developments, and in discovering more potent alternatives for more resistant bacteria. This led to a marked slowdown in the rate of development of new antimicrobials, and few patents were approved. Taking advantage of the low social and health pressure to have more effective antibiotics,pharmaceutical companies used their funds to research and develop highly profitable drugs in other fields, such as orphans or oncology. There are economic studies that show this. While one patient requires a week of antibiotics for an acute infection, another with a chronic disease requires a minimum year of treatment, for which it is estimated that 52 patients from the first group would be necessary to obtain a financial return similar to that produced by just one from the first group. group.another with a chronic disease requires a minimum year of treatment, for which it is estimated that 52 patients from the first group would be necessary to obtain a financial return similar to that produced by only one from the first group.another with a chronic disease requires a minimum year of treatment, for which it is estimated that 52 patients from the first group would be necessary to obtain a financial return similar to that produced by only one from the first group.
The top six Big Pharma with market capitalization (Pfizer, Johnson & Johnson, Merck, Roche, Glaxo Smith & Klein and Novartis) are the ones that appear signing the particular Davos call for class action. What is the cause of your attitude? First of all, as of 2007 more than 70% of bacteria were already resistant to at least one of the drugs on the market. And infections caused by multi-resistant bacteria had become one of the three leading causes of death in the United States, with a 58% increase in the number of deaths. The consequences in infected patients became relevant, not only in health but also in economic terms. It is estimated that the United States spends US $ 4 billion on hospital infections. And that resistance increases the risk of inappropriate therapy,which, while prolonging the infection, facilitates the transmission of the microorganism to other patients, generating a chain effect. Furthermore, hospital micro-epidemics generated by resistant bacteria cause a doubling of mortality, more significant in patients under conditions of immunosuppression or with underlying diseases, as a consequence of the longer hospital stay and its complications. In the European Union alone, bacterial resistance causes 25,000 deaths annually at a cost of US $ 1.5 billion between health spending and productivity losses.more significant in patients under conditions of immunosuppression or with underlying diseases, as a consequence of the longer hospital stay and its complications. In the European Union alone, bacterial resistance causes 25,000 deaths annually at a cost of US $ 1.5 billion between health spending and productivity losses.more significant in patients under conditions of immunosuppression or with underlying diseases, as a consequence of the longer hospital stay and its complications. In the European Union alone, bacterial resistance causes 25,000 deaths annually at a cost of US $ 1.5 billion between health spending and productivity losses.
Second, and paradoxically. During the 2008-2013 period, less than 1% of research funds in the UK and the rest of Europe - mostly in the hands of Big Pharma - were allocated to antibacterial research projects. A 2004 study showed that out of 500 new molecules in development, only five were antibiotics. The FDA also admitted that from 1998 to 2003, only nine different antibiotics or therapeutic applications of existing drugs had been approved, and only six were in Phase II or III of a clinical trial. Of the nine patents mentioned, four were innovations possessing a different mechanism of action, or with a different chemical structure than those existing on the market, In parallel, more than 300 other molecules,mainly for chronic pathologies, they were completing identical trial phases. Of the leading companies, Pfizer owned just three of the antimicrobial patents, of which only two included a new mechanism of action. Meanwhile, the third was a therapeutic reformulation of azithromycin. Merck, Bristol Myers, and SanofiAventis did not register any new patented antibiotics until 2004, when the latter developed t elithromycin.in which the latter developed t elithromycin.in which the latter developed t elithromycin.
In general, pharmaceutical companies' commercial strategy for an antibiotic was based on finding a new therapeutic effect for an already patented drug. Precisely, one of the keys to why new antibiotics do not appear lies in the business model of the industry. Any new molecule for innovative cardiovascular use is capable of generating a billion dollars annually in sales profit. But if it were a new highly effective antibiotic, it would be reserved for more serious patients, or cases that do not respond to the available antibiotics. And this would generate sales in small quantities. To improve profitability and be competitive, it would be necessary to set it, for example, a very high price. In other words, it would not be a great business, nor would it justify an investment in R&D that involves too much time and money.For this reason, antibiotics, today, are no longer in the pipeline of the pharmaceutical industry. Furthermore, the market prospects appear extraordinarily limited for searching for innovative antimicrobial molecules. On the other hand, there are risks inherent in the development of new molecules. In the case of telithromycin, developed by the French company Sanofi –Aventis, which received FDA approval for marketing in 2004, its efficacy was no greater than that of existing drugs on the market. Two years later, its safety was seriously affected and it had to be withdrawn from the market for causing severe liver damage and even death. Another drug such as the oral beta-lactam faropenen medoxomil or faropenen daloxate, which was initially disapproved by the FDA in 2006,required by this new studies and trials to approve all its applications. The change in approval strategy incorporated by the regulator revealed a decision to demonstrate greater rigor regarding superiority over existing drugs. The laboratories linked to the production of this drug estimated a minimum time of two years to complete them. Two of the indications required more advanced studies. This shows that although the definition of comparative relative superiority is an indicator of the greater usefulness of the product, the decisions of the regulators generate less interest in the laboratories in investigating respect for a certain therapeutic band.The change in approval strategy incorporated by the regulator revealed a decision to demonstrate greater rigor regarding superiority over existing drugs. The laboratories linked to the production of this drug estimated a minimum time of two years to complete them. Two of the indications required more advanced studies. This shows that although the definition of comparative relative superiority is an indicator of the greater usefulness of the product, the decisions of the regulators generate less interest in the laboratories in investigating respect for a certain therapeutic band.The change in approval strategy incorporated by the regulator revealed a decision to demonstrate greater rigor regarding superiority over existing drugs. The laboratories linked to the production of this drug estimated a minimum time of two years to complete them. Two of the indications required more advanced studies. This shows that although the definition of comparative relative superiority is an indicator of the greater usefulness of the product, the decisions of the regulators generate less interest in the laboratories in investigating respect for a certain therapeutic band.The laboratories linked to the production of this drug estimated a minimum time of two years to complete them. Two of the indications required more advanced studies. This shows that although the definition of comparative relative superiority is an indicator of the greater usefulness of the product, the decisions of the regulators generate less interest in the laboratories in investigating respect for a certain therapeutic band.The laboratories linked to the production of this drug estimated a minimum time of two years to complete them. Two of the indications required more advanced studies. This shows that although the definition of comparative relative superiority is an indicator of the greater usefulness of the product, the decisions of the regulators generate less interest in the laboratories in investigating respect for a certain therapeutic band.
At the same time, between 2001 and 2014, eight first-line molecules fell into the "patent abyss", such as ceftriazone, amoxicillin + clavulanic, cefepime, clarithromycin, piperacillin + tazobactan, levofloxacin, moxifloxacin and linezolid, which were quickly replaced by generics (Figure 3)
Patent expiration in time
In this way, the golden age of antibiotics seemed to be reaching its twilight. Companies' marketshare for such a therapeutic band was frankly low, and the industry in general seemed to have lost interest in researching drugs that were not of significant benefit until the sudden Davos declaration appeared.
Faced with the new emerging epidemics, very symptomatic but not therapeutically profitable, the industry reacted quickly by looking for a vaccine, and people and health organizations were demanding it. Both the crisis generated by the deadly Ebola outbreak, and now the epidemic caused by the dengue and Zika arboviruses, have highlighted the concern of developed countries to prevent the spread of such diseases, given the economic impact they would bring. And with this the need for governments to expand the economic resources destined to combat - by way of vaccines - these new Horsemen of the Apocalypse, instead of seriously investing in reducing the weight of social and environmental determinants. The same does not happen with microbial resistance,which seems to be a battle more confined to hospitals and therefore to the Health System, but of significant severity. Hence the different behavior of pharmaceutical companies.
This same situation is mirrored in the pharmaceutical industry. The British GlaxoSmithKline, listed on the NY Stock Exchange and the sixth largest sector company in the world, was the first to present itself in 2015 as a developer of the Ebola vaccine, after the cases that occurred in South West Africa and the few imported to Europe. In a very short time, 24,000 doses were available to carry out efficacy trials in the field, but did not file a single patent for a new antibiotic between 1998 and 2005. Something similar happened with the French laboratory Sanofi Pasteur, first in sales in Europe and third at the level worldwide and also a member of the NY Stock Exchange. It developed rapidly the Dengue vaccine in 2015, but it did not carry out any R&D of antibiotics in a similar period.And it has already announced the start of the development phases of its vaccine against the Zika virus, since both are closely related because they belong to the same Flavivirus genu, spread by the same species of mosquitoes and have a similar acute clinical presentation.
Conclusions
Coincidence or causality, this is the state of affairs of the diseases that are today a global cover story - such as Zika - just as Ebola was at the time. And also that of the increasingly significant bacterial resistance and the passive attitude of world pharmaceutical companies towards the issue until the Davos summit. The new 2014 report edited by the World Health Organization (WHO) - the first of a global nature regarding the advance of antimicrobial resistance, in particular antibiotics - reveals that this threat, of singular gravity, is no longer a forecast for the future. This is a reality that can affect anyone of any age in any country, beyond the benefits or defects of the Health System that provides coverage.It also points out that resistance to carbapenemic antibiotics, the last resort for life-threatening Klebsiella pneumoniae (a common intestinal bacteria), has spread to all regions of the world. And that people infected with methicillin-resistant Staphylococcus aureus have a 64% greater chance of dying than those infected by non-resistant strains. In Africa and Latin America, between 80 and 90% of infections by this bacterium are already manifestly resistant,And that people infected with methicillin-resistant Staphylococcus aureus have a 64% greater chance of dying than those infected by non-resistant strains. In Africa and Latin America, between 80 and 90% of infections by this bacterium are already manifestly resistant,And that people infected with methicillin-resistant Staphylococcus aureus have a 64% greater chance of dying than those infected by non-resistant strains. In Africa and Latin America, between 80 and 90% of infections by this bacterium are already manifestly resistant, Already in 2001, more than a decade ago, the WHO had anticipated the issue by trying to establish a global strategy, which among other points advised promoting cooperation between the pharmaceutical industry, government entities and academic institutions to research new drugs and vaccines, as well as stimulating drug development programs that seek to optimize therapeutic regimens in terms of their safety, efficacy, and risk of selection for resistant organisms. It also proposed establishing incentives for the industry to invest in research and development of new antibiotics,study the establishment or application of accelerated authorization procedures to market them and even grant patents exclusivity for a specified period of time on new formulas and indications for the use of antimicrobials. In the middle appeared the Flu A H1N1 first, then Ebola and now Zika, and the alarms sounded in another direction, towards the search for vaccines thinking about cataclysmic global epidemics. Did nothing of what was required by the WHO document happen, or did the WHO insist on the issue during the almost thirteen years leading up to the new report? Time has passed, and pharmaceutical companies continued to put profit before necessity.and the alarms sounded in another direction, towards the search for vaccines thinking of cataclysmic global epidemics. Did nothing of what was required by the WHO document happen, or did the WHO insist on the issue during the almost thirteen years leading up to the new report? Time has passed, and pharmaceutical companies continued to put profit before necessity.and the alarms sounded in another direction, towards the search for vaccines thinking of cataclysmic global epidemics. Did nothing of what was required by the WHO document happen, or did the WHO insist on the issue during the almost thirteen years leading up to the new report? Time has passed, and pharmaceutical companies continued to put profit before necessity.
Although there are some new antibiotics in development today, none of them may be fully effective in the future against the most dangerous forms of some particularly resistant bacteria. Nor is it easy to determine, in traditional trials carried out against placebo, if a new drug is better (and if possible much better) than those already present in the therapeutic market as requested by the FDA. The industry echoes that the consideration of comparative effectiveness is a regulatory requirement that is detrimental to innovation. But the truth is that any new drug should be approved only if it is at least equivalent to an existing alternative, or provides at least a marginal benefit. This is not the case with vaccines, whose effectiveness must be identical.Hence the difference with respect to the opportunities in the healthcare market.
The other question lies in the link between the causes and effects of emerging and re-emerging companies, beyond the issue of large pharmaceutical companies. And the costs, not of patient care, but of neglecting the determinants. In the case of Ebola, Zika and whatever may come in the future, improving health systems, making them reliable, and developing missing community infrastructure undoubtedly has important collateral health effects. Over the four decades until the 2014 epidemic, the Ebola deaths in sub-Saharan Africa were less than 3,000. Meanwhile, 547,322 deaths from diarrhea in 2010 and 222,767 from pneumococcal pneumonia. Many of these deaths could have been prevented by access to clean water and sanitation,beyond vaccines available to governments.
In 2014, the same Ebola epidemic claimed more than 11,000 victims as a result of the same prevention failure. But since the outbreak now occurred in West Africa, the inhabitants of Europe and North America were theoretically more exposed to a possible spread of the virus. Even when the hypothesis was relative and its level of social and health development incomparably higher, the need for a vaccine and its health and economic benefits to protect the richest nations outweighed costs, trials and even patent rights methodology.
Meanwhile, bacterial resistance diseases are still imagined reduced to their confinement in hospitals, or limited to other minor scales of appearance, ignoring their epidemiological weight and increasing costs. Today they constitute an important cause of morbidity and mortality, as well as constitute a significant economic and social burden for the patient, his family and the health system. A study carried out in two healthcare settings in Buenos Aires, Argentina, in 2001 on 173 cases - among catheter sepsis, pneumonia and urinary infection - showed that the indicator that accumulated the highest costs was the day / bed, followed by the cost of the antibiotics administered and in third place with very low incidence the cost of crops. The weight of the day / bed represents 89.7% of the additional cost in the case of catheter sepsis, 85,9% for pneumonia and 92% for urinary infection. Meanwhile, the costs of specific drugs constituted only 7 to 14% of the total cost.
The truth is that resistant Enterobacteriaceae are now advancing in urbanized metropolitan areas, outside of health care settings, presenting rising levels and about to spread to the community as is the case in the United States. About 9% of those affected by these agents died from their infection, generally from sepsis or severe pneumonia. And an increasing incidence of kidney infection by E.coli is observed in the community, without there being an adequate oral antimicrobial therapy for its treatment. In the same way, the resistance acquired by the opportunistic bacteria Clostridium difficile is capable of causing potentially lethal diarrhea in people previously subjected to potent antibiotic therapy.
All this seems to correspond to the fourth Horseman of the Apocalypse, whose threat is nothing more than the result of the negative externality that we have generated. The defect of not improving the social and health determinants associated with poverty has been a source of mutation of many viruses, which passed from animals to man. And its greater virulence has led to epidemics in developing countries and potential threats to rich countries. Also an excess in the use of antibiotics in the field of human health as in animal health has promoted bacterial resistance as well as contributed to weaken the human body's own response. Both issues hurt us. If there were less deteriorated health systems, effective policies to reduce poverty and marginalization, and basic investment in sanitation,we would have positive externalities. The same if the antibiotics worked effectively and their use was based on a precise indication. The problem is that a particular combination of poorly applied policy and technique in public health and medical care has made it possible to enhance negative externalities that cost money and lives, and to relativize positive ones. Just as the expansion of emerging viral diseases shows the loss of some key battles, bacteria have also won part of the game. In this curious imbalance today is the paradox between Zika and diseases caused by resistant bacteria.The problem is that a particular combination of poorly applied policy and technique in public health and medical care has made it possible to enhance negative externalities that cost money and lives, and to relativize positive ones. Just as the expansion of emerging viral diseases shows the loss of some key battles, bacteria have also won part of the game. In this curious imbalance today is the paradox between Zika and diseases caused by resistant bacteria.The problem is that a particular combination of poorly applied policy and technique in public health and medical care has made it possible to enhance negative externalities that cost money and lives, and to relativize positive ones. Just as the expansion of emerging viral diseases shows the loss of some key battles, bacteria have also won part of the game. In this curious imbalance today is the paradox between Zika and diseases caused by resistant bacteria.In this curious imbalance today is the paradox between Zika and diseases caused by resistant bacteria.In this curious imbalance today is the paradox between Zika and diseases caused by resistant bacteria.
As Gervas well says, “Antibiotic resistance is an example of a negative externality: the social marginal cost is higher than the private marginal cost. The cost is monetary, but also in morbidity and mortality, which many times suffer from people other than those unnecessarily treated with antibiotics ”. It will be important to regain at least a balance and find new ways to maintain it to avoid either panic of the unknown or indolence in the face of the known. It is about evaluating the costs and risks between doing and not doing. Perhaps unintentionally, as part of a kind of sanitary determinism, we have ended up discussing the eternal border between risks and benefits.
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