Tuesday, April 24, 2012

RUM 4: Dealing with Drug-Resistant Diseases

Cases of illness that are drug-resistant are a growing problem worldwide. That's because diseases -- like people, animals, insects, bacteria, plants, trees, all other living matter and organisms -- are evolving and mutating. The appearance of "superbugs" or the killer diseases that do not respond even to the strongest medicines was also noted by some sectors recently.

Do we need more government presence -- via the WHO, other foreign aid, DOH, local governments, other government agencies -- in dealing with this problem?

I have an ambivalent position on this issue. That's because I recognize that there is room for government assistance and intervention in dealing with infectious and communicable diseases, as well as pediatric diseases. But I also insist that better personal care, more personal responsibility in preventing the spread of those infectious diseases -- like washing hands more often, covering the mouth when coughing, eating healthy diet, drinking lots of water, having sufficient rest and sleep, observing rational use of medicines (RUM),  etc. -- is also important.

I am posting four articles by Reiner Gloor, the Executive Director of the Pharmaceutical and Healthcare Association of the Philippines (PHAP, http://phap.org.ph/) about this subject. These papers were posted in his weekly column in BusinessWorld (http://www.bworldonline.com/) on days indicator. He is more knowledgeable about this subject than me because they know what are those old and new or emerging diseases, as well as the existing supply of medicines, both innovator and generics, in dealing with this problem. These four papers are:

1. The fight vs. drug-resistant diseases, March 23, 2012
2. Appreciating antibiotics, April 15, 2011
3. Global action vs. AMR, April 08, 2011
4. World Health Day and drug resistance, April 01, 2011.

A bit long, enjoy reading.

(1) The fight vs drug-resistant diseases

Reiner W. Gloor
March 23, 2012


Often driven by economics and politics, humans have always been on the move. The International Organization for Migration reported that there were about 214 million global migrants in 2010 and their number could reach 405 million by year 2050.

But aside from people, drug-resistant pathogens are also constantly on the move. In her address at the conference on combating anti-microbial resistance (AMR): time for action in Copenhagen last week, World Health Organization (WHO) Director-General Margaret Chan reminded us that these pathogens are “notorious globe-trotters”.

The WHO chief said that drug-resistant microorganisms travel well in infected air passengers and through global trade in food.

And instead of providing cure for patients, some hospitals have also become hotbeds for highly resistant pathogens. Chan noted that the growth of medical tourism has expedited the international spread of hospital-acquired infections that are frequently resistant to multiple drugs.

Apart from increased mortality and substantial financial burden, AMR has consequences far beyond the patient, their families and the health sector. AMR can also leave a damaging aftermath on international travel and trade resulting from the cross-border spread of drug-resistant infections.

Almost a year after the World Health Day on AMR, we are being reminded that AMR may not be a recent phenomenon but it remains a critical public health concern today. Early this month, the WHO released a document that outlines further areas of action to fight AMR.

AMR, which is the natural process of adaptation by microorganisms, only means that the life span of antibiotics is limited. This ability of pathogens to survive is also threatening pubic health gains with the growing incidences of drug resistance for major infectious killers as well as the so-called “superbugs” that do not respond to the strongest, “last line of defense” medications.

In the case of malaria, the newly released WHO publication “The evolving threat of antimicrobial resistance: Options for action” reported that resistance to antimalarial medicines has been documented for all classes of antimalarials, including the artemisinin derivatives.

With this, changes in the national antimalarial treatment policy have been necessary in many countries due to the emergence of chloroquine resistance, which has become so widespread that a combination of medicines including artemisinin (artemisinin-based combination therapy) is now the recommended first-line treatment for uncomplicated Plasmodium falciparum malaria. P. falciparum is one of the most common types of malaria and is also the most deadly.

Resistance is also a growing problem in the treatment of tuberculosis.

The WHO estimates that 650,000 out of the 12 million cases of tuberculosis in 2010 involved multi-drug resistant TB strains. Despite the best of care, only about 50% of the patients will be cured even after a long, complicated and expensive treatment.

As for HIV/AIDS, the WHO publication indicated that resistance rates to anti-HIV drug regimens range from 10% to 20% in Europe and the United States while drug-resistant infections appear to be low in lower- and middle-income countries.

If current trends on AMR continue, some acknowledged that we may be headed towards a post-antibiotic era where a common strep throat or scratched knee could once again kill.

Modern interventions such as hip replacements, organ transplants, cancer chemotherapy, and care of preterm infants, would become more complex, dangerous and even impossible to undertake. In the absence of first-line antimicrobials, replacement treatments become more costly and may even require treatment in intensive care units.

Chan, however, noted that in terms of discovery of new replacement antibiotics, the pipeline is virtually dry, and “the cupboard is nearly bare.”

The WHO head explained that the pharmaceutical industry lacks incentives to bring new antimicrobials to market for many reasons, some of which fall on the shoulders of the medical and public health professions. Specifically, our inability to combat the gross misuse of antibiotics.

The WHO has once more urged the health care community as well as the patients to do their share in curbing the rise of AMR. Specifically, health care professionals must prescribe antibiotics appropriately and only when needed. As for the patients, we must follow treatment correctly. Stakeholders are also called on to address the problem of substandard and counterfeit medicines.

At a time of multiple calamities in the world, the Copenhagen conference stressed that we cannot allow the loss of essential antimicrobials and essential cures for many millions of people, to become the next global crisis.

(2) Appreciating antibiotics

Reiner W. Gloor
April 15, 2011

The message of the World Health Day 2011 is clear. The world is on the brink of losing its arsenal of essential medicines. If we do not take action today, health experts agree that there will be no more cure tomorrow.

The global consequences of drug resistance are also clear. No less than World Health Organization (WHO) Director General Margaret Chan said that the world is heading towards a post-antibiotic area, where many common infections will no longer have a cure and once again, instantly claim the lives of several thousands of people as diseases did before.

We attribute this threat to the rise of anti-microbial resistance (AMR), a natural biological process that allows microorganisms to adapt, mutate and survive for billions of years since creation.

The WHO pointed out that this microbial resistance is accelerated by human practices, behaviors and policy failures.

While the pharmaceutical industry has renewed its commitment to the research and development of antimicrobials, the phase by which AMR is growing has overtaken the long, extensive and expensive drug discovery process. The pharmaceutical R&D (research and development) process necessary to produce a single drug could take an average of 12 years and investments up to $1.7 billion.

As we research for cures, a superbug called New Delhimetallobeta-lactamase (NDM-1) is spreading quickly, posing a global health threat as it defies geographical borders. The Lancet has recently reported that NDM-1, an enzyme that destroys a last-defense group of antibiotics called carbapanems, is now widespread in sewage and drinking water outside the hospital environment in Delhi, India.

While the superbugs are extreme expressions of drug resistance, health experts have been discovering traces of AMR in major infectious killers such as HIV/AIDS, tuberculosis and malaria.

WHO Country Representative Dr. Soe Nyunt-U cautioned that apart from the said diseases, there have already been increasing infections of multidrug-resistant E. coli causing diarrhea, K. pneumoniae causing pneumonia and sepsis and Neisseria gonorrhoeae for sexually transmitted diseases and Shigella causing gastrointestinal infections.

On April 7, the WHO unveiled a six-point strategy package in an effort to delay AMR. The government, through Department of Health Secretary Enrique Ona, committed to the full implementation of the strategy package in the Philippines.

GlaxoSmithKline medical director Dr. Joven Tanchuco representing the Pharmaceutical and Healthcare Association of the Philippines during the World Health Day celebration announced that the industry is ready to take action.

Apart from the renewed commitment to develop new medicines and vaccines, he also addressed the issue of inappropriate and irrational use of antimicrobials. The pharmaceutical strategy involves the ethical promotion of antimicrobials to ensure the independence of health care professionals when prescribing medicines to patients.

The responsibility to turn the situation around also largely depends on the health care professionals and the patients. A change in their behaviors will be crucial if we were to achieve significant strides in the campaign against AMR.

The Centers for Disease Control and Prevention added that a patient must not share or use leftover antibiotics. To avoid this, a patient must strive not to save antibiotics for the next illness and discard any leftover medication once the prescribed course of treatment is completed. Finally, many infectious diseases could be prevented with good hygiene and getting recommended vaccines.

(3) Global action versus anti-microbial resistance

Reiner W. Gloor
April 8, 2011

Discovering a new drug is a long and difficult task. Out of the thousands of candidate compounds, some will reach the various stages of clinical trials but only one will get approved after several years of extensive and expensive research and development (R&D) process.

The R&D process is even made more complex when microorganisms such as bacteria, viruses, fungi and parasites fight back in an attempt to protect themselves when under attack. For billions of years, microorganisms have naturally found their way to survive and now, develop resistance to modern and sophisticated life-saving antimicrobial.

This ability of microorganisms to naturally survive is threatening public health with the growing incidences of drug resistance for major infectious killers such as HIV/AIDS, tuberculosis and malaria.

Strategic and concerted efforts have become more urgent than ever to curb the rise of AMR which is rendering many last defense medicines ineffective against infections to include the so-called "superbugs."

In a serious effort to avert the development of drug resistance, the World Health Organization (WHO) chose the theme "Anti-microbial resistance (AMR): no action today, no cure tomorrow" for the World Health Day 2011 on April 7.

The World Health Day theme is a fitting topic for a society that depends on antimicrobials but whose arsenal of modern medicines is now placed on the brink of extinction due to drug resistance. The troubling news is that the Philippines is not at all exempted.

WHO Country Representative Dr. Soe Nyunt-U expressed concerns over the occurrences of AMR that threaten the country’s gains in the treatment and control of HIV/AIDS, malaria and tuberculosis.
Dr. Soe shared that infections acquired in hospital settings similarly put infants at high risk of developing neonatal sepsis, a bacterial infection that affects babies younger than 90 days.

Two years ago, more than 20 newborn babies died needlessly due to neonatal sepsis in one hospital alone. As the highlight of the World Health Day, Dr. Soe revealed the six-point policy package which will serve as the global plan of action against AMR.

The first strategy as outlined in the WHO six-point policy package is committing to a comprehensive, financed national plan with accountability and civil society engagement. Second is the strengthening of surveillance and laboratory capacity. Third, ensuring uninterrupted access to essential medicines of assured quality. Fourth is regulating and promoting rational uses of medicines including animal husbandry and patient care. Also in this category is the need to reduce the use of antimicrobials in food-producing animals. Fifth is enhancing infection prevention control. Lastly, fostering innovations and research and development for new tools.

Department of Health Secretary Enrique Ona pledged support to the WHO global plan of action, saying that AMR has also become a concern for the country. Reports coming from the Research Institute for Tropical Medicine indicate a level of drug resistance among some patients.

In response to the global call, the Pharmaceutical and Healthcare Association of the Philippines (PHAP) has joined the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) in recognizing the industry’s role in the fight against AMR.

The IFPMA and PHAP pledge to continue our investment in R&D programs dedicated to the development of new anti-bacterial agents.

We also commit to work in partnership towards a responsible global approach with the WHO, national governments, health care providers, NGOs (nongovernmental organizations) and other stakeholders in the areas of education, prevention, innovation, access, financing and capacity-building initiatives.

Finally, we will also support the WHO’s work to advise on the appropriate use of these vital medicines.

The Health Secretary is right when he said that the indiscriminate and irresponsible use of antimicrobials have given rise to AMR in the Philippines.

This was echoed by Dr. Armand Crisostomo of the Council for Patient Safety who urged health care practitioners to abide by the dictum primum non nocere during a forum by the Philippine College of Physicians.

Despite all the good intentions and eagerness to help the patients, certain practices cause more harm than good. Some prescribe antimicrobials even when there is no indication. Others provide the right antimicrobials but are not giving the right amount and duration needed to kill the microorganisms.

The production of substandard drugs and counterfeiting are the other causes of AMR.
Dr. Soe urged health regulators to continue testing the quality of antimicrobials that are in the market. When medicines are either low quality or fake, there is high probability that the dosage or amount of the active ingredient required to eliminate microorganisms are not enough. So instead of eradicating them, they are given the environment to change, mutate and develop resistance against antimicrobials.

Perhaps a change in patient behavior is also in order. Some tend to self-medicate and would rely on information from well-meaning friends and the Internet. And for some patients, a good doctor is someone who would prescribe more antibiotics.

For countless years now, microbial resistance has been embedded in the nature of these microorganisms. I could only agree with Secretary Ona when he said that our goal is therefore to minimize and delay the development of AMR by having the right attitude towards our medicines.
A medicine can be a powerful intervention in helping preserve lives. At the same time, it could be powerless against infectious diseases when not used according to its indication, dosage, and duration.

While the pharmaceutical industry has renewed commitment to develop new antimicrobials, no one really knows when scientists can again discover new effective drugs that would be able to withstand AMR. However, the task remains to be difficult due to scientific, regulatory and financial limitations.

The IFPMA noted that the growth in anti-microbial resistance has been accompanied by a sharp decline in the development of new anti-bacterial medicines. Over the past three decades only two new classes of anti-bacterial medicines have been discovered, compared to 11 in the previous 50 years.

The discovery of new antibiotics is not simple. Bacteria have multiple mechanisms of resistance and it is difficult to find drug candidates to fight them. We join the IFPMA in its position that progress depends on sustained efforts by industry over a period of many years, combined with the existence of, as well as scientific progress by, diverse groups of trained scientists within academe and industry. (For the full statement, please go to www.ifpma.org)

We cannot afford to take the huge health, economic and security risks as the consequences of drug resistance. Everyone has a stake in the fight against AMR.

(4) World Health Day and drug resistance

Reiner W. Gloor
April 1, 2011

A few months ago, the world saw the emergence of a new superbug that was highly resistant to many of even the most powerful and so-called last defense antibiotics ever discovered. The bacteria that make an enzyme called New Delhi metallo-beta-lactamase found in patients across the globe, continue to cause anxiety among health experts as this new superbug could produce complex infections with no drug to cure in the horizon.
The World Health Organization (WHO) defined antimicrobial resistance (AMR) as resistance of a microorganism to an antimicrobial to which it was previously sensitive.

While AMR is an ancient phenomenon, it has become more dangerous each day. Apart from the superbugs, AMR jeopardizes health care gains in the treatment of the world’s leading infectious killers namely tuberculosis, malaria and HIV/AIDS.

Alexander Fleming’s discovery of penicillin in 1928 greatly contributed to major advancements in pharmaceutical research. Our generation is witness to these breakthroughs that continue help save, improve and prolong lives. Now, the health care community and the patients depend on antimicrobials to treat infections caused by bacteria, viruses, fungi and parasites. But when there is antimicrobial or drug resistance, standard treatments such as antibiotics, antivirals and antimalarials become ineffective.

This is the reason that the WHO has chosen the theme "Antimicrobial resistance: no action today, no cure tomorrow" for World Health Day (WHD) on April 7. Each year, the WHO chooses a pressing global health issue and spearheads international and national campaigns to address the concern. Last year, international attention was given to urbanization and health.

During the WHD 2011, the WHO will promote a six-point policy package to address AMR centering on commitment, accountability, surveillance, quality, supply, rational drug use, infection control and empowerment.

Apart from hospital-acquired infections and superbugs, the WHD will focus on the challenges and global response to AMR for HIV/AIDS, malaria and tuberculosis. To date, the WHO reported that about 440,000 new cases of multidrug-resistant tuberculosis emerge annually, causing at least 150,000 deaths. Extensively drug-resistant tuberculosis has likewise been reported in 64 countries. The report added that resistance to chloroquine and sulfadoxine-pyrimethamine is widespread in most malaria-endemic countries.

In South East Asia, falciparum malaria parasites are becoming resistant to artemisinins. Resistance is also an emerging concern for the treatment of HIV infection, following greater access to antiretroviral medicines in recent years.

Furthermore, AMR is a major threat to patient care and disease control throughout the world. AMR exposes patients to prolonged illness and thus increases the risk of disability and death. It also adds to the physical, emotional and financial burden that patients and their families go through when diseases strike.

In a borderless world, the battle against AMR is crucial. In recent years, infectious diseases of pandemic proportions claimed the lives of people from around the world. Health, trade, economies and tourism suffered a heavy blow following the spread of these infections.

As countries race against time, AMR is likewise feared to delay the progress made in health-related Millennium Development Goals aimed at reducing infant mortality, improving maternal health and in curbing HIV/AIDS, tuberculosis, malaria and other diseases by 2015.

From April 7 onwards, the WHO will call for an intensified global campaign to safeguard antimicrobial medicines for the future generation. Several events are expected to unfold on this day as the WHO brings international attention to antimicrobial resistance. In the Philippines, the WHD will be commemorated with a half-day forum that will highlight WHO’s six-point policy package to combat drug resistance.

In May, a series of follow-up multi-sectoral focused group discussions based on the WHO response will likewise be conducted. Coinciding with the National Patient Safety Day on June 25, health experts will likewise discuss the proposed national program of action.

The WHO explained that the inappropriate and irrational use of medicines provides favorable conditions for resistant microorganisms to emerge and spread. Even when the Philippines has implemented important steps to combat AMR, the WHO Country Office still called on the government and stakeholders to do a more cohesive work to address the issue.

When asked, the WHO added that national commitment to respond to AMR can still be improved in the country and that the accountabilities of national and local stakeholders are yet to be defined.

It adds that the complex problem of AMR requires a comprehensive response within and across the whole range of sectors involved, which then presents challenges in implementation.

Another challenge lies in its public good nature in AMR. Individual decisions to use antimicrobials often ignore the societal perspective or the real costs and consequences that inappropriate antimicrobial use would impact on the health service and the society.

Some may be guilty of not taking the full course of a prescribed antimicrobial. Others would self-medicate while some take antimicrobials due to common cough and colds. On the other hand, others take poor quality antimicrobials.

While the research-based pharmaceutical industry remains as committed in the development of a new drug, the long and expensive R&D (research and development) process usually takes an average of 12 to 15 years. Research investments could go way beyond $800 million. Taking chances is not an option.

We should remember that single, isolated and divided efforts to combat AMR showed little gains. Hopefully, the WHD will serve as a wake-up call and a platform for a concerted plan of action by all the stakeholders.

For more information, consult your doctor or you may log on to www.phap.org.ph orwww.phapcares.org.ph. Join us on www.facebook.com/people/Pharma-Phap/. E-mail the author at reiner.gloor@gmail.com

See also:
RUM 1: Reducing Medicine Abuse, January 25, 2012.
RUM 2: SARAH, Drug Dependence
RUM 3: On Combining Drug Molecules and Alaxan FR, fEBRUARY 03, 2012

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