Thank you Group G!

Dearest Group G=)

All I can say is that is has been a wonderful semester working with you guys and ladies. It was really a big change from my previous PCL group and I guess every group works differently.

I had fun listening to everyone's presentations and also had a fair share of laughter and joy.

This semester, unknowingly, disappeared from our sight and slipped out through our hands. Now we have come to the end of our 1st yr of the MBBS journey. All I can say is, I have made more friendships, forged more new bonds that I'm sure would stand the test of time.

Dependable, reliable and trustworthy, you people make me feel that I could fall back and rely on all of you at any time. Everyone in the group is just so forthcoming and helpful. A big thank you to all who actually helped Chloe and me during that car accident, we really appreciate your help. :)

Enough of sad stuff aside, I'm sure all of us had times we could look back and ponder. Times we can smile and reminiscence when we have graduated, or maybe when we ourselves become lecturers and teach the future doctors or even when we are grey and old.

I would like to take this opportunity to apologize if I have done any wrong to anyone unknowingly and caused any harm. I did not mean it and I would be man enough to say I'm sorry. =)

Anyway MBBS is one year down, and four more years to go. Do your best for the upcoming exams everyone:) I'm sure all of you would be studying hard and having books that are disintegrating. ALL the best. May all of you be blessed, healthy, happy and contented with life, after all we are quite lucky to not be born with any of the birth defects we see during lectures, so don't screw up your life.

I promise to be there for everyone in times of need and please do just drop a message, I would help you to the best I can. I promise. :)

All that is said and done is over, all the best group G and a big thank you to Dr Amudha. It has been an utmost pleasure having you as our PCL tutor. Meticulous and fun, you excellently facilitated our PCL and allowed us to mature and grow as individuals, as future doctors. Kudos.

Warmest Regards

Lincoln L.

Doha Declaration

- The November 2001 Doha Declaration on the TRIPS Agreement and Public Health was adopted by the WTO Ministerial Conference

- It reaffirmed flexibility of TRIPS member states in circumventing patent (rights granted by state) rights for better access to essential medicines.

Essential medicine is “Drugs that satisfy the health care needs of the majority of the population; therefore should be available at all times in adequate amounts & in appropriate dosage forms @ a price the community can afford”

-

"4. The TRIPS Agreement does not and should not prevent Members from taking measures to protect public health.

o Agreement can and should be interpreted and implemented in a manner supportive of WTO Members' right to protect public health and, in particular, to promote access to medicines for all.

o In this connection, we reaffirm the right of WTO Members to use, to the full, the provisions in the TRIPS Agreement, which provide flexibility for this purpose.

- Each Member has the right to determine what constitutes a national emergency or other circumstances of extreme urgency, it being understood that public health crises, including those relating to HIV/AIDS, tuberculosis, malaria and other epidemics, can represent a national emergency or other circumstances of extreme urgency.

6. We recognize that WTO Members with insufficient or no manufacturing capacities in the pharmaceutical sector could face difficulties in making effective use of compulsory licensing under the TRIPS Agreement. We instruct the Council for TRIPS to find an expeditious solution to this problem and to report to the General Council before the end of 2002."

These provisions in the Declaration ensure that governments may issue compulsory licenses on patents for medicines, or take other steps to protect public health.

PCL 13

What is Tuberculosis?

Tuberculosis (TB) is an infection caused by a bacteria called the tubercle bacillus or Mycobacterium tuberculosis. Until effective anti-tuberculosis drugs were introduced about 50 years ago, TB was one of the main causes of death. TB is still a major problem in many countries.
It can affect the lungs (pulmonary TB) or other parts of the body, such as the lymph nodes (tuberculous adenitis or scrofula), the skin and the bones. Tubercle bacilli can remain dormant for years before producing active disease. In most cases lung infection is well controlled by the immune system, and shows no symptoms. Active lung disease occurs if the immune system becomes less effective.
Also:
- Latent TB. In this condition, you have a TB infection, but the bacteria remain in your body in an inactive state and cause no symptoms. Latent TB, also called inactive TB or TB infection, isn't contagious.

- Active TB. This condition has clinical symptoms and signs and is contagious

Pathophysiology
Tubercle bacilli initially cause a primary infection, which only rarely causes acute illness. Most (about 95%) primary infections are asymptomatic and followed by a latent (dormant) phase. However, a variable percentage of latent infections subsequently reactivate with symptoms and signs of disease. Infection is usually not transmissible in the primary stage and is never contagious in the latent stage.

Primary infection: Infection requires inhalation of particles small enough to traverse the upper respiratory defenses and deposit deep in the lung, usually in the subpleural airspaces of the lower lung. Large droplets tend to lodge in the more proximal airways and typically do not result in infection. Infection usually begins from a single initial focus.
To initiate infection, tubercle bacilli must be ingested by alveolar macrophages. Tubercle bacilli that are not killed by the macrophages actually replicate inside them, ultimately killing the host macrophage (with the help of CD8 lymphocytes); inflammatory cells are attracted to the area, causing a focal pneumonitis that evolves into the characteristic tubercles seen histologically. In the early weeks of infection, some infected macrophages migrate to regional lymph nodes, where they access the bloodstream. Organisms may then spread hematogenously to any part of the body, particularly the apical-posterior portion of the lungs, epiphyses of the long bones, kidneys, vertebral bodies, and meninges.

In 95% of cases, after about 3 wk of uninhibited growth, the immune system suppresses bacillary replication before symptoms or signs develop. Foci of infection in the lung or other sites resolve into epithelioid cell granulomas, which may have caseous and necrotic centers. Tubercle bacilli can survive in this material for years; the balance between the host's resistance and microbial virulence determines whether the infection ultimately resolves without treatment, remains dormant, or becomes active.

Activation of the disease:
In about 10% of immunocompetent patients, latent infection develops into active disease, although the percentage varies significantly by age and other risk factors. In 50 to 80% of those who develop active disease, TB reactivates within the 1st 2 yr, but it can occur decades later. Any organ initially seeded may become a site of reactivation, but reactivation occurs most often in the lung apices, presumably because of favorable local conditions such as high O2 tension.


Signs and symptoms of active TB include:

- Unexplained weight loss
- Fatigue
- Fever
- Night sweats
- Chills
- Loss of appetite

Tuberculosis usually attacks your lungs. Signs and symptoms of TB of the lungs include:
-Coughing that lasts three or more weeks
- Coughing up blood
-Chest pain, or pain with breathing or coughing

Tuberculosis can also affect other parts of your body, including your kidneys, spine or brain. When TB occurs outside your lungs, symptoms vary according to the organs involved. For example, tuberculosis of the spine may give you back pain, and tuberculosis in your kidneys might cause blood in your urine

PCL 13- Limitations in Bringing Positive Changes to the Global Health

Limitations in Bringing Positive Changes to the Global Health

1. One important reason for this is the lack of functional health systems due to a shortage in the health workforce, management incompetence, inadequate infrastructure, and health care financing. The World Health Report 2006 estimates a global deficit of 2.3 million doctors, nurses, and midwives. Critical health workforce shortages exist in fifty-seven countries, of which thirty-seven are in sub-Saharan Africa.

2. Emphasis on vertical or disease-specific programmes such as HIV/AIDS, malaria, and tuberculosis may have further weakened the already fractured health systems, thus making delivery of general health care in low-income countries that much more difficult. Unfortunately, neither the governments of these countries nor the global donor community have invested adequately in capacity building.

3. There are more challenges facing global health. Prominent among these are the development of microbial resistance to antibiotics and disinfectants, along with the prevalence, in epidemic proportions, of non-communicable diseases and injuries in low- and middle-income countries

4. Worldwide gaps in income, opportunities and health outcomes, which motivated the quest for greater fairness in 1978, are actually greater today than at any time in recent history. Life expectancy between the richest and poorest countries differs by more than forty years. Annual government expenditure on health ranges from as little as $20 per person to more than $6,000.

5. All around the world, the costs of health care are escalating.

6. Phenomenal increases in international air travel have made emerging and epidemic-prone disease a much larger menace.

7. Universal trends, like urbanization, demographic aging, and the marketing of unhealthy lifestyles have sparked a sharp increase in chronic diseases like heart disease, stroke, cancer, and diabetes. Long considered the close companions of affluent societies, these diseases now impose around 80 per cent of their burden on low- and middle-income countries. The requirements of life-long treatment strain already weak systems of care and add to the costs.

8. Growing numbers of the frail elderly further increase the demands on health systems, the health workforce, and for social welfare.

Causes & Risk Factor for TB and Epidemiology

Causes

Tuberculosis is caused by an organism called Mycobacterium tuberculosis. The bacteria spread from person to person through microscopic droplets released into the air. This can happen when someone with the untreated, active form of tuberculosis coughs, speaks, sneezes, spits, laughs or sings. Rarely, a pregnant woman with active TB may pass the bacteria to her unborn child.

Although tuberculosis is contagious, it's not especially easy to catch. You're much more likely to get tuberculosis from a family member or close co-worker than from a stranger. Most people with active TB who've had appropriate drug treatment for at least two weeks are no longer contagious.

Risk Factors:

• Lowered immunity. A healthy immune system can often successfully fight TB bacteria, but your body can't mount an effective defense if your resistance is low. A number of factors can weaken your immune system. Having a disease that suppresses immunity, such as HIV/AIDS, diabetes, end-stage kidney disease, certain cancers or the lung disease silicosis, can reduce your body's ability to protect itself. Your risk is also higher if you take corticosteroids, certain arthritis medications, chemotherapy drugs or other drugs that suppress the immune system.
• Close contact with someone with infectious TB. In general, you must spend an extended period of time with someone with untreated, active TB to become infected yourself. You're more likely to catch the disease from a family member, roommate, friend or close co-worker.
• Country of origin. People from regions with high rates of TB — especially sub-Saharan Africa, India, China, the islands of Southeast Asia and Micronesia, and parts of the former Soviet Union — are more likely to develop TB. In the United States, more than half the people with TB were born in a different country. Among these, the most common countries of origin were Mexico, the Philippines, India and Vietnam.
• Age. Older adults are at greater risk of TB because normal aging or illness may weaken their immune systems. They're also more likely to live in nursing homes, where outbreaks of TB can occur.
• Substance abuse. Long-term drug or alcohol use weakens your immune system and makes you more vulnerable to TB.
• Malnutrition. A poor diet or one too low in calories puts you at greater risk of TB.
• Lack of medical care. If you are on a low or fixed income, live in a remote area, have recently immigrated to the United States or are homeless, you may lack access to the medical care needed to diagnose and treat TB.
• Living or working in a residential care facility. People who live or work in prisons, immigration centers or nursing homes are all at risk of TB. That's because the risk of the disease is higher anywhere there is overcrowding and poor ventilation.
• Living in a refugee camp or shelter. Weakened by poor nutrition and ill health and living in crowded, unsanitary conditions, refugees are at especially high risk of TB infection.
• Health care work. Regular contact with people who are ill increases your chances of exposure to TB bacteria. Wearing a mask and frequent hand washing greatly reduce your risk.
• International travel. As people migrate and travel widely, they may expose others or be exposed to TB bacteria.

Epidemiology

More than 2 billion people (about one-third of the world population) are estimated to be infected with tuberculosis [1].

The global incidence of TB peaked around 2003 and now appears to be declining slowly [2].

In 2006 the World Health Organization (WHO) issued the following estimates [2]:

-The prevalence of active infection was 14.4 million, corresponding to a prevalence rate of 219/100,000 persons.
-The incidence of new cases was estimated to be 9.2 million, corresponding to an incidence rate of 139/100,000.
-Twelve of the 15 countries with the highest estimated TB incidence are in Africa, where the TB incidence rate was 363/100,000 (figure 1).
-In 2006 there were 1.7 million deaths from TB worldwide, a death rate of 25/100,000.
-The epidemiology of tuberculosis varies substantially around the world (figure 2). The highest rates (100/100,000 or higher) are observed in sub-Saharan Africa, India, China, and the islands of Southeast Asia and Micronesia.

-Intermediate rates of tuberculosis (26 to 100 cases/100,000) occur in Central and South America, Eastern Europe, and northern Africa. Low rates (less than 25 cases per 100,000 inhabitants) occur in the United States, Western Europe, Canada, Japan, and Australia.

Poverty, HIV and drug resistance are major contributors to the resurging global TB epidemic [3,4].

Approximately 95 percent of TB cases occur in developing countries.

Approximately 1 in 14 new TB cases occur in individuals who are infected with HIV; 85 percent of these cases occur in Africa [2]. An estimated half million cases of multidrug resistant (MDR)-TB also occur annual in Africans; even higher rates of drug resistant infections occur in Eastern Europe.

It is estimated

that, in 2007, there were 1.37 million incident cases of HIV-positive TB (14.8%

of total incident cases) and 456 000 deaths from TB among HIV-positive people

(equivalent to 26% of deaths from TB in HIV-positive and HIV-negative people,

and 23% of an estimated 2 million HIV-related deaths) (from WHO)

Doha Declaration

Doha Declaration, was issued in November 2001, which indicated that TRIPs should not prevent states from dealing with public health crises.

- Reaffrimed flexibility of TRIPS member states in circumventing patent rights for better access to essential medicines

- Essential medicine is “Drugs that satisfy the health care needs of the majority of the population; therefore should be available at all times in adequate amounts & in appropriate dosage forms @ a price the community can afford”

- It is agreed that Each WTO member has right to deremine what constitutes a national emergency or extreme urgency, including public health crisis such as HIV/AIDS, tb, malaria and other epidemics.

- We recognize that WTO Members with insufficient or no manufacturing capacities in the pharmaceutical sector could face difficulties in making effective use of compulsory licensing under the TRIPS Agreement. We instruct the Council for TRIPS to find an expeditious solution to this problem and to report to the General Council before the end of 2002

-

PCL 13 TRIPS (Trade Related Aspects of Intelectual Property Rights)

ESSENTIAL INFORMATION

- International agreement, adminstired by World Trade Organisation

- Set standard for intelectual property regulation
~ nations law must meet for copyrights rights
~ protect confidential information
~ trademarks

- was negotiated at the end of Uruguay Round of General Agreement Tariffs and Trade (GATT)
in 1994

- most comprehensive international agreement on intelectual property



COMPULSORY LICENSING IN PUBLIC HEALTH

-enables a competent government authority to license compulsory licensing of patented
invention to a third party or government agency witouth the consent of patent holder

- Article 31 of the Agreement sets forth a number of conditions for the granting of compulsory \
licences.
~ include a case-by-case determination of compulsory licence applications,
~ the need to demonstrate prior (unsuccessful) negotiations with the patent owner for a
voluntary licence and the payment of adequate remuneration to the patent holder.
~ address a national emergency or other circumstances of extreme urgency, certain
requirements are waived in order to hasten the process, such as that for the need to have had
prior negotiations obtain a voluntary licence from the patent holder

- leaves Members full freedom to stipulate other grounds, such as those related to non-working
of patents, public health or public interest.


PARALLEL IMPORTATION

- parallel importation is importation without the consent of the patent-holder of a patented
product marketed in another country either by the patent holder or with the patent-holder’s
consent.

-the principle of exhaustion states that once patent holders, or any party authorized by him,
have sold a patented product, they cannot prohibit the subsequent resale of that product since
their rights in respect of that market have been exhausted by the act of selling the product.

- since many patented products are sold at different prices in different markets, the rationale
for parallel importation is to enable the import of lower priced patented products


EXTENSION OF TRANSITION PERIOD FOR LEAST DEVELOPED COUNTRIES

-the Doha Declaration also extended the transition period for LDCs for implementation of the TRIPS obligations from 2006 to 2016.

-however, the extension is limited to the obligations under provisions in the TRIPS Agreement relating to patents and marketing rights, and data protection for pharmaceutical products. Thus, LDCs are still obliged to implement the rest of their obligations under the TRIPS Agreement as of 2006