Tag: Tuberculosis

European Union Scientific Commission Weighs In on Importance of Primate Research

At the beginning of April the European Commission’s Scientific Steering Committee adopted a four page statement outlining, “The Need for Non-Human Primates in Biomedical Research,” that aptly made the case for the ongoing importance of medical research involving non-human primates.

The Steering Committee’s statement reads, in part,

Whether or not, eventually, non-human primates are used for research, will need to be decided upon a case-by-case basis, and following a careful assessment, which takes into account the justification below, the possible existence of alternatives, ethical considerations and the problems that could result from not using the non-human primates. The SSC stresses that unnecessary and duplicated or redundant research using non-human primates should be avoided at all costs . . . However, it considers that for certain experiments there are no alternatives to the use of non-human primates.

The rest of the four-page report is an excellent summary of the irreplaceable nature of primate research. For example, on primate research into malaria, the Steering Committee notes that animal alternatives simply cannot accomplish everything that needs to be done in investigating malaria,

Although considerable research can be done in vitro, the [malaria] parasite has obligatory intra-hepatic developmental phases that are not amenable to in vitro cultivation. To date primates have been used as pre-clinical screens for a variety of new vaccine candidates, based on recombinant sub-unit approaches and live-vectored approaches. Different malaria vaccines will require different immune responses (humoral or cellular) and well-characterized models with similar immune responses to humans (such as macaques) are essential in vaccine development. New malaria drugs will have to work effectively in vivo, and many drugs that are effective in vitro fail in vivo. Monkey models are vital to evaluate promising new drugs for efficacy.

When the Steering Committee says that the malaria parasite “has obligatory intra-hepatic developmental phases,” what it means is that when people are infected with malaria the parasites travel through the blood stream through the liver where they enter the liver’s cells and begin to multiply. Then after a period of time lasting as little 8 days to as long as several months, the malaria parasites leave the liver and enter red blood cells.

When researchers study malaria, they need to study this phase during which the malaria parasite “incubates” in the liver. It is simply not possible at the moment to study that sort of complex behavior in vivo — researchers need to infect non-human primates with malaria parasites to study it. There simply is no animal alternative.

Similarly, with tuberculosis primate studies are vital for narrowing the number of potential treatments that go into clinical trials (which are, after all, extremely expensive). The Steering Committee writes,

Mouse and guinea pig models are used to screen potential new vaccines and drugs, however their patterns of disease and their immune responses are often markedly different from those seen in humans. Recently a careful analysis of two macaque models (rhesus and cynomolgus) has shown the value of these two models and their similarity to the human situation. These models are now being used to screen and select among new candidate vaccines before embarking on the complex, protracted and expensive clinical phase.

And then there are diseases where primates are literally the only experimental model available. Such is the case with Hepatitis C,

Hepatitis C cannot be cultured and the only other species other than man that can be infected is the chimpanzee. Early HCV vaccine studies in chimpanzees have begun to show progress but non-human primate research is essential to bring a truly effective vaccine to the clinic. Thanks to studies in chimpanzees which are still alive and healthy today, millions of doses of a very successful Hepatitis B vaccine have been given World-wide. However, Hepatitis B is still transmitted and many new infections occur daily. New less expensive HBV vaccines are required for developing countries to halt and eliminate this chronic human pathogen.

And yet most European countries seem convinced that primate research can be outlawed altogether with no impact on the biomedical progress. In fact there is but a single research facility in all of Europe that conducts research involving chimpanzees and animal rights activists are pushing for a European Union-wide ban on all research involving great apes.

Source:

The Need for Non-Human Primates in Biomedical Research. Statement of the Scientific Steering Committee of the European Commission, Adopted at its Meeting of 4-5 April 2002.

WHO: Tuberculsosis Efforts Falling Behind

The World Health Organization issued a report this month noting that the world is falling behind in efforts to contain tuberculosis. According to the WHO,

A strategy that can cure up to 90% of all tuberculosis cases, and thus is the best chance for controlling the global epidemic, is reaching only 27% of the world’s TB patients. . . . According to the new WHO report, at the current rate, TB targets set for 2005 will not be reached until 2013.

Tuberculosis currently kills about 2 million people a year, and is the number one preventable cause of death in the developing world.

The main thing holding back better treatment of tuberculosis is money. WHO estimates that countries around the world need to spend about $300 million more per year to control tuberculosis.

Source:

Funding ‘hits tuberculosis fight’. The BBC, March 24, 2002.

Only a fraction of TB patients get the best care. World Health Organization, Press Release, March 22, 2002.

Better Tuberculosis Vaccine on the Way

There is a vaccine for tuberculosis available that has saved many, many lives but it has an odd feature — in some people it just doesn’t work. That would be fine if it didn’t work in a few people, as happens with many vaccines, but in some parts of the world, the vaccine has an 80 percent failure rate. What’s going on there?

Enter researcher Peter Andersen with a hypothesis about that as well as a lab full of mice to test it.

Andersen’s hypothesis was simple. The TB vaccine exposes human beings to a weakened version of Mycobacterium bovis — a from of TB that afflicts cows. Exposure to this causes an immune response which will also protect people from the human form of the disease.

So why doesn’t it always work. Well, in some parts of the world people frequently come into contact with Mycobacterium tuberculosis — the strain that causes tuberculosis in human beings — long before having the vaccine.

Andersen hypothesized that what was happening was this. Some people were being exposed to a weak strain of human TB. This produced an immune response which that rendered the vaccine ineffective. People were essentially being immunized against the vaccine. Then, later in life, they were still vulnerable to the human form of TB.

To test this theory, Andersen used a mouse model of tuberculosis. He infected mice with three strains of mycobacteria taken from a part of Malawi where the bovine version of the disease does not exist. Then, later, he exposed the mice to the Mycobacterium bovis vaccine. Lo and behold, the vaccination did not work. In each case, when later exposed to full blown tuberculosis, the mice all contracted the disease.

Vaccines made from dead versions of TB, however, did protect the mice. There are currently several vaccines being developed that used dead versions of TB rather than weakened versions of live virus, and Andersen’s research is the first suggesting that these vaccines might offer protection to people for whom the traditional vaccine will not work.

Source:

New TB vaccines ‘in pipeline’. The BBC, February 13, 2002.

Is the World Health Organization Part of the Problem?

Brian Doherty has an excellent, scathing attack on the World Health Organization for the January 2002 issue of Reason which argues that the organization is a bureaucratic nightmare more interested in self-preservation than actually doing something about improving health in the developing world.

Doherty writes that when the WHO was founded after World War II it had a substantive impact on health, especially in the developing world. WHO played a major role in tackling a number of infectious diseases, culminating with its role in the eradication of small pox in 1977.

But after the victory over small pox, WHO started turning away from focusing on infectious disease in the developing world to most First World concerns. First under Director General Hiroshi Nakajima and then Gro Harlem Brundtland, WHO began to turn away from infectious disease. Doherty writes,

In a world still fighting infectious disease, Brundtland’s WHO has issued statements, studies, and reports on such topics as blood clots in people who sit still on airplanes too long, helping people remain active while aging, the hazards of using cell phones while driving, the importance of debt relief for poor countries, how tobacco is “a major obstacle to children’s rights,” and rates of alcohol abuse among European teens.

Doherty is especially troubled by the recent WHO analysis of world health problems which relied on a measurement called the disability adjusted life year. The idea behind the DALY is that someone suffering from a severe illness or disability is living a lower quality of life than someone who is not. But WHO’s attempt to quantify produced bizarre results whereby, for example, WHO claims that 16 percent of the years lost to disability in sub-Saharan Africa come from mental illness. Any organization that thinks mental illness is one of the major health problems facing that region, however, is crazy.

Doherty’s article finishes with a stark reminder of just how ineffective WHO is and how misguided its focus on things like years lost to disability are,

Nothing condemn’s WHO’s current agenda more than some of its own pronouncements. In a 1999 press release, WHO declared that six illnesses accounted for 90 percent of all infectious disease deaths among people under 44 years: malaria tuberculosis, measles, diarrheal diseases, acute respiratory infections (including pneumonia), and AIDS. The same press release declared that “the tools to prevent deaths from each of these six diseases now cost under $20 per person at risk, and in most cases under $0.35. Yet these diseases still caused over 11 million deaths in 1998.”

. . . we have WHO declaring that 11 million deaths — 90 percent of all infectious disease deaths for people under 44 years — could have been easily prevented with an expenditure of, at its lowest, $3.9 million, and at its highest, $220 million. That is, anywhere from 0.4 percent to 20 percent of WHO’s budget for one year.

What does WHO spend its money on instead? Doherty cites an analysis of WHO’s 1994-95 budget that found WHO spent as much on its meetings and its executive board as it did on immunizations, tuberculosis and diarrheal diseases combined. Seventy percent of its budget went to administrative overhead and its Geneva headquarters.

Source:

WHO Cares? The World Health Organization cares more about its own life than the lives of the poor. Brian Doherty, Reason, January 2002.

A Better Tuberculosis Vaccine?

The World Health Organization recently released a report on the daunting numbers of tuberculosis infections. It wasn’t too long ago that scientists thought that tuberculosis was on the verge of being wiped out, but complacence about the disease as well the HIV/AIDS epidemic led to a resurgence of the disease. According to WHO regional director in Southeast Asia, Uton Muchtar Rafei, “an estimated 40 percent of the population is infected with TB in our region and more than 1.5 million people died of TB last year.”

Worldwide, tuberculosis is the second leading cause of death from a single infectious agent.

When TB was last a major epidemic, at the turn of the century, a tuberculosis vaccine was created and refined from 1906-1919. The only problem was that it was only about 50 percent effective. Now researchers at the University of California-Los Angeles believe they may have created a much more effective vaccine.

Dr. Marcus Horwitz at UCLA led a study of the new vaccine that involved taking samples of the old vaccine and genetically modifying it to add a protein that is secreted from the organism that causes tuberculosis. “Most proteins of a bacteria are inside,” Horwitz told Reuters, “but there are some proteins which are actually excreted.”

Researchers then infected guinea pigs with tuberculosis, injecting half of them with the new vaccine and leaving the others unvaccinated as a control group. “The difference between the unvaccinated guinea pigs and those that were vaccinated is just day and night,” Horwitz said. “The unvaccinated animals, their lungs just became completely covered with tubercules and destroyed and the animals with the vaccine have one or two lesions which are contained.”

Testing should begin within a year to see if the vaccine is effective in human beings. If so, Horwitz said it should be able to be produced for just pennies a dose. The only drawback is that the vaccine won’t help people with AIDS since the vaccine could potentially disease itself in people with compromised immune systems.

Sources:

WHO finds TB, malaria return in killer diseases. Reuters, November 27, 2000.

Vaccine may work against tuberculosis. Reuters, November 30, 2000.