Alexander Pardes

2007-06-05T20:50:00.000-07:00

A detailed article on TB by Issar Smith, PhD - http://cmr.asm.org/cgi/content/full/16/3/463?view=full&pmid=12857778

I learned so much about TB from this article that I realized there was a lot I didn't know about TB before. The article gave a detailed history of TB. Since TB can damage and warp bones (something I didn't know before, as all of my research had been about pulmonary TB), 4,000 year old human skeletons can prove that TB was common at that time period, and likely earlier. M. tuberculosis is believed to have evolved from a species of bacteria which only affected cattle. TB can apparently be contracted by drinking unpasteurized milk, and so it is thought that TB spread to people once the domestication of cattle became common. This reminded me of the avian flu. The oldest written records of TB include 2600 year old Assyrian clay tablets describing people coughing up blood. In the 5th century B.C. the Greek physician Hippocrates wrote about TB and called it phthitis. The word continued to be used in English, and the translation - consumption - became the most common name in English for TB until recently.

The article then skips a couple thousand years of history and mentions that TB became a very serious plague in Europe during the 16th and 17th centuries. During the early to mid 1800s, about a quarter of all deaths in Europe were attributed to TB (the article does not mention it, but I wonder if many of these people died of unknown causes and it was simply assumed that they died of TB). TB was at its worst during the 18th century, and this was due to the population explosions in overcrowded unsanitary urban centers in the recently idustrialized Europe (I vaguely remember learning about this at school). After the 1850s TB gradually became less prominent. The article says that some believe that this was because people were starting to evolve to become resistant to TB, since so many susceptable people had died. The author of the article admits that this may have been a factor, but he believes that TB death rates went down too quickly and suddenly to be explained by evolution, and he attributes the decline to improved sanitation and standards of living in Europe. In the 1920s a vaccine was produced for TB, although it was not very effective. The first antibiotic for TB, streptomycin, was invented in the 1940s and more effective ones (one of which is isoniazid, the most common TB drug in use today) were invented in the 1950s. Because of these improvements, TB cases were steadily becoming less common until the mid 1980s. At this point the spread of AIDS couple with larger amounts of homelessness and poverty caused TB to once again become a serious disease. While these are still major factors in the severity of TB, the emergence of drug resistance may soon become the most serious issue.

More to come from this website.

2007-06-04T11:14:00.000-07:00

On Saturday our group had a team meeting and we bought materials and discussed ideas. It was a very productive day. Today Phil drew the outline of South Africa. Over the weekend I also did some research on isoniazid.

2007-06-01T13:37:00.000-07:00

Chemical & Engineering News on Isoniazid - http://pubs.acs.org/cen/coverstory/83/8325/8325isoniazid.html

Isoniazid was one of the first anti-tuberculosis drugs discovered, and continues to be one of the primary drugs used.

Isoniazid was first synthesized in 1912 by two German chemists as part of their doctoral requirements; however, isoniazid's ability to fight tuberculosis was not discovered until 1951.

This website also mentions how serious drug resistant tuberculosis has become, stating that 4% of all tuberculosis cases are resistant to more than one anti-TB drug.

From what I have read, tuberculosis was a very serious disease until the 1940s and 50s, when the first anti-TB drugs were discovered. Tuberculosis has recently become very dangerous again due to the HIV epidemic and the emergence of strains of drug resistant tuberculosis. I am almost outraged that a these strains have been allowed to develop.

2007-05-31T14:13:00.000-07:00

A New York Times article on extremely drug resistant tuberculosis in South Africa -http://www.nytimes.com/2007/01/28/world/africa/28tuberculosis.html?ex=1180756800&en=4243c30d748fd857&ei=5070

This article describes the outbreak of extremely drug resistant tuberculosis (XDR-TB) in South Africa. XDR-TB is very difficult to cure, and TB experts fear that the disease may have already spread to neighboring countries. The article says that South Africa has a lack of TB testing, and so it is impossible to know the extent of the outbreak. There are 328 cases of XDR-TB that have been documented in South Africa, but it is likely that there have been far more, since many people with XDR-TB may not have ever been tested, and TB can kill an infected person before they have a chance to get treatment. Also, due to their lack of resources, South African hospitals may not take the time to record or document all cases.

I found it interesting that this article seemed to subtly suggest that South Africa adhere to the DOTS strategy. It criticized South Africa's lack of laboratories and inconsistancy with recording results.

2007-05-30T13:48:00.000-07:00

The WHO website on DOTS, their strategy for controlling tuberculosis - http://www.who.int/tb/dots/en/

DOTS has five main elements. It recommends that nations commit to fighting tuberculosis by legislating funding. Nations should then setup a network of laboratories so that people throughout the nation can be tested for tuberculosis. The third element is adopting a standardized treatment for TB, and then finding and overcoming obstacles to providing treatment to the entire population. The fourth element is to develop a consistent and adequate supply of anti-tuberculosis drugs, which the WHO recommends should be made free to all TB patients. The WHO suggests that providing free or inexpensive treatment will save governments money because fewer people will become sick in the future, as cured patients will no longer spread TB. The final element of the DOTS plan is creating a method of recording statistics about TB patients. The main purpose for this is to allow nations to identify which areas are having success treating TB, and which areas need to be improved.

2007-05-29T20:55:00.000-07:00

The USAID official website on tuberculosis in South Africa -http://www.usaid.gov/our_work/global_health/id/tuberculosis/countries/africa/safrica_profile.html
This website says that South Africa has had much less success fighting tuberculosis than many other African countries, despite both having greater wealth and fewer HIV infected persons. In 1996, South Africa began to implement DOTS, the WHO recommended tuberculosis containment plan. I plan on researching what DOTS (Directly Observed Treatment, Short-course) entails.

Approximately 60% of all South Africans with active tuberculosis also have HIV. From what I have read, this is because a large percentage of people already have latent TB, but when these people's immune systems are weakened by AIDS, the tuberculosis bacteria become active.

From 2000 to 20005, the United States spent an average of $1.6 million per year to help fight tuberculosis in South Africa.

The biggest question I have after reading this webpage is "why is the TB treatment success rate so low in South Africa?"

2007-05-29T10:19:00.000-07:00

http://www.sahealthinfo.org/tb/tbburden.htm
Lots of people in South Africa have active tuberculosis. This website says that South Africa has one of the worst TB epidemics in the world. Part of the reason for the severity of the epidemic is the large percentage of HIV infected persons in South Africa, although this does not fully explain the epidemic, since South Africa has a lower HIV rate than many other African countries. Multi-drug resistant strains of tuberculosis have also emerged in South Africa, and these are very difficult to cure. This website says that the epidemic is largely due to the low quality health services in South Africa. The information on this website appears to be ten years old, and I'm going to try to find more recent information.

2007-05-29T09:49:00.000-07:00

http://www.rnabase.org/primer/
Ribonucleic acid (RNA) is a polymer, meaning that it has many repeating structural units. The backbone of RNA is made up of alternating ribose and phosphate groups. Ribonucleic acid can serve as a temporary copy of genes to be used as a template for protein synthesis, decode the genetic code, and catalize the synthesis of proteins. I still don't really know any more about how rifampicin interacts with RNA.

2007-05-29T09:33:00.002-07:00

http://www.greatvistachemicals.com/pharmaceuticals/rifampicin.html
Rifampicin is one of the two main drugs used to treat tuberculosis. This website says that rifampicin is not very effective against gram-negative bacteria, but works well against gram-positive bacteria such as Mycobacterium tuberculosis. I wonder what those terms mean. This website says that rifampicin kills bacteria by preventing RNA synthesis. Rifampicin interacts with RNA polymerase. Rifampicin's binding site lies on the beta-subunit of the enzyme. Rifampicin does not bind to the isolated subunit, but only to the complete holo-enzyme. If I understood the terminology, this information might help me answer how the drug works on a molecular level.

2007-05-21T21:12:00.000-07:00

http://www.inchem.org/documents/pims/pharm/pim288.htm - This website has very detailed information about isoniazid, one of the main antibiotics used to treat tuberculosis. This website gives the chemical structure of isoniazid, but I don't quite understand how to read the notation. Hopefully I will learn how in Janel's class. I learned that the drug is almost always taken orally. This website says that it is not fully understood how isoniazid works to kill tuberculosis bacteria, but it is hypothesized that it prevents the creation of mycolic acid. I'm not sure what mycolic acid is, but apparently it is unique to mycobacteria (mycobacterium tuberculosis, the bacteria that causes TB, is a mycobacteria). This website has a vast amount of information about isoniazid, but most of it seems useless to me, and much of it is incomprehensible anyway.

2007-05-20T21:33:00.000-07:00

http://www.emedicinehealth.com/tuberculosis/article_em.htm - This website contained a lot of useful information about tuberculosis including symptoms of the disease and typical treatment. The website provided a lot of information about the disease, but I still don't understand why the bacteria cause the disease. So I'm wondering, how do the bacteria cause the disease? Additionally, while this website provided a list of drugs used to treat the disease, it did not explain how the drugs work. So I'm wondering, how do these drugs work?

From this website I learned that an estimated 32% of the world's population is infected with tuberculosis bacteria. This amazed me. However, most of these people have latent tuberculosis or TBI. This means that they are not sick, and cannot usually spread the bacteria, however the bacteria may remain dormant for decades within a human body. A person with active tuberculosis, or TBII, is someone who is sick from the bacteria, and can spread the disease through their saliva or mucus. I also learned that up to 25% of all deaths during the 17th and 18th centuries were attributed to tuberculosis, known then as "consumption." I did not realize how serious tuberculosis was.

2007-05-18T13:36:00.000-07:00

http://www.who.int/tb/en/ - This website was not very useful. I found several statistics from the WHO on other websites, but I couldn't find much useful information on this one.