causative organism of tb :: Article CreatorDeadly Diseases
When German biologist and doctor Robert Koch announced in 1882 that he had discovered the bacterial cause of tuberculosis, he said, "If the number of victims which a disease claims is the measure of its significance, then all diseases … must rank far behind tuberculosis." By this measure, tuberculosis today still outranks most other infectious diseases for its sheer potential to affect vulnerable populations. The World Health Organization reports that TB infects one new person every second and is the world's leading killer of women.
An ancient disease, tuberculosis has been found in the skulls and spinal cords of Egyptian mummies 3,000 years old. The Greek physician Hippocrates called "consumption" — as tuberculosis was often known in the past — the most common deadly disease of his time.
An estimated one billion people died from tuberculosis between 1700 and 1900. Even after Koch dispelled the myth that "bad air" brought about the disease by revealing its microbial cause, for decades the recommended treatment remained rest and fresh air at a sanatorium. Among those who lost their lives to TB were writers Fyodor Dostoevsky and Jane Austen, composer Frederic Chopin, and Presidents Andrew Jackson and Ulysses S. Grant.
Also known as the "white plague," tuberculosis is a contagious, airborne bacterial disease transmitted through coughing, sneezing, and talking. Even singing or laughing at close range can be dangerous. Tiny microbe-filled water droplets are expelled by one person and inhaled by another. Still, extended close contact is necessary to transmit the bacteria. A healthy adult spending eight hours a day for six months with an infected person has a 50 percent chance of becoming infected. Alarmingly, each person who has active TB may infect on average 10 to 20 others, often family members and caretakers.
Tuberculosis symptoms start with a persistent cough, fever, and night sweats. The bacteria spread rapidly, most often to the lungs, leading to tissue damage and a bloody cough. In about 15 percent of cases, the disease may spread to other parts of the body, including lymph nodes, the gastrointestinal tract, bones, and joints.
Though conventional tuberculosis is highly treatable and curable (with a 90 percent rate of success), TB kills more people worldwide in a typical year, according to the Global TB Report Card, than "all wars, earthquakes, floods, tsunamis, airline accidents, terrorist attacks, and murders" combined. Nearly two million people succumb to the disease annually, mostly in the developing world, where 98 percent of new infections arise.
Despite the overall incidence of tuberculosis dropping 20 percent since 1990, the World Health Organization still predicts 36 million TB deaths in the next 20 years. The disease has surged back in Africa, taking advantage of the vulnerability of HIV/AIDS sufferers. The frequent coexistence of the tuberculosis bacteria and the virus that causes AIDS has been dubbed the "cursed duet."
Today it's estimated that two billion people — or approximately one-third of the world's population — carry one of the three bacteria that cause TB. A healthy immune system keeps the bacteria in check in what is known as latent TB; approximately 10 percent of people with latent TB develop the active disease, and only then are they in danger of spreading it to others. But if a person's immune system becomes weakened, as in the case of HIV/AIDS patients, the TB pathogen asserts itself, and nearly 40 percent will develop active TB.
The rate of tuberculosis infection continues to decline in the United States. It fell by 3.3 percent in 2004, when there were 14,511 confirmed cases. More than half of these infections — 53.7 percent — occurred in foreign-born persons living in the country. A tuberculosis vaccine, Bacille Calmette-Guerin (BCG), exists, but its effectiveness is extremely variable, and therefore it is not recommended for use in the United States and Europe. The World Health Organization does recommend it for newborns in developing countries, because it appears to offer some protection in children. Researchers continue to seek better alternatives.
The first anti-TB drug, streptomycin, was developed in 1944, but TB has always required at least two strong antibiotics to defeat it. And treatment takes at least six months, with many patients stopping their medications as soon as they begin to feel well. Doing so allows the most resistant bacteria to remain in the person's body and spread their genes to a new generation. At the next opportunity they can attack again, with greater force. Today, to combat the growth of resistant strains, Directly Observed Treatment Short-course, or DOTS, is the conventional procedure for delivering drugs so health care workers can monitor patients fulfilling their required drug regimen. But multidrug-resistant strains of tuberculosis, called MDR-TB, are becoming extremely dangerous and require more expensive and painful drugs to cure.
A promising program in Lima, Peru, run by the Boston-based organization Partners In Health, has shown that MDR-TB in poor settings can be successfully treated with a complex regimen of drugs. But only a fraction of the estimated five million MDR-TB patients worldwide are getting the antibiotics they need. Since every TB victim is thought to infect up to 20 others, these deadly "superbugs" are spreading.
Despite the desperate need for better drugs and vaccines, it has been nearly 30 years since a new TB drug was developed. To kick-start stalled research, the Bill & Melinda Gates Foundation (The Bill & Melinda Gates Foundation is a funder of the Rx for Survival project) has donated $25 million to the Global Alliance for Tuberculosis Drug Development and $83.5 million to the Aeras Global TB Vaccine Foundation to develop new tuberculosis drugs and vaccines.
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Peat-bog Fungi Produce Substances That Kill Tuberculosis-causing Bacteria
An analysis of fungi collected from peat bogs has identified several species that produce substances toxic to the bacterium that causes the human disease tuberculosis. The findings suggest that one promising direction for development of better treatments might be to target biological processes in the bacterium that help maintain levels of compounds known as thiols. Neha Malhotra of the National Institutes of Health, U.S., and colleagues present these findings December 3 in the open-access journal PLOS Biology.
Every year, millions of people around the world fall ill from tuberculosis and more than 1 million people die, despite the disease being preventable and curable. However, treatment requires taking daily antibiotics for months, which can pose significant challenges, so new treatments that shorten the treatment period are urgently needed.
To explore potential targets for treatment-shortening strategies, Malhotra and colleagues turned to sphagnum peat bogs. These freshwater wetlands harbor abundant species of bacteria in the Mycobacterium genus -- the same genus as the tuberculosis-causing bacterium Mycobacterium tuberculosis. In these bogs, fungi compete with mycobacteria to grow within a decomposing "gray layer" that, similarly to lesions found in the lungs of tuberculosis patients, is acidic, nutrient-poor, and oxygen-poor.
In the lab, the researchers grew Mycobacterium tuberculosis alongside each of about 1,500 species of fungi collected from the gray layer of several peat bogs in the northeastern U.S. They identified five fungi that had toxic effects against the bacterium. Further laboratory experiments narrowed these effects down to three different substances produced by the different fungi: patulin, citrinin, and nidulalin A.
Each of the three compounds appears to exert its toxic effects on the tuberculosis bacterium by severely disrupting cellular levels of a class of compounds known as thiols -- several of which play essential roles in the molecular processes that help keep bacterial cells alive and functional.
The researchers note that these three compounds themselves are unlikely to be good drug candidates. However, especially given the similarity between the peat-bog environment and tuberculosis lesions, the findings provide support for a particular strategy for development of treatment-shortening drugs: targeting the biological processes that maintain thiol levels in the tuberculosis bacterium.
The authors add, "Pathogenic mycobacteria, like those causing the human diseases leprosy and tuberculosis, are found in abundance in sphagnum peat bogs where the acidic, hypoxic and nutrient-poor environment gives rise to fierce microbial competition. We isolated fungi from such bogs and screened for those that competed directly with mycobacteria by co-culture and discovered that these fungi all target the same physiological process in mycobacteria using several chemically distinct mechanisms."
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