TUBERCULOSIS (TB): HISTORY, TREATMENTS AND DRUG-RESISTANT STRAINS

TUBERCULOSIS

Tuberculosis (TB) kills more people than any other treatable infectious disease, with the exception, in recent years, of Covid-19. Approximately 1.5 million people died from tuberculosis in 2020 (including 214 000 HIV positive people). This was an increase from the previous year, the first such increase in a decade. The increase occurred mainly in the 30 countries with the highest burden of TB (See Below), with death rates from the disease projected to much higher in the early 2020s [Source: World Health Organization (WHO), October 14, 2021]

Tuberculosis is an infectious disease that can infect any body tissue, but is especially damaging to the lungs. Caused by a bacteria , it can spread when people who are sick with TB expel bacteria into the air. Most people who develop the disease are adults. In 2020, men accounted for 56 percent of all TB cases, adult women accounted for 33 percent and children for 11 percent. Many new cases of TB are attributable to five risk factors: undernutrition, HIV infection, alcohol use disorders, smoking and diabetes.

Tuberculosis usually attacks the lungs but can spread to other organs. In typical severe cases it destroys patients' lung tissue, making them cough and sneeze, and spread germs through the air. Anyone with active TB can easily infect another 10 to 15 people a year. The disease spreads through invisible respiratory droplets when an untreated person coughs, shouts, laughs or talks. Eight hours in the same room with someone with active TB is thought to be necessary to become infected.

Tuberculosis symptoms include recurring fevers, hacking cough, debilitating weakness. Many people have TB but show no symptoms. Most infected people have latent TB, in which the bacteria are kept in check by the immune system. Patients become sick only when the immune system is compromised, enabling the bacteria to become active. People with HIV are at especially high risk. TB is preventable and curable. About 85 percent of people who develop TB disease can be successfully treated with a 6-month drug regimen; treatment has the added benefit of curtailing onward transmission of infection.

Every second someone in the world is newly infected by TB. In the early 2010s, it was estimated that one-third of the world's population was infected with the bacteria that cause tuberculosis. Of these 5 percent to 10 percent became actively sick. As of 2010, there were 8.7 million cases of TB and 1.1 million cases (and 350,000 deaths) were associated with HIV-AIDS and 650,000 cases are multi-drug resistant. [Source: Reuters, WHO]

Michael Specter wrote in the The New Yorker: “Tuberculosis strikes vulnerable people with special ferocity. Victims are seized by severe night sweats, wasted by fatigue, and punished by the blood-tinged cough that is the disease's defining symbol....When an infectious person coughs, sneezes, spits, or even shouts, he sends minute particles of sputum, or phlegm, into the air-exposing anyone nearby. To fight the infection, the body's immune system forms a scar around the TB bacteria which serves as a kind of moat. Afterward, the bacteria lie dormant and cannot spread or infect others. But immune systems fail, and when that happens TB can move from the lungs to the bloodstream and then to the kidneys, the brain, and other organs. (That's why in patients with H.I.V., which ravages the cells that the body uses to defend itself, tuberculosis becomes particularly deadly.) The only way to cure the disease is with a combination of antibiotics. The treatment lasts six months because the drugs work only when the TB bacteria-which grow slowly-are dividing. [Source: Michael Specter, The New Yorker, November 15, 2010]

Websites and Resources Centers for Disease Control and Prevention (CDC) cdc.gov/DiseasesConditions ; World Health Organization (WHO) fact sheets who.int/news-room/fact-sheets ; National Institute of Health (NIH) Library Medline Plus medlineplus/healthtopics ; Merck Manuals (detailed info many diseases) merckmanuals.com/professional/index ; Global Fund to Fight AIDS, TB and Malaria theglobalfund.org

Places with High Rates of Tuberculosis

Millions of people develop TB each year, mostly in the developing countries in sub-Sahara Africa and Asia. Approximately 90 percent of those who fall sick with TB each year live in 30 countries: countries with the highest burden of TB include: Angola, Bangladesh, Brazil, Central African Republic, China, Congo, Democratic People’s Republic of Korea, Democratic Republic of Congo, Ethiopia, Gabon, India, Indonesia, Kenya, Lesotho, Liberia, Mongolia, Mozambique, Myanmar, Namibia, Nigeria, Pakistan, Papua New Guinea, Philippines, Sierra Leone, South Africa, Thailand, Uganda, United Republic of Tanzania, Viet Nam and Zambia. [Source: WHO, 2021]

Doctors Without Borders has said that about two thirds of cases of tuberculosis are undiagnosed and untreated and half the new cases are in five countries — India, China, Indonesia. Nigeria and South Africa. The disease has made a comeback with a vengeance in the developing countries, particularly ones where HIV/AIDS is prevalent.

Number of cases by region in 2010: 1) South and Southeast Asia (3.51 million cases): 2) Africa (2.32 million cases)’ 3) Western Pacific, including China and Australia (1.64 million cases); 4) Eastern Mediterranean (650,000 cases); 5) Europe (420,000 cases); 6) Americas (270,000 cases). [Source: Reuters, WHO]

Most afflicted countries (rate per 100,000 people in 2010): 1) Swaziland (1,287); 2) South Africa (981); 3) Sierra Leone (682); 4) Lesotho (633); 5) Zimbabwe (633); 6) Djibouti (620); 7) Namibia (603); 8) Gabon (553); 9) Mozambique (544); 10) Botswana (503).

Mortality rate (deaths per 100,000 people in 2010): 1) Sierra Leone (146); 2) Togo (106); 3) Marshall islands (81); 4) Mauritania (79); 5) Djibouti (71); 6) Gabon (70); 7) Senegal (62); 8) Cambodia (61); 9) Guinea (59); 10) Somalia.

Michael Specter wrote in the The New Yorker: “In the developing world tuberculosis has surged dangerously.... As people join the great migrations from villages to crowded cities, slum life and tuberculosis await them. ...Yet-no doubt owing to the fact that rich people in the West rarely get the disease-tuberculosis receives fewer resources, fewer research dollars, and less attention from the global health community than either AIDS or malaria — the two other most deadly infectious diseases. TB activists don't march on Washington or chain themselves to the gates of pharmaceutical firms to demand better treatment. [Source: Michael Specter, The New Yorker, November 15, 2010]

Tuberculosis is the leading killer in the developing world of people with AIDS, accounting for about a quarter of the 2 million AIDS deaths annually in the 2000s. In 2007, about 1.3 million tuberculosis patients not infected by HIV/AIDS died and 456,000 with HIV/AIDS died. Tuberculosis has a close association with HIV/AIDS. More careful testing and monitoring of HIV/AIDS in sub-Sahara Africa revealed how extensive the problems of “co-infection” by tuberculosis and HIV/AIDS has been. In 2007, the WHO estimated that 1.4 million people with the HIV/AIDS virus had tuberculosis, almost double from the previous year — a statistic that reflected better reporting rather an actual doubling of infections. Treatments for the “con-infection” generally focus on returning the infected person to good health so their immune system can help them. Without any treatment the likelihood of death within six months is close to 100 percent.

History of Tuberculosis

Tuberculosis has long been called the silent killer and has been known since the birth of history. It ravaged ancient Egypt and Greece. The ancient Greeks described it with the word “phthisis” , which means for a living body to “shrivel with intense heat as if placed in a flame.” Later the Romans ascribed the term “consumere” “to eat up or devour” to it. For some time scientists believed that tuberculosis first emerged in Middle Eastern cows and spread to people with the development of agriculture. Later it was introduced to the New World by Europeans, The theory was debunked when bone lesions caused by tuberculosis were found on pre-Columbian mummies from South America.

In the West tuberculosis is often seen as a disease of a bygone era — evoking images of impoverished 18th or 19th century women and children dying slowly of a disease then commonly known as "consumption". At that time it was indeed a very serious illness.Between 1800 and 1870 it accounted for one out of five deaths in the United States and was described as a plague even though in actuality it is a chronic illness. Special institutions called sanatoriums were set up to treat it and a whole culture, with separate protocols for men and women, developed around it.

Tuberculosis was called consumption in part because of the way it slowly, inexorable devoured the lungs and weakened the body. Among those that were claimed by it were the poet John Keats, the Bronte sisters, Moliere, Voltaire, Chekhov and George Orwell . Verdi and Puccini operas featured heroines struck down in their prime by the disease. Drugs discovered in the 1940s came close to eliminating the disease. But since the the disease has come back with a vengeance.

Michael Specter wrote in the The New Yorker: “For centuries, tuberculosis has been the source of misguided stereotypes, including the association of consumption with creativity and brilliance. “Doctors suspect that tuberculosis develops genius,'' a 1940 article in * Time* pointed out, “because 1) apprehension of death inspires a burning awareness of life's beauty, significance, transience, 2) the bacillus breeds restlessness and an intoxicated hypersensitiveness.” ...Nonetheless, tuberculosis has always taken its most serious toll on the industrial-labor class-not on artists. The rise of industry throughout the world has been mirrored uncannily by a rise in deaths from tuberculosis. It was the leading cause of death in Europe and the United States from the eighteenth century into the twentieth. Then prosperity-rather than medicine-drove the rate of infection down. As a society becomes richer, the conditions that allow tuberculosis to flourish start to wane. Sanitation and housing improve and so does nutrition. By the nineteen-fifties, very few people in the West were dying of the disease. [Source: Michael Specter, The New Yorker, November 15, 2010]

Tuberculosis Deaths Rise Because of Covid-19

The COVID-19 pandemic reversed years of global progress in tackling tuberculosis. In 2020, for the first time in over a decade, TB deaths have increased, according to the World Health Organization’s 2021 Global TB report.In 2020, more people died from TB, with far fewer people being diagnosed and treated or provided with TB preventive treatment compared with 2019, and overall spending on essential TB services falling.[Source: World Health Organization (WHO), October 14, 2021]

According to the WHO: The first challenge is disruption in access to TB services and a reduction in resources. In many countries, human, financial and other resources have been reallocated from tackling TB to the COVID-19 response, limiting the availability of essential services.The second is that people have struggled to seek care in the context of lockdowns.

TB services are among many others disrupted by the COVID-19 pandemic in 2020, but the impact on TB has been particularly severe. Challenges with providing and accessing essential TB services have meant that many people with TB were not diagnosed in 2020. The number of people newly diagnosed with TB and those reported to national governments fell from 7.1 million in 2019 to 5.8 million in 2020.

There was also a reduction in provision of TB preventive treatment. Some 2.8 million people accessed this in 2020, a 21 percent reduction since 2019. In addition, the number of people treated for drug-resistant TB fell by 15 percent, from 177 000 in 2019 to 150 000 in 2020, equivalent to only about 1 in 3 of those in need.

Tuberculosis Causes and Symptoms

Tuberculosis is caused by the Mycobacterium tuberculosis (tubercle bacillus), which can infect the lungs. The bacterium is protected by a thick waxy coat and can lie dormant for years.

Tuberculosis infects the lungs causing the production of large amounts of phlegm and severe coughing that in its worst cases produces uncontrollable spurts of blood. Victims often cough violently and become very thin and sometimes cough up chunks of blood and phlegm and vomit blood. When the bacteria enters a victim’s brain it causes the body to go stiff and may produce shivering and make the victim unable to swallow while thick phlegm chokes him.

Tuberculosis can be spread via airborne droplets by coughing, sneezing, singing, yelling and even laughing. Tuberculosis can begin growing in the lungs or throat of anyone who breaths the bacteria. Transmitted through the air, it is usually contacted by spending a lot of time in a closed room with someone infected by the disease who is coughing a lot. People often get it after prolonged exposure (eight hours or more) to someone with the illness.

People who are healthy are not easily infected by tuberculosis even when the TB bacteria enters their bodies. People generally get sick when the immune system weakens. Those who get tuberculosis develop symptoms within two years of infection. In rare cases it can take decades for symptoms to emerge.

Tuberculosis Treatment and DOTS

Tuberculosis is preventable and curable. About 85 percent of people who develop TB disease can be successfully treated with a 6-month drug regimen; treatment has the added benefit of curtailing onward transmission of infection. [Source: World Health Organization (WHO), October 14, 2021]

The tuberculosis bacteria can be brought under control with powerful medications. Curing ordinary tuberculosis requires taking four different antibiotics for six months. The treatment is unpleasant; the pills are difficult to swallow and have a bad taste. In 2004, a the discovery of new tuberculosis drug was announced that could shorten the treatment time from six to nine months to two months. Trials for the treatment has be conducted. The treatment involves an early accurate diagnosis and carefully following a strict drug taking regimen for six to eight weeks.

In March 1997, WHO announced a new tuberculosis treatment (called Directly Observed Treatment Shortcourse, or DOTS) with a cure rate of 85 to 96 percent compared to 41 percent for conventional methods. The treatment involves a regimen of four drugs that have to be taken according to a regimented schedule so the disease doesn't develop resistance. A key element of the treatment is having people an eye on infected people to make sure they take their medication every day. In some cases an observer is present to literally watch patients take their medicine. The treatment doubled cure rates to 84 percent and slashed death rates from 29 percent to 4 percent in India.

Michael Specter wrote in the The New Yorker: “Tuberculosis can be cured, but taking several antibiotics nearly every day for six months is not easy, particularly in parts of the world without running water or refrigeration. In 1994, the W.H.O. instituted a program called DOTS, which stands for “directly observed treatment, short course.” DOTS requires health workers to provide medicine-and then to watch people swallow it every day until they complete their treatment. Compliance is essential, because stopping treatment in the middle permits the most resilient strains of the bacteria to thrive, greatly increasing the chance that they will become resistant to basic, inexpensive drugs. Thirty-six million people have received care under the DOTS program, eight million of whom would have died without it. It has been a triumph by any measure. Even DOTS, though, has not been able to keep the disease from spreading. [Source: Michael Specter, The New Yorker, November 15, 2010]

Combating Tuberculosis

Important factors in controlling the disease include: 1) the availability of health services: 2) effectively using prevention strategies; 3) effectively using treatment strategies; 4) availability of effective vaccines; 5) availability of housing. The WHO recommends that in the first nine months of life children should get vaccinations for tuberculosis. The BCG tuberculosis vaccine should be given in the first week of life.

The United Nations Millennium Development goal is to halve the global tuberculosis infection rate by 2015. The World Health Organization (WHO) estimates that $3.2 billion a year is needed to adequately diagnose and treat tuberculosis, of which about half actually is available. About 80 percent of the money comes from domestic government s and the rest from foreign aid, the World Bank and the Global Fund to Fight AIDS, Tuberculosis and Malaria. The WHO’s “DOTS” diagnosis and treatment program is available in 187 countries.

Since it is important that patients consistently take their medicines at the prescribed time and not all patients can be looked after by hospitals and clinics an effort is being made to get family members and community leader more engaged in getting the patients to take their medicine when they are supposed to.

Global Fund to Fight AIDS, TB and Malaria (theglobalfund.org) invests US$4 billion a year to defeat HIV, TB and malaria. In July 2008 the Bush administration pledged to spend $48 billion over the next five years to help treat and prevent AIDS, tuberculosis and malaria, with $39 billion to be spent on AIDS, $5 billion on tuberculosis and $4 billion on malaria.. In January 2006, the Gates Foundation pledged $900 million by 2015 to fight tuberculosis as Bill Gates and British Prime Minister chief Gordon Brown announced the Global Plan to Stop Tuberculosis. A group called Aeras Global TB Vaccine Foundation, which has received a $82.9 million in funding from the Bill and Melinda Gates Foundation, is working with drug companies, carving up up the world into large regions, and giving certain companies rights to those regions in return for providing TB vaccines to the poor people that live there.

Michael Specter wrote in the The New Yorker: “In the nineteen-eighties, when AZT became the first effective treatment for H.I.V., the annual cost for each patient was ten thousand dollars. People in the West, who were rich or lucky enough to have good insurance, could afford it. In countries that struggle to provide basic immunizations against diseases like measles, though, AIDS treatments were a fantasy. Then various groups, including the Clinton Foundation, the Gates Foundation, and the Global Fund to Fight AIDS, Tuberculosis and Malaria, joined together to push for lower prices. Generic manufacturers, led by Cipla, the Mumbai-based pharmaceutical giant, began to churn out highly effective medicine at a small fraction of what it cost in the United States. Political pressure mounted, officials of the World Health Organization joined the call for cheaper AIDS medications, and today the governments of poor countries like India can buy those drugs for an annual price of less than a hundred dollars per patient. These drugs are normally distributed in bulk, through international AIDS organizations.[Source: Michael Specter, The New Yorker, November 15, 2010]

“A similar effort will be required to lower the cost of diagnosing tuberculosis. There will also have to be a transformation in how TB medicine is regulated. That may seem like an insurmountable barrier, but, with the proper incentives, the system could work. Again, one can look to the history with AIDS medicines for a model. Because Cipla and other Indian pharmaceutical companies are frequently inspected by international regulators-such as the U.S. Food and Drug Administration-governments are willing to buy their products. That's one reason that Indian firms have become the most important manufacturers of generic AIDS medicines in the world. Any company that sells molecular diagnostics would need the same sort of oversight. But producing cheap, internationally acceptable versions of the GeneXpert would surely lead to great profits.

Unreported Tuberculosis Cases

The WHO estimated that some 4.1 million people suffered from TB in 2021 but have not been diagnosed with the disease or have not officially reported to national authorities. This figure is up from 2.9 million in 2019.

The countries that contributed most to the global reduction in TB notifications between 2019 and 2020 were India (41 percent), Indonesia (14 percent), the Philippines (12 percent) and China (8 percent). These and 12 other countries accounted for 93 percent of the total global drop in notifications.

Reversals in progress mean that the global TB targets are off track and appear increasingly out of reach, however there are some successes. Globally, the reduction in the number of TB deaths between 2015 and 2020 was only 9.2 percent - about one quarter of the way to the 2020 milestone of 35 percent. Globally, the number of people falling ill with TB each year (relative to population) dropped 11 percent from 2015 to 2020, just over half-way to the 2020 milestone of 20 percent.

Difficulty Testing for Tuberculosis

There is no cheap, reliable test that can determine who is sick from tuberculosis and who is not.Testing for tuberculosis can be difficult. Potential victims are screened with a chest X-ray. To be sure a patient has it he has cough up some phlegm which is then examined under a microscope or cultured for the TB bacterium.

Health officials have called for better testing, under the present system it can take a week or more to get the result of a tuberculosis test. By that time someone that tests positive could have spread the disease to hundreds of others. The WHO is pushing a new rapid TB test that can yield results in as little as two hours. The main problem with the new tests is that they requires upgrading laboratory facilities and purchasing expensive machines that most facilities in poor countries, where the disease is prevalent, can’t afford.

In 2012, the World Health Organization (WHO) said blood testing kits used to detect active tuberculosis are unreliable and should be banned. Marissa Cevallos wrote in the Los Angeles Times: “The tuberculosis tests, widely used in developing countries, are dangerous because they both over-diagnose and miss true cases. The WHO’s position is based on a review of nearly 100 studies of the diagnostic tests for both tuberculosis of the lungs and of other organs. The blood tests look for antibodies the body would produce against the bacterium Mycobacterium tuberculosis, bu the results from these tests are often inconsistent, the WHO review found. The group is still reviewing blood tests for inactive (latent) tuberculosis infection. Such commercial blood tests aren’t approved by the FDA but are sold in other parts of the world, in particular where regulatory agencies are weak, the policy statement notes. More than a million of these tests, which can cost up to $30, are carried out every year.[Source: Marissa Cevallos, Los Angeles Times, July 20, 2011]

Michael Specter wrote in the The New Yorker: “Blood tests often do more harm than good. One recent study found that Indians undergo more than 1.5 million useless TB tests of this kind every year. Other approaches are almost as unreliable. Examining a person's sputum-a diagnostic procedure that was developed more than a century ago-remains the most common way to detect the infection. It is a laborious process. Technicians smear the sputum on a slide and then place the specimen under a microscope. The instructions are comically complex. “Spread sputum on the slide using a broomstick,'' a typical recipe, posted on the wall of a clinic in Patna, begins. “Allow the slide to air dry for fifteen to thirty minutes. Fix the slide by passing it over a flame from three to five times for three to four seconds each time.'' If the slide isn't held over the flame long enough, false stains will appear-suggesting that people are sick when they are not. Hold the slide too long, though, and the stain will disappear and show nothing at all. The results are accurate little more than half the time. [Source: Associated Press, September 2, 2010]

New Accurate Tuberculosis Tests

In September 2010, scientists reported a major advance in diagnosing tuberculosis: The test introduced at that time revealed in less than two hours, with very high accuracy, whether someone hads the disease and whether it was resistant to the main drug for treating it. The test revolutionized TB care and replaced the 125-year-old process used before that, which was slow and missed more than half of all cases. The best test — growing the bacteria in a lab dish from a mucus sample — takes a week or more, so the most common approach is to look at a sample under a microscope. That misses many cases. “You can tell the patient before they leave the office if they have TB and if it’s drug-resistant. It’s transformational,’’ said Dr. Peter Small, head of TB programs at the Bill & Melinda Gates Foundation, which helped fund the work.[Source: Associated Press, September 2, 2010]

In 2012, biomedical engineers at the University of California, developed a microfluidic chip to test for latent tuberculosis with the aim of making a cheaper, faster and more reliable test. "Our assay is cheaper, reusable, and gives results in real time," said Ying Liu, a research specialist working with Professor Alexander Revzin in the UC Davis Department of Biomedical Engineering.[Source: UC Davis, May 22, 2012]

Most infected people have latent TB, in which the bacteria are kept in check by the immune system. Patients become sick only when the immune system is compromised, enabling the bacteria to become active. Current tests for latent TB are based on detecting interferon-gamma, a disease-fighting chemical made by cells of the immune system. Commercially available tests require sending samples to a lab, and can be used just once.

Liu and Revzin used a novel approach: They coated a gold wafer with short pieces of a single-stranded DNA segment known to stick specifically to interferon-gamma. They then mounted the wafer in a chip that has tiny channels for blood samples. If interferon-gamma is present in a blood sample, it sticks to the DNA, triggering an electrical signal that can be read by a clinician. "If you see that the interferon-gamma level is high, you can diagnose latent TB," Liu said. The researchers plan to refine the system so that the microfluidic sensor and electronic readout are integrated on a single chip.

GeneXpert Tuberculosis Test

Michael Specter wrote in the The New Yorker: “Medicine rarely provides magic bullets, but, for the first time, a technology has been developed that might help countries escape the endless cycle of mistaken diagnoses and haphazard treatment. A company called Cepheid, based in Sunnyvale, California, now makes a device, called a GeneXpert, that allows doctors to diagnose TB in under two hours-without error or doubt. “The machine is so powerful that it could help end tuberculosis,'' Shamim Mannan, a tuberculosis expert in India said. “I don't think that is an exaggeration.'' [Source: Michael Specter, The New Yorker, November 15, 2010]

An editorial in 2010 in the New England Journal of Medicine raised the possibility that, with proper use of this device, tuberculosis could be eliminated. The cost, however, would be far too high for developing countries. Mannan said. “In the past, countries waited until they got richer and tuberculosis mostly went away. India cannot do that. The epidemic is just too big. And we are too poor.”

The GeneXpert was developed in 2002, with initial support from the Department of Defense. After the events of September 11th and the mailing of anthrax spores later that year, biological threats became a national priority. The only sure way to recognize dangerous new organisms, whether made by man or by nature, is to analyze their unique DNA, and the GeneXpert has tested billions of pieces of mail for toxins. Its diagnostic capabilities seemed even more promising, however. In 2008, with funding from the Bill and Melinda Gates Foundation, the Foundation for Innovative New Diagnostics, and the National Institutes of Health, researchers at medical centers throughout the world began to assess the machine's effectiveness in diagnosing tuberculosis.

Its success was striking. In a study published along with that editorial in the Journal, researchers reported that the GeneXpert identified more than ninety-eight per cent of active TB infections, including many that sputum smears had missed. Because the test looks for the TB bacterium itself, rather than for antibodies, latent infections don't confuse the GeneXpert as they do blood tests. The machine costs nearly twenty-five thousand dollars and each test is about twenty dollars. Prices could plunge if similar machines were introduced and used widely.

“This is absolutely transformational technology,'' Peter Small, the director of tuberculosis programs for the Gates Foundation, said. “It is a system that removes the guesswork from one of our most deadly diseases.'' Unlike the sputum technique, the molecular approach is straightforward: a patient spits into a cup, and the sample is placed in a cartridge that looks much like the pods used in many espresso machines. A computer examines the sample's DNA to see if it contains the genetic signature of TB. Results are available within hours.

The GeneXpert can even determine whether the bacteria are resistant to rifampicin, the most effective and widely used component of the four-drug cocktail commonly prescribed for TB. “People often equate sophisticated science with complexity, and this is just the opposite,” Small said. “As long as there is electricity, the tests could be carried out by unskilled workers in any village. Training them would be easy, and the potential benefits-saving billions of dollars and millions of lives-worth any effort. The question is how do we get there. I have heard people say that we should trust the government bureaucracy. But others say let's put our faith in an unregulated collection of free agents. It's hard to know which approach is more ludicrous.”

“The power of machines like the GeneXpert has already become evident at Mumbai's Hinduja Hospital, a private institution that has been using one for three years. Mumbai has one of the worst TB problems in India, particularly with drug-resistant cases. Yet at Hinduja the machine has made it possible for doctors to diagnose and treat patients before they are able to spread the disease. “There has always been a pretty standard approach to using fancy medical technology,'' Camilla Rodrigues, who runs the microbiology department, told me when I visited. “You develop it in the West and use it there. Eventually, it trickles down to the poor countries.'' [Source: Michael Specter, The New Yorker, November 15, 2010]

Rodrigues pointed out that, with tuberculosis, the pattern makes no sense. The GeneXpert was invented in the West, but India and Africa need it much more urgently. “Every time we make a correct diagnosis, we save not one life but many,'' she said, waving in the direction of the boxy metal-and-Plexiglas machine sitting in a corner of the lab. “And with this machine we make correct diagnoses in two hours.”

Tuberculosis Vaccine

The Bacille Calmette-Guerin (BCG) tuberculosis vaccine commonly used today was developed in the 1920s. Dr. Jerald Sadoff, head of a foundation that aims to create a better TB vaccine, said ,”It sort of works but it doesn’t work very well.” BCG has remained the standard treatment because it is effective preventing life-threatening forms of TB in infants and young children and because it is available, inexpensive and easy to administer to infants. The only problem is that it s not very effective in preventing the disease. Sadoff is head of the Aeras Global TB Vaccine Foundation which has opened a facility with a $60 million Gates Foundation grant to produce millions of doses of a new TB vaccine which had not been invented yet.

The WHO recommends that in the first nine months of life children should get vaccinations for tuberculosis. The BCG tuberculosis vaccine should be given in the first week of life. The World Bank has estimated the economic gain from an effective tuberculosis vaccine could exceed $1.6 trillion over a decade if it prevents the disease from progressing as it is now.

In July 2009, field testing of a new tuberculosis vaccine called MVA85A began in South Africa among 2,874 children under the age of one. Early results from he trial seemed to indicate that vaccine was safe and stimulated a high level of immune response believed to be effective combating tuberculosis the vaccine’s inventor Helen McShane of Oxford University told Reuters.

The drug companies Glaxo-SmithKline, Sanofi-Aventis and Crucell are also testing tuberculosis vaccines. In December 2009, Japanese scientists at Otsuka Pharmaceutical Co. said they had identified an anti-TB compound that prevents the tuberculosis bacteria from multiplying.

Drug-Resistant Tuberculosis

Among the different drug-resistant strains of tuberculosis are: 1) MDR-TB (Multi-drug resistant tuberculosis); 2) XDR-TB (Extensively drug resistant tuberculosis); 3) TDR-TB (Totally drug resistant tuberculosis); 4) TB-HIV (tuberculosis-HIV). The standard treatment for multi-drug resistant tuberculosis includes daily injections of toxic drugs for two years.

Drug-resistant tuberculosis is common is eastern Europe, the former Soviet Union, China and India and is on the rise in sub-Sahara Africa. MDR-TB stands for multi-drug-resistant tuberculosis that is resistant to two of the most effective first-line TB drugs. XDR-TB (extensively drug-resistant tuberculosis) describes a highly-lethal form of drug resistant tuberculosis which is resistant to three or more of the six kinds of second-line drugs as well as the first line ones. In 2006 the WHO declared these forms of tuberculosis presented a global emergency and begged the wealthiest nation to set up a $95 million fund to contain it.

XDR-TB was first identified in 2006. It is now found in 57 countries and is virtually untreatable. Widespread attention was brought to XDR-TB when Andrew Speaker, a 31-year-old American lawyer thought to have the disease strain., defied a travel ban and went to Europe for his honeymoon, sparking alerts in places that he visited in Greece, Italy and the Czech Republic. He became the first person to be placed under mandatory isolation by U.S. Health authorities in more than four decades. In the end it turned out that he didn’t have XDR-TB.

About 500,000 people have multi-drug resistant tuberculosis, with 30,000 of these considered XDR-TB. Fewer than 1 percent of the 500,000 are receiving care that meets WHO standards. Many die quickly despite treatment. Many health experts say that drug-resistant tuberculosis is a health problem of our own making caused by patients not properly taking their medicine as a result of poor health infrastructure and spotty monitoring.

What's so frustrating about that progression, Lucica Ditiu of the WHO's Stop TB Partnership, told Reuters, is that all drug-resistant TB "is a totally man-made disease". Like other bacteria, the TB bug Mycobacterium tuberculosis can evolve to fight its way past antibiotic medicines. The more treatment courses patients are given and fail to complete, the stronger and more widespread the resistance becomes. "The doctors, the healthcare workers, the nurses, entire healthcare systems have produced MDR-TB. It's not a bug that has come from nature. It's not a spontaneous mutation. It came about because patients were treated badly — either with poor quality drugs, or not enough drugs, or with insufficient observation so the patient didn't finish the treatment course," said Ditiu. [Source: Kate Kelland, Reuters, March 19, 2012]

Spread of Drug-Resistant Tuberculosis

"Hot zones" of drug-resistant tuberculosis sprung up in India, Russia, Latvia, Estonia, the Dominican Republic, Argentina and Ivory Coast, where 2 to 14 percent of all cases are drug-resistant. The problem is blamed on the fact that some infected people did not finish the full course of antibiotics, allowing drug-resistant trains to develop through mutation.

The drug-resistant tuberculosis threat grew quickly as a result of a surge of HIV/AIDS cases weakening immune systems of individuals and health care systems failing to take adequate measures to prevent and stem the spread of the disease. Dr. Jim Yong Kim, head of social medicine at Harvard Medical school, told Time, “We are still in denial about how bad this problem is and how much worse its going to get.” WHO director Margaret Chan said that if left unchecked it “could take us back to the treatment era that predates the development of antibiotics.”

Drug-resistant tuberculosis spreads quickly in hospitals, where a lack ventilation and poor protective measure permit transmission between patients and health-care workers. To prevent the disease’s spread hospitals need controlled airflow. The strain also thrives in prisons where poor sanitation and cramped conditions encourage the bacterium’s deadliest strains to grow. In poor countries, most people spread tuberculosis before they are diagnosed and treated, and many don’t return for follow-up doctor visits to get test results.

Kate Kelland of Reuters wrote: One of the biggest difficulties in tackling TB is the ease and speed with which it spreads. When patients cough, sneeze or spit, they propel thousands of germ-carrying droplets into the air around them. With people travelling the world in confined spaces, a disease like TB can easily hitch a ride. A good example is extensively drug resistant TB, which first hit world headlines during an outbreak in South Africa in 2006. Barely four years later in 2010, the WHO said drug-resistant tuberculosis was at "record levels" worldwide and a total of 58 countries had reported at least one case of XDR-TB. Ditiu fears a similar pattern could emerge with TDR-TB. "It is spreading, it's spreading as we speak right now," she said. "The situation is extremely worrying." [Source: Kate Kelland, Reuters, March 19, 2012]

Anna Watterson, who took 19 months "out of normal life" for her MDR-TB to be successfully treated but still qualified as a barrister and now works in London's law courts, can't be sure where she picked up her infection. At the time she was living in the northwest borough of Brent, an area of London with a large immigrant community and pockets of poverty. Like millions of others in the British capital, she commuted on the Tube underground train system most days.Watterson had also travelled to India a couple of years earlier, and since TB can lie dormant for long periods, it's also possible she may have contracted it there. "You can't be isolated from the rest of the world," she said. "We've become too complacent about TB, thinking that it's gone away. But the reality is that until it goes away in the developing world, it's not going away anywhere."

Image Sources:

Text Sources: Centers for Disease Control and Prevention (CDC), U.S. Department of Health and Human Services; World Health Organization (WHO) fact sheets; National Geographic, New York Times, Washington Post, Los Angeles Times, The New Yorker, Time, Reuters, Associated Press, AFP, Lonely Planet Guides and various websites books and other publications.

Last updated May 2022


This site contains copyrighted material the use of which has not always been authorized by the copyright owner. Such material is made available in an effort to advance understanding of country or topic discussed in the article. This constitutes 'fair use' of any such copyrighted material as provided for in section 107 of the US Copyright Law. In accordance with Title 17 U.S.C. Section 107, the material on this site is distributed without profit. If you wish to use copyrighted material from this site for purposes of your own that go beyond 'fair use', you must obtain permission from the copyright owner. If you are the copyright owner and would like this content removed from factsanddetails.com, please contact me.