In many ways, tuberculosis (TB) is an unusual disease, but it is certainly not uncommon. It is an infectious disease caused by transmittable bacteria. However, about nine out of ten people who are infected after exposure to Mycobacterium tuberculosis, the most common culprit, never develop symptoms. Mycobacteria are estimated to have infected as much as one third of the world’s population, or two billion people [1]! This article will look at what makes TB so highly transmittable, and since so many people are infected, what factors determine who gets the active infections. Furthermore, since TB kills nearly two million people every year [2], how can we detect and tackle a TB infection?

What are the symptoms?

An active TB infection causes fever, weight loss, fatigue and pale skin. Three quarters of cases involve the mycobacteria infecting and damaging cells in the lungs (called pulmonary TB). In the other cases, the mycobacteria get into the bloodstream and infect the nervous system, the genitals and urinary system, or bones and joints. Each of these types of TB infections has its own set of symptoms. An incessant cough, sometimes with blood being coughed up, is typical of pulmonary TB. Infections in the nervous system cause inflammation of the membranes covering the brain and spinal cord (meningitis), while infections in bones and joints lead to arthritis. “Military” TB is a particularly severe form of tuberculosis in which the bacteria spread throughout the body and cause tissue damage in a number of organs.

Who gets infected and how?

Coughing, sneezing, spitting, or even speaking, throws out mycobacteria-containing sputum (spit in which saliva and phlegm are mixed) from people with active pulmonary TB. Transmission usually occurs in crowded areas with unhygienic conditions where these bits of aerial sputum are prone to be inhaled by others. Crowded buses, trains and even poorly maintained medical facilities are often places fostering such an environment. In the United States, 10-15 million people are infected with TB. The World Health Organization (WHO) estimates that there are 9 million new cases of tuberculosis TB worldwide every year, with about 22,000 in the USA [2].

TB begins with mycobacteria invading the air sacs, or “alveoli”, in the lungs. Usually, bacteria-eating white blood cells called macrophages ingest these mycobacteria and prevent them from spreading. Mycobacteria, though, are hardy, capable of staying alive, even multiplying inside a macrophage and re-entering the bloodstream. An active immune system will quickly enclose these bacteria in a mass of cemented immune cells called a granuloma, effectively quarantining the infection. This dormant state is called a latent TB infection. However, many factors like old age, infections by other microbes (such as HIV), or malnutrition can weaken an infected person’s immune system. With a compromised immune system, the mycobacteria are able to break out of the granuloma, reinvade cells of specific tissues and cause active tuberculosis.

How is TB diagnosed?

Early diagnosis of TB infections remains a tough medical challenge. A common test for TB infection looks for a person’s immune response in what is called a “Mantoux skin test”. This test, also known as the tuberculin test, involves carefully injecting mycobacterial proteins between layers of the skin on a patient’s forearm. If the patient carries either a latent or an active infection, the injection spot becomes red and inflamed with an immune response within three days. Frustratingly, the skin test often gives positive results even when there are no infections, and the results can be ambiguous. The only definitive test directly identifies the mycobacteria from a sample of sputum or pus from an infected person. However, this testing is slow and expensive, and only an active infection can be detected this way. A chest X-ray, showing granulomas in affected lungs, is another way to look at later-stage active infections. Being able to detect an infection soon after its onset is the best way to prevent its spread. An individual carrying an active, untreated TB infection can pass on the infection to between ten and fifteen people per year [2]. Latent infections, on the other hand, are not transmittable, so if they are detected and treated early, before becoming active infections, many new cases can be prevented.

Treatment and co-infection

Treatment for TB requires the diseased person to be on specific antibiotic treatment for six to nine months. Given the historically impoverished demographics and resource-poor health care systems of the disease-afflicted populations, it is usually very difficult to achieve such a high degree of treatment compliance. Partial compliance to antibiotic treatment has led to the development of several antibiotic-resistant strains of mycobacteria. To complicate matters further, co-infection with TB and HIV (TB/HIV) is a rapidly growing problem, and 12% of all new TB patients in 2009 are also HIV-positive [3]. The rise in TB/HIV and the surge in multidrug-resistant TB are threatening to disrupt global efforts in TB control.

What about vaccines?

Bacille Calmette-Guérin (BCG) is the only TB vaccine available, given annually to more than 100 million children globally. Its effectiveness is highly variable, however, ranging from 0 to 80 percent in different parts of the world [4]. Scientists are working on developing new and more effective vaccines. The primary challenge for TB vaccine development is to achieve reproducible and sustained immunity with weakened bacteria (or parts of the bacteria) that do not cause disease.

Research and global control efforts

TB is a major concern for governments, health care programs and policy makers. However, because the disease has historically been associated with poorer, developing parts of the world, anti-tuberculosis efforts may be a low priority for commercial pharmaceutical companies. Of the 9.4 million new cases reported in 2009, 55% came from Asia, whereas less than 3% was reported from the Americas [2]. Owing to TB’s cascading and virulent spread through populations, it is imperative to address the issue when it is still restricted to a smaller fraction in developed countries. Like the flu, highly communicable infections can quickly reach epidemic proportions. Latent TB infections, with their unpredictable potential for transmission, add to the complexity of the issue.

The WHO’s ”Stop TB” initiative and the Bill and Melinda Gates Foundation are examples of global programs that support research on vaccines, effective long term cures, and diagnostic tools for TB. Their strategies focus on encouraging government commitment to control TB, diagnosis based on sputum-smear microscopy tests, short-course drug treatments (which can improve compliance), and a definite supply of drugs. DOTS (Directly Observed Therapy, Short-course) is a major part of the WHO Stop TB plan. This involves directly observing patients for at least the first two weeks of therapy, to ensure that they are taking their antibiotics regularly.

While there was a surge in the number of deaths from TB in the 1990s due mainly to the increasing numbers of TB/HIV co-infections in Africa and the spread of drug-resistant strains in Europe, global efforts have led to a reversal in the trends since 2005. The number of deaths from TB have been decreasing everywhere in the world in the last 5 years, and there is hope for achieving the WHO’s goal to eliminate TB by 2050. However, the current rate of new cases is still higher than in it was 1990, and the world needs continued and sustained large-scale efforts by researchers, healthcare professionals, governments, and other stakeholders in all countries.

–Gairik Sachdeva ( Harvard University School of Engineering and Applied Sciences


[1]     Bill and Melinda Gates Foundation “Progress Against Tuberculosis” Sept. 2009 progress sheet.

[2]    WHO Tuberculosis Factsheet, November 2010.

[3]    WHO Stop TB Partnership “2010/2011 Tuberculosis Global Facts”.

[4]    WHO discussion document “Issues relating to the use of BCG in immunization programmes”, 1999.

Useful Links:

Harvard School of Public Health Review: Infectious diseases – Tuberculosis.


Bill and Melinda Gates Foundation

Princeton Project 55 Tuberculosis Initiative

CDC tuberculosis site: