Acid-Fast Bacilli: TB and Friends
- Bryan Knowles
- Aug 8
- 6 min read
We've all heard of TB (aka tuberculosis) and leprosy in popular culture. Someone could be convinced that these types of infections are a thing of the past. Maybe you've seen Tombstone and thought that it's something from the old west - Doc Holliday's ever-worsening case of consumption. Or maybe you've read the excellent historical novel, Moloka'i by Alan Brennert (Goodreads review here). But tuberculosis and is related infections are of great medical concern and should always be considered in the case of chronic, hard to treat, hard to detect infections.
Testing for Acid-Fast Bacilli
The tests used to detect AFB infections (tuberculosis and otherwise) are generally by culture and/or microscopy. Because these organisms are extremely slow-growing in general, a culture can take as many as six weeks or more to receive final results.
Safety Precautions for Working with Possible Tuberculosis Infections
When treating patients with active tuberculosis or working up Mycobacterium tuberculosis infections in the laboratory, strict airborne and biosafety precautions are essential to prevent transmission. Clinical care requires placement of the patient in a negative-pressure airborne infection isolation room, with healthcare workers wearing fit-tested N95 or higher-level respirators, practicing meticulous hand hygiene, and limiting room entry to essential personnel. In the laboratory, all manipulations of specimens suspected of containing M. tuberculosis must be performed in a certified Class II biological safety cabinet within a Biosafety Level 3 (BSL-3) facility, using sealed centrifuge rotors, splash-proof safety equipment, and procedures that minimize aerosol generation. Laboratory staff must wear appropriate personal protective equipment, including respirators, gloves, and protective gowns, and decontaminate work surfaces with tuberculocidal disinfectants after handling specimens. These measures are critical because M. tuberculosis is transmitted via inhalation of airborne droplet nuclei, and even minimal exposure in an unprotected environment can lead to infection.
Acid-Fast Bacilli in Human Infections
Acid-fast bacilli (AFB) are a diverse group of microorganisms characterized by their resistance to decolorization by acid-alcohol following staining with carbol fuchsin in the Ziehl–Neelsen or Kinyoun staining methods. This property is due to the high lipid and mycolic acid content in their cell walls, which creates a waxy barrier to chemical penetration. While the term “acid-fast” is often used synonymously with Mycobacterium tuberculosis, it encompasses a broader spectrum of organisms, including several species of mycobacteria and certain genera outside the Mycobacteriaceae family. In human disease, the pathogenic acid-fast bacilli can be broadly divided into the Mycobacterium tuberculosis complex, nontuberculous mycobacteria, and a small number of partially acid-fast organisms of other genera.
Mycobacterium tuberculosis Complex
The Mycobacterium tuberculosis complex (MTBC) includes M. tuberculosis, M. bovis, M. africanum, M. canettii, M. caprae, and M. pinnipedii. These organisms are obligate pathogens in humans or animals and are transmitted primarily via the respiratory route, with rare zoonotic transmission from cattle, marine mammals, or other hosts. M. tuberculosis is the most prevalent species, causing pulmonary and extrapulmonary tuberculosis in millions of people worldwide. M. bovis, historically associated with unpasteurized dairy products, can cause indistinguishable clinical disease but is naturally resistant to pyrazinamide. M. africanum is largely confined to West Africa, while M. canettii is rare and often associated with a smooth colony morphology atypical for mycobacteria. The MTBC organisms are fully acid-fast on Ziehl–Neelsen staining and grow slowly on Lowenstein–Jensen or Middlebrook media, often requiring several weeks for visible colony formation.
Antibiotic resistance of TB: The most serious forms are multidrug-resistant TB (MDR-TB), defined by resistance to at least isoniazid and rifampin, and extensively drug-resistant TB (XDR-TB), which shows additional resistance to fluoroquinolones and one or more second-line injectable agents. Resistance develops when patients receive inappropriate drug regimens, when therapy is interrupted, or when transmission occurs from already resistant cases. These resistant strains require prolonged treatment with less effective, more toxic, and more expensive drugs, often for 18 months or longer, with lower cure rates than drug-susceptible TB. The rise of MDR-TB and XDR-TB poses a major global health challenge, underscoring the importance of rapid molecular diagnostics, strict adherence to directly observed therapy programs, and continued development of new anti-tubercular agents.
Mycobacterium leprae and Mycobacterium lepromatosis
Mycobacterium leprae is the causative agent of leprosy (Hansen’s disease), a chronic infection affecting the skin, peripheral nerves, and mucosa of the upper respiratory tract. It cannot be cultured in artificial media and is instead propagated experimentally in armadillos or mouse footpads. M. lepromatosis, a closely related species described more recently, is associated with diffuse lepromatous leprosy and appears to have a more restricted geographic range, notably in Mexico and the Caribbean. Both species are strongly acid-fast in tissue sections, particularly with the Fite–Faraco stain, which preserves the integrity of their lipid-rich cell walls.
Slowly Growing Nontuberculous Mycobacteria
Slowly growing nontuberculous mycobacteria (NTM) such as Mycobacterium avium complex (MAC), M. kansasii, M. xenopi, and M. marinum are opportunistic pathogens. MAC, comprising M. avium and M. intracellulare, is an important cause of disseminated disease in immunocompromised patients, especially those with advanced HIV/AIDS. M. kansasii typically produces chronic pulmonary disease resembling tuberculosis and is common in certain geographic regions. M. marinum causes “fish tank granuloma,” a cutaneous and soft tissue infection acquired from exposure to contaminated water. M. xenopi is associated with pulmonary disease and thrives in hot water systems. These species are acid-fast but may stain more faintly than MTBC, especially in paucibacillary specimens, and their growth on culture takes weeks.
Rapidly Growing Nontuberculous Mycobacteria
Rapidly growing mycobacteria, including M. fortuitum, M. chelonae, and M. abscessus, are environmental organisms capable of causing skin and soft tissue infections, post-surgical wound infections, and occasionally pulmonary disease. They are distinguished by their ability to produce visible colonies on solid media within seven days. These species are fully acid-fast on direct smears, but their clinical relevance depends on correlation with patient symptoms and specimen source, as they are frequent contaminants. Their lipid content is sufficient to retain carbol fuchsin, although some stains may require modified protocols to enhance visualization.
Partially Acid-Fast Actinomycetes
Certain non-mycobacterial organisms exhibit partial acid-fastness due to the presence of shorter-chain mycolic acids in their cell walls. The genus Nocardia is the most clinically significant example, causing pulmonary, cutaneous, and disseminated infections, particularly in immunocompromised hosts. Nocardia species are weakly acid-fast when stained with a modified acid-fast stain using a weaker decolorizing agent such as 1% sulfuric acid. These organisms display branching, filamentous morphology on microscopy, which can help differentiate them from mycobacteria. Other partially acid-fast organisms include Rhodococcus and Tsukamurella, which may cause opportunistic infections in select populations. Keep in mind, these organisms are usually detectable on a normal gram stain and culture by normal bacterial culture methods.
AFB in Popular Culture
Moloka‘i is a historical novel by Alan Brennert that tells the life story of Rachel Kalama, a Hawaiian girl born in the late 19th century who contracts leprosy (Hansen’s disease) at the age of seven. Because of the public health policies of the time, she is forcibly removed from her family and sent to live in the isolated leprosy settlement at Kalaupapa on the island of Moloka‘i.
The book follows Rachel’s life over the decades she spends in exile, portraying not only the hardships of separation, illness, and stigma but also the resilience, friendships, romances, and community she builds there. Through her experiences, the novel explores themes of loss, hope, cultural identity, and human dignity in the face of prejudice. Brennert weaves in historical detail about Hawaii’s annexation, the medical understanding of leprosy, and the evolving policies around the treatment and isolation of patients.
While fictional, Moloka‘i is grounded in real history and incorporates real events and historical figures connected to Kalaupapa. It is both a personal coming-of-age story and a broader look at a painful chapter in Hawaiian and medical history.
John Henry “Doc” Holliday’s illness in Tombstone—both in historical accounts and in dramatized portrayals—centers on his advanced tuberculosis, a chronic and ultimately fatal infection that shaped much of his adult life.
Holliday had contracted pulmonary tuberculosis, likely from his mother during childhood, in an era when the disease was poorly understood and without effective treatment. Caused by Mycobacterium tuberculosis, it progressively damaged his lungs, producing chronic cough, hemoptysis (coughing up blood), fatigue, fever, and weight loss. By the time he arrived in Tombstone, Arizona in 1880, he was already severely debilitated, his tall, thin frame and persistent cough marking the toll of the disease.
In the historical record, Holliday’s tuberculosis made life in the arid Southwest both a necessity and a gamble—the dry climate was thought to slow disease progression, though it could not cure it. His infection flared intermittently, with violent coughing fits and spells of exhaustion, but he maintained a reputation as a skilled gambler and gunman. During the events surrounding the Gunfight at the O.K. Corral in October 1881, Holliday was living with the constant background of active pulmonary infection. Accounts from the period note that stress, poor nutrition, and heavy alcohol use likely worsened his symptoms.
Tuberculosis in Holliday’s time was universally fatal in its advanced stages, and his case was no exception. The infection remained active throughout his years after Tombstone, and he died in 1887 in Glenwood Springs, Colorado, at the age of 36. His illness in Tombstone is remembered not just as a medical detail but as part of his larger legend—a man battling both mortal disease and mortal enemies in the lawless frontier.