In the evolutionary arms race between human and bacterium, Mycobacterium tuberculosis appears to be pulling ahead.
Tuberculosis (TB) evokes two images in my mind; overcrowded, TB-infected prisons expounded upon by Paul Farmer and the Hollywood film success, Moulin Rouge. But since the recent outbreak of the so-called totally-drug-resistant tuberculosis (TDR-TB) in India, TB has a new face. In the evolutionary arms race between human and bacterium, Mycobacterium tuberculosis, the causative agent of tuberculosis, appears to be pulling ahead.
M. tuberculosis is a rod-shaped bacterium that is transmitted via tiny water droplets exchanged between human hosts. On the rare occasion that the bacteria reach the small air sacs, alveoli, of the human lung, infection occurs. In the majority of cases, the body is capable of containing the TB infection. The bacteria can remain latent, or inactive, for many years inside the individual before it manifests symptoms of active disease. When containment fails, active and symptomatic TB disease can develop. The bacteria infect immune cells, which prevents our immune system’s frontline defenses from containing the bacteria and protecting us effectively. In these cases, we bring out the big guns; specialized immune cells that specifically recognize and target the bacteria. It is our own immune response to infection that results in the majority of symptoms—bloody sputum, chest pains, fever, and weight loss—that are the hallmarks of TB infection.
In its 2011 report on Global Tuberculosis, the World Health Organization (WHO) stated that tuberculosis mortality rates had fallen by over a third since 1990 and that all six WHO regions were on track to reach the Millennium Development Goal to decrease TB incidence rates by 2012. When did the tables begin to turn? And should we really be surprised?
Resistant strains of TB are classified by the WHO as either multi-drug resistant (MDR-TB) or extensively-drug resistant (XDR-TB). MDR-TB, which is characterized by resistance to two or more of the most effective first line drugs, became more prevalent in the 1990s. Next to arrive was XDR-TB, which was detected in South Africa in 2007 and showed resistance to first line drugs as well as 2nd line drugs. A natural course of progression would suggest that a totally drug resistant strain would soon be added to TB’s arsenal. However, the term TDR-TB is not yet recognized by the WHO, rather it was coined by researchers in 2009 to characterize a strain of TB that had infected 15 individuals in Iran. Consequently, the term TDR-TB has not been clearly defined for tuberculosis, and at present, the WHO considers the recently reported cases in Mumbai to be XDR-TB, not TDR-TB.
The development of resistance is a natural process that can be explained by Darwin’s theory of natural selection. Over time, a bacterium acquires random mutations in its genetic material that enable it to become resistant to a given antibiotic. The odds that a bacterium acquires a mutation that renders it resistant to a drug are very low. The likelihood it becomes resistant to two or three drugs is even lower and four drugs, lower still. Therefore, TB treatment strategy is similar to that of antiretroviral treatment for HIV/AIDS; try and knock out as many bacteria as you can early on with a cocktail of several drugs so that resistant strains cannot develop. This is where the system is failing.
A lack of patient adherence to treatment regimens and the inappropriate administration of antibiotic drugs by health professionals are two major contributors to the arrival of MDR-TB, XDR-TB, and progressively more resistant strains. A lack of adequate surveillance further exacerbates the problem. According to a 2011 WHO report, fewer than 5% of TB patients are tested for drug resistance.
The situation in India is revealing. The Director-General of India’s national TB program, Ashok Kumar, describes the poor quality of treatment of TB patients in the public system. As a result, patients leave the public system and either cease treatment all together or pay private physicians for care while their funds last. In both situations, treatment is disrupted and, subsequently, the chance of developing drug resistance increases. The story is similar in other localities where treatment is disjointed due to antibiotic shortages and/or lack of access to treatment centers. Another glaring issue arises from the inappropriate administration of antibiotics whether through ineffectual doses or inappropriate drug combinations. The WHO estimates that a mere 16% of patients with drug-resistant TB receive appropriate treatment, while a study conducted in India found that only five out of 106 private practitioners prescribed TB drugs correctly.
While a rampant, global spread of progressively more resistant TB strains could prove catastrophic, the diagnoses of TDR-TB in twelve individuals at the Hinduja Hospital at Mahim in India represents only a very tiny proportion of India’s TB-infected population. More than 1/5 of the world’s TB patients reside in India, and an estimated 1,000 Indians die of TB each day. There is still time to ramp up treatment, to educate individuals on the importance of adherence to the full course of treatment, and to ensure the delivery of appropriate drug combinations. These critical steps, paired with enhanced surveillance of resistant strains and the continued development of novel drugs, could prevent TB from spreading more widely.
By Alisha Kramer