TUBERCULOSIS (TB) is a disease most people associate with poverty or HIV/AIDS. Not so, says the head of the University of Cape Town’s Institute of Infectious Disease and Molecular Medicine, Valerie Mizrahi, who has first-hand experience of just how easily it can sweep through a middle-class family.
Twenty years ago her mother took ill with a chest complaint that had her doctors baffled. For months she was in and out of hospital, with no definitive diagnosis. "I remember asking one of her physicians if he’d done a sputum test (for TB) and my question was met with amazement. She was a middle-class Jewish woman living in the northern suburbs of Johannesburg, and doctors thought people of her phenotype just didn’t get TB," says Zimbabwean-born Mizrahi, who was just beginning her research into the bacteria that causes so much trouble, Mycobacterium tuberculosis.
Today she oversees a team at the institute that has pinpointed the role of vitamin B12 in the metabolism of TB, work they hope will help to identify novel ways for drugs to target the germ. She has a string of awards to her name, including the Christophe Mérieux Prize, a Unesco L’Oréal Women in Science Prize, and the Silver order of Mapungubwe.
Feeling quite desperate, her mother eventually took a holiday to Plettenberg Bay, hoping rest and sea air would do her some good. There, a country doctor took one look at her and diagnosed TB, says Mizrahi.
"All of a sudden I was thrust from the world of basic scientific research into the realm of the public-health sector, as my mother was treated at what is now the Sizwe Tropical Diseases Hospital. It affected me very deeply," she says, describing an agonising three-month wait for test results that confirmed the bacteria that had infected her mother were susceptible to the standard drug treatment. Even 20 years ago, patients faced the prospect of getting infected with drug-resistant strains of TB that would mean turning to much older drugs with potentially serious side effects.
Mizrahi’s mother was cured and the family thought it had put TB behind it. But five years later, her dad was laid low with a persistent cough that turned out to be TB. He also recovered.
Many people flinch when Mizrahi talks about her parents surviving TB, she says, as it is still so stigmatised. It is widely perceived as a disease of the poor or associated with HIV/AIDS, yet while both these factors increase the risk of acquiring TB, the reality is the airborne bug affects rich and healthy people too, she says.
Back in the early 1990s, when Mizrahi began working on TB, there were huge gaps in scientists’ understanding of the bacteria. Today, many of those questions remain unanswered, offering scientists an intellectually stimulating field to explore. "It is a really formidable organism, so the scientific challenges it presented 20 years ago were extraordinarily compelling. How could this bug infect one-third of humanity, ‘sleep’ in individuals for 30 years and then wake up and cause disease? We had drugs, we had vaccines, and yet the disease was completely out of control."
The numbers today are just as daunting. One third of the world’s population is still infected with TB, there are 9-million new cases each year, and it kills someone every 30 seconds. It is the leading cause of death in South Africa, responsible for about 12% of all deaths in 2010.
In a city such as Cape Town, which even before the emergence of HIV/AIDS had a sizeable TB epidemic, the statistics are even more alarming: about nine out of 10 people living in the city are infected with TB, says Mizrahi. Most of them will go through life harbouring the disease in its latent state and never get ill, but scientists still don’t know exactly what predisposes some seemingly healthy people to succumb while others hold infection at bay, she says.
TB is an ancient bacteria that has co-evolved with humanity. It has been found in Egyptian mummies and described in Chinese and Indian medical texts thousands of years old. Over the centuries, it has thus devised a host of tricks for surviving in its human host, including the ability to lie dormant for decades. "It comes equipped with its own coat of armour and its own food store, and can survive in places in the body where there is very little oxygen or nutrients," says Mizrahi.
One of the many TB puzzles is the mechanism some TB bugs use to evade antibiotics, sometimes for months at a time, she says. When TB strikes, the standard treatment is six months of daily doses of a cocktail of six antibiotics. It is an unusually long treatment, if you consider that a child with an ear or chest infection would typically be prescribed a five-day course and that would do the trick. "The bulk of the TB gets killed very fast, within about two weeks, and the patient quickly starts to feel better. But there are organisms that linger on in the host in a nonreplicating state. We think present TB antibiotics can’t ‘see’ them, because they are designed to kill dividing cells," says Mizrahi.
Understanding more about these lingering bugs is crucial for the development of new medicines, which may need to target a different aspect of the bacteria’s life cycle, she says. The global attitude to TB is very different from the 1940s and 1950s, when there was optimism about conquering the disease as a raft of new and initially highly effective antibiotics were developed. For a brief period, they turned TB from a disease that killed 80% of those it infected into one that almost everyone survived.
"The world was lulled into a false sense of complacency," says Mizrahi. There appeared to be no great incentive for pharmaceutical companies to devise new drugs, investment in the field dried up and few scientists entered the field. The disease was "utterly neglected" for decades, until the emergence of the global HIV/AIDS epidemic in the early 1990s sent TB rates soaring, even in countries that had virtually eliminated it, says Mizrahi. Drug resistance has also worsened.
With so many aspects of TB not yet understood, devising new TB medicines is a huge challenge. "It is the Mount Everest of drug discovery," says Mizrahi. To illustrate the scientific neglect of TB, Mizrahi compares it to HIV/AIDS. The epidemic quickly became a global issue, with a strong advocacy movement lobbying for funding for diagnostics and affordable treatments. Today, there are dozens of drugs for treating HIV, and blood tests that reveal exactly how much of the virus is circulating in a patient’s body and how great an effect it is having on their immune system. By contrast, TB has never had a powerful activist movement driving it to the top of the political agenda. Drug development began again in earnest only 10 years ago, when HIV/AIDS activists began clamouring for better TB treatments, and there are still no tests to gauge how much TB is in a patient’s body, determine where it is hiding, or assess how their body is faring in response.
With so many scientific questions to answer, TB will be a fascinating research field for many years to come.
"I was intrigued by TB 20 years ago, and I am equally intrigued today," says Mizrahi.
Source: BDlive