Drug-resistant TB

Drug-resistant TB a “global health security risk,” WHO says

Half a million people fell sick with dangerous superbug strains of tuberculosis (TB) in 2012, but fewer than one in four were diagnosed, putting the rest at risk of dying due to the wrong medicines or no treatment at all.

Latest data from the World Health Organization (WHO), which says drug-resistant TB is a “global health security risk,” showed a third of the estimated 9 million people who contract TB in any form each year do not get the care they need.

This has led to drug resistance spreading around the world at an alarming rate and has given rise to incurable strains of the bacterial infection — known as totally drug-resistant TB — which cannot be treated with any known medicines.

“Earlier and faster diagnosis of all forms of TB is vital,” said WHO director general Margaret Chan as the U.N. health agency published new TB data on Thursday. “It improves the chances of people getting the right treatment and being cured, and it helps stop spread of drug-resistant disease.”

Last year the WHO called for multidrug-resistant tuberculosis (MDR-TB) to be recognized as a public health crisis. It says the contagious, deadly superbug forms of the disease carry “grave consequences for those affected.”

Treating even regular TB is a long process. Patients need to take a cocktail of antibiotics for six months and many fail to complete the treatment.

This in turn has fuelled the emergence of drug-resistant TB — a man-made problem that has grown in the past decade because people sick with regular TB were either being given the wrong medicines or wrong doses or did not complete their treatment.

Diagnosis gap

Experts say one of the major hurdles to tackling drug-resistant strains effectively is that so many patients who have contracted them do not know it and so continue with the wrong treatments or are not treated at all.

Some of the poorest and most ill-equipped countries have only one central laboratory, which often has limited capacity to diagnose MDR-TB. In other cases, patient samples have to be sent to other countries for testing.

Traditional diagnostic tests can take more than two months to get results, leaving a dangerous gap in which the patient is not getting the right treatment and is putting others at risk of catching the contagious disease.

The WHO says up to 2 million people worldwide may be infected with drug-resistant TB by 2015.

Newer, speedier diagnostic tests have been developed in recent years, but the problem has been getting the technology and know-how to the countries where they are needed most.

However, Chan cited encouraging signs from an international project known as EXPAND-TB (Expanding Access to New Diagnostics for TB), financed by UNITAID, which has helped to triple the number of MDR-TB cases diagnosed in participating countries.

In 2009, UNITAID backed the EXPAND project with $87 million US to new TB diagnostic technologies in 27 low- and middle-income countries, which together account for around 40 per cent of the global MDR-TB burden.

“The gap in access to TB diagnostics and care is far from filled, but it is narrowing,” said Mario Raviglione, director of WHO’s global TB program. “Increased capacity and reduced prices mean that we can reach more people.”

Source: cbc news

Promising class of antibiotics discovered for drug-resistant TB

St Jude Children’s Research Hospital scientists have discovered a promising new class of antibiotics that could aid efforts to overcome drug-resistance in tuberculosis (TB). The drugs increased survival of mice infected with TB and were effective against drug-resistant strains of TB. St Jude led the international research effort, results of which appear in the journal Nature Medicine.

The antibiotics, called spectinamides, were created by changing the chemical structure of an existing antibiotic, spectinomycin, which does not work against TB.

In multiple trials of mice with both active and chronic TB infections, researchers report that one version of the new drug—an analogue known as 1599—was as good as or better than current TB drugs at reducing levels of the bacteria in the lungs of mice. In addition, 1599 caused no serious side effects.

“This study demonstrates how classic antibiotics derived from natural products can be redesigned to create semi-synthetic compounds to overcome drug resistance,” said corresponding author Richard Lee, a member of the St Jude Department of Chemical Biology and Therapeutics. “I hope the result will be drugs that are more effective against tuberculosis and offer a faster route to a cure with fewer side effects.”

TB remains a leading cause of global illness and death. The latest data from the World Health Organization estimates that TB kills 1.3 million persons annually and sickens 8.6 million worldwide. Current treatment requires months of multi-drug therapy to eradicate the slow-growing bacterium, which can lie dormant for years without causing symptoms and results in hard to treat chronic or latent infections. The rise of multi-drug resistant TB, including strains reportedly resistant to all available medications, has further complicated treatment.

This new class of antibiotics works against TB by disrupting the function of a part of the cell known as the ribosome, which is responsible for protein synthesis. To do that, the spectinamides bind to a particular site on ribosomes that is not shared by other TB drugs. That allows the drug to be used in combination with other medications.

For this study, researchers used an approach called structure-based design to re-engineer how spectinomycin binds to the ribosome. To guide their design efforts, scientists used a 3-D model that provided an atomic-level view of spectinomycin bound to the tuberculosis ribosome. The study reinforces the potential of structure-based design as a tool for designing other new agents to block mechanisms TB and other bacteria use to resist current antibiotics, Lee said.

The research reports on the first 20 of the more than 120 spectinomycin derivatives that have resulted from the effort. The list includes 1599 and two other analogues tested against TB in mice.

The three analogues not only bound the ribosome tightly, but they were more successful at avoiding a TB resistance mechanism called efflux. The TB bacteria use efflux pumps as a strategy to remove drugs and other threats from the cell before they can work against the bacteria. Efflux pumps, however, did not protect TB against spectinamides.

The drugs were also effective against multi-drug-resistant strains of TB growing in the laboratory. The strains had been isolated from patients with the disease.

Researchers also found no evidence that 1599 or the two other analogues tested interfered with normal functioning of human cells. Preliminary safety testing on cells grown in the laboratory showed the drugs were not toxic to mammalian cells because they only inhibit the bacterial ribosomes and not mammalian ribosomes.

Work is underway now in mice combining 1599 with new or existing TB drugs. The goal is to identify multi-drug therapy to try in a clinical trial of patients with drug-resistant TB.

Source: India medical Times

Drug-resistant TB spreading fast in Russia

scientists have found that tuberculosis strains in Russia carry mutations that not only make them resistant to antibiotics but also help them spread more effectively.

The latest study of TB cases in Russia indicates that rampant drug resistance may not be the only explanation for the TB rise in the region – biological factors also play a major role in it.

Researchers at Queen Mary University of London analysed 1,000 genomes from different TB isolates – the largest whole-genome study of a single bacterial species so far.

This enabled the team to identify previously unknown mutations linked to antibiotic resistance, as well as “compensatory mutations” that improve the ability of drug-resistant TB to spread.

Nearly half of the TB isolates were multi-drug resistant, which means that they were impervious to the two common first-line antibiotics that cure most TB infections.

Sixteen percent of these isolates also harboured mutations that made them impervious to “second-line” drugs.

These infections are more expensive to treat and patients who receive ineffective drugs are more likely to spread TB, said the research published in the journal Nature Genetics.

TB, which is caused by the bacterium Mycobacterium tuberculosis, exploded in Russia and other former Soviet nations in the early 1990s, after the collapse of the Soviet Union and its health system.

“It certainly adds an extra layer of worry, because one had assumed if you could solve ‘programmatic’ weaknesses, you would solve the problem of the drug-resistant TB,” stressed Francis Drobniewski, a microbiologist at Queen Mary University.

“Although we know the general story of TB drug resistance in Russia, these new findings are still shocking,” added Christopher Dye, an epidemiologist at the World Health Organisation (WHO) in Geneva.

According to Megan Murray, an epidemiologist at the Harvard School of Public Health in Boston, Massachusetts, the worst scenario is that the organisms are developing resistance, compensating for it, and evolving into something that’s new and different, that’s much less treatable.

Source: Sify