H5N1

France: Medical and surgical management of XDR-TB

Via Emerging Infectious Diseases, an ahead-of-print report: Preliminary Favorable Outcome for Medically and Surgically Managed Extensively Drug-Resistant Tuberculosis, France, 2009–2014. The abstract:

We report 20 cases of extensively drug-resistant tuberculosis managed in France. Treatment was individualized and included bedaquiline and linezolid for most patients and surgery in 8 patients. At last follow-up (22 months), 19 patients had achieved conversion from positive to negative on culture testing. These promising results of comprehensive management obtained in a small series deserve confirmation.

MSF in Russia: New TB drug regimen helps patients with extensive resistance to treatment

Via MSF.org: Grozny: New TB drug regimen helps patients with extensive resistance to treatment.

Médecins Sans Frontières (MSF) says a new combination of drugs created to treat extensively drug-resistant Tuberculosis (XDR-TB) is having a significant impact on a group of patients who are in the midst of a two-year treatment to cure their disease. 

In 2013, an MSF team in Grozny noticed that a growing number of patients with multi-drug resistant TB (MDR-TB) were not responding to second-line drugs, and there was no alternative medication available in the country to help them. 

MDR-TB is resistant to at least two of the best anti-TB drugs, isoniazid and rifampicin. These drugs are considered first-line drugs and are used to treat all people with TB. XDR-TB is caused by strains of MDR-TB that are also resistant to second-line drugs, including at least one from the class of fluroquinolones, and at least one of three injectable second-line drugs. 

MSF approached the Ministry of Health with a proposal to tackle XDR-TB in a new way and in April 2014, began treating patients suffering from XDR-TB with a combination of second-line TB drugs and a new TB drug called bedaquiline. Four additional re-purposed drugs recognised by the World Health Organization are also being used, including clofazimine (commonly used for leprosy), linezolid, amoxicillin/clavulanic acid and imipenem/cilastatin (commonly used for other infections). This combination of drugs has never been used before in the Russian Federation. 

To date, MSF has initiated 51 patients on the new bedaquiline drug regimen. Over the course of the two year treatment each patient will receive a different combination of drugs according to the severity of their illness. The 28 patients who require imipenem/cilastin are being treated in hospital because they need a surgical procedure to insert a catheter to administer the drug. 

MSF is now in the process of handing the management of its drug sensitive and multidrug-resistant TB patients back to the Ministry of Health in order to focus its energies on its XDR-TB patients. Dr Animesh Sinha says that the first outcomes look very promising: “With the new regimen we have seen excellent results that would have been unthinkable before.” 

MSF has also started treating patients suffering from both TB and diabetes, as people who suffer from the latter can be more prone to contracting TB. A total of 12 patients are currently enrolled in the programme.

ECDC Annual Epidemiological Report 2014: Tuberculosis

ECDC has published Annual Epidemiological Report 2014: tuberculosis. The summary:

​The Annual Epidemiological Report 2014 for respiratory tract infections - tuberculosis (TB) provides a snapshot of the epidemiological situation of TB in Europe, featuring data from 2012.  

In 2012, 68 423 cases of tuberculosis were reported in 29 EU/EEA countries, which was 6% less than in 2011, reflecting a decrease in 19 countries. The EU/EEA notification rate was 13.5 per 100 000 population. Eighty per cent of all notified TB cases were newly diagnosed and 70% of new pulmonary TB cases were culture-confirmed. Twenty-seven per cent of all TB cases were of foreign origin, mostly residing in low-incidence countries. 

Adult age groups were equally affected by TB while the notification rate in children under the age of 15 years was 3.6 per 100 0000, consistent with a slightly decreasing long-term trend. Males were over-represented in almost all EU/EEA Member States and in all adult age groups, with the greatest gender imbalance among those aged 45 to 64 years. 

Multidrug-resistant TB (MDR TB) was reported for 5% of cases with drug susceptibility testing results (3% of new pulmonary TB cases and 19% of previously treated pulmonary cases) and continues to be most prevalent in the three Baltic countries. Extensively drug-resistant (XDR) TB was reported for 14% of 978 MDR TB cases tested for second-line drug susceptibility. Five per cent of TB cases with known HIV status were co-infected with the virus.   

In total, 75% of TB cases notified in 2011, 34% of MDR TB cases notified in 2010 and 25% of XDR TB cases notified in 2009 had successfully completed their treatment.   

New publication format 

The Annual Epidemiological Report is a key ECDC publication on the epidemiology of communicable diseases of public health significance in Europe. In order to facilitate more timely publication, this year’s edition of the Annual Epidemiological Report is being first published a disease group at a time and will later be compiled into one comprehensive report.   

This report presents the epidemiological situation for tuberculosis as of 2012. Other respiratory tract infections are covered in a separate section of Chapter 2.1

WHO: Improved data reveals higher global burden of tuberculosis

WHO has published Improved data reveals higher global burden of tuberculosis. Excerpt:

Recent intensive efforts to improve collection and reporting of data on tuberculosis (TB) are shedding new light on the epidemic, revealing that there are almost half a million more cases of the disease than previously estimated. 

WHO’s "Global Tuberculosis Report 2014", published today, shows that 9 million people developed TB in 2013, and 1.5 million died, including 360 000 people who were HIV positive. 

The report stresses, however, that the mortality rate from TB is still falling and has dropped by 45% since 1990, while the number of people developing the disease is declining by an average 1.5% a year. An estimated 37 million lives have been saved through effective diagnosis and treatment of TB since 2000. 

“Following a concerted effort by countries, by WHO and by multiple partners, investment in national surveys and routine surveillance efforts has substantially increased. This is providing us with much more and better data, bringing us closer and closer to understanding the true burden of tuberculosis,” says Dr Mario Raviglione, Director of the Global TB Programme, WHO. 

Although higher, these revised figures fall within the upper limit of previous WHO estimates. The report, however, underlines that a staggering number of lives are being lost to a curable disease and confirms that TB is the second biggest killer disease from a single infectious agent. 

In addition, around 3 million people who fall ill from TB are still being ‘missed’ by health systems each year either because they are not diagnosed, or because they are diagnosed but not reported. 

Insufficient funding is hampering efforts to combat the global epidemic. An estimated US$ 8 billion is needed each year for a full response, but there is currently an annual shortfall of US$ 2 billion, which must be addressed. 

Diagnostic capacity for MDR-TB increasing faster than treatment capacity 

The multidrug-resistant TB (MDR-TB) crisis continues, with an estimated 480 000 new cases in 2013. Worldwide, about 3.5% of all people who developed TB in 2013 had this form of the disease, which is much harder to treat and has significantly poorer cure rates. 

While the estimated percentage of new TB cases that have MDR-TB globally remains unchanged, there are severe epidemics in some regions, particularly in Eastern Europe and Central Asia. In many settings around the world, the treatment success rate is alarmingly low. Furthermore, extensively drug-resistant TB (XDR-TB), which is even more expensive and difficult to treat than MDR-TB, has now been reported in 100 countries. 

Since 2009, with more laboratories rolling out rapid tests, there has been a tripling of MDR-TB cases being diagnosed. In 2013, 136 000 MDR-TB cases were detected and 97 000 people were started on treatment. 

Although the number of patients treated has increased three-fold since 2009, at least 39 000 patients, diagnosed with this form of TB, were not being treated last year and globally only 48% of patients were cured.

UK: Sewage-treatment plants described as giant 'mixing vessels' for drug-resistant bacteria

Via The Independent: Drug-resistant bacteria: Sewage-treatment plants described as giant 'mixing vessels' after scientists discover mutated microbes in British river. Excerpt:

Superbugs resistant to some of the most powerful antibiotics in the medical arsenal have been found for the first time in a British river – with scientists pinpointing a local sewage-treatment plant as the most likely source. 

Scientists discovered the drug-resistant bacteria in sediment samples taken downstream of the sewerage plant on the River Sowe near Coventry. The microbes contained mutated genes that confer resistance to the latest generation of antibiotics. 

The researchers believe the discovery shows how antibiotic resistance has become widespread in the environment, with sewage-treatment plants now acting as giant “mixing vessels” where antibiotic resistance can spread between different microbes. 

A study found that a wide range of microbes living in the river had acquired a genetic mutation that is known to provide resistance to third-generation cephalosporins, a class of antibiotics used widely to treat meningitis, blood infections and other hospital-acquired infections.     

Within the river sediment, the scientists also found human gut bacteria that had developed resistance to another kind of antibiotic, called imipenem, which is administered by intravenous injections for severe infections not normally treatable with other antibiotics. 

“These are frontline antibiotics and we were not expecting to see these kinds of levels of resistance to them in the environment. It is quite staggering,” said Professor Elizabeth Wellington of  the University of Warwick, who led the study. 

“This is a worrying development and we need to be concerned about it. We’ve completely underestimated the role waste-treatment processes can play in antibiotic resistance,” she told The Independent.

Antibiotic-resistant bugs need global response, say health experts

Via The Guardian: Antibiotic-resistant bugs need global response, say health experts. Excerpt:

Public health experts have called on world leaders to establish a global organisation to fight the rising threat from drug-resistant bugs. 

Antibiotic-resistant pathogens have reached every country, with some patients being treated with drugs that are now the last line of defence against infections. Scientists gathered at the Royal Society in London on Thursday warned the situation is so desperate that a global response in line with efforts to combat climate change is needed. 

About 5,000 people a year die in Britain from infections that are resistant to antibiotics, and drug resistance is growing steadily, eroding the effectiveness of doctors' most powerful antibiotics. 

Writing in the journal Nature, Jeremy Farrar, head of the Wellcome Trust, and Mark Woolhouse, professor of infectious disease epidemiology at Edinburgh University, urge world leaders to set up an international panel on antimicrobial resistance to keep existing drugs working and develop alternatives. 

Based on the UN's intergovernmental panel on climate change, they say it should be charged with finding ways to slash the use of antibiotics to prevent the spread of resistance, and work with industry to develop drugs and treatments to fight infections caused by bacteria, but also viruses and parasites. 

Last year, the UK introduced a five-year plan to improve use of antibiotics, bolster surveillance of resistant bugs and develop tests for the infections. Another area that needs improvement is education of medical students, who typically spend only a week learning about antibiotics. 

But Woolhouse said that, as with climate change, countries had to take action together: "A national plan is not enough. We need to address this problem internationally. We need everyone on board." 

"In terms of the threat to my own health, and that of my children, and my family's health, I am much more concerned about antimicrobial resistance than I am about climate change," Woolhouse added.

South Africa: "Give us a TB regime that works"

This is World Tuberculosis Day. Via The Guardian, a post on the Poverty Matters blog by Jennifer Hughes of MSF: Tuberculosis is an old disease with a new face – and it needs to be stopped. Excerpt:

Nearly half a million people across the globe are infected by strains of tuberculosis against which existing drugs are powerless. In South Africa, where I work, 15,000 people were diagnosed as having drug-resistant TB (DR-TB) in 2012. Up to 80% of them caught it by unknowingly breathing it. 

When they become ill, they come to see me. At those moments, I wish I had chosen to become a schoolteacher or a city planner or engineer – surely, in such professions I would be able to make a bigger difference to people's lives. 

What am I to tell my patients? That, yes, we just celebrated the cure of 30-year-old Siyabulela, but that he is one of only four patients I have treated to beat extensively drug-resistant tuberculosis (XDR-TB), which jumps to its next victim every time someone infected sneezes? That the three other people who started the same treatment at the same time are long dead? 

I can't bear having to look someone in the eye and tell them that I cannot give them better odds of survival than a roll of a dice. Roll a six, you'll live; if not, you'll be dead within two years. In South Africa, only 13% of XDR-TB patients are cured by the existing treatment regimen. 

I also have to tell them that, for that slim shot at survival, they will have to endure a harrowing two years of treatment. For at least the first six months, they will receive daily injections that hurt so much they will be unable to sit down, and the injected drugs could make them permanently deaf. 

So limited is the medical arsenal at my disposal, another drug I may be forced to prescribe might trigger mental instability, causing psychotic episodes so acute that they could be a danger to themselves. 

But, I have to explain to my patients, they will only know after two years whether it was all worth it; only then will it become clear whether their roll of the dice produced the required six. 

I'm sick and tired of using plasters to patch up gaping wounds. I need something I can really work with, something that can save lives. We need a new treatment regimen against TB that actually works. Treatment that has not been dredged up from the dark ages of modern medicine and reused because, well, it's better than nothing. 

There is some hope on the horizon. For the first time in 50 years, new drugs are being developed to treat TB. They represent great strides forward, but they can't be used in isolation. TB is so powerful that you need a full cocktail of drugs to beat it. 

The only way to beat this disease is for governments, donors, pharmaceutical firms and research organisations to find new combinations of drugs that are simple, accessible and more tolerable than current treatment and can be implemented rapidly in countries where DR-TB is rife. 

But by the time that dream is realised, 80% of the patients I see every day, who see my white doctor's coat as a life jacket, will be dead and gone, forgotten by all but their devastated families in the poorest corners of the country.

South Africa: Long-term outcomes of XDR-TB patients

Via The Lancet: Long-term outcomes of patients with extensively drug-resistant tuberculosis in South Africa: a cohort study. The summary:

Background 

Long-term treatment-related outcomes in patients with extensively drug-resistant (XDR) tuberculosis are unknown. We followed up a cohort of patients to address knowledge gaps. 

Methods 

Between March, 2008, and August, 2012, we prospectively followed up a cohort of 107 patients from three provinces in South Africa, who had been diagnosed with XDR tuberculosis between August 2002, and February, 2008. Available isolates from 56 patients were genotyped to establish strain type and used for extended susceptibility testing. 

Findings 

All patients were treated empirically as inpatients with a median of eight drugs (IQR six to ten). 44 patients (41%) had HIV. 36 (64%) of 56 isolates were resistant to at least eight drugs, and resistance to an increasing number of drugs was associated with the Beijing genotype (p=0·01). 

After 24 months of follow-up, 17 patients (16%) had a favourable outcome (ie, treatment cure or completion), 49 (46%) had died, seven (7%) had defaulted (interruption of treatment for at least 2 consecutive months), and 25 (23%) had failed treatment. 

At 60 months, 12 patients (11%) had a favourable outcome, 78 (73%) had died, four (4%) had defaulted, and 11 (10%) had failed treatment. 45 patients were discharged from hospital, of whom 26 (58%) had achieved sputum culture conversion and 19 (42%) had failed treatment. Median survival of patients who had failed treatment from time of discharge was 19·84 months (IQR 4·16—26·04). 

Clustering of cases and transmission within families containing a patient who had failed treatment and been discharged were shown with genotypic methods. Net sputum culture conversion occurred in 22 patients (21%) and median time to net culture conversion was 8·7 months (IQR 5·6—26·4). 

Independent predictors of probability of net culture conversion were no history of multidrug-resistant tuberculosis (p=0·0007) and use of clofazamine (p=0·0069). Independent overall predictors of survival were net culture conversion (p<0·0001) and treatment with clofazamine (p=0·021). Antiretroviral therapy was also a predictor of survival in patients with HIV (p=0·003). 

Interpretation 

In South Africa, long-term outcomes in patients with XDR tuberculosis are poor, irrespective of HIV status. Because appropriate long-stay or palliative care facilities are scarce, substantial numbers of patients with XDR tuberculosis who have failed treatment and have positive sputum cultures are being discharged from hospital and are likely to transmit disease into the wider community. Testing of new combined regimens is needed urgently and policy makers should implement interventions to minimise disease spread by patients who fail treatment.

South Africa risks spreading totally drug-resistant TB: study

Thanks to Andrew M. Seaman for tweeting the link to this Reuters report: South Africa risks spreading totally drug-resistant TB: study. Excerpt:

Patients with contagious and highly drug-resistant tuberculosis (TB) are being routinely discharged from hospitals across South Africa, exposing others in their communities to potentially deadly infections, researchers said on Friday. 

In a study in the medical journal The Lancet, they said the patients, with strains of TB known as extensively-drug resistant (XDR) and totally drug resistant (TDR) TB, have exhausted all available treatment options and are sent home. 

"These patients can survive for months or even years and are contributing to the community-based spread of XDR-TB," said Keertan Dheda, who led the study at the University of Cape Town's department of medicine. 

Tuberculosis infects the lungs and can spread through coughing and sneezing. In recent years, drug-resistant strains have spread around the world, batting off standard antibiotics and posing an increasingly urgent public health threat. 

The World Health Organization (WHO) estimates that in Eastern Europe, Asia and South Africa, 450,000 people have MDR-TB, and around half of these will fail to respond to existing treatments.

Yang: ‘Superbugs’ infect more than 2 million in U.S. each year, says CDC report

Via The Toronto Star, Jennifer Yang writes: ‘Superbugs’ infect more than 2 million in U.S. each year, says CDC report. Excerpt:

A landmark new report finds that more than 2 million people are now getting “superbug” infections every year in the United States, with 23,000 dying as a result — conservative estimates that likely only represent the “bare minimum” of the problem, according to the U.S. Centers for Disease Control and Prevention. 

CDC’s threat report 2013 

“Without urgent action now, more patients will be thrust back to a time before we had effective drugs,” said CDC director Dr. Thomas Frieden in a telephone press conference on Monday. 

“We talk about a pre-antibiotic era and an antibiotic era. If we’re not careful, we will soon be in a post-antibiotic era — and in fact, for some patients and some microbes, we are already there.” 

Superbugs are pathogens that are resistant to drugs and have therefore become difficult — or even impossible — to treat. Resistance is now being seen in everything from tuberculosis to gonorrhea and several high-profile health officials have recently spoken out about the growing problem, calling it a “catastrophic threat” that could spell the “end to modern medicine as we know it.”

In the new report, the CDC released its first-ever estimates for antimicrobial resistance in the United States. The public health agency estimates that drug-resistant infections are sickening more than 2,049,442 million people every year and causing more than 23,000 deaths.