North London TB Journal Club

Paper: Pasipanodya, JG & Gumbo, T. A meta-analysis of self-administered versus directly observed therapy effect on microbiologic failure, relapse, and acquired drug resistance in tuberculosis patients. Clinical Infectious Diseases (2013). Full text available online for free: http://cid.oxfordjournals.org/content/early/2013/04/25/cid.cit167.full.pdf+html

Presenter: Prof. Andrew Nunn, MRC Clinical Trials Unit

Chair: Patrick Phillips, MRC Clinical Trials Unit

Time: 12:00-1.00 pm, 21 May 2013

Venue: Room 401, MRC Clinical Trials Unit, Aviation House, 125 Kingsway

Directions: See http://www.ctu.mrc.ac.uk/about_us/contact_details.aspx. The entrance is opposite Holborn tube station and looks like the entrance to a church building.

External attendees will need to wait at reception and be taken to the meeting room. If you plan to attend, please contact Patrick Phillips on ppp@ctu.mrc.ac.uk so that reception know who is expected.

Topic: Linezolid for treatment of chronic extensively drug-resistant tuberculosis.

Lee et al. N Engl J Med. 2012 Oct 18;367(16):1508-18. doi: 10.1056/NEJMoa1201964.

Presenter: Isobella Honeyborne, Postdoctoral Scientist, Centre for Clinical Microbiology, Department of Infection, University College London

Chair: Timothy Mchugh, University College London

Time: 9 til 10.00am, 29^th April.

How do you treat extensively drug-resistant TB in patients who have not had a response to any available chemotherapeutic option during the previous 6 months?

Isobella Honeyborne will present the results of this paper which examines the use of Linezolid for treatment of chronic extensively drug-resistant tuberculosis. Isobella will also create some additional discussion around Clifton Barry’s talk at the recent Paris conference.

Join us for a good discussion.

Venue: Tutorial Room 3 (TR3), Royal Free Hospital, Hampstead

Tutorial Room 3 is on the Lower Ground Floor at the Royal Free Hospital. For a more detailed view, please click on the map. For directions to the Royal Free Hospital, please click here.

You can download the paper here.

Topic: Transmission, outbreaks and whole genome sequencing

Walker et al. Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks: a retrospective observational study. Lancet Infect Dis 2013; 13(2): 137-46.

Presenter: Jess Mears, Centre for Infectious Disease Epidemiology, UCL
Chair: Marc Lipman, Royal Free Hospital

Time: 9 til 10.00am, 5 March 2013
Venue: Tutorial Room 7 (TR7), Royal Free Hospital, Hampstead

Tutorial Room 7 is on the Lower Ground Floor at the Royal Free Hospital. For a more detailed view, please click on the map. For directions to the Royal Free Hospital, please click here.

There is growing interest in TB whole genome sequencing as an epidemiological tool. Proponents suggest we may soon be able to map chains of transmission and identify so-called super-spreaders.

Tim Walker’s paper sets out to test the technology using a set of well characterised isolates from freezers in the West Midlands. How fast does TB mutate within an individual? To what extent do the index case and the next generation differ genetically? Do epidemiological links predict genetic similarity?

Is whole genome sequencing an expensive fad or a genuinely useful epidemiological tool? Join us for a good discussion.

You can download the paper here.

Topic: Modelling TB transmission in Pollsmoor Prison, Cape Town

Johnstone-Robertson et al. Tuberculosis in a South African prison – a transmission modelling analysis. S Afr Med J 2011; 101: 809-813.

Presenter: Pete Dodd, CMMID, London School of Hygiene and Tropical Medicine

Chair: Richard White, CMMID, London School of Hygiene and Tropical Medicine

Time: 5.15pm til 6.15pm (drinks after), 11 February 2013

Venue: LG81, London School of Hygiene and Tropical Medicine, Keppel Street

Dudley Lee was detained in Pollsmoor Prison in 1999. His case took more than four years to make its way through the courts. By the time he was released in 2004, having been found innocent, he had acquired TB.

With crowded cells, poor ventilation, high HIV prevalence, and poor healthcare, South African prisons, unsurprisingly, have appalling TB control.

This modelling paper was cited in Dudley Lee’s successful claim in the Constitutional Court for compensation. It attempts to predict the likely impact of interventions, such as better case finding or improved ventilation, on TB transmission in the prison.

Join us to discuss the value and limits of mathematical models, activism, disadvantage, environmental health and TB control in high burden institutional settings.

The paper is available here.

Topic: Promising new regimens or studies of uncertain value?

Diacon et al. 14-day bactericidal activity of PA-824, bedaquiline, pyrazinamide, and moxifloxacin combinations: a randomised trial. Lancet 2012; 380: 986-93.

Presenter: Jurgens Peters, London School of Hygiene and Tropical Medicine

Chair: Patrick Phillips, MRC Clinical Trials Unit

Time: 1:00-1.50 pm, 31 January 2013

Venue: Room 402,  MRC Clinical Trials Unit, Aviation House, 125 Kingsway

Directions: See http://www.ctu.mrc.ac.uk/about_us/contact_details.aspx. The entrance is opposite Holborn tube station and looks like the entrance to a church building.

* External attendees will need to wait at reception and be taken to the meeting room. If you plan to attend, please contact Patrick Phillips on ppp@ctu.mrc.ac.uk so that reception know who is expected. *

We urgently need better drugs for TB. This would allow for shorter first line therapy and treatment for drug resistant TB this is safer and more effective with patients experiencing fewer unpleasant side effects.

This paper describes interesting data on novel drugs and combinations that seem to exhibit good ‘early bactericidal activity’. These include a regimen that might work for MDR-TB.

With the FDA advisory committee recently recommending limited approval of Bedaquiline for MDR-TB on the basis of culture conversion data from Phase II studies, the use of surrogate outcomes is topical.

Join us to discuss the design and evaluation of new TB regimens, the value of surrogate outcomes, and the future of TB therapy.

The paper is available here.

‘People come–they stay for a while, they flourish, they build–and they go. It is their way. But we remain. There were badgers here, I’ve been told, long before that same city ever came to be. And now there are badgers here again. We are an enduring lot, and we may move out for a time, but we wait, and are patient, and back we come. And so it will ever be.’

The Wind in the Willows by Kenneth Grahame, 1908

Topic: Should we kill all the badgers?

Donnelly et al. Positive and negative effects of widespread badger culling on tuberculosis in cattle. Nature 2006; 439: 843-846.

Presenter: Sarah Lou Bailey, Wellcome Trust Clinical Research Fellow, LSHTM

Chair: Dave Moore, TB Centre, LSHTM

Time: 5.15pm til 6.15pm (drinks after), Tuesday 18 December 2012

Venue: LG7, London School of Hygiene and Tropical Medicine, Keppel Street

To cull or not to cull? That is the question.

Over the past two decades the incidence and geographical extent of bovine TB have been increasing in the UK, resulting in the slaughter of increasing numbers of infected cattle and economic consequences for farmers.

This has prompted several reviews of bovine TB control measures. Patterns of infection in cattle and badgers are closely associated. Various forms of badger culling have been used in the UK over the last three decades in an attempt to control TB in cattle.

The UK Government recently proposed culling more than 70% of badgers in two pilot areas, Gloucestershire and west Somerset. Amid public protests and scientific confusion over the effectiveness of badger culling, these plans have recently been postponed – but not abandoned.

This Nature letter attempts to explain discrepancies in the evidence from cluster randomised controlled trials of badger culling with seemingly conflicting conclusions.

Join us to discuss cluster randomised controlled trials, how evidence is translated into policy and the fate of our black and white friends. Drinks after!

The paper is available here.