Catharina Boehme on a New Diagnostic Test for TB

Fast Breaking Papers Commentary, August 2011

Catharina Boehme

Article: Rapid Molecular Detection of Tuberculosis and Rifampin Resistance


Authors: Boehme, CC;Nabeta, P;Hillemann, D;Nicol, MP;Shenai, S;Krapp, F;Allen, J;Tahirli, R;Blakemore, R;Rustomjee, R;Milovic, A;Jones, M;O'Brien, SM;Persing, DH;Ruesch-Gerdes, S;Gotuzzo, E;Rodrigues, C;Alland, D;Perkins, MD
Journal: N ENGL J MED, Volume: 363, Issue: 11, Page: 1005-1015, Year: SEP 9 2010
* Fdn Innovat New Diagnost, Ave Bude 16, CH-1202 Geneva, Switzerland.
* Fdn Innovat New Diagnost, CH-1202 Geneva, Switzerland.
(Addresses have been truncated)

Catharina Boehme talks with ScienceWatch.com and answers a few questions about this month's Fast Breaking Paper paper in the field of Clinical Medicine.


SW: Why do you think your paper is highly cited?

Although rare in developed countries, tuberculosis (TB) remains one of the world's deadliest infectious diseases. TB kills approximately 1.8 million people each year, mainly in developing countries, and drug-resistant TB is a growing threat. Early detection of TB is crucial to stop the TB epidemic, because undiagnosed and untreated patients with active TB—including drug-resistant TB—can infect 10-15 other people each year.

Lack of proper diagnosis of TB costs patients and their families' valuable time and money, delays treatment, and leads to continued transmission of the disease. Mounting drug resistance and a growing number of patients co-infected with TB and HIV have highlighted the urgent need for better diagnostic tests.

While there have been a number of new diagnostic products developed in the past few years, most countries still rely on sputum smear microscopy, a 125-year old technology which is often fallible, cannot detect drug-resistant or extra-pulmonary TB, and is particularly ineffective at diagnosing TB in children and HIV-positive individuals. This paper describes a completely new approach to TB diagnosis, which brings cutting-edge molecular methods much closer to where patients first seek care, in a format that can be used safely and effectively outside of conventional laboratories.

SW: Does it describe a new discovery, methodology, or synthesis of knowledge?

Catharina Boehme
Study team at Special Treatment Institution, Baku, Azerbaijan.

View larger images of all the Study Teams in the tabs below.

The paper describes the results of the first evaluation studies of a new diagnostic test for TB and resistance to rifampicin in Peru, Azerbaijan, South Africa, and India.

SW: Would you summarize the significance of your paper in layman's terms?

The new Xpert® MTB/RIF test produces results for TB and drug resistance in less than two hours from a raw sputum sample, instead of weeks or months. It integrates sputum processing, DNA extraction and amplification for TB and rifampicin (RIF) resistance. It requires little hands-on time and minimal technical skills or laboratory facilities. As such, it has the potential to be used outside reference laboratories, at local diagnostic centers or clinics, where the need is greatest.

The study shows that Xpert MTB/RIF provides highly sensitive detection of TB and drug resistance in low resource settings more easily and in significantly less time than any current, widely used diagnostic. Xpert MTB/RIF test successfully identified 98% of all culture-confirmed TB cases, including over 90% of those with smear-negative disease. It also accurately detected resistance to the powerful anti-TB drug rifampicin in more than 97% of patients.

SW: How did you become involved in this research, and how would you describe the particular challenges, setbacks, and successes that you've encountered along the way?

The Xpert MTB/RIF test was co-developed by FIND with Cepheid and the University of Medicine and Dentistry of New Jersey, with funding from the Bill and Melinda Gates Foundation and the US National Institute of Allergy and Infectious Diseases.

FIND brings together TB organizations, diagnostic companies, funders, and others, and sustains effective partnerships between them. This model has proved critical to the successful creation, development, and delivery of new diagnostics to the most affected countries.

FIND started with scouting the landscape for what new TB diagnostics were needed, and where. We then identified partners, provided necessary financing, worked alongside our partners to refine the test, and organized the various in-country trials. Our negotiations then brought the product price as low as possible, so that the test would be available to the largest possible number of patients.

SW: Where do you see your research leading in the future?

There is still a pressing need for continued innovation in the field of TB diagnostics. FIND's highest priority is for a simple qualitative case-detection tool for point-of-care testing at the lowest level of the healthcare system, where diagnosis is currently based on clinical signs and symptoms only. This is where the majority of patients first seek care, and where early treatment and transmission interruption could have the greatest public health impact. The second priority is laboratory-based assays that are more sensitive and/or less laborious than microscopy, for use at the next level of the health system where sputum microscopy is currently the mainstay of TB diagnosis.

SW: Do you foresee any social or political implications for your research?

In December 2010, the World Health Organization (WHO) endorsed the new TB test, and recommended its use as the initial diagnostic test in individuals suspected of having MDR-TB or HIV-associated TB. The results of this study formed a large part of the evidence base used by WHO to make its recommendation. To date, almost 80 countries have shown interest in procuring the test. Some countries, such as South Africa, have decided to roll out the new test nationwide. WHO estimates that a global rollout of the new test could result in a three-fold increase in the diagnosis of patients with drug-resistant TB and a doubling in the number of HIV-associated TB cases in areas with high rates of TB and HIV.End

Dr. Catharina Boehme
Foundation for Innovative New Diagnostics
Geneva, Switzerland


ADDITIONAL INFORMATION:

 
Click tabs above to view pictures of the various study teams from participating trial sites.

Study team at Special Treatment Institution, Baku, Azerbaijan.

Study team at Special Treatment Institution, Baku, Azerbaijan.

Study team at Forschungszentrum Borstel, Germany.

Study team at Forschungszentrum Borstel, Germany.

Study team at Hinduja National Hospital and Medical Research Centre, Mumbai, India.

Study team at Hinduja National Hospital and Medical Research Centre, Mumbai, India.

Study team at Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru.

Study team at Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru.

Study Team at the Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, South Africa.

Study Team at the Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, South Africa.

Study team at the South African Medical Research Council's TB Research Unit, Durban, South Africa.

Study team at the South African Medical Research Council's TB Research Unit, Durban, South Africa.

 

KEYWORDS: MYCOBACTERIUM TUBERCULOSIS, RAPID MOLECULAR DETECTION, RIFAMPIN RESISTANCE, DRUG RESISTANCE, MDR-TB, DIAGNOSIS, HIV, TECHNOLOGY, ASSAY, ERA.

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