Global & Disaster Medicine

Archive for the ‘TB’ Category

TB in India: An estimate of 2·2 million cases, two to three times higher than currently assumed.

The Lancet

The number of privately treated tuberculosis cases in India: an estimation from drug sales data                                                 Arinaminpathy, Nimalan et al.                                                                                                                                                                                   The Lancet Infectious Diseases

SL-LPA: A rapid diagnostic test (24-48 hrs.) for identifying those MDR- or rifampicin-resistant TB patients


This test is the first and only WHO-recommended rapid test for detection of additional resistance in MDR-TB patients as well as XDR-TB.

Rapid diagnostic test and shorter, cheaper treatment signal new hope for multidrug-resistant tuberculosis patients



12 MAY 2016 | GENEVA – New WHO recommendations aim to speed up detection and improve treatment outcomes for multidrug resistant tuberculosis (MDR-TB) through use of a novel rapid diagnostic test and a shorter, cheaper treatment regimen.

“This is a critical step forward in tackling the MDR-TB public health crisis,” said Dr Mario Raviglione, Director of WHO’s Global TB Programme. “The new WHO recommendations offer hope to hundreds of thousands of MDR-TB patients who can now benefit from a test that quickly identifies eligibility for the shorter regimen, and then complete treatment in half the time and at nearly half the cost.”

Shorter treatment with better outcomes

At less than US$ 1000 per patient, the new treatment regimen can be completed in 9–12 months. Not only is it less expensive than current regimens, but it is also expected to improve outcomes and potentially decrease deaths due to better adherence to treatment and reduced loss to follow-up.

The conventional treatment regimens, which take 18–24 months to complete, yield low cure rates: just 50% on average globally. This is largely because patients find it very hard to keep taking second-line drugs, which can be quite toxic, for prolonged periods of time. They therefore often interrupt treatment or are lost to follow-up in health services.

The shorter regimen is recommended for patients diagnosed with uncomplicated MDR-TB, for example those individuals whose MDR-TB is not resistant to the most important drugs used to treat MDR-TB (fluoroquinolones and injectables), known as “second-line drugs”. It is also recommended for individuals who have not yet been treated with second line drugs.

WHO’s recommendations on the shorter regimens are based on initial programmatic studies involving 1200 patients with uncomplicated MDR-TB in 10 countries . WHO is urging researchers to complete ongoing randomised controlled clinical trials in order to strengthen the evidence base for use of this regimen.

Rapid diagnostic test to identify second-line drug resistance

The most reliable way to rule out resistance to second-line drugs is a newly recommended diagnostic test for use in national TB reference laboratories. The novel diagnostic test – called MTBDRsl – is a DNA-based test that identifies genetic mutations in MDR-TB strains, making them resistant to fluoroquinolones and injectable second-line TB drugs.

This test yields results in just 24-48 hours, down from the 3 months or longer currently required. The much faster turnaround time means that MDR-TB patients with additional resistance are not only diagnosed more quickly, but can quickly be placed on appropriate second-line regimens. WHO reports that fewer than 20% of the estimated 480 000 MDR-TB patients globally are currently being properly treated.

The MTBDRsl test is also a critical prerequisite for identifying MDR-TB patients who are eligible for the newly recommended shorter regimen, while avoiding placing patients who have resistance to second-line drugs on this regimen (which could fuel the development of extensively drug-resistant TB or XDR-TB).

“We hope that the faster diagnosis and shorter treatment will accelerate the much-needed global MDR-TB response,” said Dr Karin Weyer, Coordinator of Laboratories, Diagnostics and Drug Resistance, WHO Global TB Programme. “Anticipated cost-savings from the roll out of this regimen could be re-invested in MDR-TB services to enable more patients to be tested and retained on treatment.”

WHO is working closely with technical and funding partners to ensure adequate resources and support for the uptake of the rapid test and shorter, cheaper regimen in countries.

Quick facts

  • Resistance to standard TB drugs exists in most countries worldwide. Drug resistance, fuelled by inadequate treatment, can spread through the air, from person to person, in the same way as drug-susceptible TB.
  • Multidrug-resistant TB (MDR-TB) is caused by TB bacteria that are resistant to at least isoniazid and rifampicin, the two most effective TB drugs. Based on figures from 2014, the latest year for which data are available, WHO estimates that 5% of TB cases are multidrug-resistant. This translates into 480 000 cases and 190 000 deaths each year.
  • Extensively drug-resistant TB (XDR-TB) is a form of MDR-TB that is also resistant to any fluoroquinolone and any of the second–line anti-TB injectable agents (i.e. amikacin, kanamycin or capreomycin). About 9% of MDR-TB patients develop XDR-TB, which is even more difficult to treat.
  • The WHO “End TB Strategy“, adopted by all WHO Member States, serves as a blueprint for countries to reduce TB incidence by 80% and TB deaths by 90%, and to eliminate catastrophic costs for TB-affected households by 2030.

25 years ago, Vietnam had nearly 600 cases of TB for every 100,000 residents. Today, it has less than 200, but final victory is not in sight

NY Times


“….To reach Vietnam’s ambitious goal of pushing prevalence rates down to 20 cases per 100,000 residents — essentially eliminating tuberculosis as a public health problem — its tuberculosis-control program needs to spend at least $66 million a year. It now spends about $26 million a year.

About $19 million of that comes from foreign donors, with more than a third from the United States….”

Southeast Asia

March 24, 1882: When German microbiologist Robert Koch announced he had discovered Mycobacterium tuberculosis (Mtb), the bacterium that causes TB


On World Tuberculosis (TB) Day 2016, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, reaffirms its commitment to researching ways to better understand, prevent, diagnose and treat TB. March 24 marks the day in 1882 when German microbiologist Robert Koch announced he had discovered Mycobacterium tuberculosis (Mtb), the bacterium that causes TB — an airborne disease that most often attacks the lungs. The 2016 World TB Day theme is Unite to End TB(link is external), and today NIAID joins the World Health Organization (WHO) and the global research community in highlighting some of our extensive efforts to help reduce TB deaths by 95 percent and to reduce the TB incidence rate by 90 percent by 2035.

Despite recent advances, TB remains one of the world’s deadliest diseases. TB incidence worldwide has declined 18 percent since 2000. However, in 2014 the disease still caused 9.6 million people across the globe to be sick, and killed 1.5 million people, mainly in developing countries, according to the WHO. TB is also a leading cause of death in people with HIV/AIDS: in 2015, one in three deaths among HIV-infected individuals worldwide was due to TB.

Although most TB is curable, certain forms of the bacterium that causes TB are becoming resistant to the drugs designed to kill them. Patient adherence to therapy was already difficult as most regimens require taking medicine daily for six months to two years. The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB has caused significant setbacks in the effort to effectively treat and cure patients, and highlights the need for new medicines. According to WHO, among 480,000 total cases of MDR-TB in 2014, 190,000 people (40 percent) died. In keeping with the goals of the White House’s National Action Plan for Combating MDR-TB(link is external), NIAID’s research program supports the discovery of novel antibiotics and the conduct of clinical trials testing various drug regimens to lessen the burden of MDR-TB and XDR-TB.

NIAID supports various consortia and approaches that span all areas of TB drug discovery, from screening promising compounds in animal models to testing the safety and efficacy of candidate drugs in clinical trials. A key goal is to shorten the duration of standard treatment regimens for TB. In one NIAID-supported trial, investigators are testing a higher dose of the first-line drug rifampin over a shortened treatment period. In addition, NIAID researchers are collaborating with international investigators on studies of novel TB treatments. For example, NIAID and our collaborators conducted a trial among more than 1000 MDR-TB and XDR-TB patients in South Korea and China that demonstrated the efficacy of the drug linezolid for the treatment of XDR-TB.

New diagnostic tools are in development to detect early Mtb infection more accurately and to identify and track drug-resistant strains. Many countries still diagnose TB by examining sputum samples under a microscope to detect TB bacteria; this approach can take a day to complete and cannot diagnose drug-resistant strains. NIAID contributed to the development of the GeneXpert diagnostic test, which can detect TB and MDR-TB in two hours. The test is now used in numerous countries, and the NIAID-supported TB Clinical Diagnostic Research Consortium(link is external) — a group of researchers in the United States, South Africa, Uganda, Brazil and South Korea — is working to expand the capability of the test to accurately detect XDR-TB. NIAID is also funding a large-scale project at the Genomic Center for Infectious Diseases at the Broad Institute(link is external) to sequence the genomes of drug-resistant strains of Mtb. These data will aid the development of TB diagnostics and rapid drug susceptibility tests for MDR-TB and XDR-TB.

The WHO estimates that about one-third of the world’s population is latently infected with Mtb, meaning they do not exhibit symptoms of TB disease. A person with latent TB infection has a 5 to 10 percent risk of developing active, transmissible TB during his or her lifetime. NIAID’s Tuberculosis Research Units program has helped identify biomarkers that define the various stages of infection and is conducting animal and human studies to examine why most people with latent TB infection do not develop disease.

Safe and effective vaccines are critical to the effort to control TB globally. The Bacille Calmette-Guérin (BCG) vaccine developed in 1921 is currently the only available vaccine against TB. It provides some protection against severe forms of TB in children; however, it does not reliably protect adults. New vaccines to replace BCG or to boost the immunity conferred by BCG are urgently needed to protect against TB infection, disease, and recurrence of disease. NIAID supports basic, preclinical, and clinical research on candidate TB vaccines, including an investigational aerosol vaccine that induced potent immune responses in a small number of rhesus macaques and protected them against pulmonary infection with Mtb.

At least one-third of the 37 million people living with HIV worldwide are latently infected with Mtb and are 26 times more likely to develop active TB disease than those without HIV, according to the WHO. A 10-nation clinical trial(link is external) conducted by the NIAID-fundedAIDS Clinical Trials Group (ACTG)(link is external) recently demonstrated that isoniazid alone, compared with a standard four-drug empiric TB treatment regimen, was as effective for preventing TB and reducing death in adults with advanced HIV/AIDS in high-risk regions. Another ACTG trial is testing a novel regimen containing the drugs bedaquiline and delamanid to treat patients with MDR-TB. TB also accelerates the progression of HIV infection to AIDS, making it the leading cause of death associated with HIV infection globally. NIAID supports various studies examining optimized treatment regimens and improved diagnostic tests for people co-infected with TB and HIV.

An estimated 43 million lives were saved through appropriate TB diagnosis and treatment between 2000 and 2014, according to the WHO.  However, we still have much work to do to end the global scourge of TB. NIAID is committed to the fight against TB and accelerating the comprehensive research needed to control and ultimately eliminate this ancient disease.

Anthony S. Fauci, M.D., is the director of NIAID. Richard Hafner, M.D., is chief of the TB Clinical Research Branch in the NIAID Division of AIDS; Christine F. Sizemore, Ph.D., is chief of the Tuberculosis and Other Mycobacterial Diseases Section in the NIAID Division of Microbiology and Infectious Diseases.

NIAID conducts and supports research — at NIH, throughout the United States, and worldwide — to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit

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