New approaches in TB diagnosis and treatment Prof. M.A. Tageldin

Why We Need New Tools to Fight TB New tools are desperately needed to save millions of lives needlessly lost to TB. Todays most commonly used TB diagnostic, sputum microscopy, is more than 100 years old. It can only detect half of all active cases of TB, and does not distinguish drug-sensitive from drug-resistant disease. As a consequence, many patients are given drugs that are destined not to work. Todays first-line TB drugs are more than 40 years old and must be taken for 6-8 months, while treating MDR-TB usually takes months. Inconsistent treatment breeds drug-resistant strains that increasingly defy current medicines. Faster acting drugs are needed to shorten treatment duration, and new drugs that attack novel targets are needed to fight resistant strains of M.tb. Todays TB vaccine, which is more than 85 years old, provides some protection against severe forms of TB in children but is unreliable against pulmonary TB, which accounts for most of the worldwide disease burden.

Why We Need New Tools to Fight TB We will never defeat TB, and especially drug-resistant TB, without new and more effective tools: simpler, faster drug regimens that treat all forms of TB; rapid, more accurate diagnostic tools to quickly detect TB and its drug-resistance patterns; and a vaccine that will be effective in preventing all forms of TB. New tools will play a crucial role along side the growing commitment to more aggressive TB control and broader treatment to end the needless burden of this infectious disease.

New Grants from The Bill & Melinda Gates Foundation to Fight Tuberculosis The grants focus on three key areas: Vaccine development: $200 million over five years to the Aeras Global TB Vaccine Foundation to conduct clinical trials of up to six TB vaccine candidates Diagnostics: $62 million over five years to the Foundation for Innovative New Diagnostics (FIND) to develop TB tests that are more accurate and simpler to use Drug discovery: Nine grants totaling $18 million to identify new TB treatments to combat drug resistance

New Grants from The Bill & Melinda Gates Foundation to Fight Tuberculosis Grant to Support TB Vaccine Trials The Aeras Global TB Vaccine Foundation will use its new grant to conduct Phase I and II trials of up to six TB vaccine candidates, which are expected to involve 8,500 participants in 10 countries in Africa, Asia, Europe, and the United States. The goal is to identify the best TB vaccines for Phase III trials, the final stage of testing before a new vaccine can be licensed for use. It has been projected that even a partially effective new TB vaccine could avert more than 30 million deaths worldwide by Aeras and its partners have assembled a diverse portfolio of TB vaccine candidates that are ready, or may soon be ready, for clinical trials. Aeras has also helped establish world-class TB research centers in South Africa and India, two of the countries most seriously affected by TB.

New Grants from The Bill & Melinda Gates Foundation to Fight Tuberculosis New TB Diagnostics Within Reach The Foundation for Innovative New Diagnostics (FIND) will use its new grant to advance development of up to 10 new TB diagnostic tests, in the hope of obtaining WHO approval of one or more tests within five years. "The difficulty of diagnosing TB is one of the greatest obstacles to controlling the disease, particularly in patients who also have HIV/AIDS," The standard test used to diagnose TB misses half of cases, and requires culturing a patient's sputum sample in the laboratory and examining it with a microscope after an intensive multi-step process. It has been estimated that improved diagnostics could help save at least 400,000 lives every year.

New Grants from The Bill & Melinda Gates Foundation to Fight Tuberculosis Grants to discover Innovative TB Drugs The nine grants for early-stage discovery projects will identify leads for new TB drug compounds that are more effective than current treatment options. Developing new TB treatments is an urgent priority because resistance is growing to drugs that were once widely effective for curing the diseaselast year there were more than 400,000 cases of drug-resistant TB. In addition, there is a need for faster-acting TB drugs; current drugs must be taken for at least six months to be fully effective. To stay ahead of TB drug resistance, we need to pursue new, out-of-the-box ideas that have not yet been tested, These grants could help bring about a new generation of more effective drugs to significantly advance our ability to fight TB."

GeneXpert MTB/RIF The Xpert MTB/RIF is a cartridge-based, automated diagnostic test that can identify Mycobacterium tuberculosis (MTB)DNA and resistance to rifampicin (RIF)by nucleic acid amplification technique(NAAT) It purifies, concentrates, amplifies (by rapid, real-time PCR) and identifies targeted nucleic acid sequences in the TB genome, and provides results from unprocessed sputum samples in less than 2 hours, with minimal hands-on technical time. The concessional price for a GeneXpert system is currently USD 17,000 for a four module instrument. The cost of a test cartridge in countries eligible for concessional pricing is USD 10

Clinical trial of 9 months treatment for MDR-TB (The STREAM trial ) The need for shorter and more effective treatment regimens for MDR-TB is undisputed: Over 500,000 patients annually Low success rate Regimens prolonged duration Unacceptable adverse effects Expensive

Clinical trial of 9 months treatment for MDR-TB (The STREAM trial ) STREAM (Standardised Treatment Regimen of Anti- Tuberculosis Drugs for Patients with MDR-TB) is a clinical trial to assess a 9 months treatment regimen for MDR-TB has begun in South Africa, Ethiopia and Vietnam. The trial will involve 400 patients in Africa and Asia. The regimen to be tested is modeled on one previously used in a study in Bangladesh, which demonstrated excellent outcomes, including an 87% cure rate. Patients treated with the STREAM regimen will receive moxifloxacin, clofazimine, ethambutol and pyrazinamide for 9 months, supplemented by prothionamide, kanamycin and INH during an intensive phase of 4 months. Once the full complement of patients has been enrolled, the trial is expected to run for two years, with results available in 2016

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