World TB Day: WHO reveals progress, remaining challenges

In light of World TB Day, observed annually on March 24, WHO has called upon countries and its partners to “Unite to End Tuberculosis” by 2030, according to a press release.

New targets set under WHO’s sustainable development goals and the End TB Strategy aim to reduce TB deaths by 90%, new cases by 80%, and to eliminate overwhelming medical costs due to TB.

“That is an ambitious aim,” the WHO release said. “While there has been significant progress in the fight against TB, with 43 million lives saved since 2000, the battle is only half-won.”

TB, alongside HIV/AIDS, is the leading cause of death worldwide due to an infectious disease, the release said. According to WHO’s 2015 Global Tuberculosis Report, 9.6 million people developed TB in 2014 and 1.5 million people died from the disease — a 47% decline since 1990. Of the deaths in 2014, 140,000 occurred in children, and more than 95% occurred among people living in low- and middle-income countries. In addition, TB is the number one cause of death in people living with HIV/AIDS, and was responsible for one in three deaths in this population in 2014, according to the release.

Approximately one-third of the world’s population has latent TB, an asymptomatic and non-infectious form of the disease, according to a statement from the NIH. These patients have a 5% to 10% risk of developing active disease. In the United States, a large number of TB cases occur in populations from endemic regions who have been exposed to TB in their home country, according to Sarojini Sonia Qasba, MD, MPH, of the Suburban Hospital/Johns Hopkins Medicine.

“A huge part of TB is centering around a lack of education, both on what latent TB is and the difference between latent and active TB,” Qasba told Infectious Disease News. “It’s imperative to screen as many people as possible and offer treatment for latent TB. We see a lot of patients in the United States who either haven’t been offered screening or are choosing not to be screened or not to be treated if they have latent TB.”

Qasba said an effective way to increase screening may be to involve the participation of primary care physicians and clinics designed to offer care to patients with little or no insurance.

According to WHO, another critical step toward ending TB by 2030 involves “urgent and effective action” against multidrug-resistant TB (MDR-TB). In 2014, more patients with TB were tested for drug resistance than ever before, partly due to the implementation of rapid molecular tests, according to the report. An estimated 58% of treated patients and 12% of new TB cases were tested for resistance. Overall, 26% of MDR-TB cases (n = 123,000) were detected. WHO estimated that 480,000 people developed MDR-TB, and 190,000 had died.

WHO anticipates new TB diagnostics, drugs, vaccines

Since its 2010 recommendation, WHO reported that the use of the rapid test Xpert MTB/RIF (Cepheid) has substantially expanded, with 4.8 million test cartridges purchased by 116 low- and middle-income countries in 2014. The agency said in the report that a platform called the GeneXpert Omni (Cepheid), a point-of-care test for TB and rifampicin-resistant TB, is in the diagnostic pipeline. The platform, which WHO will evaluate later this year, uses Xpert MTB/RIF cartridges and is smaller, lighter and less expensive than current platforms. According to a statement from the NIH, the GeneXpert test produces results in 2 hours and has already been used in numerous countries. Researchers from the United States, South Africa, Uganda, Brazil and South Korea who represent the TB Clinical Diagnostic Research Consortium are working to expand the test’s capability and accuracy.

Also in the pipeline is a next-generation cartridge called Xpert Ultra (Cepheid/FIND/Rutgers New Jersey Medical School), which will likely replace the Xpert MTB/RIF cartridge and has the potential to replace conventional culture as the primary diagnostic method for TB.

Aside from diagnostics, WHO’s 2015 report states that eight new or repurposed anti-TB drugs are in advanced stages of clinical development, and the anti-TB drug candidate TBA-354 is being assessed in phase 1 testing. One trial, supported by the National Institute of Allergy and Infectious Diseases, will assess a higher dose of rifampin, the first-line drug for TB, over a shorter treatment duration, according to the NIH. Several other treatment regimens for drug-susceptible and drug-resistant TB also are being evaluated in phase 2 and phase 3 trials, according to WHO. In addition, 15 vaccine candidates currently are being assessed.

“Ending TB will only be achieved with greater collaboration within and across governments, and with partners from civil society, communities, researchers, the private sector and development agencies,” the release said. “This means taking a whole-of-society and multidisciplinary approach, in the context of universal health coverage.”

In recognition of World TB Day, Infectious Disease News has compiled a list of the top five stories on TB over the past year.

Urine-based TB test lowers mortality

Results from a randomized controlled trial suggest that an adjunctive, low-cost urine test could help reduce TB-related mortality among patients living with HIV, particularly those with advanced disease.

Although the point-of-care urine test only led to a modest decrease in death, this method of screening could potentially save thousands of lives, according to Keertan Dheda, MD, PhD, professor of respiratory medicine and head of the lung infection and immunity unit at the University of Cape Town, South Africa. Read more.

T-cell biomarkers distinguish active, latent M. tuberculosis infection

Researchers showed that blood-based biomarkers located on Mycobacterium tuberculosis-specific CD4 T-cells discriminated between pulmonary active tuberculosis and latent infections.

“In order to reduce the burden of TB globally, identifying and treating all TB cases is a critical priority,” Jyothi Rengarajan, PhD, of Emory University School of Medicine and Emory Vaccine Center, said in a press release. “However, accurate diagnosis of active TB disease remains challenging and methods for monitoring how well a patient responds to the 6- to 9-monthlong, four-drug regimen of anti-TB treatment, are highly inadequate.” Read more.

Patients with HIV play key role in TB transmission

In contrast to previous hypotheses, HIV-positive patients with pulmonary tuberculosis appear to have an important function in the onward transmission of Mycobacterium tuberculosis, according to findings presented at CROI 2015.

“HIV-positive patients with pulmonary tuberculosis are thought to be less likely to transmit M. tuberculosis, even accounting for sputum bacillary load, because they have a shorter duration of disease,” researchers wrote. “Whole-genome sequencing of M. tuberculosis can identify who transmits to whom, and provides a new method to test this hypothesis.” Read more.

Gene expression method detects active TB

Researchers have identified three genes whose expression may indicate active pulmonary tuberculosis, thereby allowing health care workers to diagnose patients without the use of sputum samples.

“The three-gene set could improve clinical diagnosis and treatment response monitoring, although this needs to be confirmed by prospective validation with a targeted assay,” the researchers wrote. “The parsimony of the three-gene set should ease translation to clinical practice and might prove cost-effective in the resource-poor environments in which tuberculosis is present.” Read more.

More than five drugs for MDR-TB improve treatment response

Findings published in PLoS Medicine suggested that treating patients with multidrug-resistant tuberculosis with a greater number of drugs than is currently recommended by WHO might improve a patient’s response to treatment. In addition, the findings showed that access to baseline drug susceptibility testing could help guide treatment. Read more.

Reference: WHO. Global Tuberculosis Report 2015. http://www.who.int/tb/publications/global_report/en/. Accessed March 23, 2016.

Disclosure: Qasba reports no relevant financial disclosures.