Tuberculosis

WCLH 2015: TB Treatment Advancing, but Not Reaching All Who Need It

Tuberculosis (TB) treatment has seen some promising recent advances -- including the promise of shorter regimens for multidrug-resistant TB and better therapies for children -- but still not enough is being done to provide access to prevention and treatment for all who need it, according to presentations at the 46th Union World Conference on Lung Health taking place this week in Cape Town.

The conference, organized by the International Union Against Tuberculosis and Lung Disease (the Union), opened Wednesday with aninaugural lecture by South African Health Minister Aaron Motsoaledi on "Turning the Tide Against Lung Disease in South Africa." South Africa has one of highest global burdens of TB as well as HIV.

The World Health Organization (WHO) last month released new data showing that TB has overtaken HIV as the leading global cause of death from infectious disease. According to WHO 1.5 million people worldwide died from TB in 2014, and it is a leading cause of death for people living with HIV.

Good News and Bad News

During a Wednesday press conference the TB Alliance and partners announced the availability of the first child-friendly TB medications. Each year at least 1 million children get TB and 140,000 die from it, according to a conference press release.

Until now providers and parents have had to approximate correct doses by cutting or crushing pills intended for adults. The new dissolvable flavored medications are fixed dose combinations containing 3 of the most widely used drugs to treat drug-sensitive TB (isoniazid, pyrazinamide, and rifampicin). The TB Alliance, UNITAID, USAID, and other funders supported an effort to work with manufacturers to develop properly formulated child-friendly TB therapies.

Studies presented at the conference offer the promise of shorter treatment options for people with multidrug-resistant TB (MDR-TB), according to another conference press release.

One study coordinated by the Union included more than 500 adults with MDR-TB in 9 sub-Saharan African countries. Early results showed that a 9-month multidrug course of therapy -- versus to the standard WHO-recommended 24-month regimen -- successfully treated 81% of patients, while 5% were considered treatment failures, 7% were lost to follow-up, and 8% died.

"These preliminary results from using a 9-month MDR-TB treatment regimen are excellent," said lead investigator Arnaud Trebucq of the Union. "Implementing the shortened regimen is proving feasible and with improved outcomes compared with the standard MDR-TB treatment regimen."

Another trial sponsored by the Union with support from the U.K. Medical Research Council and USAID is also testing a 9-month MDR-TB treatment regimen in multiple countries. The first phase of the STREAM trial is underway in Ethiopia, with other trial sites located in South Africa, Vietnam, and Mongolia -- the first randomized clinical trial of this scope conducted in Mongolia for any disease, according to the press release. Results are expected in 2017.

STREAM is now expanding to test 6- and 9-month MDR-TB treatment regimens containing the newer drug bedaquiline (approved in 2013) in more than 1100 patients in at least 10 countries. The 9-month regimen will be all-oral, unlike the current WHO-recommended regimen that requires injections.

In less encouraging news, researchers reported that tuberculosis is rampant in Brazilian prisons; TB increased by 28% among incarcerated individuals, even while falling by 12% among the non-incarcerated population.

"Brazil has the world’s fourth largest prison population, and with a high throughput of inmates, Brazil’s prisons may serve as reservoirs for TB transmission into the general population," said investigator Paul Bourdillon from Yale University. "Without intervention to address the alarming rates of TB in Brazil’s prisons, the epidemic among incarcerated persons will continue to thwart national efforts to address TB."

A study from Nigeria found a high rate of bovine TB among cattle and livestock workers. In this analysis more than 3000 cattle were tested, showing that 10% of individual cattle had positive TB cultures, as did at least some cattle from about 40% of tested herds; 86 strains of bovine TB were isolated from slaughtered cattle. Among 266 cattle butchers and marketers tested, 5%-6% had positive TB cultures.

Estimates suggest that 1.4% of all human TB cases are caused by zoonotic strains from animals, or 126,000 people annually worldwide. Neglect of zoonotic strains can lead to improper diagnosis and inadequate treatment, according to the press release. For example, Mycobacterium bovis is naturally resistant to pyrazinamide, a standard first-line TB drug, and using pyrazinamide to treat people with bovine TB increases the risks of treatment failure and drug resistance.

"The people affected by zoonotic TB who we're now identifying likely represent the tip of the iceberg," said Francisco Olea-Popelka from Colorado State University. "We must ensure that TB diagnosis can identify the specific type of TB that people are affected by in regions in which socio-cultural practices increase the risk of getting TB from infected animals or their products, especially through consumption of unpasteurized milk products. We also need to broaden our concept of TB to design strategies to prevent and control TB at the animal source to prevent transmission to humans."

Finally, a study from Uganda found that children treated for TB empirically based on symptoms -- which is often done in high-burden low-income countries due to a lack of effective available diagnostics-- die at significantly higher rates than those treated based on a confirmed diagnosis. In this analysis 12% of children undergoing empirical TB treatment died, compared with none (0%) of those with confirmed TB.

However, a decentralized investigation program that trained community health workers to find children with TB in households more than doubled the number of children properly diagnosed, from 7% to 16% of presumed TB cases. Health workers can then provide Isoniazid to prevent TB infection from progressing to active TB disease.

Need for Action

Throughout the conference and the preceding Global TB Summit researchers, advocates, and government officials called for more funding and action to prevent, diagnose, and treat TB.

More than 150 representatives from communities, civil society organizations, countries, and partners pledged their support for ending TB in a Statement of Action launched at the summit, the WHO Global TB Programme announced. The statement was developed at a WHO TB consultation in Addis Ababa in November.

"Innovative and effective strategies to reach out to communities need to be scaled-up quickly and built on existing structures, so that important gains achieved through community work is not overlooked," said Lucy Chesire of the TB Advocacy Consortium of Kenya, who presented the statement on behalf of 90 non-governmental and civil society organizations.

Similar to UNAIDS 90-90-90 targets for ending the HIV epidemic, the WHO End TB Strategy aims to reduce TB incidence by 80% and cut the number of TB deaths by 90% by 2030.

On Thursday more than 300 people living with TB, activists, medical providers, and civil society organizations including the Stop TB Partnership, Treatment Action Campaign, and Médecins Sans Frontières took part in a civil society march to the Cape Town conference center, demanding that everyone who has TB must have access to treatment.

"We can make it harder for TB to spread by improving indoor air quality and sanitation, investing in proven antipoverty measures, and expanding the social support that helps patients stay on treatment," Paula Fujiwara of the Union and Linda Gail Bekker of the University of Cape Town wrote in a recent op-ed in the South Africa Mail & Guardian. "To achieve the seismic shift necessary to end TB, we need a dramatic increase in political will to confront the disease, informed by evidence and advocacy from communities affected by TB."

12/4/15

Sources

46th Union World Conference on Lung Health. Cape Town, December 2-6, 2015. http://capetown.worldlunghealth.org.

Paula Fujiwara and LG Bekker. Turning the tide against TB: Treatment alone won’t work. South Africa Mail & Guardian. December 2, 2015.

International Union Against Tuberculosis and Lung Disease. First child-friendly TB drugs announced at Cape Town press conference. Press release. December 2, 2015.

International Union Against Tuberculosis and Lung Disease. New cohort study shows promise of dramatically shorter treatment option for multidrug-resistant TB. Press release. December 3, 2015.

International Union Against Tuberculosis and Lung Disease. Studies: Progress against TB hindered by faltering response to disease among key affected populations. Press release. December 4, 2015.

WHO Global TB Programme. Communities, nongovernmental and other civil society organizations commit to step up action to end TB. News release. December 2, 2015.

Statement of Action to enhance the engagement of communities, non-governmental and other civil society organisations in the implementation of the End TB Strategy.