Global TB Control Falling Short, Drug Resistance Rising

Megan Brooks

March 23, 2017

On the eve of World TB Day, March 24, health officials around the world say increased efforts are needed to eliminate the disease.

Provisional 2016 tuberculosis (TB) surveillance data released by the US Centers for Disease Control and Prevention (CDC) show that despite slight declines in TB case counts and incidence since 2015, the TB incidence rate remains 29 times higher than the TB elimination target rate.

"Each year, World TB Day serves as an important reminder not only of how far we've come in the fight against TB, but how far we still have to go," Philip LoBue, MD, director of the CDC's Division of TB Elimination, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, said in a statement.

The new data, he said, "suggest that unless progress against TB is accelerated in the United States, we will not be able to eliminate TB in the near future, or even this century."

A related report published today in the Lancet Respiratory Medicine warns that the global rise in multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB threatens to derail decades of progress in controlling the disease.

TB is "an epidemic that is at a crossroads," David Dowdy, MD, PhD, of Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, and coauthors write in an attached comment.

"Over the next decade, it is quite possible that we will see a drug-resistant [TB] epidemic of unprecedented global scale. But it is also possible that the next decade could witness an unprecedented reversal of the global drug-resistant [TB] burden," they say.

"The difference between these two outcomes lies less with the pathogen and more with us as a global [TB] control community and whether we have the political will to prioritize a specific response to the disease. Drug-resistant [TB] is not standing still; neither can we," the authors warn.

TB Cases at Record Low in US

A total of 9287 new TB cases were reported in the United States in 2016. This provisional count represents the lowest number of US TB cases on record and a drop of 2.7% in reported cases from 2015. The 2016 TB incidence rate of 2.9 cases per 100,000 persons represents a slight decline compared with 2015 (-3.4%), according to an article published March 24 in Morbidity and Mortality Weekly Report.

"TB cases continue to occur in every state and region in the United States," said Dr LoBue.

State-specific TB incidence in 2016 ranged from 0.2 cases per 100,000 persons in Wyoming to 8.3 in Hawaii. Twelve states – Alaska, Arkansas, California, Florida, Georgia, Hawaii, Maryland, Minnesota, New Jersey, New York, North Dakota, and Texas – and the District of Columbia reported a higher incidence of TB than the national incidence. As in previous years, four states – California, Florida, New York, and Texas – reported more than 500 cases each in 2016, accounting for 50.9% of reported cases nationwide.

Among the 9287 TB cases reported in 2016, US-born individuals accounted for about one third of cases (2935 or 31.6%), and foreign-born individuals accounted for about two thirds of cases (6307 or 67.9%); 45 (0.5%) cases of TB occurred in persons whose national origin was not known.

The incidence of TB in US-born persons (1.1 cases per 100,000) decreased 8.4% from 2015. The incidence among foreign-born persons (14.6 cases per 100,000) fell 3.2% from 2015, but was roughly 14 times the incidence among US-born persons.

Among foreign-born persons, the highest incidence of TB in 2016 was among Asians (26.9 cases per 100,000), followed by non-Hispanic blacks (22.3) and Hispanics (10.0).

The top five countries of origin for foreign-born persons with TB in the United States were Mexico, the Philippines, India, Vietnam, and China. TB cases in persons born in these countries accounted for more than half, or 54.9%, of all cases among foreign-born persons.

Four of the top five countries of origin for foreign-born persons with TB (China, India, Philippines, Vietnam) are considered by the World Health Organization (WHO) to be countries with a high burden of TB. Those countries accounted for 36% of incident TB cases among foreign-born persons in the United States, the CDC notes.

Because approximately 90% of TB cases in foreign-born persons in the United States are due to reactivation of latent TB infection (LTBI), "targeted testing for and treatment of LTBI among foreign-born persons from countries with high TB prevalence could be an effective strategy to decrease TB incidence," CDC investigators Kristine Schmit, MD, and colleagues write in the MMWR.

They also report 88 cases of MDR-TB in 2015 (the most recent year for which complete drug-susceptibility data are available). MDR-TB accounted for 0.4% and 1.2% of culture-confirmed TB cases among US-born and foreign-born persons, respectively. Among the 88 MDR-TB cases, 72 (81.8%) occurred in persons with no reported prior history of TB. In 2015, one case of XDR-TB was reported.

Global Action Needed

"Achieving our national goal for TB elimination will require not only maximizing all available tools but also continuing to engage global TB partners to reduce TB abroad," said Dr LoBue. "These partnerships will be essential, given the greater risk of TB among individuals in the US who travel to or were born in countries that lack comparable TB control systems."

In the Lancet Respiratory Medicine report, Keertan Dheda, PhD, of University of Cape Town, South Africa, and colleagues note that global TB incidence has declined only "marginally" during the past 10 years and that TB "remains out of control" in several parts of the world, including Africa and Asia. Although TB control efforts have been effective in some parts of the world, these gains are threatened by the increasing burden of MDR- and XDR-TB.

In 2015, TB killed an estimated 1.8 million around the world. About 1 in 5 cases of TB are now resistant to at least one major anti-TB drug, and about 5% of all cases of TB are classified as MDR (resistant to isoniazid and rifampicin) or XDR (also resistant to fluoroquinolones and second-line injectable drugs). Globally in 2015, there were an estimated 480,000 cases of MDR-TB.

MDR- and XDR-TB are associated with "high morbidity and substantial mortality, are a threat to health-care workers, prohibitively expensive to treat, and are therefore a serious public health problem," Dr Dheda and colleagues note.

Although a few repurposed and new drugs have recently become available to treat drug-resistant TB, the authors warn that without accurate diagnostic tests to enable delivery of individually targeted treatments, clear prescription guidelines on appropriate use, improved control efforts to prevent transmission, optimal dosing and administration guidance, and well-functioning healthcare systems, the effectiveness of the drugs could rapidly be lost.

Dr Dheda and colleagues say a "paradigm shift" is needed to take TB testing from the clinical setting into the community, "thus promoting active case finding, and the detection of the undiagnosed and unsuspected cases of community-based drug-resistant tuberculosis."

"Novel ways to reduce or eliminate the transmission of drug-resistant tuberculosis and to understand the fundamental biology of transmission are urgently required," they add.

In their 70-page report, Dr Dheda and colleagues outline priority actions for the next 2, 5, and 10 years for the research and policy communities, as well as key treatment recommendations and procedures for healthcare providers who treat patients with MDR- or XDR-TB.

WHO Issues New Ethics Guidance

The WHO has issued new TB ethics guidance in an effort to ensure that countries implementing the End TB Strategy adhere to sound, ethical standards to protect the rights of all those affected.

"TB strikes some of the world's poorest people hardest," Margaret Chan, MD, WHO director-general, said in a news release. "WHO is determined to overcome the stigma, discrimination, and other barriers that prevent so many of these people from obtaining the services they so badly need."

The guidance addresses "contentious" issues, the WHO says, including the isolation of contagious patients, the rights of TB patients in prison, and discriminatory policies against migrants affected by TB.

The WHO outlines the following five ethical obligations for governments, healthcare providers, nongovernmental organizations, researchers, and other stakeholders:

  • Provide patients with the social support they need to fulfill their responsibilities.

  • Refrain from isolating TB patients before exhausting all options to enable treatment adherence and do so only under very specific conditions.

  • Enable "key populations" to access the same standard of care offered to other citizens.

  • Ensure that all health workers operate in a safe environment.

  • Rapidly share evidence from research to inform national and global TB policy updates.

"Only when evidence-based, effective interventions are informed by a sound ethical framework and respect for human rights will we be successful in reaching our ambitious goals of ending the TB epidemic and achieving universal health coverage," Mario Raviglione, MD, director of WHO's Global TB Programme, said in the release. "The guidance we have released today aims to identify the ethical predicaments faced in TB care delivery, and highlights key actions that can be taken to address them."

Morb Mortal Wkly Rep (MMWR). 2017;66:290-294. Full text

Lancet Respir Med. Published online March 23, 2017. Abstract

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