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Enhanced diagnostic methods, treatment imperative for TB elimination
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NEW YORK — Tuberculosis infection cases increased significantly during the last 4 years due to unreported incidences in large immigrant and tourist populations and outdated diagnostic and treatment plans, according to a speaker presentation at the 2016 Infectious Diseases in Children Symposium.
In 2015, tuberculosis cases increased in the United States for first time in 23 years – 9,563 cases compared with 9,406 the year before – which suggests that national progress toward eliminating tuberculosis is significantly off-course. This significant resurgence, comparable to the spike in incidences in 1991, led the CDC to declare that a new national strategy is needed.
In his presentation on the global state of tuberculosis, Jeffrey R. Starke, MD, professor of pediatrics at Baylor College of Medicine, noted that one of the primary challenges in eliminating TB is the inability to implement effective TB detection and treatment due to declining health department budgets.
Global connection
“While WHO knew how many cases were being reported, they also knew that it was grossly under-reported for the disease,” Starke said. “Most children with TB are not being detected, not being reported and not being treated. Unfortunately, that is the state of affairs around the world.”
In the U.S., foreign-born children are at an increased risk for developing TB infection. Prior to 2007, TB tests were not required, and while current requirements include tuberculin skin tests and, if positive, chest radiographs, follow-up treatment is not mandatory. As a result, there are large cohorts of infected but untreated children in many regions of the U.S.
“Eighty percent of children with TB have an international connection,” Starke said. “One of the things we have to consider is: What is our strategy to detect these kids and get them the treatment they need? Many of them are foreign-born or immigrants, who do not have health insurance or medical homes, which represents a real challenge for pediatricians.”
Starke noted that aside from Canada, Australia, New Zealand and Western Europe, TB is burdensome to all countries, and is an exploding global public health issue.
Inefficacious testing
It is necessary to reevaluate the traditional tuberculin skin test because it produces inefficacious outcomes, according to Starke.
“We still treat TB the same way we did 30 years ago, and most clinics use the same diagnostics that have been used over 100 years,” Starke said. “Sub-Saharan Africa has the highest density in cases of TB, but the greatest number of cases is coming from Asia. Specifically, India and China mostly due to their large populations, but also for the way they are going about treating TB.
“The problems with the skin test are there are hundreds of antigens, which leads to poor specificity, low pars plana vitrectomy [PPV] when Bacille Calmette-Guerin [BCG]-vaccinated or exposure to environmental mycobacteria leads to false positives and 10% are false negatives with pulmonary disease, up to 50% with meningitis and disseminated TB,” he said.
In 10 years, the tuberculin skin test may not even be available, so we all should get comfortable with the blood test, Starke said.
In addition, there are also issues with both blood tests QuantiFERON (Qiagen) and T.Spot (Oxford Immunotec), namely that they are unable to distinguish between TB infection and TB disease.
On the other hand, recent data showed positive developments in TB disease prevention. “Previously, 9 months of isoniazid was used, and while it was effective in trials, [it was] not effective in the real world because people simply do not take it as they are prescribed,” Starke said.
A 2015 study by Villarino et al demonstrated that 4 months of rifampin was more efficacious with an 80% prevention rate compared with 40% rate for isoniazid in a trial of 7,800 patients aged 2 to 17 years. Unfortunately, there is a lack of biologics in supply, Starke said.
“We have drug and biologic shortages, we have shortages of PPV, we have shortages in isoniazid in some communities,” Starke said. “We need to learn how to address this large pool of disease vs. latent TB infection.” – by Kate Sherrer
References:
Dodd PJ, et al. Lancet Glob Health. 2014;doi:10.1016/S2214-109X(14)70245-1.
Starke JR. “The age-old threat of tuberculosis”. Presented at: IDC NY; Nov. 19-20, 2016; New York.
Villarino ME, et al. JAMA Pediatr. 2015;doi:10.1001/jamapediatrics.2014.3158.
Disclosure: Starke reports being on a data safety monitoring board for pediatric studies of delamanid (Osaka Pharmaceuticals).