Trial shows most people will complete treatment for latent TB without direct observation

1. Trial shows that most people will complete treatment for latent TB without direct observation

Self-administered once-weekly isoniazid and rifapetine proves noninferior to direct observation in phase 4 randomized clinical trial

Abstract: http://annals.org/aim/article/doi/10.7326/M17-1150

Editorial abstract: http://annals.org/aim/article/doi/10.7326/M17-2639

URLs go live when the embargo lifts

A phase 4 randomized clinical trial found that self-administered treatment for latent tuberculosis infection (LTBI) had a high rate of treatment completion in the United States, Spain, and Hong Kong among a diverse patient population. This is significant because transition from latent TB to active disease accounts for an estimated 86 percent of active TB cases in the United States. The findings are published in Annals of Internal Medicine.

Early clinical trials showed that isoniazid daily for 6 to 12 months could prevent 60 to 90 percent of active TB disease, but effectiveness has been limited by poor tolerability, long duration of treatment, and low adherence. The PREVENT TB study showed that 3 months of once-weekly isoniazid and rifapentine by directly observed therapy was effective and safe compared with 9 months of daily isoniazid by self-administered therapy. Treatment completion with the combination regimen was significantly higher than that with isoniazid. However, wide implementation of once-weekly therapy has been limited because directly observed therapy for LTBI is often unacceptable to patients, prohibitively expensive for TB programs, and unavailable through primary care providers.

Researchers for the Centers for Disease Control and Prevention conducted an open-label, phase 4 randomized clinical trial to compare treatment completion and safety of once-weekly isoniazid and rifapentine by self-administration versus direct observation. The authors assigned 1,002 adults recommended for treatment of LBTI in outpatient tuberculosis clinics in the United States, Spain, Hong Kong, and South Africa to receive once-weekly isoniazid and rifapentine by direct observation, self-administration with monthly monitoring, or self-administration with weekly text message reminders and monthly monitoring. They found that in the United States, treatment completion was about 85 percent in the direct-observation group, 78 percent in the self-administration group, and about 77 percent in the self-administration-with-reminders group. Self-administered therapy without reminders was noninferior to direct observation in the United States; no other comparisons met noninferiority criteria. Drug-related adverse events were few and similar across groups.

According to an editorial from the World Health Organization, direct observation of treatment for active TB has been a component of global control strategies, but it is not always applicable to the management of LTBI. Patient-centered interventions tailored to the specific socioeconomic situations of patients and their families are essential and should be integral to universal health coverage. It is also important that fixed-dose combinations of rifapentine and isoniazid are developed expeditiously to ease pill burden and further support adherence.

Media contacts: For an embargoed PDF, please contact Cara Graeff. The lead author, Robert Belknap, MD, can be reached through Nikki Heider at Nikki.heider@dhha.org or 303-602-3718.

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2. Ongoing surveillance and vaccination are key to prevent yellow fever outbreak in humans

Abstract: http://annals.org/aim/article/doi/10.7326/M17-1949

URLs go live when the embargo lifts

A combination of continuous monitoring of mosquitoes and non-human primate deaths, along with laboratory tests and increased vaccination, is crucial to prevent human cases of yellow fever in places where the virus is transmitted. Findings from a brief research report are published in Annals of Internal Medicine.

Yellow fever is a virus found in South America and Africa that is transmitted by infected mosquitoes. Transmission typically occurs in wild animals, but occasionally spills over to humans entering forest regions. Still, urban transmission is rare, mainly due to vaccination. Recently, concerns about reemergence of urban yellow fever have grown because of the reappearance and rapid spread of A aegypti (a type of mosquito that may carry yellow fever) in the urban environment. Further, immunization coverage for yellow fever is insufficient because it is usually administered to high-risk populations.

Researchers from the Instituto Goncalo Moniz studied the 2017 epizootic outbreak (outbreak within animals) of yellow fever in Salvador, Brazil to determine the risk for human disease. The researchers studied the temporal and spatial distribution of the yellow fever virus outbreak affecting non-human primates (small monkeys) in Salvador, by geocoding the places where the monkeys were found dead. They also collected mosquitoes at such places to investigate potential vectors. The authors found that cases of yellow fever in non-human primates in densely urbanized areas posed a considerable risk for disease resurgence in humans because of the high prevalence of the A aegypti and A albopictus mosquitoes. Salvador has long been an epicenter of dengue transmission and more recently of Zika and chikungunya viruses, all with A aegypti as the main vector.

The authors conclude that surveillance and increased vaccination, even among those not considered at high risk for infection, could help to prevent human cases of yellow fever in Brazil.

Media contacts: For an embargoed PDF, please contact Cara Graeff. The lead author, Guilherme Sousa Ribeiro, MD, MSc, PhD (guilherme.ribeiro@bahia.fiocruz.br), can be reached through his communications office at ASCOM@bahia.fiocruz.br.

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On the Communicability of Chronic Diseases

Ryan T. Demmer, MPH, PhD, and Jeremiah A. Barondess, MD

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