Research Round-up

TB Programs: WHO to Follow

Chunling Lu, PhD

Low quality of unit cost estimates for tuberculosis monitoring in resource-poor settings creates challenges when it comes to predicting what resources are needed for strengthening microbiological monitoring. In 2011, the World Health Organization (WHO) revised its recommendation for microbiological monitoring during treatment for multidrug-resistant tuberculosis (MDR-TB). WHO recommended increasing the frequency of a culture exam from quarterly to monthly.

Researchers in the BWH Division of Global Health Equity, Department of Medicine conducted a review to determine cost evidence needed for national tuberculosis programs to budget for optimal monitoring strategies. Based on a study conducted by the division, improving validity and comparability of the cost data, requires that the data collection, estimation, and reporting follow protocols proposed by the WHO.

The research team, led by Chunling Lu, PhD, conducted a systematic literature review of 26 peer-reviewed studies that reported the cost estimates in 16 predominantly high- or middle-income countries from 1993 to 2009. The review focused on unit cost estimates of three monitoring strategies: smear only, culture only, and combined smear and culture. The estimated unit cost for smear, culture and combined tests ranged from $0.26 to $10.50, $1.63 to $62.01, and $26.73 to $39.57, respectively. The ratio of culture to smear costs varied from 1.35 to 11.98. According to the researchers, the wide estimate range is likely due to using various laboratory methods and non-standardized practice in cost defining, cost data collecting, and reporting.  

 "The non-standardized cost estimates make it difficult for cross-setting comparison and making meaningful inference on cost-effectiveness analysis," said Lu. "High-quality cost data is especially important for the regions with high incidence of tuberculosis and MDR-TB, where scarce resources must be allocated efficiently. As new molecular tests are being rapidly introduced globally to diagnose patients with presumptive tuberculosis and drug-resistant tuberculosis in one step, we strongly advocate that more cost studies are conducted in these regions following the protocols proposed by the WHO."

The study was published in the February 2013 issue of the PLOS ONE.

Mechanisms Behind Pulmonary Fibrosis

Caroline Owen, MD,  PhD

A research team led by Caroline Owen, MD, PhD, and Vanessa Craig, MD, both of BWH Department of Pulmonary Medicine, has explored the specific role of matrix metalloproteinase-8 (MMP-8) in lung disease. MMP-8 is a type of collagen-degrading enzyme that has been shown to reduce lung inflammation in mouse models of acute lung injury.

Pulmonary fibrosis occurs when excess fibrous connective tissue forms in the lungs. The researchers wanted to find out whether MMP-8 regulates lung inflammatory or fibrotic responses in a mouse model of pulmonary fibrosis. The researchers applied bleomycin to wild-type mice and MMP-8-deficient mice. They found that both MMP-8 mRNA and protein levels were elevated in samples from the bleomycin-treated wild-type mice.

Vanessa Craig, MD

Bleomycin-treated MMP-8-deficient mice had reduced levels of fibrosis and greater levels of inflammation compared with wild-type bleomycin-treated controls. Moreover, MMP-8 expression was increased in leukocytes in the lungs of patients with idiopathic pulmonary fibrosis compared with control lung samples.

The levels of several pro- and anti-fibrotic mediators (TGF-beta, IL-13, MCP-1, and IFN-gamma) were comparable in the two groups, but the lungs of MMP-8-deficient mice had higher levels of MIP-1-alpha and IP-10-mediators responsible for both MMP-8-mediated increased lung inflammation and decreased fibrotic responses to bleomycin.

"By the ability to limit MIP-1-alpha and IP-10, MMP-8 can decrease lung inflammation and increase lung fibrosis," said Craig. "This makes it a potential target for therapy in fibrotic diseases of the lung."

The study was published in the April 15, 2013 issue of the Journal of Immunology.

Chip Technology: Catching HIV at the POC

Utkan Demirci, PhD

A BWH research team led by Utkan Demirci, PhD, and Hadi Shafiee, PhD, both of the BAMM (Bio-Acoustic Mems in Medicine) laboratories, in collaboration with Daniel Kuritzkes, MD, division chief, of BWH Division of Infectious Diseases, has developed a way to detect intact human immunodeficiency virus (HIV).

Their HIV detection method uses a combination of selectively capturing intact viruses, electrical sensing techniques, and impedance spectroscopy of the lysed HIV virus on a microfluidic chip. The technology can detect the virus at concentrations that occur during the acute stages of infection.

According to the researchers, their work offers an alternative technology to the antibody-based methods such as dipsticks and enzyme-linked immunosorbent assay (ELISA) currently used to detect HIV. Moreover, the method has the potential to be adapted to detect many other pathogens responsible for other infectious diseases, such as herpes, influenza, hepatitis and tuberculosis.

"We believe that our technology will fill an unmet need for pathogen detection at the point-of-care," said Shafiee.

Hadi Shafiee, PhD

"Our method provides point-of-care workers in resource-constrained settings, as well as hospital and primary-care settings, a detection technology that is fast, portable, easy to use, sensitive and inexpensive," said Demirci.

The study was published in the February 27, 2013 online issue of Small.