Microscopic observation drug susceptibility test kit evaluation
While tuberculosis (TB) is difficult to identify and diagnose accurately, it is curable with a course of antibiotic therapy, and early diagnosis and treatment can curtail the spread of the disease within the general population. To address this need, PATH aims to facilitate the use of the microscopically observed drug susceptibility (MODS) technology. To satisfy the needs of public testing facilities, the MODS kit must be safe, effective, convenient, and available at a per-test cost comparable to traditional TB culture methods. To ensure a sustainable supply of such kits, the manufacturer of the kits must be able to earn a reasonable profit on them. Therefore, the proposed MODS product has a very low cost of goods, which facilitates a low price point to the consumer and a reasonable profit margin to the manufacturer.
Dates of project
2008 – 2013
Universidada Peruana Cayetano Heredia
The Bill & Melinda Gates Foundation
TB, a highly contagious bacterial disease caused by Mycobacterium tuberculosis, is a major health problem in developing countries and is reemerging as a major health threat in the developed world. High prevalence in some developing countries is associated with human immunodeficiency virus infection and AIDS. World Health Organization statistics indicate there are 14 million cases of active TB worldwide, and approximately 9.4 million new cases occur each year. TB has the highest mortality rate of any infectious disease in the world, causing approximately 1.7 million deaths annually.
While TB is difficult to identify and diagnose accurately, it nevertheless is curable with a course of antibiotic therapy, and early diagnosis and treatment can curtail the spread of the disease within the general population.
Some progress has been made in introducing new tools to achieve early diagnosis. However, early diagnosis of TB at the peripheral level remains a significant challenge since existing methods have low sensitivity (sputum smear), take a long time to produce results (solid culture), or are highly expensive (automated liquid culture methods and automated nucleic acid amplification tests).
The MODS test was first described by the TB working group at the Universidada Peruana Cayetano Heredia (Lima, Peru) and has been in use since 2000 as a core component of national TB control policies. This original MODS test is an accurate, rapid, and inexpensive liquid culture-based method for determining TB positivity and resistance to first-line antibiotic therapies (isoniazid and rifampicin). It employs a simple, inexpensive tissue culture plate and commonly available culture media to provide results with a rapid turnaround from specimen collection to results dissemination (usually within seven days). The original platform has been validated in five countries with extremely high sensitivity and specificity. The original MODS test was subsequently endorsed by World Health Organization in 2010.
There were two issues with the original MODS test. First, reagents and consumables required for the test had to be procured independently, which was difficult for users in low-resource settings. Second, the commercially available tissue culture plate was not sealed, leading to increased risk of sample cross contamination as well as biohazard risk to laboratory personnel performing the test. Universidada Peruana Cayetano Heredia, therefore, contacted PATH and asked for assistance in making the test easier and safer to use.
The goal of this project is to facilitate the diffusion of the MODS technology. We aim to achieve this goal by 1) creating a safe, effective, and easy-to-use TB MODS test kit, and 2) generating evidence on the performance of the kit to assist national TB control programs and other stakeholders in making decisions regarding whether and how to incorporate the kit into their TB control programs.
By having all the components necessary to perform the MODS test, users will be able to procure and use the MODS technology more easily. The kit will consist of readily available components to achieve cost reduction and will include a culture plate closure to insure improved biosafety and prevention of cross contamination.
Establishment of private-public partnerships will be the key element to ensure success of this project. We will identify and collaborate with a private-sector partner to develop a TB MODS test kit leveraging that partner’s existing technologies and PATH’s expertise. We will also establish an agreement with the above private-sector partner to commercialize and market a MODS test kit in low-resource settings at a price comparable to or lower than that of the traditional culture method. Finally, we will identify either a public or private partner to carry out a field evaluation of the test.
PATH has selected and collaborated with Hardy Diagnostics (Santa Maria, CA) to develop the TB MODS Test Kit™. This kit includes everything that researchers and laboratory technicians need to perform the MODS test while simultaneously providing test standardization and convenience to users. Additionally, it includes a PATH-designed, silicone-based protective sealing lid for the culture plate to prevent cross contamination between samples and to increase biosafety. The TB MODS Test Kit™ has received a CE mark and is for sale in European countries. With commitment from Hardy Diagnostics, the TB MODS Test Kit™ can be provided at low cost to low-resource countries.
PATH has also initiated a field evaluation of the kit under controlled laboratory conditions in Peru to generate performance data, partnering with Universidada Peruana Cayetano Heredia. In this study, the TB MODS Test Kit™ is being compared with the original MODS and the Ogawa culture method, followed by a comparison with the proportion method to determine the kit’s sensitivity and specificity for detecting Mycobacterium TB as well as drug susceptibility for isoniazid and rifampin. We expect that this study will be completed in the first quarter of 2013.
Concurrently, we are undertaking a global landscape analysis on the TB MODS Test Kit™ in order to assess the potential for using this kit in countries outside of Peru.
Our field evaluation of the TB MODS Test Kit™ in Peru will generate critical test-performance data. The global landscape analysis will inform us which other countries would likely be early adopters of the kit. We plan to disseminate the results of this field evaluation study to the global TB community and to the early adopter countries we identify to raise awareness of, and interest in, the TB MODS Test Kit™.
PATH is exploring opportunities to continue to engage with key stakeholders in Peru to identify how the TB MODS Test Kit™ could be incorporated into Peru’s national TB control program and how lessons learned can then be applied to early adopter countries to spur practical discussions about implementing the kit in their respective national TB control programs.
Contact the MODS Team
Mutsumi Metzler, Project Lead
Contact PATH’s Seattle headquarters