Tuberculosis

 

Speciation test

Type of products
Test for confirming Mycobacterium tuberculosis grown in culture.

Product
Capilia TB test.

Developers
FIND and Tauns Co. Ltd.

Rationale
Not all acid-fast bacilli (AFB) grown in culture are M. tuberculosis. Existing tests for confirming identification of M. tuberculosis are time consuming and complex. The Capilia TB test is a simple and fast lateral flow technology that allows the confirmation of M. tuberculosis in cultures in 15 minutes.

Product profile
Capilia test is lateral flow (strip test) detecting a TB-specific antigen.

Stage of Development
The test is in the demonstration phase to assess effectiveness in real-life disease control programs.

WHO guidance on adoption and recommendations
The dossier on the performance of Capilia TB is expected to be submitted in May 2007 to the WHO Scientific and Technical Advisory Group (STAG) for recommendation.

Considerations
Limitations: tests intended for use where culture facilities exist or can be built.

Earliest date for availability for adoption in the public sector
Late 2008.

Back to pipeline

Liquid culture and drug susceptibility tests

Type of product
Liquid culture system.

Product
Mycobacterium Growth Indicator Tube (MGIT-TB) and MGIT-DST.

Developers
FIND and Becton, Dickinson and Company (BD).

Rationale
It is recognized that direct smear microscopy has limited sensitivity, especially in some patient groups such as children and individuals co-infected with HIV. Culture is substantially more sensitive than microscopy, with liquid culture systems being more rapid and more sensitive than solid culture.

Product profile
The MGIT-TB culture system allows for the rapid growth and detection of M. tuberculosis. The average time to detection is 10-14 days as opposed to three to four weeks with traditional solid egg or agar- based culture.

MGIT-DST can also be used to diagnose multidrug-resistant tuberculosis. FIND, together with BD, is evaluating MGIT-DST to determine the feasibility and impact of its wider use in disease endemic settings. 

Stage of Development
Both of these products are already in use in wealthier countries and in the private sector of some developing countries. Currently, MGIT-TB culture and MGIT-DST are being evaluated in demonstration projects in national control programs of low-income countries with high TB prevalence to assess their effectiveness, efficiency and impact in the typical field situation.

WHO guidelines on adoption and recommendations/Regulations
The dossier on performance of MGIT-TB and MGIT-DST is expected to be submitted to the WHO for consideration by its Strategic and Technical Advisory Committee (STAG) in May 2007. The two products are FDA registered.

Considerations
Limitations: tests intended for use where culture and biosafety facilities exist or can be built. Additional care is required to minimize contamination of culture.

Earlier date for availability for adoption in public sector
Beginning of 2008.

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Manual nucleic acid amplification test

Type of product
Molecular technique.

Products
Genotype MTBDRplus® assay – polymerase chain reaction (PCR)-based assay.

Developers
FIND and Hain Lifescience.

Rationale
The rapid detection of multidrug-resistance could facilitate early initiation of correct treatment and appropriate measures to prevent transmission. The manual-based nucleic acid amplification DST detects rifampicin and isoniazid resistance in 1 day.

Product profile
The PCR-based line-probe assay is entering evaluation phase.

WHO guidance on adoption and recommendations
The dossier on the performance of the Genotype MTBDRplus® assay is to be submitted in May 2008 to the WHO Scientific and Technical Advisory Group (STAG) for recommendation.

Considerations
Limitations: test is intended for use where culture, biosafety and PCR capabilities exist or can be assembled. Test requires specialized equipment (thermocycler) and training. The sensitivity of the assay (GenoType® MTBDRplus) for INH (isoniazid) resistance is 92%.

Earliest date for availability for adoption in public sector
2008.

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Automated nucleic acid amplification test

Type of product
Molecular technique.

Products
Xpert TB assay – real time PCR-based.

Developers
FIND and Cepheid.

Rationale
Molecular amplification is a proven technology for the detection of M. tuberculosis. Current test methods, however, are too complex for routine widespread implementation in developing countries. Sample processing and DNA extraction adds significantly to this complexity. An assay that automates all of these steps could make NAAT much simpler to implement. Molecular detection of rifampicin resistance could speed targeted treatment and other measures for controlling MDR-TB.

Product profile
FIND and Cepheid are working to develop an automated method to integrate sputum processing, DNA extraction and amplification and detection of TB DNA and rifampin-resistance encoding mutations.

Stage of Development
The test is under development with WHO guidance on adoption and recommendations.

WHO guidance on adoption and recommendations
The dossier on the performance of the Xpert TB assay is expected to be submitted in May 2010 to the WHO Scientific and Technical Advisory Group (STAG) for recommendation.

Considerations
Limitations: Requires specialized equipment and electricity in secure facilities, and some training.

Earliest date for availability for adoption in the public sector
2010.

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Light-emitting diode (LED) fluorescence microscopy

Type of products
Fluorescence microscope.

Product
LED Microscope.

Developers
FIND and commercial partner.

Rationale
Existing conventional fluorescence systems increase the sensitivity of direct smear microscopy. The LED microscope lamp is inexpensive when compared to the mercury vapor or halogen lamp used in regular fluorescent microscopy and has a life span of more than 50,000 hours.

Product profile
Simple binocular microscope incorporating LED light source.

Stage of Development
Microscope in development phase.

WHO guidance on adoption and recommendations
The dossier on the performance of the LED fluorescent microscope is expected to be presented in May 2009 to the WHO Scientific and Technical Advisory Group (STAG) for recommendation.

Considerations
Some training required. As yet, there is no EQA system for fluorescence microscopy. LED-based microscopy may represent a broad platform, with advantages in the diagnosis of other diseases; Promises considerable time-saving in microscopic examinations.

Earliest date for availability for adoption in the public sector
2009.

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Simple manual nucleic acid amplification assay (1st generation)

Type of product
Molecular technique.

Product
First generation LAMP-based assay (Loop mediated isothermal amplification technology platform).

Developers
FIND and Eiken Chemical Company.

Rationale
A simple DNA amplification method which does not require an expensive thermocycler or detection system and which allows visual detection of amplification could allow sensitive molecular methods to be used at lower levels of the health system.

Product profile
Preliminary data suggest high sensitivity and specificity. Modifications of the assay may be suitable for implementation at microscopy level. It is envisaged that the method may be applied to sputum, urine and blood specimens.

Stage of Development
The Eiken Generation 1 test is in the development phase.

WHO guidance on adoption and recommendations
The performance dossier on the first generation of the LAMP-based assay is to be submitted in May 2010 for consideration by the WHO Scientific and Technical Advisory Group (STAG) for recommendation.

Considerations
Cross-disease platform. Training required. LAMP is somewhat more complex than microscopy, but with potential for further simplification and implementation at peripheral laboratory.

Earliest date for availability for adoption in the public sector
2010.

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Urinary nucleic acid amplification test

Type of products
Molecular technology.

Products
PCR-based test method for detecting M. tuberculosis DNA in urine.

Developers
FIND and partners.

Rationale
Fragments of M. tuberculosis DNA have been shown to be excreted in urine. Urine is a less variable and easier to collect than sputum and may be safer to handle. These characteristics may make this method applicable in less complex settings if paired with an appropriately simple amplification method. 

Product profile
This is a method, not a product, and will need to be applied to an existing molecular amplification platform.

Stage of Development
It is in development phase.

WHO guidance on adoption and recommendations
The performance dossier on molecular technology is to be submitted in May 2011 to the WHO Scientific and Technical Advisory Group (STAG) for recommendation.

Considerations
Limitations: tests intended for use where PCR capabilities exist or can be built. Requires specialized equipment (thermocycler) and training.

Earliest date for availability for adoption in the public sector
2011.

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Urinary antigen detection

Type of product
Antigen detection test.

Product
Mycobacterial LAM (lipoarabinomannan) antigen detection in urine.

Sponsors
FIND and partners.

Rationale
M. tuberculosis has been shown to be excreted in the urine of TB patients. Urine specimens are easier to collect than sputum, may be less variable in quality, and are safer to handle.

Product profile
There are several versions of this assay in development, including in-tube ELISA and dipstick methods. Urinary antigen detection may be of particular value in diagnosing TB in HIV co-infected patients. There is potential for further development and simplification resulting in a lateral flow test.

Stage of Development
In development phase.

WHO guidance on adoption and recommendations
The dossier on the performance of the lateral flow test, is expected to be submitted in May 2010 to the WHO Scientific and Technical Advisory Group (STAG) for recommendation. 

Considerations
Lateral flow test – implementation could significantly increase case-finding through improving access to testing. The ELISA format has potential to increase case-finding if combined with smear microscopy and/or culture in high HIV prevalent areas. There is also possible improvement in the diagnosis of paediatric and extra-pulmonary TB. 

Earliest date for availability for adoption in the public sector
2010.

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Antibody detection tests

Type of products
Antibody detection tests.

Product
Antigen identification stage.

Developers
FIND and other partners.

Rationale
TB patients often have detectable antibodies to a variety of M. tuberculosis antigens. Currently, the commercially-available serological tests have been shown to perform poorly. FIND is systematically interrogating the proteome of M. tuberculosis for potential diagnostic antigens.

Product profile
Likely final product would be an immunochromatographic lateral flow or flow-through test.

Stage of Development
In development stage.

WHO guidance on adoption and recommendations
The performance dossier on antigen detection tests is to be submitted by May 2011 to the WHO Scientific and Technical Advisory Group (STAG) for recommendation. 

Considerations
Antibody detection may not perform well in patients with HIV-mediated immunosuppression.

Earliest date for availability for adoption in the public sector
2011.

Back to pipeline

Simple manual nucleic acid amplification test (2nd generation)

To be defined