New biomolecular assays must be tested by direct study in the developing world

EDITOR—Garner et al's editorial on appropriate diagnostics in developing countries is welcome to those who develop novel diagnostic systems for tuberculosis, which remains the most important infectious disease globally.1 Conventional diagnosis is difficult, and most developments have centred on molecular amplification techniques, often using the polymerase chain reaction, which are expensive and less sensitive than culture. 2 3 Ethical issues arise if precious samples such as cerebrospinal fluid are repeatedly subdivided for research.

Per capita healthcare spending in the developed world is low, and the validity of any test for an infectious disease such as tuberculosis will depend on whether it is being used as a clinical diagnostic or public health surveillance tool. For such a test to be useful clinically, effective treatment regimens must be available; in the case of tuberculosis, better diagnosis coupled with an inability to treat cases successfully will increase treatment failure and encourage the development of drug resistance.

We recently described a rapid mycobacteriophage method for diagnosing drug resistant Mycobacterium tuberculosis, which was developed with developing countries in mind.4 It is inexpensive, uses equipment found in many laboratories, and becomes safer over time as the virus kills the bacterium.

Samples arriving for a rapid molecular diagnosis (Fastrack, which is a national service based on the polymerase chain reaction provided by our laboratory in Britain) were also analysed by the rapid mycobacteriophage method for both diagnosis and the detection of rifampicin resistance. The specificity of the method for “precious” samples is encouraging. For example, a bronchoalveolar lavage sample that was positive for acid fast bacilli on microscopy and culture was positive both with the polymerase chain reaction and by the rapid mycobacteriophage method. Susceptibility to rifampicin was shown by the rapid mycobacteriophage method within 72 hours and confirmed by conventional culture four weeks later. A sample of cerebrospinal fluid that was negative on microscopy and culture was positive by both the polymerase chain reaction and the rapid mycobacteriophage method, and biochemical and clinical signs were consistent with tubercular meningitis. The patient responded to quadruple chemotherapy. A systematic prospective study is under way to confirm the utility of this method for diagnosis.

The robustness of new biomolecular assays can be tested only by direct study in the developing world, a process that the scientific community must actively encourage. Laboratories in the developed world need to produce innovative solutions applicable to the developing world, in addition to addressing the diagnostic needs of their own healthcare systems.