Project Grant R43AI181155

IMPROVING THE EFFECTIVENESS OF ANTI-TUBERCULOSIS DRUGS BY DEVELOPING A POINT-OF-CARE THERAPEUTIC DRUG MONITORING SYSTEM FOR AREAS WITH LIMITED MEDICAL RESOURCES - PROJECT SUMMARY / ABSTRACT EVERY YEAR, ROUGHLY 10 MILLION PEOPLE ARE DIAGNOSED WITH TUBERCULOSIS (TB) AND IT IS RESPONSIBLE FOR OVER 1.5 MILLION DEATHS ANNUALLY. CURRENTLY, TB IS TREATED WITH A FOUR-DRUG REGIMEN OVER A PERIOD OF 6 - 9 MONTHS AND IT HAS CURED ~ 85% OF THE INFECTED PEOPLE. WITH GOOD FACILITIES AND SUPPORT, RIPE REGIMEN CAN CURE UP TO 98% TB CASES. HOWEVER, IF THERE ARE NO SUFFICIENT RESOURCES TO MONITOR THE TREATMENT, SUCCESS RATE CAN QUICKLY DROP TO 65% AND UNFORTUNATELY, MOST OF THE NEW TB CASES ARE IDENTIFIED IN DEVELOPING COUNTRIES WITH LIMITED MEDICAL RESOURCES. TREATMENT FAILURE CAN LEAD TO DRUG RESISTANCE, WHICH IS HARDER, MORE EXPENSIVE AND TAKES MUCH LONGER TIME TO TREAT. TO AVOID TREATMENT FAILURE, IT IS CRUCIAL TO ENSURE AN INDIVIDUAL RECEIVE ENOUGH DRUG EXPOSURE (DRUG LEVEL IN BLOOD) FROM THE PILLS HE OR SHE INGESTED, ESPECIALLY FOR PEOPLE CO-INFECTED WITH HIV OR WITH DIABETES, SINCE THESE CONDITIONS CAN GREATLY ALTER THE DRUG EXPOSURE. FURTHERMORE, DUE TO THE NATURAL PROPERTIES OF THESE DRUGS, SIGNIFICANT BLOOD LEVEL VARIATION CAN BE OBSERVED BASED IN INDIVIDUAL'S PHYSICAL, DIETARY AND CLINICAL STATUS. IN AREAS WITH SUFFICIENT MEDICAL RESOURCES, BLOOD CONCENTRATION OF ANTI-TB DRUGS CAN BE MEASURED VIA THERAPEUTIC DRUG MONITORING (TDM) TO ASSESS DRUG EXPOSURE. HOWEVER, CURRENT TDM METHODS RELY SOLELY ON TIME CONSUMING LABORATORY ANALYSES USING INSTRUMENT THAT REQUIRES SUBSTANTIAL COST AND TRAINED PERSONNEL, WHICH ARE NOT PRACTICAL ON A LARGE SCALE IN NATIONS TRYING TO ERADICATE TB. AS A RESULT, WE PROPOSED TO DEVELOP A TDM PLATFORM FOR ANTI-DRUGS THAT IS MORE SUITABLE FOR THESE AREAS. IN THE PHASE I PROJECT, WE ARE GOING TO DEMONSTRATE THE FEASIBILITY OF SUCH TDM PLATFORM BY FIRST DEVELOPING A TEST FOR RIFAMPICIN, AN ANTI-TB DRUG USED THROUGH THE TREATMENT THAT WOULD BENEFIT FROM CLOSE MONITORING DUE TO ITS WIDE VARIATION BETWEEN INDIVIDUALS. THE PROPOSED RIFAMPICIN TEST IS BASED ON THE EXISTING BLOOD GLUCOSE METER (BGM) HARDWARE AND A DISPOSABLE CARTRIDGE TO ALLOW AFFORDABLE TESTING WITH ACCURACY, CONVENIENT OPERATION AND SHORT TESTING TIME AT THE POINT-OF-CARE. AS THE CULMINATION OF DECADES OF R & D, TODAY'S BGM IS DESIGNED FOR SMALL FOOTPRINT, SIMPLE OPERATION, AFFORDABILITY AND LARGE-SCALE PRODUCTION. LEVERAGING THE BGM TECHNOLOGY WITH A FAMILIAR ASSAY FORMAT FOR USES ALLOWS US TO REDUCE THE RISKS AND COSTS ASSOCIATED WITH DEVICE DEVELOPMENT AND SCALE-UP PRODUCTION. THE FINAL PRODUCT WE ENVISION WILL BE A COMPLETED SYSTEM THAT CAN PERFORM TDM TESTS FOR ALL FIRST-LINE DRUGS WHILE REQUIRING ONLY MINIMAL COST AND TRAINING TO OPERATE. SUCH SYSTEM, IN CONJUGATION WITH BETTER TREATMENT PROGRAM OVERSIGHT MAY PROVIDE THE FOUNDATION FOR REDUCING THE OVERALL TB BURDEN.