Since its official opening on October 9 last year, K-RITH has been ramping up to its full capacity, tackling a number of fundamental scientific questions. How have some TB variants acquired resistance to virtually all drugs, as seen in the roughly 300 new drug-resistant cases that emerge each year in KwaZulu-Natal province? How do both TB and HIV create disease reservoirs that can lurk for years before rekindling deadly infections? And how can we manipulate the response of the immune system to better thwart the TB and HIV pathogens? Right now, TB and HIV seem to know more about human biology than scientists do.
Just as important, K-RITH will address the two most pressing problems in the fight against TB—the lack of good, quick diagnostics and biomarkers, and the dearth of new drugs and treatments. The mainstay TB diagnostic is still the basic smear microscopy technique used by Robert Koch to discover M. tuberculosis in 1882: get patients to cough up a sputum sample, stain it with dye, wash it with acid alcohol and put it under a microscope to look for TB bacteria. However, the test spots only about half of those with active disease, and the failure rate is even higher in those with HIV, who often have little disease in their lungs. Most of the patients missed by the sputum test can be diagnosed with a culture test, but because M. tuberculosis grows so slowly, a culture takes 10 to 60 days. Many patients from Tugela Ferry with XDR-TB died before they were even diagnosed. And neither the sputum nor the first-line culture tests can determine whether TB strains are resistant to some or all drugs.
There has been some progress in developing better diagnostics. The GeneXpert system developed by Cepheid, Inc. and the Foundation for Innovative New Diagnostics, uses new technology to simultaneously detect DNA sequences specific both to TB and to resistance to the drug rifampicin, and has been hailed as a potential game-changer (Evans, 2011
). But the test is relatively expensive, misses a fraction of infected smear-negative TB patients, and tells us nothing about resistance to the nine other commonly used drug classes.
One of the goals of K-RITH is to train new generations of researchers and clinicians in South Africa.
That is why K-RITH will be exploring other approaches, including the development of breath tests, as well as new probes for mRNA or proteins. One of the eight labs will be led by microfluidics expert Frederick Balagaddé, who aims to create improved biomarker, diagnostic, and drug-assessment tools for TB and HIV using microfluidic chips produced in South Africa. Indeed, our larger goal is that these new tools should be invented and developed locally.
The other crucial need is for drugs. No new medicines have been approved since 1967 and successfully treating TB requires at least six months of daily doses of four different drugs. The difficulty of completing the full drug regimen in many patients has led to the increasingly urgent problem of multiple and total drug resistance (Iseman, 2007
). Our hope, even expectation, is that the intensive basic research at K-RITH will identify microbiological pathways and mechanisms that will lead to new drug targets. In addition, Jacques Grosset, scientist in residence at K-RITH, will continue his decades of effort to test new drugs in mice, while others will work on new vaccines.
Finally, it is important to remember that K-RITH's mission is not just to conduct basic and translational research. We also want to inspire, train and nurture new generations of South African students, clinicians and researchers. The institute will offer courses, workshops, and masters and PhD programs, in collaboration with UKZN and universities in the United States and Europe. It is also implementing an outreach program to supplement science learning in high schools in the nearby township of Cato Manor. The solution to the urgent global threat of TB is not just a matter of bringing technology and basic science to the heart of an outbreak. It also requires increasing South Africa's own research capabilities and taking advantage of the country's brainpower.
Admittedly, winning the battle against TB and HIV and establishing a world-class research effort are ambitious goals. It might, for instance, be a challenge to sustain K-RITH after the HHMI commitment ends in 2018. But the stark reality is that the current approach to tackling TB has fallen short, so a new approach is needed. If K-RITH stumbles, it will have been a noble experiment, teaching us valuable lessons about the design of future research enterprises. But if it succeeds, as we believe it will, it will offer a new model of science that can be brought to other deadly epidemics around the world.