Steve Lawn, from the University of Cape Town in South Africa, began his talk on diagnostics for HIV associated tuberculosis (TB) by reminding the audience of the enormous burden of TB in his country where one percent of the population develops TB disease each year. He gave his presentation to an audience at the 49th Annual Meeting of the Infectious Diseases Society of America in Boston Friday. In one city of 3.5 million people in South Africa, 30,000 TB cases were reported in 2009 alone and half of those individuals also had HIV infection. He also pointed out that tuberculosis is the only one of the three major infectious diseases that does not have a low-cost point of care diagnostic test.
Lawn identified an urgent need for new diagnostics since effective diagnostics have a central role in all interventions for HIV associated TB. Smear microscopy remains the mainstay of diagnosis in resource-limited settings where 95 percent of the HIV associated TB is found and this primitive diagnostic misses a huge amount of TB. In the antiretroviral therapy (ART) clinic in Cape Town, sputum microscopy detects less than 20 percent of TB cases. Thirty percent of people with culture-confirmed TB in this setting had a normal chest x-ray. While culture is the gold standard of TB diagnosis, it takes more than three weeks to get a confirmed culture and culture is unavailable in much of southern Africa outside of South Africa.
Lawn went on to describe the experience of using the GeneXpert rapid TB diagnostic in the ART clinic. Ultimately GeneXpert successfully diagnosed virtually all of smear positive disease but less than 50 percent of smear negative disease with only one cartridge. It was determined to be effective and cost effective to screen all patients with GeneXpert given the huge burden of TB but Lawn argued that evaluating the value of GeneXpert depends on the setting and disease prevalence.
Time for diagnosis was reduced to two days even with the placement of the GeneXpert machine in a centralized lab. And GeneXpert is extremely effective in diagnosing the sickest patients. However, the machines and the cartridges are expensive.
Lawn also highlighted an important new diagnostic tool which is the TB-LAM-Ag produced by Alere—which is a urine dipstick test which can diagnose TB in 25 minutes. It is a simple, low-cost, point-of-care test that costs about $3.50 per test. Collecting urine is simpler than collecting sputum and while this dipstick is not as effective as the GeneXpert in diagnosing TB, it is an important supplement to smear microscopy and increases the number of cases detected. Smear microscopy plus the LAM dipstick identify 44 percent of the TB cases, essentially doubling the number of cases detected just from smear microscopy. It works best in patients with advanced HIV infection and since these are the sickest and most vulnerable patients, it can be very helpful in quickly diagnosing the patients most urgently in need of treatment intervention.
Lawn characterized this assay as the first true, low-cost, point-of-care diagnostic for HIV associated TB.