Another presentation at the Retrovirus conference described skyrocketing rates of TB in a peri-urban community in South Africa. (see http://www.aidsmap.com/en/news/CE720DF3-2054-4C37-988C-409FE2B6B33E.asp). In 2005, with an HIV prevalence of 23%,the township had a TB notification rate of over 2,000 per 100,000. 62% of the cases were HIV coinfected.
This study, which has since been published in the April 1st issue of Clinical Infectious Diseases (Lawn 2005) was performed in a community with a well-implemented DOTS programme that achieved cures rates of more than 80% in smear-positive cases of tuberculosis. Nevertheless, tuberculosis rates increased 2.5-fold during the study period.
In an accompanying editorial, Dr Christopher Whalen of Case Western Reserve University writes that it is important to assess where DOTS is failing. He writes “DOTS is not optimally designed to interrupt the spread of tuberculosis.” He states that there are essentially three factors involved in the transmission of m.TB
- The number of contacts between an infectious person and susceptible contacts;
- The probability of infection (or disease) per contact for transmission
- The duration of infectiousness of the index case.
Treatment of disease only alters one of these key parameters by reducing the duration of infectiousness, but DOTS was not designed to address the number and frequency of contacts or the likelihood of disease after infection. Whalen notes that a single patient with TB is estimated to infect around 10 contacts before receiving treatment. Since people usually have a lifetime risk of developing active tuberculosis of around 10%, levels of the disease would be expected to remain static. But HIV changes the mix by greatly increasing the risk and speeding the developing active tuberculosis as well as reactivation of disease.
“The study from Cape Town illustrates the urgent need to develop novel strategies to act as companions to DOTS. These novel public health strategies should have as their primary goal to interrupt the spread of tuberculosis. Because of the potential effect of HIV infection on tuberculosis control, these strategies must also integrate with the HIV prevention and treatment programs,” concluded Dr Whalen.
STOP TB, the new strategic plan
A new plan was promised in Paris. Now focused on “enhancing and expanding” DOTS, WHO’s STOP TB department has produced a new global plan for tackling tuberculosis for 2006–2015 called Actions for life—towards a world free of tuberculosis (see http://www.stoptb.org//). Released at the World Economic Forum this past January in Davos, the plan is as much a fund-raising appeal as it is a strategic framework on how to meet Millennium Development Goals, to reduce prevalence of and deaths due to TB by 50% by 2015 (relative to 1990) and to eliminate TB as a public health problem (<1 case per million population) by 2050.
Perhaps since part of its purpose is to galvanise political will and secure financing, the plan may be forgiven some of its more optimistic projections.
The vision: by 2010, new drugs that are effective against antimicrobial resistance, that shorten treatment to two to three months, and that are compatible with antiretroviral treatment against HIV
The reality: The two leading new TB drugs (gatifloxacin and moxifloxacin) active against drug-resistant TB and compatible with HIV care are already available for other indications, however, we won’t know whether treatment duration can be shortened until the completion of large-scale studies. The other drugs? Well, time (and study) will tell.
The vision: The first in a series of new, safe, and effective vaccines is expected by 2015.
The reality: Like many vaccines, there is no guarantee that these will be effective in an HIV-infected or immune-compromised population.
The vision: For diagnostics: Rapid culture tests by 2006, a replacement for smear microscopy by 2008, and by 2010, simple, sensitive and rapid diagnostic tests that can be used by rural health workers should be available.
The reality: While some of these methods may indeed be on the cusp of being introduced, most are far from being field tested or shown to be cost-effective in low-resource settings and even further from being implemented on a wide scale in reference labs not to mention peripheral clinics. Affordable point of care tests in the bush? At present, this is wishful thinking.
This is especially true given the funding short-fall for developing new diagnostics. Despite a generous grant from the Bill and Melinda Gates Foundation,the current budget gap for tuberculosis diagnostics is more than 80% of what is needed (a $436 million gap).
So the need to promise deliverables appeal is understandable. However, to borrow a phrase from investor-seeking press releases from the financial services industry, the “forward-looking statements” regarding the diagnostics pipeline border on the insidious and could potentially detract from real-world efforts to improve diagnosis.
For example, when Dr Douglas Wilson’s recent paper on clinical algorithms for improved diagnosis appeared in the International Journal of Tuberculosis and Lung Diseases, it was instantly devalued by an accompanying editorial called “Admitting Defeat” by Perkins and Small, of FIND Diagnostics and the Gates Foundation. And yet, Dr Wilson’s paper is one of the few studies with results that could lead to improved diagnosis of TB, TODAY and not some time in the indefinite future.