Low cost tuberculosis diagnosis will help developing countries
14 May 2013
A combination of simple clinical, radiological and
laboratory tools can diagnose smear-negative tuberculosis (SN-TB)
better than current systems of diagnosis. The strategy, developed by
the Institute of Tropical Medicine (ITM) in Antwerp, outperforms
those currently directed at countries lacking the money or medical
infrastructure to use methods available in industrialised countries,
including the recommended World Health Organization (WHO) approach.
The results of a six-year study in Peru provide much needed
scientific evidence on the diagnosis of SN-TB cases in HIV-negative
patients. While strategies for diagnosing SN-TB have been recently
updated for HIV-positive cases, there was almost no evidence for
HIV-negative patients thus far.
Smear-negative tuberculosis refers to TB cases which go
undetected when sputum is examined on a microscope slide, a standard
diagnostic method. They add up to around 35% of total TB cases. When
doubts persist after a negative sputum test, WHO recommendations
include the response to an ‘empirical’ treatment with antibiotics to
decide whether a patient has SN-TB. This approach is a point of
reference for health practitioners around the world, but the
collaborative ITM study in Peru concludes that it is ineffective and
"The WHO algorithm is based on expertise rather than on
scientific evidence. Our findings show it simply doesn't work. We
put forward a tested alternative that does work, based on a
combination of accessible clinical, radiological and laboratory
tools. This evidence-based diagnosis, which also works when money or
advanced medical infrastructure are lacking, is good news for TB
patients around the world," said Dr. Alonso Ricardo Soto Tarazona of
the Hospital Nacional Hipólito Unanue, Lima, Peru.
Based on scientific evidence gained over the last few years, the
WHO has updated its approach for the diagnosis of SN-TB in patients
infected with HIV. Combined HIV-TB infections are frequent in many
African countries. Out of 8,8 million people who contracted TB
worldwide in 2010, 1,1 were also HIV-positive. Unfortunately,
recommendations for HIV-negative cases have not changed in decades.
The study in Peru, a country with a high incidence of TB and a
concentrated HIV-epidemic, therefore contributes significant
evidence to an area where scientific proof is lacking.
Diagnosing SN-TB in three simple steps
The new detection strategy is a combination of three diagnostic
- sputum concentration;
- a score-based tool to make a clinical prediction;
- manual liquid cultures, a decades old technique revived by
First, researchers analyse a concentrated extract of sputum,
obtained after centrifugation. If the bacterium is not found, the
next step is a score-based clinical prediction based on easily
identifiable symptoms and radiological findings.
“We identified coughing up blood and weight loss as symptoms
associated with an increased probability of smear-negative
tuberculosis. Ability to expectorate and age over 45 years, on the
other hand, were negatively associated. Shadows in the upper region
of the lungs or a diffuse presence of tiny dots, observed via X-ray,
increased the probability a person was ill,” said Soto Tarazona.
The resulting score (high, intermediate or low) informs further
steps. A suspected patient with a high score is immediately referred
to treatment. Patients with low probability scores should be
screened for other diseases. An intermediate score, associated with
a stagnating clinical picture, leads to step three: the use of
manual liquid cultures. Automatised liquid cultures, in which the TB
agent multiplies in a predetermined medium, are commonly used in
industrialised countries to determine the cause of infectious
diseases. However, the technology required is expensive and manual
techniques are all but lost.
“We delved into decades old scientific literature to rediscover
the origins of liquid culture, which started as a manual technique.
You can say we saved it from oblivion and showed that this technique
is still useful. Manual liquid culture is a valuable alternative
when a costly high-tech device simply is not an option. This is
often the case in developing countries, but also in emerging
economies," said Soto Tarazona.