Dr Cain has also used the preliminary data from ID-TB/HIV to analyse the performance of some of the algorithms proposed by other trials that have used the bacteriological diagnosis as a reference standard. For instance, in one of the studies in Cambodia, Dr Kimerling found that fever, rapid weight loss noticeable to the patient within the previous month and haemoptysis (coughing up blood) would be 100% sensitive for TB, but in the ID-TB/HIV study, it would be 82% sensitive.
So far in the ID-TB/HIV study, a simple screen for any one of cough, fever, weight loss has been the most sensitive symptom combination (91%).
Algorithms perform somewhat differently depending upon the CD4 cell count. For instance, the three-symptom screen mentioned above is 97% sensitive below 250 CD4 cells, and 81% sensitive above 250 CD4 cells, and a similar pattern was seen when other algorithms were assessed in the same way. ID-TB/HIV has confirmed that a host of other symptoms, signs and test results are significantly associated with TB (see box), so a large number of possible screening algorithms can be modeled with the data.
It is important to remember that these data are still preliminary and, thus far, only derived from Southeast Asia. The study that Dr Odhiambo and colleagues have planned in Kenya should expand the evidence base, as would pooling available data from other similar studies using the same reference standard.
Furthermore, Dr Getahun of WHO said that " it is imperative to replicate the type of study that Dr Varma and his group are conducting in South East Asia (ID-TB/HIV) in sub-Saharan Africa, the region most affected by the dual TB and HIV epidemic and get the results as a matter of urgency. It will help us to further address the questions we have around TB diagnosis in PLHIV and understand the situation more".
It’s not clear yet whether there will be a one-size-fits-all algorithm that will work equally well in every setting. For instance, the sensitivity of self-reported symptoms could vary by population for cultural reasons.
“The interpretation of cough, like many symptoms, is likely culturally influenced,” Dr Kimerling told HATIP. “We know from other research that patients reach some sort of threshold in interpretation of their symptoms/signs before seeking care, and the level of care they seek is influenced by other factors, traditions, access issues, costs, etc.”
In Cambodia, “there are different types of cough and for each type of cough there is one specific health-seeking behavior,” said Dr Mukadi Ya Diul of Family Health International at the UWCLH. “If it’s a cold cough, then they have to go to the traditional healer. If it’s a warm cough then they have to take this type of medicine. And so on and so on. This is really delaying access to treatment.”
Which raises another issue: Could these symptoms be so non-specific that healthcare workers won’t want to refer patients for TB diagnosis on that basis?
“So many of our patients have fevers, have weight loss, many have cough – many for reasons other than TB,” said Dr Ayles. Both Dr Harries and Dr Kimerling stressed to HATIP that weight loss and fever are very common symptoms of AIDS.
Another danger is that the quest for a perfect screening tool could postpone the use of a good one.
People may conclude that ICF implementation should wait until these studies define the optimal algorithm – but delay would put thousands of lives at risk. Implementation of a less than perfect algorithm would be progress over what is currently happening, and so far the data suggest that using any one of cough, fever and weight loss could detect up to 80% of the cases.
“Implementation should occur now,” Dr Varma told HATIP, “concurrent with research on developing better tools.”
“People are dying unnecessarily with readily diagnosable TB disease,” said Dr Kimerling. “It is the health system that is failing them, not their willingness to get screened.”
“I certainly agree that intensified TB screening for people living with HIV needs to be rapidly scaled up now,” Dr Cain told HATIP. “Data from published and ongoing studies could be used to produce interim guidelines to facilitate this. We should not delay implementing intensified case finding. It can save lives now.”
“The absence of the perfect screening algorithm is not an excuse to forego TB screening,” Dr Diane Havlir, Chair of the HIV/TB Working group of the Stop TB Partnership told HATIP. “ART programmes can and must adopt an aggressive approach to TB prevention and treatment.”