Making the process of seeking smear microscopy more convenient for people, especially for the economically disadvantaged, is the focus of one of the strategies that FIND is now moving into large scale demonstration studies: one stop diagnosis.
To increase the likelihood of detecting active TB, WHO guidelines currently recommend that people with suspected TB submit at least three sputum samples (now two in people with HIV), produced on separate occasions. Usually an ‘on-the-spot’ (or spot) specimen is produced during the first visit; and then the patient is given a sputum container to take home to collect an early morning sample to bring back to the laboratory the following morning where the third specimen is collected on-the-spot. Or in some programmes, the patient must provide a specimen on three consecutive mornings (morning specimens tend to contain more bacilli because sputum collects in airway passages at night).
Regardless, the patient has to make repeated visits to the microscopy centre before a diagnosis can be made, and then has to return yet again to get the results. In addition, the visit to the microscopy centre is rarely the patient’s first contact with the health system, since they would usually first go to a lower level health facility close to their home.
For the patient, this process is usually quite expensive in terms of transportation costs and lost wages from time off work. “These costs come out to be a large percentage of their monthly income,” said Dr Bertel Squire, of the Liverpool School of Tropical Medicine, who presented a cost analysis of different diagnostic approaches in Malawi, where TB diagnostic services are free but the incidental costs of seeking a diagnosis still add up (Squire). And if the lab services are not freely provided, the cost to the patient can be even higher. In one study from Bangalore, India, the cost of seeking a TB diagnosis represented 75% of annual household income for people in the lowest socio-economic bracket and 49% for those in the highest socio-economic strata (Unnikrishnan).
One consequence of the expense and effort of getting to the microscopy centre is that a fairly large number of people simply never complete the testing process, or don’t return to get their results.
Additional smears also increase the workload for the laboratory technicians.
But a growing number of TB experts are questioning the value of the third sputum sample. For example, a recent systematic review showed that the increase in diagnoses from third sputum was less than 5%. And a recent study in Ethiopia found that collecting two sputum samples in one day yielded the same result as three smears submitted over two days in an area with low HIV prevalence (Cambanis 2006).
One of the authors of that study, Dr. Mohammed Yassin, presented the results of another study in 224 TB suspects from Abuja, Nigeria (both HIV-negative and positive) demonstrating that the two spot collection strategy could be used for same day diagnosis — and that the number of diagnoses were comparable whether the two or three day sample method was used (although the smear-positive rate in people with HIV was very low (Yassin).
Every participant in the study provided four sputum specimens (two spot specimens collected an hour apart on the first visit, one morning specimen and a spot specimen the following morning). For purposes of analysis, data for the first two specimens were combined for the one-day strategy, and data for the first, third and fourth were combined for the two-day strategy.
Overall, about 37% of 212 cultured specimens were positive, and smear microscopy identified about 54% -56% of these. How closely the two testing strategies compared to each other depended on the case definition of TB. If two positive smears were needed to make a diagnosis, 43 (19%) of the study subjects would have been diagnosed with TB compared using the one-day (two spots) strategy while 48 would have been diagnosed with TB using the two-day strategy (three sputum samples). However, if only one positive smear was required for diagnosis, 47 would have been diagnosed with TB using the one-day strategy and the number would have remained unchanged for the two-day strategy.
“The overall increase in the yield for [the two-day strategy] for the diagnosis for patients is not very high, given the advantage of having all the results on the same day, compared to the number of patients who are dropping out of the diagnostic process, waiting for the next day sputum samples,” said Dr. Yassin.
“It’s important to recognise that TB diagnosis is not just about identifying a case, it’s about making sure that case starts treatment,” said Dr Squire. “[And…] if we are going to get people onto treatment, we have to do it fast because in these poor environments, we’re going to lose people.”
His study of one stop (using only one smear) versus the standard diagnosis procedure in Lilongwe, Malawi found that although the one-stop strategy missed a higher percentage of TB cases than in Dr Yassin’s study, it did a much better job of getting people on treatment quickly than the standard approach. The one-stop approaches only diagnosed about 46.8% of the confirmed TB cases while the standard approach diagnosed 71.4% of the confirmed TB cases. Yet, 92% of those diagnosed with the one-stop approach started treatment within five days of first going to the diagnosing facility, compared to 23% in those who were diagnosed with the standard procedure. After multiplying the rates of diagnosis and the percentages put on treatment, the overall effectiveness of the one-stop strategy was 43% compared to 16.4% for the standard procedure.
However, not every TB expert at the meeting was comfortable with this approach. For example, some thought that it would be somewhat difficult to re-orient laboratories to produce results while the patient is waiting — considering the workload and the fact that smears tend to be batched for when the technician gets a chance to examine them. Others thought that the cost of missing a diagnosis might work out to be greater than the costs of a somewhat delayed treatment.
Clearly extensive operational research would be necessary before switching entirely to this strategy. One possibility is that facilities should move towards being capable of providing same day diagnosis and treatment, while keeping those who don’t test smear-positive in the system until whatever condition they have is diagnosed. The fact that people drop out of the system doesn’t mean that programmes can’t be developed to provide better follow-up. While samples given on sequential days may not increase the likelihood of diagnosis, samples given by still ill or worsening patients on following weeks are often smear-positive.
Likewise, people with HIV are the most likely to be missed by this strategy because they are most likely to be missed by smear microscopy overall. Also, people with HIV may have more trouble producing sputum later in the day, so the loss to diagnosis efficacy of not collecting a morning sputum sample from them may be greater than that observed in other people.
But the time waiting to give a second sputum specimen or wait for results could offer an opportunity for HIV screening for those who do not yet know their status. If HIV positive, additional smear microscopy may not provide much added benefit to them, but they need to be channelled swiftly to where their condition can be diagnosed.
Another aspect of the health-seeking process is that people with symptoms are generally referred to TB diagnosis facilities after attending a primary care facility. Surely, once the referral is made, it ought to be routine that the patient be given a sputum collection container to take home to provide a morning sample to take to the laboratory.