Simple sputum test for confirmation of childhood tuberculosis

Sputum induction results in a higher rate of TB diagnosis in infants and young children than gastric lavage, the conventional and invasive procedure, according to results of a South African study published in this week's issue of The Lancet. The study also found much higher rates of smear-positive tuberculosis in young children than expected, challenging the notion that young children with TB pose a low risk of infection to others.

Diagnosis of tuberculosis is difficult in infants and young children and can be complicated by HIV infection. Gastric lavage requires the insertion of a tube through the nose and throat into the stomach after an overnight fast, usually after admission to hospital, followed by the introduction of saline solution into the stomach in order to gather a sample of fluid from the stomach that might contain TB bacteria. This procedure is distressing for the child and for health care workers, and must be carried out on three consecutive days according to current treatment guidelines.

Sputum induction in this study required the gathering of a sample of mucus that had been coughed up after administration of saline solution to the lungs through a nebuliser (a device which delivers a liquid into the lungs as tiny droplets). This procedure is much less uncomfortable, requires only a three hour fast beforehand, and can be easily carried out on an outpatient basis.

Professor Heather Zar (School of Child and Adolescent Health, University of Cape Town, South Africa) and colleagues studied 250 children aged 1 month to 5 years who were admitted for suspected pulmonary tuberculosis in Cape Town. Sputum induction and gastric lavage were done on three consecutive days according to a standard procedure.

Samples from induced sputum and gastric lavage were positive in 87% and 65% of children, respectively. This represents a 5.6% difference in yield (p=0.018). The yield from one sample from induced sputum was similar to that from three gastric lavages. In addition, almost half of all culture positive sputum samples were also smear positive, enabling rapid diagnosis and initiation of treatment. There was no difference in the reliability of diagnosis between HIV-positive and HIV-negative children. Sputum induction was useful even in young infants, with almost 40% of children with a positive sputum culture being less than one year of age.

Professor Zar comments: "In children with suspected pulmonary tuberculosis, sputum induction, not gastric lavage, should be the standard technique for microbiological diagnosis. One sample is sufficient, but if resources allow and if the child is in hospital, two or three specimens can increase microbiological yield…The important clinical usefulness of sputum induction for diagnosis of tuberculosis in this study raises possibilities for its use in primary care, and for diagnosis of other respiratory diseases in infants and young children."

However, sputum induction requires a moderate level of technical facilities that may not be available in all health care settings, and researchers in Peru have investigated whether it is possible to obtain samples from the upper gastrointestinal tract to improve TB diagnosis. They taped one end of the string to the inside of the patient’s cheek, and then asked the patient to swallow a capsule containing the string. After four hours the string was withdrawn, washed in saline and centrifuged to obtain the sample.

In 68 of 280 cases withdrawal of the string was enough to induce sputum without the use of a nebuliser. In the remaining 212 cases, where patients underwent both string test and sputum induction, 14 cases of TB were diagnosed by culture after the string test compared with eight by sputum induction. In one case multi-drug resistant TB was diagnosed only as a result of the string test.

These patients were under investigation for tuberculosis and were either unable to produce an adequate specimen or they had a previous negative specimen. 52 HIV-positive controls without symptoms of TB had the same procedure and one case of TB was diagnosed by the string test in this group.

However, Professor Zar told aidsmap.com: “I'd be wary of this test especially in children. It seems to me to be quite unpleasant - even more so that gastric lavage – requires cooperation, for swallowing the capsule and keeping the patient in situ, and has a high rate of vomiting (20%). In addition, in almost 25% of patients it induced substantial cough (so much so that sputum induction was not considered necessary, so it has the potential for aerosolising MTb and

nosocomial transmission.”

In an accompanying editorial Alwyn Mwinga of the US Centers for Disease Control Global AIDS Program in Zambia says that while these developments are welcome, the ultimate aim must be a simple blood test for active TB using a dipstick technology that can be used by any health care worker in any health care setting.