More intensive screening for TB needed for HIV-positive patients in South Africa

Many cases of tuberculosis (TB) in patients starting HIV therapy will be missed if screening for the disease relies on 2006 World Health Organization (WHO) guidelines, investigators from South Africa report in the October 1^st edition of Clinical Infectious Diseases.

The investigators found that 19% of patients had undiagnosed TB. Using current WHO screening guidelines only half of these patients would have had their TB diagnosed.

However, a combination of screening tests that included checking for other symptoms of the infection (fever, weight loss, night sweats, shortness of breath and chest pain), chest x-ray, and sputum cultures could increase the detection rate to almost 100%.

“We found an enormous tuberculosis burden”, write the investigators.

TB is the leading cause of illness and death in patients with HIV in Africa.

Current WHO guidelines recommend that HIV-positive patients with a persistent cough should have an acid-fast bacillus sputum smear to test for the presence of TB. WHO is in the process of developing new guidelines on intensified case-finding.

However, many patients with HIV have smear-negative TB. Investigators therefore speculated that more intensive monitoring is required and designed a study involving patients about to start HIV treatment in Durban, South Africa.

Between May 2007 and May 2008 a total of 1035 patients were recruited to the study.

These patients had advanced immune suppression and the median CD4 cell count was just 100 cells/mm³.

On entry to the study a total of 210 (20%) of patients were already receiving TB therapy. These patients were excluded from further analysis, leaving 825 patients.

A total of 158 (19%) of these patients had culture evidence of previously undiagnosed, active pulmonary TB.

If the investigators had relied on a persistent cough alone to diagnose TB only 52% of these infections would have been detected.

The proportion of patients with a persistent cough who had TB was 25%.

Using other TB symptoms (excluding cough) the investigators would have been able to detect 72% of cases. The specificity of these symptoms was 44%.

Of the 158 patients with a positive TB sputum culture, only 14 had a positive acid-fast bacillus smear. This meant that only 9% of TB cases would have been detected had the investigators relied on this diagnostic technique, due to the very high frequency of smear-negative TB in people with HIV. However, positive acid-fast bacillus screening had a specificity of 88%.

Most (83%) patients with a positive TB culture had an abnormal chest x-ray. However, abnormal chest x-ray results had only a 35% specificity to TB, indicating that if doctors relied on this method alone to diagnose TB or order further tests, many people without TB would be tested or treated unnecessarily.

PCR diagnostics would have been able to detect 50% of TB cases.

The investigators calculated that when combined, cough and acid-fast bacillus screening would have led to the diagnosis of 56% of TB cases in their study.

However, the investigators demonstrated that checking for a range of symptoms and not just cough, chest x-ray, and acid-fast bacillus testing would lead to the detection of 93% of TB cases. Adding in PCR screening increased the detection rate to 96%.

More intensive screening would be affordable. The investigators calculated that using WHO guidelines, the cost of diagnosing each TB case was $240. This increased to $300 using more intensive screening methods. Therefore, the incremental cost to identify all TB cases (cost per case diagnosed beyond those using cough alone) was $360 per case.

The investigators believe that their study had clinical implications and “points to the need to dramatically lower the threshold for tuberculosis screening and to improve the screening diagnostic capacity for HIV-infected people living in areas where tuberculosis is endemic”.

They conclude, “accurate screening for tuberculosis with sputum microscopy and culture at the entry into care, regardless of symptoms should be considered in populations such as that of South Africa where tuberculosis and HIV are both common and deadly.”

Bassett IV et al. Intensive tuberculosis screening for HIV-infected patients starting antiretroviral therapy in Durban, South Africa. Clinical Infectious Diseases, 51: 823-29, 2010.