A point-of-care test for C-reactive protein (CRP) may detect tuberculosis in people with HIV and low CD4-cell counts who are starting antiretroviral therapy (ART), researchers suggest.
“Current tools to screen people living with HIV for active pulmonary TB are limited to symptom-based screening, which has an unacceptably high false-positive rate (up to 90%), and chest x-ray, which misses up to 20% of TB cases, has high infrastructure requirements and requires trained interpreters, both of which are not routinely available in most health care centers in TB-endemic areas,” Dr. Adithya Cattamanchi and Dr. Christina Yoon of the University of California, San Francisco, told Reuters Health.
“The high false-positive rate of the symptom screen is an important problem because it would require nearly all people with HIV without active TB to undergo costly and unnecessary confirmatory Xpert MTB/RIF testing while simultaneously denying eligible patients access to TB preventive therapy,” they explained in a joint email.
To investigate the utility of the point-of-care CRP test, Drs. Cattamanchi, Yoon and colleagues used it to screen 1,177 HIV-infected adults (median age, 33; 53% women; median CD4 count, 165 cells per microliter) for TB between July 2013 and December 2015. A total of 163 (14%) participants had culture-confirmed TB.
CRP concentrations were measured at baseline using blood obtained by fingerprick (concentrations of at least 10 mg/L defined a positive screen for TB). Sputum samples were collected for Xpert MTB/RIF confirmation and culture.
As reported in The Lancet Infectious Diseases, online August 25, the CRP test had 89% sensitivity and 72% specificity for culture-confirmed TB. Compared with WHO symptom-based screening, the CRP test had a lower sensitivity (89% CRP vs. 96% WHO) but much higher specificity (72% vs. 14%).
When Xpert MTB/RIF results were used as the reference standard, the sensitivity of the two screens were similar (94% CRP vs. 99% WHO).
The findings support CRP’s use as a TB screening test “for people living with HIV with CD4 count less than or equal to 350 cells per microliter who are initiating ART,” the authors conclude.
“For HIV clinics,” Drs. Cattamanchi and Yoon said, “our study suggests that replacing symptom-based TB screening with CRP-based screening would reduce the proportion of people with HIV requiring Xpert MTB/RIF confirmatory testing by more than half (60% absolute reduction) and increase the proportion of people with HIV immediately eligible for TB preventive therapy by more than fivefold.”
“In addition,” they noted, “for the vast majority of high-burden countries that use Xpert MTB/RIF as the confirmatory test, CRP-based TB screening can be expected to detect nearly all (94%) Xpert-positive TB cases – those cases that pose the greatest infectious risk to the community – while substantially reducing the costs of TB diagnosis.”
“Future studies should evaluate CRP-based TB screening in other outpatient HIV subgroups . . . and other outpatient populations targeted for systematic TB screening, such as household contacts of TB cases, miners, prisoners, etc.,” they conclude.
Dr. Annemieke Geluk of Leiden University Medical Center in the Netherlands, coauthor of a related editorial, told Reuters Health, “The strength of (the) study lies in prospectively demonstrating that fingerstick CRP reaches WHO criteria for sensitivity and specificity.”
However, “despite being highly sensitive for active TB, elevations of CRP are far from specific for TB as they are elevated also in many other diseases, so the interpretation of CRP results needs to be done with care, as other infections or health problems can affect these levels,” she said by email.
“Also, the immunology of TB is complicated, and TB comprises several stages of infection, which definitely can’t all be captured using one biomarker,” she observed.
“Future research in TB diagnostics should include more as well as other types of markers, such as transcriptomic markers, to develop a more specific point-of-care test for the most deadly infectious disease in the world,” she concluded.
Dr. Divya Reddy of Albert Einstein College of Medicine in New York City told Reuters Health, “The results are impressive and make a strong argument for the use of point-of-care CRP testing as a TB screening strategy in select HIV patients in resource-poor countries in Africa and Asia.”
“Although a formal cost-effective analysis hasn’t been done,” she said by email, “I suspect integration in public health programs will be easy and likely identify more TB cases at lower costs, thereby influencing the global TB epidemic.”
SOURCES: http://bit.ly/2xOlE0h and http://bit.ly/2eFFna3
Lancet Infect Dis 2017.