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TB biomarker predicts mortality risk in children with HIV

Children with HIV in Kenya whose urine samples tested positive for lipoarabinomannan (LAM) – biomarker of tuberculosis – had a nearly five-fold increased risk for mortality compared with children with negative LAM results, Healio reports according to recent data. The association between positive LAM results and mortality was particularly high in children with unconfirmed TB, which suggests that the antigen may identify children at risk for death whose TB infection may have been missed by respiratory sampling, Dr Sylvia M LaCourse, acting instructor in the department of medicine, division of allergy and infectious diseases at the University of Washington – Seattle, and colleagues report.

LAM is a component of the Mycobacterium tuberculosis cell wall that is detectable in the urine of patients with TB, according to the researchers. LAM testing is performed with a low-cost, point-of-care assay that uses a dipstick to detect the antigen. The World Health Organisation (WHO) recommends LAM testing in patients with HIV who have a low CD4 count or are critically ill. Previous data has shown that adults coinfected with HIV and TB who test positive for LAM have twice the risk for morality compared with adults who test negative for LAM. However, less is known about LAM’s prognostic performance for mortality in children, the researchers noted.

“The underlying pathway between LAM and TB mortality is not completely clear,” they wrote. “LAM may be a marker of disseminated TB or higher mycobacterial burden, both associated with worse prognosis. Additionally, LAM may function as a virulence factor, inhibiting macrophage function and proinflammatory cytokines, and enhancing anti-inflammatory cytokines.”

For their study, LaCourse and colleagues examined data from 137 hospitalised children (median age, 26 months) with HIV initiating ART – a population in which TB is often overlooked, according to the researchers. All participants provided urine samples for LAM testing and sputa or gastric aspirates, which were cultured for TB.

Among the cohort, 6.6% of children had confirmed TB and 43.1% had unconfirmed TB – 11% of children had positive LAM results, including 33.3% with confirmed TB and 20% with unconfirmed TB. Over a 6-month follow-up period, 15.3% of children had died.

The 6-month risk for mortality was higher in children with positive LAM results vs those with negative LAM results (adjusted HR = 4.92; 95% CI, 1.79-13.49). Among children with unconfirmed TB, a positive LAM result was associated with a 10-fold increased risk for mortality (HR = 10.4; 95% CI, 0.94-115.18).

“These children may benefit from treatment even in the absence of microbiologically confirmed TB, and urine LAM could reduce time to treatment in children at highest risk for death,” the report says the researchers noted.

Positive LAM results also predicted mortality among children with HIV-related severe immunosuppression (HR = 4.69; 95% CI, 1.73-12.70) and malnutrition (HR = 5.35; 95% CI, 1.03-27.70).

“These data provide evidence to support WHO’s recommendation that urine LAM is helpful for TB diagnosis in severely ill HIV-infected children, including those at greatest mortality risk,” the researchers concluded. “Future studies are needed to confirm whether incorporation of urine LAM can prevent mortality in HIV-infected children.”

Despite diagnostic performance limitations, urine lipoarabinomannan (LAM) predicts death in HIV-infected adults with TB. Pediatric data are limited. Among 137 hospitalized HIV-infected children, mortality was 4.9-fold higher among LAM-positives (127 vs. 31/100 py, aHR 4.92 [95%CI 1.79-13.49]; p=0.002). LAM identifies HIV-infected children at risk for death potentially missed by respiratory sampling.

Sylvia M LaCourse, Lisa M Cranmer, Irene N Njuguna, John Gatimu, Joshua Stern, Elizabeth Maleche-Obimbo, Judd L Walson, Grace John-Stewart, Patricia Pavlinac

[link url=""]Healio report[/link]
[link url=""]Clinical Infectious Diseases abstract[/link]

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