Mycobacterium tuberculosis in patients with HIV carries mortality risk
A new study by investigators at the University of Liverpool’s Institute of Infection and Global Health, as well as colleagues in Africa, reveals that Mycobacterium tuberculosis carries a significant risk of mortality for patients with HIV and is often underdiagnosed. The study appeared in The Lancet.
The team conducted a review of studies that involved routine
mycobacterial blood culture as well as a meta-analysis of
individual patient data. Subjects analyzed were at least
13-year-old, HIV positive, had available CD4 counts, and
experienced symptoms in accordance with the World Health
Organization’s (WHO) definition of suspected tuberculosis.
Nearly three-quarters of the patients (74%) were in sub-Saharan
Africa.
The investigators employed mixed-effects modeling in order to
predict the prevalence of M tuberculosis in
this patient population, which was estimated at 45% in
hospitalized HIV patients with tuberculosis and who had
WHO-defined tuberculosis symptoms and a median CD4 count of 76
cells per uL. However, the diagnostic yield—or
proportion—of positive patient
sputum
samples within the population of subjects infected with
M tuberculosis was 77%, the investigators
found. Once they added the results of urine lipoarabinomannan
(LAM) testing, the diagnostic yield rose to 89%.
Looking at patient outcomes, it became clear to the study team
that thepresenceof M tuberculosis was a
significant predictor of mortality within 30 days of
tuberculosis diagnosis, although there was no increased risk of
death after 30 days. The team also found that subjects whose
anti-tuberculosis treatment began more than 4 days after
diagnosis had an increased mortality rate. Some patients may
experience delays of 3 to 5 days before treatment is initiated,
reflecting the WHO suggestion of an observation period should
rapid testing not yield a diagnosis.
The investigators stressed that clinicians who rely solely on
blood testing to diagnose tuberculosis and don’t take into
account the results of sputum or urine testing are putting
patients at a disadvantage. “Most settings with
generalized HIV epidemics have no access to mycobacterial blood
culture,” they wrote in their report. “Even where
available, an average 3-week delay between culture and
detection, combined with high early mortality, means that
tuberculosis blood culture has limited diagnostic
value.”
The study results show that M tuberculosis is
a frequent presentation of the disease in people living with HIV
who are hospitalized in lower-resource settings, with the
infection generally underestimated. This has considerable
implications for clinical treatment, the investigators said.
Although rapid sputum testing is recommended by the WHO, the
investigators suggest adding urine LAM testing as well to
maximize the chance of an accurate result.
Regarding the WHO treatment algorithm of a 3- to 5-day delay in
treatment initiation, the study’s authors warned that it
puts vulnerable patients at risk. “Our study raises a
concern that this delay is associated with an increase in early
mortality,” they wrote. “Trials of presumptive
tuberculosis therapy in people with HIV had negative results but
recruited ambulant (without danger signs) outpatients, and so
will have largely excluded patients with M
tuberculosis BSI (bloodstream infection), in whom the
benefit of early empirical therapy is most likely.”
Source:
Contagion
