Undiagnosed tuberculosis (TB) is common
among patients receiving routine HIV care in South Africa, a study published in
the online edition of the Journal of
Acquired Immune Deficiency Syndromes suggests, reinforcing World Health Organization guidance regarding routine screening of people with HIV for TB.
An international team of investigators
found that 12% of patients had confirmed or suspected TB. A low CD4 cell count,
even in people taking HIV therapy, was a risk factor, as was low haemoglobin
and a low body weight.
"TB symptoms and previously undiagnosed TB
were common in this group of ambulatory HIV clinic patients,” write the
investigators. “CD4+ T-cell count was the dominant factor associated with
having TB, regardless of ART [antiretroviral therapy] status.”
The single biggest worldwide cause of serious illness and
death in people with HIV is TB. To reduce the burden of TB in HIV-positive people, the World Health Organization (WHO) endorses a so-called Three I's
strategy: intensified TB case finding;isoniazid preventive therapy; and
However, global implementation of this
strategy has been poor in some settings and there are limited data describing the
prevalence and risk factors for undiagnosed TB among HIV-positive people
receiving routine care.
Therefore, an international team of
investigators designed a study involving 422 people who were seen at an HIV
primary-care facility in Gauteng Province, South Africa, between 2009 and 2010.
The clinic provided HIV therapy to people
with a CD4 cell count below 200 cells/mm3 (the threshold at that time for
the initiation of treatment in South Africa).
screened for TB by checking for symptoms (cough, fever, night sweats and weight
loss). Sputum and/or blood culture, chest X-ray and fine-needle aspiration of
enlarged lymph nodes were used to confirm suspected cases.
Most of the
patients (66%) were female and their median age was 37 years. The overall
median CD4 cell count was 215 cells/mm3. A total of 196 patients
(47%) were taking HIV therapy and the median duration of treatment was 21
alone, 86% of people were identified as potentially having TB. This
prevalence did not differ between the patients taking HIV therapy and those who
were not (83 vs 88%).
prevalence of symptoms was significantly higher in people with a CD4 cell
count below 100 cells/mm3,compared to people with a CD4 cell
count above 200 cells/mm3 (p = 0.027).
suspected TB was diagnosed in a total of 50 patients.
was bacteriologically confirmed in 27 patients; in the other patients it was
diagnosed on the basis of chest X-ray or aspiration.
of undiagnosed TB was therefore 12%. This was similar in the patients taking
HIV therapy and in those who were treatment naive (10 vs 13%). One or more
symptom suggestive of TB was reported by 98% of patients with confirmed or
“It is possible
that some patients were not appropriately screened for TB prior to ART
initiation or during routine visits, and that some TB cases were missed during
this screening process,” suggest the authors. “Undiagnosed TB during the first
6 months of ART may also be due to reactivation of latent TB infection or
unmasking of TB as part of an immune reconstitution syndrome.”
Patients with a
CD4 cell count below 100 cells/mm3 were significantly more likely to
have bacteriologically undiagnosed TB than patients with a CD4 cell count above
200 cells/mm3 (OR = 5.05; 95% CI, 1.69-15.12). They also had an
increased risk of any form of TB (OR = 2.35; 95% CI, 1.07-5.17).
haemoglobin below 10 g/dl had a
significantly increased risk of bacteriologically confirmed TB (OR = 2.25; 95%
A low body
weight (body mass index [BMI] below 18.5 m2) was also associated
with an increased risk of having any form of TB (OR = 2.70; 95% CI, 1.39-5.26).
where large proportions of patients are symptomatic, TB symptom screening alone
may not be useful,” write the authors. “Algorithms which may include BMI,
haemoglobin levels and CD4+ T-cell count testing to better target individuals
more likely to have undiagnosed TB are needed.”
believe their findings have implications for the Three I’s strategy.
Individuals who did
not have symptoms of TB would have been candidates for isoniazid preventive
therapy. The results of the study showed that only one patient eligible for this
treatment had undiagnosed TB. Although the use of isoniazid preventive therapy by this
patient could have resulted in the development of drug resistance, as the authors suggest, it is important to note that WHO guidelines also recommend repeated screening for TB symptoms in people receiving isoniazid preventive therapy.
“Almost half the
TB cases in our study were sputum smear or culture positive, indicating that
there was a risk of nosocomial [hospital-acquired] transmission of TB in the clinic,” observe the
investigators. “We cannot overstate the need to strengthen implementation of
administrative and environmental infection control measures.”
“Earlier initiation of ART is encouraged to prevent TB and reduce mortality
among those who do develop TB."