Silent TB could be devastating, experts say

Previous assumptions about the diagnosis of TB in HIV-infected people may need to be revised, according to findings from a Tanzanian study suggesting that a significant minority of HIV-positive people have active and in some cases potentially infectious tuberculosis, without any symptoms or indications of active TB in a sputum test.

It is well established that HIV infection can make it hard to diagnose cases of tuberculosis (TB).

TB skin tests and sputum smears are often negative despite active infection, and chest X-rays cannot distinguish TB from other ailments common in people with HIV.

But these are usually problems related to proving that TB is the cause of apparent symptoms such as a fever or persistent cough.

A paper in the current issue of the journal Clinical Infectious Diseases focuses on another confounding aspect of TB and HIV management.

In the paper, researchers screening people living with HIV for a TB vaccine study in Tanzania were surprised to discover a high rate of unrecognised and sometimes even subclinical TB cases without persistent coughing or other obvious symptoms.

Their findings suggest that people living with HIV in areas with a high burden of TB may commonly harbour silent and unrecognised, yet active, TB infections that may only be detected by proactive screening.

Still, just because symptoms are not noticeable it does not mean these cases are harmless.

In fact, the consequences could be quite serious if patients start their treatment with either TB prophylaxis or antiretroviral therapy (ART).

TB and HIV coinfection

In the developing world TB is the leading cause of death among people with HIV infection.

Efforts to control the disease are failing in regions where HIV infection is common, particularly in sub-Saharan Africa, partly because advanced HIV disease foils the standard tests used to diagnose TB.

TB control efforts are based upon isoniazid (INH) treatment to keep latent infections from becoming active, and combination therapy to cure infectious pulmonary TB.

But latent infections must first be diagnosed with skin tests based on an immune response to TB antigens which is often absent in patients with advanced immune suppression.

However, it can be difficult to rule out active infection in people with HIV. Sputum smear microscopy, the primary diagnostic test for active (and infectious) tuberculosis, involves looking for TB microbes (acid-fast bacilli/AFBs) in a dye-treated sputum sample under a microscope.

However, experts now believe that this method cannot detect TB that has spread from the lungs to other parts of the body, which is a common complication in people with HIV.

The difficulty in diagnosing active TB has led some healthcare providers to ignore a WHO recommendation to treat smear negative latent TB infections with INH prophylaxis.

According to a Médecins Sans Frontières's (MSF) report last year, “MSF programmes generally do not implement this recommendation because there is no way of knowing whether an asymptomatic smear-negative HIV positive patient has active TB, latent TB or no TB at all, and administering prophylaxis could create drug resistance".

Tanzanian TB test

MSF’s concerns appear to be corroborated by the Tanzanian findings. The researchers, looking for potential participants for a TB vaccine study in Dar es Salaam, were recruiting only HIV positive adults with CD4 cell counts of 200 cells/mm3 or over, and without active tuberculosis.

Screening included a physical examination and a standardised interview with questions about weight loss in the past three months, and about the presence and duration of any cough or fever. TB skin tests were also performed to check for TB exposure.

Patients with positive TB skin tests were then screened for active TB with chest x-rays, sputum smear microscopy and culturing (either of sputum or blood), and laboratory tests were conducted looking for immunologic reactions to TB in a sample of the patient’s blood.

Of the first 93 HIV positive adults screened with CD4 cell counts over 200 cells/mm3, 14 were found to have active TB.

Four of these cases had no symptoms (subclinical TB). At this point of the study, researchers decided to exclude any patient when there was even the slightest suspicion of TB.

Despite this, six of 407 more patients deemed eligible for the study were subsequently determined to have subclinical TB at baseline on the basis of positive sputum culture results.

In regions where HIV and TB coinfection is common, waiting until people develop a cough or fever before screening them for TB may be too late.
Additional reports by Henry Neondo

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