Treatment for tuberculosis infection of the membrane around the heart

What is the issue?

Tuberculosis infection of the pericardium surrounding the heart is uncommon but life-threatening.

What is the aim of this review?

The aim of this Cochrane Review was to assess the effects of treatments for people with tuberculous pericarditis.

What is this important?

Doctors prescribe antituberculous drugs for six months, drain fluid from the pericardium if the patient has heart failure, and sometimes remove the pericardium if it is thick and making the patient ill and sometimes give corticosteroids to reduce the effects of the inflammation.

What are the main results of the review?

Cochrane researchers collected and examined all potentially relevant studies and found seven trials, all conducted in sub-Saharan Africa. Six trials evaluated corticosteroids. Other treatments evaluated included Mycobacterium indicus pranii immunotherapy, colchicine, and surgical removal of fluid under general anaesthesia. This review is a new edition of the 2002 review.

In people not infected with HIV, six trials found that additional steroids may reduce deaths overall (low certainty evidence) and probably reduce deaths caused by pericarditis (moderate certainty evidence). Steroids may prevent reaccumulation of fluid in the pericardial space (low certainty evidence). However, we do not know whether or not corticosteroids have an effect on constriction or cancer among HIV-negative people (very low certainty evidence).

In people living with HIV, most people evaluated in the included trials were not on antiretroviral drugs. For these patients, corticosteroids may reduce constrictive pericarditis (low certainty evidence), but we do not know if this translates into a reduction in the number of deaths or cancer (very low certainty evidence). Corticosteroids may have little or no effect on reaccumulation of fluid in the pericardial space (low certainty evidence).

Colchicine was evaluated in one trial of 33 people, with insufficient data to make any conclusions about an effect.

Based on one trial, it is uncertain whether adding M. indicus pranii immunotherapy to antituberculous drugs has an effect on any outcome in people with tuberculous pericarditis regardless of their HIV status (very low certainty evidence).

Open surgical drainage of the fluid accumulating between the heart and the membrane using general anaesthesia may be associated with less life-threatening reaccumulation of fluid in people who are not infected with HIV, but conclusions are not possible as the number of participants studied was too small. We did not find an eligible trial that assessed the effects of open surgical drainage in people living with HIV.

The review authors found no eligible trials that examined the length of antituberculous treatment needed nor the effects of other adjunctive treatments for tuberculous pericarditis.

How up-to-date is this review?

The review authors searched for trials published up to 27 March 2017.

Authors' conclusions: 

For HIV-negative patients, corticosteroids may reduce death. For HIV-positive patients not on antiretroviral drugs, corticosteroids may reduce constriction. For HIV-positive patients with good antiretroviral drug viral suppression, clinicians may consider the results from HIV-negative patients more relevant.

Further research may help evaluate percutaneous drainage of the pericardium under local anaesthesia, the timing of pericardiectomy in tuberculous constrictive pericarditis, and new antibiotic regimens.

Read the full abstract...
Background: 

Tuberculous pericarditis can impair the heart's function and cause death; long term, it can cause the membrane to fibrose and constrict causing heart failure. In addition to antituberculous chemotherapy, treatments include corticosteroids, drainage, and surgery.

Objectives: 

To assess the effects of treatments for tuberculous pericarditis.

Search strategy: 

We searched the Cochrane Infectious Diseases Group Specialized Register (27 March 2017); the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library (2017, Issue 2); MEDLINE (1966 to 27 March 2017); Embase (1974 to 27 March 2017); and LILACS (1982 to 27 March 2017). In addition we searched the metaRegister of Controlled Trials (mRCT) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal using 'tuberculosis' and 'pericard*' as search terms on 27 March 2017. We searched ClinicalTrials.gov and contacted researchers in the field of tuberculous pericarditis. This is a new version of the original 2002 review.

Selection criteria: 

We included randomized controlled trials (RCTs) and quasi-RCTs.

Data collection and analysis: 

Two review authors independently screened search outputs, evaluated study eligibility, assessed risk of bias, and extracted data; and we resolved any discrepancies by discussion and consensus. One trial assessed the effects of both corticosteroid and Mycobacterium indicus pranii treatment in a two-by-two factorial design; we excluded data from the group that received both interventions. We conducted fixed-effect meta-analysis and assessed the certainty of the evidence using the GRADE approach.

Main results: 

Seven trials met the inclusion criteria; all were from sub-Saharan Africa and included 1959 participants, with 1051/1959 (54%) HIV-positive. All trials evaluated corticosteroids and one each evaluated colchicine, M. indicus pranii immunotherapy, and open surgical drainage. Four trials (1841 participants) were at low risk of bias, and three trials (118 participants) were at high risk of bias.

In people who are not infected with HIV, corticosteroids may reduce deaths from all causes (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.59 to 1.09; 660 participants, 4 trials, low certainty evidence) and the need for repeat pericardiocentesis (RR 0.85, 95% CI 0.70 to 1.04; 492 participants, 2 trials, low certainty evidence). Corticosteroids probably reduce deaths from pericarditis (RR 0.39, 95% CI 0.19 to 0.80; 660 participants, 4 trials, moderate certainty evidence). However, we do not know whether or not corticosteroids have an effect on constriction or cancer among HIV-negative people (very low certainty evidence).

In people living with HIV, only 19.9% (203/1959) were on antiretroviral drugs. Corticosteroids may reduce constriction (RR 0.55, 0.26 to 1.16; 575 participants, 3 trials, low certainty evidence). It is uncertain whether corticosteroids have an effect on all-cause death or cancer (very low certainty evidence); and may have little or no effect on repeat pericardiocentesis (RR 1.02, 0.89 to 1.18; 517 participants, 2 trials, low certainty evidence).

For colchicine among people living with HIV, we found one small trial (33 participants) which had insufficient data to make any conclusions about any effects on death or constrictive pericarditis.

Irrespective of HIV status, due to very low certainty evidence from one trial, it is uncertain whether adding M. indicus pranii immunotherapy to antituberculous drugs has an effect on any outcome.

Open surgical drainage for effusion may reduce repeat pericardiocentesis In HIV-negative people (RR 0.23, 95% CI 0.07 to 0.76; 122 participants, 1 trial, low certainty evidence) but may make little or no difference to other outcomes. We did not find an eligible trial that assessed the effects of open surgical drainage in people living with HIV.

The review authors found no eligible trials that examined the length of antituberculous treatment needed nor the effects of other adjunctive treatments for tuberculous pericarditis.