Journal of the Pediatric Infectious Diseases Society
BRIEF REPORT
Tuberculous Pericardial
Effusions in Children
Ndidi J. Obihara,1 Elisabetta Walters,2 John Lawrenson,3
Anthony J. Garcia-Prats,2 Anneke C. Hesseling,2 and H. Simon Schaaf2
Faculty of Medical Sciences, Radboud University, Nijmegen, the Netherlands; and
1
Desmond Tutu TB Centre, 3Department of Paediatrics and Child Health, Faculty of
2 val, 0.2%–2.1%) [5].
Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
Current data on tuberculous pericardial effusion in children are
limited. In this study, the cases of 30 children with tuberculous
pericardial effusion were reviewed retrospectively. The prev-
alence of human immunodeficiency virus and of culture-con-
firmed tuberculosis was high. Chest radiography provided lower
diagnostic sensitivity than sonography but detected all large
and complicated effusions. Outcomes were generally good, and
residual complications were mainly due to comorbidity.
Keywords.  child; lung disease; pericarditis; sub-Saharan
Africa.
In children, up to 25% of cases of tuberculosis (TB) are of
extrapulmonary TB (EPTB) [1]. Tuberculous pericardial effu-
sion (TB-PE), a rare manifestation of EPTB, is the most com-
mon cause of pericardial effusion in high-TB-burden settings
[2]. Characteristic symptoms/signs of TB-PE are shortness of
breath, raised venous jugular pressure, impalpable apex or muf-
fled heart sounds, and chest pain [3]. TB-PE in adults has been
associated with human immunodeficiency virus (HIV) infec-
tion, and 40% of such patients die within 6 months of onset [4].
Studies of TB-PE in children have been rare, and none have
been performed in the era of HIV [3]. We describe here the
clinical presentation, diagnosis, management, and outcome of
children with TB-PE, including children with and those with-
out HIV, managed at 2 hospitals in Cape Town, South Africa.
METHODS
This retrospective descriptive study included both HIV-positive and
HIV-negative children <13 years old (pediatrics admission criteria)
diagnosed with bacteriologically confirmed or probable TB-PE at
Tygerberg Hospital (TBH), a tertiary referral hospital, or Brooklyn
Received 17 February 2017; editorial decision 8 September 2017; accepted 14 September 2017;
published online October 31, 2017.
Correspondence: N. J. Obihara, Bachelor of Medical Sciences, Faculty of Medical Sciences,
Radboud University, Comeniuslaan 4, Nijmegen 6525HP, Netherlands (n.obihara@student.ru.nl).
Journal of the Pediatric Infectious Diseases Society   2018;7(4):346–9
© The Author(s) 2017. Published by Oxford University Press on behalf of The Journal of the
Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail:
journals.permissions@oup.com.
DOI: 10.1093/jpids/pix087
346 • JPIDS 2018:7 (December) •  BRIEF REPORT
Chest Hospital (BCH), a long-term TB care facility, in Cape Town,
South Africa, between January 2011 and December 2015.
In 2013, the Western Cape TB notification rate for children
aged 0 to 14 years was 411 in 100 000 (personal communication,
Western Cape ETR.Net), whereas in 2012, the HIV prevalence
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in children aged 2 to 14 years was 0.7% (95% confidence inter-
Study children from TBH were identified from the hospital
discharge codes “pericardial effusion” and “pericarditis” in an
ongoing clinical database of all culture-confirmed TB in chil-
dren, and those from BCH were identified from clinical notes
of all children admitted to the hospital within the study period.
The diagnosis of TB-PE was supported by chest radiography
(CXR) revealing cardiomegaly with or without pleural effusion,
or it was reported incidentally at the time of an ultrasound (US)
examination for suspected abdominal TB.
Data were extracted from patient hospital folders using a
standard data-collection tool. Chest radiographs were reviewed
by a pediatric TB expert (H. S.  S.) using a standard tool. All
echocardiography, US, and chest computed tomography (CT)
reports were reviewed.
Bacteriologically confirmed TB-PE was diagnosed by echo-
cardiography (by a cardiologist), US (by a radiologist), or CT
and a positive culture result for Mycobacterium tuberculosis
from any site. Probable TB-PE was defined as culture results
negative or unavailable for M tuberculosis and PE diagnosed as
described above plus a clinical TB diagnosis based on chronic
symptoms or signs of TB, contact with an infectious TB source
case, and a positive tuberculin skin test result.
PEs were classified according to echocardiography by the
cardiologist (J. L.) or from US reports as small (≤3 mm diame-
ter at widest point), moderate (4–10 mm), or large (>10 mm or
required pericardiocentesis).
TB was classified as pulmonary TB or EPTB. The sever-
ity of each patient’s TB disease was assessed using an adapted
Wiseman classification [6]. Only large or complicated PEs (tam-
ponade, TB-PE that required pericardiocentesis or pericardiec-
tomy, or constrictive pericarditis) were considered severe. Small
and moderate TB-PEs without complications were considered
nonsevere. Other nonpericardial TB manifestations were used
for the final classification of disease severity.
In the study setting, 2 or more relevant specimens for
mycobacterial investigation were collected from all children
with possible TB for automated liquid culture. Mycobacterial
identification and testing of positive cultures for susceptibility
to isoniazid and rifampicin were completed using GenoType
MTBDRplus (Hain Lifescience, Nehren, Germany).
Descriptive analyses were performed with IBM SPSS
Statistics 22 (SPSS, Inc, Chicago).
 The Stellenbosch University Health Research Ethics Table 1.  Demographics, Clinical Presentation, and Outcome of Children
With TB-PE
Committee (approval N15/11/125) and the Western Cape
Health Research Committee (approval WC_2016RP54_361)
HIV Positive HIV Negative Total Group
approved this study. Characteristic (n = 9) (n = 21) (n = 30)
Age (median [IQR]) (mo) 44 (27–77) 50 (16–111) 47 (20–93)
Sex, male (n [%]) 4 (44) 14 (67) 18 (60)
RESULTS
Contact with TB source case (n [%]) 6 (67) 8 (38) 14 (47)
Thirty children with TB-PE were included in this study; 18 (60%) Type of TB (excluding TB-PE) (n [%])

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  PTB only 2 (22) 3 (14) 5 (17)
were male, and the median age was 47 months (interquartile range
  EPTB only 1 (11) 4 (19) 5 (17)
[IQR], 20–93 months) (Table 1). At presentation, TB was clinically
  Both PTB and EPTB 6 (67) 13 (62) 19 (63)
considered in 23 (77%) of 30 children (Table 1). Of these children, 3   No PTB or EPTB 1 (5) 1 (3)
had symptoms suggestive of TB-PE (chest pain, difficulty breathing, EPTB typeb (n [%]) 7 17 24
jugular vein distention, and/or muffled heart sounds). Of the 7 chil-   Abdominal TB 5 (71) 10 (59) 15 (63)
dren for whom TB was not considered initially, 3 were found to have   Peripheral lymphadenopathy 5 (71) 8 (47) 13 (54)
 PEs 2 (28) 8 (47) 10 (42)
cardiac tamponade, 1 had heart failure, 1 had an isolated PE, and 2
  Miliary TB 2 (28) 4 (24) 6 (25)
had TB-PE associated with either pulmonary TB (lung collapse) or   TB meningitis 1 (14) 2 (12) 3 (13)
TB meningitis. Of 5 (17%) of the 30 children with previous TB dis-   Paraspinal abscess 1 (6) 1 (4)
ease (1 with previous TB-PE), only 2 completed treatment.   TB chest wall abscess 1 (6) 1 (4)
PE was suspected in 18 (62%) of 29 children by CXR. Presenting symptomb,c (n [%])

Diagnosis of PE was made in 29 (97%) of 30 children by sonog-   Weight loss/failure to thrive 9 (100) 16 (76) 25 (83)
  Cough for >2 wk 8 (89) 12 (57) 20 (67)
raphy: 22 (76%) of 29 by echocardiography, 20 (69%) of 29 by
 Fever 4 (44) 9 (43) 13 (43)
US, and 13 (45%) of 29 by both echocardiography and US. In 1   Difficulty breathing 1 (11) 7 (33) 8 (27)
child, CT was the only diagnostic method used. In 7 (23%) of 30   Weight-for-age z score less than –2 2 (22) 4 (19) 6 (20)
children, the TB-PEs were large, in 8 (27%) they were moderate,   Night sweats 1 (11) 3 (14) 4 (13)
and in 13 (43%) they were small; no size was reported for 2 (7%)   Abdominal pain 4 (19) 4 (13)
 Diarrhea 2 (22) 2 (10) 4 (13)
of the children. Of the 11 children who had PEs that were not
 Vomiting 1 (11) 3 (14) 4 (13)
suspected on CXR, 1 (9%) was unclassified, 6 (55%) were small,
  Chest pain 3 (14) 3 (10)
and 4 (37%) were moderate. Presenting clinical signs (n [%])b,c
Pulmonary TB was present in 24 (80%) of 30 children and  Hepatomegaly 8 (89) 13 (62) 21 (72)
EPTB in 24 (80%), the latter excluding PE (Table 1). TB was   Peripheral lymphadenopathy 6 (67) 13 (62) 19 (63)
severe in 17 (57%) children and nonsevere in 12 (40%). One   Distended abdomen 4 (44) 6 (29) 10 (33)
 Anemia 2 (22) 6 (29) 8 (27)
child’s TB could not be classified (no CXR available).
 Tachypnea 7 (33) 7 (23)
Nine (30%) children were HIV positive. The median CD4
  Edema (nutritional)d 2 (22) 5 (24) 7 (23)
count (n = 8) was 423.5 cells/mm3 (IQR, 375.3–524.0), and the  Splenomegaly 1 (11) 5 (24) 6 (20)
median CD4 percentage was 18.4% (IQR, 12.2%–24.4%). The  Clubbing 2 (22) 2 (10) 4 (13)
median viral load (n = 7) was 5.5 log10 copies (IQR, 5.2–6.4 log10   Pericardial friction rub 3 (14) 3 (10)
copies). One (11%) child was started on antiretroviral therapy  Rash 2 (22) 1 (5) 3 (10)
PE size (n [%])
3 years before his TB-PE diagnosis but was found to have poor
 Large 2 (22) 5 (24) 7 (23)
virologic control (viral load, 10 744 copies/mL), whereas 8  Moderate 2 (22) 6 (29) 8 (27)
(89%) children were newly diagnosed and started antiretroviral  Small 4 (44) 9 (43) 13 (43)
therapy within a median 17.5 days (IQR, 11.5–27.75 days) after   Not classified 1 (11) 1 (5) 2 (7)
admission. One child developed signs of immune reconstitu- TB disease classification (n [%])

tion inflammatory syndrome after initiating ART but did not  Severe 5 (56) 12 (57) 17 (57)
 Nonsevere 4 (44) 8 (38) 12 (40)
experience worsening of TB-PE.
  Not classified 1 (5) 1 (3)
All children received susceptibility-appropriate antitu- TB-PE culture confirmation (n [%])
berculosis treatment. When recorded, the median treatment   Culture-confirmed TB-PE 7 (88) 16 (76) 23 (77)
duration for children with drug-susceptible TB was 9 months   Probable TB-PE 2 (22) 5 (24) 7 (23)
(range, 6–12 months). In 2 children with drug-resistant TB, TST results (n [%]) 8 10 18
 Positive 4 (50) 7 (70) 11 (61)
the treatment duration was 19 and 24 months on second-line
Mycobacterium tuberculosis culture 8 20 28
drug regimens; the third child had no documented treatment specimens (n [%])
duration. Prednisone was started in 24 (80%) of 30 children.   Respiratory specimens 7 (88) 12 (60) 19 (68)
The indication for steroid therapy in 13 (54%) of 24 children   Peripheral lymph node aspirates 1 (13) 5 (25) 6 (21)

BRIEF REPORT • JPIDS 2018:7 (December) • 347
Table 1. Continued DISCUSSION

HIV Positive HIV Negative Total Group To our knowledge, this is the second largest study of TB-PE in children
Characteristic (n = 9) (n = 21) (n = 30) to have been performed and the first to have included HIV-positive
  Pericardial fluid/tissue 2 (10) 2 (7) children [3]. The prevalences of HIV and of culture-confirmed TB
  Cerebrospinal fluid 1 (5) 1 (4)
were high. The HIV prevalence (30%) was higher than that in other
DST results (n [%]) 6 16 22
hospital-based studies of children with TB during the same time in
  Drug-susceptible TB 5 (83) 14 (88) 19 (86)
  MDR TB 2 (13) 2 (9) our setting [7, 8]. However, HIV-positive children presented simi-

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  RMR TB 1 (17) 1 (5) larly to HIV-negative children; they both had similar proportions of
Complicationb (n [%]) 3 9 12 EPTB, large TB-PEs, severe TB, and previous TB.
  Cardiac tamponade 1 (11) 2 (10) 3 (10) In HIV-positive and HIV-negative children with TB-PE, the
  Constrictive pericarditis 1 (11) 2 (10) 3 (10)
clinical presentation was mostly nonspecific; only 3 children
  Recurrent PE 1 (5) 1 (3)
  Residual signs/symptomsa 1 (11) 5 (24) 6 (20)
had specific symptoms. A  majority (97%) of the children had
 Death 1 (5) 1 (4) other manifestations of pulmonary TB or EPTB together with
Surgical intervention (n [%]) pericardial involvement, which highlights the value of exam-
 Pericardiocentesis 1 (11) 3 (14) 4 (13) ining additional sites for TB disease, including specimens col-
 Pericardiectomy 1 (5) 1 (3) lected for mycobacteriology.
  Pericardiocentesis and 1 (5) 1 (3)
pericardiectomy
In the majority of children, CXR that revealed a large globu-
Outcome (n [%]) lar heart was the first indication of possible pericardial effusion.
  Completed treatment or cured 6 (67) 14 (67) 20 (67) US for either abdominal TB or pleural effusion identified the
  No outcome documented 3 (33) 4 (19) 7 (23) condition in almost all the other children.
  Lost to follow-up 2 (10) 2 (7)
The rate of bacteriological confirmation, mostly from respi-
 Death 1 (5) 1 (3)
ratory specimens and peripheral lymph node aspirates, was
Abbreviations: DST, drug-susceptibility testing; EPTB, extrapulmonary tuberculosis; HIV, human immunode-
ficiency virus; IQR, interquartile range; MDR, multidrug-resistant; PE, pericardial effusion; PTB, pulmonary
higher than that typically achieved for pediatric TB (77%) [9,
tuberculosis; RMR, rifampicin monoresistant; TB-PE, tuberculous pericardial effusion; TST, tuberculin skin test. 10]. Only 2 children had M tuberculosis isolated from pericar-
a
Residual signs/symptoms included 1 patient with residual pericardial effusion, 1 patient readmitted with
hypoxic pneumonia, 1 patient with tuberculous meningitis with spastic diplegia, 1 patient with tuberculous dial tissue or fluid specimens. In a case series by Hugo-Hamman
meningitis with developmental delay, 1 patient with seizures and developmental delay, and 1 patient with et al [3], only 13% of the cases were confirmed bacteriologically.
residual lymphadenopathy, clubbing, and pallor.
b
Children could be counted in >1 category. The more severe spectrum of TB in our study, with its associ-
c
Presenting symptoms and signs that occurred in <3 children of the total group are not mentioned.
d
Of the 7 children with nutritional edema, 5 had bacteriologically confirmed tuberculosis, and all 7 had chest
ated higher bacterial burden, might have contributed to the
radiographs with typical signs of tuberculosis, aside from the pericardial effusion (mediastinal lymphadenop- higher rate of M tuberculosis detection.
athy with 2 also miliary and 3 also unilateral pleural effusion); we conclude that the etiology of the pericardial
effusion was more likely to be tuberculosis than a hypoproteinemic state. In our series, children presented mainly with features of
clinically severe TB in other sites, and most TB-PEs observed
were small, asymptomatic, and diagnosed incidentally; cardiac
tamponade was found in only 3 children. In contrast, 90% of
children in the Hugo-Hamman et al [3] study had cardiac tam-
was treatment for PE (median dose, 2  mg/kg for a median ponade, and 64% had large effusions or constrictive pericarditis.
4-week duration) and in 11 (38%) of 24 for airway compres- CXR provided lower diagnostic sensitivity than sonography
sion, immune reconstitution inflammatory syndrome, or TB but detected all large and complicated effusions. With sonogra-
meningitis. Three (10%) children were treated for cardiac fail- phy (both US and echocardiography) more readily available in
ure with diuretics. Five (17%) children with large PEs had 6 our setting, TB-PE might be diagnosed at an earlier stage, and
therapeutic pericardiocenteses, 1 was treated medically, and 1 interventions such as medical and surgical therapy might pre-
had no PE treatment. The median volume of pericardial fluid vent complications. Because of our retrospective study design
drained was 465 mL (IQR, 275–737.5 mL). Two (7%) children and the absence of routine sonography in all children with TB,
had a pericardiectomy. however, we could not determine the true diagnostic value
Cure or treatment completion was documented for 20 of sonography. We found it reassuring that cardiomegaly was
(67%) children, 1 (3%) HIV-negative child died as a result found with CXR in all children with large effusions and in most
of disseminated drug-susceptible TB, 2 (7%) children were children with clinically significant effusions.
lost to follow-up, and for 7 (23%) children, the final outcome The clinical relevance of small and moderate TB-PEs in the
was not documented at the clinic. Of 6 (20%) children with absence of cardiac symptoms requires additional study. Our
residual signs/symptoms after hospital discharge, only 1 had data suggest that moderate and small effusions diagnosed inci-
a residual PE. dentally resolved without surgical intervention, but the cutoff

348 • JPIDS 2018:7 (December) •  BRIEF REPORT

for drainage of larger effusions has not been established. We
graded the size of TB-PEs according to the method used by
our local pediatric cardiologists. An evidence-based gradation
method might be useful for predicting the risk of complications
and determining the need for drainage.
Twenty percent of the children in our study required sur-
gical intervention; 1 child developed recurrent PEs, and 1 had
residual PEs. Early PE-TB diagnosis, interventions including
medical and surgical management, and routine administration
of steroids to all HIV-negative children with probable TB-PE at
our hospital might explain why our recurrence rate was lower
than that observed by Hugo-Hamman et al [3], who found that
14% of children in their study developed constrictive pericardi-
tis after surgery (none had received steroids), and 8% had recur-
rent effusions.
In contrast to the high mortality rate reported for adults with
TB-PE [4], only 1 child in our study died as a result of dissemi-
nated TB. Residual morbidity, observed in 20% of the children,
was related primarily to TB meningitis (Table 1), although both
morbidity and death might have been underestimated because
of missing follow-up data, particularly for the HIV-positive
children.
CONCLUSIONS
Despite the high HIV prevalence in this study, most children
with TB-PE presented with small or moderate effusions but
had additional manifestations of TB in other sites. Although
20% needed surgical intervention, their outcomes were
generally good, and residual complications were mainly due to
comorbidity.
Notes
Acknowledgments.  We thank Barend Fourie and Karen Du Preez for
assisting with data collection.
Financial support.  This work was supported by the Van Walree Grant
of the Royal Netherlands Academy of Arts and Sciences (N. J. O.) and the
South African National Research Foundation (H. S. S.).
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Potential conflicts of interest.  All authors: No reported conflicts of
interest. All authors have submitted the ICMJE Form for Disclosure of
Potential Conflicts of Interest. Conflicts that the editors consider relevant to
the content of the manuscript have been disclosed.
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