Paediatrica Indonesiana

p-ISSN 0030-9311; e-ISSN 2338-476X; V ol.57, No.2(2017). p. 63-6; doi: http://dx.doi.org/10.14238/pi57.2.2017

.63-6

Original Article

Risk factors for miliary

tuberculosis in children
Clarissa Cita Magdalena1, Budi Utomo2, Retno Asih
Setyoningrum3
Abstract Results A total of 72 children were
Background Miliary tuberculosis (TB) analyzed, with 36 case and 36 control
is a fatal form of tuberculosis with subjects. Nutritional status had a
severe clinical symptoms and significant associatation with miliary TB
complications. The mortality rate from in children (OR 3.182; 95%CI 1.206 to
this disease remains high, therefore, it 8.398; P=0.018) in both bivariate and
is important to identify the risk factors multivariate analyses. The probability
for miliary TB for early detection and of a child with moderate or severe
treatment. undernutrition developing miliary TB
was 76.09%. Other factors were not
Objective To identify risk factors for
significantly associated with miliary TB.
miliary tuberculosis in children.
Conclusion Nutritional status is
Methods A case-control study of
significantly associated with miliary TB
children aged 0-14 years with miliary
in children, and moderate or severe
TB was conducted in Dr. Soetomo
undernutrition increases the risk for
Hospital from 2010 to 2015. Data were
developing miliary TB. [Paediatr
taken from medical records. Case
Indones. 2017;57:63-6. doi:
subjects were children with miliary TB,
http://dx.doi.org/10.14238/
and control subjects were children with
pi57.2.2017.63-6 ].
pulmonary TB. Patients with incomplete
medical records were excluded. Case
subjects were identified from the total Keywords: miliary
tuberculosis; children; risk

M
patient population; control subjects factors
were included by purposive sampling, iliary tuberculosis
with case:control ratio of 1:1. Potential (TB) is caused by
risk factors were age, nutritional status,
hematogenous and
BCG immunization status, and history
lymphatogenous
of contact with TB patients. Statistical
dissemination of
analyses were done with Chi-square
Mycobacterium tuberculosis
and logistic regression tests. P values <
bacteria in the body, infecting
0.05 were considered to be statistically
multiple organs. It accounts for 3–
significant.
7% of all TB cases.1 Although there
have been few reports on the
prevalence of miliary TB in
Indonesian children, the Indonesian
Ministry of Health reported 1,168
cases of pediatric pulmonary acid-
fast bacilli (AFB) positive TB in
2014.2 The mortality rate from
Paediatr Indones, Vol. 57, No. 2, March 2017
miliary TB is usually around 25%,
• 63
Clarissa Cita Magdalena et al: Risk factors for miliary
tuberculosis in children
but may reach 100% if left problem in Indonesia, we aimed to
untreated.3 identify risk factors for miliary TB
Complications from the disease in children, in order to facilitate
include respiratory distress early prevention and intervention.
syndrome, renal failure,
pericarditis, shock, disseminated
intravascular coagulation, and Methods
3,4
acute respiratory failure. Miliary
TB in children has been closely We conducted a hospital-based,
linked to the pathogenesis of TB case-control, retrospective study
meningitis (TBM), the most fatal using secondary data from medical
form of TB. The proportion of records of pediatric patients
children with miliary TB who suffer admitted to the Division of
TBM is larger than that of adults Respirology, Department of Child
with miliary TB.4,5 Health, Airlangga University
Medical School, Dr. Soetomo
Some proposed risk factors for
Hospital, Surabaya from 2010 to
developing miliary TB in children
2015. This study was approved by
have been younger age,
the Medical Ethics Committee of
malnutrition, lack of BCG
Dr. Soetomo Hospital, Surabaya,
immunization, and history of
East Java, Indonesia.
contact with tuberculosis
Subjects were divided into case
patients.4,6-8 Since pediatric TB and
and control groups. Children under
the severe complications of miliary
14 years of age and diagnosed
TB are a health
with miliary TB were selected as
case subjects. Children under 14
years of age and diagnosed with
pulmonary TB using Indonesian
From the Medical Student1, Department of Public Health
and Preventive Medicine , and Department of Child
2 Pediatric Tuberculosis Scoring
Health3, Airlangga University Medical System1 with a diagnostic score
School/Dr.
Soetomo Hospital Surabaya, East Java, Indonesia.
≥6 were selected as control
subjects. The scoring system was
Reprint requests to: Clarissa Cita Magdalena, Airlangga
University Medical School Surabaya, Jl. Mayjen Prof. Dr.
used only for the control subjects.
Moestopo 47, Surabaya, East Java, Indonesia. Tel. +62-
31-5020251; E-mail: citamagdalena@ gmail.com Children with incomplete medical
records were excluded. Cases
were taken from the total
population of those with miliary TB, period, 46 had miliary TB. Ten
while controls were included by patients were excluded, leaving
purposive sampling, with a case: 36 subjects in the case group.
control ratio of 1:1. Thirty-six pulmonary TB patients
Potential risk factors analyzed were included as the control
were age, nutritional status, BCG group. The characteristics of the
immunization status, and history of subjects are presented in Table
contact with TB patients. Age was 1.
categorized as ≤2 years or >2
Table 1. Characteristics of subjects
years. Nutritional status was
determined using the Characteristics N=72
weight/height WHO curves for
Age, n(%)
subjects under 5 years or the CDC < 2 years 25 (34.7)
curves for those over 5 years,1 ≥ 2 years 47 (65.3)
according to subject’s sex. All data Nutritional status, n(%)
Moderate or severe undernutrition 40 (55.6)
were taken from the medical Normal 32 (44.4)
records. We performed bivariate BCG immunization status, n(%)
Chi-square and multivariate logistic No 12 (16.7)
regression analyses using SPSS Yes 60 (83.3)
version 20 software. Results with P History of contact with TB patients, n(%)
Yes 53 (73.6)
values <0.05 were considered to No 19 (26.4)
be statistically significant, with Bivariate analysis of the
95% confidence intervals. possible risk factors showed that
only nutritional status was
significantly associated with
Results miliary TB in children (OR 3.182;
95%CI 1.206 to 8.398; P=0.018).
Out of 1,184 TB patients
Age, BCG
admitted during the study
Table 2. Bivariate analysis of miliary tuberculosis risk factors in children
Case Control
Variables (n=36) OR 95%CI P value
(n=36)
Age, n
16 9
< 2 years 2.400 0.882 to 6.528 0.083
20 27
≥ 2 years
Nutritional status, n
Moderate or severe undernutrition 25 15 3.182 1.206 to 8.398 0.018
Normal 11 21
BCG immunization status, n
No 9 3 3.667 0.902 to 14.901 0.058
Yes 27 33
History of contact with TB patients, n
Yes 25 28 0.649 0.225 to 1.871 0.422
No 11 8
64 • Paediatr Indones, Vol. 57, No. 2, March 2017
Clarissa Cita Magdalena et al: Risk factors for miliary
tuberculosis in children
immunization status, and history of 95%CI 1.206 to 8.398; P=0.018).
contact with associated with Age, BCG immunization status, and
miliary TB in children (OR 3.182; history of contact with TB patients
were not significantly associated age, BCG immunization status, or
with miliary TB (Table 2). history of contact with TB patients
Multivariate analysis revealed and the incidence of miliary TB in
similar results, with nutritional children. However, we suggest that
status as the only significant risk younger age and negative BCG
factor of miliary TB in children immunization status may also
(Table 3). The probability of a child increase the risk of miliary TB, as
with moderate or severe reported by previous studies.6,7
undernutrition developing miliary The difference between our
TB was found to be 76.09%. findings and those of previous
from active TB disease and TB studies may be due to several
infection. reasons. First, age in our study
We found no statistically may have been affected by the
significant associations between

Discussion decrease of one BMI unit.11

The relationship between
We identified moderate/severe nutritional status in children and
malnutrition as a significant risk miliary tuberculosis incidence
factor for miliary TB in children. may be explained by Jaganath
Similarly, a study in India found et al. who suggested that
that malnutrition was a risk nutrient deprivation may have a
factor for miliary tuberculosis.4 detrimental effect on Th1 cells,
Also, another study in India which act as an important
found a significant association component in cell-mediated
between nutritional status and immune system defense against
Table 3. Multivariate analysis of miliary risk factors in children
Variables Coefficient (B) OR 95%CI P value
Age 0.702 2.017 0.653 to 6.235 0.223
Nutritional status 1.165 3.204 1.166 to 8.805 0.024
BCG immunization status 0.891 2.437 0.527 to 11.263 0.254
the incidence of pulmonary miliary TB.12 A previous study
tuberculosis infections.9 A reported that cell-mediated
previous study in Peru also immunity is a key factor in host
found a significant association defense mechanisms against
between malnutrition and the progression of TB infection
mortality in children with TB.10 to active TB disease.13 Therefore,
Furthermore, a systematic the compromised cellular
review of studies in developed immune system in children with
countries like the United States, undernutrition possibly
Hong Kong, Finland, and increases the risk of developing
Norway, found a consistent miliary TB higher prevalence of
relationship between the older pediatric TB patients. A
incidence of TB and the body previous study noted that even
mass index (BMI) of the though an age under 2 years
patients, with a 14% increased was a risk factor of miliary TB,
risk of TB for a most children with TB infection
 in endemic areas were older subjects who had no history of

Clarissa Cita Magdalena et al: Risk factors for miliary

tuberculosis in children
than 2 years, so there was a contact with TB patients.8,17
higher chance of more children
over 2 years suffering from
miliary TB.6 Another study in
Paediatr Indones, Vol. 57, No. 2, March
England and Wales also found
2017 • 65
more miliary TB in older
Therefore, contact tracing is an
children, which indicated the
important task, but the precise
possible reactivation of latent
relationship between contact and
disease.14 Thus, we suggest that
miliary TB needs further study.
miliary TB should be suspected
A limitation of this study was
in children of any age. Second,
the use of secondary data which
BCG immunization coverage was
could create a bias in the
high in our study. According to a
information we received. We
systematic review by Trunz et
propose future studies with better
al., the estimated efficacy of
methodologies, preferably with a
BCG prevention of miliary TB
prospective design.
reached 77%, but in Asian
In conclusion, moderate/severe
countries, there might be an
malnutrition is a significant risk
overestimation of the number,
factor for miliary TB in children.
due to the inclusion of studies of
Further study is needed to
countries with higher
elucidate the pathogenic
immunization coverage than
mechanism between
Asian countries but with lower
undernutrition and miliary TB.
risk of infection, while Asian
countries have higher rate of
infection and reinfection despite
the high immunization Conflict of interest
coverage.15 Moreover, Fine None declared.
found that the protective effect
of BCG was influenced by
geographic location, as the
protective effect declined in
References
regions closer to the equator.16 1. Kementrian Kesehatan RI. Petunjuk
BCG immunization itself should teknis manajemen TB anak. Jakarta:
continue to be administered as Kementrian Kesehatan Indonesia;
regulated, but we suggest 2013. p.13,18, 85-96.
continuing future study for a 2. Kementrian Kesehatan RI. Profil
better vaccine. Third, the kesehatan Indonesia 2014.
majority of our subjects reported Jakarta: Kementrian Kesehatan Indonesia;
a positive history of contact with 2015. p.110.
TB patients, in contrast to 3. Hagan G, Nathani N. Clinical review:
previous studies with more tuberculosis on the intensive care unit.
Crit Care. 2013;17:240.
4. Sharma SK, Mohan A, Sharma A. Kampmann B. Paediatric tuberculosis.
Challenges in the diagnosis &
treatment of miliary tuberculosis.
Indian J Med Res.
2012;135:703-30.
5. Donald PR, Schaaf HS, Schoeman JF.
Tuberculous meningitis and miliary
tuberculosis: the Rich focus revisited. J
Infect.
2005;50:193-5.
6. Marais BJ, Gie RP, Schaaf HS, Hesseling
AC, Obihara CC, Starke JJ, et al. The
natural history of childhood intra- Lancet Infect Dis.
thoracic tuberculosis: a critical review
of literature from the prechemotherapy
era. Int J Tuberc Lung Dis. 2004;8:392–
402.
7. Newton SM, Brent AJ, Anderson S,

2008;8:498-510.
8. Gomes VF, Andersen A, Wejse C,
Oliveira I, Vieira FJ, Joaquim LC, et al.
Impact of tuberculosis exposure at
home on mortality in children under 5
years of age in Guinea-Bissau.
Whittaker E, 66 • Paediatr Indones, Thorax. 2011;66:163-7.
9. Singh M, Mynak ML, Kumar L, Mathew
JL, Jindal SK. Prevalence and risk
factors for transmission of infection
among children in household contact
with adults having pulmonary
tuberculosis. Arch Dis Child.
2005;90:624-8.
10. Drobac PC, Shin SS, Huamani P,
Atwood S, Furin J, Franke MF, et al. Risk
factors for in-hospital mortality among
children with tuberculosis: the 25-year
experience in Peru. Pediatrics.
2012;130:e373-9.
Vol. 57, No. 2, March 2017 11. Lönnroth K, Williams BG, Cegielski P,
Dye C. A consistent log-linear
relationship between tuberculosis
 incidence and body mass index. Int J
Epidemiol. 2010;39:149-155.
12. Jaganath D, Mupere E. Childhood
tuberculosis and malnutrition. J Infect
Dis. 2012;206:1809-15.
13. Cegielski JP, McMurray DN. The
relationship between malnutrition and
tuberculosis: evidence from studies in
humans and experimental animals. Int
J Tuberc Lung Dis.
2004;8:286–98.
14. Kruijshaar M, Abubakar I. Increase in
extrapulmonary tuberculosis in
England and Wales 1999-2006. Thorax.
2009; 64:1090-5.
15. Trunz BB, Fine P, Dye C. Effect of BCG
vaccination on childhood tuberculous
meningitis and miliary tuberculosis
worldwide: a meta-analysis and
assessment of costeffectiveness.
Lancet. 2006;367:1173-80.
16. Fine PE. Variation in protection by BCG:
implications of and for heterologous
immunity. Lancet. 1995;346:1339–45.
17. Rakhmawati W, Fatimah S, Nurhidayah
I. Hubungan status gizi, imunisasi &
riwayat kontak dengan kejadian
tuberkulosis pada anak di wilayah kerja
puskesmas Ciawi kabupaten
Tasikmalaya [final research report].
Bandung: Universitas Padjajaran; 2008.
[cited 2016 November 25]. Available
from:
http://repository.unpad.ac.id/4895/.