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
Keywords: miliary tuberculosis; children; risk
Abstract

M
factors
Background Miliary tuberculosis (TB) is a fatal form of iliary tuberculosis (TB) is caused by
tuberculosis with severe clinical symptoms and complications. hematogenous and lymphatogenous
The mortality rate from this disease remains high, therefore, it
dissemination of Mycobacterium
is important to identify the risk factors for miliary TB for early
tuberculosis bacteria in the body, infecting
detection and treatment.
multiple organs. It accounts for 3–7% of
Objective To identify risk factors for miliary tuberculosis in 1
all TB cases. Although there have been few reports on
children.
the prevalence of miliary TB in Indonesian children,
Methods A case-control study of children aged 0-14 years with
the Indonesian Ministry of Health reported 1,168 cases
miliary TB was conducted in Dr. Soetomo Hospital from 2010
of pediatric pulmonary acid-fast bacilli (AFB) positive
to 2015. Data were taken from medical records. Case subjects
TB in 2014.2 The mortality rate from miliary TB is
were children with miliary TB, and control subjects were
usually around 25%, but may reach 100% if left
children with pulmonary TB. Patients with incomplete medical
untreated.3
records were excluded. Case subjects were identified from the
total patient population; control subjects were included by Complications from the disease include
purposive sampling, with case:control ratio of 1:1. Potential respiratory distress syndrome, renal failure,
risk factors were age, nutritional status, BCG immunization pericarditis, shock, disseminated intravascular
status, and history of contact with TB patients. Statistical coagulation, and acute respiratory failure.3,4 Miliary TB
analyses were done with Chi-square and logistic regression in children has been closely linked to the pathogenesis
tests. P values < 0.05 were considered to be statistically of TB meningitis (TBM), the most fatal form of TB.
significant. The proportion of children with miliary TB who suffer
Results A total of 72 children were analyzed, with 36 case and TBM is larger than that of adults with miliary TB.4,5
36 control subjects. Nutritional status had a significant Some proposed risk factors for developing miliary
associatation with miliary TB in children (OR 3.182; 95%CI TB in children have been younger age, malnutrition,
1.206 to 8.398; P=0.018) in both bivariate and multivariate lack of BCG immunization, and history of contact with
analyses. The probability of a child with moderate or severe tuberculosis patients.4,6-8 Since pediatric TB and the
undernutrition developing miliary TB was 76.09%. Other severe complications of miliary TB are a health
factors were not significantly associated with miliary TB.
Conclusion Nutritional status is significantly associated with
miliary TB in children, and moderate or severe undernutrition
increases the risk for developing miliary TB. [Paediatr Indones.
2017;57:63-6. doi: http://dx.doi.org/10.14238/
pi57.2.2017.63-6 ].
 history of contact with TB patients. Age was categorized
as ≤2 years or >2 years. Nutritional status was
From the Medical Student1, Department of Public Health and Preventive
determined using the weight/height WHO curves for
Medicine2, and Department of Child Health3, Airlangga University
Medical School/Dr. Soetomo Hospital Surabaya, East Java, Indonesia. subjects under 5 years or the CDC curves for those over
5 years,1 according to subject’s sex. All data were taken
Reprint requests to: Clarissa Cita Magdalena, Airlangga University
Medical School Surabaya, Jl. Mayjen Prof. Dr. Moestopo 47, Surabaya,
from the medical records. We performed bivariate Chi-
East Java, Indonesia. Tel. +62-31-5020251; E-mail: citamagdalena@ square and multivariate logistic regression analyses
gmail.com
using SPSS version 20 software. Results with P values
<0.05 were considered to be statistically significant,
with 95% confidence intervals.
Paediatr Indones, Vol. 57, No. 2, March 2017 • 63
Clarissa Cita Magdalena et al: Risk factors for miliary tuberculosis in children
problem in Indonesia, we aimed to identify risk factors
for miliary TB in children, in order to facilitate early
Results
prevention and intervention. Out of 1,184 TB patients admitted during the study
period, 46 had miliary TB. Ten patients were
excluded, leaving 36 subjects in the case group.
Methods Thirty-six pulmonary TB patients were included as
the control group. The characteristics of the subjects
We conducted a hospital-based, case-control,
are presented in Table 1.
retrospective study using secondary data from medical
records of pediatric patients admitted to the Division Table 1. Characteristics of subjects
of Respirology, Department of Child Health, Airlangga
Characteristics N=72
University Medical School, Dr. Soetomo Hospital,
Surabaya from 2010 to 2015. This study was approved Age, n(%)
by the Medical Ethics Committee of Dr. Soetomo < 2 years 25 (34.7)
≥ 2 years 47 (65.3)
Hospital, Surabaya, East Java, Indonesia.
Nutritional status, n(%)
Subjects were divided into case and control Moderate or severe undernutrition 40 (55.6)
groups. Children under 14 years of age and diagnosed Normal 32 (44.4)
with miliary TB were selected as case subjects. Children BCG immunization status, n(%)
under 14 years of age and diagnosed with pulmonary No 12 (16.7)
Yes
TB using Indonesian Pediatric Tuberculosis Scoring 60 (83.3)
History of contact with TB patients, n(%)
System1 with a diagnostic score ≥6 were selected as Yes 53 (73.6)
control subjects. The scoring system was used only for No 19 (26.4)
the control subjects. Children with incomplete medical Bivariate analysis of the possible risk factors
records were excluded. Cases were taken from the total showed that only nutritional status was significantly
population of those with miliary TB, while controls associated with miliary TB in children (OR 3.182;
were included by purposive sampling, with a case: 95%CI 1.206 to 8.398; P=0.018). Age, BCG
control ratio of 1:1.
Potential risk factors analyzed were age,
nutritional status, BCG immunization status, and
Table 2. Bivariate analysis of miliary tuberculosis risk factors in children
Case Control
Variables (n=36) (n=36) OR 95%CI P value

Age, n
< 2 years 16 9
2.400 0.882 to 6.528 0.083
≥ 2 years 20 27

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 contact with from active TB disease and TB infection.
associated with miliary TB in children (OR 3.182; We found no statistically significant associations
95%CI 1.206 to 8.398; P=0.018). Age, BCG between age, BCG immunization status, or history of
immunization status, and history of contact with TB contact with TB patients and the incidence of miliary
patients were not significantly associated with miliary TB in children. However, we suggest that younger age
TB (Table 2). and negative BCG immunization status may also

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
Multivariate analysis revealed similar results, increase the risk of miliary TB, as reported by previous
with nutritional status as the only significant risk studies.6,7
factor of miliary TB in children (Table 3). The The difference between our findings and those
probability of a child with moderate or severe of previous studies may be due to several reasons.
undernutrition developing miliary TB was found to First, age in our study may have been affected by the
be 76.09%.
Discussion undernutrition possibly increases the risk of
developing miliary TB higher prevalence of older
We identified moderate/severe malnutrition as a pediatric TB patients. A previous study noted that
significant risk factor for miliary TB in children. even though an age under 2 years was a risk factor
Similarly, a study in India found that malnutrition of miliary TB, most children with TB infection in
was a risk factor for miliary tuberculosis.4 Also, endemic areas were older than 2 years, so there was
another study in India found a significant a higher chance of more children over 2 years
association between nutritional status and the suffering from miliary TB.6 Another study in
incidence of pulmonary tuberculosis infections.9 A England and Wales also found more miliary TB in
previous study in Peru also found a significant older children, which indicated the possible
association between malnutrition and mortality in reactivation of latent disease.14 Thus, we suggest
children with TB.10 Furthermore, a systematic that miliary TB should be suspected in children of
review of studies in developed countries like the any age. Second, BCG immunization coverage was
United States, Hong Kong, Finland, and Norway, high in our study. According to a systematic review
found a consistent relationship between the by Trunz et al., the estimated efficacy of BCG
incidence of TB and the body mass index (BMI) of prevention of miliary TB reached 77%, but in Asian
the patients, with a 14% increased risk of TB for a countries, there might be an overestimation of the
decrease of one BMI unit.11 number, due to the inclusion of studies of countries
The relationship between nutritional status in with higher immunization coverage than Asian
children and miliary tuberculosis incidence may be countries but with lower risk of infection, while
explained by Jaganath et al. who suggested that Asian countries have higher rate of infection and
nutrient deprivation may have a detrimental effect reinfection despite the high immunization
on Th1 cells, which act as an important component coverage.15 Moreover, Fine found that the
in cell-mediated immune system defense against protective effect of BCG was influenced by
miliary TB.12 A previous study reported that cell- geographic location, as the protective effect
mediated immunity is a key factor in host defense declined in regions closer to the equator.16 BCG
mechanisms against the progression of TB infection immunization itself should continue to be
to active TB disease.13 Therefore, the compromised administered as regulated, but we suggest
cellular immune system in children with continuing future study for a better vaccine. Third,
 the majority of our subjects reported a positive 7. Newton SM, Brent AJ, Anderson S, Whittaker E, 66 •
history of contact with TB patients, in contrast to
previous studies with more subjects who had no
history of contact with TB patients.8,17

Paediatr Indones, Vol. 57, No. 2, March 2017 • 65

Clarissa Cita Magdalena et al: Risk factors for miliary tuberculosis in children
Therefore, contact tracing is an important task, but the
precise relationship between contact and miliary TB
needs further study.
A limitation of this study was the use of secondary
data which could create a bias in the information we
Paediatr Indones, Vol. 57, No. 2, March 2017 Kampmann
received. We propose future studies with better
methodologies, preferably with a prospective design.
In conclusion, moderate/severe malnutrition is a
significant risk factor for miliary TB in children.
Further study is needed to elucidate the pathogenic
mechanism between undernutrition and miliary TB.

Conflict of interest
None declared.

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