Background
Until recent years, the diagnosis of tuberculosis (TB) disease in children has remained challenging. The majority of studies conducted globally have revealed that childhood TB remains under-recognised and underdiagnosed [
1]. This is due to the non-specific presentation of the cases and the paucibacillary characteristics of the smear finding. The World Health Organization (WHO) classifies childhood TB as children aged 0–14 years with
Mycobacterium tuberculosis infection [
2]. The infection is acquired through the inhalation of aerosol droplets containing bacilli expectorated by an active TB patient, especially in smear-positive pulmonary TB [
3]. Therefore, the likelihood of infection is higher when children are close contacts of TB cases [
4].
According to the WHO, close contact is defined as a person ‘living in the same household or in frequent contact with the source case’ [
5]. The source case is a TB case that results in infection among their contacts [
5]. The definition of household contact commonly used in TB contact tracing programmes is ‘a person or group of people, related or unrelated to each other, who live together in the same dwelling unit and share a common source of food’ [
1]. To improve the detection of TB cases, the WHO and the International Union Against TB and Lung Disease recommend that contact tracing be included in national TB programmes (NTP) [
5]. This is because, in childhood TB, early detection is one of the fundamental aspects of reducing morbidity and mortality [
6]. Most childhood TB cases are related to close contact with TB disease [
1,
5]. A meta-analysis found that children who were household contacts had four times higher chances of acquiring infection compared to non–household contact children [
7].
Currently, contact tracing is widely practised in low–TB burden countries [
8]. In Malaysia, it is routinely performed after an active TB case is detected and notified to the health department. According to the Malaysian Clinical Practice Guidelines for TB, a child contact must be screened within 6 weeks of diagnosis of the index case [
9]. However, previous studies conducted in Malaysia have revealed that most diagnosed TB cases remain heavily dependent on passive case detection, where patients have already developed sufficiently significant symptoms spurring them to seek medical treatment [
10]. This is an undesirable outcome for any NTP, as TB is still prevalent in the country. The WHO reported that childhood TB incidence had increased to 1 million cases worldwide in 2016 [
11]. Regionally, the WHO Western Pacific Region has also shown a 6% increase in total childhood TB compared to the previous report in 2015 [
12].
A similar pattern has surfaced in Malaysia, with the estimated incidence increasing from 2800 cases to 3700 cases in the latest available report [
11]. Even though Malaysia is classified as an intermediate–TB burden country by the WHO, TB nevertheless poses a great threat, as the neighbouring countries are high–TB burden countries, e.g. Indonesia and Thailand [
11]. Moreover, Malaysia, particularly the capital city of Kuala Lumpur, receives an influx of immigrants from other high–TB burden countries from time to time. Therefore, contact tracing plays an important role in the TB prevention and control, apart from high-risk groups screening in the community. This situation indicates a further need to explore the predictors of TB disease in children who are household contacts to aid health authorities in developing a more strategic and efficient TB control and prevention programme. Hence, the present study aimed to identify the prevalence and the factors associated with TB disease in children who are household contacts of active TB cases to improve understanding of this issue.
Results
Between 1 January 2014 and 31 December 2017, a total of 2793 children aged 0–14 years who were registered with the JKWPKL TBIS were identified as household contacts. The prevalence of TB disease in children who were household contacts of active TB cases was 1.5% (95% CI: 1.31, 1.77%).
The children with TB disease had a lower mean age [5.4 (SD 0.65) years] compared to children without TB disease [7.4 (SD 0.09) years]. In the children with TB disease (
n = 43), the sex distribution was almost equal, and most were from the main ethnic group, i.e. the Malays (74.4%). Clinically, 95.3% (
n = 41) had TB symptoms, 48.8% (
n = 21) had positive TST, 86.0% (
n = 37) showed lesions on chest X-ray and had negative sputum culture (90.7%). Table
1 presents the sociodemographic and clinical characteristics of the children with and without TB who were household contacts.
Table 1
The children characteristics who are household contact of TB cases in an urban setting in Malaysia
Sociodemographic characteristics (n = 2793) |
Age group (years) |
< 5 | 22 (2.7) | 806 (97.3) |
5–14 | 21 (1.1) | 1944 (98.9) |
Sex |
Male | 21 (1.4) | 1468 (98.6) |
Female | 22 (1.7) | 1282 (98.3) |
Race |
Malay | 32 (1.7) | 1800 (98.3) |
Chinese | 3 (0.8) | 367 (99.2) |
Indian | 2 (0.8) | 258 (99.2) |
Others | 6 (1.8) | 325 (98.2) |
Nationality |
Malaysian | 32 (1.3) | 2442 (98.7) |
Non-Malaysian | 11 (3.4) | 308 (96.6) |
Residential location |
Kepong | 17 (1.6) | 1024 (98.4) |
Cheras | 8 (1.0) | 763 (99.0) |
Titiwangsa | 12 (1.6) | 736 (98.4) |
Lembah Pantai | 6 (2.6) | 227 (97.4) |
Type of housing |
Low cost | 13 (1.4) | 893 (98.6) |
Non low-cost | 30 (1.6) | 1857 (98.4) |
Clinical characteristics (n = 2793) |
Symptoms of TB |
No | 2 (0.1) | 2748 (99.9) |
Yes | 41 (95.3) | 2 (4.7) |
Tuberculin skin test |
Negative | 12 (0.5) | 2520 (99.5) |
Positive | 21 (47.7) | 23 (52.3) |
Not Done | 10 (4.6) | 207 (95.4) |
Chest X-ray |
No lesion | 5 (0.6) | 811 (99.4) |
Cavitation | 37 (100.0) | 0 (0.0) |
Not Done | 1 (0.1) | 1939 (99.9) |
Sputum |
Negative | 39 (4.2) | 888 (95.8) |
Positive | 3 (100.0) | 0 (0.0) |
Not Done | 1 (0.1) | 1862 (99.9) |
Interval of diagnosis (weeks) |
≤ 6 | 23 (1.0) | 2350 (99.0) |
> 6 | 20 (4.8) | 400 (95.2) |
Table
2 shows the factors associated with TB disease in the children. Simple logistic regression analysis indicated six variables with
p < 0.25, which were included in the multiple logistic regression analysis. Adjusted analysis showed that children aged < 5 years, with positive TST and investigation period of > 6 weeks had higher odds for TB disease compared to children aged 5–14-years, with negative TST and investigation period of ≤6 weeks, respectively.
Table 2
Factors associated with TB disease among children who are household contact of TB cases
Age group (years) | | | < 0.001 | | | < 0.001 |
5–14 | 1 | | | 1 | | |
< 5 | 3.84 | (1.90,7.77) | | 9.48 | (3.41,26.36) | |
Sex | | | 0.238 | NS | NS |
Male | 1 | | | |
Female | 1.52 | (0.76,3.04) | | |
Race | | | 0.381 | NS | NS |
Non-Malay | 1 | | | | |
Malay | 1.41 | (0.65,3.05) | | | |
Nationality | | | 0.003 | NS | NS |
Malaysian | 1 | | | |
Non-Malaysian | 3.20 | (1.47,6.95) | | |
Residential location | | | 0.331 | NS | NS |
Kepong | 1 | | | |
Cheras | 0.43 | (0.16,1.19) | | |
Titiwangsa | 0.84 | (0.36,1.92) | | |
Lembah Pantai | 1.32 | (0.43,4.02) | | |
Type of housing | | | 0.183 | NS | NS |
Low cost | 1 | | | |
Non low-cost | 1.77 | (0.76,4.09) | | |
Tuberculin skin test (TST) | | | < 0.001 | | | < 0.001 |
Negative | 1 | | | 1 | | |
Positive | 191.74 | (84.49,435.13) | | 395.73 | (134.17,1167.13) | |
Investigation period (weeks) | | | < 0.001 | | | < 0.001 |
≤ 6 | 1 | | | 1 | | |
> 6 | 4.01 | (1.99,8.06) | | 7.48 | (2.88,19.43) | |
Discussion
The main objective of the present study was to identify the prevalence and factors associated with TB disease in children who are household contacts of active TB cases. We found lower prevalence of TB disease in the studied population compared to previous studies conducted in Southeast Asia, which reported 3.3–5.5% prevalence [
18]. However, we postulate that the low prevalence in the present study represents the prevalence of TB in children in Kuala Lumpur, as it is lower than national prevalence of childhood TB of 3.1% [
19]. Nevertheless, given the previous evidence of under-reporting [
1,
20], the actual prevalence may be higher or the same as that in other studies in neighbouring countries. In fact, Fox et al. (2013) concluded in their meta-analysis that the overall prevalence of active TB among all household contacts is 3.1% [
21]. The possibility of underdiagnosis in the child contact should be explored and may be due to failure to identify children with household contacts, and failure to screen the contact after the identification [
1].
In addition, we show that children aged < 5 years had higher chances of contracting active TB. This result is consistent with that of other studies carried out globally [
7,
22]. This can be explained by age and immunological response being important drivers for the progression of the disease [
23]. The risk of TB infection from household contacts is high during the first 2 years of life, and the risk of dissemination in this group is the highest compared to other non-immunocompromised groups [
23]. This is because infants and young children tend to have inadequate or incomplete immune responses due to age-related deficiency, with or without downregulation of the key immune responses [
24]. Such a condition therefore leads to a more disseminated disease in the group [
24].
Another significant finding was the TST result. In Malaysia, induration of > 5 mm and > 10 mm in immunocompromised and non-immunocompromised children, respectively, is considered a positive TST [
25]. This supports the usefulness of the TST as a screening method despite its limitations [
26,
27]. As microscopic diagnosis is difficult and often negative in children, TST results may provide a guide for predicting the likelihood of infection, as TB symptoms are sometimes non-specific in this age group [
28]. However, the TST should not be used as the only tool for deciding on infection to increase the effectiveness of the screening programme [
29].
Apart from the above, the results also highlight the importance of early contact screening once an index case has been diagnosed. According to Malaysian guidelines, the time frame of not more than 6 weeks is recommended and the contact should be followed-up in a sequential interval for 12 months after the first investigation [
9]. This is because previous studies have reported that the median incubation period is 6 weeks [
28,
30]. Therefore, it emphasises the need for following-up with the contact after the first investigation and highlights the importance of not delaying the first investigation, so that anti-TB prophylaxis can be administered to the high-risk groups.
In the present study, housing location and type were not significantly associated with TB in the studied population. A study on urbanisation in Malaysia suggested that high-rise flats with poor ventilation could increase the risk of TB infection [
31]. Nevertheless, the present study shows that the low-cost flats provided by the government to the urban poor in Kuala Lumpur are not significantly associated with TB in the children studied. However, we did not explore the crowdedness of households, as this is not captured in the TBIS.
The limitation of this study is that it used secondary unprocessed data, where the data are collected by different officers in charge of different districts. All data were assumed to be entered in accordance with standard operating procedures outlined by the Ministry of Health and verified by the district health officers in charge.
In addition, as data were limited to the first investigation only, the exact timing of active infection could not be determined. The TBIS database should include data on subsequent follow-up for further evaluation. As the number of household contacts who contracted active TB was low, we only included the variable with event per variable of > 10 in multivariate analysis to avoid sparse data bias. Further research is suggested to follow the cohort for follow-up to evaluate the outcome of contact tracing.
Conclusions
The prevalence of TB disease in children who are household contacts of TB cases in Kuala Lumpur is lower than the national prevalence. Children with household contacts of TB cases aged < 5 years, positive TST and index–contact investigation period of > 6 weeks were associated with TB disease. Hence, the contact tracing programme should be empowered to reduce missed opportunities for diagnosing childhood TB. Our study highlights the high-risk groups for TB prevention, the usefulness of the TST for screening, and the importance of follow-up in contact tracing for children who are household contacts of active TB cases.
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