Lower vitamin D level is associated with higher prevalence of pulmonary tuberculosis in under-five children actively living in tropical countries

Lianda Tamara; Bakhtiar Bakhtiar; Anggraini Alam; Cissy B. Kartasasmita; Dida A. Gurnida

doi:10.12688/f1000research.111282.1

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Research Article

Lower vitamin D level is associated with higher prevalence of pulmonary tuberculosis in under-five children actively living in tropical countries

[version 1; peer review: 2 approved with reservations]

Lianda Tamara ^1-3, Bakhtiar Bakhtiar⁴, Anggraini Alam¹, Cissy B. Kartasasmita¹, Dida A. Gurnida¹

Lianda Tamara ^1-3, Bakhtiar Bakhtiar⁴, [...] Anggraini Alam¹, Cissy B. Kartasasmita¹, Dida A. Gurnida¹

PUBLISHED 21 Apr 2022

Author details Author details

¹ Department of Child Health, Faculty of Medicine, Universitas Padjadjaran, West Java, Indonesia
² RS Paru Provinsi Jawa Barat, Cirebon, West Java, Indonesia
³ Department of Child Health, Faculty of Medicine, Universitas Pasundan, West Java, Indonesia
⁴ Department of Child Health, Faculty of Medicine, Universitas Syah Kuala, Banda Aceh, Indonesia

Lianda Tamara
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Bakhtiar Bakhtiar
Roles: Methodology, Supervision, Writing – Review & Editing

Anggraini Alam
Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing

Cissy B. Kartasasmita
Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing

Dida A. Gurnida
Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing

OPEN PEER REVIEW

REVIEWER STATUS

Abstract

Objective: Indonesia accounted for 845.000 tuberculosis (TB) cases, ranked as the second-highest TB incidence in the world. Various studies in childhood TB and vitamin D has overgrown in recent years, but there is no study for vitamin D status in under-five children with pulmonary tuberculosis in Indonesia as tropical country that has an abundant sun exposure. This study evaluates the vitamin D level in under-five children with pulmonary TB compared with healthy children control group.
Materials and Methods: This comparative study with a cross-sectional design was conducted in outpatient clinic from February 2019 – February 2020. We selected children ≤5 years old, diagnosed with pulmonary TB; the control group was the random siblings or neighbors who did not have tuberculosis. Differences in 25-hydroxyvitamin D levels in both groups were statistically analyzed with independent t-test. The vitamin D cutoff values were determined using receiver operating characteristic (ROC) curve analysis.
Results: A total of 70 patients aged ≤5 years old met the inclusion criteria, 35 childrens were assigned for each group. The 25-hydroxy vitamin D mean level in the TB group was 42.72 nmol/L and 97.74 nmol/L in control group. The TB group has significantly lower 25-hydroxy vitamin D levels than control group (p<0.001). With sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 100%, 97.1%, 97.2%, and 100%, respectively, the optimal cutoff point level for 25-hydroxy vitamin D was 80nmol/L.
Conclusion: Serum levels of 25-hydroxy vitamin D in children with pulmonary TB are significantly lower than in healthy children. Further study should be conducted to determine the efficacy of vitamin D supplementation in the treatment of children with tuberculosis.

Keywords

under-five children, pulmonary tuberculosis, 25-Hydroxy vitamin D, tropical country

Corresponding author: Lianda Tamara

Competing interests: No competing interests were disclosed.

Grant information: The author(s) declared that no grants were involved in supporting this work.

Copyright: © 2022 Tamara L et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Tamara L, Bakhtiar B, Alam A et al. Lower vitamin D level is associated with higher prevalence of pulmonary tuberculosis in under-five children actively living in tropical countries [version 1; peer review: 2 approved with reservations]. F1000Research 2022, 11:445 (https://doi.org/10.12688/f1000research.111282.1) First published: 21 Apr 2022, 11:445 (https://doi.org/10.12688/f1000research.111282.1) Latest published: 21 Apr 2022, 11:445 (https://doi.org/10.12688/f1000research.111282.1)

Introduction

In 2020, WHO reported 638.000 children aged less than 15 years out of 5.8 million people with tuberculosis (TB).¹ Indonesia accounted for 824.000 TB cases with 99.000 childhood TB, ranked as the second-highest TB incidence in the world.¹ The global TB data in children represent a significant burden, with TB treatment progress in children being slower than overall treatment progress.¹ Despite the inconsistent quality of notification data and challenges in TB diagnosis and treatment, various studies in childhood TB has overgrown in recent years.²^–⁵ However, most of the study in childhood TB were related to diagnosis, supplementation, and treatment of childhood TB.⁴

There have been various studies conducted to analyse the association between vitamin D and TB, mostly in adults, while studies in children are still lacking. ⁶^–¹⁹ According to a study conducted in Indonesia, despite year-round sun exposure, nearly one-third of primary school-aged children had low vitamin D levels.²⁰ Another significant study conducted in Indonesia discovered no link between vitamin D level and the occurrence of latent tuberculosis in children under the age of five.²¹ Globally, studies have found an association between a low level of vitamin D and less immunity of the host against tuberculosis infection.¹⁴^,²² Indonesia has an abundant sun exposure that theoretically has an essential role in the formation of vitamin D. Therefore, evaluating vitamin D in children actively living in tropical country will be practically significant. This study evaluates the vitamin D level in under-five children with pulmonary TB compared with healthy children control group.

Methods

This comparative study with a cross-sectional design was conducted at Rumah Sakit Paru Provinsi Jawa Barat (Lung Hospital of West Java Province) from February 2019 – February 2020. The study protocol was approved by the Research Ethics Committee of the Universitas Padjadjaran with the letter number 0818101481. The inclusion criteria were children under five years old, newly diagnosed with pulmonary TB and have not receive antituberculosis therapy. Prior to participating in this study, all subjects’ parents provided written consent. In this study, the 95% confidence level (Zα = 1.65 one-sided test) and 80% power test (Zβ = 0.84) were selected. The calculation of the sample size determined 35 people for each group.

Diagnosis of TB case was performed by using the scoring system of the Indonesian Pediatric TB Scoring System based on history taking, common tuberculosis clinical findings such as fever and cough, laboratory (tuberculin skin test, gram staining from sputum or gastic lavage) and radiology (chest X-ray) results. Scoring ranges from zero to three for each variable; score of more than six from a fourteen maximum score are considered as tuberculosis diagnosis.²³ The isolation of Mycobacterium tuberculosis using nucleic acid testing was conducted in this study using sputum induction technique.

The selection of control group subjects was carried out in age and gender who lived in the same environment as TB subjects, did not meet the tuberculosis criteria based on the scoring system, and had negative tuberculin test. We excluded children with liver or kidney abnormalities, immune-compromised, and children who already received vitamin D supplementation. Consecutively, subjects for the TB group were selected until a minimal sample size was obtained. After obtaining written consent, all subjects had their blood specimens drawn to measure 25-hydroxy vitamin D serum using the enzyme-linked immunosorbent assay (ELISA) method. The 25-hydroxy vitamin D (25(OH)D) is the most frequent metabolite in circulation and its measurement is the barometer of vitamin D status.²⁴ In this study, vitamin D deficiency is defined as serum 25-hydroxyvitamin D levels less than 50 nmol/L, insufficiency is defined as values between 50 and 75 nmol/L, and normal levels are greater than 75 nmol/L.¹⁴ The primary outcome measures in this study are the comparison of 25-hydroxyvitamin D serum level in children with pulmonary TB and control group.

Bias is avoided by establishing stringent inclusion and exclusion criteria, particularly for subjects in the control group. Proximity to the researcher, close interaction with other subjects, and parental expectations of involvement in the study had no influence on the selection criteria. There were no missing data in this study because data collection occurred only once during the subject’s assignment as part of the study.

The confounding factors in this study included milk intake and nutritional status analyzed with the chi-square and Fisher Exact test. All data obtained were recorded and tabulated, then an analysis was performed to compare the differences in 25-hydroxy vitamin D mean by the independent t-test. Values of p<0.05 were considered statistically significant. All calculations were assisted with SPSS version 17. The cutoff values for 25-hydroxy vitamin D levels, sensitivity, and specificity were determined using receiver operating characteristic (ROC) curve analysis.

Results

We assessed 83 patients for eligibility to participate in the study: 41 were assessed for TB group and 42 were assessed for control group. In TB group 5 patients were ineligible and one patient declined to participate. In control group 2 patients were ineligible and five patients declined to participate. The flowchart is shown in Figure 1. The study included 70 children who met the inclusion criteria and consent to participate, 35 patients for each group. Table 1 shows the overall characteristics of the research subjects.

Figure 1. Flowchart of the exclusion process.

Abbreviations: TB, Tuberculosis; HIV, human immunodeficiency virus

Table 1. Characteristics of research subjects.

Characteristics	Tuberculosis group (n=35)	Control group (n=35)	P
Sex			1.0*
Male	17	17
Female	18	18
Age (months)			0.167**
Mean (SD)	35.8 (15.9)	30.8 (13.8)
Median	37	33

* : Chi-square test,

** : t-test.

Table 1 shows that the number of boys and girls in both groups was equal. The TB group had a mean age of 39.4 months, while the control group had a mean age of 30.8 months. Subjects in the TB group were newly diagnosed children under five years old with pulmonary TB and have not receive antituberculosis therapy. Thirty-five children with pulmonary TB had a score of more than six based on the scoring system of the Indonesian Pediatric TB Scoring System (≥6 from 14 maximum) and positive tuberculin skin test. Chest x-ray results showed enlargement of lymph nodes from 33 children (94.28%), and two children (5.72%) showed miliary TB. Two children were confirmed to have miliary TB based on the positive results on sputum smear and sensitive Xpert MTB/RIF. The other 33 TB children had negative results on sputum smear and undetected MTB on Xpert. The basic characteristics of the subjects for both group were sex matched and the age difference were statistically insignificant (p=0.167).

Factors related to vitamin D levels assessed in this study included milk intake and nutritional status. Most subjects (88.57%) in both groups received formula milk consumed every day. In the TB group, 57.14% of subjects had moderate or severe malnutrition, and 42.86% of subjects were stunted. All subjects in the control group had good nutritional and height status. Most of the research subjects, both in the control and TB groups, came from families with lower-middle economic backgrounds. The association between milk intake, nutritional status, and height status is shown in Table 2.

Table 2. Factors related to vitamin D levels.

Risk factors	Tuberculosis group	Control group	p
Milk intake			1.0**
Breastfeed	4	4
Formula	31	31
Nutritional status			<0.001*
Good nutrition	15	35
Moderate malnutrition	15	0
Severe malnutrition	5	0
Height status			<0.001**
Normal height	20	35
Stunted	15	0

* : Chi-square test,

** : Exact Fisher test.

Table 2 shows there is no correlation between vitamin D levels and milk intake (p> 0.05). Based on that result, milk intake is not considered as confounding factor. There is a significant correlation between nutritional status, height status, and vitamin D level (p<0.001). Table 3 displays the independent t-test results for differences in vitamin D levels between the two groups.

Table 3. Differences in vitamin D levels (25 hydroxyvitamin D) between the tuberculosis group and the control group.

Vitamin D (nmol/L)	Tuberculosis group (n=35)	Control group (n=35)	p
Mean (SD)	42.7 (20.2)	97.7 (10.3)	<0.001*
Range	7.6 – 80.0	73.2–123.3	<0.001*
Vitamin D status			<0.001**
Normal	1	34
Insufficiency	12	1
Defficiency	22	0

* : t-test,

** : Chi-square test.

The mean vitamin D level in the TB group was 42.7, with a range of 7.6-80.0, whereas the mean vitamin D level in the control group was 97.7, with a range of 73.2-123.3. In the control group, none of the subjects experienced vitamin D deficiency. In the TB group, 23 of 35 children (65.71%) had vitamin D deficiency and others (34.29%) had vitamin D insufficiency. Vitamin D levels in the TB group were substantially lower than in the control group (p<0.001), this findings was based on the t-test results.

Based on Figure 2 of the receiver operating characteristic (ROC) curve analysis, the optimal vitamin D level cutoff values for TB were ≤80 nmoL/L, with sensitivity, specificity, PPV, and NPV of 100%, 97.1 percent, 97.2 percent, and 100%, respectively (area under the curve [AUC]: 0.998; Figure 2).

Figure 2. Receiver operating characteristic (ROC) curve of Vitamin D level.

Discussion

This research is the first study in Indonesia to evaluate vitamin D level in under-five children with pulmonary tuberculosis actively living in tropical country. In this study, vitamin D levels in TB group were significantly lower compared to healthy children in the control group. This result align with systematic review result done by Sutaria.²⁵ Previous studies conducted by Venturini et al. with subjects aged <18 years, in children with latent and active TB, showed that hypovitaminosis D was significantly associated with TB infection.¹⁴ Yani et al. discovered that the incidence of latent tuberculosis was 1.44 and 1.67 times greater in patients with vitamin D insufficiency and deficiency, respectively, than in subjects with adequate vitamin D.²¹

Factors affecting vitamin D levels include genetics, geographical location, tropical climate, skin color, race, food intake, and exposure to sunlight.¹⁴^,²⁶ A typical symptom in children with tuberculosis is a loss of appetite, which leads to a drop in nutritional intake and a low level of vitamin D. Malnutrition has been connected with an increased risk of TB. Nutrition has a vital role in generating proper innate immune responses to TB. Specifically, vitamin D itself is essential for downstream gene expression important for the immune response against Mycobacterium tuberculosis. The result of this study shows similar result with available study that nutritional status affects the risk and progression of tuberculosis.²⁷

Food intake in this study was limited to milk, and other types of foods were not taken into account. There is no significant difference between breastfed milk and formula, so it did not affect the results of this study. Other factor that is not included in this study is determination of vitamin D composition in each brand of consumed milks; although most of the milks in Indonesia are vitamin D fortified, some milks might not fortified with vitamin D. This study did not trace the source of milk consumed by the subjects due to high variability of milks that can be randomly consumed. Although this study did not stratify the respondents’ socioeconomic condition, the majority of the subjects’ parents are uneducated (below the junior high school level) and unemployed or working as informal laborers. As a result, the type and amount of milk consumed can vary substantially depending on the parents’ uncertain economic circumstances, assistance or support from donors, and government engagement at specific times.

It was possible to exclude risk factors such as geographical location (tropical climate), skin color, and race in both study groups, because both groups had the same risk factors. Both groups belonged to the Malay ethnicity and were natives of the West Java region, making them geographically and climatically similar. It is assumed that all participants were under the age of five and lived in the same location, and that there were no practical instruments to measure the wide range of clothing and everyday activities. Because there was no standardized way for assessing the quantity of sun exposure, the amount of sunlight exposure was not measured.²⁸ This study’s findings contrast significantly from those of an Indonesian study of school-aged children, which revealed that one in every three youngsters lacked adequate vitamin D levels.²⁰ Different research locations (rural and urban) and other activities (indoor and outdoor) may have contributed to the level of vitamin D.

The TB subjects in this study met clinical TB criteria, but only two subjects were bacteriologically confirmed. Lack of bacterial confirmation can be caused by difficulties in obtaining a bacterial sample. This condition leads to a burden in assessing TB diagnosis on under-five children. Our study shows that examination of vitamin D levels carried out by taking blood samples can be considered as supplementary in TB diagnosis (p<0.001, sensitivity 100% and specificity 97.1%) because children with TB significantly have low vitamin D levels. These findings can encourage further research for the use of examination of serum vitamin D levels to determine hipovitaminosis D as a risk factor for tuberculosis in under-five children. Currently, the examination of serum vitamin D levels cannot be done at an affordable cost, but with the great challenge in establishing the diagnosis of TB due to the difficulty of sample extraction in under-five children, the development of cost effective examination technique for serum vitamin D levels can be an alternative modality.

A previous study in adults showed that sufficient level of vitamin D as protective factor against TB in adult, while low serum of vitamin D can increase the progression to TB up to 5-fold increased risk.²⁹^–³¹ There is limited study in under-five children to conclude those same protective and risk factors of vitamin D level against tuberculosis. A study in the United Kingdom with child subject suggest a high utilization of vitamin D which served as a host defense mechanism towards Mycobacterium tuberculosis, starting from the incubation period until the development of disease.³² This proposition might support the hypotheses of vitamin D as protective agent in tuberculosis and the mechanism of vitamin D high utilization can lead to a low level of vitamin D.

This was a cross-sectional study with no subsequent follow-up and assessment of clinical problems, changes in vitamin D levels over time, or any vitamin D status intervention. Additional multi-center studies and monitoring of vitamin D levels throughout tuberculosis treatment may provide additional knowledge about vitamin D and tuberculosis. The number of factors that affect vitamin D is a big challenge in research related to vitamin D status. However, from the existing studies, a significant assumption can be concluded from the low levels of vitamin D in TB cases and an increased risk of progression in latent TB cases to TB.²¹ The low level of vitamin D in children with TB is an indication that they are given vitamin D in addition to TB drugs. This presented a concern about the significance of vitamin D in boosting the in vitro antibacterial action of TB patients that might operate synergistically with TB medications in eliminating TB.⁹

Conclusion

In this study serum levels of vitamin D in children with TB were significantly lower than in healthy children. Study with a larger sample size and age stratified are required for providing more profound evidence regarding vitamin D level in tuberculosis. Further research on the use of vitamin D supplementation in the treatment of children with tuberculosis has the potential to make substantial scientific and therapeutic contributions.

Data availability

Figshare. Dataset TB-N70FIG.xlsx. DOI: https://doi.org/10.6084/m9.figshare.19524229.v2³³

This project contains the following underlying data:

- This is a dataset for research in vitamin D level under-five children with Tuberculosis.

Competing interests

No competing interests were disclosed.

Grant information

The author(s) declared that no grants were involved in supporting this work.

Acknowledgments

We thank Hadyana Sukandar and Fushen for the assistance with statistical analysis.

References

1. World Health Organization: Global Tuberculosis Report 2021.2021. Reference Source
2. J. Marais B, S. Schaaf H, R. Donald P: Management of Tuberculosis in Children and New Treatment Options. Infectious Disorde Drug Targets. 2012; 11(2): 144–156. Publisher Full Text
3. Nturibi E: Tuberculosis registers in Africa: a review. Afr. Health. 2010; 3: 11–13.
4. Jenkins HE: Global burden of childhood tuberculosis. Pneumonia. 2016 Dec 24; 8(1): 24. PubMed Abstract | Publisher Full Text
5. Sugawara E, Nikaido H: Properties of AdeABC and AdeIJK efflux systems of Acinetobacter baumannii compared with those of the AcrAB-TolC system of Escherichia coli. Antimicrob. Agents Chemother. 2014 Dec; 58(12): 7250–7257. PubMed Abstract | Publisher Full Text
6. Soeharto DA, Rifai DA, Marsudidjadja S, et al.: Vitamin D as an Adjunctive Treatment to Standard Drugs in Pulmonary Tuberculosis Patients: An Evidence-Based Case Report. Adv. Prev. Med. 2019 Jun 20; 2019: 1–10. PubMed Abstract | Publisher Full Text Reference Source
7. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al.: Evaluation, treatment, and prevention of vitamin D deficiency: An endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 2011; 96(7): 1911–1930. PubMed Abstract | Publisher Full Text
8. Martineau AR, Wilkinson RJ, Wilkinson KA, et al.: A single dose of vitamin D enhances immunity to mycobacteria. Am. J. Respir. Crit. Care Med. 2007; 176(2): 208–213. PubMed Abstract | Publisher Full Text
9. Martineau AR, Timms PM, Bothamley GH, et al.: High-dose vitamin D(3) during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. Lancet. 2011 Jan 15; 377(9761): 242–250. PubMed Abstract | Publisher Full Text
10. Nursyam EW, Amin Z, Rumende CM: The effect of vitamin D as supplementary treatment in patients with moderately advanced pulmonary tuberculous lesion. Acta Med. Indones. 2006; 38(1): 3–5. PubMed Abstract
11. Finklea JD, Grossmann RE, Tangpricha V: Vitamin D and chronic lung disease: a review of molecular mechanisms and clinical studies. Adv. Nutr. 2011 May; 2(3): 244–253. PubMed Abstract | Publisher Full Text
12. Aibana O, Huang C-C, Aboud S, et al.: Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis. PLoS Med. 2019; 16(9): e1002907. PubMed Abstract | Publisher Full Text
13. Naik AL, Rajan MG, Manjrekar PA, et al.: Effect of DOTS Treatment on Vitamin D Levels in Pulmonary Tuberculosis. J. Clin. Diagn. Res. 2017 Apr; 11(4): BC18–BC22. PubMed Abstract | Publisher Full Text
14. Venturini E, Facchini L, Martinez-Alier N, et al.: Vitamin D and tuberculosis: a multicenter study in children. BMC Infect. Dis. 2014 Dec 11; 14(652): 652. PubMed Abstract | Publisher Full Text
15. Battersby AJ, Kampmann B, Burl S: Vitamin D in early childhood and the effect on immunity to mycobacterium tuberculosis. Clin. Dev. Immunol. 2012; 2012: 1–10. PubMed Abstract | Publisher Full Text
16. Jolliffe DA, Camargo CA, Sluyter JD, et al.: Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials. Lancet Diabetes Endocrinol. 2021; 9(5): 276–292. PubMed Abstract | Publisher Full Text
17. Ganmaa D, Giovannucci E, Bloom BR, et al.: Vitamin D, tuberculin skin test conversion, and latent tuberculosis in Mongolian school-age children: a randomized, double-blind, placebo-controlled feasibility trial. Am. J. Clin. Nutr. 2012 Aug; 96(2): 391–396. PubMed Abstract | Publisher Full Text
18. Mehta S, Mugusi FM, Bosch RJ, et al.: A randomized trial of multivitamin supplementation in children with tuberculosis in Tanzania. Nutr. J. 2011 Oct 31; 10(1): 120. PubMed Abstract | Publisher Full Text
19. Morcos MM, Gabr AA, Samuel S, Kamel M, et al.: Vitamin D administration to tuberculous children and its value. Boll Chim Farm. 1998 May; 137(5): 157–64. PubMed Abstract
20. Pulungan A, Soesanti F, Tridjaja B, et al.: Vitamin D insufficiency and its contributing factors in primary school-aged children in Indonesia, a sun-rich country. Ann. Pediatr. Endocrinol. Metab. 2021 Jun 30; 26(2): 92–98. PubMed Abstract | Publisher Full Text
21. Yani FF, Lipoeto NI, Supriyatno B, et al.: Vitamin D status in under-five children with a history of close tuberculosis contact in Padang, West Sumatra. Asia Pac. J. Clin. Nutr. 2017; 26(94): S68–S72.
22. Chang SW, Lee HC: Vitamin D and health - The missing vitamin in humans. Pediatr. Neonatol. 2019; 60(3): 237–244. PubMed Abstract | Publisher Full Text
23. Triasih R, Graham SM: Limitations of the Indonesian Pediatric Tuberculosis Scoring System in the context of child contact investigation. Paediatr. Indones. 2011; 51(6): 332–337. Publisher Full Text
24. Tang JCY, Jackson S, Walsh NP, et al.: The dynamic relationships between the active and catabolic vitamin D metabolites, their ratios, and associations with PTH. Sci. Rep. 2019; 9(6974): 1–10.
25. Sutaria N, Liu CT, Chen TC: Vitamin D status, receptor gene polymorphisms, and supplementation on tuberculosis: A systematic review of case-control studies and randomized controlled trials. J. Clin. Transl. Endocrinol. 2014; 1(4): 151–160. PubMed Abstract | Publisher Full Text
26. Gou X, Pan L, Tang F, et al.: The association between vitamin D status and tuberculosis in children: A meta-analysis. Medicine. 2018 Aug; 97(35): e12179. PubMed Abstract
27. Jaganath D, Mupere E: Childhood tuberculosis and malnutrition. J. Infect. Dis. 2012 Dec 15; 206(12): 1809–1815. Publisher Full Text Reference Source
28. Rey C, Sáncheza-Arango D, Lópeza-Herce J, et al.: Vitamin D deficiency at pediatric intensive care admission. J. Pediatr. 2014; 90(2): 135–142. Publisher Full Text
29. Arnedo-Pena A, Juan-Cerdán JV, Romeu-García MA, et al.: Vitamin D status and incidence of tuberculosis infection conversion in contacts of pulmonary tuberculosis patients: A prospective cohort study. Epidemiol. Infect. 2015; 143: 1731–1741. PubMed Abstract | Publisher Full Text
30. Talat N, Perry S, Parsonnet J, et al.: Vitamin D deficiency and tuberculosis progression. Emerg. Infect. Dis. 2010; 16(5): 853–855. PubMed Abstract | Publisher Full Text
31. Ho-Pham LT, Nguyen ND, Nguyen TT, et al.: Association between vitamin D insufficiency and tuberculosis in a vietnamese population. BMC Infect. Dis. 2010; 10(306). PubMed Abstract | Publisher Full Text
32. Ahmed M, Aslam M: A study of vitamin D status in children with tuberculosis in Peterborough, United Kingdom. International Journal of Contemporary Pediatrics. 2015; 2(2): 69–71. Publisher Full Text
33. Tamara L: Dataset TB-N70FIG.xlsx. figshare. Dataset. 2022. Publisher Full Text

Comments on this article Comments (0)

Version 1

VERSION 1 PUBLISHED 21 Apr 2022

Author details Author details

¹ Department of Child Health, Faculty of Medicine, Universitas Padjadjaran, West Java, Indonesia
² RS Paru Provinsi Jawa Barat, Cirebon, West Java, Indonesia
³ Department of Child Health, Faculty of Medicine, Universitas Pasundan, West Java, Indonesia
⁴ Department of Child Health, Faculty of Medicine, Universitas Syah Kuala, Banda Aceh, Indonesia

Lianda Tamara
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Bakhtiar Bakhtiar
Roles: Methodology, Supervision, Writing – Review & Editing

Anggraini Alam
Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing

Cissy B. Kartasasmita
Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing

Dida A. Gurnida
Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing

Competing interests

No competing interests were disclosed.

Grant information

The author(s) declared that no grants were involved in supporting this work.

Article Versions (1)

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Published: 21 Apr 2022, 11:445

https://doi.org/10.12688/f1000research.111282.1

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© 2022 Tamara L et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Tamara L, Bakhtiar B, Alam A et al. Lower vitamin D level is associated with higher prevalence of pulmonary tuberculosis in under-five children actively living in tropical countries [version 1; peer review: 2 approved with reservations]. F1000Research 2022, 11:445 (https://doi.org/10.12688/f1000research.111282.1)

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Reviewer Report 22 Jun 2023

Andrew McArdle, Department of Infectious Disease, Imperial College London, London, UK

Approved with Reservations

https://doi.org/10.5256/f1000research.122985.r145193

This article adds to a body of literature demonstrating an association between vitamin D levels and TB infection or TB disease. As with any valid scientific study, the findings deserve to be shared, even though the novelty may be limited ... Continue reading

This article adds to a body of literature demonstrating an association between vitamin D levels and TB infection or TB disease. As with any valid scientific study, the findings deserve to be shared, even though the novelty may be limited (I should declare my own publication in this area). The fact the study is from a country with a high burden of TB disease and with high sun exposure are strengths.

Language and general points
======================
The language is not idiomatic but I found it generally clear and believe it would be accessible to an international audience. I recommend periods be replaced with commas or spaces for thousand delimiters for better clarity. "Living" seems sufficient, without "actively."

I am unaware of specific policy of the journal, but please report exact p values when non-significant (as you have in some instances). I would also recommend including point estimates and confidence intervals for all measures of association. This will allow readers to assess whether a clinically significant association has been excluded or not.

Background
=========
The authors could helpfully explain to an international audience whether there may be any reasons in Indonesia why sun exposure of children under 5 may be limited to explain the high background prevalence of vitamin D deficiency.

Please explain more about the clinical service. Are you seeing highly selected patients (i.e. a tertiary service) or providing TB care for all children in a defined geographic catchment? How many children with TB are treated per year? Do you see children as contacts for screening?

Methods
=======
More detail is required on cases. Did you recruit cases presenting as symptomatic, or also as contacts detected at screening? If so, please provide a breakdown of the numbers. Please provide a summary of severity using the TB scoring system (ideally broken down by scoring domain).

More detail is required on the recruitment of control subjects. The abstract refers to "random siblings or neighbors" without reference to matching. The body text makes no reference to paired recruitment of siblings or neighbours, but mentions age, gender and environment without language clear enough to indicate matching of controls or something more relaxed. Matching is referred to in the results for sex alone. If the control group are healthy community controls as indicated, they should not be referred to as "patients."

The equal numbers of males and females supports matching by sex. However, the age distributions are different suggesting no close matching by age.

Results
======
I am surprised to see all children under 12 months are breastfed (n=8) and all children 12-60 months are receiving formula milk. Can you be more specific about what you mean by formula milk? Is it typical in Indonesia for all children up to 5 years to receive formula milk?

The magnitude of the difference in vitamin D levels between the groups is striking with only two TB patients exceeding the lowest concentration exhibited by a control subject. This is a much more stark difference than those seen, for example, in the published systematic review you reference.

I am not sure the ROC analysis is useful, since there is no suggestion the specific cut-off would be valid in a different population.

Additional analyses
===============
Since vitamin D deficiency may be a consequence of illness, it would be helpful to see if there is a relationship between vitamin D level and severity of TB among the TB group (and duration of symptoms, if this is available).

Discussion
========
"There is no significant difference [in the proportions consuming] breastmilk or formula"

"It is assumed that all participants are under 5" - this is a strange expression given that the age of all participants is presented and all are under 5 years!

"The low level of vitamin D in children with TB is an indication that they [should be] given vitamin D in addition to TB drugs."

"This presented a concern about the significance of vitamin D in boosting the in vitro antibacterial action of TB patients that might operate synergistically with TB medications in eliminating TB" - although I can presume what is meant, this sentence needs rephrasing for clarity, e.g. "It is possible that supplementation of vitamin D could aid in host defence against TB and operate synergistically..."

Is the work clearly and accurately presented and does it cite the current literature?

Partly
Is the study design appropriate and is the work technically sound?

Yes
Are sufficient details of methods and analysis provided to allow replication by others?

Partly
If applicable, is the statistical analysis and its interpretation appropriate?

Yes
Are all the source data underlying the results available to ensure full reproducibility?

Yes
Are the conclusions drawn adequately supported by the results?

Yes

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: I am a clinician practicing in paediatric infectious diseases and have participated in similar research into the association between vitamin D levels and TB status.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

CITE

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Reviewer Report 06 Jun 2022

Kok-Yong Chin, Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia

Approved with Reservations

https://doi.org/10.5256/f1000research.122985.r138614

The authors compared the 25-hydroxyvitamin D level between children under 5 years with or without TB in Indonesia. This is a small-scaled cross-sectional study, so the causal relationship between vitamin D and TB cannot be inferred. This should be acknowledged ... Continue reading

The authors compared the 25-hydroxyvitamin D level between children under 5 years with or without TB in Indonesia. This is a small-scaled cross-sectional study, so the causal relationship between vitamin D and TB cannot be inferred. This should be acknowledged in the manuscript.

Introduction:

Please edit the numbers 638.000, 824.000 and 99.000, to 638,000, 824,000 and 99,000.
The high prevalence of vitamin D deficiency among tropical populations is not unusual due to various sun avoidance practices. I think this should be mentioned in the introduction.

Methods:

Assuming that the authors calculated the sample size based on prevalence, what are the P and Q values used for the calculation? Cite the source of these values as well.
“The selection of control group subjects was carried out in age and gender who lived in the same environment…” - do the authors mean “The age and sex-matched control subjects were selected from the same environment as the patients…”?
Briefly describe the assessment of milk intake and nutritional status of the subjects.
For the classification of vitamin D, I suggest the authors to cite the original paper by the Institute of Medicine.

Results:

I wonder about the comparison of vitamin D level between the two groups. Body weight should be adjusted because body fat can sequester vitamin D and lower blood level.
It is not sure how the optimal level of ≤ 80 nmol/L was identified. Usually, it is done with coordinate tracing and calculation of the Youden-index. Figure 2 doesn’t depict a ROC curve for coordinate tracing. Do bear in mind that 80 nmol/L is actually very high and I wonder if the values would be useful to help to detect who is vulnerable for infection?

Discussion:

Due to the cross-sectional nature of this study, it cannot be ascertained whether low vitamin D causes TB infection, or TB causes low vitamin D level (due to physical inactivity). Both possibilities need to be considered.
Vitamin D assay could be expensive in the other countries, so I wonder how this test is going to help to detect the children vulnerable to TB?

Overall, the paper needs to be proofread so that the language is more concise.

Is the work clearly and accurately presented and does it cite the current literature?

Yes
Is the study design appropriate and is the work technically sound?

Yes
Are sufficient details of methods and analysis provided to allow replication by others?

No
If applicable, is the statistical analysis and its interpretation appropriate?

Partly
Are all the source data underlying the results available to ensure full reproducibility?

No
Are the conclusions drawn adequately supported by the results?

Partly

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Vitamin D, osteoporosis, osteoarthritis

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

CITE

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VERSION 1 PUBLISHED 21 Apr 2022

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Version 1 21 Apr 22	read	read

Kok-Yong Chin, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
Andrew McArdle, Imperial College London, London, UK

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22 Jun 2023 | for Version 1

Andrew McArdle, Department of Infectious Disease, Imperial College London, London, UK

6 Views Cite this report Responses(0)

Approved With Reservations

This article adds to a body of literature demonstrating an association between vitamin D levels and TB infection or TB disease. As with any valid scientific study, the findings deserve to be shared, even though the novelty may be limited (I should declare my own publication in this area). The fact the study is from a country with a high burden of TB disease and with high sun exposure are strengths.

Language and general points
======================
The language is not idiomatic but I found it generally clear and believe it would be accessible to an international audience. I recommend periods be replaced with commas or spaces for thousand delimiters for better clarity. "Living" seems sufficient, without "actively."

I am unaware of specific policy of the journal, but please report exact p values when non-significant (as you have in some instances). I would also recommend including point estimates and confidence intervals for all measures of association. This will allow readers to assess whether a clinically significant association has been excluded or not.

Background
=========
The authors could helpfully explain to an international audience whether there may be any reasons in Indonesia why sun exposure of children under 5 may be limited to explain the high background prevalence of vitamin D deficiency.

Please explain more about the clinical service. Are you seeing highly selected patients (i.e. a tertiary service) or providing TB care for all children in a defined geographic catchment? How many children with TB are treated per year? Do you see children as contacts for screening?

Methods
=======
More detail is required on cases. Did you recruit cases presenting as symptomatic, or also as contacts detected at screening? If so, please provide a breakdown of the numbers. Please provide a summary of severity using the TB scoring system (ideally broken down by scoring domain).

More detail is required on the recruitment of control subjects. The abstract refers to "random siblings or neighbors" without reference to matching. The body text makes no reference to paired recruitment of siblings or neighbours, but mentions age, gender and environment without language clear enough to indicate matching of controls or something more relaxed. Matching is referred to in the results for sex alone. If the control group are healthy community controls as indicated, they should not be referred to as "patients."

The equal numbers of males and females supports matching by sex. However, the age distributions are different suggesting no close matching by age.

Results
======
I am surprised to see all children under 12 months are breastfed (n=8) and all children 12-60 months are receiving formula milk. Can you be more specific about what you mean by formula milk? Is it typical in Indonesia for all children up to 5 years to receive formula milk?

The magnitude of the difference in vitamin D levels between the groups is striking with only two TB patients exceeding the lowest concentration exhibited by a control subject. This is a much more stark difference than those seen, for example, in the published systematic review you reference.

I am not sure the ROC analysis is useful, since there is no suggestion the specific cut-off would be valid in a different population.

Additional analyses
===============
Since vitamin D deficiency may be a consequence of illness, it would be helpful to see if there is a relationship between vitamin D level and severity of TB among the TB group (and duration of symptoms, if this is available).

Discussion
========
"There is no significant difference [in the proportions consuming] breastmilk or formula"

"It is assumed that all participants are under 5" - this is a strange expression given that the age of all participants is presented and all are under 5 years!

"The low level of vitamin D in children with TB is an indication that they [should be] given vitamin D in addition to TB drugs."

"This presented a concern about the significance of vitamin D in boosting the in vitro antibacterial action of TB patients that might operate synergistically with TB medications in eliminating TB" - although I can presume what is meant, this sentence needs rephrasing for clarity, e.g. "It is possible that supplementation of vitamin D could aid in host defence against TB and operate synergistically..."

Is the work clearly and accurately presented and does it cite the current literature?

Partly
Is the study design appropriate and is the work technically sound?

Yes
Are sufficient details of methods and analysis provided to allow replication by others?

Partly
If applicable, is the statistical analysis and its interpretation appropriate?

Yes
Are all the source data underlying the results available to ensure full reproducibility?

Yes
Are the conclusions drawn adequately supported by the results?

Yes

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

I am a clinician practicing in paediatric infectious diseases and have participated in similar research into the association between vitamin D levels and TB status.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

Respond to this report

Responses (0)

Back to all reports

Reviewer Report

15 Views

06 Jun 2022 | for Version 1

Kok-Yong Chin, Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia

15 Views Cite this report Responses(0)

Approved With Reservations

The authors compared the 25-hydroxyvitamin D level between children under 5 years with or without TB in Indonesia. This is a small-scaled cross-sectional study, so the causal relationship between vitamin D and TB cannot be inferred. This should be acknowledged in the manuscript.

Introduction:

Please edit the numbers 638.000, 824.000 and 99.000, to 638,000, 824,000 and 99,000.
The high prevalence of vitamin D deficiency among tropical populations is not unusual due to various sun avoidance practices. I think this should be mentioned in the introduction.

Methods:

Assuming that the authors calculated the sample size based on prevalence, what are the P and Q values used for the calculation? Cite the source of these values as well.
“The selection of control group subjects was carried out in age and gender who lived in the same environment…” - do the authors mean “The age and sex-matched control subjects were selected from the same environment as the patients…”?
Briefly describe the assessment of milk intake and nutritional status of the subjects.
For the classification of vitamin D, I suggest the authors to cite the original paper by the Institute of Medicine.

Results:

I wonder about the comparison of vitamin D level between the two groups. Body weight should be adjusted because body fat can sequester vitamin D and lower blood level.
It is not sure how the optimal level of ≤ 80 nmol/L was identified. Usually, it is done with coordinate tracing and calculation of the Youden-index. Figure 2 doesn’t depict a ROC curve for coordinate tracing. Do bear in mind that 80 nmol/L is actually very high and I wonder if the values would be useful to help to detect who is vulnerable for infection?

Discussion:

Due to the cross-sectional nature of this study, it cannot be ascertained whether low vitamin D causes TB infection, or TB causes low vitamin D level (due to physical inactivity). Both possibilities need to be considered.
Vitamin D assay could be expensive in the other countries, so I wonder how this test is going to help to detect the children vulnerable to TB?

Overall, the paper needs to be proofread so that the language is more concise.

Is the work clearly and accurately presented and does it cite the current literature?

Yes
Is the study design appropriate and is the work technically sound?

Yes
Are sufficient details of methods and analysis provided to allow replication by others?

No
If applicable, is the statistical analysis and its interpretation appropriate?

Partly
Are all the source data underlying the results available to ensure full reproducibility?

No
Are the conclusions drawn adequately supported by the results?

Partly

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Vitamin D, osteoporosis, osteoarthritis

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

Respond to this report

Responses (0)

[1] 1. World Health Organization: Global Tuberculosis Report 2021.2021. Reference Source

[2] 2. J. Marais B, S. Schaaf H, R. Donald P: Management of Tuberculosis in Children and New Treatment Options. Infectious Disorde Drug Targets. 2012; 11(2): 144–156. Publisher Full Text

[3] 3. Nturibi E: Tuberculosis registers in Africa: a review. Afr. Health. 2010; 3: 11–13.

[4] 4. Jenkins HE: Global burden of childhood tuberculosis. Pneumonia. 2016 Dec 24; 8(1): 24. PubMed Abstract | Publisher Full Text

[5] 5. Sugawara E, Nikaido H: Properties of AdeABC and AdeIJK efflux systems of Acinetobacter baumannii compared with those of the AcrAB-TolC system of Escherichia coli. Antimicrob. Agents Chemother. 2014 Dec; 58(12): 7250–7257. PubMed Abstract | Publisher Full Text

[6] 6. Soeharto DA, Rifai DA, Marsudidjadja S, et al.: Vitamin D as an Adjunctive Treatment to Standard Drugs in Pulmonary Tuberculosis Patients: An Evidence-Based Case Report. Adv. Prev. Med. 2019 Jun 20; 2019: 1–10. PubMed Abstract | Publisher Full Text Reference Source

[7] 7. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al.: Evaluation, treatment, and prevention of vitamin D deficiency: An endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 2011; 96(7): 1911–1930. PubMed Abstract | Publisher Full Text

[8] 8. Martineau AR, Wilkinson RJ, Wilkinson KA, et al.: A single dose of vitamin D enhances immunity to mycobacteria. Am. J. Respir. Crit. Care Med. 2007; 176(2): 208–213. PubMed Abstract | Publisher Full Text

[9] 9. Martineau AR, Timms PM, Bothamley GH, et al.: High-dose vitamin D(3) during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. Lancet. 2011 Jan 15; 377(9761): 242–250. PubMed Abstract | Publisher Full Text

[10] 10. Nursyam EW, Amin Z, Rumende CM: The effect of vitamin D as supplementary treatment in patients with moderately advanced pulmonary tuberculous lesion. Acta Med. Indones. 2006; 38(1): 3–5. PubMed Abstract

[11] 11. Finklea JD, Grossmann RE, Tangpricha V: Vitamin D and chronic lung disease: a review of molecular mechanisms and clinical studies. Adv. Nutr. 2011 May; 2(3): 244–253. PubMed Abstract | Publisher Full Text

[12] 12. Aibana O, Huang C-C, Aboud S, et al.: Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis. PLoS Med. 2019; 16(9): e1002907. PubMed Abstract | Publisher Full Text

[13] 13. Naik AL, Rajan MG, Manjrekar PA, et al.: Effect of DOTS Treatment on Vitamin D Levels in Pulmonary Tuberculosis. J. Clin. Diagn. Res. 2017 Apr; 11(4): BC18–BC22. PubMed Abstract | Publisher Full Text

[14] 14. Venturini E, Facchini L, Martinez-Alier N, et al.: Vitamin D and tuberculosis: a multicenter study in children. BMC Infect. Dis. 2014 Dec 11; 14(652): 652. PubMed Abstract | Publisher Full Text

[15] 15. Battersby AJ, Kampmann B, Burl S: Vitamin D in early childhood and the effect on immunity to mycobacterium tuberculosis. Clin. Dev. Immunol. 2012; 2012: 1–10. PubMed Abstract | Publisher Full Text

[16] 16. Jolliffe DA, Camargo CA, Sluyter JD, et al.: Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials. Lancet Diabetes Endocrinol. 2021; 9(5): 276–292. PubMed Abstract | Publisher Full Text

[17] 17. Ganmaa D, Giovannucci E, Bloom BR, et al.: Vitamin D, tuberculin skin test conversion, and latent tuberculosis in Mongolian school-age children: a randomized, double-blind, placebo-controlled feasibility trial. Am. J. Clin. Nutr. 2012 Aug; 96(2): 391–396. PubMed Abstract | Publisher Full Text

[18] 18. Mehta S, Mugusi FM, Bosch RJ, et al.: A randomized trial of multivitamin supplementation in children with tuberculosis in Tanzania. Nutr. J. 2011 Oct 31; 10(1): 120. PubMed Abstract | Publisher Full Text

[19] 19. Morcos MM, Gabr AA, Samuel S, Kamel M, et al.: Vitamin D administration to tuberculous children and its value. Boll Chim Farm. 1998 May; 137(5): 157–64. PubMed Abstract

[20] 20. Pulungan A, Soesanti F, Tridjaja B, et al.: Vitamin D insufficiency and its contributing factors in primary school-aged children in Indonesia, a sun-rich country. Ann. Pediatr. Endocrinol. Metab. 2021 Jun 30; 26(2): 92–98. PubMed Abstract | Publisher Full Text

[21] 21. Yani FF, Lipoeto NI, Supriyatno B, et al.: Vitamin D status in under-five children with a history of close tuberculosis contact in Padang, West Sumatra. Asia Pac. J. Clin. Nutr. 2017; 26(94): S68–S72.

[22] 22. Chang SW, Lee HC: Vitamin D and health - The missing vitamin in humans. Pediatr. Neonatol. 2019; 60(3): 237–244. PubMed Abstract | Publisher Full Text

[23] 23. Triasih R, Graham SM: Limitations of the Indonesian Pediatric Tuberculosis Scoring System in the context of child contact investigation. Paediatr. Indones. 2011; 51(6): 332–337. Publisher Full Text

[24] 24. Tang JCY, Jackson S, Walsh NP, et al.: The dynamic relationships between the active and catabolic vitamin D metabolites, their ratios, and associations with PTH. Sci. Rep. 2019; 9(6974): 1–10.

[25] 25. Sutaria N, Liu CT, Chen TC: Vitamin D status, receptor gene polymorphisms, and supplementation on tuberculosis: A systematic review of case-control studies and randomized controlled trials. J. Clin. Transl. Endocrinol. 2014; 1(4): 151–160. PubMed Abstract | Publisher Full Text

[26] 26. Gou X, Pan L, Tang F, et al.: The association between vitamin D status and tuberculosis in children: A meta-analysis. Medicine. 2018 Aug; 97(35): e12179. PubMed Abstract

[27] 27. Jaganath D, Mupere E: Childhood tuberculosis and malnutrition. J. Infect. Dis. 2012 Dec 15; 206(12): 1809–1815. Publisher Full Text Reference Source

[28] 28. Rey C, Sáncheza-Arango D, Lópeza-Herce J, et al.: Vitamin D deficiency at pediatric intensive care admission. J. Pediatr. 2014; 90(2): 135–142. Publisher Full Text

[29] 29. Arnedo-Pena A, Juan-Cerdán JV, Romeu-García MA, et al.: Vitamin D status and incidence of tuberculosis infection conversion in contacts of pulmonary tuberculosis patients: A prospective cohort study. Epidemiol. Infect. 2015; 143: 1731–1741. PubMed Abstract | Publisher Full Text

[30] 30. Talat N, Perry S, Parsonnet J, et al.: Vitamin D deficiency and tuberculosis progression. Emerg. Infect. Dis. 2010; 16(5): 853–855. PubMed Abstract | Publisher Full Text

[31] 31. Ho-Pham LT, Nguyen ND, Nguyen TT, et al.: Association between vitamin D insufficiency and tuberculosis in a vietnamese population. BMC Infect. Dis. 2010; 10(306). PubMed Abstract | Publisher Full Text

[32] 32. Ahmed M, Aslam M: A study of vitamin D status in children with tuberculosis in Peterborough, United Kingdom. International Journal of Contemporary Pediatrics. 2015; 2(2): 69–71. Publisher Full Text

[33] 33. Tamara L: Dataset TB-N70FIG.xlsx. figshare. Dataset. 2022. Publisher Full Text

Lower vitamin D level is associated with higher prevalence of pulmonary tuberculosis in under-five children actively living in tropical countries

Abstract

Keywords

Introduction

Methods

Results

Figure 1. Flowchart of the exclusion process.

Table 1. Characteristics of research subjects.

Table 2. Factors related to vitamin D levels.

Table 3. Differences in vitamin D levels (25 hydroxyvitamin D) between the tuberculosis group and the control group.

Figure 2. Receiver operating characteristic (ROC) curve of Vitamin D level.

Discussion

Conclusion

Data availability

Competing interests

Grant information

Acknowledgments

References

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