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Published in: BMC Infectious Diseases 1/2017

Open Access 01-12-2017 | Research article

Association of high serum vitamin D concentrations with active pulmonary TB in an HIV co-endemic setting, Harare, Zimbabwe

Authors: Cuthbert Musarurwa, Lynn Sodai Zijenah, Doreen Zvipo Duri, Kudzie Mateveke-Dangaiso, Kudakwashe Mhandire, Maria Mary Chipiti, Marshall Wesley Munjoma, Witmore Bayayi Mujaji

Published in: BMC Infectious Diseases | Issue 1/2017

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Abstract

Background

There is paucity data on the association of vitamin D deficiency (VDD) and active tuberculosis (TB) in southern Africa where the human immunodeficiency virus (HIV) is co-endemic. We examined the association of serum vitamin D concentrations with active pulmonary tuberculosis (PTB) in HIV-infected (n = 284) and uninfected (n = 267) Black Zimbabweans, in Harare, Zimbabwe.

Methods

We conducted a cross-sectional study of 551 participants comprising 145 HIV+/PTB +, 139 HIV+/PTB, 134 HIV/PTB+ and 133 HIV/PTB. PTB status was confirmed using sputum by culture, or smear microscopy, or GeneXpert MTB/RIF. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured using a competitive chemiluminescent immunoassay prior to commencement of anti-TB treatment.

Results

In all four groups, the median vitamin D concentrations were above the 20 ng/ml cut off for VDD. However, the median vitamin D concentrations in all the four groups were below the cut off for vitamin D sufficiency ≥30 ng/ml. The median vitamin D concentrations were significantly higher in PTB+ cases; 24.2 ng/ml (IQR: 18.8–32.0) compared to PTB controls 20.9 ng/ml (IQR: 17.1–26.9), p < 0.0001 regardless of HIV status. The HIV+/PTB+ group had the highest median vitamin D concentration (25.3 (IQR: 18.0–33.7 ng/ml) whilst the HIV+/PTB group had the lowest; 20.4 ng/ml (IQR: 14.6–26.9), p = 0.0003. Vitamin D concentration <30 ng/ml was associated with 43% lower odds of being PTB+ OR 0.57 (95% CI 0.35–0.89).

Conclusions

Our results are not in agreement with the generally accepted hypothesis that VDD is associated with active PTB. To the contrary our results showed an association of higher vitamin D concentrations with active TB irrespective of HIV status. Although findings from the available pool of case control studies remain inconsistent, the results from the current study provide further rationale for larger-scale, prospectively designed studies to evaluate whether sufficient vitamin D concentrations do indeed precede the development of active PTB in our setting.
Literature
2.
go back to reference Sita-Lumsden A, Lapthorn G, Swaminathan R, Milburn HJ. Reactivation of tuberculosis and vitamin D deficiency: the contribution of diet and exposure to sunlight. Thorax. 2007;62:1003–7.CrossRefPubMedPubMedCentral Sita-Lumsden A, Lapthorn G, Swaminathan R, Milburn HJ. Reactivation of tuberculosis and vitamin D deficiency: the contribution of diet and exposure to sunlight. Thorax. 2007;62:1003–7.CrossRefPubMedPubMedCentral
3.
go back to reference Leandro ACCS, Rocha MA, Cardoso CSA, Bonecini-Almeida MG. Genetic polymorphisms in vitamin D receptor, vitamin D-binding protein, Toll-like receptor 2, nitric oxide synthase 2, and interferon- -γ genes and its association with susceptibility to tuberculosis. Braz J Med Biol Res. 2009;42:312–22.CrossRefPubMed Leandro ACCS, Rocha MA, Cardoso CSA, Bonecini-Almeida MG. Genetic polymorphisms in vitamin D receptor, vitamin D-binding protein, Toll-like receptor 2, nitric oxide synthase 2, and interferon- -γ genes and its association with susceptibility to tuberculosis. Braz J Med Biol Res. 2009;42:312–22.CrossRefPubMed
4.
go back to reference Nava-Aguilera E, Andersson N, Harris E, Mitchell S, Hamel C, Shea B, et al. Risk factors associated with recent transmission of tuberculosis: systematic review and meta-analysis [Review article]. Int J Tuberc Lung Dis. 2009;13:17–26.PubMed Nava-Aguilera E, Andersson N, Harris E, Mitchell S, Hamel C, Shea B, et al. Risk factors associated with recent transmission of tuberculosis: systematic review and meta-analysis [Review article]. Int J Tuberc Lung Dis. 2009;13:17–26.PubMed
5.
go back to reference Wu G, Zhao M, Gu X, Yao Y, Liu H, Song Y. The effect of P2X7 receptor 1513 polymorphism on susceptibility to tuberculosis: A meta-analysis. Infect Genet Evol. 2014;24:82–91.CrossRefPubMed Wu G, Zhao M, Gu X, Yao Y, Liu H, Song Y. The effect of P2X7 receptor 1513 polymorphism on susceptibility to tuberculosis: A meta-analysis. Infect Genet Evol. 2014;24:82–91.CrossRefPubMed
6.
go back to reference Martineau AR, Wilkinson KA, Newton SM, Floto RA, Norman AW, Skolimowska K, et al. IFN-γ-and TNF-independent vitamin D-inducible human suppression of mycobacteria: the role of cathelicidin LL-37. J Immunol. 2007;178:7190–8.CrossRefPubMed Martineau AR, Wilkinson KA, Newton SM, Floto RA, Norman AW, Skolimowska K, et al. IFN-γ-and TNF-independent vitamin D-inducible human suppression of mycobacteria: the role of cathelicidin LL-37. J Immunol. 2007;178:7190–8.CrossRefPubMed
7.
go back to reference Liu PT, Stenger S, Tang DH, Modlin RL. Cutting edge: vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin. J Immunol. 2007;179:2060–3.CrossRefPubMed Liu PT, Stenger S, Tang DH, Modlin RL. Cutting edge: vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin. J Immunol. 2007;179:2060–3.CrossRefPubMed
8.
go back to reference Gombart AF, Borregaard N, Koeffler HP. Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1, 25-dihydroxyvitamin D3. FASEB J. 2005;19:1067–77.CrossRefPubMed Gombart AF, Borregaard N, Koeffler HP. Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1, 25-dihydroxyvitamin D3. FASEB J. 2005;19:1067–77.CrossRefPubMed
9.
go back to reference Ramanathan B, Davis EG, Ross CR, Blecha F. Cathelicidins: microbicidal activity, mechanisms of action, and roles in innate immunity. Microb Infect. 2002;4:361–72.CrossRef Ramanathan B, Davis EG, Ross CR, Blecha F. Cathelicidins: microbicidal activity, mechanisms of action, and roles in innate immunity. Microb Infect. 2002;4:361–72.CrossRef
10.
go back to reference Campbell GR, Spector SA. Vitamin D inhibits human immunodeficiency virus type 1 and Mycobacterium tuberculosis infection in macrophages through the induction of autophagy. PLoS Pathog. 2012;8(5):e1002689. Campbell GR, Spector SA. Vitamin D inhibits human immunodeficiency virus type 1 and Mycobacterium tuberculosis infection in macrophages through the induction of autophagy. PLoS Pathog. 2012;8(5):e1002689.
11.
go back to reference Zijenah LS, Kadzirange G, Bandason T, Chipiti MM, Gwambiwa B, Makoga F, et al. Comparative performance characteristics of the urine lipoarabinomannan strip test and sputum smear microscopy in hospitalized HIV-infected patients with suspected tuberculosis in Harare, Zimbabwe. BMC Infect Dis. 2016;16:1. Zijenah LS, Kadzirange G, Bandason T, Chipiti MM, Gwambiwa B, Makoga F, et al. Comparative performance characteristics of the urine lipoarabinomannan strip test and sputum smear microscopy in hospitalized HIV-infected patients with suspected tuberculosis in Harare, Zimbabwe. BMC Infect Dis. 2016;16:1.
12.
go back to reference Peter JG, Zijenah LS, Chanda D, Clowes P, Lesosky M, Gina P, et al. Effect on mortality of point-of-care, urine-based lipoarabinomannan testing to guide tuberculosis treatment initiation in HIV-positive hospital inpatients: a pragmatic, parallel-group, multicountry, open-label, randomised controlled trial. Lancet. 2016;387:1187–97.CrossRefPubMed Peter JG, Zijenah LS, Chanda D, Clowes P, Lesosky M, Gina P, et al. Effect on mortality of point-of-care, urine-based lipoarabinomannan testing to guide tuberculosis treatment initiation in HIV-positive hospital inpatients: a pragmatic, parallel-group, multicountry, open-label, randomised controlled trial. Lancet. 2016;387:1187–97.CrossRefPubMed
13.
15.
go back to reference Jones G. Pharmacokinetics of vitamin D toxicity. Am J Clin Nutr. 2008;88:582S–6.PubMed Jones G. Pharmacokinetics of vitamin D toxicity. Am J Clin Nutr. 2008;88:582S–6.PubMed
16.
go back to reference Conesa-Botella A, Goovaerts O, Massinga-Loembe M, Worodria W, Mazakpwe D, Luzinda K, et al. Low prevalence of vitamin D deficiency in Ugandan HIV-infected patients with and without tuberculosis. Int J Tuberc Lung Dis. 2012;16:1517–21.CrossRefPubMed Conesa-Botella A, Goovaerts O, Massinga-Loembe M, Worodria W, Mazakpwe D, Luzinda K, et al. Low prevalence of vitamin D deficiency in Ugandan HIV-infected patients with and without tuberculosis. Int J Tuberc Lung Dis. 2012;16:1517–21.CrossRefPubMed
18.
go back to reference Dawson-Hughes B, Heaney RP, Holick MF, Lips P, Meunier PJ, Vieth R. Estimates of optimal vitamin D status. Osteoporos Int. 2005;16:713–6.CrossRefPubMed Dawson-Hughes B, Heaney RP, Holick MF, Lips P, Meunier PJ, Vieth R. Estimates of optimal vitamin D status. Osteoporos Int. 2005;16:713–6.CrossRefPubMed
19.
go back to reference Wejse C, Olesen R, Rabna P, Kaestel P, Gustafson P, Aaby P, et al. Serum 25-hydroxyvitamin D in a West African population of tuberculosis patients and unmatched healthy controls. Am J Clin Nutr. 2007;86:1376–83.PubMed Wejse C, Olesen R, Rabna P, Kaestel P, Gustafson P, Aaby P, et al. Serum 25-hydroxyvitamin D in a West African population of tuberculosis patients and unmatched healthy controls. Am J Clin Nutr. 2007;86:1376–83.PubMed
20.
go back to reference Melamed ML, Michos ED, Post W, Astor B. 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med. 2008;168:1629–37.CrossRefPubMedPubMedCentral Melamed ML, Michos ED, Post W, Astor B. 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med. 2008;168:1629–37.CrossRefPubMedPubMedCentral
21.
go back to reference Zittermann A, Schleithoff SS, Frisch S, Götting C, Kuhn J, Koertke H, et al. Circulating calcitriol concentrations and total mortality. Clin Chem. 2009;55:1163–70.CrossRefPubMed Zittermann A, Schleithoff SS, Frisch S, Götting C, Kuhn J, Koertke H, et al. Circulating calcitriol concentrations and total mortality. Clin Chem. 2009;55:1163–70.CrossRefPubMed
22.
go back to reference Martineau AR, Nhamoyebonde S, Oni T, Rangaka MX, Marais S, Bangani N, et al. Reciprocal seasonal variation in vitamin D status and tuberculosis notifications in Cape Town, South Africa. Proc Natl Acad Sci. 2011;108:19013–7.CrossRefPubMedPubMedCentral Martineau AR, Nhamoyebonde S, Oni T, Rangaka MX, Marais S, Bangani N, et al. Reciprocal seasonal variation in vitamin D status and tuberculosis notifications in Cape Town, South Africa. Proc Natl Acad Sci. 2011;108:19013–7.CrossRefPubMedPubMedCentral
23.
go back to reference Wilkinson RJ, Llewelyn M, Toossi Z, Patel P, Pasvol G, Lalvani A, et al. Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in west London: a case–control study. Lancet. 2000;355:618–21.CrossRefPubMed Wilkinson RJ, Llewelyn M, Toossi Z, Patel P, Pasvol G, Lalvani A, et al. Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in west London: a case–control study. Lancet. 2000;355:618–21.CrossRefPubMed
24.
go back to reference Nielsen NO, Skifte T, Andersson M, Wohlfahrt J, Søborg B, Koch A, et al. Both high and low serum vitamin D concentrations are associated with tuberculosis: a case control study in Greenland. Br J Nutr. 2010;104:1487–91.CrossRefPubMed Nielsen NO, Skifte T, Andersson M, Wohlfahrt J, Søborg B, Koch A, et al. Both high and low serum vitamin D concentrations are associated with tuberculosis: a case control study in Greenland. Br J Nutr. 2010;104:1487–91.CrossRefPubMed
25.
go back to reference Friis H, Range N, Changalucha J, PrayGod G, Jeremiah K, Faurholt-Jepsen D, et al. Vitamin D status among pulmonary TB patients and non-TB controls: A cross-sectional study from Mwanza, Tanzania. PLoS One. 2013;8:e81142.CrossRefPubMedPubMedCentral Friis H, Range N, Changalucha J, PrayGod G, Jeremiah K, Faurholt-Jepsen D, et al. Vitamin D status among pulmonary TB patients and non-TB controls: A cross-sectional study from Mwanza, Tanzania. PLoS One. 2013;8:e81142.CrossRefPubMedPubMedCentral
28.
go back to reference Mutt SJ, Hyppönen E, Saarnio J, Järvelin MR, Herzig KH. Vitamin D and adipose tissue—more than storage. Front Physiol. 2014;5(228):1–9. Mutt SJ, Hyppönen E, Saarnio J, Järvelin MR, Herzig KH. Vitamin D and adipose tissue—more than storage. Front Physiol. 2014;5(228):1–9.
29.
go back to reference Davies PD, Church HA, Brown RC, Woodhead JS. Raised serum calcium in tuberculosis patients in Africa. Eur J Respir Dis. 1987;71:341–4.PubMed Davies PD, Church HA, Brown RC, Woodhead JS. Raised serum calcium in tuberculosis patients in Africa. Eur J Respir Dis. 1987;71:341–4.PubMed
30.
go back to reference Mastala Y, Nyangulu P, Banda RV, Mhemedi B, White SA, Allain TJ. Vitamin D deficiency in medical patients at a central hospital in Malawi: a comparison with TB patients from a previous study. PLoS One. 2013;8:e59017.CrossRefPubMedPubMedCentral Mastala Y, Nyangulu P, Banda RV, Mhemedi B, White SA, Allain TJ. Vitamin D deficiency in medical patients at a central hospital in Malawi: a comparison with TB patients from a previous study. PLoS One. 2013;8:e59017.CrossRefPubMedPubMedCentral
32.
go back to reference Grange JM, Davies PDO, Brown RC, Woodhead JS, Kardjito T. A study of vitamin D levels in Indonesian patients with untreated pulmonary tuberculosis. Tubercle. 1985;66:187–91.CrossRefPubMed Grange JM, Davies PDO, Brown RC, Woodhead JS, Kardjito T. A study of vitamin D levels in Indonesian patients with untreated pulmonary tuberculosis. Tubercle. 1985;66:187–91.CrossRefPubMed
33.
go back to reference Chan TY, Poon P, Pang J, Swaminathan R, Chan CH, Nisar M, et al. A study of calcium and vitamin D metabolism in Chinese patients with pulmonary tuberculosis. J Trop Med Hyg. 1994;97:26–30.PubMed Chan TY, Poon P, Pang J, Swaminathan R, Chan CH, Nisar M, et al. A study of calcium and vitamin D metabolism in Chinese patients with pulmonary tuberculosis. J Trop Med Hyg. 1994;97:26–30.PubMed
34.
go back to reference Hong JY, Kim SY, Chung KS, Kim EY, Jung JY, Park MS, et al. Association between vitamin D deficiency and tuberculosis in a Korean population. Int J Tuberc Lung Dis. 2014;18:73–8.CrossRefPubMed Hong JY, Kim SY, Chung KS, Kim EY, Jung JY, Park MS, et al. Association between vitamin D deficiency and tuberculosis in a Korean population. Int J Tuberc Lung Dis. 2014;18:73–8.CrossRefPubMed
35.
go back to reference Sarin P, Duffy J, Mughal Z, Hedayat E, Manaseki-Holland S. Vitamin D and tuberculosis: review and association in three rural provinces of Afghanistan. Int J Tuberc Lung Dis. 2016;20:383–8.CrossRefPubMed Sarin P, Duffy J, Mughal Z, Hedayat E, Manaseki-Holland S. Vitamin D and tuberculosis: review and association in three rural provinces of Afghanistan. Int J Tuberc Lung Dis. 2016;20:383–8.CrossRefPubMed
36.
go back to reference Ho-Pham LT, Nguyen ND, Nguyen TT, Nguyen DH, Bui PK, Nguyen VN, et al. Association between vitamin D insufficiency and tuberculosis in a Vietnamese population. BMC Infect Dis. 2010;10:306.CrossRefPubMedPubMedCentral Ho-Pham LT, Nguyen ND, Nguyen TT, Nguyen DH, Bui PK, Nguyen VN, et al. Association between vitamin D insufficiency and tuberculosis in a Vietnamese population. BMC Infect Dis. 2010;10:306.CrossRefPubMedPubMedCentral
37.
go back to reference Mao X, Zheng H, Liu Z, Wu Y, Na R, Wang C, et al. Analysis of 25 (OH) D serum concentrations of hospitalized elderly patients in the shanghai area. PLoS One. 2014;9:e90729.CrossRefPubMedPubMedCentral Mao X, Zheng H, Liu Z, Wu Y, Na R, Wang C, et al. Analysis of 25 (OH) D serum concentrations of hospitalized elderly patients in the shanghai area. PLoS One. 2014;9:e90729.CrossRefPubMedPubMedCentral
Metadata
Title
Association of high serum vitamin D concentrations with active pulmonary TB in an HIV co-endemic setting, Harare, Zimbabwe
Authors
Cuthbert Musarurwa
Lynn Sodai Zijenah
Doreen Zvipo Duri
Kudzie Mateveke-Dangaiso
Kudakwashe Mhandire
Maria Mary Chipiti
Marshall Wesley Munjoma
Witmore Bayayi Mujaji
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2017
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-017-2243-x

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