Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis

English version

Autoři: Omowunmi Aibana ^aff001; Chuan-Chin Huang ^aff002; Said Aboud ^aff003; Alberto Arnedo-Pena ^aff004; Mercedes C. Becerra ^aff002; Juan Bautista Bellido-Blasco ^aff004; Ramesh Bhosale ^aff005; Roger Calderon ^aff006; Silvia Chiang ^aff007; Carmen Contreras ^aff006; Ganmaa Davaasambuu ^aff008; Wafaie W. Fawzi ^aff009; Molly F. Franke ^aff002; Jerome T. Galea ^aff010; Daniel Garcia-Ferrer ^aff011; Maria Gil-Fortuño ^aff012; Barbará Gomila-Sard ^aff012; Amita Gupta ^aff013; Nikhil Gupte ^aff014; Rabia Hussain ^aff015; Jesus Iborra-Millet ^aff011; Najeeha T. Iqbal ^aff016; Jose Vicente Juan-Cerdán ^aff011; Aarti Kinikar ^aff017; Leonid Lecca ^aff006; Vidya Mave ^aff014; Noemi Meseguer-Ferrer ^aff004; Grace Montepiedra ^aff018; Ferdinand M. Mugusi ^aff019; Olumuyiwa A. Owolabi ^aff020; Julie Parsonnet ^aff021; Freddy Roach-Poblete ^aff022; Maria Angeles Romeu-García ^aff004; Stephen A. Spector ^aff023; Christopher R. Sudfeld ^aff009; Mark W. Tenforde ^aff024; Toyin O. Togun ^aff025; Rosa Yataco ^aff006; Zibiao Zhang ^aff026; Megan B. Murray ^aff002
Působiště autorů: Department of Internal Medicine, McGovern Medical School at the University of Texas Health Science Center, Houston, Texas, United States of America ^aff001; Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, United States of America ^aff002; Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Upanga West, Dar es Salaam, Tanzania ^aff003; Epidemiology Division, Public Health Center, Castellon, Spain ^aff004; Department of Obstetrics & Gynecology, Byramjee Jeejeebhoy Government Medical College, Pune, India ^aff005; Partners in Health—Socios En Salud Sucursal, Lima, Peru ^aff006; Department of Pediatrics, Alpert Medical School of Brown University, Providence, Rhode Island, United States of America ^aff007; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America ^aff008; Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America ^aff009; School of Social Work, University of South Florida, Tampa, Florida, United States of America ^aff010; Biochemical Laboratory, Hospital General, Castellon, Spain ^aff011; Microbiology Laboratory, Hospital General, Castellon, Spain ^aff012; Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America ^aff013; Byramjee Jeejeebhoy Government Medical College-Johns Hopkins University CRS, Pune, India ^aff014; Department of Pathology and Microbiology, Aga Khan University, Karachi, Pakistan ^aff015; Department of Pediatrics and Child Health and Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan ^aff016; Department of Pediatrics, Byramjee Jeejeebhoy Government Medical College, Pune, India ^aff017; Center for Biostatistics in AIDS Research and Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America ^aff018; Department of Internal Medicine, Muhimbili University of Health and Allied Sciences, Upanga West, Dar es Salaam, Tanzania ^aff019; Medical Research Council Gambia at London School of Hygiene and Tropical Medicine, Banjul, The Gambia ^aff020; Departments of Medicine and of Health Research and Policy, Stanford University School of Medicine, Stanford, California, United States of America ^aff021; Laboratory Hospital Regional Antofagasta, Antofagasta, Chile ^aff022; Division of Infectious Diseases, Department of Pediatrics, University of California San Diego, La Jolla, California, United States of America ^aff023; Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America ^aff024; Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada ^aff025; Division of Global Health Equity, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America ^aff026
Vyšlo v časopise: Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis. PLoS Med 16(9): e32767. doi:10.1371/journal.pmed.1002907
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pmed.1002907

Souhrn

Background

Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk.

Methods and findings

We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. For each case, we randomly selected four controls from among contacts who did not develop TB disease, matching on gender and year of age. We also conducted a one-stage individual-participant data (IPD) meta-analysis searching PubMed and Embase to identify prospective studies of vitamin D and TB disease until June 8, 2019. We included studies that assessed vitamin D before TB diagnosis. In the primary analysis, we defined vitamin D deficiency as 25–(OH)D < 50 nmol/L, insufficiency as 50–75 nmol/L, and sufficiency as >75nmol/L. We estimated the association between baseline vitamin D status and incident TB using conditional logistic regression in the Lima cohort and generalized linear mixed models in the meta-analysis. We further defined severe vitamin D deficiency as 25–(OH)D < 25 nmol/L and performed stratified analyses by HIV status in the IPD meta-analysis. In the Lima cohort, we analyzed 180 cases and 709 matched controls. The adjusted odds ratio (aOR) for TB risk among participants with baseline vitamin D deficiency compared to sufficient vitamin D was 1.63 (95% CI 0.75–3.52; p = 0.22). We included seven published studies in the meta-analysis and analyzed 3,544 participants. In the pooled analysis, the aOR was 1.48 (95% CI 1.04–2.10; p = 0.03). The aOR for severe vitamin D deficiency was 2.05 (95% CI 0.87–4.87; p trend for decreasing 25–(OH)D levels from sufficient vitamin D to severe deficiency = 0.02). Among 1,576 HIV-positive patients, vitamin D deficiency conferred a 2-fold (aOR 2.18, 95% CI 1.22–3.90; p = 0.01) increased risk of TB, and the aOR for severe vitamin D deficiency compared to sufficient vitamin D was 4.28 (95% CI 0.85–21.45; p = 0.08). Our Lima cohort study is limited by the short duration of follow-up, and the IPD meta-analysis is limited by the number of possible confounding covariates available across all studies.

Conclusion

Our findings suggest vitamin D predicts TB disease risk in a dose-dependent manner and that the risk of TB disease is highest among HIV-positive individuals with severe vitamin D deficiency. Randomized control trials are needed to evaluate the possible role of vitamin D supplementation on reducing TB disease risk.

Klíčová slova:

Medicine and health sciences – Infectious diseases – Bacterial diseases – Tuberculosis – Tropical diseases – Diagnostic medicine – Tuberculosis diagnosis and management – Pathology and laboratory medicine – Pathogens – Physical sciences – Chemistry – Chemical compounds – Organic compounds – Vitamins – Organic chemistry – Mathematics – Statistics – Research and analysis methods – Mathematical and statistical techniques – Statistical methods – Metaanalysis – Research design – Cohort studies – Biology and life sciences – Nutrition – Nutritional deficiencies – Vitamin D deficiency – Microbiology – Medical microbiology – Microbial pathogens – Viral pathogens – Immunodeficiency viruses – HIV – Retroviruses – Lentivirus – Organisms – Viruses – RNA viruses – Bacteria – Actinobacteria – Mycobacterium tuberculosis

Zdroje

1. World Health Organization (WHO). Global Tuberculosis Report 2017. Available from: http://www.who.int/tb/publications/global_report/en/

2. Palacios C, Gonzalez L. Is vitamin D deficiency a major global public health problem? J Steroid Biochem Mol Biol. 2014;144: 138–145. doi: 10.1016/j.jsbmb.2013.11.003 24239505

3. Hilger J, Friedel A, Herr R, Rausch T, Roos F, Wahl DA, et al. A systematic review of vitamin D status in populations worldwide. Br J Nutr. 2014;111(1): 23–45. doi: 10.1017/S0007114513001840 23930771

4. Chun RF, Liu PT, Modlin RL, Adams JS, Hewison M. Impact of vitamin D on immune function: lessons learned from genome-wide analysis. Front Physiol. 2014;5: 151. doi: 10.3389/fphys.2014.00151 24795646

5. 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(4): 2060–2063. doi: 10.4049/jimmunol.179.4.2060 17675463

6. Fabri M, Stenger S, Shin DM, Yuk JM, Liu PT, Realegeno S, et al. Vitamin D is required for IFN-gamma mediated antimicrobial activity of human macrophages. Sci Transl Med. 2011;3(104): 104ra102. doi: 10.1126/scitranslmed.3003045 21998409

7. Sly LM, Lopez M, Nauseef WM, Reiner NE. 1alpha,25-dihydroxyvitamin D3-induced monocyte antimycobacterial activity is regulated by phosphatidylinositol 3-kinase and mediated by the NADPH-dependent phagocyte oxidase. J Biol Chem. 2001;276: 35482–35493. doi: 10.1074/jbc.M102876200 11461902

8. Hmama Z, Sendide K, Talal A, Garcia R, Dobos K, Reiner NE. Quantitative analysis of phagolysosome fusion in intact cells: inhibition by mycobacterial lipoarabinomannan and rescue by an 1alpha,25-dihydroxyvitamin D3-phosphoinositide 3-kinase pathway. J Cell Sci. 2004;117: 2131–2140. doi: 10.1242/jcs.01072 15090599

9. Nnoaham KE, Clarke A. Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis. Int J Epidemiol. 2008;37: 113–119. doi: 10.1093/ije/dym247 18245055

10. Sutaria N, Liu CT, Chen TV. 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. doi: 10.1016/j.jcte.2014.08.001 25599020

11. Zeng J, Wu G, Yang W, Gu X, Liang W, Yao Y, et al. A serum vitamin D level < 25 nmol/l pose high tuberculosis risk: a meta-analysis. PLoS ONE. 2015;10(5): e0126014. doi: 10.1371/journal.pone.0126014 25938683

12. Huang SJ, Wang XH, Liu ZD, Cao WL, Han Y, Ma AG, et al. Vitamin D deficiency and the risk of tuberculosis: a meta-analysis. Drug Des Devel Ther. 2016;11: 91–102. doi: 10.2147/DDDT.S79870 28096657

13. Aibana O, Franke MF, Huang CC, Galea JT, Calderon R, Zhang Z, et al. Impact of vitamin A and carotenoids on the risk of tuberculosis progression. Clin Infect Dis. 2017;65(6): 900–909. doi: 10.1093/cid/cix476 28531276

14. Aibana O, Franke MF, Huang CC, Galea JT, Calderon R, Zhang Z, et al. Vitamin E status is inversely associated with risk of incident tuberculosis disease among household contacts. J Nutr. 2018;148(1): 56–62. doi: 10.1093/jn/nxx006 29378042

15. Peru Ministerio de Salud. Norma Técnica de Salud para el Control de la Tuberculosis. Dirección General de Salud de las Personas. Estrategia Sanitaria Nacional de Prevención y Control de la Tuberculosis. 2006. Available from: ftp://ftp2.minsa.gob.pe/descargas/dgsp/ESN-tuberculosis/normaspublicaciones/NTSTBC.pdf

16. El-Sohemy A, Baylin A, Kabagambe E, Ascherio A, Spiegelman D, Campos H. Individual carotenoid concentrations in adipose tissue and plasma as biomarkers of dietary intake. Am J Clin Nutr. 2002;76: 172–179. doi: 10.1093/ajcn/76.1.172 12081831

17. Institute of Medicine. Dietary reference intakes for calcium and vitamin D. Washington, DC: National Academies Press (US); 2011.

18. Rice AL, West KP Jr, Black RE. Vitamin A deficiency. Global and regional burden of disease attributable to selected major risk factors. Vol 1. World Health Organization; 2004. Available from: http://www.who.int/healthinfo/global_burden_disease/cra/en/

19. World Health Organization (WHO). Child growth standards. 2011. Available from: http://www.who.int/childgrowth/software/en/

20. Odone A, Calderon R, Becerra MC, Zhang Z, Contreras CC, Yataco R, et al. Acquired and Transmitted Multidrug Resistant Tuberculosis: The Role of Social Determinants. PLoS ONE. 2016;11(1): e0146642. doi: 10.1371/journal.pone.0146642 26765328

21. World Meteorological Organization. World Weather Information Service. Available from: http://worldweather.wmo.int/en/city.html?cityId=108

22. Pearce N. Analysis of matched case-control studies, BMJ. 2016;352: i969. doi: 10.1136/bmj.i969 26916049

23. Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med. 2009;6(7): e1000097. doi: 10.1371/journal.pmed.1000097 19621072

24. Riley RD, Lambert PC, Abo-Zaid G. Meta-analysis of individual participant data: rationale, conduct, and reporting. BMJ. 2010;340: c221. doi: 10.1136/bmj.c221 20139215

25. Wells GA, Shea B, O'Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp

26. Chen B, Benedetti A. Quantifying heterogeneity in individual participant data meta-analysis with binary outcomes. Syst Rev. 2017;6(1): 243. doi: 10.1186/s13643-017-0630-4 29208048

27. Bates D, Maechler M, Bolker B, Walker S. Fitting linear mixed-effects models using lme4. Journal of Statistical Software. 2015;67(1): 1–48.

28. Arnedo–Pena A, Juan-Cerdán JV, Romeu-García A, García-Ferrer D, Holguín-Gómez R, Iborra-Millet J, et al. Vitamin D status and incidence of tuberculosis among contacts of pulmonary tuberculosis patients. Int J Tuberc Lung Dis. 2015;19(1): 65–69. doi: 10.5588/ijtld.14.0348 25519792

29. Gupta A, Montepiedra G, Gupte A, Zeldow B, Jubulis J, Detrick B, et al. Low vitamin-D levels combined with PKP3-SIGIRR-TMEM16J host variants is associated with tuberculosis and death in HIV-infected and -exposed infants. PLoS ONE. 2016;11(2): e0148649. doi: 10.1371/journal.pone.0148649 26872154

30. Mave V, Chandanwale A, Bhosale R, Shere D, Gupte N, Suryavanshi N, et al. Vitamin D deficiency and risk of postpartum tuberculosis among HIV-infected breastfeeding mothers in India. Int J Tuberc Lung Dis. 2015;19(3): 302–304. doi: 10.5588/ijtld.14.0658 25686138

31. Owolabi O, Agbla S, Owiafe P, Donkor S, Togun T, Sillah AK, et al. Elevated serum 25-hydroxy (OH) vitamin D levels are associated with risk of TB progression in Gambian adults. Tuberculosis (Edinb). 2016;98: 86–91. doi: 10.1016/j.tube.2016.02.007 27156622

32. Sudfeld C, Giovannucci EL, Isanaka S, Aboud S, Mugusi FM, Wang M, et al. Vitamin D status and incidence of pulmonary tuberculosis, opportunistic infections, and wasting among HIV-infected Tanzanian adults initiating antiretroviral therapy. J Infect Dis. 2013;207(3): 378–385. doi: 10.1093/infdis/jis693 23162137

33. Talat N, Perry S, Parsonnet J, Dawood G, Hussain R. Vitamin D deficiency and tuberculosis progression. Emerg Infect Dis. 2010;16(5): 853–855. doi: 10.3201/eid1605.091693 20409383

34. Tenforde MW, Yadav A, Dowdy DW, Gupte N, Shivakoti R, Yang WT, et al. Vitamin A and D deficiencies associated with incident tuberculosis in HIV-infected patients initiating antiretroviral therapy in multinational case-cohort study. J Acquir Immune Defic Syndr. 2017;75(3): e71–e79. doi: 10.1097/QAI.0000000000001308 28169875

35. Price P, Haddow LJ, Affandi J, Agarwal U, Easterbrook PJ, Elliott J, et al. Short Communication: Plasma levels of vitamin D in HIV patients initiating antiretroviral therapy do not predict immune restoration disease associated with Mycobacterium tuberculosis. AIDS Res Hum Retroviruses. 2012;28(10): 1216–1219. doi: 10.1089/AID.2011.0272 22280097

36. Conesa-Botella A, Meintjes G, Coussens AK, van der Plas H, Goliath R, Schutz C, et al. Corticosteroid therapy, vitamin D status, and inflammatory cytokine profile in the HIV-tuberculosis immune reconstitution inflammatory syndrome. Clin Infect Dis. 2012;55(7): 1004–1011. doi: 10.1093/cid/cis577 22715179

37. Musselwhite LW, Andrade BB, Ellenberg SS, Tierney A, Belaunzaran-Zamudio PF, Rupert A, et al. Vitamin D, d-dimer, interferon γ, and sCD14 levels are independently associated with immune reconstitution inflammatory syndrome: a prospective, international study. EBioMedicine. 2016;4: 115–123. doi: 10.1016/j.ebiom.2016.01.016 26981576

38. Wingfield T, Schumacher SG, Sandhu G, Tovar MA, Zevallos K, Baldwin MR, et al. The seasonality of tuberculosis, sunlight, vitamin D, and household crowding. J Infect Dis. 2014;210(5): 774–783. doi: 10.1093/infdis/jiu121 24596279

39. Maceda EB, Gonçalves CCM, Andrews JR, Ko AI, Yeckel CW, Croda J. Serum vitamin D levels and risk of prevalent tuberculosis, incident tuberculosis and tuberculin skin test conversion among prisoners. Sci Rep. 2018;8(1): 997. doi: 10.1038/s41598-018-19589-3 29343733

40. Keflie TS, Nölle N, Lambert C, Nohr D, Biesalski HK. Vitamin D deficiencies among tuberculosis patients in Africa: a systematic review. Nutrition. 2015;31: 1204–1212. doi: 10.1016/j.nut.2015.05.003 26333888

41. Daley P, Jagannathan V, John KR, Sarojini J, Latha A, Vieth R, et al. Adjunctive vitamin D for treatment of active tuberculosis in India: a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2015;15(5): 528–534. doi: 10.1016/S1473-3099(15)70053-8 25863562

42. Xia J, Shi L, Zhao L, Xu F. Impact of vitamin D supplementation on the outcome of tuberculosis treatment: a systematic review and meta-analysis of randomized controlled trials. Chin Med J (Engl). 2014;127: 3127–3134. 25189958

43. Wallis RS, Zumla A. Vitamin D as adjunctive host-directed therapy in tuberculosis: a systematic review. Open Forum Infect Dis. 2016;3(3): ofw151. doi: 10.1093/ofid/ofw151 27800526

44. Zittermann A, Pilz S, Hoffmann H, März W. Vitamin D and airway infections: a European perspective. Eur J Med Res. 2016;21: 14. doi: 10.1186/s40001-016-0208-y 27009076

45. Afzal A, Rathore R, Butt NF, Randhawa FA. Efficacy of Vitamin D supplementation in achieving an early Sputum Conversion in Smear positive Pulmonary Tuberculosis. Pak J Med Sci. 2018;34(4): 849–854. doi: 10.12669/pjms.344.14397 30190740

46. Wu HX, Xiong XF, Zhu M, Wei J, Zhuo KQ, Cheng DY. Effects of vitamin D supplementation on the outcomes of patients with pulmonary tuberculosis: a systematic review and meta-analysis. BMC Pulm Med. 2018;18(1):108. doi: 10.1186/s12890-018-0677-6 29954353

47. Jolliffe DA, Ganmaa D, Wejse C, Raqib R, Haq MA, Salahuddin N, et al. Adjunctive vitamin D in tuberculosis treatment: meta-analysis of individual participant data. Eur Respir J. 2019;53(3) pii: 1802003. doi: 10.1183/13993003.02003-2018 30728208

48. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311(5768): 1770–1773. doi: 10.1126/science.1123933 16497887

49. Coussens A, Timms PM, Boucher BJ, Venton TR, Ashcroft AT, Skolimowska KH, et al. 1alpha,25-dihydroxyvitamin D3 inhibits matrix metalloproteinases induced by Mycobacterium tuberculosis infection. Immunology. 2009;127: 539–548. doi: 10.1111/j.1365-2567.2008.03024.x 19178594

50. Saul L, Mair I, Ivens A, Brown P, Samuel K, Campbell JDM, et al. 1,25-Dihydroxyvitamin D3 Restrains CD4+ T Cell Priming Ability of CD11c+ Dendritic Cells by Upregulating Expression of CD31. Front Immunol. 2019;10: 600. doi: 10.3389/fimmu.2019.00600 30984180

51. Mitri J, Pittas AG. Vitamin D and diabetes. Endocrinol Metab Clin North Am. 2014;43(1): 205–232. doi: 10.1016/j.ecl.2013.09.010 24582099

52. Bourlon PM, Billaudel B, Faure-Dussert A. Influence of vitamin D3 deficiency and 1,25 dihydroxyvitamin D3 on de novo insulin biosynthesis in the islets of the rat endocrine pancreas. J Endocrinol. 1999;160: 87–95. doi: 10.1677/joe.0.1600087 9854180

53. Jeon CY, Murray MB. Diabetes mellitus increases the risk of active tuberculosis: a systematic review of 13 observational studies. PLoS Med. 2008;5(7): e152. doi: 10.1371/journal.pmed.0050152 18630984

54. Harries AD, Satyanarayana S, Kumar AMV, Nagaraja SB, Isaakidis P, Malhotra S, et al. Epidemiology and interaction of diabetes mellitus and tuberculosis and the challenges for care: a review. Public Health Action. 2013;3: S3–S9. doi: 10.5588/pha.13.0024 26393066

55. Chen C, Liu Q, Zhu L, Yang H, Lu W. Vitamin D receptor gene polymorphisms on the risk of tuberculosis, a meta-analysis of 29 case-control studies. PLoS ONE. 2013;8(12): e83843. doi: 10.1371/journal.pone.0083843 24349552

56. Gao L, Tao Y, Zhang L, Jin Q. Vitamin D receptor genetic polymorphisms and tuberculosis: updated systematic review and meta-analysis. Int J Tuberc Lung Dis. 2010;14(1):15–23. 20003690

57. Lee SW, Chuang TY, Huang HH, Liu CW, Kao YH, Wu LS. VDR and VDBP genes polymorphisms associated with susceptibility to tuberculosis in a Han Taiwanese population. J Microbiol Immunol Infect. 2016;49(5): 783–787. doi: 10.1016/j.jmii.2015.12.008 26869016

58. 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(9204): 618–621. doi: 10.1016/S0140-6736(99)02301-6 10696983

59. 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 USA. 2011;108(47): 19013–19017. doi: 10.1073/pnas.1111825108 22025704

60. Parrinello CM, Crossa A, Harris TG. Seasonality of tuberculosis in New York City, 1990–2007. Int J Tuberc Lung Dis. 2012;16(1): 32–37. doi: 10.5588/ijtld.11.0145 22236842

61. Fares A. Seasonality of tuberculosis. J Glob Infect Dis. 2011;3(1): 46–55. doi: 10.4103/0974-777X.77296 21572609

62. Getz HR, Long ER, Henderson HJ. A study of the relation of nutrition to the development of tuberculosis; influence of ascorbic acid and vitamin A. Am Rev Tuberc. 1951;64: 381–393. 14885669

63. Wheelwright M, Kim EW, Inkeles MS, De Leon A, Pellegrini M, Krutzik SRet al. All-trans retinoic acid-triggered antimicrobial activity against Mycobacterium tuberculosis is dependent on NPC2. J Immunol. 2014; 192(5): 2280–2290. doi: 10.4049/jimmunol.1301686 24501203

64. Anand P, Kaul KD, Sharma M. Synergistic action of vitamin D and retinoic acid restricts invasion of macrophages by pathogenic mycobacteria. J Microbiol Immunol Infect. 2008;41: 17–25. 18327422

65. Jiménez-Sousa MÁ, Martínez I, Medrano LM, Fernández-Rodríguez A, Resino S. Vitamin D in Human Immunodeficiency Virus Infection: Influence on Immunity and Disease. Front Immunol. 2018;9: 458. doi: 10.3389/fimmu.2018.00458 29593721

66. Ezeamama AE, Guwatudde D, Wang M, Bagenda D, Kyeyune R, Sudfeld C, et al. Vitamin-D deficiency impairs CD4 + T-cell count recovery rate in HIV-positive adults on highly active antiretroviral therapy: a longitudinal study. Clin Nutr. 2016;35(5): 1110–1117. doi: 10.1016/j.clnu.2015.08.007 26371397

67. Mehta S, Giovannucci E, Mugusi FM, Spiegelman D, Aboud S, Hertzmark E, et al. Vitamin D status of HIV-infected women and its association with HIV disease progression, anemia, and mortality. PLoS ONE. 2010;5(1): e8770. doi: 10.1371/journal.pone.0008770 20098738

68. Coussens AK, Naude CE, Goliath R, Chaplin G, Wilkinson RJ, Jablonski NG. High-dose vitamin D3 reduces deficiency caused by low UVB exposure and limits HIV-1 replication in urban Southern Africans. Proc Natl Acad Sci U S A. 2015;112(26): 8052–8057. doi: 10.1073/pnas.1500909112 26080414

69. Thieden E, Philipsen PA, Heydenreich J, Wulf HC. Vitamin D level in summer and winter related to measured UVR exposure and behavior. Photochem Photobiol. 2009;85(6): 1480–1484. doi: 10.1111/j.1751-1097.2009.00612.x 19709382

70. 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. doi: 10.1371/journal.ppat.1002689 22589721

71. Sudfeld CR, Mugusi F, Aboud S, Nagu TJ, Wang M, Fawzi WW. Efficacy of vitamin D supplementation in reducing incidence of pulmonary tuberculosis and mortality among HIV-infected Tanzanian adults initiating antiretroviral therapy: study protocol for a randomized controlled trial. Trials. 2017;18(1): 66. doi: 10.1186/s13063-017-1819-5 28183335

72. Sterne JAC, Egger M, Moher D. Chapter 10: Addressing reporting biases. In: Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0. Cochrane; 2011. Available from: https://handbook-5-1.cochrane.org/chapter_10/10_4_3_1_recommendations_on_testing_for_funnel_plot_asymmetry.htm