INT J TUBERC LUNG DIS 19(3):302–304 Q 2015 The Union http://dx.doi.org/10.5588/ijtld.14.0658
Vitamin D deficiency and risk of postpartum tuberculosis among HIV-infected breastfeeding mothers in India V. Mave,*† A. Chandanwale,* R. Bhosale,* D. Shere,* N. Gupte,*† N. Suryavanshi,* V. Kulkarni,* A. Kagal,* R. Bharadwaj,* S. Joshi,* R. C. Bollinger,*† A. Gupta,*† for the SWEN (Six Weeks Extended Nevirapine India) and Byramjee-Jeejeebhoy Medical College Clinical Trials Unit Study team *Byramjee-Jeejeebhoy Medical College Clinical Trials Unit, Pune, India; †Johns Hopkins University School of Medicine, Baltimore, Maryland, USA SUMMARY
Some studies have associated low vitamin D levels with the risk of tuberculosis (TB), but its association in human immunodeficiency virus (HIV) infected mothers in a TB-endemic region has not been well studied. We conducted a nested 1:2 case-control study among HIVinfected mothers in western India to evaluate the association between maternal vitamin D levels and the
risk of postpartum TB. Vitamin D insufficiency, moderate deficiency and severe deficiency were observed in a high proportion of HIV-infected mothers, but were not associated with the risk of postpartum TB. K E Y W O R D S : vitamin D deficiency; HIV/AIDS; tuberculosis; India; pregnancy; maternal health
TUBERCULOSIS (TB) is the most common human immunodeficiency virus 1 (HIV-1) related illness and cause of mortality in women of reproductive age in Asia and Africa.1 HIV and TB are independent risk factors for maternal mortality,2 and maternal TBHIV co-infection is an important risk factor for paediatric TB and mortality and may be associated with increased perinatal HIV transmission.3 Studies of both HIV-infected and non-HIV-infected population groups have identified higher TB risk in postpartum than in non-pregnant women; however, risk factors for the development of TB in postpartum women have not been well studied. One such risk factor may be low concentrations of Vitamin D. The induction of antimycobacterial activity by vitamin D within macrophages and upregulated innate responses have been demonstrated in vitro.4 Low vitamin D levels have been associated with higher risks of developing TB, reactivation of TB and poor anti-tuberculosis treatment response.5 However, these associations have been reported inconsistently.6 Pregnant women often have low vitamin D levels,7,8 but it is unknown whether low vitamin D levels in pregnancy are associated with increased risk of postpartum TB. India has both the world’s highest burden of TB1 and a high reported prevalence of vitamin D deficiency in the general population.8 In this casecontrol study, we examined the association between
vitamin D levels and the risk of TB among breastfeeding HIV-infected mothers in India.
METHODS Study population We conducted a retrospective nested case-control study within a cohort of 737 HIV-infected motherinfant pairs enrolled in the Six Weeks Extended Nevirapine (SWEN) India trial funded by the National Institutes of Health (Bethesda, MD, USA).9 The parent trial was conducted between August 2002 and September 2007 at ByramjeeJeejeebhoy Medical College-Sassoon General Hospitals (BJMC-SGH), Pune, India, a large urban public teaching hospital that serves urban, semi-urban and rural populations. In this study, we identified 90 mothers: 30 cases (16 pulmonary TB, 12 extra-pulmonary TB and 2 both) and 60 controls (1:2 case-control ratio). A case was defined as an HIV-infected mother who had developed incident postpartum TB within 12 months of delivery; a control was defined as an HIV-infected mother who did not. Incident TB was defined as a new diagnosis of maternal TB according to the World Health Organization (WHO) definitions of confirmed, probable or suspected TB.10 TB was confirmed if culture was positive and was probable when 1) maternal sputum smear was positive; and 2)
Correspondence to: Vidya Mave, 1st Floor, Pathology Museum, BJ Medical College, Jai Prakash Narayan Road, Pune, Maharashtra 411001, India. Tel: (þ91) 95036 46148. Fax: e-mail: [email protected] Article submitted 4 September 2014. Final version accepted 8 November 2014.
Vitamin D and TB among HIV-infected mothers
303
Table Correlates of postpartum incident TB among HIV-infected mothers who developed TB (cases) and those who did not (controls) in Pune, India
Characteristic Age, years, median [IQR] Education: ,primary Occupation: housewife Religion: Hindu Maternal HAART Vitamin D ,20 ng/ml Vitamin D ,10 ng/ml
Overall (n ¼ 99) n (%)
Cases (n ¼ 30) n (%)
Controls (n ¼ 60) n (%)
23 [19–30] 56 (62) 68 (76) 62 (70) 10 (11) 69 (77) 22 (24)
25 [21–27] 15 (50) 18 (60) 20 (69) 3 (11) 24 (80) 6 (20)
23 [21–25] 41 (68) 50 (83) 42 (70) 7 (12) 45 (75) 16 (27)
OR (95%CI) 1.12 0.44 0.28 0.93 0.76 1.42 0.66
(0.97–1.30) (0.17–1.13) (0.10–0.77) (0.36–2.44) (0.17–3.31) (0.48–4.15) (0.21–2.02)
Adjusted OR* (95%CI) 1.07 (0.91–1.27) Not included 0.33 (0.11–1.002) Not included Not included 1.57 (0.49–4.98) 0.84 (0.26–2.76)
* Adjusted for age and occupation. TB ¼ tuberculosis; HIV ¼ human immunodeficiency virus; OR ¼ odds ratio; CI ¼ confidence interval; IQR ¼ interquartile range; HAART ¼ highly active antiretroviral therapy.
histological and clinical features were suggestive of TB and the patient responded to anti-tuberculosis treatment. All cases and a random selection of 60 controls from among 704 controls with available archived baseline serum samples (within 4 months of delivery) underwent matching for maternal CD4 cell counts (CD46350 and CD4.350 cells/mm3) and maternal HIV viral load (VL) (log10 7 5 and log10 , 5 copies/ ml). We defined vitamin D insufficiency as vitamin D level ,32 ng/ml, moderate deficiency as ,20 ng/ml and severe deficiency as ,10 ng/ml.8 Institutional review board approval was obtained from Johns Hopkins University and BJMC. Laboratory methods Blood samples obtained for the SWEN study at enrolment and/or follow-up were stored at 6708C. Maternal serum 25-hydroxyvitamin D levels were assessed using the DiaSorinw RIA (DiaSorin-25hydroxyvitamin D125I RIA kit, DiaSorin, Saluggia, Italy) method. Statistical analysis Statistical analysis was performed using STATA version 11.1 (StataCorp, College Station, TX, USA), and the results were verified using Splus version 8.1 (TIBCO Software Inc, Palo Alto, CA, USA). Continuous variables were summarised using medians and interquartile ranges (IQR); frequencies (percentages) were used for categorical variables. As the data were matched, baseline variables across cases and controls were compared using McNemar’s v2 test if the variable was categorical; the Wilcoxon matched-pair signedrank test was used to compare medians. Conditional logistic regression analysis was performed to assess the association between 25-hydroxyvitamin D levels and maternal TB, adjusting for age and occupation.
RESULTS Of 90 women who underwent 25-hydroxyvitamin D testing, the median age was 23 years (IQR 19–30);
median CD4 counts and VLs were respectively 342 cells/ml (IQR 220–524) and 8356 copies/ml (IQR 1070–84 234). Among women with TB, median CD4 was 322 cells/ml (IQR 154–412), and it was 374 cells/ ml among those without TB (IQR 259–550) (P ¼ 0.06). Median log 10 VL among women with TB was 4.42 (IQR 3.15–4.92) compared to 3.82 (2.98–5.01) among those without TB (P ¼ 0.40). The median 25-hydroxyvitamin D levels among cases and controls were the same, at 15 ng/ml (IQR 10–19). Among cases and controls, 25-hydroxyvitamin D insufficiency was observed in respectively 29 (97%) and 59 (98%) women, moderate deficiency in 25 (83%) and 49 (82%), and severe deficiency in 6 (20%) and 16 (27%). There were no differences in median 25-hydroxyvitamin D levels across seasons (P ¼ 0.59). Neither moderate (adjusted odds ratio [aOR] 1.78, 95% confidence interval [CI] 0.56–5.67) nor severe (aOR 0.92, 95%CI 0.31–2.7) 25-hydroxyvitamin D deficiency was associated with postpartum incident TB (Table).
DISCUSSION Our study did not find any association between low 25-hydroxyvitamin D levels and postpartum incident TB, adding to the continuing debate as to whether or not vitamin D is associated with TB risk.6 Some prospective studies, including a household contact study in Pakistan, have provided evidence of antecedent vitamin D deficiency and the risk of developing active TB.11–13 A meta-analysis of the published studies, however, was unable to conclusively establish causality between vitamin D levels and TB.6 A few studies from India conducted among non-HIV-infected patients have suggested an association between low vitamin D levels and TB.14,15 However, the lack of association between vitamin D and TB in our study could be explained by the high prevalence of vitamin D insufficiency, deficiency and severe deficiency among Indian HIV-infected mothers with or without TB. Our study underlines the widespread prevalence of vitamin D deficiency in HIV-infected mothers, which
304
The International Journal of Tuberculosis and Lung Disease
may potentially impact placental development, foetal well-being and, possibly, increase the risk of motherto-child HIV transmission or death.7 Several studies from India have reported a high prevalence of vitamin D deficiency (,15 ng/ml) among non-HIV-infected breastfeeding mothers and the general population.7,8 Whether the widespread vitamin D deficiency is one of the reasons for India’s high TB burden needs to be further investigated. It remains unclear whether population-based strategies for vitamin D supplementation, such as food fortification, will improve TB burden and control. Further well-designed prospective trials and longitudinal studies are needed to confirm the role of vitamin D in TB among HIVinfected mothers in India. Acknowledgements The authors thank the study participants and the staff for their immense contribution. This study was supported by the US National Institutes of the Health (NIH), US National Institute of Allergy and Infectious Diseases (R01AI45462) and the NIH-Fogarty International Center NIH Program of International Training Grants in Epidemiology Related to AIDS (D43-TW0000) (Bethesda, MD, USA). VM, NG, NS, VK, RCB, AG are supported by the NIH BJMC HIV Clinical trials Unit (U01 AI069497). VM, NG, AG are also supported by Gilead Foundation (Los Angeles, CA, USA) and the Ujala Foundation (New Town Square, PA, USA). AG and NG are also supported by the US National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA (R 01A1080417). Conflicts of interest: none declared.
References 1 World Health Organization. Global tuberculosis control, 2010. WHO/HTM/TB/2010.7. Geneva, Switzerland: WHO, 2010. 2 Gupta A, Nayak U, Ram M, et al. Postpartum tuberculosis incidence and mortality among HIV-infected women and their infants in Pune, India, 2002–2005. Clin Infect Dis 2007; 45: 241–249. 3 Gupta A, Bhosale R, Kinikar A, et al; Six-Week Extended-Dose
4
5
6
7
8 9
10 11
12
13
14
15
Nevirapine (SWEN) India Study Team. Maternal tuberculosis and mother-to-child transmission of HIV. J Infect Dis 2011; 203: 358–363. Liu P T, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 2006; 311: 1770–1773. Ralph A P, Lucas R M, Norval M. Vitamin D and solar ultraviolet radiation in the risk and treatment of tuberculosis. Lancet Infect Dis 2013; 13: 77–88. Nnoaham K E, Clark A. Low serum vitamin D and tuberculosis: a systematic review and meta-analysis. Int J Epidemiol 2008; 37: 113–119. Mave V, Shere D, Gupte N, et al. Vitamin D deficiency is common among HIV-infected breastfeeding mothers in Pune, India, but is not associated with mother-to-child HIV transmission. HIV Clin Trials 2012; 13: 278–283 Ritu G, Gupta A. Vitamin D deficiency in India: prevalence, causalities and interventions. Nutrients 2014; 6: 729–775. Bedri A, Gudetta B, Isehak A, et al. Extended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda: an analysis of three randomised controlled trials. Lancet 2008; 372: 300–313. World Health Organization. TB/HIV: a clinical manual. WHO/ HTM/TB/2004.329. 2nd ed. Geneva, Switzerland: WHO, 2004. Talat N, Perry S, Parsonnet J, Dawood G, Hussain R. Vitamin D deficiency and tuberculosis progression. Emerg Infect Dis 2010; 16: 853–855. Sudfeld C R, Giovannucci E L, Isanaka S, 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: 378– 385. Mehta S, Mugusi F M, Bosch R J, et al. Vitamin D status and TB treatment outcomes in adult patients in Tanzania: a cohort study. BMJ Open 2013; 3: e003703. Wilkinson R J, Llewelyn M, Toossi Z et al. Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in west London: a casecontrol study. Lancet 2000; 355: 618–621. Rathored J, Sharma S K, Singh B, et al. Risk and outcome of multidrug-resistant tuberculosis: vitamin D receptor polymorphisms and serum 25(OH)D. Int J Tuberc Lung Dis 2012; 16: 1522–1528.
Vitamin D and TB among HIV-infected mothers
i
RESUME
Certaines e´ tudes ont associ´e de faibles taux de vitamine D avec le risque de tuberculose (TB), mais cette association n’a pas e´ t´e bien e´ tudi´ee chez des m`eres infect´ees par le virus de l’immunod´eficience humaine (VIH) dans une r´egion d’end´emie tuberculeuse. Nous avons r´ealis´e une e´ tude cas-t´emoins 1:2 parmi des m`eres infect´ees par le VIH dans l’ouest de l’Inde afin d’´evaluer
l’association entre le taux maternel de vitamine D et le risque de TB postpartum. Un d´eficit en vitamine D, discret, mod´er´e ou grave, a e´ t´e mis en e´ vidence chez une grande proportion de m`eres infect´ees par le VIH, mais il n’´etait pas associ´e a` un risque plus e´ lev´e de TB du postpartum.
RESUMEN
En algunos estudios se ha comunicado una asociacion ´ entre las bajas concentraciones de vitamina D y el riesgo de contraer la tuberculosis (TB). Esta asociacion ´ no se ha estudiado bien en las madres infectadas por el virus de la inmunodeficiencia humana (VIH) en regiones end´emicas de TB. Se llevo´ a cabo un estudio comparativo, anidado (un caso por dos testigos) de las embarazadas infectadas por el VIH en la India occidental, con el objeto de
evaluar la asociacion ´ entre las concentraciones sangu´ıneas de vitamina D y el riesgo de contraer la TB en el puerperio. Se observo´ una alta proporcion ´ de carencia de vitamina D, deficiencia moderada o deficiencia grave, en las madres infectadas por el VIH, pero no se puso en evidencia ninguna asociacion ´ con el riesgo de contraer la TB durante el puerperio.
Vitamin D deficiency and risk of postpartum tuberculosis among HIV-infected breastfeeding mothers in India V. Mave,*† A. Chandanwale,* R. Bhosale,* D. Shere,* N. Gupte,*† N. Suryavanshi,* V. Kulkarni,* A. Kagal,* R. Bharadwaj,* S. Joshi,* R. C. Bollinger,*† A. Gupta,*† for the SWEN (Six Weeks Extended Nevirapine India) and Byramjee-Jeejeebhoy Medical College Clinical Trials Unit Study team *Byramjee-Jeejeebhoy Medical College Clinical Trials Unit, Pune, India; †Johns Hopkins University School of Medicine, Baltimore, Maryland, USA SUMMARY
Some studies have associated low vitamin D levels with the risk of tuberculosis (TB), but its association in human immunodeficiency virus (HIV) infected mothers in a TB-endemic region has not been well studied. We conducted a nested 1:2 case-control study among HIVinfected mothers in western India to evaluate the association between maternal vitamin D levels and the
risk of postpartum TB. Vitamin D insufficiency, moderate deficiency and severe deficiency were observed in a high proportion of HIV-infected mothers, but were not associated with the risk of postpartum TB. K E Y W O R D S : vitamin D deficiency; HIV/AIDS; tuberculosis; India; pregnancy; maternal health
TUBERCULOSIS (TB) is the most common human immunodeficiency virus 1 (HIV-1) related illness and cause of mortality in women of reproductive age in Asia and Africa.1 HIV and TB are independent risk factors for maternal mortality,2 and maternal TBHIV co-infection is an important risk factor for paediatric TB and mortality and may be associated with increased perinatal HIV transmission.3 Studies of both HIV-infected and non-HIV-infected population groups have identified higher TB risk in postpartum than in non-pregnant women; however, risk factors for the development of TB in postpartum women have not been well studied. One such risk factor may be low concentrations of Vitamin D. The induction of antimycobacterial activity by vitamin D within macrophages and upregulated innate responses have been demonstrated in vitro.4 Low vitamin D levels have been associated with higher risks of developing TB, reactivation of TB and poor anti-tuberculosis treatment response.5 However, these associations have been reported inconsistently.6 Pregnant women often have low vitamin D levels,7,8 but it is unknown whether low vitamin D levels in pregnancy are associated with increased risk of postpartum TB. India has both the world’s highest burden of TB1 and a high reported prevalence of vitamin D deficiency in the general population.8 In this casecontrol study, we examined the association between
vitamin D levels and the risk of TB among breastfeeding HIV-infected mothers in India.
METHODS Study population We conducted a retrospective nested case-control study within a cohort of 737 HIV-infected motherinfant pairs enrolled in the Six Weeks Extended Nevirapine (SWEN) India trial funded by the National Institutes of Health (Bethesda, MD, USA).9 The parent trial was conducted between August 2002 and September 2007 at ByramjeeJeejeebhoy Medical College-Sassoon General Hospitals (BJMC-SGH), Pune, India, a large urban public teaching hospital that serves urban, semi-urban and rural populations. In this study, we identified 90 mothers: 30 cases (16 pulmonary TB, 12 extra-pulmonary TB and 2 both) and 60 controls (1:2 case-control ratio). A case was defined as an HIV-infected mother who had developed incident postpartum TB within 12 months of delivery; a control was defined as an HIV-infected mother who did not. Incident TB was defined as a new diagnosis of maternal TB according to the World Health Organization (WHO) definitions of confirmed, probable or suspected TB.10 TB was confirmed if culture was positive and was probable when 1) maternal sputum smear was positive; and 2)
Correspondence to: Vidya Mave, 1st Floor, Pathology Museum, BJ Medical College, Jai Prakash Narayan Road, Pune, Maharashtra 411001, India. Tel: (þ91) 95036 46148. Fax: e-mail: [email protected] Article submitted 4 September 2014. Final version accepted 8 November 2014.
Vitamin D and TB among HIV-infected mothers
303
Table Correlates of postpartum incident TB among HIV-infected mothers who developed TB (cases) and those who did not (controls) in Pune, India
Characteristic Age, years, median [IQR] Education: ,primary Occupation: housewife Religion: Hindu Maternal HAART Vitamin D ,20 ng/ml Vitamin D ,10 ng/ml
Overall (n ¼ 99) n (%)
Cases (n ¼ 30) n (%)
Controls (n ¼ 60) n (%)
23 [19–30] 56 (62) 68 (76) 62 (70) 10 (11) 69 (77) 22 (24)
25 [21–27] 15 (50) 18 (60) 20 (69) 3 (11) 24 (80) 6 (20)
23 [21–25] 41 (68) 50 (83) 42 (70) 7 (12) 45 (75) 16 (27)
OR (95%CI) 1.12 0.44 0.28 0.93 0.76 1.42 0.66
(0.97–1.30) (0.17–1.13) (0.10–0.77) (0.36–2.44) (0.17–3.31) (0.48–4.15) (0.21–2.02)
Adjusted OR* (95%CI) 1.07 (0.91–1.27) Not included 0.33 (0.11–1.002) Not included Not included 1.57 (0.49–4.98) 0.84 (0.26–2.76)
* Adjusted for age and occupation. TB ¼ tuberculosis; HIV ¼ human immunodeficiency virus; OR ¼ odds ratio; CI ¼ confidence interval; IQR ¼ interquartile range; HAART ¼ highly active antiretroviral therapy.
histological and clinical features were suggestive of TB and the patient responded to anti-tuberculosis treatment. All cases and a random selection of 60 controls from among 704 controls with available archived baseline serum samples (within 4 months of delivery) underwent matching for maternal CD4 cell counts (CD46350 and CD4.350 cells/mm3) and maternal HIV viral load (VL) (log10 7 5 and log10 , 5 copies/ ml). We defined vitamin D insufficiency as vitamin D level ,32 ng/ml, moderate deficiency as ,20 ng/ml and severe deficiency as ,10 ng/ml.8 Institutional review board approval was obtained from Johns Hopkins University and BJMC. Laboratory methods Blood samples obtained for the SWEN study at enrolment and/or follow-up were stored at 6708C. Maternal serum 25-hydroxyvitamin D levels were assessed using the DiaSorinw RIA (DiaSorin-25hydroxyvitamin D125I RIA kit, DiaSorin, Saluggia, Italy) method. Statistical analysis Statistical analysis was performed using STATA version 11.1 (StataCorp, College Station, TX, USA), and the results were verified using Splus version 8.1 (TIBCO Software Inc, Palo Alto, CA, USA). Continuous variables were summarised using medians and interquartile ranges (IQR); frequencies (percentages) were used for categorical variables. As the data were matched, baseline variables across cases and controls were compared using McNemar’s v2 test if the variable was categorical; the Wilcoxon matched-pair signedrank test was used to compare medians. Conditional logistic regression analysis was performed to assess the association between 25-hydroxyvitamin D levels and maternal TB, adjusting for age and occupation.
RESULTS Of 90 women who underwent 25-hydroxyvitamin D testing, the median age was 23 years (IQR 19–30);
median CD4 counts and VLs were respectively 342 cells/ml (IQR 220–524) and 8356 copies/ml (IQR 1070–84 234). Among women with TB, median CD4 was 322 cells/ml (IQR 154–412), and it was 374 cells/ ml among those without TB (IQR 259–550) (P ¼ 0.06). Median log 10 VL among women with TB was 4.42 (IQR 3.15–4.92) compared to 3.82 (2.98–5.01) among those without TB (P ¼ 0.40). The median 25-hydroxyvitamin D levels among cases and controls were the same, at 15 ng/ml (IQR 10–19). Among cases and controls, 25-hydroxyvitamin D insufficiency was observed in respectively 29 (97%) and 59 (98%) women, moderate deficiency in 25 (83%) and 49 (82%), and severe deficiency in 6 (20%) and 16 (27%). There were no differences in median 25-hydroxyvitamin D levels across seasons (P ¼ 0.59). Neither moderate (adjusted odds ratio [aOR] 1.78, 95% confidence interval [CI] 0.56–5.67) nor severe (aOR 0.92, 95%CI 0.31–2.7) 25-hydroxyvitamin D deficiency was associated with postpartum incident TB (Table).
DISCUSSION Our study did not find any association between low 25-hydroxyvitamin D levels and postpartum incident TB, adding to the continuing debate as to whether or not vitamin D is associated with TB risk.6 Some prospective studies, including a household contact study in Pakistan, have provided evidence of antecedent vitamin D deficiency and the risk of developing active TB.11–13 A meta-analysis of the published studies, however, was unable to conclusively establish causality between vitamin D levels and TB.6 A few studies from India conducted among non-HIV-infected patients have suggested an association between low vitamin D levels and TB.14,15 However, the lack of association between vitamin D and TB in our study could be explained by the high prevalence of vitamin D insufficiency, deficiency and severe deficiency among Indian HIV-infected mothers with or without TB. Our study underlines the widespread prevalence of vitamin D deficiency in HIV-infected mothers, which
304
The International Journal of Tuberculosis and Lung Disease
may potentially impact placental development, foetal well-being and, possibly, increase the risk of motherto-child HIV transmission or death.7 Several studies from India have reported a high prevalence of vitamin D deficiency (,15 ng/ml) among non-HIV-infected breastfeeding mothers and the general population.7,8 Whether the widespread vitamin D deficiency is one of the reasons for India’s high TB burden needs to be further investigated. It remains unclear whether population-based strategies for vitamin D supplementation, such as food fortification, will improve TB burden and control. Further well-designed prospective trials and longitudinal studies are needed to confirm the role of vitamin D in TB among HIVinfected mothers in India. Acknowledgements The authors thank the study participants and the staff for their immense contribution. This study was supported by the US National Institutes of the Health (NIH), US National Institute of Allergy and Infectious Diseases (R01AI45462) and the NIH-Fogarty International Center NIH Program of International Training Grants in Epidemiology Related to AIDS (D43-TW0000) (Bethesda, MD, USA). VM, NG, NS, VK, RCB, AG are supported by the NIH BJMC HIV Clinical trials Unit (U01 AI069497). VM, NG, AG are also supported by Gilead Foundation (Los Angeles, CA, USA) and the Ujala Foundation (New Town Square, PA, USA). AG and NG are also supported by the US National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA (R 01A1080417). Conflicts of interest: none declared.
References 1 World Health Organization. Global tuberculosis control, 2010. WHO/HTM/TB/2010.7. Geneva, Switzerland: WHO, 2010. 2 Gupta A, Nayak U, Ram M, et al. Postpartum tuberculosis incidence and mortality among HIV-infected women and their infants in Pune, India, 2002–2005. Clin Infect Dis 2007; 45: 241–249. 3 Gupta A, Bhosale R, Kinikar A, et al; Six-Week Extended-Dose
4
5
6
7
8 9
10 11
12
13
14
15
Nevirapine (SWEN) India Study Team. Maternal tuberculosis and mother-to-child transmission of HIV. J Infect Dis 2011; 203: 358–363. Liu P T, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 2006; 311: 1770–1773. Ralph A P, Lucas R M, Norval M. Vitamin D and solar ultraviolet radiation in the risk and treatment of tuberculosis. Lancet Infect Dis 2013; 13: 77–88. Nnoaham K E, Clark A. Low serum vitamin D and tuberculosis: a systematic review and meta-analysis. Int J Epidemiol 2008; 37: 113–119. Mave V, Shere D, Gupte N, et al. Vitamin D deficiency is common among HIV-infected breastfeeding mothers in Pune, India, but is not associated with mother-to-child HIV transmission. HIV Clin Trials 2012; 13: 278–283 Ritu G, Gupta A. Vitamin D deficiency in India: prevalence, causalities and interventions. Nutrients 2014; 6: 729–775. Bedri A, Gudetta B, Isehak A, et al. Extended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda: an analysis of three randomised controlled trials. Lancet 2008; 372: 300–313. World Health Organization. TB/HIV: a clinical manual. WHO/ HTM/TB/2004.329. 2nd ed. Geneva, Switzerland: WHO, 2004. Talat N, Perry S, Parsonnet J, Dawood G, Hussain R. Vitamin D deficiency and tuberculosis progression. Emerg Infect Dis 2010; 16: 853–855. Sudfeld C R, Giovannucci E L, Isanaka S, 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: 378– 385. Mehta S, Mugusi F M, Bosch R J, et al. Vitamin D status and TB treatment outcomes in adult patients in Tanzania: a cohort study. BMJ Open 2013; 3: e003703. Wilkinson R J, Llewelyn M, Toossi Z et al. Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in west London: a casecontrol study. Lancet 2000; 355: 618–621. Rathored J, Sharma S K, Singh B, et al. Risk and outcome of multidrug-resistant tuberculosis: vitamin D receptor polymorphisms and serum 25(OH)D. Int J Tuberc Lung Dis 2012; 16: 1522–1528.
Vitamin D and TB among HIV-infected mothers
i
RESUME
Certaines e´ tudes ont associ´e de faibles taux de vitamine D avec le risque de tuberculose (TB), mais cette association n’a pas e´ t´e bien e´ tudi´ee chez des m`eres infect´ees par le virus de l’immunod´eficience humaine (VIH) dans une r´egion d’end´emie tuberculeuse. Nous avons r´ealis´e une e´ tude cas-t´emoins 1:2 parmi des m`eres infect´ees par le VIH dans l’ouest de l’Inde afin d’´evaluer
l’association entre le taux maternel de vitamine D et le risque de TB postpartum. Un d´eficit en vitamine D, discret, mod´er´e ou grave, a e´ t´e mis en e´ vidence chez une grande proportion de m`eres infect´ees par le VIH, mais il n’´etait pas associ´e a` un risque plus e´ lev´e de TB du postpartum.
RESUMEN
En algunos estudios se ha comunicado una asociacion ´ entre las bajas concentraciones de vitamina D y el riesgo de contraer la tuberculosis (TB). Esta asociacion ´ no se ha estudiado bien en las madres infectadas por el virus de la inmunodeficiencia humana (VIH) en regiones end´emicas de TB. Se llevo´ a cabo un estudio comparativo, anidado (un caso por dos testigos) de las embarazadas infectadas por el VIH en la India occidental, con el objeto de
evaluar la asociacion ´ entre las concentraciones sangu´ıneas de vitamina D y el riesgo de contraer la TB en el puerperio. Se observo´ una alta proporcion ´ de carencia de vitamina D, deficiencia moderada o deficiencia grave, en las madres infectadas por el VIH, pero no se puso en evidencia ninguna asociacion ´ con el riesgo de contraer la TB durante el puerperio.
