Publications by authors named "Mallika Alexander"

11 Publications

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Stages of pregnancy and HIV affect diagnosis of tuberculosis infection and Mycobacterium tuberculosis (MTB)-induced immune response: Findings from PRACHITi, a cohort study in Pune, India.

Int J Infect Dis 2021 Sep 10. Epub 2021 Sep 10.

Byramjee Jeejeebhoy Government Medical College- Johns Hopkins University Clinical Trials Unit, 1st Floor, ENT department, Jai Prakash Narayan Rd. Pune, 411001, Maharashtra, India; Weill Cornell Medical College, 402 E. 67th Street, 2nd floor, New York, NY 10065, USA.

Background: Accurate tuberculosis infection (TBI) tests are critical for pregnant women, especially with HIV, who have a high risk of TB disease.

Methods: We enrolled interferon gamma release assay (IGRA)+ pregnant women with and without HIV in a longitudinal study, followed at delivery and 6 months postpartum. Tuberculin skin test (TST) and IGRA were compared by HIV status at each timepoint.

Results: Of 165 enrolled IGRA+ pregnant women: 35 (21%) had HIV and were on antiretroviral therapy with median CD4 of 476 (IQR 399-586). Compared to antepartum, significantly fewer women remained IGRA+ at delivery [HIV+ n=21/35 (62%, p=0.009); HIV- n=100/130 (77%, p=0.002)] and postpartum [HIV+ n=30/35 (87%, p=0.03); HIV- n=116/130 (89%, p=0.01)]. IGRA/TST discordance was high in pregnant women (HIV+: 51%; HIV-: 25%). Median IFN-γ was lowest for all women at delivery; significantly lower in women with HIV at all timepoints compared to women without HIV. TB incidence was 50/ 1000 person-years and 18/1000 person-years among women with and without HIV respectively.

Conclusions: Pregnancy affects TBI test results and reduces IFN-γ response to M. tuberculosis stimulation. Despite adequate CD4 counts, women with HIV express less IFN-γ than women without HIV , which may explain the high TB incidence in postpartum women with HIV.
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http://dx.doi.org/10.1016/j.ijid.2021.09.010DOI Listing
September 2021

Impact of HIV status on systemic inflammation during pregnancy.

AIDS 2021 Jul 8. Epub 2021 Jul 8.

Department of Epidemiology, Columbia University Mailman School of Public Health, New York, USA Department of Medicine, Weill Cornell Medical College, New York, USA Department of Biostatistics, Columbia University Mailman School of Public Health, New York, USA Department of Obstetrics and Gynecology, Byramjee Jeejeebhoy Government Medical College, Pune, India Byramjee-Jeejeebhoy Government Medical college-Johns Hopkins University Clinical Research Site, Pune, India Instituto Goncalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil Multinational Organization Network Sponsoring Translational and Epidemiological Research, (MONSTER) Initiative, Salvador, Brazil Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Brazil Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Brazil Universidade Salvador (UNIFACS), Laureate Universities, Salvador, Brazil Escola Bahiana de Medicina e Saúde Pública (EBMSP), Salvador, Brazil National Institutes of Health, National Institute for Research in Tuberculosis, International Center for Excellence in Research, Chennai, India Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA.

Objective: There are limited studies on the association of HIV infection with systemic inflammation during pregnancy.

Design: A cohort study (N = 220) of pregnant women with HIV (N = 70) (all on antiretroviral therapy) and without HIV (N = 150) were enrolled from an antenatal clinic in Pune, India.

Methods: The following systemic inflammatory markers were measured in plasma samples using immunoassays: soluble CD163 (sCD163), soluble CD14 (sCD14), intestinal fatty acid-binding protein (I-FABP), C-reactive protein (CRP), alpha 1-acid glycoprotein (AGP), interferon-β (IFNβ), interferon-γ (IFNγ), interleukin (IL)-1β, IL-6, IL-13, IL-17A and tumor necrosis factor α (TNFα). Generalized estimating equation (GEE) and linear regression models were used to assess the association of HIV status with each inflammatory marker during pregnancy and by trimester, respectively.

Results: Pregnant women with HIV had higher levels of markers for gut barrier dysfunction (I-FABP), monocyte activation (sCD14) and markers of systemic inflammation (IL-6 and TNFα), but surprisingly lower levels of AGP, an acute phase protein, compared to pregnant women without HIV, with some trimester-specific differences.

Conclusions: Our data show that women with HIV had higher levels of markers of gut barrier dysfunction, monocyte activation and systemic inflammation. These markers, some of which are associated with preterm birth, might help explain the increase in adverse birth outcomes in women with HIV and could suggest targets for potential interventions.
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http://dx.doi.org/10.1097/QAD.0000000000003016DOI Listing
July 2021

Systemic Inflammation in Pregnant Women With Latent Tuberculosis Infection.

Front Immunol 2020 27;11:587617. Epub 2021 Jan 27.

Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, United States.

Background: Recent studies in adults have characterized differences in systemic inflammation between adults with and without latent tuberculosis infection (LTBI+ . LTBI-). Potential differences in systemic inflammation by LTBI status has not been assess in pregnant women.

Methods: We conducted a cohort study of 155 LTBI+ and 65 LTBI- pregnant women, stratified by HIV status, attending an antenatal clinic in Pune, India. LTBI status was assessed by interferon gamma release assay. Plasma was used to measure systemic inflammation markers using immunoassays: IFN, CRP, AGP, I-FABP, IFN, IL-1, soluble CD14 (sCD14), sCD163, TNF, IL-6, IL-17a and IL-13. Linear regression models were fit to test the association of LTBI status with each inflammation marker. We also conducted an exploratory analysis using logistic regression to test the association of inflammatory markers with TB progression.

Results: Study population was a median age of 23 (Interquartile range: 21-27), 28% undernourished (mid-upper arm circumference (MUAC) <23 cm), 12% were vegetarian, 10% with gestational diabetes and 32% with HIV. In multivariable models, LTBI+ women had significantly lower levels of third trimester AGP, IL1β, sCD163, IL-6 and IL-17a. Interestingly, in exploratory analysis, LTBI+ TB progressors had significantly higher levels of IL1, IL-6 and IL-13 in multivariable models compared to LTBI+ non-progressors.

Conclusions: Our data shows a distinct systemic immune profile in LTBI+ pregnant women compared to LTBI- women. Data from our exploratory analysis suggest that LTBI+ TB progressors do not have this immune profile, suggesting negative association of this profile with TB progression. If other studies confirm these differences by LTBI status and show a causal relationship with TB progression, this immune profile could identify subsets of LTBI+ pregnant women at high risk for TB progression and who can be targeted for preventative therapy.
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http://dx.doi.org/10.3389/fimmu.2020.587617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873478PMC
July 2021

Validation of New Interactive Nutrition Assistant - Diet in India Study of Health (NINA-DISH) FFQ with multiple 24-h dietary recalls among pregnant women in Pune, India.

Br J Nutr 2021 Oct 28;126(8):1247-1256. Epub 2020 Dec 28.

Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY10032, USA.

Adequate dietary intake is critical to prevent adverse pregnancy outcomes. India has a high burden of maternal and child morbidity and mortality, but there is a lack of adequate tools to assess dietary intake. We validate an FFQ, New Interactive Nutrition Assistant - Diet in India Study of Health (NINA-DISH), among pregnant women living with and without HIV in Pune, India. Women were selected from a cohort study investigating immune responses to HIV and latent tuberculosis during pregnancy. The FFQ was administered during the third trimester and validated against multiple 24-h dietary recalls (24-HDR) collected in second and third trimesters. Data for analysis were available from fifty-eight women out of seventy enrolled into this sub-study, after excluding those with incomplete data or implausible energy intake. The median (Q1, Q3) age of study participants was 23 (20, 25) years. Median (Q1, Q3) daily energy intakes were 10 552 (8000, 11 958) and 10 673 (8510, 13 962) kJ by 24-HDR and FFQ, respectively, with FFQ overestimating nutrient intake. Pearson correlations between log-transformed estimates from FFQ and 24-HDR for energy, protein, carbohydrate, fat, Fe and Zn were 0·47, 0·48, 0·45, 0·33, 0·4 and 0·54, respectively. Energy-adjusted and de-attenuated correlations ranged from 0·41 (saturated fat) to 0·73 (Na). The highest misclassification into extreme tertiles was observed for fat (22 %), saturated fat (21 %) and Na (21 %). Bias existed at higher intake levels as observed by Bland-Altman plots. In conclusion, NINA-DISH is a valid and feasible tool for estimating dietary intakes among urban pregnant women in Western India.
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http://dx.doi.org/10.1017/S0007114520005188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236492PMC
October 2021

Association of Vegetable and Animal Flesh Intake with Inflammation in Pregnant Women from India.

Nutrients 2020 Dec 8;12(12). Epub 2020 Dec 8.

Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY 10032, USA.

In pregnant women, studies are lacking on the relationship of vegetable and animal flesh (poultry, red meat and seafood) intake with inflammation, especially in low- and middle-income countries. We conducted a cohort study of pregnant women receiving antenatal care at BJ Medical College in Pune, India. The dietary intake of pregnant women was queried in the third trimester using a validated food frequency questionnaire. Twelve inflammatory markers were measured in plasma samples using immunoassays. Only 12% of the study population were vegetarians, although animal flesh intake levels were lower compared to Western populations. In multivariable models, higher intakes of total vegetables were associated with lower levels of the T-helper (Th) 17 cytokine interleukin (IL)-17a ( = 0.03) and the monocyte/macrophage activation marker soluble CD163 (sCD163) ( = 0.02). Additionally, higher intakes of poultry were negatively associated with intestinal fatty-acid binding protein (I-FABP) levels ( = 0.01), a marker of intestinal barrier dysfunction and Th2 cytokine IL-13 ( = 0.03), and higher seafood was associated with lower IL-13 ( = 0.005). Our data from pregnant women in India suggest that a higher quality diet emphasizing vegetables and with some animal flesh is associated with lower inflammation. Future studies should confirm these findings and test if modulating vegetables and animal flesh intake could impact specific aspects of immunity and perinatal health.
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http://dx.doi.org/10.3390/nu12123767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762525PMC
December 2020

Intensified Short Symptom Screening Program for Dengue Infection during Pregnancy, India.

Emerg Infect Dis 2020 04;26(4):738-743

Mosquitoborne diseases (e.g., malaria, dengue, and chikungunya) are endemic to India and pose diagnostic challenges during pregnancy. We evaluated an intensified short symptom screening program in India to diagnose dengue during pregnancy. During October 2017-January 2018, we screened pregnant women during antenatal surveillance for symptoms of mosquitoborne diseases (fever only, fever with conjunctivitis, fever with rash, or all 3 symptoms) within the previous 15 days. Of 5,843 pregnant women screened, 52 were enrolled and tested for dengue, chikungunya, and Zika viruses by using a Trioplex real-time reverse transcription PCR. Of 49 who had complete results, 7 (14%) were dengue positive. Of these ocular pain was seen in 4 (57%) and conjunctivitis in 7 (100%). Intensified symptom screening using conjunctivitis, in addition to rash, in pregnant women with fever might improve dengue case detection and can be included in routine symptom screening during pregnancy.
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http://dx.doi.org/10.3201/eid2604.191476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101120PMC
April 2020

Screening and diagnosis of gestational diabetes in India: a systematic review and meta-analysis.

Acta Diabetol 2018 Jun 26;55(6):613-625. Epub 2018 Mar 26.

Departments of Medicine and OB-GYN, Weill Cornell Medicine, New York, NY, USA.

Aims: Although diabetes is rapidly increasing in India, there is no national consensus on best practices for screening, diagnosis, and management of gestational diabetes mellitus (GDM). The goal of this study was to systematically review the literature for studies reporting the prevalence and screening and diagnostic methods for gestational diabetes in India.

Methods: We searched MEDLINE, Embase, and POPLINE for studies on screening for GDM in India. We included English-language full reports and conference abstracts of cross-sectional studies, prospective, and retrospective cohorts that reported the screening method and prevalence of GDM. We performed descriptive analysis on all studies and meta-analysis, meta-regression, and subgroup meta-analysis on studies with medium or low risk of bias.

Results: We included 64 studies reporting 90 prevalence estimates. Prevalence estimates ranged from 0 to 41.9%. Subset meta-analyses showed that the IADPSG diagnostic criteria found significantly more GDM cases (prevalence = 19.19% [15.5, 23.6], p < 0.05) than the WHO 1999 criteria (10.13% [8.17, 12.50]) and DIPSI criteria (7.37% [5.2, 10.16]). Studies that compared the IADPSG and WHO 1999 criteria showed poor positive agreement (33-79%). Studies specifying time of GDM diagnosis showed that patients (11-60%) develop GDM as early as the first trimester, but many GDM cases (16-40%) are missed if screened only at first visit.

Conclusions: In India, prevalence estimates of GDM vary substantially by diagnostic criteria. When evaluating screening and diagnostic criteria for GDM, providers should consider their patients' needs and correlate screening criteria with pregnancy outcomes.
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http://dx.doi.org/10.1007/s00592-018-1131-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999405PMC
June 2018

Prevalence of anal human papillomavirus infection among HIV-infected women from India.

J Acquir Immune Defic Syndr 2014 Nov;67(3):e111-4

*Epidemiology & Biostatistics †Microbiology & Clinical Pathology ‡Clinical sciences §National AIDS Research Institute, ICMR, Pune, India.

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http://dx.doi.org/10.1097/QAI.0000000000000328DOI Listing
November 2014

Prevalence of anal human papillomavirus infection among HIV-infected women from India.

J Acquir Immune Defic Syndr 2014 Nov;67(3):e111-4

*Epidemiology & Biostatistics †Microbiology & Clinical Pathology ‡Clinical sciences §National AIDS Research Institute, ICMR, Pune, India.

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http://dx.doi.org/10.1097/QAI.0000000000000328DOI Listing
November 2014

Correlates of premarital relationships among unmarried youth in Pune district, Maharashtra, India.

Int Fam Plan Perspect 2007 Dec;33(4):150-9

Research scientist, KEM Hospital Research Centre, Pune, India.

Context: Although premarital partnerships-whether or not they involve sex-are widely discouraged in India, some youth do form such partnerships. It is important to know more about the nature of and the factors associated with these relationships.

Methods: Data are drawn from a community-based study of 15-24-year-olds in urban slum and rural settings in Pune District, Maharashtra. Multivariate analyses were conducted to identify associations between youths' individual, peer and family factors and their experience of romantic relationships and physical intimacy, including intercourse.

Results: Among young men, 17-24% had had a romantic relationship, 20-26% had engaged in some form of physical intimacy and 16-18% had had sex; the proportions among young women were 5-8%, 4-6% and 1-2%, respectively. Exposure to alcohol, drugs or pornographic films and having more frequent interaction with peers were positively associated with romantic and sexual relationships for both young women and young men. Educational attainment was negatively associated with both types of relationships for young women, but only with sexual relationships for young men. Closeness to parents was negatively associated with relationships only for young women. Young women whose father beat their mother were more likely than other young women to form romantic partnerships, and those beaten by their family had an elevated risk of entering romantic and sexual partnerships. Youth who reported strict parental supervision were no less likely than others to enter relationships.

Conclusions: Program interventions should ensure that youth are fully informed and equipped to make safe choices and negotiate wanted outcomes, while positively influencing their peer networks; encourage closer interaction between parents and children; and be tailored to the different circumstances and experiences of young women and men.
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http://dx.doi.org/10.1363/ifpp.33.150.07DOI Listing
December 2007

Romance and sex: pre-marital partnership formation among young women and men, Pune district, India.

Reprod Health Matters 2006 Nov;14(28):144-55

Research Scientist, KEM Hospital Research Centre, Pune, India.

Using qualitative and survey data in a rural and an urban slum setting in Pune district, India, this paper describes patterns of pre-marital romantic partnerships among young people aged 15-24, in spite of norms that discourage opposite-sex interaction before marriage. 25-40% of young men and 14-17% of young women reported opposite-sex friends. Most young people devised strategies to interact with others, largely from the same neighbourhood. There were wide gender differences with regard to making or receiving romantic proposals, having a romantic partner and experiencing hand-holding, kissing and sexual relations. For those who engaged in sexual relations, the time from the onset of the partnership to having sexual relations was short. Sex most often took place without protection or communication, and for a disturbing minority of young women only after persuasion or without consent. Among those who were unmarried, a large percentage had expected to marry their romantic partner, but for a third of young women and half of young men the relationship had been discontinued. Partnership formation often leads to physical intimacy, but intimacy should be wanted, informed and safe. Findings call for programmes that inform youth in non-threatening, non-judgmental and confidential ways, respect their sexual rights and equip them to make safe choices and negotiate wanted outcomes.
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http://dx.doi.org/10.1016/S0968-8080(06)28265-XDOI Listing
November 2006
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