{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T04:16:36Z","timestamp":1747196196029,"version":"3.40.5"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T00:00:00Z","timestamp":1641513600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000030","name":"Centers for Disease Control and Prevention","doi-asserted-by":"crossref","award":["#1U51GH001209-01"],"award-info":[{"award-number":["#1U51GH001209-01"]}],"id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Bacillus Calmette-Gu\u00e9rin (BCG) vaccination has recently been found to have beneficial effects among children infected other than <jats:italic>Mycobacterium tuberculosis<\/jats:italic>. Due to the paucity of data on the outcomes of children who had successful BCG vaccination following Expanded Programme on Immunization (EPI) schedule, we aimed to investigate the characteristics of such children and their outcomes who were hospitalized for severe malnutrition.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>A prospective observational study was conducted to determine the viral etiology of pneumonia in severely malnourished children those were admitted to the Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) between April 2015 and December 2017, constituted the study population. Using a case-control design for the analysis, children having BCG vaccination prior hospital admission were treated as cases (n = 611) and those without vaccination, constituted as controls (n = 83). Bi-variate analysis was conducted using socio-demographic, clinical, laboratory, and treatment characteristics on admission and outcomes during hospitalization. Finally, log-linear binomial regression analysis was done to identify independent impact of BCG vaccination.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>The cases more often presented with older age, have had lower proportion of maternal illiteracy, higher rate of breastfeeding, severe wasting and lower rate of hypoglycemia, compared to the controls. The cases were also found to have lower risk of severe sepsis and deaths, compared to the controls (for all, p&lt;0.05). However, in log-linear binomial regression analysis, after adjusting for potential confounders, BCG vaccination following EPI schedule (RR:0.54; 95%CI = 0.33\u20130.89; p = 0.015) and breastfeeding (RR:0.53; 95%CI = 0.35\u20130.81; p = 0.003) were found to be protective for the development of severe sepsis.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>BCG vaccination and breastfeeding were found to be protective for the development of severe sepsis in hospitalized severely malnourished under-five children which underscores the importance of continuation of BCG vaccination at birth and breastfeeding up to two years of age.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0262391","type":"journal-article","created":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T18:33:07Z","timestamp":1641580387000},"page":"e0262391","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Characteristics of severely malnourished under-five children immunized with Bacillus Calmette-Gu\u00e9rin following Expanded Programme on Immunization schedule and their outcomes during hospitalization at an urban diarrheal treatment centre, Bangladesh"],"prefix":"10.1371","volume":"17","author":[{"given":"Mst. Mahmuda","family":"Ackhter","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7759-974X","authenticated-orcid":true,"given":"Abu Sadat Mohammad Sayeem Bin","family":"Shahid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tahmeed","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parag","family":"Palit","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irin","family":"Parvin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Md. Zahidul","family":"Islam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tahmina","family":"Alam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shamsun Nahar","family":"Shaima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5676-3280","authenticated-orcid":true,"given":"Lubaba","family":"Shahrin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farzana","family":"Afroze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monira","family":"Sarmin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shoeb Bin","family":"Islam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zubair","family":"Akhtar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammod Jobayer","family":"Chisti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fahmida","family":"Chowdhury","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,1,7]]},"reference":[{"key":"pone.0262391.ref001","doi-asserted-by":"crossref","DOI":"10.1016\/j.prrv.2020.08.004","article-title":"Bacille Calmette Gu\u00e9rin (BCG) and new TB vaccines: specific, cross-mycobacterial and off-target effects.","author":"N Fritschi","year":"2020"},{"key":"pone.0262391.ref002","first-page":"35","article-title":"Socioeconomic factors associated with full childhood vaccination in Bangladesh, 2014.","volume":"69","author":"ML Boulton","year":"2018"},{"key":"pone.0262391.ref003","first-page":"173","article-title":"Co-administration of BCG and diphtheria-tetanus-pertussis (DTP) vaccinations may reduce infant mortality more than the WHO-schedule of BCG first and then DTP.","volume":"22","author":"P Aaby","year":"2017","journal-title":"A re-analysis of demographic surveillance data from rural Bangladesh."},{"issue":"3","key":"pone.0262391.ref004","first-page":"255","article-title":"Protective vaccination against tuberculosis with special reference to BCG vaccination.","volume":"58","author":"JDJArot Aronson","year":"1948"},{"issue":"1","key":"pone.0262391.ref005","first-page":"5","article-title":"BCG Vaccination of Indian Infants in Saskatchewan.","volume":"30","author":"R Ferguson","year":"1949","journal-title":"(A Study carried out with Financial Assistance from the National Research Council of Canada.)."},{"key":"pone.0262391.ref006","first-page":"413","article-title":"BCG and Vole Bacillus Vaccines in the Prevention of Tuberculosis in Adolescents.","author":"PAJBMJ HART","year":"1956","journal-title":"First (Progress) Report to the Medical Research Council by their Tuberculosis Vaccines Clinical Trials Committee."},{"issue":"6","key":"pone.0262391.ref007","first-page":"517","article-title":"Results of BCG immunization in New York city.","volume":"53","author":"MI Levine","year":"1946"},{"issue":"5","key":"pone.0262391.ref008","first-page":"690","article-title":"BCG vaccination in tuberculous households.","volume":"84","author":"SR Rosenthal","year":"1961"},{"issue":"2","key":"pone.0262391.ref009","first-page":"245","article-title":"Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period?","volume":"204","author":"P Aaby","year":"2011"},{"issue":"10","key":"pone.0262391.ref010","first-page":"1193","article-title":"Heterologous effects of infant BCG vaccination: potential mechanisms of immunity.","volume":"13","author":"E Butkeviciute","year":"2018"},{"issue":"9","key":"pone.0262391.ref011","first-page":"431","article-title":"A small jab\u2013a big effect: nonspecific immunomodulation by vaccines.","volume":"34","author":"CS Benn","year":"2013"},{"issue":"43","key":"pone.0262391.ref012","first-page":"17537","article-title":"Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes.","volume":"109","author":"J Kleinnijenhuis","year":"2012"},{"issue":"5","key":"pone.0262391.ref013","first-page":"355","article-title":"microbe","volume":"9","author":"MG Netea","year":"2011","journal-title":"Trained immunity: a memory for innate host defense."},{"issue":"6","key":"pone.0262391.ref014","first-page":"417","volume":"2","author":"RM Welsh","year":"2002","journal-title":"No one is naive: the significance of heterologous T-cell immunity"},{"issue":"12","key":"pone.0262391.ref015","first-page":"e032844","article-title":"Study protocol for the Melbourne Infant Study: BCG for Allergy and Infection Reduction (MIS BAIR), a randomised controlled trial to determine the non-specific effects of neonatal BCG vaccination in a low-mortality setting.","volume":"9","author":"NL Messina","year":"2019"},{"issue":"4","key":"pone.0262391.ref016","first-page":"2249","article-title":"Newborns develop a Th1-type immune response to Mycobacterium bovis bacillus Calmette-Guerin vaccination.","volume":"163","author":"A Marchant","year":"1999"},{"issue":"2","key":"pone.0262391.ref017","first-page":"152","article-title":"Long-lasting effects of BCG vaccination on both heterologous Th1\/Th17 responses and innate trained immunity.","volume":"6","author":"J Kleinnijenhuis","year":"2014"},{"issue":"12","key":"pone.0262391.ref018","first-page":"1484","article-title":"Infection","volume":"25","author":"N Messina","year":"2019","journal-title":"The impact of vaccines on heterologous adaptive immunity."},{"issue":"11","key":"pone.0262391.ref019","first-page":"1611","article-title":"Nonspecific (heterologous) protection of neonatal BCG vaccination against hospitalization due to respiratory infection and sepsis.","volume":"60","author":"MJ de Castro","year":"2015"},{"issue":"1","key":"pone.0262391.ref020","first-page":"e73","article-title":"Acute lower respiratory infection among Bacille Calmette-Gu\u00e9rin (BCG)\u2013vaccinated children.","volume":"133","author":"M-G Hollm-Delgado","year":"2014"},{"key":"pone.0262391.ref021","article-title":"Systematic review of the non-specific effects of BCG.","author":"J Higgins","year":"2014","journal-title":"DTP and measles containing vaccines"},{"issue":"1","key":"pone.0262391.ref022","first-page":"1","article-title":"Different forms of malnutrition among under five children in Bangladesh: a cross sectional study on prevalence and determinants.","volume":"3","author":"S Das","year":"2017"},{"issue":"2","key":"pone.0262391.ref023","first-page":"e0228329","article-title":"Viral etiology of pneumonia among severely malnourished under-five children in an urban hospital, Bangladesh.","volume":"15","author":"F Chowdhury","year":"2020"},{"issue":"4","key":"pone.0262391.ref024","first-page":"e93776","article-title":"A prospective study of the prevalence of tuberculosis and bacteraemia in Bangladeshi children with severe malnutrition and pneumonia including an evaluation of Xpert MTB\/RIF assay.","volume":"9","author":"MJ Chisti","year":"2014"},{"issue":"2","key":"pone.0262391.ref025","first-page":"277","article-title":"Bacillus Calmette-Guerin vaccination and infant mortality.","volume":"5","author":"A Roth","year":"2006"},{"issue":"2","key":"pone.0262391.ref026","doi-asserted-by":"crossref","first-page":"e0228329","DOI":"10.1371\/journal.pone.0228329","article-title":"Viral etiology of pneumonia among severely malnourished under-five children in an urban hospital, Bangladesh.","volume":"15","author":"F Chowdhury","year":"2020","journal-title":"PloS one"},{"issue":"3","key":"pone.0262391.ref027","doi-asserted-by":"crossref","first-page":"151","DOI":"10.2165\/00128072-200305030-00002","article-title":"Treatment of infectious diarrhea in children.","volume":"5","author":"NH Alam","year":"2003","journal-title":"Pediatric Drugs"},{"key":"pone.0262391.ref028","first-page":"59","article-title":"Treatment of childhood pneumonia in developing countries.","author":"H Ashraf","year":"2010","journal-title":"Health management Sciyo"},{"issue":"5","key":"pone.0262391.ref029","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1111\/apa.15634","article-title":"Early management of hypokalaemia in severely malnourished children under five could help to reduce deaths in developing countries","volume":"110","author":"ASMSB Shahid","year":"2021","journal-title":"Acta Paediatrica"},{"issue":"2","key":"pone.0262391.ref030","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1007\/s00134-009-1738-3","article-title":"The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis.","volume":"36","author":"MM Levy","year":"2010","journal-title":"Intensive care medicine"},{"issue":"10","key":"pone.0262391.ref031","article-title":"Erratum: The international society of heart and lung transplan-tation Guidelines for the management of pediatric heart failure: Executive summary (Journal of Heart and Lung Transplantation (2014) 33: 9 (888\u2013909)).","volume":"33","author":"R Kirk","year":"2014","journal-title":"Journal of Heart and Lung Transplantation"},{"issue":"7","key":"pone.0262391.ref032","doi-asserted-by":"crossref","first-page":"e0181160","DOI":"10.1371\/journal.pone.0181160","article-title":"Clinical outcomes and mortality before and after implementation of a pediatric sepsis protocol in a limited resource setting: A retrospective cohort study in Bangladesh.","volume":"12","author":"TB Kortz","year":"2017","journal-title":"Plos one"},{"issue":"11","key":"pone.0262391.ref033","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1111\/j.1365-3156.2010.02619.x","article-title":"Evaluation of simple laboratory investigations to predict fatal outcome in infants with severe malnutrition presenting in an urban diarrhoea treatment centre in Bangladesh.","volume":"15","author":"MJ Chisti","year":"2010","journal-title":"Tropical Medicine & International Health."},{"issue":"7","key":"pone.0262391.ref034","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1177\/0009922815627346","article-title":"Hypernatremia in children with diarrhea: presenting features, management, outcome, and risk factors for death","volume":"55","author":"MJ Chisti","year":"2016","journal-title":"Clinical pediatrics"},{"issue":"10","key":"pone.0262391.ref035","doi-asserted-by":"crossref","first-page":"e0139966","DOI":"10.1371\/journal.pone.0139966","article-title":"Severe sepsis in severely malnourished young Bangladeshi children with pneumonia: a retrospective case control study.","volume":"10","author":"MJ Chisti","year":"2015","journal-title":"PLoS One"},{"issue":"5","key":"pone.0262391.ref036","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1097\/INF.0b013e3181c91361","article-title":"Randomized trials to study the nonspecific effects of vaccines in children in low-income countries","volume":"29","author":"F Shann","year":"2010","journal-title":"The Pediatric infectious disease journal"},{"issue":"2","key":"pone.0262391.ref037","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.clinthera.2013.01.007","article-title":"Nonspecific effects of vaccines and the reduction of mortality in children","volume":"35","author":"F. Shann","year":"2013","journal-title":"Clinical therapeutics"},{"issue":"6","key":"pone.0262391.ref038","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1111\/j.1651-2227.2009.01281.x","article-title":"Breastfeeding duration and exclusivity associated with infants\u2019 health and growth: data from a prospective cohort study in Bavaria","volume":"98","author":"B Rebhan","year":"2009","journal-title":"Germany. Acta Paediatrica"},{"issue":"1","key":"pone.0262391.ref039","doi-asserted-by":"crossref","first-page":"e18","DOI":"10.1542\/peds.2008-3256","article-title":"Prolonged and exclusive breastfeeding reduces the risk of infectious diseases in infancy","volume":"126","author":"L Duijts","year":"2010","journal-title":"Pediatrics"},{"issue":"3","key":"pone.0262391.ref040","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1136\/adc.88.3.224","article-title":"Breast feeding and respiratory morbidity in infancy: a birth cohort study","volume":"88","author":"W Oddy","year":"2003","journal-title":"Archives of disease in childhood"},{"issue":"1","key":"pone.0262391.ref041","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1046\/j.1442-200X.2002.01504.x","article-title":"Incidence of acute respiratory infections and the relationship with some factors in infancy in Antalya, Turkey.","volume":"44","author":"N Etiler","year":"2002","journal-title":"Pediatrics international"},{"issue":"9","key":"pone.0262391.ref042","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1093\/oxfordjournals.aje.a009540","article-title":"Breastfeeding reduces risk of respiratory illness in infants","volume":"147","author":"AH Cushing","year":"1998","journal-title":"American journal of epidemiology"},{"issue":"2","key":"pone.0262391.ref043","article-title":"Breastfeeding protects against illness and infection in infants and children: a review of the evidence.","volume":"9","author":"WH Oddy","year":"2001","journal-title":"Breastfeeding Review"},{"key":"pone.0262391.ref044","doi-asserted-by":"crossref","first-page":"167","DOI":"10.2147\/NDS.S249045","article-title":"Time to Death and its Predictor Among Children Under Five Years of Age with Severe Acute Malnutrition Admitted to Inpatient Stabilization Centers in North Shoa Zone, Amhara Region, Ethiopia.","volume":"12","author":"YE Ashine","year":"2020","journal-title":"Nutrition and Dietary Supplements"},{"issue":"1821","key":"pone.0262391.ref045","first-page":"20143085","article-title":"Evolution of the immune system in humans from infancy to old age. Proceedings of the Royal Society B","volume":"282","author":"AK Simon","year":"2015","journal-title":"Biological Sciences"},{"issue":"4","key":"pone.0262391.ref046","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1017\/S0950268814001368","article-title":"Lack of BCG vaccination and other risk factors for bacteraemia in severely malnourished children with pneumonia","volume":"143","author":"M Chisti","year":"2015","journal-title":"Epidemiology & Infection"},{"issue":"12","key":"pone.0262391.ref047","doi-asserted-by":"crossref","first-page":"e1655","DOI":"10.1016\/S2214-109X(19)30444-9","article-title":"Potential effect of age of BCG vaccination on global paediatric tuberculosis mortality: a modelling study","volume":"7","author":"P Roy","year":"2019","journal-title":"The Lancet Global Health"},{"issue":"50","key":"pone.0262391.ref048","doi-asserted-by":"crossref","first-page":"7300","DOI":"10.1016\/j.vaccine.2012.09.035","article-title":"Non-specific and sex-differential effects of vaccinations on child survival in rural western India","volume":"30","author":"S Hirve","year":"2012","journal-title":"Vaccine"},{"issue":"30","key":"pone.0262391.ref049","doi-asserted-by":"crossref","first-page":"3098","DOI":"10.1016\/j.vaccine.2013.03.059","article-title":"Non-specific effect of Bacille Calmette-Guerin vaccine on the immune response to routine immunisations","volume":"31","author":"N Ritz","year":"2013","journal-title":"Vaccine"},{"issue":"1","key":"pone.0262391.ref050","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12889-015-1497-8","article-title":"Child survival and BCG vaccination: a community based prospective cohort study in Uganda.","volume":"15","author":"V Nankabirwa","year":"2015","journal-title":"BMC Public Health"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0262391","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T18:33:30Z","timestamp":1641580410000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0262391"}},"subtitle":[],"editor":[{"given":"Frederick","family":"Quinn","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,1,7]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0262391","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2022,1,7]]}}}