Assessment of Immunity to Diphtheria in Mothers And
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ASSESSMENT OF IMMUNITY TO DIPHTHERIA IN MOTHERS AND THEIR NEWBORNS AT THE UNIVERSITY OF BENIN TEACHING HOSPITAL, BENIN CITY. A DISSERTATION SUBMITTED TO THE NATIONAL POST-GRADUATE MEDICAL COLLEGE OF NIGERIA IN PART FULFILMENT OF THE REQUIREMENTS FOR THE AWARD OF THE FELLOWSHIP OF THE COLLEGE IN PAEDIATRICS. BY DR CUMMINGS HENRY MB, BS (ILORIN) 2001. MAY, 2012 i Declaration I hereby declare that this dissertation is original unless otherwise acknowledged. It has not been submitted to any college for the purpose of a fellowship examination. Signature: …………………………………………………… Date:…………………………………………………………. Name of Candidate: Dr CUMMINGS Henry ii Certification We certify that Dr CUMMINGS Henry of the Department of Child Health, University of Benin Teaching Hospital, Benin City, prepared this dissertation under our supervision. FIRST SUPERVISOR: DR (MRS) A. E. SADOH STATUS: CONSULTANT PAEDIATRICIAN/ SENIOR RESEARCH FELLOW ADDRESS: DEPARMENT OF CHILD HEALTH, UBTH, BENIN CITY SIGNATURE: ………………………………………………………. DATE:………………………………………………………. SECOND SUPERVISOR: DR (PROF.) O. OVIAWE STATUS: CONSULTANT PAEDIATRICIAN ADDRESS: DEPARTMENT OF CHILD HEALTH, UBTH, BENIN CITY SIGNATURE: ………………………………………………………. DATE:……………………………………………………………….. iii DEDICATION This book is dedicated to all children who have suffered from diphtheria. Then to my wife, Mrs. Omonigho Cummings and daughter, Efemena for their unwavering support. iv ACKNOWLEDGEMENT To God be the glory for the journey so far. I am heartily thankful to my supervisors- Professor O. Oviawe and Dr (Mrs) A.E. Sadoh for their guidance and support. My appreciation also goes to my teachers – Professors Ibadin M.O, Okolo A.I, Omoigberale A.I, Eregie C.O, Drs Sadoh W.E, Ofovwe G.E, Onyiriuka A.N, Odunvbun M, Iduoriyekemwen N, and to all my consultants; words cannot express the values you have invested in me. To Dr A. Ande of the feto-maternal unit, Obstetrics and Gynaecology department, UBTH, thank you for your valuable support and contribution. To all mothers and their babies who made this work possible, I am eternally grateful. My gratitude also goes to Mr A.O. Oladipo and Dr E.B. Etenobo who assisted in the laboratory aspects of the study. Finally, I wish to express my loving thanks to my wife and daughter for their understanding and encouragement. v Table of Contents Title page……………………………………………………………. i Declaration………………………………………………………….. ii Certification………………………………………………………… iii Dedication…………………………………………………………... iv Acknowledgment…………………………………………………… v Table of contents…………………………………………………… vi List of Tables……………………………………………………….. vii List of Figures………………………………………………………. viii List of Abbreviations……………………………………………….. ix Definition of terms…………………………………………………. .x Summary……………………………………………………………. xii Introduction ………………………………………………………… 1 Literature review ………………………………………………….... 4 Justification of study ………………………………………………. 49 Aims and Objectives ………………………………………………. 51 Subjects and Methods………………………………………………. 52 Data analysis ……………………………………………………….. 65 Results……………………………………………………………… 67 vi Discussion…………………………………………………………... 79 Conclusion………………………………………………………….. 85 Recommendation…………………………………………………… 86 Limitation of study…………………………………………………. 87 Future line of study………………………………………………… 88 References ………………………………………………………….. 89 Appendices ………………………………………………………… 102 vii LIST OF TABLES Page Table I: Socio-demographic characteristics of the subjects (mothers) 68 Table II: Characteristics of babies 69 Table III: Immunity status for diphtheria in mother-baby pairs 70 Table IV: Association between babies’ characteristics and their anti- diphtheria immunity 71 Table V: Association between maternal age groups and anti-diphtheria immunity in mother- baby pairs 74 Table VI: Association between maternal vaccination status and anti-diphtheria immunity in mother- baby pairs 75 Table VII: Association between maternal ethnicity and anti-diphtheria immunity in mother-baby pairs 76 Table VIII: Association between maternal place of abode and anti- diphtheria immunity in mother-baby pairs 76 Table IX: Association between household size and anti-diphtheria immunity in mother-baby pairs 77 Table X: Association between family socio-economic status and anti-diphtheria immunity in mother-baby pairs 78 viii LIST OF FIGURES Page Figure 1: Age distribution of mothers 67 Figure 2: Prevalence of protective immunity in mother-baby pairs 70 Figure 3: Relationship between antibody titres in mother-baby pairs 72 ix List of Abbreviations ANC - Antenatal care ANOVA - Analysis of variance CI - Confidence interval df - degree of freedom DT - Diphtheria-tetanus vaccine (paediatric type) dT - Diphtheria-tetanus vaccine (adult type) DPT - Diphtheria-pertusis-tetanus vaccine D & D - Dubowitz and Dubowitz gestational age estimation chart EIA - Enzyme immunoassay ELISA - Enzyme-linked immunosorbent assay EPI - Expanded Programme on Immunization IgG - Immunoglobulin G IM - Intramuscular IU - International unit IV - Intravenous Kg - kilogram LMP - Last menstrual period ml - Millilitres x NIS - Newly Independent States NPI - National Programme on Immunization OD - Optic density “r” - Pearson correlation coefficient r2 - Regression Tdap - Tetanus-diphtheria-accellular pertusis vaccine UBTH - University of Benin Teaching Hospital UK - United Kingdom USA - United States of America WHO - World Health Organization xi Definition of Terms Diphtheria: An infectious disease due to the bacterium Corynebacterium diphtheriae and its highly potent toxin; characterized by the formation of a highly adherent pseudomembrane on the mucous membrane of the nose, pharynx and sometimes the tracheobronchial tree.1 Infectious disease: A disease capable of being transmitted from person to person, with or without actual contact.1 Infection: Invasion of the body with organisms that have the potential to cause disease.1 Newborn: Synonymous with neonate; refers to an infant aged 28 days or younger.1, 2 Antibody: An immunoglobulin molecule produced by B-lymphoid cells that combines specifically with an antigen.1 Immune: Free from the possibility of acquiring a given infectious disease.1 Immunity: The status or quality of being immune.1 Active immunity: Resistance to disease resulting from previous exposure of an individual to an infectious agent or antigen.1 Passive immunity: Immunity acquired through transfer of antibodies from another person or animal, either naturally, as from mother to fetus, or by intentional inoculation.1 Toxin: A noxious or poisonous substance that is formed or elaborated either as integral part of the cell or tissue (endotoxin), as an extracellular product (exotoxin), xii or as a combination of the two, during the metabolism and growth of certain microorganisms and some higher plants and animal species.1 Toxoid: A toxin that has been treated (commonly with formaldehyde) so as to destroy its toxic property but retain its antigenicity, that is, its capability of stimulating the production of antitoxin antibodies and thus of producing an active immunity.1 Vaccine: Any preparation intended for active immunologic prophylaxis.1 Vaccination: The act of administering a vaccine.1 Immunization: Protection of susceptible individuals from communicable diseases by administration of a vaccine.1 Booster dose: Additional dose given at some time after an initial dose to enhance the effect of the initial dose.1 Epidemic: The occurrence in a community or region of cases of an illness, specific health-related behaviour, or other health-related events clearly in excess of normal expectancy.1 Endemic: Denoting a temporal pattern of disease occurrence in a population in which the disease occurs with predictable regularity with only relatively minor fluctuations in its frequency over time.1 xiii SUMMARY Immunity to diphtheria has been noted to wane with age such that a significant proportion of women of reproductive age have been reported to have inadequate levels of immunity to diphtheria. Thus, it is envisaged that a significant proportion of newborns may inherit inadequate levels of immunity to diphtheria from their mothers. To evaluate this hypothesis, a cross-sectional analytical study was carried out to determine the prevalence of the different levels of anti-diphtheria immunity in mothers and their newborns at the Labour ward of the University of Benin Teaching Hospital (UBTH), Benin City. The study further evaluated the relationship between anti-diphtheria antibody titres in mother-baby pairs as well as associations between some socio-demographic factors and the levels of anti- diphtheria immunity in mothers and their babies. Antibody titres of two hundred and thirty one mother-baby paired sera were assayed using Enzyme-linked immunosorbent assay (ELISA) technique. Data was analyzed using Statistical package for Social sciences (SPSS) version 18.0 with level of significance set at 0.05 or less at 95% confidence interval. As much as 29.9% of both mothers and their babies had no protection (antibody titre < 0.01IU/ml) from diphtheria. Ninety (39.0%) mothers and 107 (46.3% ) babies were inadequately protected (antibody titre < 0.1IU/ml) from diphtheria. The difference in the mean antibody titres of mothers and babies was not found to be statistically significant (p= 0.12). There was a strong positive linear correlation between maternal and newborn antibody titres (“r” = 0.982, p= < 0.0001), such that, as mothers antibody titres increased, those of babies also increased in a linear pattern. Mothers who reside in urban settings had xiv significantly lower mean anti-diphtheria