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Renal Function Impairment As a Manifestation of Severe Malaria in Children Aged 1-5 Years Seen at the University of Benin Teaching Hospital (Ubth), Benin City

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Renal Function Impairment As a Manifestation of Severe Malaria in Children Aged 1-5 Years Seen at the University of Benin Teaching Hospital (Ubth), Benin City RENAL FUNCTION IMPAIRMENT AS A MANIFESTATION OF SEVERE MALARIA IN CHILDREN AGED 1-5 YEARS SEEN AT THE UNIVERSITY OF BENIN TEACHING HOSPITAL (UBTH), BENIN CITY. A DISSERTATION SUBMITTED TO THE NATIONAL POSTGRADUATE MEDICAL COLLEGE OF NIGERIA IN PART FULFILMENT OF THE AWARD OF THE FELLOWSHIP OF THE COLLEGE IN PAEDIATRICS BY IMOLELE VALENTINE EHIMARE MBBS (BENIN) 2000 MAY, 2016 0 DECLARATION I hereby declare that this dissertation is original. It has not been submitted to any other college for the purpose of a fellowship examination. Signature: …………………………………………………… Name of Candidate: Dr IMOLELE, Valentine Ehimare 1 CERTIFICATION We certify that this dissertation was done by Dr IMOLELE Valentine Ehimare of the Department of Child Health, University of Benin Teaching Hospital, Benin City, under our supervision. FIRST SUPERVISOR: M.O. IBADIN STATUS: CONSULTANT/PROFESSOR ADDRESS: DEPARTMENT OF CHILD HEALTH, UBTH, BENIN CITY SIGNATURE: ………………………………………………………. SECOND SUPERVISOR: A.I. OMOIGBERALE STATUS: CONSULTANT/PROFESSOR ADDRESS: DEPARTMENT OF CHILD HEALTH, UBTH, BENIN CITY SIGNATURE: ………………………………………………………. DR. MRS BLESSING ABHULIMHEN-IYOHA HEAD , DEPARTMENT OF PAEDIATRICS UNIVERSITY OF BENIN TEACHING HOSPITAL(UBTH), BENIN CITY SIGNATURE……………………………………………………………… 2 DEDICATION This book is dedicated to Jesus Christ my lord, my savior, and comforter. Also to all children with severe malaria, who had renal function impairment: God shall grant you all speedy recovery, and the love and care that you deserve all the days of your life…Amen 3 ACKNOWLEDGEMENT Thank you Lord for this journey, it wouldn’t have been possible without you. My sincere thanks to my supervisors- Professor M.O Ibadin, and Professor A.I Omoigberale for the time spent in bringing out the best in this work. Also special thanks to the Head of Department, Child Health(Professor Sadoh W) for the huge encouragement and moral support throughout the period of the study. To my teachers- Professors Eregie C.O, Oviawe O.O, Okolo A.I, Ofovwe G.E, Dr Sadoh A.E, Amiegheme R(R.I.P), Onyiriuka A.N, Odunvbun M, Iduoriyekemwen, Okunola, Osarigiagbon, Atimati, Amuabunosi. I thank you all for investing so much in me. Special thanks to Dr Nwaneri D.U for your time and wonderful support, you are deeply appreciated, may God bless you abundantly. Dr Eki-Udoko Fidelis, I appreciate your sincere concern, God shall meet your needs at all times. To Drs Fasoranti, Akpan, Mbarie, Ewa, Umoru, Ighosewe, Oluwabiyi, Akinsete, Medupin, Adanna, Ehirim, Okposio, Azunna ,Ezomo, Eguagie, Anighoro, Adigueme- you have been a great source of inspiration. Thank you Mr Ehigie, for your assistance in the laboratory aspect of this work. God bless you richly. My sincere gratitude goes to my caring father in-law(Edward Egbadon Ijeh), who is resting in the bosom of the Lord, and my ever loving mother in-law(Catherine Omone Ijeh) for her relentless prayers. My siblings-Julie, Dora, Esther who is now resting in the bosom of the lord, and Anselm, for their prayers and encouragement. God bless my parents(Honorable and Mrs D.O. Imolele) for bringing me up as a true child of God. To my beautiful, and adorable wife (Helen), the love of my life, and my lovely children-Odianosen, Eimioshior, Emakhumen and 4 Omotese, who have been the great pillar behind my success. We shall together get to the promise land that God has destined for us. I love you all! TABLE OF CONTENTS Title page ………………………………………………………… … ………i Declaration …………………………………………………………………. ..1 Certification …………………………………………………………………..2 Dedication …………………………………………………………… ……..3 Acknowledgement ………………………………………...………………….4 Table of contents ……………………………………………………………..5 List of Tables ...………………………………………………………… .......6 List of Figures…………………………………………………………… …..7 List of Abbreviations………………….…………………………….………...8 Definition of Terms………………….…………………………….…... ….....9 Summary………………………………………………………….…..……..11 Introduction... ……………………………………………………..……..….12 Justification of research…………………………………………..……........14 Literature review.……………………….……………………………...........15 Aims and Objectives.………………………………………….………….…33 Subjects and Methods…..…………………………………….……………..34 Ethical approval………………………………………………..……………44 Data Handling and Analysis…………………….………………..…………45 Results …………………………………….……………………….…..……46 Discussion ……………………………….…………………………....…….62 Conclusion ………………………………………………………………….69 Recommendations..……………………………….………………….……...70 Limitations of Study …………………………….………………….……....71 Future line of study …………………………….……………………..…….72 References.….………………………………….………………………........73 Appendices …………………………………..…………………………...…87 5 Ethical clearance……………………………………………………………..96 LIST OF TABLES Table I: Criteria for malaria severity as defined by WHO 19 Table II: Age distribution and socio-demographic characteristics of the study population 47 Table III: Symptoms of children with severe malaria , who had ARF, as a form of renal function impairment. 48 Table IV: Signs and laboratory features of children with severe malaria, who had ARF. As a form of renal function impairment. 49 Table V: Symptoms of children with severe malaria, who had abnormal eGFR, as form of renal function impairment. 50 Table VI: Signs and laboratory features of children with severe malaria, who had abnormal eGFR, as a form of renal function impairment. 51 Table VII: Spectrum of symptoms, signs, and laboratory features in children with severe malaria 52 Table VIII :Spectrum of manifestation of severe malaria based on WHO criteria 53 Table IX; Prevalence of proteinuria and haematuria / social class distribution of children with Severe malaria 55 Table X: Prevalence of protein by forms of severe malaria 56 Table X:I Prevalence of haematuria by forms of severe malaria 57 Table XII: Pattern of eGFR by gender in children aged 12-60months with severe Malaria 58 Table XIII: Distribution of eGFR by age in children 12-60months(1-5years) with severe malaria. 59 Table XIV: Distribution of children(according to gender, age group, and social class), with renal function impairment using eGFR values. 61 Table XV: Incidence of acute renal failure by gender, age group and social class. 62 6 LIST OF FIGURES Figure I: Pathophysiology of Renal function impairment(ARF) in severe Malaria 23 7 LIST OF ABBREVIATIONS MDGs-Millinium Development Goals42 RBM – Roll Back Malaria93 MNC - Mononuclear cells93 93 IRBCS – Infected red bood cells ROI – Reactive oxygen intermediates93 NO – Nitric oxide93 RAAS - Reninangiotensin-aldosterone system93 H+ - Hydrogen ion93 8 DEFINITION OF TERMS Endemic Malaria – This is applied to areas where there is a constant incidence of malaria cases and natural transmission over a succession of years.24 Epidemic Malaria – Where the incidence of malaria cases in an area rises rapidly and notably above the usual level or where the disease suddenly occurs in an area previously regarded as non-malarious.24 Imported Malaria – When malaria is acquired outside the area and brought in.24 Malaria Endemicity – Endemicity of malaria describes the amount and severity of malaria in a community or region. It is classified into four categories according to parasite and spleen rate determined in children aged 2-9 years in the population.24 1. Hypoendemicity: Parasite or spleen rate of 0-10 percent. 2. Meosendemicity: Parasite or spleen rate, of between 11-50 percent. 3. Hyperendemicity – Parasite or spleen rate persistently greater than 50 percent with adult spleen rate greater than 25%.24 4. Holoendermicity – Parasite or spleen rate persistently greater than 75% with low adult spleen rate.24 Stable Malaria – Malaria is stable when there is a high degree of transmission, with little or no changes from season to season or year to year. Epidemiological evidence shows that P. 9 falciparum is the dominant parasite in such areas which include many countries of Sub-Sahara Africa. In unstable malaria, malaria transmission varies considerably from year to year or season to season while community immunity is low and epidemics of malaria may occur. Both P. falciparum and P. vivax are found in such areas. Oliguria – urine volume <0.5ml/kg/hr.47 Acute renal failure (ARF) – oliguria and serum creatinine >3mg/dl.47 Glomerular filteration rate(GFR) – Defined by Schwartz as the product of a constant(K) and height(cm), divided by the serum creatinine level(mg/dl), expressed in ml/min/1.73m2.113,114 K for this study age group is 0.55,110 (normal GFR = ≥ 90mls/min/1.73m2, abnormal GFR = <90mls/min/1.73m2).118 Cerebral malaria – Unarousable coma in a child with falciparum malaria, persisting more than 30mins after a generalized convulsion(to make the distinction from transient post ictal phase), and not attributable to any other cause(like trauma, infections which include meningitis and encephalitis, neoplasm, hypoglycemia and drug ingestion like barbiturates). 10 SUMMARY Children suffer the severest forms of malaria the most. Fever and pallor are common features striking the attending Physician. Renal complications which can be life threatening when they occur, even in centers that have facilities for dialysis, may be easily overlooked. To evaluate the extent of renal involvement, a cross-sectional study was carried out on 200 children aged 1-5years(12 to 60months), seen at the University of Benin Teaching Hospital with severe malaria, over a period of 8 months, between September 2012, and May 2013. Urinalysis, serum bilirubin, electrolyte, urea and creatinine, random blood sugar, packed cell volume and blood film for malaria parasites were done for the children. The prevalence
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