RESEARCH PROPOSAL

HEARING LOSS AMONG CHILDREN WITH SICKLE CELL ANAEMIA AGED 5 – 16YEARS IN AHMADU BELLO UNIVERSITY TEACHING HOSPITAL (ABUTH),

ZARIA

A PROPOSAL FOR THE PART TWO (FINAL) EXAMINATION OF THE FACULTYOF PAEDIATRICS, NATIONAL POSTGRADUATE MEDICAL COLLEGE OF

NIGERIA

BY

DR. SOLOMON AMOS, MBBS (ABU 2003)

SUPERVISORS

DR. AHMAD HAFSAT RUFAI, FWACP

DEPARTMENT OF PAEDIATRICS,

AHMADU BELLO UNIVERSITY TEACHING HOSPITAL, ZARIA

DR. ABDULKADIR ISA, FMCPaed

DEPARTMENT OF PAEDIATRICS,

AHMADU BELLO UNIVERSITY TEACHING HOSPITAL, ZARIA

DR. AMINU BAKARI, FWACS

DEPARTMENT OF OTORHINOLARYNGOLOGY,

AHMADU BELLO UNIVERSITY TEACHING HOSPITAL, ZARIA

ii

NATIONAL POSTGRADUATE MEDICAL COLLEGE OF NIGERIA

RESEARCH PROPOSAL AND TITLE REGISTRATION ASSESSMENT FORM

PART II CANDIDATE

1. Name of Candidate: DR. SOLOMON AMOS

2. Faculty of Candidate: PAEDIATRICS

3. Name of Training Institute: ABU TEACHING HOSPITAL (ABUTH), ZARIA

4. Address of Training Institute: ABU TEACHING HOSPITAL (ABUTH). ZARIA

5. Name of Supervisor: DR. AHMAD HAFSAT RUFAI

6. Address of Supervisor: DEPARTMENT OF PAEDIATRICS, ABUTH, ZARIA

7. Name of Second Supervisor: DR. ABDULKADIR ISA

8. Second Supervisor Address: DEPARTMENT OF PAEDIATRICS, ABUTH, ZARIA

9. Name of Third Supervisor: DR. AMINU BAKARI

10. Address of Third Supervisor: DEPARTMENT OF E.N.T, ABUTH, ZARIA

11. Month and Year Part 1 Passed: NOVEMBER, 2013

12. Proposed Examination Date: NOVEMBER, 2015

13. Proposed Tittle of Project: HEARING LOSS AMONG CHILDREN WITH SICKLE

CELL ANAEMIA AGED 5 – 16YEARS IN AHMADU BELLO UNIVERSITY TEACHING

HOSPITAL, ZARIA.

iii

TABLE OF CONTENTS

CONTENTS PAGE

TITLE PAGE ii

TABLE OF CONTENTS iii

LIST OF FIGURES iv

DEFINITION OF TERMS v

LIST OF ABBREVIATIONS vi

INTRODUCTION 1

LITERATURE REVIEW 4

AIMS AND OBJECTIVES 20

PROPOSED METHODOLOGY 21

REFERENCES 28

APPENDICES 32

iv

LIST OF FIGURES

FIGURE PAGE

Fig.1 Types of tympanogram 32

Fig.2 Normal Audiogram 33

v

DEFINITIONS OF TERMS

Deaf/Deafness: refers to a person who has a profound hearing loss and uses sign

language.18,51

Hard of hearing: refers to a person with a hearing loss who relies on residual hearing to

communicate through speaking and lip-reading.18, 51

Hearing impaired: is a general term used to describe any deviation from normal hearing,

whether permanent or fluctuating, and ranging from mild hearing loss to profound

deafness.18, 51

Residual hearing: refers to the hearing that remains after a person has experienced a hearing

loss. It is suggested that greater the hearing loss, the lesser the residual hearing.18, 51

Sensorineural hearing loss (SNHL): happens when there is damage to the inner ear

(cochlea) or to the nerve pathways from the inner ear to the brain. Most of the time, SNHL

cannot be medically or surgically corrected. This is the most common type of permanent

hearing loss.18

Conductive hearing loss (CHL): occurs when sound is not sent easily through the outer

ear canal to the eardrum and the tiny bones (ossicles) of the middle ear.18

Mixed hearing loss: occurs when a conductive hearing loss happens in combination with

an SNHL. In other words, there may be damage in the outer or middle ear and in the inner

ear (cochlea) or auditory nerve.18

Degree of hearing loss: range and volume of sounds that are not heard. It ranges from mild

hearing loss to profound deafness or total deafness.51

Configuration of hearing loss: range of pitches or frequencies at which the loss has

occurred. It could Flat, Slopping, Rising or Trough-shaped.51

vi

LIST OF ABBREVIATIONS

ABUTH -Ahmadu Bello University Teaching Hospital

ABR -Auditory brainstem response

BTE -Behind the ear

CHL -Conductive hearing loss

CI -Cochlear implant

dB -Decibel

dBHL -Decibel of hearing loss

daPa -Decapascal

EAC -External auditory canal

ECV -Ear canal volume

EDTA -Ethylene diamine tetraacetic acid

eNOS -Endothelial Nitric oxide Synthase

ET-1 -Endothelial - 1

FM -Frequency modulation

Hb -Haemoglobin

Hb A -Normal haemoglobin phenotype

Hb AS -Heterozygote phenotype

Hb F -Fetal haemoglobin

Hb S -Sickle cell haemoglobin

Hb SS -Homozygous sickle cell haemoglobin

Hz -Hertz

vii

ICAM – 1 -Intracellular cell adhesion molecule - 1

IDT -Infant distraction test

ISC -Irreversibly sickle cell

ISO -International organization for standardization

LH -Labyrinthine haemorrhage

LO -Labyrinthine ossification

MCV -Mean corpuscular haemoglobin

NO -Nitric oxide

NICE -National institute for Health and Clinical Excellence

OAE -Otoacoustic emissions

PTA -Pure tone audiometry

PE -Pressure equalization

PECAM -Platelet Endothelial cell adhesion molecule

RBC -Red blood cell

SCA -Sickle cell anaemia

SCD -Sickle cell disease

S-HPFH -Sickle cell - hereditary persistence of fetal haemoglobin

SNHL -Sensori-neural hearing loss

TM -Tympanic membrane

VCAM – 4 -Vascular cell adhesion molecule - 4

VRA -Visual Reinforcement Audiometer

WHO -World Health Organization

1

INTRODUCTION

Sickle cell disease (SCD) refers to a collection of genetic blood disorders characterized by a

haemoglobin variant called sickle cell haemoglobin (HbS). It is incontrovertible that SCD remains

the most debilitating genetic disorder plaguing the Black race today. Individuals who are affected

with sickle cell anaemia have two copies of this beta globin variant, and the primary haemoglobin

present in their red blood cells is (HbS). Carriers, or heterozygotes (AS individuals), inherit an

HbS allele from one parent and an HbA allele from the other. These individuals are usually

asymptomatic.1 SCD is particularly common among people whose ancestors come from sub-

Saharan Africa; Spanish-speaking regions (South America, Cuba, Central America); Saudi Arabia;

India; and Mediterranean countries such as Turkey, Greece, and Italy.1

Nigeria has the largest number of SCD in the world and recent WHO report shows that one in

every four Nigerians have the sickle cell trait with the potential of transmitting the disorder to their

children. About 2% of all newborn Nigerian children have sickle cell anaemia (SCA) by virtue of

having inherited the sickle cell gene from each parent, giving a total of 150,000 affected children

born every year. 2

SCA is associated with multisystemic complications caused by the resultant vaso-occlusive state

and virtually no system is spared of it long time complications.1 The central nervous system (CNS)

is frequently affected by SCD, particularly in children who are not under optimal care, and the

major pathologies are due to cerebrovascular disease. Because CNS is quite sensitive to hypoxia,

incidence of peripheral and central auditory dysfunction is higher among SCA than the normal

population.3

2

Sensorineural hearing loss (SNHL) is a well-recognized complication of SCD for over 40 years

and it has been reported that patients with SCD have a higher incidence of this complication than

the rest of the population, though in varying degrees of severity.4 The frequency of SNHL ranges

from 3.8% to 29%. In Nigeria, prevalence of SNHL have been documented in 8% (Benin),5 29%

(Enugu),6 21.4% (Ile-Ife),7 and 3.8% (Ilorin) 8 of children with sickle cell anaemia. Other studies

in different part of the world found prevalence of 12% (USA),9 13.5% (United Kingdom),10 19%

(Qatif - Saudi-Arabia),11 21.4% (Saudi Arabia),12 21.7% (Jamaica),13 16% (Kenya)14 and 29%

(Ghana)15 among children with sickle cell anaemia. Studies from developed countries revealed

much lower frequency which may suggest that better care may decrease the incidence of SNHL.

The concern with the early diagnosis of hearing impairment has been a constant issue, since the

loss caused by such impairment, often times is irreversible, affecting not only the speech and

academic performance but child’s global development. Since hearing loss in children may be silent

and hidden, great emphasis is placed on the importance of early detection, reliable diagnosis, and

timely intervention. 16

JUSTIFICATION FOR THE STUDY

Nigeria has one of the largest burden of sickle cell disease in the world and the population growth

rate is still relatively high with high frequencies of HbS so that, the number of AS and SS cases

and associated care costs will substantially increase over the coming decades and with these large

population of children with SCA, SNHL may indeed be common.2, 17

The magnitude of the problem of hearing impairment is indicated by the estimates with regard to

children of school age. In addition there are thousands of children of preschool age with hearing

loss - in many cases undetected during a period when treatment should be under way. Too many

3

children are classified as backward, dull, mal-adjusted misfits, when in reality their difficulty is

attributable to hearing impairment which can be alleviated or, if irreversible, overcome as a

handicap to normal living in society. Early identification and appropriate intervention have been

demonstrated to prevent or reduce many of the adverse consequences and to facilitate language

acquisition and child’s overall development.18, 19

While the prevalence of SNHL among children with sickle cell anaemia in the Western, 8, 20-22

Southern 5 and Eastern 6 part of Nigeria has been documented, such prevalence among children

with SCA in Zaria (Northern Nigeria) is unknown and therefore routine screening of hearing loss

is not part of their routine care. Often, poor performance in school, delayed in language acquisition

and global developments have been blamed largely on absenteeism from school with no emphasis

on possibility of SCA related hearing problems. Hence, this study is aimed at determining the

prevalence and possible risk factors of SNHL among children with Sickle cell anaemia in Zaria.

The findings of this study will help to improve care of children with SCA, and add to the body of

knowledge of paediatrics and child health in Nigeria. It will also help to influence policies with

regards to health care and education of children with SCA in Nigeria and Africa at large.

4

LITERATURE REVIEW

EPIDEMIOLOGY OF SICKLE CELL DISEASE

The highest frequency of SCD is found in tropical regions, particularly sub-Saharan Africa, India

and the Middle-East. Migration of substantial populations from these high prevalence areas to low

prevalence countries in Europe has dramatically increased in recent decades and in some European

countries SCD has now overtaken more familiar genetic conditions such as haemophilia and cystic

fibrosis.17 A recent WHO report estimated that around 2% of newborns in Nigeria were affected

by SCA, giving a total of 150,000 affected children born every year in Nigeria alone. The carrier

frequency ranges between 10% and 40% across equatorial Africa, decreasing to 1–2% on the North

African coast and <1% in South Africa. It is estimated that 2.5 million Americans are heterozygous

carriers for the sickle cell trait and that 90,000 are affected by SCD.23

GENETICS AND ORIGIN OF SICKLE CELL GENE

The sickle cell gene is the result of a point mutation (GAG → GTG) in the sixth codon of the gene

for beta globin. So, the sixth amino acid in the beta chain of haemoglobin S (HbS) is valine, instead

of glutamic acid as found in the usual adult haemoglobin (HbA). This amino acid substitution is

expressed as β6 glu → val. Some, but not all, the haemoglobin variants that interact with HbS to

cause clinical illness (i.e. sickle cell disease, SCD) in the compound heterozygous state also have

amino acid substitutions in the beta globin chain. HbC, a result of the mutation GAG → AAG in

the sixth codon, has lysine as the sixth amino acid of the beta chain; β6 glu →lys. In HbD Punjab

(Los Angeles) glutamine replaces glutamic acid in position 121; β121 glu → gln. HbE is the result

of a similar mutation that gave rise to HbC, but in the 26th codon: β26 glu → lys. HbO-Arab has

a similar amino acid substitution in position 121, β121 glu → lys, and migrates like HbC on

electrophoresis.24

5

PATHOPHYSIOLOGY OF SICKLE CELL ANAEMIA

During the deoxygenation which follows the passage of RBCs in the microcirculation the Hb

molecule undergoes a conformational change. In HbS, replacement of the hydrophilic glutamic

acid at position 6 in the β-globin chain by the hydrophobic valine residue makes that this last one

establishes hydrophobic interactions with other hydrophobic residues on the β-globin chain of

another deoxy-HbS molecule. A polymer forms and lengthens in helical fibres which, grouped

together, stiffen, and induce the characteristic SS-RBC shape change, classically in the shape of a

sickle.25 This process needs a certain time to be primed, the so-called “delay time”, which is

inversely proportional to the intracellular concentration of HbS. The formation of these long

polymer fibres triggers a cascade of several other cellular abnormalities which participate in the

overall pathophysiological mechanism. The rate and extent of polymer formation in a circulating

SS red cell depend primarily on three independent variables: the cell’s degree of deoxygenation,

the intracellular haemoglobin concentration, and the presence or absence of haemoglobin F.26

Formation of the deoxy-HbS polymer fibres triggers a whole series of changes of the red blood

cell membrane with the resultant dysregulation of Red-Cell Volume.27 Dense SS cells are much

more likely to become distorted and rigid and thus contribute disproportionately to the vaso-

occlusive and haemolytic aspects of the disease. SS red cells have increased amounts of calcium

that is compartmentalized within intracellular vesicles, with normal steady-state concentrations of

Ca++ in the cytosol. When the cell membrane is distorted by sickling, however, there is a transient

increase in cytosolic Ca++. This increase is sufficient to trigger the Ca++ -dependent (Gardos) K+

channel, thereby providing a second pathway for sickling induced loss of K+ and water and leading

to cell dehydration. This accelerated in vivo dehydration is the most relevant pathophysiologic

consequence of the membrane lesion in SS red cells.28

6

Anything that retards the transit of SS red cells in the microcirculation can have a critical effect on

the pathogenesis of vaso-occlusion in SCD. Advances in the pathophysiology of SCD revealed

that in addition to the obvious shape changes that result from the formation of intracellular

haemoglobin polymers, the polymers can have a direct impact on the RBC plasma membrane,

leading to the extracellular exposure of protein epitopes and glycolipids that are normally found

inside the cell. These changes and the aberrant expression of adhesion molecules on stress

reticulocytes likely explain the increased adherence of sickle RBC to vascular endothelium. During

the two decades that followed, multiple studies implicated virtually all major adhesion pathways

in the interactions between sickle cells and endothelial cells. These pathways include those

involving the integrins (α4β1, αVβ3)29 and their receptors; immunoglobulin family members

(VCAM-1, ICAM-4);30 the endothelial selectins;31 soluble adhesion proteins such as

thrombospondin,32 fibrinogen,33 fibronectin,34 von Willebrand factor;35 and other exposed

membrane components such as Band-3 and sulfated glycolipids.36 Thus, inasmuch as sickle

adhesion to the endothelium plays a role in sickle cell vaso-occlusion, the presence of such diverse

mechanisms of adhesion presents an enormous challenge for delineating physiologically relevant

therapeutic targets. Interestingly, recent studies have suggested that targeting a specific adhesion

pathway may be sufficient to reduce vaso-occlusion.37

The role of chronic haemolysis in the pathogenesis of SCA is crucial. Free Hb from haemolysis of

sickled RBCs destroys Nitric oxide (NO) and generates free radicals one thousand times more

quickly than Hb in the RBC. This depletion of NO is still majored by the fact that haemolysis also

releases erythroid arginase in plasma where this enzyme degrades L-arginine, the substrate of the

NO producing enzyme, i.e. the endothelial NO synthase (eNOS).38 Thus the mechanism of NO

depletion is double: destruction of NO by free Hb and reduced NO production by depletion of its

7

precursor. Haemolysis-induced NO depletion is responsible for a set of abnormalities, the first of

which being the essential loss of the vasodilator potential, incapable to counteract the

vasoconstrictive action of endothelin-1 (ET-1), but also a facilitation of platelet activation and an

endothelial dysfunction with an abnormal expression of adhesion molecules. There are two sub-

phenotypes of haemolysis-induced NO depletion complications of SCA, one referred to as

“hyperviscosity – vaso-occlusion” and the other one “haemolysis - endothelial dysfunction”, each

associated with different complications of the disease. The first one was preferentially associated

with VOC, acute chest syndrome and femoral head osteonecrosis and the second one with a greater

risk of developing arterial pulmonary hypertension (APHT), a complication with a severe

prognosis and relatively underestimated until then in SCD, leg ulcer, SNHL, priapism, and

possibly stroke. These sub-phenotypes, however, are overlapping and simultaneously present in

all the patients, but certain patients would express preferentially a sub-phenotype with regard to

the other one and would develop preferentially the complications specifically associated to this

sub-phenotype.39

Thus, it is clear that, even though complex abnormal phenomena are at play, HbS is indeed the

basic and the sole defect responsible of the SCD pathology, and in fine of the vaso-occlusive

events. Complications of SCA are enormous through interplay of these molecular phenomena

especially in individuals not receiving optimal comprehensive care.24 the vaso-occlusion of

cochlear vessels by this molecular interplay of sickled RBCs with other cells cause hypoxia and

consequent ischaemic damage and fibrosis to the cochlear structures and overtime lead to

sensorineural hearing loss (cochlear hearing loss).10

8

SICKLE CELL ANAEMIA AND HEARING LOSS

HISTORY AND PATTERN OF SNHL IN SCA

Morgenstein and Menace in 1967 conducted a post mortem histopathological study of temporal

bone of sickle cell disease patients and concluded that the compression of the auditory canal, by

the expanded bone marrow of the petrous temporal bone and ischaemic damage to the hair cells of

organ of corti of the cochlea due to microthrombotic occlusions of the cochlear venous system

could lead to hearing loss.4

The Morgenstein et al study was the first study in the literature to come up with this observation

and linked them to possible cause(s) of sensorineural hearing loss in patients with SCD. The

feasibility of the relationship between sickle cell anaemia and hearing loss encouraged further

aetiopathological and prevalence studies which revealed that SCD patients had a higher incidence

of this complication than the rest of the population, with a variable degree of severity in a

significant proportion of subjects.5, 13, 20

Several pattern of sensorineural hearing loss between 1980 and 2005, among individuals with

sickle cell disease have been described and different aetiopathological processes and risk factors

identified. Some authors report that the hearing deficit concurrent to sickle cell anemia is not

associated with the classic symptoms, but rather to its pathogenesis.20

Although sudden and severe SNHL has been occasionally reported among individual with sickle

cell anaemia crisis, it not the usual pattern observed in SCD and this pattern have been ascribed to

spontaneous labyrinthine haemorrhage, thromboembolism, vasospasm and vascular obstruction of

larger cerebral and cerebellar vessels by the “sickling cells”. Haemorrhagic sudden hearing loss in

a patient with sickle cell disease indicates a sickling crisis of the labyrinthine capillary bed, either

9

in the distribution of the anteroinferior cerebellar artery or a branch of the basilar artery, which

should be considered equivalent to other intracranial sickling events.40, 41

The usual sensori-neural hearing loss complicating sickle cell anaemia is that which is seen in

individual with SCA in relative stable state, it appear ‘silent and hidden’ and running a protracted

course with or without apparent symptoms until profound or total hearing loss set in – the period

at which reversibility become nearly impossible. It is postulated that early and repeated vaso-

occlusive crisis play a vital role in aetiopathogenesis of cochlear hearing loss.7 The fact that the

cochlea is highly sensitive to vessel occlusion and mainly fed by one single artery, the labyrinthine

artery, which can be a terminal artery, makes the inner ear very much prone to circulatory changes,

with resultant ischemia and cochlear anoxia, because of the sickle cells which preclude blood flow

to the cochlear epithelium.7, 11, 13 The hearing loss of this pattern usually affect both ears (bilateral

SNHL) but unilateral cochlear hearing loss complicating SCA have also being reported (having

evaluate and exclude retrocochlear pathology).7, 42

PREVALENCE OF SNHL IN SICKLE CELL ANAEMIA

Sensorineural hearing loss (SNHL) is a well-recognized complication of sickle cell disease, and

many studies have reported a high prevalence of SNHL among those with the disease. SNHL

occurs in 3.8% – 21.4% of children (those younger than 15 years) with sickle cell disease,

compared with 0% – 6.2% in age-matched control groups.6 In adults (those 15 years and older)

with sickle cell disease, the prevalence of SNHL is 46% – 66%, compared with 7.5% – 47% in

control groups.21 These wide ranges of prevalence may be due to the geographic locations of study

populations and the type of haemoglobin gene abnormalities in these patients.5-7

10

In Nigeria, Adekile and Odetoyinbo 7 at Ile-Ife in a prospective study of 56 children with SCA

aged 6-15 years found SNHL greater than or equal to 25dB in two or more frequencies with a

prevalence rate of 21.4%. Pure tone audiometry was used as the major audiologic test and analysis

of the data revealed a significant association between SNHL and homozygous SCD and early

occurrence of first vaso-occlusive crisis (age ≤ 6 years) suggesting that the microvasculature of

the cochlea in young infants may be more susceptible to occlusion during sickle cell crisis.7 The

prevalence rate in this study was much higher than other series from other centers in Nigeria, as

Mgbor and Emodi,6 in Enugu who studied similar age group (6-19 years) of 52 children with

sickle cell anaemia reported 13.4% prevalence rate of SNHL. The authors stressed that

geographical locations (environmental factors), socio-economic class, age differences and

adherence to clinic follow-up might accounted for some of these differences.6

Ogisi and Okafor in Benin,5 compared the auditory function of 30 children with homozygous SCD

to a control group of 20 children with a normal HbAA and found a prevalence rate of 8% SNHL

among homozygous SCD group. Pure tone audiometry and tympanometry was used as method of

evaluation just as for other previous workers however, the prevalence rate of 8% is quite low in

comparism to those found by other workers around the same period.7, 20 Method of recruitment,

small sample size (30 HbSS children) and possibly the geographical locations might accounted for

the low prevalence rate in this study.6

Alabi and Ernest,8 in a prospective study over a one year period at Ilorin evaluated for pattern of

hearing loss among 80 children with homozygous SCA aged 4-15years attending sickle cell clinic

and reported 3.8% prevalence rate of mild bilateral high frequency SNHL among other ear

pathology detected using tympanometry and audiometry hearing tests. The prevalence rate in this

11

study is much lower than the previous and recent studies done in other centers in Nigeria. Even

though the authors stressed that this could be due in part to the fact that the children with SCA in

their study were crisis free and are seen regularly in the clinics and that more than half of the

parents were literate civil servants in the middle socio-economic class who value the importance

of regular clinic follow-up and balanced diets for these children however, the method of

recruitment of the SCA subject over the one year period was not stated and more so the definition

of ‘stable state’ was not given - since less frequent crisis and optimal care invariably lessen the

chance of developing SNHL and may explain the low prevalence rate in this study.7, 20

In other African countries, such as Kenya, Tsibulevskaya et al. 14 demonstrated 40% prevalence

rate (Bilateral SNHL registered 16%) for slow onset SNHL of 30dB and above among 62 Kenya

sickle cell anaemia patients aged 7-30 years. Both sexes were equally affected (in contrast to

Aderibigbe et al. 22 who demonstrated that female SCA persistently had worse hearing threshold

than their male counterparts in all frequencies tested in both right and left ears). The high risk of

deafness in Kenya and other African countries (Astina et al.15 in Ghana reported 29%, and Todd

et al.13 in Jamaica reported 21.7% SNHL), were linked to their specific haematological profile

(Kenya - haplotype 20 with low HbF level and resultant severe and frequent sickle cell crisis), the

level of medical care available and the geographical distribution in the tropics.13-15

In a Saudi Arabia study, Ibrahim and Raj, 11 conducted a prospective case - controlled study in

which 100 patients with sickle cell anaemia, aged 5-40 years were studied. No case of SNHL was

detected in the control group, while it was recorded in 19 (19%) of SCA patients. The study

demonstrated significant association between the SNHL and the onset of first vaso-occlusive crisis

at 6 years of age or less (as suggested by Odetoyinbo and Adekile,7 who found that more than

12

90% of those who developed SHNL had their first vaso-occlusive crisis before the age of 5 years).

They also demonstrated lower HbF and MCV haematological parameters in those with statistically

significant SNHL.11

In USA, Friedman and Herer,9 studied hearing loss among 43 homozygous sickle cell anaemia

patients, aged 7 – 18 years, who received otologic and audiologic examinations. Bilaterally normal

hearing was found in 88% of the sickle cell subjects. Unilateral or bilateral mild high frequency

sensorineural hearing loss was demonstrated in 12% (5 of 43 homozygous SCA). This study and

others from developed countries revealed much lower frequency of this complication and this

finding may suggest that better care may decrease the incidence of SNHL.9, 10

Ajulo et al. 10 in his study in United Kingdom, found SNHL(˃ 20Db) prevalence rate of 13.5%

among 52 homozygous SCA patients studied. The study shows the incidence of SNHL in the UK

to be similar to that reported in the USA and much lower than that found in malaria endemic areas

of the tropics. The authors highlighted the factors which they consider responsible for these

differences and suggest that the crucial period in the development of SNHL in sickle cell disease

may be intra-uterine or during the first few years of life.

POTENTIAL RISK FACTORS FOR SNHL IN SCA

SNHL development and severity have been unarguably linked with such disease modifiers such

that age at first sickle cell crisis and subsequent frequent recurrent vaso-occlusive crisis, parental

level of education and social class, clinic attendance and adherence to routine medications,

specialist and comprehensive care.43

The identifiable risk factors for SNHL as a complication of SCA includes: (1) Beta-globin

genotype inheritance pattern (Children with sickle cell anemia and sickle β0-thalassemia have

13

higher rates of pain, acute chest syndrome, and stroke, and invariably higher prevalence of SNHL

than do those who have sickle-hemoglobin C or sickle β+-thalassemia) ;24 (2) Beta S gene cluster

haplotype (The SEN and Arab-Indian haplotypes are associated with the mildest disease; BEN is

between CAR and SEN. CAR and BEN haplotypes have high incidence of SNHL); 14, 24 (3) Sickle

cell - hereditary persistence of fetal haemoglobin (S-HPFH) - the amount of fetal hemoglobin

(HbF) in the red blood cells modifies the expression of sickle cell disease and decreases, the

clinical severity, complications (SNHL) and mortality in children and adults; 11, 14 (4) Age, sex and

frequency of vaso - occlusive crisis ( ˂ 5years at first onset of vaso - occlusive crisis and subsequent

frequent episodes of vaso - occlusive crisis has been identified as a predisposing factors to

developing SNHL as a complication of SCD); 10 (5) low mean corpuscular volume - chronic

anaemic state with resultant hypoxia involving the inner ear structures can cause cochlear damage

over time. Ibrahim et al.11 in their study found statistically significant relationship between low

MCV and SNHL among the studied group of SCA population.11

AETIOPATHOGENESIS OF SNHL IN SICKLE CELL ANAEMIA

The identifiable specific aetiology for sensorineural hearing loss in sickle cell disease includes:

1. Recurrent vaso-occlusion of the labyrinthine blood vessels: the most accepted pathogenesis

of inner ear involvement is recurrent vaso-occlusion of the labyrinthine artery (an end artery that

supply the inner ear), which can result in labyrinthine haemorrhage (LH) and labyrinthine

ossification (LO). LH is thought to result from altered capillary hemodynamics or reperfusion

injury.44 The association between LH and LO has not been fully demonstrated, but it is theorized

that LH incites a reparative response that cascades from fibrosis to sclerosis and ultimately

ossification of the inner ear structures and resultant SNHL. LH seems to occur in HbSC

predominantly. LO, by contrast, based on observations, seem to be more prevalent among patients

14

with HbSS. Patients with SCA, the most severe type, have more vaso-occlusive episodes in the

inner ear structures and therefore a higher probability of acquiring LO and consequent SNHL.45

2. Petrous temporal bone expansion and compression of auditory canal: Morgenstein et al4,

in the histopathologic examination of temporal bone of SCA patients, concluded that the

compression of the auditory canal, by the expanded and diffusely hyperplastic bone marrow of the

petrous temporal bone and accompanied degenerative ischaemic damage to the hair cells of organ

of corti of the cochlea due to microthrombotic occlusions of the cochlear venous system could lead

to sensorineural hearing loss in individual with SCA.4

3. Chronic anaemia and hypoxic state in sickle cell anaemia: anaemia has been proposed as an

aetiologic factor in sensorineural deafness for many years, but there is little supporting evidence.

Grant commented on anaemia as a cause of slow onset nerve deafness and there have been many

references to chronic anaemic states in association with this type of hearing loss.46 Ibrahim et al,

in their study found statistically significant relationship between low MCV and SNHL among the

studied group of SCA population and proposed that chronic anaemic state and hypoxia involving

inner ear structure is significant in the aetiopathogenesis of cochlear hearing loss in SCD.11 Lower

packed-cell volume in SCD, may put additional hemodynamic stress on SCA patients and probably

predispose them to worse cochlea damage during vaso-occlusive crisis.14

4. Sickle cell disease as a chronic inflammatory disease: Suzuki and Harris,47 investigated the

presence of ICAM-1 within the inner ear following induction of labyrinthitis. They detected the

expression of ICAM-1 within the spiral modiolar vein and collecting venules of the cochlea

suggesting that ICAM-1 expression may play a role in inner ear inflammation. Zhang et al.48

demonstrated VCAM-1 expression on the endothelial surface of the spiral modiolar vein and

15

collecting venules in induced labyrinthitis. VCAM-1 expression persisted for up to 2weeks. Zhang

et al. suggested that VCAM-1 is linked to infiltration of inflammatory cells into the cochlear. Such

an inflammatory response can lead to cochlear damage and hearing loss overtime.48, 49

CLINICAL PRESENTATION OF SNHL IN SICKLE CELL DISEASE

The hearing deficit concurrent to sickle cell anaemia is not associated with the classic symptoms,

but rather to its pathogenesis.40 SCA related hearing loss in children is often a ‘silent and hidden’

handicap. Children with this pattern of hearing loss frequently appear to be normal, and often their

handicaps are not apparent except for periods of acute crisis exercitations and features of sickle

cell disease (sickle cell habitus). Onakoya et al.21 reported that the awareness of SNHL in patients

themselves is very low as was observed in his study in which only 11% could volunteer such

history or have perceived the hearing loss.50

DIAGNOSIS OF SENSORINEURAL HEARING LOSS IN SCD

A comprehensive hearing loss diagnosis consists of four major components, hearing history, visual

inspection (both external and otoscopic), tympanometry and pure tone audiometry.51

Otoscopy of the tympanic membrane (TM) to ascertain integrity, translucency, and the presence

or absence of middle ear disease is a key component of the physical examination for hearing loss.

The otoscopy examination help rule out conductive hearing loss as it evaluate for the functional

state of middle ear structures.52

Once hearing loss is suspected, the degree of loss needs to be quantified. Different modalities are

used to determine hearing in infants, children, and adults. The audiologic tests available for this

are: tympanometry, pure tone audiometry, otoacoustic emissions and auditory brainstem response

testing. Infants and young children may not be able to actively participate during auditory testing

16

and therefore, passive techniques, such as tympanometry, otoacoustic emissions (OAEs), and

auditory brainstem response (ABR) testing, are used.51

Tympanometry determines compliance of the TM and is useful for identifying middle ear effusions

and perforations. It involves a small tube being placed in the child’s ear, through which air is gently

blown. This will test if the eardrum is adequately flexible to allow sounds to pass through to the

inner ear. It therefore, help exclude middle ear problems. Tympanometry is not a test of hearing

and it is important to remember that the purpose of tympanometry in the screening process is to

identify possible disorders in the middle ear with the intention of referral. It is not used as a

diagnostic tool. Results are plotted on a graph called a tympanogram (see appendix I) and

categorized as either a Type A, B, or C. Type A refers to eardrum movement within normal limits.

Type B indicates little or no eardrum movement suggesting fluid in the middle ear space. Type C

refers to a middle ear with negative pressure. Such a tympanogram may be caused by retraction of

the eardrum or blockage of the Eustachian tube. A child with this type of tympanogram is

monitored and may need medical attention.51, 53

Otoacoustic Emissions (OAE) Test is a straightforward procedure that can be done in a few

minutes, offering instant results. It involves an investigative tool being placed into the ear canal,

of which a speaker and microphone are attached. Then, through the speakers, quiet clicking noises

are played, and the microphone records the response of the ear to the sounds. OAEs test the

function of the cochlear outer hair cells and are an excellent screening tool for hearing loss in the

infant or child. The EAC and middle ear must be normal for reliable OAE testing; therefore,

otoscopy must be accomplished before testing. Presence of OAEs indicate normal hearing (with

the exception of auditory neuropathy), whereas their absence suggests a loss of 30 dB or greater.

17

In auditory neuropathy the affected individual has normal OAEs; however, transmission of the

signal through the auditory pathways is impaired producing an abnormal ABR test.51

Auditory brain response (ABR) is a test typically conducted in an audiology clinic, and gives more

comprehensive results than the OAE test. It involves tiny electrical sensors being placed on the

child’s forehead, and on each ear lobe. Earphones are then placed over the ears, through which

quiet clicking noises are played. The sensors measure the response of different areas of the brain

to the sounds. The test takes 30-60 minutes, depending on the hearing threshold and on the

cooperation of the tested person. Since ABR is a time-consuming method, requiring expensive

equipment and specifically trained personnel, this method is not fit for screening. 51

Pure tone audiometry test is a test for children of about 4 -5 years of age, and is used to determine

the threshold of a child’s hearing. It involves headphones being placed over the child’s head, and

the child then having to raise their hand or press a button when they hear a sound played through

headphones. This procedure includes both air and bone conduction testing to determine hearing

sensitivity. Air conduction testing is performed in the soundbooth using either speakers,

headphones, or insert earphones.54 This test evaluates the function of the outer, middle, and inner

ear systems. Bone conduction testing is also performed in the soundbooth but uses a bone

conduction vibrator positioned behind the ear on the mastoid or on the forehead. This test evaluates

the function of the inner ear system. Tones are presented at different pitches ranging from very

low to very high. A threshold is determined at the lowest sound level that the child can hear the

tone 50% of the time. Results are plotted on a graph called an audiogram (see appendix II), and a

pure tone average (PTA) is determined from the thresholds at 500, 1000, and 2000 Hz.54

18

MANAGEMENT OF SENSORINEURAL HEARING LOSS IN SCA

Management of SNHL in children with SCA is multidisciplinary involving different specialists,

with the paediatrician specialist in haemoglobinopathies and Otorhinolaryngologist been the

coordinating head of the team. Management in the form of medical, surgical, and amplification

can have a dramatic impact on function and quality of life for the hearing impaired child..55

Conventional hearing aids are indicated in children with moderate to severe hearing loss inducing

delayed speech or articulation disorders. Throughout the world, there are considerable variation in

practices in the management of children with mild and unilateral hearing losses. Few studies have

systematically addressed the effectiveness of hearing devices (hearing aids or frequency

modulation [FM] system) in the treatment of this population.56

All children with severe to profound hearing loss should be considered for cochlear implantation.

The first paediatric cochlear implant programme was established at the House Ear Institute in 1980.

Currently, more than 80,000 children are CI recipients worldwide. CI is the most effective way to

correct a severe acoustic damage not amendable with conventional hearing aids.57

Indications for cochlear implantation are constantly changing and are influenced by developments

in technology, disease knowledge and experience of the physicians involved. The Guidelines

adopted by most European centres are those issued by the National Institute for Health and Clinical

Excellence (NICE, UK, 2009). In this report, the unilateral CI is recommended for children with

severe-to-profound hearing loss, defined as a hearing threshold higher than 90 dB HL at

frequencies of 2-4 kHz without hearing aids, and without an adequate benefit from hearing aids,

defined for children as no achievement of speech, language and listening skills appropriate for age,

19

developmental stage and cognitive abilities. As part of the assessment, children should also have

had a valid trial with a conventional hearing aid for at least 3 months.58

PROGNOSIS OF SNHL IN SICKLE CELL DISEASE

Diagnosis of SNHL does not mean that these patients will have permanent sequelae. On the other

hand, they need better health care, careful follow-up, good education and regular hearing

assessment. A careful plan by both the paediatrician and the otolaryngologist should be put forward

to suit each patient on his own. The patient may just need reassurance at one end or provision of a

hearing aid, and speech or occupational rehabilitation at the other end.59

PREVENTION OF SENSORINEURAL HEARING LOSS IN SCD

The primary prevention is genetic counselling to discontinue births of sickle cell patients, which

can be achieved by genetic counselling to avoid marriage between carriers of sickle cell trait and

beta thalassaemia minor, and secondarily, prevention of complications. The later can be achieved

by diagnosing at infancy, early penicillin prophylaxis and proper immunization. Proper

Immunization should be started in time. Routine screening evaluations for chronic end-organ

damage (in this case SNHL) should start in mid-childhood.60

Parental education regarding complications is essential and education must be to teach parents to

avoid, anticipate and recognize haemoglobinopathy- related problems in the child. All teaching

must be geared to the client’s level of understanding. Encourage bonding from a very early stage

between the newborn and every member of the family. Parental education includes giving them

basic information on the signs and symptoms of the condition; stressing the importance of

healthcare maintenance such as immunization, diet, hygiene and compliance with prescribed

medications and prophylaxis.50

20

AIMS AND OBJECTIVES OF THE STUDY

General Aim:

To evaluate hearing loss among children with sickle cell anaemia in steady state aged 5 – 16 years

attending the paediatric Haematology clinic of Ahmadu Bello University Teaching Hospital Zaria

using otologic clinical evaluation, tuning fork tests (Weber and Rinne tests), tympanometry and

pure tone audiometry (PTA).

Specific objectives:

The specific objectives of this study are to determine/document:

1. The prevalence of sensori-neural hearing loss among children with sickle cell anaemia in

steady state.

2. The risk factors associated with sensori-neural hearing loss among children with sickle cell

anaemia.

3. The relationship between sensori-neural hearing loss and haematological indices in

children with sickle cell anaemia in steady state.

21

PROPOSED METHODOLOGY

STUDY AREA

The study will be conducted at the Paediatric Haematology clinic of ABUTH, Zaria. ABUTH is a

tertiary center which offers service to people from Zaria and its environs. It also serves as a referral

center to neighbouring states (Katsina, Kano, Niger, Zamfara, Kebbi and Jigawa) as well as people

from other states of the country. The hospital is located in Zaria Local Government of Kaduna

State. Zaria is located within the Guinea savannah belt of Nigeria, about 70 kilometers north of

Kaduna, the capital city of Kaduna State.61

Zaria has population of 408,198 according to the 2006 National population Census figures.62 It is

predominantly populated by the Hausa-Fulani indigenes, most of whom are Muslims and farmers.

The indigenes mostly live within the ancient walled city.63 The non-indigenes come from more

than 120 other Nigerian ethnic groups and are mostly civil servants, traders and craft men. They

live mostly in other areas of Zaria outside the ancient walled city.61

STUDY DESIGN

The study will be a hospital-based cross-sectional case-control study.

STUDY POPULATION

The study population will include children with SCA between the ages of 5 – 16 years in steady

state (subject will be assumed to be in steady state when in a state of wellbeing without any

symptoms or signs suggestive of crisis established by a careful history and complete physical

examination)64, 65 presenting to the haematology clinic in Shika and ICH Banzauzau. Apparently

healthy children within the ages of 5-16years whose phenotype are AA coming for follow-up in

general paediatrics outpatient departments who meet the criteria will be enrolled as controls.

22

Inclusion Criteria

1. All subjects with haemoglobin SS or SS+F aged between 5 and 16years as confirmed by

electrophoresis using cellulose acetate paper at pH 8.6.

2. Subjects in steady state at time of recruitment attending the sickle cell clinics.

Exclusion Criteria

1. Subjects with haemoglobin SS and acute or chronic suppurative otitis media.

2. Subjects with haemoglobin SS and family history of hearing loss, or children who had head

trauma, meningitis, mump (parotid swelling), measles and those on ototoxic drugs.

3. Subjects with haemoglobin SS in acute crisis.

Inclusion criteria for control group

1. All apparently healthy Children aged between 5 and 16years whose phenotype are AA

coming for follow-up in general paediatric outpatient departments.

Exclusion criteria for control group

1. Children with history of head trauma, ear discharge, on ototoxic drugs, or family history

of hearing loss.

2. Children with history of meningitis, mumps (or parotid swelling), measles or previous

history of hearing loss or ear abnormalities.

3. Children with other chronic haemolytic anaemia and malignancies.

All the provision of the Helsinki-declaration shall be obtained (see appendix III, IV & Page 47).66

23

SAMPLE SIZE DETERMINATION

Sample size of the study will be calculated using the formula:67

=మ୮୯

మ

Where:

n = the desired sample size

z = the standard normal deviate, set at 1.96, which corresponds to the 95 percent

confidence level

p = the prevalence of the condition under study

q = 1.0 – p equivalent to the proportion of the population without the condition under study

d = degree of accuracy which will be set at 0.05 for the purpose of this study

No studies on sensorineural hearing loss among children with sickle cell anaemia in Zaria were

found, so a prevalence rate of 8% 5 will be chosen for the purpose of this study. Therefore,

=(1.96)ଶ(0.08)(1 − 0.08)

(0.05)ଶ

n = 113

Thus, a minimum of 113 children with sickle cell anaemia and 113 control group shall be studied.

SAMPLING METHOD

A simple random sampling will be carried out among eligible children with SCA that fulfill the

inclusion criteria, until the total sample size is obtained. Diagnosis of SCA will be based on

24

documented evidence of SCA in patient’s case notes by the attending physician. Controls will be

recruited in the same manner until sample size is obtained.67

DATA COLLECTION PROCEDURE

The study will be explained to each participant and understood, informed consent obtained (see

Appendix III). The researcher would undergo skill acquisition training in ENT department through

Otorhinolaryngologist specialist and clinical audiologist, to be well equip to carry out the research.

Structured Questionnaire: information such as: initials, serial number, age, sex, hospital number,

ethnicity, address religion, and occupation will be obtained. Also, medical history including age

at diagnosis of SCA, age at first vaso – occlusive crisis, number of scheduled clinic missed per

year, school record performance, and number of vaso – occlusive crisis per year, otologic

symptoms and findings, frequency of hospital admission including the cause and course,

estimation of parent’s socioeconomic status using the format described by Olusanya et al.68 Each

patient will have their temperature, weight, height, pulse rate and blood pressure taken as

documented in the proforma (see Appendix V).

Otologic Examination Procedure: The participant will be asked to sit in front of the principal

investigator and made comfortable. Examination of the pinna and external ear cannal (EAC) will

be done using the bright headlight and Heinne’s otoscope with appropriate speculum. Those with

wax obstruction in the ear canal, will have the wax removed before Audiometry and tympanometry

done. Wax obstructing a quarter of per tensa will be taken as significant, and when it totally

covered the tympanic membrane will be termed wax impaction. The participant with intact but

dull/opalescent drum head retracted tympanic membrane (TM) with or without fluid will be termed

otitis media with effusion. Tympanic membrane perforation with or without ear discharge of

25

greater than 2 weeks shall be labeled chronic suppurative otitis media, ear discharge up to 2 weeks

will be labeled acute suppurative otitis media. The exclusion criteria would be applied

appropriately. The services of an audiology technician in the division of otorhinolaryngology of

the department of surgery will be employed, who will be briefed on the study.

Tuning fork tests procedures: The participant will be asked to sit in front of the principal

investigator and made comfortable and procedure explained. The Weber and Rinne tests which are

screening examinations that can assist in differentiating between conductive and sensorineural

deficits will be carried out appropriately.

Tympanometry procedure: the addition of tympanometry to the hearing screening protocol

complements the overall objectives of a hearing screening program (visual inspection, pure-tone

sweep screening, threshold and tympanometry). Two components of tympanometry will be

considered in interpreting results and making referrals. The parameters are Compliance (mobility)

of the ear drum and Pressure (measured in decaPascals (daPa) at which the ear drum moves best).

Otoscopic inspection will be performed prior to tympanometry to identify obstruction of the ear

canal, the presence of Pressure Equalization (PE) tubes or any obvious signs of external or middle

ear disease. Tympanometry will be carried out in all children recruited for the study who were

above 5 years of age using Tymp 87 clinical middle ear analyzer (Hortmann-Neuro-Otometrie).

Tympanometer will be introduced gently into the ear canal to the tympanic membrane having

explained the procedure to the child, parent or the guardian. Child will be instructed not to swallow

or talk during the procedure. The interpretation will be recorded as pass (which signify Ears that

demonstrate normal pressure –compliance curves: Pressure (daPa) → +50 to –150 for

children/adults; Compliance (cm3/ml) → 0.3 to 0.9 (child) and 0.3 to 1.4 (adult); Ear Canal

26

Volume (ECV) → 0.4 to 1.0 (child) and 0.6 to 1.5 (adult) represented on a graph called

tympanogram and tables. All patients with abnormal tympanogram will be excluded from the study

and those who pass the test will proceed to have pure tone audiometry.

Pure tone audiometry procedure: This will be carried out in all children recruited for the study

who were above 5 years of age after the procedure have been fully explained to child and the

parent/guardian/care-giver. PTA will be done in a sound proof booth using a diagnostic

audiometer [ITERA MADSEN SN211149] which has been calibrated to ISO standard (last

calibration done November 2013) on all participants with ambient noise at >30 decibel hearing

level outside the booth. . The sound proof booth to be used will be lit with minimal littering to

minimize the child’s distraction and also well ventilated and large enough to accommodate the

child and parent/guardian, tester, and distractor. The main outcome measure will be presence or

absence of sensorineural hearing loss in the children.

Blood sample collection: the procedure will be explained to the child and their parents or care

givers. 3 milliliter of blood would be taken from the dorsum of the hand or forearm after thorough

cleaning of the site with isopropyl alcohol solution. 3 milliliter of blood will be drawn into 5 mls

syringe affixed to a 21G needle. Gentle pressure would be applied with a clean dry cotton ball after

removing the needle until haemostasis is achieved The blood will be emptied into EDTA bottle

for Complete blood count and Hb electrophoresis (for control group). Phenotype for the children

with SCA will be retrieved through their clinic folders.

INTERPRETATION OF RESULTS

A systematic inspection of the eternal ear and otoscopic examination will be considered Normal

when there is absence of ear discharge, a previously undetected structural deficit, ear canal

27

abnormalities i.e. obstruction, impacted cerumen, foreign object, blood or secretion, stenosis or

atresia; otitis externa, a perforated tympanic membrane (TM) or other abnormality of the TM.69

Tympanometry screening will be reported as Normal (pass) or Abnormal (fail). It will be Normal

when Ears demonstrate normal Pressure – Compliance Curves with: Pressure (daPa) = +50 – 150;

Compliance (cm3/ml) = 0.3 to 0.9; and Ear Canal Volume (ECV) = 0.4 to 1.0. The result will be

regarded as Abnormal when Ear pressure and/or Compliance falls outside the guidelines above.

Those with abnormal tympanogram will be screened out of the study.51

The mean hearing threshold for each octave frequency from 125 to 8000Hertz will be determined

and degree of hearing loss of 25 dB or more in one or more test frequencies from 125 to 8000 Hz

will be considered a hearing loss for the purpose of this study and the results will represented on

graph called audiogram and tables. Furthermore, degree of hearing loss classification will be taken

as: 0-15dBHL (within normal limit); 15-25dBHL (Slight hearing loss); 25-30dBHL (Mild hearing

loss); 30-60dBHL (moderate hearing loss); 60-90dBHL (severe hearing loss); 90-120dBHL

(profound hearing loss); and 120+ (total deafness).70

DATA ANALYSIS

Data obtained from the study will be analyzed using Statistical package for social sciences (SPSS)

version 16 or later versions. Results will be presented in figures, tables and graphs as appropriate.

Student’s t-test will be used to compare means of normally distributed continuous variables, while

chi-square test will be used to establish the relationship between the variables. Level of statistical

significance will be set at p-value of <0.05, 95% confidence interval.

28

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and adults with severe to profound deafness. London: National Health Service. 2009 [cited;

Available from: http://www.nice.org.uk/nicemedia/live/12122/42854/42854.pdf].

59. Urban GE. Reversible sensorineural hearing loss associated with sickle cell crisis. Laryngoscope

1973;83:633–38.

60. Howard A, Pearson MD. Sickle Cell Diseases: Diagnosis and Management in Infancy and

Childhood. Pediatrics in Review 1987;9:121-30.

61. Mortimore MJ. Zaria and its Region - A Nigerian Savannah city and its environment. 1970;4:4.

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63. Ologe KO. Gullies in Zaria area. A preliminary study of headscarp recession. Savannah 1972;1:55-

56.

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during infections. West Afr J Med 2000;19:55-58.

65. Ballas SK More definitions in sickle cell disease: Steady state v base line data. Am J Hematol

2012;87(3):338.

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involving human subjects. Bull World Health Organ 2001;79:373-74.

67. Araoye MO. Research Methodology with Statistics for Health and Social Sciences. 2004, Saw-

Mill, Ilorin, Nigeria: Nathadex Publishers. pg 115-21.

68. Olusanya O, Okpere E, Ezimokhai M. The importance of social class in voluntary fertility control

in a developing country. West Afr J Med 1985;4:205-12.

69. American Academy of Pediatrics, Committee on Practice and Ambulatory Medicine. Hearing

assessment in infants and children: recommendations beyond neonatal screening. AAP

2009;124(4):1253-63.

70. British Association of Otolaryngology and British Society of Audiology. Method for assessment

of hearing disability. Brit. J. Audiol 1983;17:203-12.

32

APPENDIX I

TYPES OF TYMPANOGRAM

Negative 0 Positive

Air Pressure

Figure 1. Tympanogram progressions with various stages of Otitis Media (OM). Type A = Normal, Type

C = Early OM with negative middle air pressure, Type B = Advance OM with fluid. 53

Figure 1. Shows the Tympanogram as a “tent-shaped” graph. The horizontal axis shows negative,

neutral, and positive air pressure. The air pressure units on the horizontal axis are either mm H2O

or decaPascals (daPa). These pressure units are essentially the same in value. The vertical axis

shows compliance (inverse of stiffness), from minimum at the bottom towards maximum as you

go up the axis. The compliance units have is designated in milliliters (ml) or cubic centimeters

(cc’s) of air. Patient don’t swallows, talks, laughs, or coughs etc. during tympanometry test.53

HIGH

LOW

TYPE C

TYPE A

TYPE C GOING TO TYPE B

COMPLIANCE

TYPE B

33

APPENDIX II

NORMAL AUDIOGRAM

Fig. 2: Normal audiogram. 54

Loudness is measured in decibels hearing level (dB HL) and shown on the left side of the

audiogram, loudness ranges from 0 dB HL (very soft) to 110 dB HL (very loud); frequency or

pitch is measured in Hertz (Hz.) and shown from left to right on the audiogram, frequency ranges

from 250Hz (very low pitch) to 8000 Hz (very high pitch). The degree of hearing loss ranges from:

mild, moderate, moderately-severe, severe and profound; the right ear thresholds are recorded on

the audiogram as an O (circle) and the left ear thresholds are represented by an X. In this case, all

thresholds fall within the normal hearing range (0 - 20 dB HL on the vertical axis). 54

34

APPENDIX III

PATIENT INFORMATION SHEET

Sickle cell anaemia is an inherited blood disease. A person with this lifelong blood disease has an

abnormal shaped red blood cell. All complications of the disease can be traced to changes in the

makeup of the red cells that causes it to “sickle” that is to assume a new moon shape, thus making

it unusually fragile and sometimes very rigid.

Hearing loss is among the most disabling complications of sickle cell anaemia in children and its

prevalence reported in various states in Nigeria and worldwide is high when compared to healthy

child without SCD. It is often silent in its occurrence and therefore, not diagnosed early until it is

late. Hearing loss if not diagnosed early and manage appropriately, can affect social,

psychological, and physical development of the child. It will be of benefit to you and your child if

the problem with hearing can be detected on time and manage appropriately.

You will be asked some questions and a questionnaire administered to you about your child and

the child will be examined by the doctor. The study will involve looking at the ears with some

instrument, and attaching some instruments to the ears to assess the hearing. They are non-invasive

painless procedures. No exposure to irradiation. Some small amount of blood will be taken as well.

Additional information will also be obtained from the case note. The tests will be done at no cost

to you. However, there may be pain and discomfort at the site of needle prick for blood collection.

Participation in this study is voluntary, and you may decide to withdraw your child anytime. This

will in no way affect your child’s care in this hospital. Information obtained in this study will be

treated with utmost confidentiality.

THANK YOU.

35

APPENDIX IV

CONSENT FOR PARTICIPATION

I am a resident doctor with Department of paediatrics Ahmadu Bello University Teaching

Hospital, Zaria, I am conducting a research on hearing loss among children with sickle cell

anaemia in Ahmadu Bello University Teaching Hospital, Zaria in order to identify any abnormality

or risk factors for developing hearing loss. It will be appreciated if you give consent to include

your child in this study as a participant.

I have read the information provided in the patient information sheet and has been adequately

explained to me.

I have had the opportunity to ask questions about it and any question I have asked have been

answered to my satisfaction. I voluntarily accept to allow my child to participate in this study and

understand that I have the right to withdraw from the study at any time, without compromising the

quality of care I deserve.

YES ( ) NO ( )

Name of Patients: Hospital Number:

Name of Parent/Caregiver:

Signature/thumb print/ Date:

Name of Researcher:

Signature / Date:

GSM/ Telephone Number:

36

APPENDIX V

PROPOSED PROFORMA

HEARING LOSS AMONG SICKLE CELL ANAEMIA CHILDREN AGED 5-16 YEARS IN

AHMADU BELLO UNIVERSITY TEACHING HOSPITAL, ZARIA.

BIODATA

1. Hospital No. ………..

2. Serial No…………..

3. Date…………………

4. Name (Surname first) ………………….

5. Sex : Female ( ) Male ( )

6. Age (Date of Birth) ……………

7. Date of Birth………….

8. Hb Electrophoresis pattern. SS ( ) AA ( ) SS+f ( )

9. Age at Diagnosis of SCA………………………

10. Stable state haematocrit level …………………..

11. Address (Residential)………………………………………………….........

12. Telephone……………………………………….

13. Ethnicity ……………………………………………………………………

14. Father’s Occupation ……………………………………………………….

15. Father’s Educational level……………………………………………………

16. Mother’s Occupation ……………………………………………………….

17. Mother’s level of Education ……………………………………………….

CLINICAL HISTORY

18. Age at first crisis …………..

19. Number of hospital admission in the past: None ( ) 1 ( ) 2 ( ) 3 ( ) ≥ 4 ( )

37

20. Clinic follow-up and care:

I. Is your child regular on clinic visit YES ( ) NO ( )

II. Is your child regular on routine drugs YES ( ) NO ( )

21. Average number of crisis:

I. Average number of crisis had since diagnosed ………..

II. Type of crisis had – (tick as appropriate)

a. Painful crisis ( )

b. Anaemic crisis ( )

c. Both ( )

22. History of otitis media YES ( ) NO ( )

23. Family history of hearing loss YES ( ) NO ( )

24. History of ear surgery YES ( ) NO ( )

PHYSICAL EXAMINATION

25. Weight (Kg)

26. Height (Cm)

27. Blood pressure (mmHg)

28. Temperature (⁰C)

29. Palour …………………………. YES ( ) NO ( )

30. Jaundice ………………………. YES ( ) NO ( )

OTOLOGIC STATE AND EXAMINATION

31. Facial appearance – Normal YES ( ) NO ( )

32. If NO, Specify ……………………………………………..

33. Auricle – Normal YES ( ) NO ( )

34. If NO, Specify ……………………………………………..

38

35. Tuning fork test Right Ear Left Ear

WEBER TEST ………… ………….

RINNE TEST ………….. ………….

35. Otoscopy assessment Right Ear Left Ear

Otorrhoea ………….. …………..

Auditory Canal ………….. ……………

Tympanic membrane ………….. …………….

36. Hearing tests Right Ear Left Ear

Tympanometry ………….. …………….

PTA (dB) ………….. …………….

LABORATORY RESULTS

37. PCV (%)

38. Hb level (g/dl)

39. RBC

40. WBC

41. Platelet Count

42. Reticulocyte count

43. Reticulocyte index

44. MCV

45. MCH

46. MCHC

39

Application supported by:

a. Head of Department/ Supervisor

Name:

If a fellow, Year of fellowship:

Signature and Date:

b. Second Supervisor

Name:

If a fellow, Year of fellowship:

Signature and Date:

c. Third Supervisor

Name:

If a fellow, Year of fellowship:

Signature and Date:

d. Candidate’s Name:

Signature and Date:

40

HEALTH RESEARCH ETHICS COMMITTEEAHMADU BEILO UNIVERSITY TEACHING HOSPITAL

SHIKA-ZARIA, NIGERIA.E-mail: abuth@yahoo.com Website: www.abuth.org

Chairman of Board; Chlef. Shualb Oyedokun Afolabi Fnii

Chief Medical Director: Prof. Lawal Khalid, MBBS, FMCS, FWACS, FRCS(ED) mni Chairman,

Medical Advisory Committee: Prof. Abdullah! Mohammed, MBBS, FWACP, FICS Director of

Administration: Barr. Ishak Bello, LL.B, BL., LL.M, PGDM.AHAN, FCAI

ABUTH/HREC/TRG /36 27tfl May, 2014

------------------------------ ABUTH HREC FULL ETHICAL CLEARANCE CERTIFICATE

Re: Hearing Loss among Sickle Cell Anaemia Children aged 5-16 years in ABUTH, Zaria.

ABUTH Ethics Committee assigned number: ABUTH/HREC/K66/2014

Name of the principal Investigator: Dr. Solomon Amos

Address of the Principal Investigator: Department of Paediatrics, ABUTH

Zaria.

Date of receipt of valid application: 23th April, 2014Date of meeting when final determinationon ethical approval was made: 20th & 21st of May, 2014

This is to inform you that the research described in the submitted protocol, the consent forms and otherparticipant information materials have been reviewed and given full approval by the Health Research EthicsCommittee.

Please note: this approval dates from 27th May, 2014- 27th May, 2015.

No participant recruitment into this research may be conducted outside these dates.

All informed consent forms in this study must carry the ABUTH HREC number assigned to this research andthe duration of ABUTH HREC approval of the study.

This HREC expects that you submit your application as well as an annual report for ethical clearancerenewal 3 months prior to expiration of study dates. This is to enable you obtain renewal of your approval and avoidinterruption of your research.

If there is delay in starting the research, please inform the ABUTH HREC so that starting dates can beadjusted accordingly.

No changes are permitted in the research without prior approval by ABUTH HREC, except incircumstances outlined in national code for Health Research Ethics: http://www.nhrec.net.

ABUTH HREC reserves the right to conduct compliance assessment visits to your research site without prior

notification.,

Prof. A. I. Mamman

Chairman, ABUTH HREC