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ABSTRACT

The Human immunodeficiency virus (HIV) infection is one of the most important
emerging infections of this century. The human immunodeficiency virus (HIV)
infection causes the Acquired Immune Deficiency Syndrome (AIDS) which is a
systemic disorder characterized by deficiency in cellular immune responses.
Haematological complications that accompanied HIV infections have been
documented to be the second most common causes of morbidity and mortality in
children. The haematological complications such as anaemia, neutropenia and
thrombocytopenia are associated with HIV disease progression and reduced
survival. Hence, this study sought to assess the haematological parameters in HIV
positive ART-naïve children and compare with the HIV negative children. This
study was a prospective observational study involving a total of 200 children (100
test subjects and 100 test controls). Biodata was collected with a proforma
designed by the researcher. Blood samples were collected and analyzed for full
blood count (FBC) and CD4 counts. Data generated were analyzed with Statistical
Package for Social Sciences (SSPS) version 22. The result showed that anaemia
with a prevalence of 60%, is significantly associated with HIV infections unlike
neutropenia and thrombocytopenia. It was also shown that the age of the children
was inversely and significantly associated with anaemia but not with neutropenia
and thrombocytopenia. Likewise, CD4 count was inversely and significantly
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associated with anaemia. It is concluded that anaemia is quite common and more
prominent with decreasing age of the children and it is recommended that
haemoglobin concentration less than 10mg/dl can be used as one of the criteria for
commencement of anti-retroviral medications especially in resource poor centers
or localities where CD4 count is not readily available.

TABLE OF CONTENTS

1. Title……………………………………………………………………..i
2. Attestation………………………………………………………………ii
3. Certification……………………………………………………………..iii
4. Dedication….……………………………………………………………iv
5. Acknowledgement……….………………………………………….…..v
6. Table of Contents….……………………………………….……………vi
7. List of Figures……………………………………………………………ix
8. List of Abbreviations……………………………………………………..xii
9. Abstract…………………………………………………………………..xiv
Chapter One: Introduction…………………………………………………1
1.1 Justification for the Study……………………………………………4
1.2 Aims and Objectives………………………………………………….6
1.2.1. Specific Aim………………………………………………………….6
1.2.2. General Objectives……………………………………………….…..6
Chapter Two: Literature Review……………………………………………7
2.1. Anaemia……………………………………………………………….11
vii
2.2. Thrombocytopenia…………………………………………………….16
2.3. Neutropenia…………………………………………………………….19
2.4. CD4 Count and Cytopenias……………………………………………21
ChapterThree: Methodology…………………………….…………………..25
3.1.0. Study Design…………………………………………………………25
3.2.0. Clinical and Laboratory Data…………………………………….…25
3.3.0. Laboratory Methods…………………………………………………26
3.4.0. Study Area…………………………………………………………..26
3.5.0. Study Site……………………………………………………………27
3.6.0. Study Population…………………………………………………….27
3.7.0. Ethical Clearance and Consent……………………………………….28
3.8.0. Sample Size Estimation………………………………………………28
3.9.0. Inclusion Criteria…………………………………………………….29
3.10.0. Exclusion Criteria…………………………………………………….30
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3.11.0. Data Presentation and Analysis…………………………………….30
Chapter Four: Results………………………………………………………32
4.1.0. Sex and Age Distribution of Subjects and Controls………………..32
4.2.0. Comparison of Haematological Parameters in the
Subjects and Controls……………………………………………….34
4.3.0. Prevalence of Haematological Abnormalities and Their
Associations with Subjects and Controls……………………………37
4.4.0. Comparison of Haematological Parameters in Male and
Female Subjects……………………………………………………..39
4.4.1. Comparison of Haematological Parameters in Male and
Female Controls…………………………………………………….41
4.5.0. Relationship between Age and Haematological Parameters
in the Subjects………………………………………………………43
ix
4.5.1. Relationship between Age and Haematological Parameters
in the Controls……………………………………………………….45
4.6.0. Prevalence of Different Levels of CD4 Counts
in the Subjects…………………………………………….…………..47
4.7.0. Relationship between Levels of Haematological Parameters
and CD4 Counts of the Subjects………………………………………49
4.8.0. Relationship between Levels of Haemoglobin Concentrations
and CD4 Counts of the Subjects……………………………………….51
4.8.1. Relationship between Levels of Absolute Neutrophil Counts
and CD4 Counts of the Subjects……………………………………….53
4.8.2. Relationship between Levels of Platelet Counts
and CD4 Counts of the Subjects……………………………………….55
Chapter Five: Discussions, Conclusion and Recommendation…………………57
Chapter Six: References……………………………………………………..…..62
Chapter Seven: Appendices……………………………………………………..74

CHAPTER ONE

INTRODUCTION
The Human Immunodeficiency Virus (HIV) is one of the most important emerging
infections of this century. The HIV infection causes the Acquired
Immunodeficiency Syndrome (AIDS), which is a systemic disorder characterized
by deficiency in cellular immune responses. It is probably one of the diseases with
multiple impacts on persons, families, communities and the entire society. Over 3
million children were noted to be living with HIV around the world at the end of
2013 (UNAIDS, 2014).
Haematological complications have been documented to be the second most
common causes of morbidity and mortality in HIV positive persons (Adetifa et al,
2006). A variety of haematological manifestations is seen at every stage of HIV
and often life-threatening and impairs the quality of life of these patients (Coyle,
1997). Haematological abnormalities have been documented as strong independent
predictors of morbidity and mortality in HIV infected children (Coyle, 1997).
Although it is not part of the criteria for initiating therapy nor used by the World
Health Organization (WHO) for staging HIV, peripheral blood cell abnormalities
in an abnormal haemogram are important prognostic tools for morbidity in HIV
infection and AIDS (Coyle, 1997). Haematological manifestations in HIV infected
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patients often pose a great challenge in the comprehensive management of such
patients and may cause symptoms that are life-threatening and impair the quality of
life of these patients (Volberding, 2003; Baker, 2003; Levine, 2003). These
complications in HIV infected ART-naïve patients usually result in poor ARTtreatment
outcome when they will eventually become eligible for ART and
strongly predict poor prognosis and increase mortality (Liebman, 2008). These
complications when present must be addressed appropriately and in good time.
Anaemia in children is defined as haemoglobin level less than 10g/dl and is the
most common haematological abnormalities in HIV patients. Its prevalence ranges
from 1.3% to 95%, normocytic normochromic anaemia being the predominant type
followed by microcytic anaemia (Patwardhan et al, 2002). Several factors play a
role in the development of anaemia in patients with HIV including chronic disease,
opportunistic infections, nutritional deficiencies and toxicities from medications
(Patwardhan et al, 2002). The consequences of untreated anaemia may lead to
multisystem disabling symptoms and fatigue, exhaustion, increased risk of HIV
dementia and poor quality of life. On the other hand, survival time in HIV infected
persons may be enhanced after recovery from anaemia (Mocroft et al, 1999).
Thrombocytopenia is defined as platelet level less than 150,000 cells/mm3 and is
the second most frequent complication of HIV infection which is found in 3 to
40% of individual with HIV infection and could occur at any stage of HIV
3
infection. The possible mechanisms that have been reported are immune-mediated
destruction of platelets by antibodies, cross-reacting antibodies that are directed
towards HIV proteins, particularly gp120 and p-24 (Kouri et al, 2008). This type of
platelet destruction is called immune thrombocytopenic purpura (ITP) which is
characterized by low platelet counts with normal haematocrit and white blood cell
count (Liebman, 2007; Stasi, 2007). Thrombocytopenia has been identified as a
strong independent predictor for mortality in HIV positive patients. Increased
platelet destruction due to an autoimmune etiology offers an explanation for the
decrease lifespan of platelets that is observed in the context of HIV-associated
thrombocytopenia (Alcantara, 2009).
Neutropenia is defined as absolute neutrophil count less than 1500 cells/mm3 and is
the most common leucopenia occurring in HIV infected individuals. Neutropenia is
common and its incidence rises from 13% to 44% with disease progression from
HIV to AIDS (Dikshit, 2009). HIV infection suppresses the bone marrow and
leads to decreased levels of granulocyte colony-stimulating factor, the factor that
stimulates production of white blood cells in the bone marrow and affects the
granulocte-macrophage lineage, resulting in leucopenia and neutropenia (Dikshit,
2009). Neutropenia can also result from other opportunistic infections including
cytomegalovirus, tuberculosis, histoplasmosis and leishmaniasis. Hence, HIV
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patients with cytopenias may require bone marrow examination to determine the
cause and to direct therapy (Dikshit et al, 2009).
Low CD4 count is defined as CD4 count less than 500 cells/mm3. Low CD4 count
has been associated with prevalent anaemia, neutropenia and thrombocytopenia
(Levine et al, 2001). HIV preferentially infects CD4 cells causing their destruction.
It has been calculated that each day, more than 1 billion CD4 cells are destroyed.
The decline in CD4 count is linked to viral load and is used as a measure of disease
progression (Davidson’s principles and practice of medicine, 2009).
Although haematological abnormalities are common manifestations of HIV
infection and may have considerable impact on patients’ well being, treatment and
care, few studies on haematological parameters in HIV infected children have been
undertaken in Africa especially in Nigeria but none in Enugu, to the best of
author’s knowledge. Such information for HIV infected children in Enugu may
help to forestall potential treatment failure later.
1.1 Justification of the Study
Africa is the epicenter of the HIV epidemic as reported by the World Health
Organization (WHO) and Sub Saharan Africa contributes about 60% of the burden
worldwide. About 3.4 million Nigerians were living with the virus in 2012 which
represents a national prevalence of 5.8% (WHO, 2012).
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Haematological complications such as anaemia, neutropenia and thrombocytopenia
are associated with HIV disease progression and subsequent reduced survival
(Adetifa et al, 2006). Anaemia has been reported to influence the natural history of
HIV disease by increasing the rate of disease progression and mortality in both
developed and developing countries. It has been noted that large decline in platelet
level in HIV positive patient is a pointer for later development of HIV induced
CNS disease which is by all means catastrophic to the patients. (Liebman et al,
2008). These complications in HIV infected ART naïve patients usually result in
poor ART- treatment outcome when they will eventually become eligible for ART
and strongly predict poor prognosis and increase mortality. These complications
when present must be addressed appropriately and in good time.
Studies on haematological problems in HIV infected children are very scanty in
Nigeria, hence the compelling need to carry out this vital and essential study and
hopefully go a long way in averting the potential problems this might cause to the
patients. This study will also provide baseline information for the country as well
as provide data on which further studies on the topic can be developed.
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1.2 Aims and Objectives
1.2.1 Specific Aim
To study the effects of Human Immunodeficiency Virus (HIV) infection on
haematological parameters in HIV positive ART-naive children seen at University
of Nigeria Teaching Hospital (UNTH), Enugu.
1.2.2 General Objectives
1. To assess the level of haemoglobin concentration in an ART-naïve HIV
positive patients and compare to the uninfected patients (control).
2. To assess the level of absolute neutrophil count (ANC) in an ART-naïve
HIV positive patients and compare to the control.
3. To assess the level of platelet count in an ART-naïve HIV positive patients
and compare to the control.
4. To relate the haematological complications with the level of CD4 counts

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