Medicine and Health Sciences Commons^™

Relationship Between Crown Like Structures And Body Mass Index In Breast Cancer, Sophie Wanjiru Irungu

Theses & Dissertations

Introduction: Breast cancer (BC) is the most common malignancy in women worldwide, including Kenya. Globally, increasing incidences of BC have paralleled those of obesity. The mechanism by which obesity contributes to BC is still an active area of research but white adipose tissue inflammation characterized by crown-like structures (CLS), which are macrophages surrounding dying adipocytes, is considered an important contributor.

Objectives: The primary objective was to determine the association between CLS and body mass index (BMI) in BC patients. The secondary objectives were to determine the association of CLS with BC risk factors specifically, age, menopausal status, subtypes of BC, …

The Association Of Immune And Genomic Biomarkers And Response To Neoadjuvant Chemotherapy In Breast Cancer Patients At Aga Khan University Hospital Nairobi, Catherine Wairimu Mutahi

Theses & Dissertations

Introduction: Breast Cancer (BC) is the most diagnosed cancer among women worldwide and in Kenya. It is a highly heterogeneous disease requiring patient specific treatment and strategies to monitor response to therapy, especially in the neoadjuvant (NAC) setting. Currently, there are no reliable markers in use that can predict response to chemotherapy among patients receiving NAC. Tumour Infiltrating Lymphocytes (TILs) and Cell free DNA (cfDNA) are biomarkers that could possibly bridge this gap. However, limited studies have been carried out on the African population. With the increasing mortality rates attributable to BC in Sub-Saharan Africa, coupled with the growing preference …

A Pilot Study Comparing Pre-Analytic Tissue Processes Before And After Implementation Of A Quality Improvement Program For Handling Breast Cancer Specimens, Joseph Gatheru Macharia

Theses & Dissertations

Background: Breast cancer as the most frequently occurring cancer in women is highly heterogeneous in its pathological characteristics. Assessment of tumor biologic characteristics including hormone receptor profile and growth factor receptor activity is important in characterizing the pathologic nature of such cancers. Tumor biomarker activity plays a big role in diagnosis and management of invasive breast cancer (IBC). Biological specimens are the primary sources of this molecular information. Optimal handling of the specimen through the various analytic phases assures of the validity of the final pathologic diagnosis.

Objective: To assess the feasibility of implementing an intervention plan to improve specific …

Comparison Of Two Immunoassays For Detection Of Anti-Sars Cov-2 Antibodies Among Healthcare Workers At A Tertiary Referral Hospital In Nairobi, Kenya, Patrick Muriuki Mugaine

Theses & Dissertations

Background: Tests for antibodies against severe acute respiratory syndrome coronavirus 2, the aetiologic agent of coronavirus disease 2019, provide evidence of past infection or immunization. At the individual level, they are useful as markers of protection against severe disease and in cases where the diagnosis by nucleic acid amplification is inconclusive. At the population level, they are an indirect measure of exposure and may be useful in monitoring changes in viral infection or uptake of immunization over time. The interpretation and optimal use of antibody assays on populations requires an appreciation of the wide variability in individual antibody responses, the …

Comparison Of Maldi-Tof Ms And 16s Rrna Sequencing For Identification Of A Collection Of Clinical Isolates Of Nonntuberculous Mycobacteria In Kenya And Describing Their Antimicrobial Susceptibilities, David Enoch Kawalya

Theses & Dissertations

Study background: non-tuberculous mycobacteria (NTM) are members of the genus Mycobacteria that are ubiquitous in the environment. They are increasingly documented to cause multi-drug resistant human and animal infections in immunocompromised as well as immunocompetent hosts and thus, they are a huge burden on public health resources. Diagnosis and treatment of these infections is particularly challenging due to their variable clinical presentation and the lack of easily accessible identification methods. MALDI-TOF MS is a proteomic method that has gained traction in the identification of microbial organisms in clinical practice due to its fast turn-around time, high resolution, and cost-effectiveness but …

Immunophenotypic Expression Profile Of Multiple Myeloma Cases At A Tertiary Hospital In Nairobi, Kenya, Isabella Chelagat Mengich

Theses & Dissertations

Background; Multiple myeloma (MM) is a heterogeneous disease with variable patient outcomes ranging from indolent to aggressive disease. GLOBOCAN data places Kenya amongst the top five African countries for MM incidence and MM-related mortality. Aberrant expression of CD56, CD117, Cyclin D1 and Ki-67 on neoplastic plasma cells has been demonstrated to be useful in disease prognostication. However, majority of the data on MM comes from western countries. The significance of expression of this markers is uncertain in our population. The aim of this study was to determine the immunophenotypic expression profile of CD56, CD117, Cyclin D1 and Ki-67 in a …

Comparison Of Ajcc 7th Edition (Anatomic) Vs Ajcc 8th Edition (Prognostic) Staging Systems For Breast Cancer, Issack Mohamed Abdi

Theses & Dissertations

Background; Staging is key for the appropriate management of breast cancer. It is based upon the size of tumour, status of lymph nodes and the presence or absence of distant metastasis, to provide an overall estimate of tumour burden. In its latest (8th) edition, the American Joint Committee on Cancer (AJCC) made a radical change in staging, creating a new prognostic staging system for breast cancer by adding biological factors to the purely anatomical based staging system of the prior editions.

Study Objectives; This study aimed to retrospectively evaluate the changes in staging between the AJCC 7th (anatomic) and AJCC …

Association Of Helicobacter Pylori Caga And Vaca Genotypes With Gastric Adenocarcinoma In Kenya, Priscilla Waithira Njenga

Theses & Dissertations

Background: Helicobacter pylori infects approximately half of the world’s population. The main virulence factors, CagA and VacA, are associated with chronic gastritis and cancer. Notable geographic and temporal variations in the prevalence and genotypes of H. pylori in relation to gastric pathologies have been observed, however, their significance and trends in African populations is scantly described. The aim of this study was to investigate the association of H. pylori and its respective CagA and VacA genotypes with gastric adenocarcinoma and to describe the trends of H. pylori genotypes over the last 8 years (2012-2019).

Materials and Methods: A total of …

Comparison Of Staphylococcus Aureus Nasal Carriage By Patients And Healthcare Workers In Selected Dialysis Centers In Nairobi And Neighbouring Counties, Enock Serem

Theses & Dissertations

No abstract provided.

Analysis Of Terminal Duct Lobular Unit Involution In Luminal, Her-2enriched And Triple Negative Breast Cancer Subtypes, Joseph Nyaguti Kiwinga

Theses & Dissertations

Introduction: The terminal duct lobular unit (TDLU) of the breast is the most common origin of most breast cancers (BC). With increasing age and menopause, physiologic involution of TDLU occurs with a reduction in both the number and size of the lobules. Reduced TDLU involution is associated with a higher mammographic breast density (MBD) which by itself is a strong breast cancer risk factor. Recent studies have shown that TDLU involution is associated with a reduced risk of breast cancer and involution also differs with molecular subtypes of BC.

Studies have shown that the etiology, pathogenesis and prognosis of the …

Von Willebrand Disease Among Women Of African Descent Attending The Aga Khan University Hospital Nairobi, With Menorrhagia, Angela Nabutilu Munoko

Theses & Dissertations

Introduction: Von Willebrand Disease (VWD) is the most common heritable bleeding disorder with equal prevalence reported across the races. Women are more likely to present with excessive bleeding due to menstruation and child bearing. Studies have found that 5-24% of women presenting with menorrhagia have VWD.

Women of African descent are under-represented in studies carried out on Von Willebrand disease and lower prevalence has been reported in this population. VWD has variable penetrance and racial differences in genetic mutations may influence presentation and disease severity. It was predicted that the standardization of the study conditions (case definition of menorrhagia, use …

Etiologies Of Lower Respiratory Tract Infections Among Adult Patients Presenting To A Tertiary Institution In Nairobi, Mary Achakolong

Theses & Dissertations

Background: Lower respiratory tract infections continue to contribute significantly to morbidity and mortality across all age groups globally. Viral pathogens in isolation or as co-infections are an important cause of pneumonia and associated with several life threatening syndromes that warrant appropriate and timely lifesaving diagnosis. Many viral respiratory infections demonstrate substantial regional and seasonal variations which are poorly understood. In addition, there are very few studies in sub-Saharan Africa that have examined the role of viruses as causes of community acquired pneumonia. The availability of molecular techniques such as multiplex PCR that are much more sensitive than traditional methods and …

The Predictive Value Of Urine Dipstick Glucose Test In The Screening For Gestational Diabetes Mellitus In A Tertiary Private Hospital In Kenya, Janet Maranga

Theses & Dissertations

Background: Worldwide, there is no consensus on the best approach to diagnose gestational diabetes mellitus (GDM) and though oral glucose tolerance testing (OGTT) is considered the gold standard, practices in the administration and interpretation of the test differ depending on the guidelines in use. Previous studies have questioned the utility of glycosuria as a screening test for GDM. Since the studies were conducted, there have been diagnostic threshold changes that might impact its utility.

Justification: Diagnostic cut-offs of OGTT used in GDM diagnosis have evolved over time necessitating re-evaluation of glycosuria. The study was aimed at re-assessing the utility of …

Is There An Association Between Placental Inflammatory Lesions And Vaginal Microbiota In Preterm Labour? A Case Control Study, David Ogechi Atandi

Theses & Dissertations

Background: Preterm birth continues to be a significant contributor to neonatal mortality and morbidity despite diverse unique interventional strategies. There is need for better understanding of differences and influences of the now characterized vaginal microbiome on terminal inflammatory effects in the uterine microenvironment in term and preterm labour to improve on current strategies. How the existence of a postulated placenta microbiome also affects this understanding should be considered.

Objectives: The aim of this study was to explore the association between the maternal vaginal microbiota and placental inflammatory lesions in preterm labour and to determine the presence of a placenta microbiome …

Acceptability And Adequacy Of Vaginal Self Sampling For Hpv Dna Testing In Cervical Cancer Screening Among Women Attending A Tertiary Hospital Clinics In Nairobi Kenya, Sagal Omar Salad

Theses & Dissertations

Background: Cervical cancer is a main concern of women’s health globally. In Kenya, Cervical cancer is the second most common cancer in women and the leading causes of cancer related deaths.

Several screening methods exist including cytology, human papilloma virus DNA test and visual inspection with Acetic Acid or Lugol’s Iodine (VIA/VILI). The current screening rate uptake in Kenya is poor, HPV DNA self-sampling may have a role in increasing the screening uptake as many studies have shown that self-sampling for HPV DNA testing is acceptable, though some others favoured over self-sampling. This study aims to assess whether vaginal HPV …

Evaluation Of Breast Cancer Biomarkers Using Genexpert® On Core Biopsy-A Retrospective Laboratory Based Validation Study., Erick Chesori

Theses & Dissertations

Introduction: Breast cancer is the most common malignancy in women worldwide. It is a significant cause of cancer related morbidity and mortality among Kenyan women. Evaluation of Estrogen receptor (ER), Progesterone receptor (PR), and Human epidermal growth factor receptor 2 (HER2) in breast cancer tissue is standard of care as these biomarkers have been shown to have both prognostic and predictive utility. Immunohistochemistry (IHC) is the gold standard for evaluation of ER/PR/HER2, but its availability in Kenya is limited due to the high operational cost. There have been recent developments in alternative cheaper and readily accessible molecular based testing platforms …

Association Of Tissue Vitamin D Receptor Expression With Breast Cancer Molecular Subtypes In Kenyan Women, Mutambuki Kimondo

Theses & Dissertations

Background: Previous studies have shown that reduced vitamin D receptor expression in breast cancer tissue is associated with worse disease outcomes. Furthermore, studies show that estrogen negative and triple negative breast cancer is associated with a poor prognosis and a low breast tissue vitamin D receptor (VDR) expression. Other studies also report that low serum vitamin D levels are associated with more aggressive breast cancer.

Methods: This was a cross-sectional study with both a retrospective and a prospective arm. The retrospective part was nested within a larger study; previously constructed tissue microarray blocks (TMA) blocks were used for analysis …

Reference Intervals For Prothrombin Time And Activated Partial Thromboplastin Time Derived From Black African Blood Donors At A University Teaching Hospital In Nairobi, Kenya, Abubakar Abdillah

Theses & Dissertations

Introduction: Prothrombin time (PT) and activated partial thromboplastin time (APTT) are important coagulation screening tests that give an insight into how well the extrinsic and intrinsic arms of the coagulation cascade are performing. For correct interpretation of laboratory results and avoidance of errors and misdiagnosis, population specific RIs are most appropriate. In a healthcare setting, it is up to the laboratory to establish RIs for use for the particular analytes that they run, or at least verify the RIs availed by the manufacturer of the reagents for a particular analyte.

Objectives: This study aimed to establish reference intervals (RIs) for …

Comparison Of Xpert Mtb/Rif With Histology For The Detection Of Mycobacterium Tuberculosis In Formalin Fixed Paraffin Embedded Tissues At Aga Khan University Hospital, Nairobi, Njau Allan Njoroge

Theses & Dissertations

Background: Diagnosis of extrapulmonary tuberculosis (EPTB) continues to be a challenge due to the complexity of the causative organism and the wide array of pathologic features seen in this infection. A number of studies have shown polymerase chain reaction (PCR) for EPTB to be a feasible, sensitive and specific test for diagnosis of tuberculosis (TB) of which, the World Health Organisation (WHO) has given recommendations. As pertains EPTB, Xpert MTB/RIF may be used in place of conventional tests such as microscopy, histopathology and culture in lymph nodes and other tissues from patients suspected to have EPTB. It has been demonstrated …

Diagnostic Accuracy Of Hba1c Test In Diagnosis Of Diabetes And Prediabetes In A Multiethnic Population At Aga Khan University Hospital, Nairobi., Francis Kiigu Wathigo

Theses & Dissertations

Introduction: Diabetes mellitus is a metabolic disease characterized by hyperglycaemia secondary to impaired insulin secretion, impaired insulin action or both. In Kenya, an estimated 750,000 people are diabetic with more than 50% estimated to be unaware of their status.

Conventionally, diagnosis has been based on plasma glucose levels. In 2010, Haemoglobin A1c (HbA1c) was approved by the American Diabetes Association (ADA) and World Health Organisation (WHO) for diagnosis of diabetes. However, different studies have shown variations in diagnostic performance of HbA1c.

Research question: What is the diagnostic sensitivity and specificity of HbA1c in diagnosis of diabetes and prediabetes at Aga …

Prevalence Of Double Myc/Bcl2 Expression And The Cell Of Origin In Diffuse Large B-Cell Lymphomas Diagnosed At A Tertiary Level Referral Laboratory, Jonathan Wawire

Theses & Dissertations

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most commonly diagnosed non-Hodgkin’s lymphoma in adults worldwide. In Kenya DLBCL accounts for 64% of all non-Hodgkin’s lymphomas diagnosed in adults. It is a heterogeneous disease and patients show varying outcomes despite standard treatment. This variability is attributed to the differences in the biology and molecular pathogenesis of DLBCL.

The five most important prognostic factors for DLBCL include scores for the revised international prognostic index (R-IPI), the cell of origin (COO), presence of myelocytomatosis (MYC) and B-cell lymphoma 2 (BCL2) gene rearrangements by fluorescent in situ hybridisation (FISH) or …

Comparison Of The Sensitivity Of Biomarker Based Matrix Assisted Laser Desorption Ionization-Time Of Flight Mass Spectrometry (Maldi-Tof Ms) And Conventional Methods In The Identification Of Clinically Relevant Bacteria And Yeast, Ali Abdow Kassim

Theses & Dissertations

Background: MALDI-TOF MS is an analytical method that has recently become integral in the identification of microorganisms in clinical laboratories. It relies on databases that majorly employ pattern recognition or fingerprinting. Biomarker based databases have also been developed and there is optimism that these may be superior to pattern recognition based databases. This study compared the performance of ribosomal biomarker based MALDI-TOF MS and conventional methods in the identification of selected bacteria and yeast.

Methodology: The study was a cross sectional study carried out in collaboration with the Swiss Tropical and Public Health Institute, Switzerland and Mabritec laboratory, Riehen, Switzerland. …

Recurrent Mutations Of T-Cell Receptor And Co-Stimulatory Signaling Proteins In Peripheral T-Cell Lymphomas, Joseph Rohr

Theses & Dissertations

Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of mature T-cell neoplasms with a poor prognosis. Recently, mutations in TET2 and other epigenetic modifiers as well as RHOA have been identified in these diseases, particularly in angioimmunoblastic T-cell lymphoma (AITL). CD28 is the major co-stimulatory receptor in T-cells which, upon binding ligand, induces sustained T-cell proliferation and cytokine production when combined with T-cell receptor stimulation, through many signaling molecules including VAV1. This thesis identifies recurrent mutations in CD28 in PTCLs, as well as mutations in VAV1. Two residues of CD28 – D124 and T195 – were recurrently mutated in 11.3% …

Vitamin D Levels In Black African Adults At The Aga Khan University Hospital Nairobi, Elizabeth Muringa Kagotho

Theses & Dissertations

Introduction: Vitamin D has been known for centuries for its benefits in bone health. Recent observational studies have however demonstrated its benefits in infectious diseases such as tuberculosis and non-communicable diseases such as diabetes mellitus, cardiovascular diseases and cancer. This has led to a dramatic increase in testing among adults. The cut-offs for vitamin D deficiency have been debated for decades and the current cut off is derived from a Caucasian population. Studies done among black African adults in Africa are few and have shown that vitamin D deficiency ranges from 5-91%. In view of the difference in skin colour, …

The Heart Weight–Body Weight Coefficient In Kenyans Aged 14 Years And Above, Mbayah Etabale

Theses & Dissertations

Background: The heart size has traditionally been assessed using absolute reference weights. But the heart weight (HW) has been shown to depend on one’s body size hence a better measure is the ratio of the HW to the body weight (BW) – the HW-BW coefficient. Initially noted to be 0.43% and 0.40% in males and females respectively, recent studies have shown an increase of up to 0.51%.

Objective: To determine the HW-BW coefficient in Kenyans aged 14 years and above.

Methods: One hundred and four deceased Kenyans aged 14 years and above, with no heart or chronic lung disease, were …

The Prevalence Of Malaria And Assessment Of The Uptake Of Malaria Prevention Measures In Blood Donors In Two Regional Blood Transfusion Centres In Kenya, Valerie Magutu

Theses & Dissertations

Transfusion transmitted malaria is one of the most common transfusion transmissible infections and is a threat to blood safety and malaria control in Sub-Saharan African countries where malaria is endemic. The majority of healthy adults living in malaria endemic areas have some degree of immunity to the disease and an asymptomatic low-level parasitaemia is known to exist in a subset of this population. Blood donors recruited from the population are screened using a donor-selection criteria that includes age, weight, self-declared well-being and measurement of vital signs but not history of recent malaria infection or treatment. The Kenya National Blood Transfusion …

Androgen Receptor Expression And Associated Clinico-Pathologic Features In Primary Breast Cancer From Kenya, Joshua Kibera Chege

Theses & Dissertations

Introduction: Breast cancer is a heterogeneous group of diseases classified into various subtypes according to clinical, histological and molecular features as well as by the expression of prognostic and predictive biomarkers. New biomarkers are being studied which may be therapeutic targets in various breast cancer subtypes particularly triple-negative breast cancer. Recent studies show that androgen receptor (AR) expression can be used as a prognostic marker and there is evidence that anti-androgen therapy may be beneficial in oestrogen receptor negative breast cancer. Retrospective studies show that patients with breast cancers co-expressing androgen receptor and oestrogen receptor have a favourable prognosis and …

Expression Of Mismatch Repair Proteins In Colorectal Cancer At Aga Khan University Hospital, Nairobi, Charles M. Wahome

Theses & Dissertations

Introduction: Microsatellite instability is one of three molecular pathways described in the pathogenesis of colorectal carcinoma. The presence of microsatellite instability in patients with colorectal cancer has implications for prognosis and family counselling. Deficiency in mismatch repair genes leads to microsatellite instability and this can be reliably demonstrated in formalin fixed paraffin embedded tissue by methods, which include immunohistochemistry for the detection of mismatch repair proteins.

Local data show a disproportionately large number of younger patients with colorectal cancer compared to that documented in Caucasians. Colorectal cancer in younger ages is often attributed to deficient mismatch repair.

The objective of …

Early Onset Type 2 Diabetes And Associated Risk Factors, Grace Nyambura Kiraka

Theses & Dissertations

Background: The incidence of type 2 diabetes in patients below the age of 40 (early onset diabetes) is markedly on the rise and has been linked increased prevalence of risk factors such as the metabolic syndrome and family history of diabetes.

Objective: To determine the proportion of patients with type 2 diabetes at Aga Khan University Hospital Nairobi (AKUHN) who have early onset type 2 diabetes and the association of age of onset with risk factors (family history of diabetes, obesity, waist circumference, hypertension, low HDL cholesterol and hypertriglyceridaemia) in this group of patients.

Methods: This was a …

Primary Antiretroviral Drug Resistance Profiles Among Hiv-1 Therapy Naïve Patients In Two Referral Hospitals In Kenya, Simon Onsongo Nyangena

Theses & Dissertations

Objective: To characterize antiretroviral drug resistance mutations among drug naïve patients in two referral hospitals in Kenya

Background: Acquired immunodeficiency syndrome (AIDS) caused by Human immunodeficiency virus (HIV) was first described in 1982. Since then the virus has spread globally to infect millions of people. HIV was first described in Kenya in the period between 1984/1985. Currently, Kenya has an estimated HIV-1 prevalence of 6.2% with a country population of about 40 million people. With the introduction of antiretroviral drugs, the survival of most HIV patients has been prolonged markedly. However this is greatly threatened by increasing rates of antiretroviral …