3. Electronic Theses and Dissertations (ETDs) - All submissions

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    Functional iron deficiency anaemia and its genetics in a black South African population with chronic kidney disease
    (2019) Nalado, Aishatu Muhammad
    Background: Anaemia of chronic kidney disease (CKD) and iron deficiency anaemia (IDA) has been associated with morbidity and mortality in patients with CKD. Consequences of these changes differ across different races. Diagnosis of IDA is usually straightforward, except when it occurs in the context of inflammatory disorders such as CKD, where the conventional parameters used to diagnose IDA are not definitive. Hence, there is a need for newer and more accurate biomarkers in the diagnosis of IDA in CKD patients. Studies in developed countries have reported the usefulness of newer parameters in IDA diagnosis; however, the role of these newer biomarkers in IDA diagnosis in Africa is unknown. It remains unclear whether genetic factors may increase susceptibility to the development of IDA in CKD patients. Therefore, this study has been conducted to determine the prevalence and racial prevalence of IDA; to determine the utility of newer biomarkers in the diagnosis of IDA and the effect of these biomarkers on disease outcomes; and to provide important insights into the prevalence and genetic susceptibility of IDA in CKD patients in sub-Saharan Africa. Methods: This was a cross-sectional study carried out from May 2016 to December 2018, involving 365 CKD patients from the Renal Outpatient Clinic of the Charlotte Maxeke Johannesburg Academic Hospital, South Africa, and 144 age- and gender-matched healthy controls comprising hospital staff and the patients’ relatives. The study was approved from the Human Research Ethics Committee of the University of the Witwatersrand (clearance certificate number, 150929). The first part of the study described the prevalence of anaemia and IDA in a multi-ethnic CKD population. The second part of the study determined the utility of reticulocyte haemoglobin content (CHr), and % hypochromic red cells (%HYPO), in the diagnosis of IDA, followed by role of novel biomarkers, GDF-15 and hepcidin, as diagnostic markers of IDA. Hepcidin and GDF-15 were measured using mass spectrometry and ELISA, respectively and was followed by the genetic aspect of the study that determined the susceptibility of a genetic variant to IDA. The last part of the study looked at role of GDF-15 and hepcidin in disease progression and mortality using Spearman’s rank correlation and linear and logistic regression analysis. Receiver operator curves (ROCs) were used to evaluate the diagnostic utility of biomarkers. Using Cox proportional hazard models, a composite endpoint of CKD progression was also investigated. Results: The prevalence of anaemia (Hb < 13 g/dl in males and < 12 g/dl in females) among black CKD patients was 46.9 %, with 26.1% of the sample population suffering from IDA, which proved to be three times more frequent among the CKD patients than among the controls. The proportions of functional iron deficiency anaemia (18.6 % vs 1.4 %) and absolute iron deficiency anaemia (16.7 % vs 7.8 %) were higher among the CKD patients than among the controls. However, 32.3 % (95% CI: 27.90 %– 37.10 %) of the study population presented with iron deficiency without anaemia. The mean age of the CKD patients was higher than that of the controls (52.7  14.3 vs 40.4  12.6 years, P < 0.001). The sensitivity and specificity values for diagnosing IDA among CKD participants were 62.6 % and 80.2 % respectively for CHr at a cut-off value lower than 28 pg, and 63.3 % and 79.8 % for the proportion of hypochromic red cells (%HYPO), respectively. The (define here) AUC of CHr (0.81, 95 % CI: 0.76-0.87) was higher than the AUC of %HYPO (0.76, 95 % CI: 0.76-0.87). The predictive value of diagnosing IDA among CKD patients using GDF-15 and hepcidin was high (AUC= 0.723 and 0.714, respectively). The prevalence of rs 855791 C homozygosity was similar for the iron-deficient and non-iron-deficient anaemia groups (86.1 % vs 84.2 %, p= 0.723). When the analysis was confined to participants with or without functional IDA, however, the C homozygote (88.3 % vs 84.4 %, p= 0.425) value was similar for both groups. Patients with high levels of hepcidin were up to six times more likely to be at risk of dying as opposed to patients with normal levels of hepcidin (HR: 6.14; P< 0.001). On the other hand, it was determined that the levels of GDF-15 and IDA were not associated with mortality in CKD patients. Higher plasma levels of hepcidin were strongly associated with CKD progression when compared to normal hepcidin levels (HR: 3.09; P= 0.002). The risk of CKD progression was two times higher in the presence of hypocalcaemia as opposed to normocalcaemia (HR: 2.24; P= 0.021). The death rate increased with declining haemoglobin levels from 0.96 among patients with mild anaemia, to 4.29 per 100-person years, among patients with severe anaemia. Anaemic patients with a glomerular filtration rate (GFR) of less than 30 mls/min were susceptible to a significantly greater risk of death, due mainly to end stage kidney disease (ESKD) and failure to commence haemodialysis because of a lack of funding (HR 11.51: 95% CI 1.62–78.32, P < 0.001). Participants with hyperphosphatemia had about a 2.6-fold increased risk of death (HR, 2.60; 95% CI, 1.09-6.20, P= 0.02). Although the odds of anaemia were 3.8-fold higher (odds ratio = 3.8, P = 0.059) among CKD stage 5 participants as opposed to those with CKD stage I, the relationship between anaemia and the stages of CKD proved to be non-linear. Conclusions: Anaemia and IDA were common in our pre-dialysis CKD patients. Anaemia, elevated hepcidin levels, hypocalcaemia and low estimated glomerular filtration rates (eGFRs), were found to be associated with an increased risk of death among pre-dialysis CKD patients. Our study also highlighted that newer biomarkers (novel) can be useful in the diagnosis of IDA and can perform more effectively than the conventional parameters (transferrin saturation (TSAT) and ferritin) in an African CKD population. In addition, our study showed that newer biomarkers can be used to predict disease progression and mortality in a CKD population. This suggests that health care services for chronic diseases should be prioritise pre-dialysis CKD patients.
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    Investigation of the role of human parvovirus B19 in chronic anaemia of hiv infected TB patients
    (1994-09-30) van Niekerk, Albetus. Bernhardus. Willer.
    This study was undertaken to determine the role of human parvovirus B19 (B19) in chronic anaemia of HIV infected TB patients. Patients were selected from an existing databank of 307 patients included in a MRC HIV/TB study. Twenty-nine patients, 15 coinfected with HIV/TB and 14 infected with TB only, were identified for further evaluation. These patients’ sera were subjected to serological and DNA detection studies using IgG and IgM ELISA methods and a nested polymerase chain reaction (PCR) assay.
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    Spatially adjusted determinants of Malaria and Anaemia Morbidity among children under age 5 years in Ghana, 2014
    (2018) Blam, Stephen Nuerteye
    Background: Malaria and anaemia pose significant public health challenges to most developing countries. Sub-Saharan Africa continues to carry a disproportionately high share of the global malaria burden. Recent WHO (2015) global estimates on disease burden shows the African region accounted for 88% of the 214 million new malaria cases in 2015. This statistic further highlighted that the region accounted for 90% of malaria deaths in 2015. Similarly, anaemia, defined as low hemoglobin concentration, is estimated to globally affect 43% of children under five years of age. Anemia prevalence is very high among Ghanaian children under 5 years of age. The objectives of this study were to determine the prevalence and spatial distribution of malaria morbidity in children under age 5 years in Ghana in 2014, to ascertain the prevalence and spatial distribution of childhood anaemia morbidity in Ghanaian children under age 5 years in 2014, to determine the spatial distribution of factors associated with malaria morbidity in Ghana in 2014, and to determine the spatial distribution of factors associated with anaemia morbidity in Ghana in 2014. Objectives: The aim of the study is to determine spatial distribution and factors associated with malaria and anaemia morbidity among Ghanaian children under 5 years of age in 2014. Methods: This study analysed malaria and anaemia morbidity and prevalence using data from the Ghana 2014 Demographic and Health Survey. These data captured malaria related information on children under 5 years. Survey logistic and ordered logistic multivariable regression was done to determine associations between the singular outcomes malaria and anaemia and several explanatory variables. The regression models were employed and results thereof were used to produce maps illustrating the predicted risk of malaria and anaemia occurrence. The generalized linear mixed model was used to simultaneously identify the risk factors of malaria and anaemia of children under five years and how these are spatially distributed. Multilevel survey adjusted logistic and ordinal logistic regression models with non-spatial random effects were fitted for malaria and anaemia respectively. A Bayesian approach was employed to further adjust for spatial random effects on the convolution models for the two main outcomes. Results: The sample in this study was made up of 2727 children under age 5 years, of which 783 tested positive for malaria and 1873 had anaemia, resulting in an observed malaria and anaemia prevalence of 28.71% and 68.68% respectively. Spatially adjusted significant variables were: Child’s age; type of place of residence; mother’s highest education level, wealth index; child’s altitude adjusted haemoglobin level; cluster altitude; severe anaemia vomiting; severe anaemia extreme weakness. Children from the Western, Central, Greater Accra, Eastern, and Brong Ahafo regions were more likely to have malaria compared to northern region. Malaria was 1.46 times more likely to occur among children residing in rural than urban areas [OR=1.46, (95% CI: 1.02-2.16); p=0.05]. Vomiting as well as extreme weakness were 6.37 [OR=6.37 (95% CI: 2.16- 18.75); p<0.001] and 7.63 [OR=7.63 (95% CI: 3.02-19.22); p<0.001] times more likely to have anaemia than those without these symptoms. Children residing at higher altitude were 0.98 times less likely to have anaemia compared to those at lower altitude [OR=0.98 (95% CI: 0.97-0.99); p=0.01]. Conclusion: Recent reports in Ghana indicate that malaria and anaemia related deaths in children under age 5 years are on the ascendancy. In spite of this, there is a dearth of empirical research that establishes our understanding on the prevalence of malaria and anaemia in the endemic regions of Ghana. Understanding the prevalence of malaria and anaemia in terms of spatial risk factors, will provide more insight and practical guidelines to the formulation of policies aimed at fighting the spread of malaria and anaemia. Hence, directing health interventions to higher risk areas and ensuring nationwide coverage are promising strategies for promoting equity and reducing risk of malaria and anaemia. This study showed that Brong Ahafo, Eastern, Northern, Western, Volta and Upper East regions were the hotspot zones with greatest disease burden. Keywords: Ghana, Anaemia morbidity, Malaria morbidity, Malaria Indicator Survey (MIS), Demographic and Health Survey (DHS), spatial mapping, West Africa.
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    Risk factors associated with anaemia among children under five years of age in Uganda
    (2018) Ali, Muhammad Mustanser
    Background Anaemia remains a public health challenge, especially in developing countries because of its relationship to neurocognitive delays, especially among children under five. According to the World Health Organization (WHO) report for 1993-2005, 293.1 million children were affected by anaemia globally. Risk factors for anaemia that need to be examined in children include socio-demographic characteristics, infection with the Human Immunodeficiency virus (HIV), malnutrition and malaria. Objectives The objectives of the study were to estimate the prevalence of anaemia and identify the potential risk factors (including socio-demographic factors) among children under five years of age who participated in a cross-sectional survey in Uganda in 2011. Methods Data that were collected in a cross-sectional survey during 2011 in Uganda (N = 1 808) were analysed. Children were defined as being anaemic if their haemoglobin levels were below 11.0 g/dl, as per the WHO definition. Cross tabulations, and ordinary and ordinal logistic regression analysis were the primary methods used. Results The main finding was that the prevalence of anaemia in children under five years of age was high, at 50.3% (95% CI: 46% - 54%). Of those with anaemia 1.6% had severe anaemia, 26.2% had moderate anaemia, and 22.6% had mild anaemia. From the multiple ordinary and ordinal logistic regression analyses, age group of the child, region, breastfeeding status of the mother, v use of antenatal health care facilities, household wealth index, household age group, marital status of household head, and literacy level of the household head were associated with childhood anaemia. Children with anaemia were more likely to be younger than 24 months old, have had malaria, have poor nutritional status, and live in rural areas. The children were also more likely to be anaemic if their mothers had a high education, and were young , and if they lived with a household head aged 79-95 years. They were less likely to be anaemic if they had a household head in one of the relatively higher wealth indices, a household head with a literacy level of ‘medium’, and a household head who was divorced. Conclusion Anaemia was highly prevalent among children under five years of age in Uganda in 2011. Several child- maternal- and household head-related risk factors were identified. Modifiable risk factors should be targeted in Uganda to reduce anaemia in children. Malaria and nutrition programmes (including iron supplementation) should be stepped up, and pregnant women and mothers of new born children should be encouraged to attend health care centres, including antenatal care facilities. Children with un-modifiable risk factors, such as living in rural or low GDP areas should be closely monitored for risk factors that predispose them to anaemia.
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    Birth outcomes and associated risk factors of anaemia in early pregnancy in a nulliparous cohort
    (2015-09-08) Masukume, Gwinyai
    Background Anaemia in pregnancy is a major public health and economic problem worldwide, that contributes to both maternal and fetal morbidity and mortality. Clinical manifestations of anaemia in pregnancy include fetal growth restriction, preterm delivery, low birth weight, impaired lactation, poor maternal/infant behavioural interactions and post partum depression. Objective The aim of the study was to calculate the prevalence of anaemia in early pregnancy in a cohort of ‘low risk’ women participating in a large international multicentre prospective study (n = 5 609), to identify the modifiable risk factors for anaemia in pregnancy in this cohort, and to compare the birth outcomes between pregnancies with and without anaemia in early gestation. Methods The study is an analysis of data that were collected prospectively during the Screening for Pregnancy Endpoints (SCOPE) study. Anaemia was defined according to the World Health Organization’s definition of anaemia in pregnancy (haemoglobin < 11g/dL). Binary logistic regression with adjustment for potential confounders (country, maternal age, having a marital partner, ethnic origin, years of schooling, and having paid work) was the main method of analysis. Results The hallmark findings were the low prevalence of anaemia (2.2%), that having no marital partner was an independent risk factor for having anaemia (OR 1.34, 95% CI 1.01-1.78), and that there was no statistically significant effect of anaemia on adverse pregnancy outcomes (small for gestational age, pre-tem birth, mode of delivery, low birth weight, APGAR score < 7 at one and five minutes). Adverse pregnancy outcomes were however more common in those with anaemia than in those without. Conclusion The absence of a marital partner is an important non-modifiable factor that should be added to the conceptual framework of anaemia’s determinants. Although not statistically significant, clinically, a trend towards a higher risk of adverse pregnancy outcomes was observed in women that were anaemic in early pregnancy.
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    Phenotypic consequences in black South African Fanconi anaemia patients homozygous for a FANCG 637-643 deletion mutation
    (2012) Feben, Candice
    Fanconi anaemia (FA) is a genotypically and phenotypically heterogeneous genetic condition , characterized microscopically by chromosomal breakage and instability and usually inherited in an autosomal recessive manner. Affected individuals often present with a diverse variety of physical congenital abnormalities and most progress to haematological disease including bone marrow aplasia and myelodysplasia in early childhood. In South Africa, Black individuals with FA share a common causative founder deletion mutation in the Fanconi G gene (FANCG del) in 82% cases. They are thus an ideal patient cohort for a genotype-phenotype correlation study. Thirty Black patients, homozygous for FANCG del, were ascertained from haematology/oncology clinics in Johannesburg and Bloemfontein. They were subjected to a comprehensive clinical examination to a document their physical features. A concurrent review of each participant's hospital file allowed data to be collected regarding disease presentation and haematological progression . Significant growth abnormalities and a high frequency of skin of skin pigmentary anomalies were found in the research cohort. Although subtle, anomalies of the eye, ears, and hands were noted in a high frequency. The overall physical phenotype does not appear to be appreciably different from that described in other Fanconi anaemia cohorts; however, affected Black individuals may present with more severe haematological indices and have poorer outcome that FA individuals of heterogeneous genotype. Further, it would appear that haematological disease progression cannot be predicted by the presence of abnormalities.
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