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Ladu, Adama (2023) Evaluation of Spleen Size and Function: Relationship with Malaria and Bacterial Infections in Sickle Cell Disease Patients in North-Eastern Nigeria, Thesis (Doctoral), Liverpool School of Tropical Medicine.
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A Ladu_Final version of thesis - 0025204.pdf - Accepted Version Download (6MB) | Preview |
Abstract
Sickle cell disease (SCD) is a collective name for a group of conditions that cause clinical symptoms from the formation of sickled red cells. The spleen is one of the earliest organs affected in SCD. During the course of the disease, the spleen declines in both its structure and function; however, the course of events is variable amongst individuals with the disease and depends on clinical and biological factors. The loss of splenic function may be associated with increased susceptibility to infection; however, spleen function is rarely documented among SCD patients in Africa, due partly to the non-availability of sophisticated techniques such as scintigraphy and pitted red cell counts by contrast-enhancing microscopy, thus the role of splenic dysfunction and infections have not been well studied.
With the aim of better understanding the spleen size and function among our SCD patients, and the risk associated with infections, I investigated: 1) baseline spleen sizes amongst the SCD patients and healthy controls based on ultrasonography and the clinical and laboratory correlates associated with splenic size preservation. 2) splenic function by comparing the frequencies of red cells containing Howell-Jolly bodies (HJB) and argyrophilic inclusions (AI) in SCD patients with those of healthy controls, and explored factors associated with splenic dysfunction. 3) the prevalence of malaria infection in SCD patients and healthy controls, the prevalence of bacterial infection in acutely-ill SCD patients, and their association with spleen size and function.
On the evaluation of baseline spleen sizes, about half of the SCD patients had no visible spleens on ultrasonography (47%). The spleen was visualised in all the children aged five years and below. The spleen size in SCD patients during the first two years of life was three-fold higher than those of age-group matched, healthy controls, then followed by a progressive age-related decline in size. Among the laboratory factors explored, high HbF and low mean corpuscular haemoglobin concentration (MCHC) were associated with preservation of the spleen.
In the spleen function assessment study, the frequency of HJB and AI- containing red cells were higher in the SCD patients than healthy controls. The HJB and AI counts were higher in patients without visible spleens than patients whose spleens were visualised on ultrasonography. The percentages of HJB- and AI- red cells rose significantly with increasing age, and both counts showed a significant positive association with MCH and a negative association with HbF level.
In the spleen and infection study, P. Falciparum prevalence and parasite densities were higher among the acutely-ill SCD patients than steady-state SCD controls. Severe malaria events were more frequent among the less than five years old SCD patients. There was no significant association between prevalence of parasitaemia or parasite density and the visualisation or non-visualisation of the spleen on ultrasonography, nor with the frequency of HJB red cells. The overall prevalence of bacteraemia among the SCD patients in the study was low (5.2%), and the majority of isolates cultured were Gram-negative organisms. There was no significant association between prevalence of bacteraemia and the visualisation or non-visualisation of the spleen on ultrasonography, nor with the frequency of AI and HJB red cell counts.
Overall, by exploring spleen size, spleen function and infections risk related to splenic parameters, my research has provided new insights into the spleen and SCD among patients in an African setting. It showed that the spleen can be visualised among SCD patients up to the age of five years before autosplenectomy occurs. It provides evidence that assessment of spleen function is feasible among SCD patients even in resource-limited settings. Importantly, my research provides evidence about the consistency of HbF as predictor of both spleen size preservation and function among our SCD patients. Lastly, evidence regarding the role of the spleen in malaria and bacterial infection was obtained, thereby filling an important gap in knowledge regarding the role of the spleen and risk of infection.
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