Data for this review were identified by searches of Medline, Current Contents, and references from relevant articles; numerous articles were identified through searches of the authors' extensive files. Searches were done for the period 1970–2005 combining the terms “thalassaemia” and “infections”, “bacterial infections”, “viral infections”, “fungal infections”, “treatment”, and “immunology”. Papers were selected on the basis of the best level of available evidence for each specific aspect
ReviewInfections and thalassaemia
Introduction
The term thalassaemia (derived from the Greek “thalassa”, which means “the sea”—referring to the Mediterranean—and “emia”, meaning “related to blood”) indicates a heterogeneous group of genetic disorders of haemoglobin synthesis characterised by a disturbance of the production of globin chains, leading to anaemia, ineffective erythropoiesis, and destruction of erythroblasts in the bone marrow and of erythrocytes in the peripheral blood.1 In individuals that produce normal haemoglobin, two types of polypeptide chains (α and non-α) pair with each other at a ratio close to 1/1 to form normal haemoglobin molecules. In thalassaemic patients, an excess of the normally produced type accumulates in the cell as an unstable product, leading to the destruction of the cell. This imbalance is the hallmark of all forms of thalassaemia. Types of thalassaemia are usually named after the underproduced chain or chains.
Thalassaemias are found in all parts of the world, and the often used name “Mediterranean anaemia” is misleading. α-Thalassaemia may be the most common single gene disorder in the world (percentage of gene carriers in the middle east is 5–10%, 20–30% in west Africa, and up to 68% in the South Pacific), although the gene prevalence in northern Europe and Japan is less than 1%.1 In β-thalassaemia, the frequency of the gene is greater than 1% in the Mediterranean basin, India, southeast Asia, north Africa, and Indonesia (figure).4
Clinical severity varies widely, ranging from asymptomatic forms to severe or even fatal entities. In the severe forms of thalassaemia—eg, Cooley's anaemia or thalassaemia major—the large numbers of abnormal red blood cells processed by the spleen and its haematopoietic response to the anaemia lead to massive splenomegaly and consequent manifestations of hypersplenism, resulting in the need for splenectomy. If chronic anaemia in thalassaemic patients is corrected with regular blood transfusions (with the aim of maintaining the pretransfusional haemoglobin concentration at 9 g/dL or higher), another source of iron is added, which, together with the excessive iron absorption normally present in such cases, leads to a state of iron overload. Iron accumulates in various organs, especially in the heart and the liver, resulting in substantial damage. Morbidity in patients with severe thalassaemia is usually the result of iron-related heart failure, serious infections, or the complications of splenectomy. Bloodborne viral infections (mainly hepatitis C and B), infections with unusual organisms whose presence is favoured by iron overload or by the chelation therapy needed to reduce it, and post-splenectomy infections all contribute substantially to morbidity and mortality in thalassaemic patients, making infections the second most common cause of death after heart failure.5
Section snippets
Immune abnormalities in thalassaemic patients
Numerous immune abnormalities have been described in thalassaemic patients (panel 1). As far as T lymphocytes are concerned, greater numbers and activity of CD8 suppressor cells, decreased CD4/CD8 ratio, and reduced proliferation have been reported.6, 7, 8, 9, 10 B lymphocytes have been found to be increased in numbers, activated, and with impaired differentiation.6, 9, 11 Increased levels of IgG, IgM, and IgA have also been described,12, 13 and neutrophils and macrophages appear to have
Yersinia enterocolitica
Clinical reports of desferrioxamine-treated thalassaemic patients that developed fulminant Y enterocolitica septicaemia are numerous.42, 43, 44, 45 However, while common in western countries,42, 43 Y enterocolitica is an uncommon cause of severe infections in thalassaemic patients in the east.46, 47, 48 The reasons underlying these differences are unknown.
Clinical manifestations include enterocolitis (which can cause rectal bleeding and perforation of the ileum), polyarthritis, pharyngitis, and
Conclusions
Clinicians must be aware of the potential life-threatening infections of patients with thalassaemia major, especially if splenectomised. Predisposing factors for infections such as severe anaemia and iron overload should be controlled by regular blood transfusions and proper iron-chelating therapy in countries that can afford these expensive treatments, and patients should be educated to seek early care when fever develops. Fever without any apparent cause, especially when associated with
Search strategy and selection criteria
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Cited by (167)
Hypoferremia of inflammation: Innate host defense against infections
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2021, Journal of Trace Elements in Medicine and BiologyCitation Excerpt :Frequent RBC transfusions may cause a state of iron overload, which may cause precipitation of iron in most vital organs [4–6]. As a consequence, patients with transfusion-dependent thalassemia (TDT) frequently develop immune disorders including decreased synthesis or increased consumption of complement factors (C3 and C4) [7], aberrations in cell-mediated immunity [8], lymphocyte proliferative responses to mitogens and antigens [9], and antibody production and responses, decreased activity of T- and B-lymphocytes, alterations in cytokine responses [10], changes in natural killer cell activity, neutrophil chemotaxis, phagocytic and chemotaxis activity of macrophages, and increased susceptibility to infections [11–14]. Moreover, the accumulation of iron in various tissues is associated with the induction of macrophage polarization [15] and increased gene expression of inflammatory molecules [16], frequently causing harmful inflammatory responses [17].
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