MEDITERRANEAN JOURNAL OF HEMATOLOGY AND INFECTIOUS DISEASES www.mjhid.org ISSN 2035-3006
MJHID Educational Material
Sickle Cell Disease: Management Options and Challenges in Developing Countries Daniel Ansong1,2, Alex Osei Akoto1,2, Delaena Ocloo2 and Kwaku Ohene-Frempong3 1
School of Medical Sciences,- Kwame Nkrumah University of Science and Technology, Kumasi-Ghana Department of Child Health, Komfo Anokye Teaching Hospital, Kumasi-Ghana 3 Children’s Hospital of Philadelphia, Director, Comprehensive Sickle Cell Centre, USA 2
Correspondence to: Daniel Ansong, Komfo Anokye Teaching Hospital, Post Office Box 1934, Kumasi. Tel: +233 20 8168767. Email: [email protected]. Competing interests: The authors have declared that no competing interests exist. Published: November 4, 2013 Received: June 23, 2013 Accepted: October 15, 2013 Citation: Mediterr J Hematol Infect Dis 2013, 5(1): e2013062, DOI: 10.4084/MJHID.2013.062 This article is available from: http://www.mjhid.org/article/view/11899 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract. Sickle Cell Disease (SCD) is the most common genetic disorder of haemoglobin in subSaharan Africa. This commentary focuses on the management options available and the challenges that health care professionals in developing countries face in caring for patients with SCD. In a developing countries like Ghana, new-born screening is now about to be implemented on a national scale. Common and important morbidities associated with SCD are vaso-occlusive episodes, infections, Acute Chest Syndrome (ACS), Stroke and hip necrosis. Approaches to the management of these morbidities are far advanced in the developed countries. The differences in setting and resource limitations in developing countries bring challenges that have a major influence in management options in developing countries. Obviously clinicians in developing countries face challenges in managing SCD patients. However understanding the disease, its progression, and instituting the appropriate preventive methods are paramount in its management. Emphasis should be placed on early counselling, new-born screening, anti-microbial prophylaxis, vaccination against infections, and training of healthcare workers, patients and caregivers. These interventions are affordable in developing countries. Introduction. Sickle Cell Disease (SCD) is the most common genetic disorder of haemoglobin in subSaharan Africa.1,2 In Africa it is estimated that about 200,000 children are born with the disease annually.3 A point mutation on the 6th codon of the beta-globin gene located on the short arm of chromosome 11 produces a defective beta globin chain, which under low oxygen tension polymerizes into long fibres that eventually lead to abnormally deformed (sickled) red cell. The red cells thus become sticky, adhere to endothelium and Mediterr J Hematol Infect Dis 2013; 5; Open Journal System
clump together plugging micro-vessels4 and also damage large blood vessels that can become severely stenotic or occluded. In addition, sickle red cells have a much-shortened life span making chronic haemolytic anaemia a constant feature of SCD. The combination of vaso-occlusion and haemolytic anaemia contributes to the basic presentation of the disease and associated complications of which some are life threatening. Biomedical technology is moving very fast to use hematopoietic stem cell transplantation and gene
therapy in the management of the disease in developed countries. However, only very few SCD patients have been successfully treated with hematopoietic stem cell transplantation5 and, gene therapy has not been successful yet in curing SCD.6 In general, the disease is managed using a combination of preventive and symptomatic therapies.7 This commentary focuses on the management options available and the challenges that health care professionals in developing countries face in caring for patients with SCD. Sickle Cell Vaso-Occlusive Episodes. The hallmark of SCD is the occurrence of vaso-occlusive episodes. These are characterized clinically by pain in the affected sites of the body. Pain episodes are largely unpredictable and but can be prevented and in more than 80% of the episodes, there is no potential precipitating cause.8 The pathophysiology of the pain is as a result of hypoxia and release of inflammatory mediators and pain neurotransmitters.9–11 Infections are thought to be playing a role in the pathogenesis of vaso-occlusive episodes,12 making the occurrence of vaso-occlusive episode a trigger to alerting potential problems in SCD. The severity of pain in people with SCD varies from mild to severe and the management is determined by accurate estimation of the severity and the associated pre-morbid conditions.7 Management Options. The choice of an analgesic is of importance for effective pain management and so is the identification of the underlying cause that precipitated the occurrence of the episodes. The range of analgesics used to manage pain in SCD patients is similar in developed and developing countries. The analgesic spans from acetaminophen, non-steroidal antiinflammatory drugs (NSAID) to opioids.13,14 There are several behavioural and non-medicinal therapies that are also available in the management of pain. There is evidence to show that hydroxyurea ameliorates the episodes of vaso-occlusive crisis in adults15,16 and in children in the recent BABY HUG study.17 Hydroxyurea can be used in SCD patient to achieve great benefit in preventing painful episodes. It is worthy of note that the use of hydroxyurea comes with caution because of the risk of neutropenia. Challenges. The long-term use of the analgesics comes with major challenges and complications. Patients develop gastric erosion and ulcers when they are placed on NSAIDs. In addition, the long-term use of these drugs can have effects on the kidneys. Clinicians are also confronted with side effect of the long-term use of opioids like pethidine, codeine and morphine in the management of pain without significantly causing respiratory depression with parenteral use and tolerance with long term use.18 Clinicians in developing Mediterr J Hematol Infect Dis 2013; 5: Open Journal System
countries should therefore use opioids with caution for the fear of respiratory depression as well as development of tolerance. The option of hydroxyurea to ameliorate the episodes of vaso-occlusive episode would need more research in the African population. Infections in Sickle Cell Disease. The risk of infection in SCD patient is well established because of several factors, namely, hyposplenism or asplenia and also, the availability of free iron radicals for growth of bacteria, defective chemotaxis and opsonisation, and presence of dead necrotic tissue in some parts of the body especially the bones.4,11 Children with SCD are particularly prone to infection by encapsulated organisms like Strep pneumoniae, Haemophilus influenza B and Salmonella typhi19–21 as well as intracellular organisms like Mycoplasma pneumoniae. Falciparum malaria is an important infection in SCD patients and contributes to the development of anaemia and hospitalization.20,22 Malnutrition is a risk factor for infection. Infections and the existence of malnutrition in African is a major concern. A study in Ghana revealed that the prevalence of malnutrition was 61.3% among SCD subjects and 28.6% among controls, (p
MJHID Educational Material
Sickle Cell Disease: Management Options and Challenges in Developing Countries Daniel Ansong1,2, Alex Osei Akoto1,2, Delaena Ocloo2 and Kwaku Ohene-Frempong3 1
School of Medical Sciences,- Kwame Nkrumah University of Science and Technology, Kumasi-Ghana Department of Child Health, Komfo Anokye Teaching Hospital, Kumasi-Ghana 3 Children’s Hospital of Philadelphia, Director, Comprehensive Sickle Cell Centre, USA 2
Correspondence to: Daniel Ansong, Komfo Anokye Teaching Hospital, Post Office Box 1934, Kumasi. Tel: +233 20 8168767. Email: [email protected]. Competing interests: The authors have declared that no competing interests exist. Published: November 4, 2013 Received: June 23, 2013 Accepted: October 15, 2013 Citation: Mediterr J Hematol Infect Dis 2013, 5(1): e2013062, DOI: 10.4084/MJHID.2013.062 This article is available from: http://www.mjhid.org/article/view/11899 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract. Sickle Cell Disease (SCD) is the most common genetic disorder of haemoglobin in subSaharan Africa. This commentary focuses on the management options available and the challenges that health care professionals in developing countries face in caring for patients with SCD. In a developing countries like Ghana, new-born screening is now about to be implemented on a national scale. Common and important morbidities associated with SCD are vaso-occlusive episodes, infections, Acute Chest Syndrome (ACS), Stroke and hip necrosis. Approaches to the management of these morbidities are far advanced in the developed countries. The differences in setting and resource limitations in developing countries bring challenges that have a major influence in management options in developing countries. Obviously clinicians in developing countries face challenges in managing SCD patients. However understanding the disease, its progression, and instituting the appropriate preventive methods are paramount in its management. Emphasis should be placed on early counselling, new-born screening, anti-microbial prophylaxis, vaccination against infections, and training of healthcare workers, patients and caregivers. These interventions are affordable in developing countries. Introduction. Sickle Cell Disease (SCD) is the most common genetic disorder of haemoglobin in subSaharan Africa.1,2 In Africa it is estimated that about 200,000 children are born with the disease annually.3 A point mutation on the 6th codon of the beta-globin gene located on the short arm of chromosome 11 produces a defective beta globin chain, which under low oxygen tension polymerizes into long fibres that eventually lead to abnormally deformed (sickled) red cell. The red cells thus become sticky, adhere to endothelium and Mediterr J Hematol Infect Dis 2013; 5; Open Journal System
clump together plugging micro-vessels4 and also damage large blood vessels that can become severely stenotic or occluded. In addition, sickle red cells have a much-shortened life span making chronic haemolytic anaemia a constant feature of SCD. The combination of vaso-occlusion and haemolytic anaemia contributes to the basic presentation of the disease and associated complications of which some are life threatening. Biomedical technology is moving very fast to use hematopoietic stem cell transplantation and gene
therapy in the management of the disease in developed countries. However, only very few SCD patients have been successfully treated with hematopoietic stem cell transplantation5 and, gene therapy has not been successful yet in curing SCD.6 In general, the disease is managed using a combination of preventive and symptomatic therapies.7 This commentary focuses on the management options available and the challenges that health care professionals in developing countries face in caring for patients with SCD. Sickle Cell Vaso-Occlusive Episodes. The hallmark of SCD is the occurrence of vaso-occlusive episodes. These are characterized clinically by pain in the affected sites of the body. Pain episodes are largely unpredictable and but can be prevented and in more than 80% of the episodes, there is no potential precipitating cause.8 The pathophysiology of the pain is as a result of hypoxia and release of inflammatory mediators and pain neurotransmitters.9–11 Infections are thought to be playing a role in the pathogenesis of vaso-occlusive episodes,12 making the occurrence of vaso-occlusive episode a trigger to alerting potential problems in SCD. The severity of pain in people with SCD varies from mild to severe and the management is determined by accurate estimation of the severity and the associated pre-morbid conditions.7 Management Options. The choice of an analgesic is of importance for effective pain management and so is the identification of the underlying cause that precipitated the occurrence of the episodes. The range of analgesics used to manage pain in SCD patients is similar in developed and developing countries. The analgesic spans from acetaminophen, non-steroidal antiinflammatory drugs (NSAID) to opioids.13,14 There are several behavioural and non-medicinal therapies that are also available in the management of pain. There is evidence to show that hydroxyurea ameliorates the episodes of vaso-occlusive crisis in adults15,16 and in children in the recent BABY HUG study.17 Hydroxyurea can be used in SCD patient to achieve great benefit in preventing painful episodes. It is worthy of note that the use of hydroxyurea comes with caution because of the risk of neutropenia. Challenges. The long-term use of the analgesics comes with major challenges and complications. Patients develop gastric erosion and ulcers when they are placed on NSAIDs. In addition, the long-term use of these drugs can have effects on the kidneys. Clinicians are also confronted with side effect of the long-term use of opioids like pethidine, codeine and morphine in the management of pain without significantly causing respiratory depression with parenteral use and tolerance with long term use.18 Clinicians in developing Mediterr J Hematol Infect Dis 2013; 5: Open Journal System
countries should therefore use opioids with caution for the fear of respiratory depression as well as development of tolerance. The option of hydroxyurea to ameliorate the episodes of vaso-occlusive episode would need more research in the African population. Infections in Sickle Cell Disease. The risk of infection in SCD patient is well established because of several factors, namely, hyposplenism or asplenia and also, the availability of free iron radicals for growth of bacteria, defective chemotaxis and opsonisation, and presence of dead necrotic tissue in some parts of the body especially the bones.4,11 Children with SCD are particularly prone to infection by encapsulated organisms like Strep pneumoniae, Haemophilus influenza B and Salmonella typhi19–21 as well as intracellular organisms like Mycoplasma pneumoniae. Falciparum malaria is an important infection in SCD patients and contributes to the development of anaemia and hospitalization.20,22 Malnutrition is a risk factor for infection. Infections and the existence of malnutrition in African is a major concern. A study in Ghana revealed that the prevalence of malnutrition was 61.3% among SCD subjects and 28.6% among controls, (p
