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Sickle Cell Disease

The Need for a Public Health Agenda

      Abstract

      Sickle cell disease (SCD) is a collection of inherited blood disorders that affect a substantial number of people in the U.S., particularly African Americans. People with SCD have an abnormal type of hemoglobin, Hb S, which polymerizes when deoxygenated, causing the red blood cells to become misshapen and rigid. Individuals with SCD are at higher risk of morbidity and mortality from infections, vaso-occlusive pain crises, acute chest syndrome, and other complications. Addressing the public health needs related to SCD is an important step toward improving outcomes and maintaining health for those affected by the disorder. The objective of this study was to review public health activities focusing on SCD and define the need to address it more comprehensively from a public health perspective. We found that there has been some progress in the development of SCD-related public health activities. Such activities include establishing newborn screening (NBS) for SCD with all states currently having universal NBS programs. However, additional areas needing focus include strengthening surveillance and monitoring of disease occurrence and health outcomes, enhancing adherence to health maintenance guidelines, increasing knowledge and awareness among those affected, and improving healthcare access and utilization. These and other activities discussed in this paper can help strengthen public health efforts to address SCD.

      Introduction

      Sickle cell disease (SCD) comprises a group of inherited blood disorders that are life-long and affect many people globally. The WHO estimates that SCD affects 275,000 conceptions each year.
      • Modell B.
      • Darlison M.
      Global epidemiology of haemoglobin disorders and derived service indicators.
      • Weatherall D.J.
      • Clegg J.B.
      Inherited haemoglobin disorders: an increasing global health problem.
      Sickle Cell Disease Guideline Panel
      Sickle cell disease: screening, diagnosis, management, and counseling in newborns and infants.
      In the U.S., SCD is seen more commonly among people of African descent and people (or their descendants) from parts of tropical and subtropical regions where malaria is or was common, such as individuals with an Hispanic, Mediterranean, or Southeast Asian background. However, because the U.S. population is not ethnically homogenous, it is important that SCD not be seen as occurring exclusively among these groups.
      The purpose of this paper is to assess existing public health programs and define the need to achieve a more comprehensive public health approach for reducing morbidity and mortality related to SCD in the U.S. Using the essential public health services as a framework, we examined existing public health–related activities addressing SCD; we also identified opportunities—while assessing gaps—toward a greater and broader public health focus on health promotion and disease prevention.

      Disease Characteristics

      Sickle cell disease is characterized by the presence of sickle hemoglobin (Hb S) in red blood cells.
      • Bunn H.F.
      Pathogenesis and treatment of sickle cell disease.
      • Lane P.A.
      Sickle cell disease.
      It is an autosomal recessive genetic disorder. Individuals who are heterozygous are carriers and are referred to as having sickle cell trait (SCT). Individuals who are homozygous or compound heterozygous for the mutation have SCD. Most SCD in the U.S. comprises one of four genotypes: sickle cell anemia (Hb SS); sickle-hemoglobin C disease (Hb SC); and two types of sickle β-thalassemia (Sβ+-thalassemia and Sβ0-thalassemia). Among disorders identified by newborn screening (NBS), SCD is the most common, with approximately 1800 births recorded by states that reported cases in 2006 (genes-r-us.uthscsa.edu).
      Among people with SCD, sickled red blood cells may occlude small blood vessels and capillaries, resulting in a lack of oxygen for the tissues. This causes the episodes of pain—which can be severe—that many people with SCD suffer. It also can result in acute and chronic organ damage. Children with SCD are at risk of life-threatening infections.
      • Lane P.A.
      Sickle cell disease.
      People with SCD also are at higher risk of stroke, acute chest syndrome, leg ulcers, pulmonary hypertension, and other complications.
      • Lane P.A.
      Sickle cell disease.
      Although SCT generally is a benign and asymptomatic state, red blood cell sickling and splenic infarction can occur at low oxygen levels such as at high altitudes. Research suggests that SCT is associated with a number of other complications that are usually relatively infrequent or occur under conditions of severe biological stress.
      • Tsaras G.
      • Owusu-Ansah A.
      • Boateng F.O.
      • Amoateng-Adjepong Y.
      Complications associated with sickle cell trait: a brief narrative review.
      • Mitchell B.L.
      Sickle cell trait and sudden death—bringing it home.
      • Makaryus J.N.
      • Catanzaro J.N.
      • Katona K.C.
      Exertional rhabdomyolysis and renal failure in patients with sickle cell trait: is it time to change our approach?.

      Public Health and Reducing Disease and Disability

      The goals of public health are to prevent disease and injury and promote health. Strategies to improve health and prevent disease have a major focus on the healthy state of individuals, and this applies also to improving and maintaining health among people with SCD. In addition, strategies also need to be undertaken to prevent mortality, disability, and other morbidity. This has particular considerations related to individuals with chronic genetic disorders such as SCD as many such people are at a greater risk for morbidity and mortality.
      Health promotion, early detection and intervention, and other activities discussed in this paper are integral to the purposes of public health and are consistent with the Ten Essential Public Health Services
      CDC
      National Public Health Performance Standards Program: 10 essential public health services.
      defined by the collaborative effort of national organizations and federal agencies; these are:
      • 1
        monitor health status to identify and solve community health problems;
      • 2
        diagnose and investigate health problems and health hazards in the community;
      • 3
        inform, educate, and empower people about health issues;
      • 4
        mobilize community partnerships to identify and solve health problems;
      • 5
        develop policies and plans that support individual and community health efforts;
      • 6
        enforce laws and regulations that protect health and ensure safety;
      • 7
        link people to needed personal health services and assure the provision of health care when otherwise unavailable;
      • 8
        assure a competent public and personal healthcare workforce;
      • 9
        evaluate effectiveness, accessibility, and quality of personal and population-based health services; and
      • 10
        research for new insights and innovative solutions to health problems.

      Sickle Cell Disease Newborn Screening

      Newborn screening for SCD consists of identifying a neonate's sickle cell hemoglobin status at the time of or soon after birth. An early NBS program for SCD was implemented in New York State in 1975.
      • Olney R.S.
      Newborn screening for sickle cell disease: public health impact and evaluation.
      • Lerner N.B.
      • Platania B.L.
      • LaBella S.
      Newborn sickle cell screening in a region of Western New York State.
      In the late 1970s and early 1980s, statewide programs were implemented in Colorado, Texas, and Georgia. These programs showed the effectiveness of these approaches and provided valuable knowledge on different strategies for NBS.
      • Harris M.S.
      • Eckman J.R.
      Georgia's experience with newborn screening: 1981 to 1985.
      • Therrell B.L.
      • Simmank J.L.
      • Willborn M.
      Experiences with sickle hemoglobin testing in the Texas Newborn Screening Program.
      • Lloyd-Puryear M.A.
      • Therrell B.L.
      • Mann M.Y.
      • Eckman J.R.
      • Telfair J.
      The role of the federal government in supporting state newborn screening programs.
      As of January 2006, all states and Puerto Rico and the Virgin Islands had implemented universal screening for SCD. State NBS programs use filter paper for their screening tests, placing blood on the filter paper.
      • Pass K.A.
      • Lane P.A.
      • Fernhoff P.M.
      • et al.
      U.S. newborn screening system guidelines II: follow-up of children, diagnosis, management, and evaluation Statement of the Council of Regional Networks for Genetic Services.
      NIH
      The management of sickle cell disease.
      Confirmatory testing of infants with positive neonatal screening results and diagnosis require hemoglobin separation by electrophoresis (cellulose acetate and citrate agar), isoelectric focusing, or high-performance liquid chromatography. Depending on state policies, NBS programs vary as to whom they report positive screening results and whether all, some, or no carriers of hemoglobinopathies are actively followed up.
      • Kavanagh P.
      • Wang C.J.
      • Therrell B.L.
      • Sprinz P.G.
      • Bauchner H.
      Communication of positive newborn screening results for sickle cell disease and sickle cell trait: variation across states.
      There also is variation in the methods used for communicating results to those followed up with and in screening and information disclosure–related consent procedures.
      • Kavanagh P.
      • Wang C.J.
      • Therrell B.L.
      • Sprinz P.G.
      • Bauchner H.
      Communication of positive newborn screening results for sickle cell disease and sickle cell trait: variation across states.
      • Therrell B.L.
      • Johnson A.
      • Williams D.
      Status of newborn screening programs in the United States.
      A number of recent studies provide information indicating effectiveness of NBS programs in the U.S. and elsewhere
      • Lerner N.B.
      • Platania B.L.
      • LaBella S.
      Newborn sickle cell screening in a region of Western New York State.
      • Frempong T.
      • Pearson H.A.
      Newborn screening coupled with comprehensive follow-up reduced early mortality of sickle cell disease in Connecticut.
      • King L.
      • Fraser R.
      • Forbes M.
      • Grindley M.
      • Ali S.
      • Reid M.
      Newborn sickle cell disease screening: the Jamaican experience (1995–2006).
      • Bardakdjian-Michau J.
      • Guilloud-Bataille M.
      • Maier-Redelsperger M.
      • et al.
      Decreased morbidity in homozygous sickle cell disease detected at birth.
      • Rahimy M.C.
      • Gangbo A.
      • Ahouignan G.
      • Alihonou E.
      Newborn screening for sickle cell disease in the Republic of Benin.
      (Table 1). A recent study by Frempong and Pearson
      • Frempong T.
      • Pearson H.A.
      Newborn screening coupled with comprehensive follow-up reduced early mortality of sickle cell disease in Connecticut.
      found that there were fewer SCD-related deaths among children after implementation of universal NBS in Connecticut in 1990. In the NBS program studied, if the screening result indicated a major hemoglobinopathy, the delivery provider, pediatrician (if known), parents, and one of the sickle cell centers were informed. For successful health outcomes, the study suggested the need for comprehensive follow-up care of infants as well as further screening tests. Another recent study that evaluated a NBS program in Jamaica also reported that hospital admissions and occurrence of serious illness were reduced among patients with SCD because of NBS and early interventions.
      • King L.
      • Fraser R.
      • Forbes M.
      • Grindley M.
      • Ali S.
      • Reid M.
      Newborn sickle cell disease screening: the Jamaican experience (1995–2006).
      Table 1Selected recent studies assessing impact of NBS programs for SCD
      StudyCharacteristics of the screening program
      As described in this paper.
      Findings related to impact of the program
      • Frempong and Pearson (2007)
        • Frempong T.
        • Pearson H.A.
        Newborn screening coupled with comprehensive follow-up reduced early mortality of sickle cell disease in Connecticut.
      • Newborn Screening Program in Connecticut
      • All newborns are screened for SCD
      • When a newborn is putatively identified with a major hemoglobinopathy, the hospital, birthing physician, child's pediatrician, a regional sickle cell center, and the child's parents are informed.
      • Follow-up at a sickle cell center by age 3 months is suggested, confirmatory testing is done, and the recommended treatment to be followed includes frequent visits at an early age, penicillin prophylaxis and PCV7 vaccination, and education and genetic counseling.
      • No deaths caused by SCD were reported from 1990 to 2002, when universal NBS was in place, compared to 13 deaths between 1970 and 1988 when there was no NBS.
      • During 1988–1990, when limited NBS was in place, five children with SCD, who may have been born in the state and who later died, were not tested.
      • King et al. (2007)
        • King L.
        • Fraser R.
        • Forbes M.
        • Grindley M.
        • Ali S.
        • Reid M.
        Newborn sickle cell disease screening: the Jamaican experience (1995–2006).
      • Newborn screening program in three hospitals in Kingston or St. Katherine Parish, Jamaica
      • Children screening positive for hemoglobinopathy receive further testing at the SCU, and those with confirmed diagnosis are enrolled at the SCU clinic.
      • Patient follow-up activities include parent education and counseling, including training on how to palpate for spleen enlargement, nutrition and psychological support, routine visits, low-threshold sick visits, penicillin prophylaxis, and pneumococcal immunization, and other activities related to extensive health maintenance.
      • The mortality rate (1.8%) was less in the current study cohort (395 children with Hb SS screened between 1995 and 2006 and followed up a mean of 5.1 years, range 0.2–11.0) than in an earlier study cohort (17.6%) of children of same age with Hb SS screened between 1973 and 1981.
      • The percentage of children who died by age 2 years was lower in the current cohort compared to an earlier cohort when early-age interventions had not been implemented (1% vs 14%).
      • There was a significantly lower percentage with serious illness of acute chest syndrome, stroke, culture-positive sepsis, and acute splenic sequestration in the recent cohort overall.
      • For children screened positive, the screening program and the child's PCP are informed of the results with request to the physician for obtaining blood sample for confirmatory testing and informing the family if confirmed positive.
      • Follow-up activities include provision of education materials to provider; home visit for provision of SCD-related counseling, teaching, and written material to parents/caregivers; and informing PCP of home visit result and requesting that child be referred to hemoglobinopathy clinic program
      • The program also includes hemoglobinopathy trait notification and education-related activities.
      • From 1990 through 2006, 12% of children identified with SCD did not enroll or were lost to follow-up at the specialty clinic, compared with 2% from 2000 to 2006.
      • The mortality rate attributable to SCD was 0.16 per 100 patient-years of follow-up.
      • Newborn screening appears to have increased seeking of specialized medical care related to SCD.
      • Bardakdjian-Michau et al. (2002)
        • Bardakdjian-Michau J.
        • Guilloud-Bataille M.
        • Maier-Redelsperger M.
        • et al.
        Decreased morbidity in homozygous sickle cell disease detected at birth.
      • France
      • When there is a positive screening result, it is followed up with family genetic counseling and confirmation of diagnosis.
      • Children with SCD are put on prophylactic penicillin; parental teaching and education is provided; written information and instructions are provided to other physicians who may care for the child; and child is followed regularly at a specialized center.
      • The occurrence of pain crisis and splenic sequestration was significantly less among 38 children with Hb SS diagnosed at birth than among 69 children with Hb SS diagnosed at mean age of 24 months with mean age of last medical follow-up of approximately 6 years in both groups.
      • Rahimy et al. (2009)
        • Rahimy M.C.
        • Gangbo A.
        • Ahouignan G.
        • Alihonou E.
        Newborn screening for sickle cell disease in the Republic of Benin.
      • Pilot program in two largest maternity services in Cotonou, Benin
      • Children with SCD whose mothers volunteered were enrolled in comprehensive follow-up and received evaluations at specified intervals.
      • Follow-up activities include parental education, pneumococcal and malaria prophylaxis, EPI and specific immunizations, and micronutrient supplementation.
      • In an analysis of 840 years of follow-up among children with Hb SS, SC, or CC enrolled in the program, the mortality rate was 15.5 per 1000, which is approximately 10 times less than the overall rate of mortality for children aged <5 years in the country.
      EPI, Expanded Program on Immunizations; Hb CC, homozygous hemoglobin C disease; Hb SC, sickle-hemoglobin C disease; Hb SS, sickle cell anemia; NBS, newborn screening; PCP, primary care provider; PCV7, heptovalent pneumococcal-conjugated vaccine; SCD, sickle cell disease; SCU, sickle cell unit
      a As described in this paper.
      Newborn screening program activities are mechanisms by which public health has helped to reduce morbidity and mortality and improve the well-being of people with SCD. The activities of state NBS programs in the U.S., for example, apply principles related to detection of health problems, implementing policies and practices to address these, promoting partnerships and coordination among various entities, informing and educating the public, and linking people to health services. These activities are consistent with the essential services of public health. However, more needs to be done. Currently, there are no standardized NBS follow-up guidelines for SCD. Such guidelines could include information related to whom to follow-up with positive results, what information to convey, provider follow-up protocols, and what modes of communication are best. NBS programs have also been less successful in providing an ongoing and systematic approach of long-term follow-up, along with health promotion and disease prevention interventions for individuals with SCD beyond the newborn period and for activities related to SCT.

      Surveillance and Monitoring

      Epidemiologic information—such as incidence and prevalence of disease, risk factors, and health impact—helps in developing and strengthening strategies for reducing morbidity and mortality from SCD. Recent studies assessing SCD prevalence in the U.S. estimate that approximately 90,000 people have SCD.
      • Brousseau D.C.
      • Panepinto J.A.
      • Nimmer M.
      • Hoffmann R.G.
      The number of people with sickle-cell disease in the United States: national and state estimates.
      • Hassel K.L.
      Population estimates of sickle cell disease in the U.S..
      Among neonates with SCD in California, the prevalence of SCD was reported to be one per 396 births among African Americans; 6% of neonates with SCD were reported to be among Hispanic Americans.
      • Lorey F.W.
      • Arnopp J.
      • Cunningham G.C.
      Distribution of hemoglobinopathy variants by ethnicity in a multiethnic state.
      A study assessing NBS among infants born in California, Massachusetts, North Carolina, and Wisconsin reported rates of occurrence of 17.7, 17.4, and 2.0 per 10,000 births for Hb SS, Hb SC, and Hb S/β-thalassemia, respectively, during the time period 2001–2006.
      • Therrell B.
      • Lorey F.
      • Eaton R.
      • et al.
      Impact of expanded newborn screening—United States, 2006.
      Although a number of individual studies have focused on the epidemiology SCD, population-based disease surveillance activities and disease registries are also needed. Surveillance information is needed for the development and implementation of programs and strategies for reducing morbidity and mortality, such as through appropriate follow-up, referral, and delivery of services. Public health activities need to be implemented at state and local levels for continued collection, assessment, and use of information related to SCD occurrence. Coordination and support at the national level should help facilitate this. Clinical registries obtain longitudinal information and are effective mechanisms for researching and identifying the effectiveness of treatments and assessing improvements in outcomes. Public health efforts should focus on the development of model procedures, tools, evaluation steps, and related research. Implementing and strengthening surveillance-related genetic and biomolecular laboratory support at national, state, and local levels, as applicable, are also imperative.
      Recent efforts to improve surveillance and monitoring related to SCD include the Registries and Surveillance for Hemoglobinopathies (RuSH) project coordinated by government agencies including the CDC, Health Resources and Services Administration, the NIH, and seven pilot states (www.cdc.gov/sicklecell). The immediate goals of the RuSH project are to find out the number of people that have SCD or clinically significant thalassemia, develop plans for a national surveillance system to acquire better knowledge about the disorders, and improve knowledge and awareness among the general public about the disorders. The RuSH project will help to develop better knowledge about how people's health is affected by SCD and thalassemia.

      Prevention of Complications and Improvement of Health Outcomes

      Sickle cell disease has a deleterious effect on immune system functions, and thus children with SCD are at increased risk of life-threatening infections, especially with Streptococcus pneumoniae and Haemophilus influenzae.
      • Gill F.M.
      • Sleeper L.A.
      • Weiner S.J.
      Clinical events in the first decade in a cohort of infants with sickle cell disease Cooperative study of sickle cell disease.
      • Overturf G.D.
      Prevention of invasive pneumococcal infection in sickle cell disease: on the threshold of a new era of successes?.
      • Leikin S.R.
      • Gallagher D.
      • Kinney T.R.
      • et al.
      Mortality in children and adolescents with sickle cell disease.
      • Wong W.-Y.
      • Overturf G.D.
      • Powars D.R.
      Infection caused by Streptococcus pneumoniae in children with sickle cell disease: epidemiology, immunologic mechanism, prophylaxis, and vaccination.
      However, many of the infections are preventable. The strong protective effect of penicillin prophylaxis has been demonstrated by several studies.
      • Wong W.-Y.
      • Overturf G.D.
      • Powars D.R.
      Infection caused by Streptococcus pneumoniae in children with sickle cell disease: epidemiology, immunologic mechanism, prophylaxis, and vaccination.
      • Powars D.
      • Overturf G.
      • Weiss J.
      • Lee S.
      • Chan L.
      Pneumococcal septicemia in children with sickle cell anemia.
      • Gaston M.H.
      • Verter J.I.
      • Woods G.
      • et al.
      Prophylaxis with oral penicillin in children with sickle cell anemia.
      • Zarkowski H.S.
      • Gallagher D.
      • Gill F.M.
      • et al.
      Bacteremia in sickle hemoglobinopathies.
      • Pegelow C.H.
      • Armstrong F.D.
      • Light S.
      • Toledano S.R.
      • Davis J.
      Experience with the use of prophylactic penicillin in children with sickle cell anemia.
      According to a clinical guideline for the management of SCD, children with Hb SS or sickle Sβ0-thalassemia should receive regular penicillin prophylaxis from as early as age 2 months through 5 years, and parents should have the option to continue prophylaxis for patients aged more than 5 years; for patients with Hb SC, penicillin prophylaxis has been stated to be probably wise.
      NIH
      The management of sickle cell disease.
      In addition to antibiotic prophylaxis, children with SCD need to be up to date with routinely recommended vaccines, including pneumococcal and H. influenzae type b (Hib) vaccines. Children with SCD should receive both the 13-valent pneumococcal-conjugated vaccine (PCV13) starting at age 2–6 months and the 23-valent polysaccharide vaccine from age 2 years.
      NIH
      The management of sickle cell disease.
      In a study conducted among children with SCD in metropolitan Atlanta, having one or more doses of heptovalent PCV (PCV7) was 81.4% effective in preventing pneumococcal infection after controlling for herd immunity.
      • Adamkiewicz T.V.
      • Silk B.J.
      • Howgate J.
      • et al.
      Effectiveness of the 7-valent pneumococcal conjugate vaccine in children with sickle cell disease in the first decade of life.
      Yanni and colleagues
      • Yanni E.
      • Grosse S.D.
      • Yang Q.
      • Olney R.S.
      Trends in pediatric sickle cell disease-related mortality in the United States, 1983–2002.
      found significant declines in mortality rates among children aged 0–3 years from the period 1994–1998 to the period 1999–2002 after not decreasing during the 1990s, and proposed that the decline in the mortality rate was related to the implementation of PCV7 vaccination beginning in 2000.
      Available information suggests that nonadherence to regular prophylaxis may be occurring among a substantial proportion of children with sickle cell anemia.
      • Pegelow C.H.
      • Armstrong F.D.
      • Light S.
      • Toledano S.R.
      • Davis J.
      Experience with the use of prophylactic penicillin in children with sickle cell anemia.
      • Buchanan G.R.
      • Siegel J.D.
      • Smith S.J.
      • DePasse B.M.
      Oral penicillin prophylaxis in children with impaired splenic function: a study of compliance.
      • Buchanan G.R.
      • Smith S.J.
      Pneumococcal septicemia despite pneumococcal vaccine and prescription of penicillin prophylaxis in children with sickle cell anemia.
      • Adamkiewicz T.V.
      • Sarnaik S.
      • Buchanan G.R.
      • et al.
      Invasive pneumococcal infections in children with sickle cell disease in the era of penicillin prophylaxis, antibiotic resistance, and 23-valent pneumococcal polysaccharide vaccination.
      Limited information is available on immunization rates among children with SCD. The failure to have all children with SCD receive appropriate prophylaxis may result in pneumococcal as well other organism infections among these children that could be prevented. These not only cause pain and suffering, but also result in healthcare and related expenditures. Public health efforts, when appropriate, are needed for the promotion of adherence among children prescribed regular penicillin prophylaxis and the receipt of all recommended pneumococcal and other vaccines.
      Investigators have used counseling during clinic visits as a mechanism for improving compliance with penicillin prophylaxis among patients with SCD.
      • Buchanan G.R.
      • Siegel J.D.
      • Smith S.J.
      • DePasse B.M.
      Oral penicillin prophylaxis in children with impaired splenic function: a study of compliance.
      Elliot and colleagues
      • Elliot V.
      • Morgan S.
      • Day S.
      • Mollerup L.S.
      • Wang W.
      Parental health beliefs and compliance with prophylactic penicillin administration in children with sickle cell disease.
      found that the number of hospitalizations and demographic and socioeconomic factors (such as the number of adults and children in the household and having a car) were related to compliance ratings associated with penicillin prescribed in liquid form. Evidence-based strategies, such as reminders and provider and/or patient education, have been developed for improvement of various health-related practices.
      • Grimshaw J.
      • Eccles M.
      • Thomas R.
      • et al.
      Toward evidence-based quality improvement Evidence (and its limitations) of the effectiveness of guideline dissemination and implementation strategies 1966–1998.
      • Haywood C.
      • Beach M.C.
      • Lanzkron S.
      A systematic review of barriers and interventions to improve appropriate use of therapies for sickle cell disease.
      These principles can be helpful toward guiding activities related to SCD. Development, translation, and broader implementation of strategies for prophylaxis adherence and immunization, as appropriate, should help to improve health outcomes for people with SCD. These types of strategies also may be applicable for other interventions.
      • Simon K.
      • Lobo M.L.
      • Jackson S.
      Current knowledge in the management of children and adolescents with sickle cell disease: part 1, physiological issues.
      For example, patients with SCD who receive chronic blood transfusions may be at greater risk of developing iron overload. Ensuring compliance among patients prescribed iron chelation therapy is therefore very important.
      • Wood J.C.
      Cardiac iron across different transfusion-dependent diseases.
      • Porter J.B.
      Concepts and goals in the management of transfusional iron overload.
      • Alvarez O.
      • Rodriquez-Cortes H.
      • Robinson N.
      • et al.
      Adherence to deferasirox in children and adolescents with sickle cell disease during 1-year of therapy.
      Causes of death among patients with SCD include cardiopulmonary causes such as cardiac arrest, heart failure, and pulmonary embolism, infections, stroke, and multiorgan failure.
      • Gill F.M.
      • Sleeper L.A.
      • Weiner S.J.
      Clinical events in the first decade in a cohort of infants with sickle cell disease Cooperative study of sickle cell disease.
      • Steiner C.A.
      • Miller J.L.
      Sickle cell disease patients in U.S. hospitals, 2004.
      • Fitzhugh C.D.
      • Lauder N.
      • Jonassaint J.C.
      • et al.
      Cardiopulmonary complications leading to premature deaths in adult patients with sickle cell disease.
      Among children hospitalized with SCD, frequent complications include infections and pulmonary conditions.
      • Steiner C.A.
      • Miller J.L.
      Sickle cell disease patients in U.S. hospitals, 2004.
      A longitudinal study of patients with SCD in several clinical centers reported sickle cell pain crisis and acute chest syndrome as the most frequent clinical events during the first 10 years of life.
      • Gill F.M.
      • Sleeper L.A.
      • Weiner S.J.
      Clinical events in the first decade in a cohort of infants with sickle cell disease Cooperative study of sickle cell disease.
      Pain crisis is a common cause of emergency department visits among both children and adults with SCD and is also a frequent cause of hospitalization.
      • Fosdal M.B.
      • Wojner-Alexandrov A.W.
      Events of hospitalization among children with sickle cell disease.
      • Yusuf H.R.
      • Atrash H.K.
      • Grosse S.D.
      • Parker C.S.
      • Grant A.M.
      Emergency department visits made by patients with sickle cell disease: a descriptive study.
      • Lanzkron S.
      • Carroll C.P.
      • Haywood Jr, C.
      The burden of emergency department use for sickle-cell disease: an analysis of the national emergency department sample database.
      Improvements are needed in pain management among patients with SCD, identification of best practices for such care, and the development of management guidelines, for example, in emergency departments.
      • Haywood Jr., C.
      • Beach M.C.
      • Lanzkron S.
      • et al.
      A systematic review of barriers and interventions to improve appropriate use of therapies for sickle cell disease.
      • Hassell K.
      • Pace B.
      • Wang W.
      • et al.
      Sickle cell disease summit: from clinical and research disparity to action.
      • Ballas S.K.
      • Bauserman R.L.
      • McCarthy W.F.
      • et al.
      Utilization of analgesics in the multicenter study of hydroxyurea in sickle cell anemia: effect of sex, age, and geographical location.
      As asthma may affect outcomes in SCD, research should be implemented to better understand the association and appropriate management in such cases.
      • Boyd J.H.
      • Macklin E.A.
      • Strunk R.C.
      • DeBaun M.R.
      Asthma is associated with increased mortality in individuals with sickle cell anemia.
      • Field J.J.
      • DeBaun M.R.
      Asthma and sickle cell disease: two distinct diseases or part of the same process?.
      Blood transfusions are a therapeutic measure among many people with SCD. Among hospitalized patients with SCD, transfusions are a frequent procedure.
      • Steiner C.A.
      • Miller J.L.
      Sickle cell disease patients in U.S. hospitals, 2004.
      • Slonim A.D.
      • Joseph J.G.
      • Turenne W.M.
      • Sharangpani A.
      • Luban N.L.
      Blood transfusions in children: a multi-institutional analysis of practices and complications.
      In this regard, it is important to maintain and improve as necessary blood product transfusion safety.
      • Slonim A.D.
      • Joseph J.G.
      • Turenne W.M.
      • Sharangpani A.
      • Luban N.L.
      Blood transfusions in children: a multi-institutional analysis of practices and complications.
      Improvements are also needed in other aspects of medical care for patients with SCD, including preventing organ damage and other complications and maintaining health.
      Over the past years, considerable progress has been achieved in reducing morbidity and mortality related to SCD among children.
      • Yanni E.
      • Grosse S.D.
      • Yang Q.
      • Olney R.S.
      Trends in pediatric sickle cell disease-related mortality in the United States, 1983–2002.
      • Fullerton H.J.
      • Adams R.J.
      • Zhao S.
      • Johnston S.C.
      Declining stroke rates in Californian children with sickle cell disease.
      For example, a study by Fullerton et al.
      • Fullerton H.J.
      • Adams R.J.
      • Zhao S.
      • Johnston S.C.
      Declining stroke rates in Californian children with sickle cell disease.
      indicated that the incidence of stroke among children with SCD in California declined after 1998. According to the authors, it was possible that the decline may have been related to preventive transfusions among children with high-risk SCD. However, as discussed in the previous text, more improvements are urgently needed to improve health outcomes among people with SCD. Comprehensive efforts to address this should include improving knowledge and understanding through research, identification of effective interventions and strategies, and promoting translation and implementation.

      Increasing Knowledge and Awareness and Health Promotion

      For people with SCD and the parents of children with SCD, knowledge related to complication prevention and health maintenance is imperative. These include preventing dehydration; avoiding exposure to severe cold or heat; preventing infections; maintaining appropriate nutrition, recognizing and getting early medical follow-up for symptoms such as fever; and implementing pain evaluation and management.
      NIH
      The management of sickle cell disease.
      • Wethers D.L.
      Sickle cell disease in childhood: part I laboratory diagnosis, pathophysiology, and health maintenance.
      Additionally, it is important to provide SCD-related genetic counseling and information about the health risks and options to those who are affected.
      • Creary M.
      • Williamson D.
      • Kulkarni R.
      Sickle cell disease: current activities, public health implications, and future directions.
      A survey of state and territorial NBS programs in 1998 reported substantial variation among the programs in providing counseling (e.g., variation in the diseases and the type of test result related to which counseling is provided).
      • Farrell M.H.
      • Certain L.K.
      • Farrell P.M.
      Genetic counseling and risk communication services of newborn screening programs.
      Information and awareness-related activities, therefore, should be an important component of effective public health strategies for reducing morbidity and mortality among people with SCD. Follow-up of infants with positive NBS results and provider contacts are among opportunities of where to try to enhance complication prevention knowledge and practice. Possible methods for delivery of such information include direct counseling, provision of information material, and referral to other sources. In a study evaluating written informational materials provided to children with SCD and their family members; nearly all respondent caregivers (96%) indicated that they found the materials to be helpful.
      • Mahat G.
      • Scoloveno M.A.
      • Donnelly C.B.
      Written educational materials for families of chronically ill children.
      Awareness activities through community-based organizations, support groups, and advocacy organizations also may provide effective avenues to reach people with SCD.

      Facilitating Better Healthcare Utilization

      People with SCD need to receive comprehensive medical care that includes specialized care by a hematologist.
      NIH
      The management of sickle cell disease.
      Children should have routine health visits approximately every 2–3 months during their first 2 years of life, and after that, visits should be as needed, but at least semiannually.
      NIH
      The management of sickle cell disease.
      Specialized treatment centers, such as comprehensive SCD treatment centers, can provide disease-specific comprehensive care encompassing various medical expertise and services.
      • Grosse S.D.
      • Schechter M.S.
      • Kulkarni R.
      • Lloyd-Puryear M.A.
      • Strickland B.
      • Trevathan E.
      Models of comprehensive multidisciplinary care for individuals in the United States with genetic disorders.
      • Aisiku I.P.
      • Penberthy L.T.
      • Smith W.R.
      Patient satisfaction in specialized vs. non-specialized adult sickle cell care centers.
      However, the number of specialized centers is limited, and sufficient access to them does not exist nationwide. Health services delivered through a primary care provider–coordinated medical home or a chronic care model may be better geared to provide primary and preventive care services.
      • Grosse S.D.
      • Schechter M.S.
      • Kulkarni R.
      • Lloyd-Puryear M.A.
      • Strickland B.
      • Trevathan E.
      Models of comprehensive multidisciplinary care for individuals in the United States with genetic disorders.
      American Academy of Pediatrics, Section on Hematology/Oncology, Committee on Genetics
      Health supervision for children with sickle cell disease.
      Day hospitals also have been reported to be a useful and effective health service delivery mechanism, particularly for treatment of sickle cell crisis or pain episodes.
      • Raphael J.L.
      • Kamdar A.
      • Wang T.
      Day hospital versus inpatient management of uncomplicated vaso-occlusive crises in children with sickle cell disease.
      • Benjamin L.J.
      • Swinson G.I.
      • Nagel R.L.
      Sickle cell anemia day hospital: an approach for the management of uncomplicated painful crises.
      These are ambulatory-type settings that are geared to manage uncomplicated vaso-occlusive crises.
      A substantial proportion of both children and adults with SCD rely on Medicaid for healthcare coverage.
      • Mayer M.
      • Konrad T.R.
      • Dvorak C.C.
      Hospital resource utilization among patients with sickle cell disease.
      • Woods K.
      • Karrison T.
      • Koshy M.
      • Patel A.
      • Friedmann P.
      • Cassel C.
      Hospital utilization patterns and costs for adult sickle cell patients in Illinois.
      A study assessing hospitalizations in the U.S. among patients with SCD found that the primary payer type for 66% of hospitalizations with a principal diagnosis of SCD was Medicaid.
      • Steiner C.A.
      • Miller J.L.
      Sickle cell disease patients in U.S. hospitals, 2004.
      Better understanding is needed on health insurance coverage among people with SCD.
      • Kass N.E.
      • Medley A.M.
      • Natowicz M.R.
      • et al.
      Access to health insurance: experiences and attitudes of those with genetic versus non-genetic medical conditions.
      • Hall M.A.
      • McEwan J.E.
      • Barton J.C.
      • et al.
      Concerns in a primary care population about genetic discrimination by insurers.
      • Roth M.T.
      • Painter R.B.
      Genetic discrimination in health insurance: an overview and analysis of the issues.
      In a study conducted between 1996 and 2000, Kass and colleagues
      • Kass N.E.
      • Medley A.M.
      • Natowicz M.R.
      • et al.
      Access to health insurance: experiences and attitudes of those with genetic versus non-genetic medical conditions.
      interviewed parents of children and people with or at higher risk of selected genetic or chronic diseases or HIV and found that 27% of respondents reported having experienced difficulty obtaining health insurance, and one third thought they would face difficulty obtaining health insurance in the future.
      Improving utilization will require focus in terms of needs assessments, identification of gaps and barriers, development of applicable strategies, and evaluation. In this regard, more research is needed related to how to best provide health care to people with SCD. Research findings have suggested that the frequency of primary care provider visits, as well as visits to specialists, among people with SCD may be less than optimal.
      • Raphael J.L.
      • Dietrich C.L.
      • Whitmire D.
      • Mahoney D.H.
      • Meuller B.U.
      • Giardino A.P.
      Health care utilization and expenditures for low income children with sickle cell disease.
      • Kuhlthau K.
      • Ferris T.G.
      • Beal A.C.
      • Gortmaker S.L.
      • Perrin J.M.
      Who cares for Medicaid-enrolled children with chronic conditions?.
      Studies also have indicated that people with SCD are much more likely to use emergency department services than the general population.
      • Raphael J.L.
      • Dietrich C.L.
      • Whitmire D.
      • Mahoney D.H.
      • Meuller B.U.
      • Giardino A.P.
      Health care utilization and expenditures for low income children with sickle cell disease.
      • Shankar S.M.
      • Arbogast P.G.
      • Mitchel E.
      • Cooper W.O.
      • Wang W.C.
      • Griffin M.R.
      Medical care utilization and mortality in sickle cell disease: a population-based study.
      Information also is needed on access to and utilization of appropriate treatment. For example, are all patients who should receive hydroxyurea receiving the therapy? Reported barriers to therapy have included issues related to compliance and laboratory monitoring.
      • Brandow A.M.
      • Jirovec D.L.
      • Panepinto J.A.
      Hydroxyurea in children with sickle cell disease: practice patterns and barriers to utilization.
      In addition, there is need for increased availability of providers with knowledge and expertise on SCD. Considerations to achieve this include increased medical training options related to SCD management.
      Recently, the USDHHS was given a charge to make SCD a priority focus area (www.minorityhealth.hhs.gov/templates/browse.aspx?lvl=2&lvlid=206). The substantial need for more efforts to increase access and improve health care and outcomes for people with SCD was a principle guiding the endeavor. To address this need, DHHS has charted actions related to improving surveillance activities, access to health care and other services, development of new drugs, and research with a biomedical and behavioral focus.

      Conclusion

      It has been almost 4 decades since the passage of the National Sickle Cell Anemia Control Act of 1972. This Act aimed to address the early identification of individuals with SCD and their ongoing treatment in a comprehensive manner. This article focused on several issues related to health among people with SCD. There are also other important areas that need to be included in public health efforts, for example, pregnancy and childbirth, psychological effects such as depression, social effects such as lower educational achievement and difficulty finding employment, as well as important considerations and deliberations related to genetic counseling such as carrier status knowledge and prenatal diagnosis. Although we did not discuss these in this article because of space limitations, no less importance is implied, because these and other issues also should be considerations of public health activities addressing SCD.
      There has been progress in public health activities addressing SCD. However, more efforts are needed. Issues needing more focus include that, to date, there are no standardized NBS-related follow-up procedures across the U.S. There are gaps in surveillance and monitoring efforts, research delineating disease epidemiology, and population-based programs that can help reduce morbidity and mortality among people with SCD. In addition, healthcare access and utilization is less than optimal. Most people with SCD are African Americans and other ethnic or racial minorities. As such, historical and cultural contexts are important to consider. Also important to consider is that programs and strategies focused on or coordinated with socioeconomic and environmental factors that affect health may often be more effective. For example, poverty, unemployment, lack of education, weak social support structures, and related disparities are factors that may affect health and well-being, and these considerations could help efforts to improve health.
      Nationally, we need a public health agenda for SCD that has as its basis the essential services of public health. Addressing issues and concerns discussed in this paper, as well as others, can help strengthen the public health focus on SCD.
      Publication of this article was supported by the Centers for Disease Control and Prevention through a Cooperative Agreement with the Association for Prevention Teaching and Research award # 09-NCBDDD-01.
      The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC Health Resources and Services Administration or the DHHS.
      No financial disclosures were reported by the authors of this paper.

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