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JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
SEPTEMBER 1976
Prevalence of Hemoglobin S in Black and Non-Black Childrent PHILIP R. FINE, Ph.D., M.S.P.H., Director of Research, Medical Rehabilitation Research and Planning Center, University of Alabama in Birmingham CRAIG W. THOMAS, B.A., D. V. M. ,* and BRUCE A. FLASHNER, M.D., M.A., Arthur Young and Company, Washington, D.C.
H E MOGLOBIN S and its associated pathological manifestations have long been considered a characteristic essentially confined to Negroes. Isolated cases of sickle cell anemia in "non-blacks" have been reported in individuals of Eastern Mediterranean ancestry. 1-3 The intention of those reports appears to have been the demonstration of hemoglobin S in individuals without African ancestry. Little attention, however, has been given to the actual prevalence of hemoglobin S-from whatever source-in Americans who, to the casual observer, appear to be and who describe themselves as something other than "black." Three early workers in the field, Diggs,4 Miyamoto,; and Sydenstricked6 tested, in aggregate, more than 700 "'whites" and found no evidence of sickling by the methods of that day. Those works appear to have been the last published evidence of any interest of the American medical community on the issue. This paper describes another study of "non-black" children and hemoglobin S. It might seem at first glance a needless repetition of the earlier works; however, those studies were done 40 years ago and do not reflect the effect of any sociological changes in the intervening years that may have influenced the amount of hemoglobin S found in "non-black" Americans. In addition they included residents of only one area of the country, the South. Recent reports have suggested that the amount of hemoglobin S associated with the tFrom the Illinois Department of Public Health, Springfield, Illinois. *Currently studying in New Zealand.
sickle cell trait may result in serious illness and/or death under some circumstances. 7 Several other pathological conditions have been found in association with sickle cell trait (Table 1). Whether these conditions are a result of hemoglobin S or are merely concomitant, has not been proven. One would expect, however, that if these conditions are a result of hemoglobin S that they might occur with the same frequency and severity in all individuals who possess the trait regardless of the percentage of their ancestry that is African. For these reasons then, it was thought worthwhile to test for hemoglobin S in "nonblack" children from an area of the northern United States. Black children from the same areas were also tested for hemoglobin S. MATERIALS AND METHODS
The testing program, of which this hemoglobinopathy study was a part, was organized primarily in order to study pediatric blood lead levels in downstate Illinois.8 Fourteen cities of the 149 in Illinois with populations between 10,000 and 150,0009 were chosen for the program according to criteria described earlier.8 Children one to six years of age from low income areas of older housing were the target population. In a few cases, children under one year of age or over six years of age who were siblings of other children being tested were also included in the sampling but only if they were within a few months of the age limitations. Liberal use of mass media communication was employed to attract children to the program.
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It must be stressed that the authors did not conduct detailed genealogical investigations into the ancestry of these children and in that regard this report is generally different from case reports of sickle cell anemia in "whites" that have appeared in the literature. The authors attempted instead to gather data for this study in a manner that, as closely as possible, resembled the history taking technique employed in most physicians' ofTable 1 PATHOLOGICAL CONDITIONS FOUND IN ASSOCIATION WITH SICKLE CELL TRAIT (HEMOGLOBIN SA) Gross hematuria Splenic infarction associated with high altitude flight Massive necrosis of the spleen with formation of a pseudo-cyst Sudden death following exertion soon after arrival at moderate altitude Death during anesthesia Renal infarction and perirenal hematoma Primary cardiomyopathy associated with chronic alcohol ingestion Superior longitudinal sinus thrombosis Bizarre cerebral manifestations Acute abdominal pain Increased prevalence of bacturia in older women Increased prevalence of bactufia in pregnant women Increased prevalence of electrocardiographic abnormalities and symptoms suggestive of angina pectoris Pulmonary infarction Increased prevalence of toxemia and complications dufing pregnancy Bladder atony Avascular necrosis of the femoral head Priapism
fices and hospitals. The parent or guardian of each child was asked to complete a series of questions about the child detailing his name, address, birthdate, sex, race, etc., and the information given in response to those questions was used unless it differed markedly from the child's general appearance. Specifically in regard to the question of race, each parent or guardian had the choice of "white", "black" or "Spanish-American." "'White" and "'Spanish-American" were grouped by the authors as "non-black." The testing programs relied largely on lay volunteers from the local communities for support services and on professional personnel from local hospitals and clinics who also volunteered their time. This enabled program dollars to be spent on laboratory expenses
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instead of staff services and thus allowed more children to be screened. More importantly, it provided a mechanism for involving groups and individual members of the local communities in their own health care programs. Sickle cell buffers were prepared# using the solubility process outlined by previous workers10'11 with only minor modifications. This method has been shown to detect individuals with sickle cell trait (AS), sickle cell and beta thalassemia, hemoglobin SC disease, homozygous sickle cell anemia (SS), and hemoglobin C Harlem. Hemoglobin C does not react positively to this test, however," Positive specimens were then verified and the different hemoglobin types identified by electrophoresis. The Titian III cellulose acetate procedure was used. * RESULTS
A total of 5,206 children from the lead poisoning study were tested for hemoglobin type. All of the specimens collected in one city were lost in transit and hence, the data presented here are for only 13 instead of 14 cities. In addition there were several hundred children not included in the hemoglobin study because their specimens were inadequate for hemoglobin type determination after portions of the specimen had been extracted for blood lead level determinations. A total of 2,214 "non-black" children were tested for hemoglobin type, an average of 3.1%of each city's total "non-black" population ages one to six. There is no way to estimate the percentage of each city's low income children one to six who were tested. Seven (0.3%) of the 2,214 "non-black" children tested possessed an abnormal hemoglobin type. In every case this abnormal hemoglobin was type SA, sickle cell trait. At least one "non-black" individual demonstrated hemoglobin S in six of the 13 cities. A total of 2,992 "black" children were #The authors thank Dr. Henry Ainis, Department of Hematology, Hektoen Institute, Cook County Hospital, Chicago, Illinois, for the solubility and electrophoresis test his laboratory performed. *SupreHeme, Helena Laboratories, Beaumont, Texas.
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also tested for hemoglobin type. This was a minimum of 4.4% and an average of 12.8% of the black population ages one to six in each city. The percentage of "black" children with evidence of hemoglobin S varied from 0% in East Moline to 9.9% in Aurora. These two prevalence rates and the 2.4% found in Rock Island were found to be significantly different (P.05), however. DISCUSSION
The only previous testing of "non-blacks" for hemoglobin S was conducted in the American South over 40 years ago. This current study was undertaken to determine whether, after the passage of time and the occurrence of the resulting changes in society, hemoglobin S could be detected in individuals who did not classify themselves as "black," and who did not fit the stereotype appearance of the American Negro. We leave to the sociologists all discussions of whether low income, middle income, or upper income groups have the greatest possibility of genetic exchange with Negroes. We were presented with an opportunity to obtain hemoglobin samples from a large number of low income residents of areas of old and deteriorating housing in several Illinois communities. Because these individuals were fairly evenly divided between white and black races, the possibility of comparing the prevalence of hemoglobin S in members of the same neighborhoods, yet of different races, became possible. The demonstration of hemoglobin S in 0.3% of the "'non-black" children tested, while not making hemoglobin S-associated disease a top priority health problem in "non-black" Americans, is, however, possibly indicative of a relatively new health hazard in this group. This prevalence in " non-blacks" obviously cannot be applied to all Illinois "non-blacks". Whether the same prevalence of hemoglobin S could be found in different socio-economic groups of "nonblacks"' is unknown. The differences between the findings of this report and the result of the previous workers4-6 who studied "'non-black" populations are worth considering. The effect of the passage of time has already been discussed. Additionally this current study may have tested members of different socio-economic groups than did the earlier workers who
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provided only limited demographic data for their sample groups. Diggs tested medical students from the University of Tennessee and patients of Memphis General Hospital.' Miyamoto5 and Sydenstricked6 tested hospital patients but did not describe their subject's socio-economic status. There is also a definite geographical difference. The earlier works were conducted in the southern part of the country: Tennessee,4 St. Louis,5 and Georgia,6 while the present study, with the exception of East St. Louis, was conducted in the industrial areas of northern and central Illinois. Whatever cultural differences there are between the different geographical areas that may have influenced mixing of the gene pools of the two ethnic groups must be taken into account. Additionally, there may be a factor associated with the differences between the South and the northern Midwest that influences the manner in which individuals and others perceive one's race that may have influenced the classification of individuals of mixed race into "black" or "non-black" groups. Regardless of the reasons for the differences between the results of the earlier works4-6 and this one, it appears that hemoglobin S may currently be found in individuals in Illinois who do not, to the casual observer, appear to be, nor whom regard themselves as "black." Hence Illinois physicians may occasionally be presented with cases of hemoglobin S-associated disease such as those described in Table 1 in individuals who do not fit the stereotyped appearance of an American Negro. Turning now to the 2,992 "black" children's hemoglobin results, only two cases of sickle cell anemia seem at first glance hardly indicative of a major health problem. Yet the prevalence found in this and other studies, sickle cell anemia outranks cystic fibrosis, childhood leukemia and phenylketonuria in numbers of cases occurring annually in most of our major population centers.13 The presence of sickle cell anemia relative to the total amount of hemoglobin S detected in this study is considerably less than in other reports in the literature. 14 The total prevalence of hemoglobin S
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found in this study (5.9%) is also less than most figures reported.4'14 Whether this report's variance from other figures in the literature is an oddity of this sample, a prevalence peculiar to downstate Illinois or, less likely, a result of actual changes in the prevalence of hemoglobin S in American blacks in unknown. Boyle15 has theorized that for a variety of reasons, among them the substantial reduction of malaria as an endemic American disease and the increasing social and geographical mobility of the American Negro, the incidence of the sickling gene will decline over time in the United States. That this decrease could have occurred by 1971 seems unlikely, however. The significant difference between the prevalence rates of the abnormal hemoglobin types in "black" children in different Illinois cities followed a geographic pattern to some extent. East Moline and Rock Island, the two cities with the lowest prevalence rates of hemoglobin S, are adjacent communities on the banks of the Mississippi River in northwestern Illinois. Why this should be so is uncertain. SUMMARY
Blood specimens from over 5000 low income children of all races from 13 downstate Illinois communities were tested for hemoglobin type in conjunction with a lead poisoning testing program in the summer of 1971. Children described by their parents as either ''white'' or ''Spanish-American'' were found to possess hemoglobin S (the sickling hemoglobin) at a prevalence 1/20 of that of children described by their parents as "black." Earlier studies conducted in the American South in the 1920's had not detected hemoglobin S in "white" populations. Possible reasons for the difference between the earlier studies and this one, including the effects of sampling different socio-economic groups, different geographical groups, and sociological changes associated with the passage of 40 years, are discussed. (Concluded on page 397)
Compluteriz-ed Axial Tomography
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cisterns. Diagnosis: Moderate degree of hydrocephalus and multiple calcifications due to previous tuberculous meningitis (Fig. 4). Case No. 5. The patient is a six year old boy with hydrocephalus and mental retardation. CT scan shows a huge cystic area (diminished density) which communicates with the left lateral ventricle, higher cuts will show the extension of the lesion. Also both frontal horns are displaced laterally in a bat-wing fashion. The right occipital horn is moderately dilated and displaced laterally. Diagnosis: 1) Large porencephalic cyst communicating with the left lateral ventricle. 2) Hydrocephalus and 3) Agenesis of the corpus callosum (Fig. 5). DISCUSSION
The accuracy of computerized scanning and its non-invasive nature make this an ideal screening procedure. Angiography or pneumoencephalography may be performed as needed (Case 1). In the presence of hydrocephalus or localized intracranial tumors, surgical correction may be immediately undertaken without additional investigative procedures. In addition to providing more accurate diagnosis of chronic intracranial pathology, the patient may be treated without
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undergoing a battery of diagnostic tests. Definitive surgical correction now follows many computerized scans without resorting to other invasive procedures. LITERATURE CITED
1. HOUNSFIELD, G. N. Computerized Transverse Axial Tomography. 2nd Congress of European Association of Radiology Amsterdam June 1971. 2. HOUNSFIELD, G. N. and J. AMBROSE. New Technqiues for Diagnostic Radiology. 32nd Annual Congress of the British Institute of Radiology London, April 1972. 3. NEW, P. F. J. and W. R. SCOTT, J. A. SCHNUR, et al. Computerized Axial Tomography with the EMI Scanner. Radiology, 110:109-123, 1974. 4. DAVIS, D. 0. and B. D. PRESSMAN. Computerized Tomography of the Brain. Radiolog. Clin. N. Amer., 12:297-313, 1974. 5. GAWLER, J., J. W. D. B ULL, G. H. DUB OULAY and J. MARSHALL. Computer Assisted Tomography-Its Place in Investigation of Suspected Intracranial Tumors. Lancet, 2:419-423, 1974. 6. GREITZ, T. and T. HINDMARSH. Computer Assisted Tomography of Intracranial CSE Circulation Using a Water-soluble Contrast Medium. Acta Radiologica, 15:5-12, 1974.
(Fine et al., from page 373)
LITERATURE CITED
1. WEINER, S. B. Sickle Cell Anemia in an Italian Child. J. Mt. Sinai Hosp., 4:88-91, 1937. 2. GUYTON, R. A. and R. W. HEINLE. Sickle Cell Anemia in the White Race. Am. J. Med. Sci., 220:272-275, 1950. 3. COOLEY, T. B. and P. LEE. Sickle Cell Anemia in a Greek Family. Am. J. Dis. Child., 38:103-106, 1929. 4. DIGGS, L. W. and C. F. AHMANN and J. BIBB. The Incidence and Significance of the Sickle Cell Trait. Ann. Int. Med., 7:769-778, 1933. 5. MIYAMOTO, K. and J. H. KORB. Meniscocytosis (Latent Sickle Cell Anemia); Its Incidence in St. Louis. South. Med. J., 20:912-916, 1927. 6. SYDENSTRICKED, V. P. and W. A. MULHERIN and R. W. HOUSEAL. Sickle Cell Anemia. Am. J. Dis. Child., 26:132-154, 1923. 7. JONES, S. R. and R. A. BINDER and E. M. DONOWHO. Sudden Death in Sickle Cell Trait. N. Eng. J. of Med., 282:323-325, 1970. 8. FINE, P. R. and C. W. THOMAS, R. H. SUHS, R. E. COHNBERG and B. A. FLASHNER. Pediatric Lead Levels; A Study in 14 Illinois Cities of Intermediate Population.
J.A.M.A., 221:1475-1479, 1972. 9. U.S. Bureau of the Census, Census of Population: 1970 General Population Characteristics Final Report, PC (l)-B15. Illinois U.S. Gov't Printing Office, Washington, D.C. 1971. 10. HELLER, P. and V. YAKULIS. A Simple and Reliable Test for Sickling. J.A.M.A., 203:990, 1968. 11. LOH, W. P. A New Solubility Test for Rapid Detection of Hemoglobin S. J. Ind. Med. Assc., 61:1651-1652, 1968. 12. GREENBERG, M. S. and H. A. HARVEY and C. MORGAN. A Simple and Inexpensive Screening Test for Sickle Hemoglobin. N. Eng. J. Med., 286:1143-1144, 1972. 13. SCOTT, R. E. Sickle Cell Anemia-High Prevalence and Low Priority. New Eng. J. Med., 282: 164-165, 1970. 14. MEYERSON, R. M. and E. HARRISON and H. W. LOHMULLER. Incidence and Significance of Abnormal Hemoglobins. Am. J. Med., 26:543-546, 1959. 15. BOYLE, E. and C. THOMPSON- and H. A. TYROLER. Prevalence of Sickle Cell Trait in Adults of Charleston County S.C. Arch. Envir. Hlth., 17:891-898, 1968.