Point-of-care screening for sickle cell disease in low-resource settings: A multi-center evaluation of HemoTypeSC, a novel rapid test.

Sickle cell disease (SCD) is a common, life-threatening genetic disorder that is best managed when diagnosed early by newborn screening. However, SCD is most prevalent in low-resource regions of the world where newborn screening is rare and diagnosis at the point-of-care is challenging. In many such regions, the majority of affected children die, undiagnosed, before the age of 5 years. A rapid and affordable point-of-care test for SCD is needed. The diagnostic accuracy of HemoTypeSC, a point-of-care immunoassay, for SCD was evaluated in individuals who had SCD, hemoglobin C disease, the related carrier (trait) states, or a normal hemoglobin phenotype. Children and adults participated in low-, medium- and high-resource environments (Ghana [n = 383], Martinique [n = 46], and USA [n = 158]). Paired blood specimens were obtained for HemoTypeSC and a reference diagnostic assay. HemoTypeSC testing was performed at the site of blood collection, and the reference test was performed in a laboratory at each site. In 587 participants, across all study sites, HemoTypeSC had an overall sensitivity of 99.5% and specificity of 99.9% across all hemoglobin phenotypes. The test had 100% sensitivity and specificity for sickle cell anemia. Sensitivity and specificity for detection of normal and trait states were >99%. HemoTypeSC is an inexpensive (<$2 per test), accurate, and rapid point-of-care test that can be used in resource-limited regions with a high prevalence of SCD to provide timely diagnosis and support newborn screening programs.

Hemoglobinosis C in Morocco : A report of 111 cas.

BACKGROUND: - Hemoglobin C is a hemoglobin variant encountered worldwide. The regionswith high prevalence are West Africa and South-East Asia.The objective of this study is to report cases of hemoglobin C disease brought together during these last twelve years in the Laboratory of Biochemistry and Toxicology of RabatMilitary Hospital Mohammed V (MHIMV). METHODS: - This was a retrospective study including111 cases of hemoglobin C disease collected in the Laboratory of Biochemistry of the MHIMVover the past 12 years. A questionnairewasfulfilledwith the epidemiological data,clinical data and the results of the biological explorations. The screening of the hemoglobin variant in this study included several biochemical (hemoglobin electrophoresis at acid and alkalinepH) and hematological tests. RESULTS: - Sex-ratio was equal to 1,22. The age at the time of diagnosis ranges between 4 and 80years old, with the mean of 38. North-West regions of Morocco seem most affected. The most frequent reasons for prescription of the hemoglobin's studywere: biological abnormalities, splenomegaly and anemic syndrome. Blood smear reveals frequently anisopoikilocytosis and red blood target. The biochemical tests contribute to the diagnosis and reveal various and varied etiological groups: heterozygous A/C (75%),homozygous C/C (8%), double heterozygous S/C (9%),C/ß+-thal (6%) andC/O-Arab (2%). Conclusion - The results of the present descriptive study are in line with the literature data. The importance of genetic counseling and the installation of a national card of systematic neonatal tracking seemto be unavoidable.

Blood typing profile of a school-aged population of a North Togo township.

The aim of this study was the determination of hemoglobin (Hb) variants and ABO blood groups in a school population aged 6 to 9 years in the township of Agbandé-Yaka in North Togo. A cross-sectional study was carried out on 570 children of four primary schools at Agbande-Yaka, between March and July 2010. Hemoglobin characterization was done by alkaline buffer electrophoresis and the blood types ABO-Rhesus (Rh) D by immuno-hematological methods. A Hb variant was detected in 37.0% of the schoolchildren. Among them, the AS trait accounted for 11.9% and the AC trait for 20.2%. Homozygous Hb S (HBB: c.20A>T) was not found but Hb C (HBB: c.19G>A) appeared at a frequency of 3.3%, while compound heterozygotes carrying Hb SC were seen at a frequency of 1.6%. The O, B and A blood groups accounted for 49.0, 26.8 and 21.9%, respectively. The Hb anomalies reached a high prevalence in this school population. These results are remarkable by the absence of homozygous Hb S individuals compared to homozygous Hb C individuals, which were as numerous as expected. The frequencies of the ABO blood groups are similar to what has been found in other West African populations.

The distribution of haemoglobin C and its prevalence in newborns in Africa.

Haemoglobin C (HbC) is one of the commonest structural haemoglobin variants in human populations. Although HbC causes mild clinical complications, its diagnosis and genetic counselling are important to prevent inheritance with other haemoglobinopathies. Little is known about its contemporary distribution and the number of newborns affected. We assembled a global database of population surveys. We then used a Bayesian geostatistical model to create maps of HbC frequency across Africa and paired our predictions with high-resolution demographics to calculate heterozygous (AC) and homozygous (CC) newborn estimates and their associated uncertainty. Data were too sparse outside Africa for this methodology to be applied. The highest frequencies were found in West Africa but HbC was commonly found in other parts of the continent. The expected annual numbers of AC and CC newborns in Africa were 672,117 (interquartile range (IQR): 642,116-705,163) and 28,703 (IQR: 26,027-31,958), respectively. These numbers are about two times previous estimates.

Forecasting hemoglobinopathy burden through neonatal screening in Omani neonates.

To evaluate the incidence of hemoglobinopathies in Omani subjects and to forecast its future burden on health resources, we initiated a prospective neonatal screening program in two major cities of the Sultanate of Oman. Consecutive cord blood samples from a total of 7,837 neonates were analyzed for complete blood counts and for hemoglobin (Hb) profile by high performance liquid chromatography (HPLC). No case with Hb H (beta4) was detected. We observed that the overall incidence of alpha-thalassemia (alpha-thal) was 48.5% [based on the presence of Hb Bart's (gamma4)] and the beta-globin-related abnormalities accounted for 9.5% of the samples (4.8% sickle cell trait, 2.6% beta-thal trait, 0.9% Hb E trait, 0.8% Hb D trait, 0.08% Hb C trait, 0.3% sickle cell disease and 0.08% homozygous beta-thal). This is also the first large study to establish reference ranges of cord red blood cell (RBC) indices for Omani neonates.

[Hemoglobin sickle cell disease: experience of the Yalgado Ouedraogo University Hospital of Ouagadougou, Burkina Faso]. / Le syndrome drépanocytaire de type hémoglobine SC : expérience du CHU Yalgado Ouédraogo de Ouagadougou (Burkina Faso).

OBJECTIVES: To evaluate the clinical features of children with hemoglobin sickle cell disease (HbSC) and compare them to children with sickle cell anemia (HbSS). POPULATION AND METHODS: This was a descriptive and retrospective study. New patients with sickle cell disease who consulted at the Yalgado Ouédraogo University Hospital's Pediatric Center in Ouagadougou, Burkina Faso, between May 2005 and June 2006, were included. They were free of any major disease unrelated to sickle cell disease. Clinical and laboratory results reported for these children were based on their health book and medical records. RESULTS: Sixty-one children were included in the study, 38 and 23 children were positive for HbSC and HbSS, respectively; there was no significant difference between the 2 groups in terms of sex ratio or mean age at inclusion. Mean age at diagnosis was 5 years and 2 years for HbSC and HbSS children, respectively. The first clinical event appeared at a significantly later age for HbSC than HbSS children (4 years versus 2 years). Painful episodes were equivalent in mean number per year and mean length per episode between the 2 groups; the median hemoglobin (Hb) level at inclusion was significantly higher for HbSC than for HbSS children, i.e., 95 g/l versus 70 g/l. CONCLUSION: At the Yalgado Ouédraogo University Hospital Pediatric Center, children with HbSC disease presented clinical and biological features very similar to those with HbSS.

[Biological signifiance of 410 microcytosis]. / Signification biologique de 410 microcytoses de découverte fortuite chez des adultes jeunes.

We have detected 410 microcytosis among biological tests of military people. These microcytosis are principally coumpounded by haemoglobin's abnormalities (minor thalassemia, sickle cell diseases, E haemoglobin cases and cases of C haemoglobin) and cases of iron deficiency, usually among women.

Hemoglobinas anormales en la población neonatal de Costa Rica

Abnormal haemoglobins in the newborn human population of Costa Rica. Hemoglobinopathies are hereditary autosomic recessive diseases. A total of 70 943 samples of whole blood collected by heel prick in filter paper (S&S 903) from throughout Costa Rica (October 2005-October 2006) were analyzed to detect variants of hemoglobin by the iso-electric focusing technique. Eight hundred ninety one cases presented some variant, for a frecuency of 1/79. Five cases are homozygous for hemoglobin S (sickle cell disease) and one shows the double heterozygous genotype SC. in this study the S and C variants of hemoglobin, although with some local differences, are widespread all over the country. Thus, the prevention of new cases is important through the testing of hemoglobin in the Costa Rican National Newborn Screening Program, together with a interdisciplinary National Program of Education for the disease and carrier status (AS/AC) for patients, families and medicar personnel. This is the basis for proper genetic counseling, to improve treatment and to reduce morbi-mortality. Rev. Biol. Trop. 56 (3): 995-1001. Epub 2008 September 30.

Se han analizado un total de 70 943 muestras de sangre total en papel filtro S&S 903 de neonatos de Costa Rica (octubre 2005 a Octubre 2006) con el fin de detectar variantes de hemoglobina mediante la técnica de isoelectroenfoque. Se detectaron 891 casos con alguna variante para una frecuencia de 1/79. Se clasifican 5 casos homocigotos para hemoglobina S (anemia drepanocítica o anemia falciforme) y un caso doble heterocigoto para SC. En este estudio se demuestra que las variantes fenotípicas de hemoglobina S como la C, se encuentran distribuidas por todo el país con algunas diferencias locales, razón por la cual es importante que la prevención de nuevos casos se realicé a través de nuestro Programa Nacional de Tamizaje de Hemoglobinas junto con un Programa Nacional interdisciplinario de Educación para el portador del rasgo (AS/AC) como, para el enfermo y su familia; al igual que la instauración de programas dirigidos a médicos generales y enfermeras en todas las regiones de salud del país, para asegurar consejo genético a portadores y enfermos, y a la vez, mejorar los sistemas de tratamiento a los pacientes para reducir la morbi -mortalidad.

Genetic epidemiology of susceptibility to malaria: not only academic exercises.

Descriptive genetic epidemiology represents the initial step of a logical procedure of linked and consequential phases spanning from the identification of genes involved in the resistance/susceptibility to diseases, to the determination of the underlying mechanisms and finally to the possible translation of the acquired knowledge in new control tools. In malaria, the rational development and potential of this pathway is based on complementary interactions of heterogeneus disciplines going from epidemiology (the transmission, the infection, the disease) to vaccinology passing through genetics, pathogenesis, and immunology. Several epidemiological approaches can be applied in the study of the genetic susceptibility to Plasmodium falciparum malaria: intra-ethnic case-control studies comparing genetic candidates of resistance/susceptibility between subjects with different presentation of malaria (from severe disease to asymptomatic infection) and the general healthy population is the classic approach; inter-ethnic comparative analyses among populations with different genetic backgrounds, exposed to the same epidemiological context and showing different susceptibility to the disease is a further, complementary, strategy.

[Abnormal haemoglobins in the newborn human population of Costa Rica]. / Hemoglobinas anormales en la población neonatal de Costa Rica.

Hemoglobinopathies are hereditary autosomic recessive diseases. A total of 70 943 samples of whole blood collected by heel prick in filter paper (S&S 903) from throughout Costa Rica (October 2005-October 2006) were analyzed to detect variants of hemoglobin by the iso-electric focusing technique. Eight hundred ninety one cases presented some variant, for a frecuency of 1/79. Five cases are homozygous for hemoglobin S (sickle cell disease) and one shows the double heterozygous genotype SC. In this study the S and C variants of hemoglobin, although with some local differences, are widespread all over the country. Thus, the prevention of new cases is important through the testing of hemoglobin in the Costa Rican National Newborn Screening Program, together with a Interdisciplinary National Program of Education for the disease and carrier status (AS/AC) for patients, families and medicar personnel. This is the basis for proper genetic counseling, to improve treatment and to reduce morbi-mortality.

Perinatal and maternal outcomes in women with sickle or hemoglobin C trait.

OBJECTIVE: Recent studies have reported increased fetal loss and preeclampsia in women with sickle cell trait (hemoglobin [Hb] AS). There is a paucity of studies of outcomes in carriers of hemoglobin C. We examined the prevalence of hemoglobin C and S carrier status (Hb AC and Hb AS, respectively) and their effect on pregnancy outcomes. METHODS: This was a retrospective cohort study using data prospectively collected from 1991 to 2006. Perinatal and maternal outcomes for African-American women with Hb AS and Hb AC were compared with those with normal hemoglobin (Hb AA). Multivariable regression was performed by applying generalized estimating equations to account for correlation between births from the same woman. RESULTS: Among 22,096 eligible African-American women (36,897 pregnancies) with routine antenatal hemoglobin electrophoresis, 88.5% had a normal (Hb AA) pattern. Hemoglobin AS was identified in 8.2% and Hb AC in 2.4% of women. Hemoglobin SS and Hb SC each accounted for less than 0.2% and Hb CC for 0.01%. Prevalence and relative risks for adverse outcomes in 3,019 AS pregnancies (3,062 births) and 875 AC (886 births), compared with 32,724 AA pregnancies (33,213 births), were not increased. Adjusted relative risks (95% confidence intervals) for perinatal mortality and preeclampsia were 0.7 (0.5-1.0) and 1.0 (0.8-1.2), respectively, for AS and 0.7 (0.3-1.4) and 1.0 (0.6-1.3), respectively, for AC. Risks of stillbirths and pregnancy-associated hypertension were also not increased. CONCLUSION: Contrary to other recent reports, perinatal mortality and preeclampsia are not increased in carriers of sickle cell trait or hemoglobin C. LEVEL OF EVIDENCE: II.

Association between haemoglobin variants S and C and Mycobacterium ulcerans disease (Buruli ulcer): a case-control study in Benin.

Risk factors for Buruli ulcer (BU) are poorly understood. We conducted a case-control study in southern Benin to investigate the association between haemoglobin variants S or C and BU, and particularly the association between haemoglobinopathies HbSS/SC and BU osteomyelitis. We compared the haemoglobin genotype of 179 patients with BU and 44 with BU osteomyelitis to that of 242 community controls. We found no evidence of an increased risk of BU according to the presence of haemoglobin variants S and/or C [odds ratio adjusted for sex, age, region of residence and ethnicity: 1.24 (95% CI: 0.80-1.93), P = 0.34]. Haemoglobin variants S and C are unlikely to play a role in the BU burden. However, haemoglobinopathies HbSS/SC were more frequent among BU osteomyelitis patients than among controls (6.8% vs. 1.0%, Fisher's exact P-value = 0.045), which may suggest that those disorders facilitate growth of Mycobacterium ulcerans in the bone matrix.

Incidence of haemoglobinopathies detected through neonatal screening in the United Arab Emirates.

In January 2002, a pilot programme of neonatal screening for sickle cell disease was launched in the United Arab Emirates (UAE) in 3 districts of Abu Dhabi emirate. This paper reports the incidence of sickle cell diseases, other haemoglobinopathies and haemoglobinopathy carriers over a 12-month period using high performance liquid chromatography as a primary screening method. The overall incidence of sickle cell disease among 22 200 screened neonates was 0.04% (0.07% for UAE citizens and 0.02% for non-UAE citizens). The incidence of sickle cell trait was 1.1% overall (1.5% for UAE citizens and 0.8% for non-UAE citizens). Universal neonatal screening for sickle cell haemoglobin at the national level should be considered.

[Hemoglobinopathy C and splenomegaly in an Ivory Coast patient. Value of splenectomy]. / Hémoglobinopathie C et splénomégalie chez un patient ivoirien. Intérêt de la splénectomie.

We report the case of a young patient native of the Ivory Coast who suffered from homozygous hemoglobin C disease. He presented with the usual findings of this hemoglobinopathy: a moderate hemolytic anemia and a massive, painful and even disabling splenomegaly. Pain completely disappeared following splenectomy. However, postoperative course was complicated by portal venous thrombosis, which was medically treated. No deficiency of natural coagulation inhibitors could be demonstrated, so splenectomy was the only factor predisposing to thrombosis. We consider that in only very few cases of hemoglobin C disease, splenectomy (preceded by prophylactic antipneumococcic vaccine) may be indicated from pain and risk of spontaneous splenic rupture.

Frequency of haemoglobinopathies and glucose-6-phosphate dehydrogenase deficiency in Basra.

Basra, southern Iraq, was mapped for haemoglobinopathies and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Of 1064 couples aged 14-60 years recruited from the Public Health Laboratory, 49 had beta-thalassaemia trait, 69 had sickle-cell trait, 2 had haemoglobin D trait, 2 had haemoglobin C trait and 1 had high persistent fetal haemoglobin. Carriers of major beta-globin disorders comprised 11.48%. G6PD deficiency was detected in 133 individuals (12.5%). Only 10 couples (0.94%) were at risk of having children affected with either sickle-cell disease or beta-thalassaemia major. These defects constitute a real health problem and necessitate a management plan and public health education for early diagnosis and therapy.

Student screening for inherited blood disorders in Bahrain.

In Bahrain and neighbouring countries inherited disorders of haemoglobin, i.e. sickle-cell disease, thalassaemias and glucose-6-phosphate dehydrogenase (G6PD) deficiency, are common. As part of the National Student Screening Project to determine the prevalence of genetic blood disorders and raise awareness among young Bahrainis, we screened 11th-grade students from 38 schools (5685 students), organized lectures and distributed information about these disorders. Haemoglobin electrophoresis, high performance liquid chromatography, blood grouping and G6PD deficiency testing were performed. Prevalences were: 1.2% sickle-cell disease; 13.8% sickle-cell trait; 0.09% beta-thalassaemia; 2.9% beta-thalassaemia trait; 23.2% G6PD deficiency; 1.9% G6PD deficiency carrier. Health education, carrier screening and premarital counselling remain the best ways to reduce disease incidence with potentially significant financial savings and social and health benefits.

Modification in the frequency of Hb C and Hb S in Burkina Faso: an influence of migratory fluxes and improvement of patient health care.

The incidence of hemoglobinopathies (Hb C and Hb S) is relatively high in West Africa. In order to calculate the gene frequency of these hemoglobinopathies, 6619 students from 23 local schools in Ouagadougou, Burkina Faso, West Africa, and 2582 individuals living in five villages near Ouagadougou, all situated in Savanna, were studied. As expected, the gene frequency in the city schools was 0.111 for the betaC gene and 0.051 for the betaS gene; in the five villages it was 0.122 for the betaC gene and 0.047 for the betaS gene. This data is somewhat different from that published in a previous study by Labie et al. [2] in the humid Savanna region, that showed a higher prevalence of betaC (0.14) than betaS (0.03), and is in contrast to data from the arid Sahel region that showed a higher prevalence of betaS (0.1) compared to betaC (0.05). The higher rate of betaS and lower rate of betaC in students in Ouagadougou, and in the individuals living in the five villages near Ouagadougou, suggest the possible influence of migratory fluxes of the betaS gene from the country region of Sahel. The dramatic increase in the prevalence of Hb SS patients, not reported in the study of Labie et al., [2] may be the result of reduced mortality due to environmental change. In addition, the improved health conditions of Hb SC and the increased life expectancy of Hb SS, may also have facilitated the increase of the betaS gene and the focus on secondary prevention for the control of correlated diseases.

Biological and clinical presentation of patients with hemoglobinopathies attending an urban hospital in Ouagadougou: confirmation of the modification of the balance between Hb S and Hb C in Burkina Faso.

The incidence of hemoglobinopathies (Hb C and Hb S) is relatively high in West Africa. In order to characterize the clinical phenotypes of these hemoglobinopathies 10,166 subjects were studied for suspected hemoglobinopathies at the Laboratory of the Centre Medical Saint Camille (CMSC), Ouagadougou, Burkina Faso. A high rate of Hb SC (6.49%) and Hb SS (1.93%) individuals were detected at the CMSC as a consequence of a selective process, whereby patients with anemia or symptoms of vascular occlusive crisis underwent blood tests. The higher frequency of Hb SC may be explained by the fact that this condition is less severe than the SS status, and it requires frequent clinical and laboratory review. On the other hand, the frequency of Hb CC is very low because it does not interfere with their health status. Moreover, the high percentage of Hb S (12.29%) and Hb C (19.28%) trait individuals may be explained by the fact that, in general, all Hb SS and Hb SC patients followed at the CMSC have parents, siblings and other relatives who could have been referred by the center to receive blood tests. The dramatic increase over the past few years in the prevalence of Hb SS [who were absent in the 1984 study of Labie et al. [5]] and of Hb SC, may be attributed to its reduced lethality due to social and health changes. In conclusion, secondary prevention for the control of concurrent and associated diseases is essential in Hb SS and Hb SC patients for improving health and life expectancy.

[Neonatal screening for hemoglobinopathies: a pilot study in Porto Alegre, Rio Grande do Sul, Brazil]. / Triagem neonatal para hemoglobinopatias: um estudo piloto em Porto Alegre, Rio Grande do Sul, Brasil.

This study was conducted to establish the frequency of hemoglobinopathies among newborns undergoing screening tests for metabolic diseases at the University Hospital (Hospital de Clínicas) in Porto Alegre, Rio Grande do Sul, Brazil. Testing for abnormal hemoglobins was performed by isoelectric focusing electrophoresis on agarose gel with blood obtained by heel stick and applied to filter paper. For confirmatory testing of abnormal neonatal screening, a venopuncture blood sample was obtained from the infant and parents and then submitted to hemoglobin electrophoresis on cellulose acetate at pH 8.6 and citrate agar at pH 6.2. A total of 1,615 subjects were studied: 20 samples showed the Hb S pattern and six samples showed Hb C. Thus, frequency of the sickle cell gene was 1.2% and that of the Hb C gene was 0.4%, regardless of race or origin. These data suggest that the inclusion of universal neonatal screening for hemoglobinopathies in the ongoing projects for the detection of phenylketonuria and congenital hypothyroidism has many advantages and should be considered in health programs.