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Haemoglobin S (HbS; beta6Glu-->Val) and HbC (beta6Glu-->Lys) strongly protect against clinical Plasmodium falciparum malaria. HbS, which is lethal in homozygosity, has a multi-foci origin and a widespread geographic distribution in sub-Saharan Africa and Asia whereas HbC, which has no obvious CC segregational load, occurs only in a small area of central West-Africa. To address this apparent paradox, we adopted two partially independent haplotypic approaches in the Mossi population of Burkina Faso where both the local S (S(Benin)) and the C alleles are common (0.05 and 0.13). Here we show that: both C and S(Benin) are monophyletic; C has accumulated a 4-fold higher recombinational and DNA slippage haplotypic variability than the S(Benin) allele (P = 0.003) implying higher antiquity; for a long initial lag period, the C alleles did apparently remain very few. These results, consistent with epidemiological evidences, imply that the C allele has been accumulated mainly through a recessive rather than a semidominant mechanism of selection. This evidence explains the apparent paradox of the uni-epicentric geographic distribution of HbC, representing a 'slow but gratis' genetic adaptation to malaria through a transient polymorphism, compared to the polycentric 'quick but costly' adaptation through balanced polymorphism of HbS.

Conclusive evidence exists on the protective role against clinical Plasmodium falciparum malaria of Haemoglobin S (beta 6Glu-->Val) and HbC (HbC; beta 6Glu-->Lys), both occurring in sub-Saharan Africa. However, the mechanism/s of the protection exerted remain/s debated for both haemoglobin variants, HbC and HbS. Recently, an abnormal display of PfEMP1, an antigen involved in malaria pathogenesis, was reported on HbAC and HbCC infected erythrocytes that showed reduced cytoadhesion and impaired rosetting in vitro. On this basis it has been proposed that HbC protection might be attributed to the reduced PfEMP1-mediated adherence of parasitized erythrocytes in the microvasculature. Furthermore, impaired cytoadherence was observed in HbS carriers suggesting for the first time a convergence in the protection mechanism of these two haemoglobin variants. We investigated the impact of this hypothesis on the development of acquired immunity against P. falciparum variant surface antigens (VSA) encoding PfEMP1 in HbC and HbS carriers in comparison with HbA of Burkina Faso. Higher immune response against a VSA panel and several malaria antigens were observed in all adaptive genotypes containing at least one allelic variant HbC or HbS in the low transmission urban area whereas no differences were detected in the high transmission rural area. In both contexts the response against tetanus toxoid was not influenced by the beta-globin genotype. Thus, these findings suggest that both HbC and HbS affect the early development of naturally acquired immunity against malaria. We reviewed the hypothesized mechanisms so far proposed in light of these recent results.

A recently proposed mechanism of protection for haemoglobin C (HbC; beta6Glu-->Lys) links an abnormal display of PfEMP1, an antigen involved in malaria pathogenesis, on the surface of HbC infected erythrocytes together with the observation of reduced cytoadhesion of parasitized erythrocytes and impaired rosetting in vitro. We investigated the impact of this hypothesis on the development of acquired immunity against Plasmodium falciparum variant surface antigens (VSA) encoding PfEMP1 in HbC in comparison with HbA and HbS carriers of Burkina Faso. We measured: i) total IgG against a single VSA, A4U, and against a panel of VSA from severe malaria cases in human sera from urban and rural areas of Burkina Faso of different haemoglobin genotypes (CC, AC, AS, SC, SS); ii) total IgG against recombinant proteins of P. falciparum asexual sporozoite, blood stage antigens, and parasite schizont extract; iii) total IgG against tetanus toxoid. Results showed that the reported abnormal cell-surface display of PfEMP1 on HbC infected erythrocytes observed in vitro is not associated to lower anti- PfEMP1 response in vivo. Higher immune response against the VSA panel and malaria antigens were observed in all adaptive genotypes containing at least one allelic variant HbC or HbS in the low transmission urban area whereas no differences were detected in the high transmission rural area. In both contexts the response against tetanus toxoid was not influenced by the beta-globin genotype. These findings suggest that both HbC and HbS affect the early development of naturally acquired immunity against malaria. The enhanced immune reactivity in both HbC and HbS carriers supports the hypothesis that the protection against malaria of these adaptive genotypes might be at least partially mediated by acquired immunity against malaria.

Because of the importance of preventive activities in fighting sickle cell disease, we sought to assess the vaccination status of children with this disease in Burkina-Faso. This cross-sectional study used a questionnaire to collect information from outpatients of the pediatric department of the Yalgado Ouédraogo hospital center and of Saint Camille medical center, also in Ouagadougou, from October 2005 through March 2006. The study included 122 children, 52.5% of whom had an SC phenotype. Coverage for vaccinations included in the WHO expanded vaccination programme was 97.5%. For other specific vaccines, coverage varied from 5.7% for the anti-Haemophilus influenzae vaccine to 65.8% for the 23 pneumococci included in pneumo23. The major reasons for non-vaccination were ignorance and the prohibitive cost of these vaccines for the families who knew about them. These results suggest the need for a national program against sickle cell disease, which should enable treatment centers to include in their preventive activities a specific vaccination program. Only in this way can we reduce the mortality rates among those younger than 5 years by 40% by 2015, the goal of the International Organization against sickle cell disease, to which Burkina-Faso belongs.

A retrospective study of twelve cases of Felty's syndrome was performed. The main points of this syndrome (clinical presentation, physiopathology, complications, treatment) are described.

A prevalence study was carried out on 125 mothers and their newborns in Lome (Togo): at delivery 48% of the mothers and 30% of the newborns were anaemic according to WHO criteria. Iron deficiency was the major determinant of anaemia in the mothers, as three out of four showed at least one biochemical indicator of iron deficiency. Folate deficiency was detected in 68% of the mothers but did not influence their haematological parameters. Severe iron deficiency in the mothers (serum iron < 7 mumol/l) was associated with a decrease in serum iron in the newborns, thus demonstrating an impaired iron transfer to the fetus. Folate supplementation of the mothers during pregnancy improved their newborn's folate status. A systematic ferro-folic supplementation is needed during pregnancy and would be beneficial to both mothers and newborns. Supplements could be given to women at prenatal care clinics. Attendance in these centers by 98% of pregnant women in Lomé allows us to anticipate a good coverage for such an intervention.

We have studied the haematological and iron state of 203 women from the sixth month of pregnancy till two months after delivery, and of their newborn from birth to the age of two months. Iron deficiency affects more than a third of women with a higher risk for multipara and for immigrants. The only sure way of screening for this is by estimating the plasma ferritin. When iron was given routinely as a supplement we found that the tissue reserves of iron rose from the third trimester onwards and two months later were entirely normal in treated women, but an iron deficiency persisted in women who were not treated. The transfer of iron to the fetus in the third trimester of pregnancy is related to the quantity of iron given to the mother in her diet. The iron reserves in the tissues of these children were higher at two months of age when the mothers had been treated with iron during the pregnancy. The value of estimating ferritin in the blood as an indicator of tissue reserves should be considered in the neo-natal period.

Three studies of materno-fetal iron and folate status are analyzed. Repercussions of maternal iron and folate deficiencies on neonates are investigated. The incidence of iron deficiency is high during pregnancy and increases in multiparous and alien women. Although no correlation was found between mothers' and neonates' ferritinemia, maternal iron deficiency was shown to influence fetal hemoglobin synthesis and iron stores. Folate deficiency in mothers had no obvious incidence on hematological parameters in neonates. However it does influence gestation duration and therefore birthweight.

1. Iron status has been assessed in 171 blood donors and 58 controls. 2. In men, ferritinemia was lower in blood donors, as compared to controls, but hemoglobin and erythrocytes values are found normal. 3. In women, both M.C.V. and ferritinemia were lower in donors. Ferritinemia could reach values below the threshold of iron deficiency. Microcytosis occurred 7 times. It appeared to be related either to the association of hypermenorrhea with blood donation, or to a number of 4 blood donations a year. 4. Iron supplementation was randomized. The comparison of the two groups of donors with and without iron supplementation showed that supplementation had no effect on male blood donors, but improved both ferritinemia and M.C.V. values in females. 5. However, systematic iron supplementation does not seem to be appropriate in France, as long as one excludes hypermenorrheic women, and if the periodicity of blood donation does not exceed three times a year for females.

The number of persons suffering from anaemia in the world is estimated at fifty million to one billion. Most of these are children, since they are more vulnerable than adults as regards nutrition and they constitute the bulk of the population in developing countries. Depending on the region, the prevalence of anaemia among children varies from 15 to 25 p. 100 in Latin America and Indonesia and from 70 to 80 p. 100 in Africa south of the Sahara desert and in India. Anaemia results from multiple deficiencies simultaneously involving iron, folic acid and proteins. The responsibility of each of these deficiencies is difficult to determine and probably varies from one region to another. The causes of these deficiencies are multiple; they include insufficient intake, inadequate absorption, increased needs and excessive losses. The only efficient measure would be an improvement in the level of life.

A study of 72 children, aged between 6 and 24 months who came from socio-economic background has shown: plasma ferritin levels decrease gradually between 3 weeks and 6 months of age. Between 6 months and two years, levels reach a plateau but the values are lower than those of adults. The mean ferritin level is lower at any given age in children with iron deficiency but plasma ferritin levels may be in the normal range although there is obvious iron deficiency. By contrast the saturation of siderophillin can be used to determine inadequate supplies of iron to the marrow. The frequency of iron dificiency in infants under 1 year was similar in the two socio-economic groups. However between 1 and 2 years no iron deficiency was detected in the children under regular supervision but all the infants who were socially disadvantaged became iron-deficient demonstrating the need for regular iron supplements.

Hereditary elliptocytosis (HE) is a genetically determined disorder of the red cell membrane. The main protein which composes the proteinaceous skeleton of the membrane is an elongated molecule named spectrin which is a heterodimer composed of two chains, alpha and beta. In the membrane spectrin dimers are associated head-to-head to form tetrameric structures. We and other authors have reported that spectrin studied from many HE patients exhibited a dimer self-association defect (type I HE). A mutation in the head of the spectrin alpha chain was mostly found in type I HE. We have previously described one of the three known spectrin pathological variants shown on mild tryptic digest pattern. This variant was characterized by the appearance of an abnormal 65,000-dalton peptide (Sp alpha I/65). Using nondenaturating gel electrophoresis, we describe in this paper a triplicated pattern of the spectrin tetramer bands which is found in heterozygous HE cases displaying the 65,000-dalton variant. Study of a homozygous case allowed us to characterize the electrophoretic mobility of the abnormal symmetrical spectrin tetramer (alpha 2I/65-beta 2) and to study the correlation between the fraction of this abnormal symmetrical tetramer found in heterozygous patients and the amount of the 65,000-dalton peptide observed in spectrin tryptic digests.