There is a significant correlation between severity of PK deficiency and extent of protection against malaria.[44]. The spleen plays important roles in regard to red blood cells (erythrocytes) and the immune system. The "C" designation for HbC is from the name of the city where it was discovered—Christchurch, New Zealand. Human genetic resistance to malaria refers to inherited changes in the DNA of humans which increase resistance to malaria and result in increased survival of individuals with those genetic changes. All of these are in malarious areas. The potent effect of genetically controlled innate resistance is reflected in the probability of survival of young children in areas where malaria is endemic. [69] To balance the polymorphism, Anthony Allison estimated that the fitness of the AS heterozygote would have to be 1.26 times than that of the normal homozygote. There are three major forms of hereditary elliptocytosis: common hereditary elliptocytosis, spherocytic elliptocytosis and southeast Asian ovalocytosis. [26], This has led to the hypothesis that while homozygotes for the sickle cell gene suffer from disease, heterozygotes might be protected against malaria. The frequency of such transmission is still unknown. It is one of the most prevalent hemoglobinopathies with 30 million people affected. [31], There is evidence that the persons with α-thalassemia, HbC and HbE have some degree of protection against the parasite. In Gambians, it was estimated that AS heterozygotes have 90% protection against P. falciparum-associated severe anemia and cerebral malaria,[59] whereas in the Luo population of Kenya it was estimated that AS heterozygotes have 60% protection against severe malarial anemia. G6PD is present in all human cells but is particularly important to red blood cells. α-thalassemia, which attains frequencies of 30% in parts of West Africa; β-thalassemia, with frequencies up to 10% in parts of Italy; concurrent polymorphisms – double heterozygotes for HbS and β-thalassemia, and for HbS and HbC, suffer from variant forms of sickle-cell disease, milder than SS but likely to reduce fitness before modern treatment was available. [jargon][51] In widely cited in vitro and in vivo studies, Miller et al. It is at least conceivable that they are also more resistant to attacks by the sporozoa which cause malaria. These qualitative defects create a red blood cell membrane that is less tolerant of shear stress and more susceptible to permanent deformation. However, the early contributions on malaria remain as classical examples of innate resistance, which have stood the test of time. Human genetic resistance to malaria refers to inherited changes in the DNA of humans which increase resistance to malaria and result in increased survival of individuals with those genetic changes. Malaria has placed the strongest known selective pressure on the human genome since the origin of agriculture within the past 10,000 years. The first line of defense against malaria is mainly exerted by abnormal hemoglobins and glucose-6-phosphate dehydrogenase deficiency. Other genetic mutations besides hemoglobin abnormalities that confer resistance to Plasmodia infection involve alterations of the cellular surface antigenic proteins, cell membrane structural proteins, or enzymes involved in glycolysis. [60][61], Some studies suggest that high levels of fetal hemoglobin (HbF) confer some protection against falciparum malaria in adults with Hereditary persistence of fetal hemoglobin. Clusters of parasitized red blood cells can exceed the size of the capillary circulation, adhere to the endothelium, and block circulation. [48] Adhesion of P. falciparum-infected red blood cells to CD36 is enhanced by the cerebral malaria-protective SAO trait . There is a deletion of codons 400–408 in the gene, leading to a deletion of 9 amino-acids at the boundary between the cytoplasmic and transmembrane domains of band 3 protein. Some of these disorders are known by fanciful and cryptic names like sickle-cell anemia, thalassaemia, glucose-6-phosphate dehydrogenase deficiency, ovalocytosis, elliptocytosis and loss of the Gerbich antigen and the Duffy antigen. Most women will dream about one or more of three common things during pregnancy – frogs, worms and potted plants! The existence of these genotypes is likely due to evolutionary pressure exerted by parasites of the genus Plasmodium which cause malaria. [54] The Malagasy people on Madagascar have an admixture of Duffy-positive and Duffy-negative people of diverse ethnic backgrounds. In many African populations the AS frequency is about 20%, and a fitness superiority over those with normal hemoglobin of the order of 10% is sufficient to produce a stable polymorphism. Two independent preliminary analyses of GWA association with severe falciparum malaria in Africans have been carried out, one by the Malariagen Consortium in a Gambian population and the other by Rolf Horstmann (Bernhard Nocht Institute for Tropical Medicine, Hamburg) and his colleagues on a Ghanaian population. [30] Endogamy along caste and ethnic lines appear to have prevented these genes from being more widespread in neighboring populations. It also acts as the receptor for the P. falciparum erythrocyte binding protein. Those homozygous for α-thalassemia also suffer from anemia and there is some degree of selection against the gene. [1][2] Plasmodium falciparum was probably not able to gain a foothold among African populations until larger sedentary communities emerged in association with the evolution of domestic agriculture in Africa (the agricultural revolution). Since malaria … There are four alleles of the gene which encodes the antigen, Ge-1 to Ge-4. AHRQ Publishing and Communications Guidelines, Healthcare Cost and Utilization Project (HCUP), Quality Indicator Tools for Data Analytics, United States Health Information Knowledgebase, Funding Opportunities Announcement Guidance, AHRQ Informed Consent & Authorization Toolkit for Minimal Risk Research, Public Access to Federally Funded Research, Grant Application, Review & Award Process, Study Sections for Scientific Peer Review, Getting Recognition for Your AHRQ-Funded Study, AHRQ Research Summit on Diagnostic Safety, AHRQ Research Summit on Learning Health Systems, Information about the National Clearinghouse, U.S. Department of Health & Human Services. The mechanisms by which erythrocytes containing abnormal hemoglobins, or are G6PD deficient, are partially protected against P. falciparum infections are not fully understood, although there has been no shortage of suggestions. HbE erythrocytes have an unidentified membrane abnormality that renders the majority of the RBC population relatively resistant to invasion by P falciparum.[37]. Malarial forests were intentionally maintained by the rulers of Nepal as a defensive measure. Haldane was the first to give a hypothesis on the relationship between malaria and the genetic disease. In this condition, a lack of pyruvate kinase slows down the process of glycolysis. During the late stages of parasite replication red cells are adherent to venous endothelium, and inhibiting this attachment could suppress replication. [21] To try to detect these small differences, Ingram combined paper electrophoresis and the paper chromotography methods. This is about 1000 times greater than mutation rates measured in Drosophila and other organisms and much higher than recorded for the sickle-cell locus in Africans. To balance this loss of sickle-cell genes, a mutation rate of 1:10.2 per gene per generation would be necessary. In West Africa, they account for as great a reduction in disease incidence as the sickle-cell hemoglobin variant. Weight loss can be intentional, such as from dieting and exercise, or unintentional and be a manifestation of illness. More recently, Duffy negative individuals infected with two different strains of P. vivax were found in Angola and Equatorial Guinea; further, P. vivax infections were found both in humans and mosquitoes, which means that active transmission is occurring. Tens of thousands of individuals have been studied, and high frequencies of abnormal hemoglobins have not been found in any population that was malaria free. Some early contributions on innate resistance to infections of vertebrates, including humans, are summarized in Table 1. Such changes might arise by a process of mutation in the gene that codes for the protein. [66] Many SS children still died before they attained one year of age. It’s quite an experience hearing the sound of your voice carrying out to a over 100 first year dental students. Tryptase is an enzyme that is released, along with histamine and other chemicals, from mast cells when they are activated as part of a normal immune response as well as in allergic (hypersensitivity) responses. In most populations ovalocytosis is rare, but South-East Asian ovalocytosis (SAO) occurs in as many as 15% of the indigenous people of Malaysia and of Papua New Guinea. In malaria, as in other diseases, innate immunity leads into, and stimulates, adaptive immunity. persons with the relatively rare phenotype Ge-1,-2,-3, are less susceptible (~60% of the control rate) to invasion by P. falciparum. G6PD deficient persons are also sensitive to several drugs in addition to primaquine. SAO is caused by a mutation in the gene encoding the erythrocyte band 3 protein. However, observations have accumulated showing that the original Miller report needs qualification. [55] 72% of the island population were found to be Duffy-negative. Higher efficiency of sequestration via CD36 in SAO individuals could determine a different organ distribution of sequestered infected red blood cells. In West Africa an HLA class I antigen (HLA Bw53) and an HLA class II haplotype (DRB1*13OZ-DQB1*0501) are independently associated with protection against severe malaria. [27] Malaria remains a selective factor for the sickle cell trait. It is necessary to study innate immunity in the susceptible age group (younger than four years), because in older children and adults, the effects of innate immunity are overshadowed by those of adaptive immunity. An enlarged spleen or splenomegaly, is generally caused by other diseases or conditions such as infections, cancers, blood disorders, or decreased blood flow. Therefore, pyruvate kinase deficiency can cause hemolytic anemia. These inherited changes to hemoglobin or other characteristic proteins, which are critical and rather invariant features of mammalian biochemistry, usually cause some kind of inherited disease. As cells die and toxic products of invasive organism replication accumulate, disease symptoms appear. [68] In the Baamba population living in the Semliki Forest region in Western Uganda the sickle-cell heterozygote (AS) frequency is 40%, which means that the frequency of the sickle-cell gene is 0.255 and 6.5% of children born are SS homozygotes. This effect is especially devastating in cells that lack mitochondria, because these cells must use anaerobic glycolysis as their sole source of energy because the TCA cycle is not available. When the P. falciparum parasite infects a host cell, it alters the characteristics of the red blood cell membrane, making it "stickier" to other cells. By this combination he created a two-dimensional method that enabled him to comparatively "fingerprint" the hemoglobin S and A fragments he obtained from the tryspin digest. Pyruvate kinase (PK) deficiency, also called erythrocyte pyruvate kinase deficiency, is an inherited metabolic disorder of the enzyme pyruvate kinase. The thalassemias have a high incidence in a broad band extending from the Mediterranean basin and parts of Africa, throughout the Middle East, the Indian subcontinent, Southeast Asia, Melanesia, and into the Pacific Islands. Eryptosis normally occurs at the same rate as erythropoiesis, keeping the total circulating red blood cell count in a state of equilibrium. One example is red blood cells, which in a state of pyruvate kinase deficiency rapidly become deficient in ATP and can undergo hemolysis. You could remove your stomach, spleen, one lung, appendix, a kidney, and still survive perfectly fine. Individuals homozygous for β-thalassemia have severe anemia and are unlikely to survive and reproduce, so selection against the gene is strong. 5600 Fishers Lane )Basics topics Patients with end-stage kidney disease (ESKD)… It was also the first example of genetically controlled innate immunity that operates early in the course of infections, preceding adaptive immunity which exerts effects after several days. Pauling introduced his fundamentally important concept of sickle cell anemia as a genetically transmitted molecular disease. In 1956 Alving and colleagues showed that in some African Americans the antimalarial drug primaquine induces hemolytic anemia, and that those individuals have an inherited deficiency of G6PD in erythrocytes. It is a reasonable assumption that until modern treatment was available three quarters of the SS homozygotes failed to reproduce. [67] This does not imply that HbS is the only gene conferring innate resistance to falciparum malaria; there could be many such genes exerting more modest effects that are challenging to detect by GWA because of the low levels of linkage disequilibrium in African populations. Malaria does not occur in the cooler, drier climates of the highlands in the tropical and subtropical regions of the world. [59] However, HLA correlations vary, depending on the genetic constitution of the polymorphic malaria parasite, which differs in different geographic locations. Amethyst Strong healing and cleansing powers. Elliptocytosis a blood disorder in which an abnormally large number of the patient's erythrocytes are elliptical. In red cells containing abnormal hemoglobins, or which are G6PD deficient, oxygen radicals are produced, and malaria parasites induce additional oxidative stress. [50] Frequencies of Duffy negativity are as high in East Africa (above 80%), where the parasite is transmitted, as they are in West Africa, where it is not. HbC modifies the quantity and distribution of the variant antigen P. falciparum erythrocyte membrane protein 1 (PfEMP1) on the infected red blood cell surface and the modified display of malaria surface proteins reduces parasite adhesiveness (thereby avoiding clearance by the spleen) and can reduce the risk of severe disease. The authors suggest that among Malagasy populations there are enough Duffy-positive people to maintain mosquito transmission and liver infection. This condition is characterized by confusion, disorientation, and often terminal coma. Find information on the legacy National Guideline Clearinghouse (NGC) and National Quality Measures Clearinghouse (NQMC). In α-thalassemia, which is relatively frequent in Africa and several other countries, production of the α-chain of hemoglobin is impaired, and there is relative over-production of the β-chain. Vernon Ingram deserves the credit for explaining the genetic basis of different forms of thalassemia as an imbalance in the synthesis of the two polypeptide chains of hemoglobin.[29]. The existence of these genotypes is likely due to evolutionary pressure exerted by parasites of the genus Plasmodium which cause malaria. These alterations which protect against malarial infections but impair red blood cells are generally considered blood disorders, since they tend to have overt and detrimental effects. The name is derived from the Greek words for sea (thalassa), meaning the Mediterranean Sea, and blood (haima). Helps to overcome addictions and blockages of all kinds. Rare mutations of glycophorin A and B proteins are also known to mediate resistance to P. falciparum. The association has also been studied in individuals, which is possible because the enzyme deficiency is sex-linked and female heterozygotes are mosaics due to lyonization, where random inactivation of an X-chromosome in certain cells creates a population of G6PD deficient red blood cells coexisting with normal red blood cells. Since mature red blood cells lack nuclei and cytoplasmic RNA, they cannot synthesize new enzyme molecules to replace genetically abnormal or ageing ones. It is also necessary to study populations in which random use of antimalarial drugs does not occur. TORCH panel includes tests for toxoplasmosis, rubella, cytomegalovirus (CMV) and herpes. If the change is in the gamete, that is, the sperm or egg that join to form a zygote that grows into a human being, the protective mutation will be inherited. Children who are heterozygous for the sickle cell gene have only one-tenth the risk of death from falciparum as do those who are homozygous for the normal hemoglobin gene. [10] This can result in changes in red cell membranes, including translocation of phosphatidylserine to their surface[jargon], followed by macrophage recognition and ingestion. SAO is associated with protection against cerebral malaria in children because it reduces sequestration of erythrocytes parasitized by P. falciparum in the brain microvasculature. [20], The molecular basis of sickle cell anemia was finally elucidated in 1959, when Ingram perfected the techniques of tryptic peptide fingerprinting. Eventually, unchecked replication causes the cells to burst, killing the cells and releasing the infectious organisms into the bloodstream where they can infect other cells. Frequencies of sickle-cell heterozygotes were 20–40% in malarious areas of. Therefore, mutations that protect against malaria infection and lethality pose a significant advantage. Hemoglobin C (HbC) is an abnormal hemoglobin with substitution of a lysine residue for glutamic acid residue of the β-globin chain, at exactly the same ß-6 position as the HbS mutation. The lower Himalayan foothills and Inner Terai or Doon Valleys of Nepal and India are highly malarial due to a warm climate and marshes sustained during the dry season by groundwater percolating down from the higher hills. The potency of P. vivax as an agent of natural selection is unknown, and may vary from location to location. Small differences in hemoglobin A and S will result in small changes in one or more of these peptides . Plasmodium vivax has a wide distribution in tropical countries, but is absent or rare in a large region in West and Central Africa, as recently confirmed by PCR species typing. Genotyping indicated that multiple P. vivax strains were invading the red cells of Duffy-negative people. Humans attempting to live in this zone suffered much higher mortality than at higher elevations or below on the drier Gangetic Plain. Several abnormalities of SAO erythrocytes have been reported, including increased red cell rigidity and reduced expression of some red cell antigens. The consequences of the simple replacement of a charged amino acid with a hydrophobic, neutral amino acid are far ranging, Recent studies in West Africa suggest that the greatest impact of Hb S seems to be to protect against either death or severe disease—that is, profound anemia or cerebral malaria—while having less effect on infection per se. Human leucocyte antigen (HLA) polymorphisms common in West Africans but rare in other racial groups, are associated with protection from severe malaria. Learn more about the status of the site. View the criteria guidelines and measures had to meet to be included in NGC and NQMC, respectively. It is a common hematology test. HbC represents 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. We would like to show you a description here but the site won’t allow us. If you don’t have blue eyes now, you were born … In Mediterranean countries such individuals can develop a hemolytic diathesis (favism) after consuming fava beans. [28], It has long been known that a kind of anemia, termed thalassemia, has a high frequency in some Mediterranean populations, including Greeks and southern Italians. Therefore, they are commonly referred to by the names of the blood disorders associated with them, including sickle-cell disease, thalassemia, glucose-6-phosphate dehydrogenase deficiency, and others. [17][32] Between 2 and 16 months the mortality in AS children was found to be significantly lower than that in AA children. When these blockages form in the blood vessels surrounding the brain, they cause cerebral hypoxia, resulting in neurological symptoms known as cerebral malaria. The spleen possesses a slow, tortuous microcirculation that renders it quite susceptible to congestion, sludging, and polymerization. [9] It is likely that HbS in endocytic vesicles is deoxygenated, polymerizes and is poorly digested. These names refer to various proteins, enzymes, and the shape or function of red blood cells. [Note 2] These blood disorders cause increased morbidity and mortality in areas of the world where malaria is less prevalent. Since malaria infects red blood cells, these genetic changes are most commonly alterations to molecules essential for red blood cell function (and therefore parasite survival), such as hemoglobin or other cellular proteins or enzymes of red blood cells. Three types of Ge antigen negativity are known: Ge-1,-2,-3, Ge-2,-3 and Ge-2,+3. This question has been studied in isolated populations where antimalarial drugs were not used in Tanzania, East Africa[41] and in the Republic of the Gambia, West Africa, following children during the period when they are most susceptible to falciparum malaria. The three major types of inherited genetic resistance – sickle cell disease, thalassemias, and G6PD deficiency – were present in the Mediterranean world by the time of the Roman Empire. [47] Band 3 serves as the principal binding site for the membrane skeleton, a submembrane protein network composed of ankyrin, spectrin, actin, and band 4.1. Weight loss can result from a decrease in body fluid, muscle mass, or fat. Because this process involves specific proteins produced by the infectious organism as well as the host cell, even a very small change in a critical protein may render infection difficult or impossible. Sickle cell anemia is congenital, meaning it is present at birth, and symptoms vary between individuals depending on severity. [35][36], Hemoglobin E is due to a single point mutation in the gene for the beta chain with a glutamate-to-lysine substitution at position 26. [33][34] Several inherited variants in red blood cells have become common in parts of the world where malaria is frequent as a result of selection exerted by this parasite. Telephone: (301) 427-1364. [23], Protection also derives from the instability of sickle hemoglobin, which clusters the predominant integral red cell membrane protein (called band 3) and triggers accelerated removal by phagocytic cells. In the mid-1950s, one of the newest and most reliable ways of separating peptides and amino acids was by means of the enzyme trypsin, which split polypeptide chains by specifically degrading the chemical bonds formed by the carboxyl groups of two amino acids, lysine and arginine. [11] The authors suggest that this mechanism is likely to occur earlier in abnormal than in normal red cells, thereby restricting multiplication in the former. Shoutout to my amazing research mentor Dr. Sly for easing my nerves and helping my first lecture be a success! Further details may exist on the, If the frequency of the heterozygote is 0.40 the sickle-cell gene frequency (q) can be calculated from the, Learn how and when to remove these template messages, Learn how and when to remove this template message, glucose-6-phosphate dehydrogenase deficiency, Evolutionary_baggage § Sickle-Cell and Malaria, "How malaria has affected the human genome and what human genetics can teach us about malaria", "Population genetics of malaria resistance in humans", "The relationship between blood groups and disease", "Protection Afforded by Sickle-cell Trait Against Subtertian Malarial Infection", "The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults", "Four distinct pathways of hemoglobin uptake in the malaria parasite Plasmodium falciparum", "Excess heme in sickle erythrocyte inside-out membranes: possible role in thiol oxidation", "Suicide for survival--death of infected erythrocytes as a host mechanism to survive malaria", "Impaired cytoadherence of Plasmodium falciparum-infected erythrocytes containing sickle hemoglobin", "Sickle hemoglobin confers tolerance to Plasmodium infection", "Biochemical and immunological mechanisms by which sickle cell trait protects against malaria", "Global distribution of the sickle cell gene and geographical confirmation of the malaria hypothesis", "Hemoglobin variants and disease manifestations in severe falciparum malaria", "Sickle cell anemia, a molecular disease", "Sickle-Cell Anemia Hemoglobin: The Molecular Biology of the First "Molecular Disease"—The Crucial Importance of Serendipity", "An immune basis for malaria protection by the sickle cell trait", "Malaria continues to select for sickle cell trait in Central Africa", "Protection Against Malaria Morbidity: Near Fixation of the α-Thalassemia gene in a Nepalese Population", "Influence of hemoglobin E trait on the severity of Falciparum malaria", "Haemoglobin S and haemoglobin C: 'quick but costly' versus 'slow but gratis' genetic adaptations to Plasmodium falciparum malaria", "Hemoglobin C is associated with reduced Plasmodium falciparum parasitemia and low risk of mild attack", "Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect against malaria", "Hemoglobin E: a balanced polymorphism protective against high parasitemias and thus severe P. falciparum malaria", 10.1182/blood.V100.4.1172.h81602001172_1172_1176, "Malaria in African Children with Deficient Erythrocyte Glucose-6-phosphate Dehydrogenase", "Genetics of red cells and susceptibility to malaria", "Deletion in erythrocyte band 3 gene in malaria-resistant Southeast Asian ovalocytosis", "Prevention of cerebral malaria in children in Papua New Guinea by southeast Asian ovalocytosis band 3", "Failure to detect Plasmodium vivax in West and Central Africa by PCR species typing", "Duffy blood group gene polymorphisms among malaria vivax patients in four areas of the Brazilian Amazon region", "Plasmodium vivax clinical malaria is commonly observed in Duffy-negative Malagasy people", "Strong selection during the last millennium for African ancestry in the admixed population of Madagascar", "Duffy Negative Antigen Is No Longer a Barrier to Plasmodium vivax – Molecular Evidences from the African West Coast (Angola and Equatorial Guinea)", "In vitro evaluation of the role of the Duffy blood group in erythrocyte invasion by Plasmodium vivax", "Common west African HLA antigens are associated with protection from severe malaria", "Foetal haemoglobin and the dynamics of paediatric malaria", Brenda AkinyiI Webala, "Prevalence of Fetal Hemoglobin and Antibody Responses to, "The 1948 international congress of genetics in Sweden: people and politics", "J. [40] The enzyme deficiency is common in many countries that are, or were formerly, malarious, but not elsewhere. There is no longer doubt that malarial selection played a major role in the distribution of all these polymorphisms. 5.Erythrocyte Sedimentation Rate (ESR) The erythrocyte sedimentation rate (ESR), is the rate at which red blood cells sediment in a period of one hour. However, these changes also alter the functioning and form of red blood cells that may have visible effects, either overtly, or by microscopic examination of red blood cells. "[64] This became known as 'Haldane's malaria hypothesis', or concisely, the 'malaria hypothesis'.[65]. Being pregnant can cause some weird things to happen. In a large case–control study performed in Burkina Faso on 4,348 Mossi subjects, that HbC was associated with a 29% reduction in risk of clinical malaria in HbAC heterozygotes and of 93% in HbCC homozygotes. People who have this disease, particularly children, may have episodes of abdominal and joint pain, an enlarged spleen, and mild jaundice, but they do not have severe crises, as occur in sickle cell disease. [25] Targeting the stimuli that lead to endothelial activation will constitute a promising therapeutic strategy to inhibit sickle red cell adhesion and vaso-occlusion. Development of genetic resistance to malaria, Glucose-6-phosphate dehydrogenase deficiency, Hereditary persistence of fetal hemoglobin, Please expand the section to include this information. There is a negative correlation between frequencies of HbS and β-thalassemia in different parts of Greece and of HbS and HbC in West Africa. [13] Other mechanisms, such as enhanced tolerance to disease mediated by HO-1 and reduced parasitic growth due to translocation of host micro-RNA into the parasite, have been described.[14]. Glucose-6-phosphate dehydrogenase (G6PD) is an important enzyme in red cells, metabolizing glucose through the pentose phosphate pathway, an anabolic alternative to catabolic oxidation (glycolysis), while maintaining a reducing environment. Normal values : Men - 2-10 mm/hr Women - 2-15 mm/hr 50. P. vivax positivity was found in 8.8% of 476 asymptomatic Duffy-negative people, and clinical P. vivax malaria was found in 17 such persons. [43] An evolutionary genetic analysis of malarial selection of G6PD deficiency genes has been published by Tishkoff and Verelli. Such individuals have a subtype of a condition called hereditary elliptocytosis, characterized by oval or elliptical shape erythrocytes. [22], HbS has a lower negative charge at physiological pH than does normal adult hemoglobin. [38] G6PD deficiency is sex-linked, and common in Mediterranean, African and other populations. Microscopic parasites, like viruses, protozoans that cause malaria, and others, cannot replicate on their own and rely on a host to continue their life cycles. It removes old red blood cells and holds a … The fitnesses of different genotypes in an African region where there is intense malarial selection were estimated by Anthony Allison in 1954.