Ovalocytosis Protects against Severe Malaria Parasitemia in the Malayan Aborigines

Foo, L C; Rekhraj, V; Chiang, G. L.; Mak, Joon Wah

doi:10.4269/ajtmh.1992.47.271

Cited by 32 publications

(30 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Protection against malarial infection by ovalocytoses of unspecified genotypes has also been demonstrated in populations in nearby Southeast Asia (8,68). Ovalocytic RBCs resist invasion by P. falciparum (110) and by Plasmodium knowlesi (85), a simian malaria parasite with similar RBC invasion characteristics to P. vivax.…”

Section: Ovalocytosismentioning

confidence: 99%

Evolutionary and Historical Aspects of the Burden of Malaria

2002

View full text Add to dashboard Cite

Malaria is among the oldest of diseases. In one form or another, it has infected and affected our ancestors since long before the origin of the human line. During our recent evolution, its influence has probably been greater than that of any other infectious agent. Here we attempt to trace the forms and impacts of malaria from a distant past through historical times to the present. In the last sections, we review the current burdens of malaria across the world and discuss present-day approaches to its management. Only by following, or attempting to follow, malaria throughout its evolution and history can we understand its character and so be better prepared for our future management of this ancient ill

show abstract

Section: Ovalocytosismentioning

confidence: 99%

Evolutionary and Historical Aspects of the Burden of Malaria

2002

View full text Add to dashboard Cite

show abstract

“…On the other hand, SAO individuals are fully susceptible to severe malaria anemia and clinical uncomplicated malaria. 18 Although early studies, conducted before the presence of the SAO trait could be determined unambiguously by polymerase chain reaction (PCR), suggested that SAO individuals exhibit some degree of protection against prevalence of malaria parasites or against high-density P falciparum infections, [20][21][22] later studies demonstrated that SAO individuals suffer high-density infections by P falciparum and this trait only has minor effects, if any, on the prevalence and density of P falciparum infections. 18,23 Our recent finding that SAO infected RBCs (IRBCs) have altered adherence properties compared with normal IRBCs (A.C., M. Mellombo, C.S.…”

Section: Introductionmentioning

confidence: 99%

Ability of Plasmodium falciparum to invade Southeast Asian ovalocytes varies between parasite lines

Cortés

Benet

Cooke

et al. 2004

Blood

View full text Add to dashboard Cite

IntroductionInvasion of host red blood cells (RBCs) by the merozoite is a pivotal step in the life cycle of the malaria parasite Plasmodium falciparum and a clear target for vaccine development. The process of invasion is complex and involves multiple ligand-receptor interactions that are still poorly understood. Additional complexity of this process comes from the heterogeneity among P falciparum lines in the use of particular receptors, as demonstrated by experiments with enzyme-treated and mutant RBCs. 1,2 Malaria is presumed to be the single infectious disease that has had the biggest impact on the human genome, with some genetic traits maintained at relatively high frequencies in malaria endemic populations because of the selective advantage that they confer against this disease. 3 Many of these polymorphisms involve proteins that are expressed in the RBC, including hemoglobin and proteins located at the surface of RBCs. However, it is not completely clear yet whether any of these polymorphisms confers a selective advantage against malaria by preventing invasion by P falciparum merozoites.Southeast Asian ovalocytosis (SAO) is a peculiar RBC abnormality that results from a 27-bp deletion in the gene encoding band 3 (AE1⌬27), 4 the major transmembrane protein in the RBC. Band 3 has a cytoplasmic N-terminal domain and a C-terminal domain with 12 or 14 membrane-spanning regions. 5 This protein functions as an anion transporter but also has a role in maintaining the integrity of the RBC by anchoring the membrane to the underlying cytoskeleton. The 9-amino acid deletion that defines the SAO trait is located at the boundary between the cytoplasmic domain and the first transmembrane segment and results in major alterations in the folding and function of the membrane domain. 6-9 The SAO trait is found only in the heterozygous state and is presumed to be lethal when homozygous, 10 but the presence of mutated band 3 has dominant effects. The mutant band 3 induces conformational changes in essentially all of the normal fraction of the protein, 7 which is explained by the predominance of band 3 heterotetramers, higher order hetero-oligomers, and aggregates in SAO RBCs, in contrast to normal RBCs where band 3 is mainly found as dimers. 7,11,12 SAO RBCs are deficient in anion transport 9 and their mechanical properties are also dramatically altered. These RBCs are oval in shape and exhibit reduced cell deformability and an extreme increase in membrane rigidity. [13][14][15] Furthermore, mutant band 3 results in a decrease in the expression of several RBC antigens. 8,16 SAO also has an effect on susceptibility to malaria. Despite lethal selection against homozygous SAO carriers, this trait reaches high prevalence in some parts of the Western Pacific, 17 and the prevalence of this trait correlates with malaria endemicity in Papua New Guinea (PNG). 10 Two independent epidemiologic studies demonstrated that the SAO trait confers a striking protection against cerebral malaria, 18,19 one of the most devastating complications of...

show abstract

“…The higher frequencies of SAO found in adults than in the young of the same population in malaria endemic areas (Baer et al, 1976) also supported this hypothesis and suggested a selective advantage of SAO in such areas. However, several studies on malaria resistance of SAO are controversial in terms of parasite density or Plasmodium species (Baer et al, 1976;Serjeantson et al, 1977;Cattani et al, 1987;Foo et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Ovalocytosis without band 3 gene 27-bp deletion and malaria infection

Kimura

Soemantri

Siswanto³

et al. 2006

View full text Add to dashboard Cite

Genetic adaptation to malaria is a longstanding research topic in anthropology and human genetics. Southeast Asian ovalocytosis (SAO) has been documented to have resistance to malaria; however, the implications of existing data are controversial. In particular, SAO resistance to malaria is unlcear in terms of the types of SAO, with/without the 27-base pair deletion in the band 3 gene (B3∆27). To shed light on the relationships between SAO and malaria, we surveyed Plasmodium infection, erythrocyte morphology, and the presence of the B3∆27 among the residents of a selected area in East Kalimantan, Indonesia where malaria is endemic. We screened peripheral blood smears (n = 128) for Plasmodium infection and erythrocyte morphology under a microscope, and then DNA was extracted from the smears to be used as a template for a polymerase chain reaction to detect the B3∆27. The prevalence of infection with Plasmodium including Plasmodium vivax and Plasmodium falciparum was approximately 30%. Among a total of 128 subjects, 9.4% and 18.0% showed moderate (ovalocytic cells: 30-49%) and severe (ovalocytic cells: 50-100%) ovalocytosis, respectively. A total of three B3∆27 carriers were identified. The data set was statistically analyzed and we observed that (1) higher ovalocytic rate resulted in lower malaria infection and (2) the B3∆27 did not prevent malaria infection. These results suggest that resistance of SAO to malaria is due to SAO without the B3∆27.

show abstract

Ovalocytosis Protects against Severe Malaria Parasitemia in the Malayan Aborigines

Cited by 32 publications

References 0 publications

Evolutionary and Historical Aspects of the Burden of Malaria

Evolutionary and Historical Aspects of the Burden of Malaria

Ability of Plasmodium falciparum to invade Southeast Asian ovalocytes varies between parasite lines

Ovalocytosis without band 3 gene 27-bp deletion and malaria infection

Contact Info

Product

Resources

About