Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
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A distinctive type of hereditary ovalocytosis has been found in Papua New Guinea and a few areas of Southeast Asia. Its main features include a high incidence among tropical lowland dwellers, autosomal recessive inheritance, specific depression of a number of red cell antigens, a characteristic morphology in blood films, and an effect on the erythrocyte sedimentation rate. Speculation has occurred as to whether the high incidence of ovalocytosis in malarious areas may be related to a selective advantage possessed by ovalocytics with regard to severe malaria. Preliminary data tend to support this hypothesis, but the evidence is not conclusive and much further work is needed.
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PMID:Hereditary ovalocytosis in Melanesians. 26 77

Hereditary ovalocytosis in Papua New Guinea is restricted to areas of endemic malaria and may confer increased resistance to the disease. The incidence of malaria was investigated in 1616 Melanesiams of known red cell morphology and severity of infection determined in a smaller subsample. Ovalocytics tended to be more resistant to severe malarial infections than normocytics. The ratio of parasitaemia in 112 ovalocytics compared with 741 normocytic children was 1.05 for P. falciparum; 0.90 for P. vivax; 0.54 for P. malariae, and 0.91 for infection with any species. The difficulties in conclusively demonstrating any selective advantage of the condition are discussed.
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PMID:Malaria and hereditary ovalocytosis. 32 70

The malaria parasite rates and densities were compared in 79 ovalocytic-normocytic pairs of Malayan Aborigines matched for age, sex, proximity of residence to each other, and use of bednets when sleeping in their jungle settlement in central Peninsular Malaysia. Malaria infection was detected from thick and thin Giemsa-stained blood films collected monthly for a 6-month period. Blood films from ovalocytic individuals were found to be positive for malaria less often than in those individuals with normal red blood cells (p0.05). Malaria infections/100 person-months at risk were 9.7 in the ovalocytic group as compared with 15.19 in the other group. Among those parasitemic at any time, heavy infections (or= 10,000 parasites/cu.mm of blood) with Plasmodium falciparum, P. vivax, and P. malariae were seen only in normocytic subjects, approximately 12.5% of the malaria-positive persons in this group. In an earlier survey of 629 settlers who identified subjects for the above study, the prevalence of ovalocytosis was found to increase significantly with age. The above field observations support the view that ovalocytic individuals might have a survival advantage in the face of malaria. Consideration of the ovalocytic factor is indicated in future evaluations of malaria control measures in those areas where ovalocytosis is prevalent.
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PMID:Ovalocytosis protects against severe malaria parasitemia in the Malayan aborigines. 152 39

Hereditary ovalocytosis is common in some areas of Melanesia and South East Asia where malaria is endemic. These red cells resist invasion by malarial parasites in vitro and ovalocytic individuals are less parasitized than normal. This has been attributed to the greater rigidity of ovalocytic red cells. It has been suggested that South East Asian ovalocytosis results from the heterozygous presence of an altered membrane anion transporter (band 3). We have used the polymerase chain reaction to clone the abnormal band 3 complementary DNA from an ovalocytic of Indian origin and found two changes from the normal protein: a point mutation (Lys 56----Glu) and the deletion of the sequence AFSPQVLAA (residues 400-408), but no evidence for an N-terminal extension. The deletion is also found in the abnormal band 3 of South East Asian ovalocytes and seems to be responsible for the unusual properties of the ovalocytic red cell. We show here that the membrane domain of the abnormal ovalocyte band 3 has a substantially altered structure and that the protein is defective in anion transport activity. The changed transport properties of the red cells may have a role in the reduced parasitaemia of ovalocytic individuals.
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PMID:Defective anion transport activity of the abnormal band 3 in hereditary ovalocytic red blood cells. 153 63

Previous studies in Madang have demarcated 2 groups of women, one with high spleen rates (HS group) and the other with low spleen rates (LS group). An association between glucose 6-phosphate dehydrogenase (G6PD) deficiency and low spleen rates was investigated in 196 HS and 106 LS group men. Prevalence was 12.2 and 9.4%, respectively. Parasite and spleen rates were lower in deficients in the HS group. Differences in prevalence between HS group villages were observed which may be related to the interaction of G6PD deficiency with other haemoglobinopathies such as ovalocytosis. An effect on malaria endemicity at the village level may only occur when G6PD deficiency is a predominant trait.
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PMID:Malaria and glucose 6-phosphate dehydrogenase deficiency in populations with high and low spleen rates in Madang, Papua New Guinea. 217 19

The human innate resistance to P. falciparum malaria is based on genetic features that affect several stages of the intraerythrocytic cycle of the plasmodia. HbS, HbE and alpha and beta thalassemia (in addition to G-6PD deficiency) are protective to the carriers, because they inhibit the intraerythrocytic growth period, and in the case of AS red cells, in addition, parasitosis make them detectable expeditiously by the spleen. Blood group polymorphisms can interfere with red cell invasion by plasmodia. HbC belongs to a special category, since it apparently interferes with the cycle at the moment of cell lysis and release of merozoites. Finally, ovalocytosis observed in South East Asia, which most likely corresponds to a cytoskeleton or membrane protein defect, protects from malaria by inhibiting invasion. It should be kept in mind that many of these red cell defects might protect individuals in the critical first 5 years of life by retarding the switch of HbF to adult hemoglobin, since the HbF containing red cells are less than hospitable to the parasite.
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PMID:Innate resistance to malaria: the intraerythrocytic cycle. 225 17

There is a high prevalence of the erythrocyte polymorphism ovalocytosis associated with reduced susceptibility to malaria in Papua New Guinea. The major erythrocyte integral membrane protein, Band-3, showed markedly increased phosphorylation in whole cells or isolated ghosts from ovalocytic individuals. The cytoplasmic domain of the ovalocyte Band-3 was found to be approx. 3 kDa larger than the normocytic protein. The N-terminal sequence of the ovalocytic Band-3 was different from the reported sequence for human Band-3, suggesting that the increased size results from an N-terminal extension. Since this is the region of Band-3 which is phosphorylated and interacts with the red cell cytoskeleton, it is likely that this alteration in ovalocytic Band-3 is the underlying cause of the diverse alterations in ovalocytic cells including increased phosphorylation, increased membrane rigidity, decreased agglutinability by blood group antibodies and refractoriness to invasion by malarial parasites.
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PMID:Human erythrocyte Band-3 has an altered N terminus in malaria-resistant Melanesian ovalocytosis. 226 83

We report the distribution of two genetic traits, glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and hereditary ovalocytosis (HO) in a number of populations living in the Ok Tedi impact region of Papua New Guinea. Significant interpopulation heterogeneity in the distributions of G-6-PD deficiency and HO was observed. The highlands populations of the region did not show any G-6-PD deficiency, but in the highlands fringe and lowland populations the trait has achieved polymorphic frequencies. Hereditary ovalocytosis is significantly more common in the region and is present in all the populations studied, including those in the highland valleys. Distribution patterns of the two genetic markers correspond well with the pattern of malaria endemicity in the region, providing support for the hypothesis that relates the distribution of these polymorphisms to that of malaria.
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PMID:Glucose-6-phosphate dehydrogenase deficiency and hereditary ovalocytosis in the Ok Tedi impact region of Papua New Guinea. 280 63

A study of the distribution of alpha-thalassemia in Papua New Guinea (PNG) was carried out by DNA analysis. A total of 664 DNA samples were screened for alpha-thalassemia 2 and alpha-thalassemia 1 caused respectively by either deletion of one or both of the duplicated alpha-globin genes. alpha-Thalassemia 2 was detected in high frequencies in coastal and lowland regions where malaria has been holo- to hyperendemic but in low frequencies in non-malarious highland regions. The highest frequency was observed in the north coast of PNG. The distribution of alpha-thalassemia 2 seems to be in accordance with other conditions such as ovalocytosis and G6PD deficiency which are also prevalent in this population, suggesting that they may interact in protection against malaria. However, it appears to be negatively correlated with beta-thalassemia and alpha-thalassemia 1, the latter being extremely rare in this population. Analysis of the types and subtypes of the single alpha-globin gene deletion revealed a predominance of the -alpha 4.2 type in general, except in some regions in the south where the -alpha 3.7 type is prevalent. The -alpha 3.7 I subtype is the common form of the -alpha 3.7 deletion in the PNG mainland. The -alpha 3.7 III subtype, previously reported to be unique in Melanesians and Polynesians, was detected in an offshore island of PNG. However, this subtype is very rare in Melanesians from the PNG mainland.
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PMID:Alpha-thalassemia in Papua New Guinea. 287 71

Ovalocytosis, an hereditary condition in which most erythrocytes are oval in shape, is a polymorphism that occurs in up to 20% or more of the population in Papua New Guinea and Malaysia. Due to the geographical correlation of the trait with endemic malaria, the possibility of a selective advantage in resistance to malaria has been raised. In a study of 202 individuals with greater than or equal to 50% oval red cells matched by age, sex and village of residence with controls having less than or equal to 30% oval cells, ovalocytic subjects had blood films negative for Plasmodium vivax (P = 0.009), for P. falciparum (P = 0.044), and for all species of malaria parasites (P = 0.013), more often than controls. Among individuals parasitaemic at any time there were no clear differences in density of parasitaemia. However, in children 2 to 4 years old, parasite densities of both species were lower in ovalocytic subjects than in controls (0.01 less than P less than 0.025). The differential susceptibility to malaria infection suggested by this study has implications for the evaluation of interventions, including possible future vaccine field trials, in populations where high-frequency ovalocytosis is present.
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PMID:Hereditary ovalocytosis and reduced susceptibility to malaria in Papua New Guinea. 332 76


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