Human genetic polymorphisms and asymptomatic Plasmodium falciparum malaria in Gabonese schoolchildren

Several studies have focused their attention on the relationship between host genetic factors and susceptibility/resistance to severe malaria. However, there is a paucity of information concerning the role of host genetic factors in asymptomatic malaria, a form of low-grade Plasmodium falciparum infection without clinical symptoms. We investigated in this study the potential relationship between the host (human) genetic polymorphisms (glucose-6-phosphate dehydrogenase [G6PD], mannose binding lectin [MBL], tumor necrosis factor alpha [TNFalpha](-308) and (-238), and nitric oxide synthase 2 [NOS2](-954)) and the prevalence and profile of asymptomatic P. falciparum infection in 158 Gabonese schoolchildren. We found that G6PD A- heterozygous females (18 of 74) have a low prevalence of asymptomatic malaria (38.9% versus 67.3%; P = 0.03, by chi-square test). Children heterozygous for TNFalpha(-238) (25 of 156) carry high number of diverse infecting parasite genotypes (2.5 versus 1.99; variance F = 3.05). No statistically significant association was found between MBL, TNFalpha(-308), or NOS2 polymorphisms and asymptomatic malaria. Upon combining our data on asymptomatic forms with those from the literature for others forms, we conclude that G6PD A- heterozygous females are protected against all forms of P. falciparum malaria, and that the TNFalpha(-238A) allele confers protection against clinical malaria.     

Epidemiology and burden of malaria in pregnancy

We reviewed evidence of the clinical implications and burden of malaria in pregnancy. Most studies come from sub-Saharan Africa, where approximately 25 million pregnant women are at risk of Plasmodium falciparum infection every year, and one in four women have evidence of placental infection at the time of delivery. P falciparum infections during pregnancy in Africa rarely result in fever and therefore remain undetected and untreated. Meta-analyses of intervention trials suggest that successful prevention of these infections reduces the risk of severe maternal anaemia by 38%, low birthweight by 43%, and perinatal mortality by 27% among paucigravidae. Low birthweight associated with malaria in pregnancy is estimated to result in 100,000 infant deaths in Africa each year. Although paucigravidae are most affected by malaria, the consequences for infants born to multigravid women in Africa may be greater than previously appreciated. This is because HIV increases the risk of malaria and its adverse effects, particularly in multigravidae, and recent observational studies show that placental infection almost doubles the risk of malaria infection and morbidity in infants born to multigravidae. Outside Africa, malaria infection rates in pregnant women are much lower but are more likely to cause severe disease, preterm births, and fetal loss. Plasmodium vivax is common in Asia and the Americas and, unlike P falciparum, does not cytoadhere in the placenta, yet, is associated with maternal anaemia and low birthweight. The effect of infection in the first trimester, and the longer term effects of malaria beyond infancy, are largely unknown and may be substantial. Better estimates are also needed of the effects of malaria in pregnancy outside Africa, and on maternal morbidity and mortality in Africa. Global risk maps will allow better estimation of potential impact of successful control of malaria in pregnancy.     

Adolescent pregnancy and the risk of Plasmodium falciparum malaria and anaemia-a pilot study from Sekondi-Takoradi metropolis, Ghana

The problem of malaria in adolescence has been surpassed by the immense burden of malaria in children, most especially less than 5. A substantial amount of work done on malaria in pregnancy in endemic regions has not properly considered the adolescence. The present study therefore aimed at evaluating the prevalence of Plasmodium falciparum and anaemia infection in adolescent pregnant girls in the Sekondi-Takoradi metropolis, Ghana. The study was carried out at four hospitals in the Sekondi-Takoradi metropolis of the western region of Ghana from January 2010 to October 2010. Structured questionnaires were administered to the consenting pregnant women during their antenatal care visits. Information on education, age, gravidae, occupation and socio-demographic characteristics were recorded. Venous bloods were screened for malaria using RAPID response antibody kit and Geimsa staining while haemoglobin estimations were done by cyanmethemoglobin method. The results revealed that adolescent pregnant girls were more likely to have malaria infection than the adult pregnant women (34.6% verses 21.3%, adjusted OR 1.65, 95% CI, 1.03-2.65, P=0.039). In addition, adolescent pregnant girls had higher odds of anaemia than their adult pregnant women equivalent (43.9% versus 33.2%; adjusted OR 1.63, 95% CI, 1.01-2.62, P=0.046). Taken together, these data suggest that adolescent pregnant girls were more likely to have malaria and anaemia compared to their adult pregnant counterpart. Results from this study shows that proactive adolescent friendly policies and control programmes for malaria and anaemia are needed in this region in order to protect this vulnerable group of pregnant women.     

Haptoglobin phenotypes and malaria infection in pregnant women at delivery in western Cameroon

Plasmodium falciparum-infected erythrocytes have been reported to sequester in the placenta by adhering to chondroitin 4-sulfate during pregnancy. Earlier studies have highlighted higher susceptibility of primigravidae to P. falciparum compared to multigravidae living within the same endemic areas. The haptoglobin phenotype (Hp1-1) has been associated with susceptibility to severe P. falciparum malaria and the presence of Hp in human endometrium has been reported. The possible role of different Hp phenotypes in susceptibility to or protection from placental infection by P. falciparum in both primigravid and multigravid women at delivery in western Cameroon was investigated in this study. Only the three major haptoglobin phenotypes; Hp1-1, Hp2-1 and Hp2-2, were found in the study population with the Hp1-1 phenotype being the predominant (53%). There was no significant difference in the distribution of the three Hp phenotypes between the two gravidity groups. Women carrying the Hp1-1 phenotype had higher parasite prevalences in both peripheral blood (21.6% against 9.1%) and placentas (42% against 16.7%) when compared to those with the Hp2-2 phenotype. The difference in the parasite density between women carrying the Hp1-1 and Hp2-2 phenotypes was statistically significant for placental infection (P=0.001) but not for maternal peripheral blood infection. Placental parasitaemias without peripheral blood parasitaemias were detected in 42.6% of all the P. falciparum positive women while 27.7% of the women had peripheral blood parasitaemias in the absence of placental infection and 29.8% of the women had both placental and peripheral blood parasitaemias. A statistically significant difference was observed between the primigravidae and multigravidae in the parasite density in placental biopsies (P=0.02) but not for maternal peripheral blood parasitaemia. Our data suggest that the Hp1-1 phenotype may play a role in susceptibility to placental infection by P. falciparum during pregnancy.     

Anaemia in pregnancy: Plasmodium falciparum infection is an important cause in primigravidae in Hoima district, western Uganda

Infection with Plasmodium falciparum is a major cause of anaemia in pregnancy, especially in primigravidae. Of 853 primigravidae visiting an antenatal clinic in Hoima district, western Uganda, for the first time, 530 (62.1%) were found to have P. falciparum parasitaemias and 305 (57.5%) of these had at least 1000 parasites/microliter blood. Plasmodium falciparum parasitaemia was significantly associated with anaemia (relative risk = 0.84, with 95% confidence limits = 0.74-0.96; P = 0.01). Malarial parasites were detected in > 80% of the women who had severe anaemia (P = 0.0008) and haemoglobin concentrations decreased with increasing intensity of infection (P = 0.03). Malarial hyper-reactive splenomegaly was associated with high parasite density (P = 0.01) and low haemoglobin level (P < 0.0001). Effective measures aimed at prevention of malaria and anaemia in pregnancy, especially in primigravidae, would significantly reduce anaemia and its deleterious effects on both the mother and the baby.     

Falciparum malaria and beta-thalassaemia trait in northern Liberia

In a study in northern Liberia of the malaria and beta-thalassaemia hypothesis, the frequencies of beta-thalassaemia and HbS traits were 9.1 and 3.4% in the Mano and 9.5 and 1.7% in the Gio tribal samples. HbC and HbN were present at low frequency. G6PD deficiency was found in 16% of males. An observed increase with age of beta-thalassaemia trait frequencies was consistent with the selection hypothesis. However, we could not entirely exclude that associated iron deficiency influenced the results in the six to 11 month age group. Malaria was holoendemic; Plasmodium falciparum predominated, P. malariae and P. ovale were also identified. Plasmodium falciparum prevalence rates were similar in normal and beta-thalassaemia trait children but parasite densities were consistently lower in the latter. Using the criterion of a falciparum parasite density of 1 x 10(9) 1(-1) or greater to indicate a potentially important infection, the relative risk in beta-thalassaemia traits one to four years old from the cross-sectional study was 0.45 (upper 95% confidence interval 0.79) and 0.41 (0.61) in two to nine year trait carriers from a longitudinal study. Plasmodium falciparum gametocyte rates were lower in beta-thalassaemia trait children (P less than 0.005). The geometric mean titre of P. falciparum antibodies was lower in beta-thalassaemia trait children from the one to four year group (P less than 0.05). Otherwise immunological studies showed little difference between the different Hb types. Parasitological findings were consistent with relative resistance of HbS trait carriers towards P. falciparum infection. We found no evidence for relative resistance of beta-thalassaemia traits towards P. malariae infection nor that G6PD deficient males were more resistant to P. falciparum than those with normal activity. We conclude that the results are consistent with relative resistance of beta-thalassaemia trait carriers to P. falciparum malaria.     

Glucose-6-phosphate dehydrogenase deficiency.

Glucose-6-phosphate dehydrogenase (G6PD) is expressed in all tissues, where it catalyses the first step in the pentose phosphate pathway. G6PD deficiency is prevalent throughout tropical and subtropical regions of the world because of the protection it affords during malaria infection. Although most affected individuals are asymptomatic, there is a risk of neonatal jaundice and acute haemolytic anaemia, triggered by infection and the ingestion of certain drugs and broad beans (favism). A rare but more severe form of G6PD deficiency is found throughout the world and is associated with chronic non-spherocytic haemolytic anaemia. Many deficient variants of G6PD have been described. DNA sequence analysis has shown that the vast majority of these are caused by single amino acid substitutions. The three-dimensional structure of G6PD shows a classical dinucleotide binding domain and a novel beta + alpha domain involved in dimerization.     

Microscopic and sub-microscopic Plasmodium falciparum infection, but not inflammation caused by infection, is associated with low birth weight

Pregnancy-associated malaria is one of the leading causes of low birth weight in malaria endemic areas. In this study, 145 parturient women residing in areas endemic for Plasmodium falciparum in Lambaréné, Gabon, were recruited into the study after delivery, and the association of maternal P. falciparum infection, inflammatory response, and birth weight was studied. At delivery, 10% (15) of the mothers (12 were positive in both peripheral and placental blood smears, 1 was positive in peripheral blood only, and 2 were positive in placenta blood only) were positive for P. falciparum by microscopy and 23% (30) by real-time polymerase chain reaction (PCR). The level of C-reactive protein (CRP) was significantly elevated in microscopically P. falciparum-positive pregnant women (34 mg/L; 95% CI: 3-458) but not in those with sub-microscopic infections (6 mg/L; 95% CI: 1-40) compared with those free of P. falciparum infection (7 mg/L; 95% CI: 1-43). In a multivariate analysis, the presence of microscopic (adjusted OR = 28.6, 95% CI = 4.8-169.0) or sub-microscopic (adjusted OR = 13.2, 95% CI = 2.4-73.0) P. falciparum infection in pregnant women and age of mothers < 21 years (adjusted OR = 9.7 CI = 1.0-89.7), but not CRP levels, were independent predictors for low birth weight. This finding may have important operational implications and emphasizes the need for appropriate diagnostic methods in studies evaluating the outcome of pregnancy-associated malaria.     

Association of ABO blood group and P. falciparum malaria related outcomes: a cross-sectional study in Ethiopia

Studies elucidate conflicting results about the relationships between ABO blood groups and Plasmodium infection outcomes in humans. This study examined association between ABO blood group and Plasmodium falciparum (P. falciparum) malaria related outcomes among 1065 malaria suspected febrile patients who attended Dore Baafano Health Center, southern Ethiopia, between December, 2010 and February, 2011. Blood specimens were collected and examined for malaria using Giemsa-staining, while stool specimens were examined for helminth infections using Kato-Katz method. Haemoglobin level and blood group were determined using hemocue machine and antisera hemagglutination test, respectively. Clinical data were also collected for the patients. Among the study participants, the proportion of O, A, B and AB blood groups were 40.1%, 30.1%, 29.0% and 14.3%, respectively, and P. falciparum malaria cases in the corresponding blood groups were 14.8%, 14.0%, 13.4% and 15.7%. The odds of non-severe P. falciparum malaria were not significantly different between individuals of blood group A versus O or B versus O or AB versus O. Mean haemoglobin concentration was significantly lower in P. falciparum infected blood type A individuals compared to P. falciparum infected blood type O (β=-1.25, 95% CI=-2.31 to -0.19) or non-A (β=-1.27, 95% CI=-2.23 to -0.32) individuals. The odds of P. falciparum malaria related anaemia was about three times higher in individuals with blood type A compared to those with blood type O (adjusted OR=2.82, 95% CI=1.05-7.56) or non-A individuals (adjusted OR=2.84, 95% CI=1.15-7.01). However, mean P. falciparum density did not significantly differ among patients according to their blood groups. In conclusion, individuals with blood group A had higher risk of anaemia compared to those with O and non-A phenotypes among P. falciparum malaria patients. However, there is a need to investigate the mechanism.     

Glucose-6-phosphate dehydrogenase deficiency

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect, being present in more than 400 million people worldwide. The global distribution of this disorder is remarkably similar to that of malaria, lending support to the so-called malaria protection hypothesis. G6PD deficiency is an X-linked, hereditary genetic defect due to mutations in the G6PD gene, which cause functional variants with many biochemical and clinical phenotypes. About 140 mutations have been described: most are single base changes, leading to aminoacid substitutions. The most frequent clinical manifestations of G6PD deficiency are neonatal jaundice, and acute haemolytic anaemia, which is usually triggered by an exogenous agent. Some G6PD variants cause chronic haemolysis, leading to congenital non-spherocytic haemolytic anaemia. The most effective management of G6PD deficiency is to prevent haemolysis by avoiding oxidative stress. Screening programmes for the disorder are undertaken, depending on the prevalence of G6PD deficiency in a particular community.     

Malaria in pregnancy: adverse effects on haemoglobin levels and birthweight in primigravidae and multigravidae

BACKGROUND: In areas of endemic transmission, malaria in pregnancy is associated with severe maternal anaemia and low birthweight babies. The prevalence of infection is highest in primigravidae (PG), and hence control efforts are usually geared towards this high risk group. Using a sensitive measure of placental infection, we investigated the relationship between active-acute, active-chronic and past placental infection with maternal anaemia and low birthweight in women of all gravidities. METHODS: Between January 1996 and July 1997, 912 women delivering in Kilifi District Hospital, Kenya, were recruited. Haemoglobin and peripheral malaria slides were taken prior to delivery, placental biopsies and smears were taken at the time of delivery and birthweight and maternal height and weight were measured soon after birth. Information was obtained on socio-economic and educational status. The association between placental malaria, severe anaemia and low birthweight was investigated for women of different gravidities. FINDINGS: By placental histology, the prevalence of active or past malaria in all gravidities was high, ranging from 64% in PG to 30% in gravidities 5 and above. In gravidities 1-4, active malaria infection was associated with severe maternal anaemia, adjusted OR 2.21 (95% CI 1.36, 3.61). There was a significant interaction between chronic or past malaria and severe anaemia in their effects on birthweight, whereby the risk of low birthweight was very high in women with both chronic or past placental malaria and severe anaemia: OR 4.53 (1.19, 17.2) in PG; 13.5 (4.57, 40) in gravidities 2-4. INTERPRETATION: In this area of moderate malaria transmission, women of all parities have substantially increased risk of low birthweight and severe anaemia as a result of malaria infection in pregnancy. The risk of low birthweight is likely to be particularly high in areas with a high prevalence of severe anaemia.     

Clinical features of children hospitalized with malaria--a study from Bikaner, northwest India

Severe Plasmodium vivax malaria in adults has been reported from Bikaner (northwestern India) but the reports on children are scanty. This prospective study was done on 303 admitted children of malaria. The diagnosis was done by peripheral blood smear and rapid diagnostic test. Further confirmation of severe P. vivax monoinfection was done by polymerase chain reaction (PCR). The proportion of P. falciparum, P. vivax, and mixed (P. falciparum and P. vivax) infection was 61.01%, 33.99%, and 4.95%, respectively. Severe disease was present in 49.5% (150/303) children with malaria, with the risk greatest among P. vivax monoinfection (63.1% [65/103]) compared with P. falciparum, either alone (42.7% [79/185]; odds ratio [OR] = 2.3 [95% confidence interval (CI) = 1.40-3.76], P = 0.001) or mixed infections (40% [6/15]; OR = 2.57 [95% CI = 0.88-7.48]). In children < 5 years of age, the proportion of severe malaria attributable to P. vivax rose to 67.4% (31/46) compared with 30.4% (14/46) of P. falciparum (OR = 4.7 [95% CI = 2.6-8.6], P < 0.0001) and 2.2% (1/46) of mixed infection (OR = 92 [95% CI = 24.6-339.9], P < 0.0001). The proportion of patients having severe manifestations, which included severe anemia, thrombocytopenia, cerebral malaria, acute respiratory distress syndrome, hepatic dysfunction, renal dysfunction, abnormal bleeding was significantly high in association with P. vivax monoinfection in 0-5 year age group, while the same was significantly high in association with P. falciparum monoinfection in 5-10 year age group. Similarly P. vivax monoinfection had greatest propensity to cause multiorgan dysfunction in 0-5 year age group (34.1% [17/41], P < 0.0001) in comparison to P. falciparum monoinfection, which had similar propensity in 5-10 year age group (36.8% [35/95], P = 0.039). Plasmodium vivax monoinfection was almost equally serious to cause significant mortality in comparison to P. falciparum (case fatality rate of severe P. vivax was 3.9% versus 3.2% of severe P. falciparum malaria; P = 1.0). This study reaffirms the evidence of severe P. vivax malaria in children in Bikaner.     

Prevalence and risk of Plasmodium falciparum and P. vivax malaria among pregnant women living in the hypoendemic communities of the Peruvian Amazon

The Amazon region of Iquitos, Peru is hypoendemic for Plasmodium vivax and P. falciparum. There is limited information regarding the epidemiology of malaria during pregnancy in this region. Passive surveillance for clinical malaria among pregnant women was conducted in eight health posts in 2004 and 2005. Community-based active surveillance was conducted to determine the incidence of malarial infection among pregnant women in the community of Zungarococha in 2004 and 2005. Passive surveillance demonstrated that pregnant women had a prevalence of clinical malaria of 7.5% in 2004 and 6.6% in 2005 compared with 20.6% and 22.4% of the total population. Active surveillance showed that pregnant women were 2.3 (95% confidence interval = 1.32-3.95, P = 0.004) times more likely to have a P. falciparum infection compared with non-pregnant women. This study demonstrated that because of detection bias, passive surveillance underestimates the burden of malarial infection during pregnancy, and that subclinical malarial infections may occur frequently among pregnant women in this region. Furthermore, pregnant women in this low-transmission and P. vivax-dominant setting, experience an increased risk for P. falciparum infection, but not P. vivax infection.     

The aetiology of severe anaemia in pregnancy in Ndola, Zambia

The aetiology of severe anaemia (haemoglobin less than 7.0 g dl-1) has been studied in 37 pregnant Zambians. Aetiology was usually multiple; 31 (84%) had Plasmodium falciparum malaria, 23 (62%) were folate deficient, 13 (35%) were iron deficient, one had sickle-cell anaemia and one had the acquired immunodeficiency syndrome (AIDS). Folate deficiency was most often secondary to malarial haemolysis: iron deficiency was nutritional, but hookworm was contributory in about one-third of patients. The anaemia of malaria and folate deficiency was both more common and more severe than anaemia due to iron deficiency; it was seen in younger women although primigravidae were not over-represented, it occurred earlier in pregnancy, and was associated with low birthweight. AIDS must now be included in the differential diagnosis of anaemia in pregnancy. Vigorous antimalarial treatment and prophylaxis are essential in the management and prevention of anaemia in pregnancy. Total dose iron infusion is indicated only when severe iron deficiency anaemia has been proven, and must be accompanied by antimalarial therapy and folic acid supplements. Because of the risk of transmission of human immunodeficiency virus, it is more important than ever to prevent anaemia and malaria in pregnancy, and to give blood transfusion only as a life-saving treatment.     

Plasmodium falciparum and helminth coinfection in a semi urban population of pregnant women in Uganda

BACKGROUND: Helminth infections and malaria are widespread in the tropics. Recent studies suggest helminth infections may increase susceptibility to Plasmodium falciparum infection. If confirmed, this increased susceptibility could be particularly important during pregnancy-induced immunosuppression. OBJECTIVE: To evaluate the geographical distribution of P. falciparum-helminth coinfection and the associations between P. falciparum infection and infection with various parasite species in pregnant women in Entebbe, Uganda. METHODS: A cross-sectional study was conducted at baseline during a trial of antihelminthic drugs during pregnancy. Helminth and P. falciparum infections were quantified in 2,507 asymptomatic women. Subjects' socioeconomic and demographic characteristics and geographical details were recorded. RESULTS: Hookworm and Mansonella perstans infections were associated with P. falciparum infection, but the effect of hookworm infection was seen only in the absence of M. perstans infection. The odds ratio [OR] for P. falciparum infection, adjusted for age, tribe, socioeconomic status, HIV infection status, and location was as follows: for individuals infected with hookworm but not M. perstans, 1.53 (95% confidence interval [CI], 1.09-2.14); for individuals infected with M. perstans but not hookworm, 2.33 (95% CI, 1.47-3.69); for individuals infected with both hookworm and M. perstans, 1.85 (CI, 1.24-2.76). No association was observed between infection with Schistosoma mansoni, Trichuris, or Strongyloides species and P. falciparum infection. CONCLUSIONS: Hookworm-P. falciparum coinfection and M. perstans-P. falciparum coinfection among pregnant women in Entebbe is more common than would be expected by chance. Further studies are needed to elucidate the mechanism of this association. A helminth-induced increase in susceptibility to P. falciparum could have important consequences for pregnancy outcome and responses to P. falciparum infection in infancy.     

Glucose-6-phosphate dehydrogenase (G6PD) deficiency--a cause of anaemia in pregnant women

Glucose-6-phosphate dehydrogenase (G6PD) is one of the most important cytoprotective enzymes for oxidative stress. The WHO classification of G6PD deficiency, based on enzyme activity and clinical significance, distinguishes five variants. Chronic haemolytic process is rare and the main factors causing haemolysis are: infections, substances derived from plants, drugs with high oxidation-reduction potential, stress, ketoacidosis in diabetes and surgery operations. We report two cases of women belonging to the class 3 of the WHO classification in whom haemolysis occured during pregnancy. One of the patients developed two incidents of haemolytic anaemia. The cause of the first episode, nine months before pregnancy, was probably infection of the urinary tract caused by Escherichia coli, but the influence of the drugs also cannot be excluded. Because of the genetic background of this enzymopathy we also examined members of the patients, families but did not find any evidence of G6PD deficiency among them. The reported cases indicate that haemolytic anaemia caused by G6PD deficiency may occur during pregnancy what can lead to many not only haematological but also serious obstetrical complications such as infertility, fetus malformations and even its death. We also draw attention to several difficulties in diagnosing G6PD deficiency especially during haemolysis.     

Both heterozygous and homozygous alpha+ thalassemias protect against severe and fatal Plasmodium falciparum malaria on the coast of Kenya

Although the alpha+ thalassemias almost certainly confer protection against death from malaria, this has not been formally documented. We have conducted a study involving 655 case patients with rigorously defined severe malaria and 648 controls, frequency matched on area of residence and ethnic group. The prevalence of both heterozygous and homozygous alpha+ thalassemia was reduced in both case patients with severe malaria (adjusted odds ratios [ORs], 0.73 and 0.57; 95% confidence intervals [95% CIs], 0.57-0.94 and 0.40-0.81; P = .013 and P = .002, respectively, compared with controls) and among the subgroup of children who died after admission with severe malaria (OR, 0.60 and 0.37; 95% CI, 0.37-1.00 and 0.16-0.87; P = .05 and P = .02, respectively, compared with surviving case patients). The lowest ORs were seen for the forms of malaria associated with the highest mortality-coma and severe anemia complicated by deep, acidotic breathing. Our study supports the conclusion that both heterozygotes and homozygotes enjoy a selective advantage against death from Plasmodium falciparum malaria.     

Association of FCgamma receptor IIA (CD32) polymorphism with malarial anemia and high-density parasitemia in infants and young children

Protective immunity against Plasmodium falciparum is partially mediated through binding of malaria-specific IgG antibodies to Fcgamma receptors. Polymorphic variability in Fcgamma RIIa (H/R-131) is associated with differential binding of IgG subtypes and malaria disease outcomes. However, the role of Fcgamma RIIa-131 variability in conditioning susceptibility to severe malarial anemia, the primary manifestation of severe malaria in holoendemic P. falciparum transmission areas, is largely undefined. Thus, Fcgamma RIIa-H131R polymorphism was investigated in 493 children who came to a hospital with acute malaria. Variation in Fcgamma RIIa-131 was not significantly associated with severe malarial anemia (hemoglobin [Hb] < 6.0 g/dL) or malaria anemia (Hb < 8.0 g/dL). However, relative to the heterozygous genotype, homozygotes for the R131 alleles were protected against high-density parasitemia (>or= 10,000 parasites/microL; odds ratio [OR] = 0.58, 95% confidence interval [CI] = 0.37-0.92, P = 0.02), while homozygotes for the H131 alleles were mildly protective (OR = 0.71, 95% CI = 0.45-1.13, P = 0.14). Additional multivariate analyses showed that infection with human immunodeficiency virus type 1 did not influence the associations between FcgammaRIIa-H131R polymorphism and malaria disease outcomes. Genotypic results presented here parallel data illustrating that parasite density is unrelated to the severity of anemia in children with acute malaria. Thus, although homozygosity for the R131 allele protects against high-density parasitemia, FcgammaRIIa-131 polymorphism does not protect against malaria anemia.     

Red cell glucose-6-phosphate dehydrogenase status and pyruvate kinase activity in a Nigerian population

Glucose-6-phosphate dehydrogenase A- (G6PD A-) deficiency is a common enzymopathy in Africa that sporadically leads to manifest haemolytic anaemia. It is not exactly known how far the haematological status of individuals with either homozygous or heterozygous G6PD A- deficiency differs from that of individuals with normal G6PD activity. In a field study in Nigeria, we determined G6PD gene variants, the corresponding G6PD and pyruvate kinase (PK) activities, and basic haematological parameters in clinically healthy individuals, who were, in part, asymptomatically infected by malaria parasites. Red blood cell counts and haemoglobin levels were lower in G6PD A- deficient than in G6PD normal subjects. PK activities were higher in G6PD deficients, indicating a younger red cell population in these individuals. These findings suggest that G6PD A- deficiency is accompanied by chronic subclinical haemolysis. As a consequence, the reduced life span of red cells leads to an impaired diagnosis of G6PD heterozygosity when applying routine biochemical methods.