Febrile status, malarial parasitaemia and gastro-intestinal helminthiases in schoolchildren resident at different altitudes, in south-western Cameroon

In the many areas where human malaria and helminthiases are co-endemic, schoolchildren often harbour the heaviest infections and suffer much of the associated morbidity, especially when co-infected. In one such area, the Buea district, in south-western Cameroon, two cross-sectional surveys, together covering 263 apparently healthy schoolchildren aged 4-12 years, were recently conducted. The prevalences of fever, malarial parasitaemia and intestinal helminth infections, the seroprevalences of anti-Plasmodium falciparum IgG and IgE and anti-glycosylphosphatidylinositol (anti-GPI) IgG, plasma concentrations of total IgE, and the incidence of anaemia were all investigated. The mean (S.D.) age of the study children was 7.56 (1.82) years. Overall, 156 (59.3%) of the children were found parasitaemic, with a geometric mean parasitaemia of 565 parasites/microl. Parasitaemia and fever were significantly associated (P=0.042). The children who lived at low altitude, attending schools that lay 400-650 m above sea level, had significantly higher parasitaemias than their high-altitude counterparts (P<0.01). At low altitude, the children attending government schools had significantly higher parasitaemias than their mission-school counterparts (P=0.010). Of the 31 children (11.9%) found anaemic, 22 (70.4%) had mild anaemia and none had severe anaemia. A significant negative correlation (r=-0.224; P=0.005) was observed between haemoglobin concentration and level of parasitaemia. Infection with Plasmodium appeared to reduce erythrocyte counts (P=0.045), a condition that was exacerbated by co-infection with helminths (P=0.035). Plasma concentrations of total IgE were higher in the children found to be excreting helminth eggs than in those who appeared helminth-free, while levels of anti-P. falciparum IgE were higher in the children with low-grade parasitaemias than in those with more intense parasitaemias. Levels of anti-GPI IgG increased with age and were relatively high in the children who lived at low altitude and in those who were aparasitaemic. The survey results confirm that asymptomatic malarial parasitaemia frequently co-exists with helminth infections in schoolchildren and indicate links with fever, altitude and school type. Immunoglobulin E may play a role in immune protection against helminthiasis whereas anti-GPI antibodies may be important in the development of antimalarial immunity in such children. In Cameroon, as in other areas with endemic malaria, control programmes to reduce the prevalences of infections with intestinal helminths and malarial parasites in schoolchildren, which may effectively reduce the incidence of anaemia, are clearly needed.     

Severe anaemia in Zambian children with Plasmodium falciparum malaria

BACKGROUND: Severe anaemia and cerebral malaria are highly prevalent complications of Plasmodium falciparum malaria among African children. The mechanisms of severe malarial anaemia, and the relative importance of this condition in comparison to cerebral malaria, are not known for many regions of Africa. METHODS We reviewed the records of 6200 children up to 6 years of age admitted to one rural Zambian hospital between 1994 and 1996. Severe malarial anaemia was defined as an haemoglobin concentration < 5.0 g/dl in a patient with asexual forms of P. falciparum in the peripheral blood. Cerebral malaria was defined as impaired consciousness (Blantyre coma score < 5) not attributable to any other cause in a patient with a positive malaria smear. RESULTS Severe malarial anaemia was found in 590 children (9.5% of paediatric admissions) and strictly defined cerebral malaria occurred in 286 children (4.6% of paediatric admissions); 98 of these patients had the combination of both complications. Severe malarial anaemia correlated strongly with the degree of parasitaemia, with malnutrition as indicated by low weight for age, with absence of fever and with presentation late in the malaria season. In comparison, patients with cerebral malaria were more often febrile and presented earlier in the malaria season. The case fatality rate of severe malarial anaemia (0.088) was about half that of cerebral malaria (0.189), but because severe malarial anaemia was more common, these two forms of complicated malaria were implicated in similar numbers of in-hospital paediatric deaths. CONCLUSION Severe anaemia is a more common complication of P. falciparum malaria in hospitalized Zambian children than cerebral malaria and is associated with a similar number of deaths. Malnutrition and changes in immune response patterns due to prolonged exposure to P. falciparum may contribute to the development of this complication.     

Effect of triiodothyronine on reactive oxygen species generation by leukocytes, indices of oxidative damage, and antioxidant reserve

We have examined the effect of short-term triiodothyronine (T3) administration on reactive oxygen species (ROS) generation by leukocytes in 9 euthyroid subjects. At a dose of 60 microg/d orally for 7 days, T3 induced a significant increase in ROS generation by mononuclear cells (MNCs) from 183 +/- 102 mV at baseline to 313 +/- 111 mV on the seventh day (P < .02), and by polymorphonuclear leukocytes (PMNLs) from 195 +/- 94 mV at baseline to 302 +/- 104 mV on the seventh day (P < .02). There was also a significant increase in meta-tyrosine (P < .001) and ortho-tyrosine (P < .001), known indices of oxidative damage to proteins and amino acids. However, there was no increase in plasma thiobarbituric acid-reactive substances (TBARS), an index of oxidative damage to lipids, and in the level of carbonylated proteins, a less sensitive index to assess protein oxidation. There was no decrease in the level of antioxidants such as alpha-tocopherol, vitamin A, beta-carotene, lycopene, and lutein/zeaxanthin. The stimulatory effect on ROS generation may reflect a generalized increase in metabolic activity or may be a specific effect on NADPH oxidase in leukocyte membranes. The absence of a significant change in TBARS, carbonylated proteins, alpha-tocopherol, vitamin A, beta-carotene, lycopene, and lutein/zeaxanthin may reflect the short duration of the increased ROS load.     

Age-dependent effect of plasma nitric oxide on parasite density in Ghanaian children with severe malaria

Nitric oxide (NO) has toxic properties against Plasmodium falciparum. While high blood levels have been associated with protection against severe malarial disease, they may also contribute to the pathophysiology of cerebral malaria and severe anaemia. Promoter variants in the inducible nitric oxide synthase (iNOS) gene have been shown to influence NO concentrations and disease manifestation. However, findings are conflicting. We examined associations of plasma NO metabolites (NOx) with symptoms of severe malaria, particularly malarial anaemia and cerebral malaria, and with iNOS promoter variants. In 210 Ghanaian children with severe malaria, we measured plasma nitrite, nitrate, and S-nitrosothiol, and genotyped the iNOS promoter variants -954G-->C, -1173C-->T, and the -2.5 kb (CCTTT)(n) microsatellite. NOx levels decreased with age. In young children (<24 months), high NOx was associated with reduced parasite density. This was not seen in patients of 24-48 months of age and reversed in older children. Subgroup analysis revealed that in children with severe anaemia but without cerebral involvement (prostration, impaired consciousness, convulsions), high NOx levels correlated with low parasitaemia (P = 0.02). In these children, elevated NOx levels were also associated with the iNOS-954C-->T/(CCTTT)(8) haplotype (P = 0.03). No association between NOx or iNOS genotypes and cerebral malaria was observed. Our findings suggest that in young children with severe malaria NOx reduces parasitaemia. This effect wanes at higher ages and may reflect a predominance of unspecific immune responses to infection in early childhood. This finding may have importance for the understanding of associations between iNOS variants and severe malaria in regions of differing disease manifestation.     

Red cell acetylcholinesterase activity in Plasmodium falciparum malaria

Red cell ACHE activity was determined in 19 patients with P. falciparum malaria, 13 patients during convalescence as well as in 6 normal subjects. There was no significant difference between the mean values of ACHE in red cells of these 3 groups. After separation these blood samples into 2 portions by centrifugation in 5% Ficoll solution, the parasitized red cells in the lower portion which are mostly ring forms contained the same amount of ACHE activity as those of the normal subjects and the non-parasitized red cells. However, the parasitized red cells in the upper portion which contained predominantly mature asexual forms revealed a significantly higher ACHE activity than those of the normal red cells. There was also a reverse relationship between red cell ACHE activity and the parasitaemia from this portion of blood sample. These findings indicated that although malarial parasite invaded and caused the red cell membrane damage, it did not inactivate ACHE. It may be concluded that ACHE was not responsible for the anaemia and excessive erythrocyte destruction in patients with P. falciparum malaria.     

Severe anaemia in children living in a malaria endemic area of Kenya

Severe anaemia is an important cause of morbidity and mortality in African children, but the causes, particularly falciparum malaria, are difficult to determine. We assessed the contribution of falciparum malaria to anaemia in Kenyan children by clinical examination and measurement of parasitaemia and haemoglobin (Hb) concentration in 559 children in the community and in 2412 children admitted to Kilifi district hospital during a 2‐year period. We also attempted to characterize severe malarial anaemia by examining the causes and pathophysiology of anaemia in 101 children admitted with Hb concentration 50 g/l during a 1‐year period. Plasmodium falciparum infection was associated with reduced Hb concentration in children in the community and in those admitted to hospital irrespective of diagnosis. Falciparum malaria was the primary cause in 46 cases (46%) of severe anaemia admitted to hospital. There was no difference in the frequency of haemolysis or dyserythropoiesis in the children with malarial anaemia and those with anaemia from other causes, such as iron deficiency or sickle cell disease. The mortality rate in the children with severe malarial anaemia was 8.6% compared with 3.6% in children with severe anaemia due to other causes. Falciparum malaria does not present with a characteristic clinical or haematological picture, but is a major cause of the morbidity and mortality in children with severe anaemia who live on the Kenyan coast, a malaria endemic area.     

Relationships between maternal malaria and malarial immune responses in mothers and neonates

Immune responses of 97 Gambian women and their neonates were studied. New methods distinguished between active and previous placental malaria, were used to examine relationships between maternal malaria and neonatal immune responses. Many placentas (61%) had active or previous malarial infection. Maternal and cord malarial IgG levels correlated ( P < 0–001). Malarial IgG was raised in cord blood in active placental malaria; IgM was not detected. Mean lymphoproliferation and the proportion of responders to soluble P. falciparum antigens (F32) and conserved regions of p190 expressed on trophozoites and schizonts (190L and 190N) were higher in neonates than mothers. There was no clear relationship between maternal malaria and neonatal mean lymphoproliferation to malarial antigens, although fewer neonates responded when mothers were actively infected. Matched maternal and neonatal lymphoproliferation responses did not correlate. However, first born neonatal lymphoproliferation to PPD and malarial antigens appeared lower than other neonates, in agreement with lower lymphoproliferation in primigravidae compared with multigravidae. Also in common with mothers, autologous plasma suppressed neonatal lymphoproliferation to PPD and malarial antigens, suggesting common immunoregulation. Higher Cortisol or other circulating factors in first pregnancies may be implicated. The relevance of cell-mediated malarial immune responses detected at birth remains to be established.     

Markers of inflammation in children with severe malarial anaemia

OBJECTIVE: To investigate if severe malarial anaemia is associated with a specific immune response pattern, we determined serum levels of neopterin (a marker of activation of macrophages by interferon-gamma) and of the anti-inflammatory cytokines, interleukins 4 and 10. METHODS: Zambian children < 6 years of age presenting to a rural hospital with cerebral malaria were studied. Twenty-one children with admission haemoglobin concentrations /= 7 g/dl served as a control group. RESULTS: Logistic regression modelling indicated that a 10-fold rise in serum neopterin concentrations was associated with a 50-fold increase in the estimated odds of having severe anaemia (P = 0.015), while a 10-fold rise in serum interleukin 4 concentrations was associated with a 10-fold decrease in the estimated odds of having severe anaemia (P = 0.023). Increasing serum interleukin 10 concentrations, measured in less than half of the subjects, were associated with a nonsignificant reduction in the odds of having severe anaemia (P = 0.095). CONCLUSION: Development of severe malarial anaemia may be directly associated with serum neopterin concentrations and inversely correlated with serum interleukin 4 levels.     

Elevated levels of nitric oxide and low levels of haptoglobin are associated with severe malarial anaemia in African children

Severe malarial anaemia (SA) is a major complication of malaria and an important cause of child mortality and morbidity. However, the pathogenesis behind SA is poorly understood. Nitric oxide (NO) is known to play a protective role against clinical malaria but is also suggested to have a pathogenic role in cerebral malaria (CM). Erythrophagocytosis by splenic macrophages has been implicated in the pathogenesis of SA. In this study, plasma levels of NO, neopterin, haptoglobin and C-reactive protein (CRP) were measured in paediatric patients with CM, n=77, SA (n=28) and uncomplicated malaria (UM n=53). Haptoglobin levels were significantly lower in SA (median (interquartile range) 25 (17-59) mg/l) than in both CM and UM (40 (24-80) mg/l and 110 (60-160) mg/l, respectively, P<0.001). In contrast, NO levels were higher in SA (38 (28-51) micromol/l) than in CM and UM (21 (15-32) micromol/l and 10.3 (5.6-17) micromol/l, respectively, P<0.001). A significant negative correlation between haptoglobin and NO was seen in the SA group. No such correlation was observed within the UM or CM groups. No significant differences in neopterin levels were observed between any of the three groups, neither was there any correlation between parasitaemias and neopterin levels. The low haptoglobin and high levels of NO in this SA group may contribute to haemolysis. Taken together our results support the hypothesis that immune-mediated erythrocyte destruction is involved in the pathogenesis of malarial anaemia.     

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.     

Age-related changes in alpha-tocopherol dynamics with relation to lipid hydroperoxide content and fluidity of rat erythrocyte membrane.

Age-related changes in alpha-tocopherol dynamics in plasma and erythrocyte membranes of 10- to 120-week-old rats were investigated by high-performance liquid chromatography (HPLC) with redox detection mode. Furthermore, changes in lipid hydroperoxide content and fluidity of erythrocyte membrane with age were assessed using chemiluminescence-HPLC and Fourier transform infrared spectrophotometer, respectively. A slight increase in the alpha-tocopherolquinone/alpha-tocopherol ratio in erythrocyte membrane and a decrease in the alpha-tocopherol in erythrocyte membrane/alpha-tocopherol in plasma ratio were observed. A significant increase in lipid hydroperoxide content and a marked decrease in the fluidity of erythrocyte membrane were seen with age. These findings suggest that alpha-tocopherol uptake in erythrocyte membrane declines, and utilization rate of alpha-tocopherol in erythrocyte membrane increases age-dependently. These changes, which enhanced lipid peroxidation and consequently reduced membrane fluidity, may be caused by the impairment of this transfer mechanism.     

Immune mimicry in malaria: Plasmodium falciparum secretes a functional histamine-releasing factor homolog in vitro and in vivo

The Plasmodium falciparum translationally controlled tumor protein (TCTP) is a homolog of the mammalian histamine-releasing factor (HRF), which causes histamine release from human basophils and IL-8 secretion from eosinophils. Histamine, IL-8, and eosinophils have been reported to be elevated in patients with malaria. This study was undertaken to determine whether malarial TCTP is found in the plasma of malaria-infected patients and to determine whether it has HRF biologic activity. Malarial TCTP was found in lightly infected human volunteers and in heavily infected Malawian children, but not in uninfected patients. Recombinant malarial TCTP, like HRF, stimulated histamine release from basophils and IL-8 secretion from eosinophils in vitro. Whereas malarial TCTP was less active than HRF, the concentrations that were effective in vitro could be achievable in vivo. These data suggest that malarial TCTP, present in human plasma during a malarial illness, may affect host immune responses in vivo.     

Complexity of the msp2 locus and the severity of childhood malaria, in south-western Nigeria

As the genetic diversity of Plasmodium falciparum infections in humans is implicated in the pathogenesis of malaria, the association between P. falciparum diversity at the merozoite surface protein-2 (msp2) locus and the severity of childhood malaria was investigated in Ibadan, in south-western Nigeria. The 400 children enrolled had acute uncomplicated malaria (144), cerebral malaria (64), severe malarial anaemia (67) or asymptomatic infections with P. falciparum (125). Nested PCR was used to investigate the msp2 genotype(s) of the parasites infecting each child. In terms of the complexity of infection and frequency of polyinfection, the children with asymptomatic infection were significantly different from those with uncomplicated malaria or severe malaria. The median number of FC27 alleles detected was higher in the asymptomatic children than in the symptomatic. After controlling for age and level of parasitaemia (with 'asymptomatic infection' as the reference category), a child in whom no FC27 alleles were detected was found to be at five-fold greater risk of uncomplicated malaria, and a child without polyinfection was found to have a three-fold increased risk of severe malarial anaemia and a six-fold increased risk of cerebral malaria. It therefore appears that msp2 genotypes are associated with asymptomatic carriage and that children with mono-infections are more likely to develop severe malaria than children with polyinfection.     

Mean arterial blood pressure and serum levels of the molar ratio of insulin-like growth factor-1 to its binding protein-3 in healthy centenarians

OBJECTIVE: Healthy centenarians have a greater molar ratio of plasma insulin-like growth factor-1 to insulin-like growth factor binding protein-3 than that of aged subjects. We investigated the question of whether differences in mean arterial pressure and in this plasma ratio were related in healthy centenarians. SUBJECTS AND METHODS: We studied 52 subjects in total, 30 aged subjects (70-99 years) and 22 healthy centenarians (> 100 years) to determine differences in mean arterial pressure, endothelial function and intracellular cation levels. RESULTS: In the healthy centenarians, the molar ratio of fasting plasma insulin-like growth factor-1 to its binding protein-3 was significantly correlated with mean arterial pressure (r = -0.66, P < 0.001). Baseline (19.3 +/- 1.5 versus 27.6 +/- 2.2 mumol/l, P < 0.05) and L-arginine-stimulated percentage increases in the plasma total nitrate: nitrite ratio (67 +/- 3.4 versus 48 +/- 4.5%, P < 0.03) were greater in the healthy centenarians than in the aged subjects. An L-arginine bolus elicited an increase in forearm blood flow which was correlated with the percentage increase in the plasma total nitrate: nitrite ratio (r = 0.79, P < 0.001) and with the fasting erythrocyte magnesium concentration (r = 0.80, P < 0.001) in healthy centenarians. Both correlations remained significant (P < 0.01) after adjustment for sex, body mass index and the waist: hip ratio. Moreover, the fasting plasma molar ratio of insulin-like growth factor-1 to its binding protein-3 was correlated with the percentage increase in forearm blood flow (r = 0.59, P < 0.005) and with the percentage increase in the plasma total nitrate: nitrite ratio (r = 0.54, P < 0.009) in healthy centenarians. The centenarians had higher baseline total erythrocyte magnesium and lower calcium concentrations than the aged subjects. The addition of insulin growth factor-1 to the incubation medium increased the total intracellular erythrocyte magnesium content and decreased the calcium content in both groups of subjects. Nevertheless, the percentage increase in total erythrocyte magnesium (33 +/- 3.8 versus 12 +/- 3.4%, P < 0.03) and decline in intracellular calcium (17 +/- 2.8 versus 8 +/- 3.1%, P < 0.02) concentrations were greater in the healthy centenarians than the aged subjects. CONCLUSION: In healthy centenarians, insulin-like growth factor-1 may preserve endothelial function and modulate the intracellular cation content, thus contributing to a lower mean arterial pressure than that in aged subjects.     

Antioxidant defences and oxidative stress markers in erythrocytes and plasma from normally nourished elderly Alzheimer patients.

OBJECTIVES: to investigate blood markers of oxidative stress, and enzymatic and non-enzymatic antioxidants in normally nourished elderly people with Alzheimer's disease. DESIGN: case-control study. SUBJECTS: twenty patients with Alzheimer's disease and 23 elderly control subjects, living at home, free from disease and not undergoing any treatment known to have a strong influence on blood oxidative stress markers or antioxidant defence systems. METHODS: we performed a nutritional evaluation, including anthropometric and biological measures and a 3-day dietary record. We determined concentrations of antioxidant vitamins (alpha-tocopherol, retinol) and malondialdehyde in plasma and erythrocytes. We also measured erythrocyte enzymatic activities of glutathione peroxidase and copper-zinc superoxide dismutase. RESULTS: the two groups were similar in age, body mass index, dietary record and serum albumin concentration. After adjustment for age, sex and cardiovascular co-morbidity, mean plasma concentration of alpha-tocopherol was lower in those with Alzheimer disease than in control subjects (15+/-3.5 mg/l compared with 18.2+/-3.5; P=0.002), as was the mean plasma concentration of retinol (0.54+/-0.2 mg/l vs 0.7+/-0.2; P=0.014). The mean concentration of free plasma malondialdehyde was higher in those with Alzheimer's disease (0.70+/-0.2 mmol/l vs 0.5+/-0.1; P=0.036). In Alzheimer disease patients, free plasma malondialdehyde concentrations were inversely correlated with levels of alpha-tocopherol (P=0.002) and retinol (P=0.025). Erythrocyte levels of vitamins and enzymatic activities were similar in the two groups. CONCLUSION: lower plasma concentrations of alpha-tocopherol and retinol in normally nourished elderly patients with Alzheimer's disease than in controls could suggest that these antioxidant vitamins had been consumed as a result of excessive production of free radicals.     

Apolipoprotein E gene polymorphism is related to metabolic abnormalities, but does not influence erythrocyte membrane lipid composition or sodium-lithium countertransport activity in essential hypertension

The aim of this study was to analyze the influence of the apolipoprotein E (apoE) gene polymorphism on insulin resistance and plasma lipid composition of essential hypertensive patients. A secondary objective was to analyze if differences regarding plasma lipids had an effect on the erythrocyte membrane lipid composition and the activity of the erythrocyte membrane sodium-lithium countertransport. We studied 128 untreated nondiabetic essential hypertensive patients enrolled from our outpatient clinic. We considered as hyperinsulinemic all subjects having more than 80 mU/L of plasma insulin 120 minutes after a 75-g oral glucose intake. The number of hyperinsulinemic subjects among carriers of the epsilon4 allele was higher that in epsilon4 noncarrier subjects (13 of 19 v45 of 109, P < .05; odds ratio [OR], 3.08; confidence interval [CI], 0.99-10.57). Plasma insulin at baseline and plasma insulin and glucose at 120 minutes after overload was higher in carriers of the epsilon4 allele (respectively, 17.5 +/- 6.9 v 12.4 +/- 4.9 mU/L, P < .01; 111.9 +/- 39.9 v 88.7 +/- 48.2, P < .05; and 143.8 +/- 29.3 v 121.2 +/- 30.8 mg/dL, P < .005). Subjects with the epsilon4 allele had a plasma lipid profile more atherogenic than those without this allele. This profile was mainly characterized by higher levels of low-density lipoprotein (LDL) cholesterol (150.1 +/- 31.2 v 133.0 +/- 34.3 mg/dL, P < .05) and very-low-density lipoprotein (VLDL) triglycerides (134.7 +/- 85.5 v 99.2 +/- 68.8 mg/dL, P < .05) and by lower levels of high-density lipoprotein (HDL) cholesterol (41.8 +/- 10.7 v 50.0 +/- 14.7 mg/dL, P < .05). There were no differences between groups regarding erythrocyte membrane cholesterol or phospholipids composition and sodium-lithium countertransport (SLC) activity.     

Normal riboflavin status in malaria patients in Gabon

Previous publications reported commonly the occurrence of riboflavin deficiency and a positive correlation between riboflavin status and parasitemia in patients with Plasmodium falciparum malaria. In these studies, riboflavin status was determined by erythrocyte glutathione reductase activation coefficients (EGRACs). Inherited low erythrocyte glutathione reductase activity is highly prevalent in malarial regions, however. To rule out falsely diagnosed riboflavin deficiency in affected patients, we conducted an investigation using a high-performance liquid chromatography method (HPLC) instead of the EGRAC method. In 29 infants (age range, 1-5 years), 22 schoolchildren (age range, 6-12 years), and 33 adolescents and adults (age range, 13-74 years) from Lambaréné, Gabon, with acute P. falciparum malaria, plasma concentrations of riboflavin, flavin mononucleotide (FMN), and flavin adenine dinucleotide (FAD) were measured by HPLC. Results were correlated with parasite densities. Profiles of plasma concentrations of all 3 flavin compounds were within the normal range in all patients. Concentrations of free riboflavin were not different between the 3 age groups. In adolescents and adults, FMN and FAD concentrations were higher than in infants (P = 0.002 and P = 0.001) and schoolchildren (P = 0.003 and P = 0.002). Comparing children with hyperparasitemic and uncomplicated malaria, no difference in the concentrations of either flavin compound was found. Neither the concentrations of free riboflavin nor the concentrations of one of the flavin nucleotides correlated with parasitemia within subgroups of age or of children with uncomplicated and hyperparasitemic malaria. Our data indicate that nutritional riboflavin deficiency might have been overestimated in previous malaria studies and do not support a relationship between flavin concentrations and parasitemia in P. falciparum malaria.     

The epidemiology of malaria in Bolifamba, a rural community on the eastern slopes of Mount Cameroon: seasonal variation in the parasitological indices of transmission

The prevalences of malarial parasitaemia, fever, splenomegaly and anaemia and the levels of parasitaemia were investigated, through part of one wet season (in 2001) and the following dry season (in 2002), in 2157 subjects in the village of Bolifamba, in south-western Cameroon. Overall, 55.9% of the villagers checked in the wet season but only 49.5% of those examined in the dry season were found smear-positive for malaria (P<0.0001). Rainfall was found to be significantly associated with the mean level of parasitaemia (P=0.001). The prevalences of fever (40.3% v. 19.6%), splenomegaly (37.4% v. 4.0%) and marked splenomegaly (i.e. a Hackett's score of 2 or higher; 25.8% v. 2.4%) were all significantly higher in the wet season than in the dry (P<0.0001 for each). No seasonal difference was observed, however, in the prevalence of anaemia. Parasitaemia, fever, splenomegaly and anaemia were all significantly more common in the young children investigated (i.e. those aged < 5 years) than in the older subjects.When the data were subjected to a multiple logistic regression, age-group, anaemia, fever, and month of examination were all found to be significantly associated with the presence of malarial parasitaemia. The results of this large-scale study, the first of its kind in the Buea district of Cameroon, indicate the intense transmission of malarial parasites in rural Bolifamba, with young children at greatest risk. The data collected provide a useful 'base line' for an ongoing study to assess the immune status of the residents of Bolifamba.     

Impact of malaria control on childhood anaemia in Africa -- a quantitative review

OBJECTIVE: To review the impact of malaria control on haemoglobin (Hb) distributions and anaemia prevalences in children under 5 in malaria-endemic Africa. METHODS: Literature review of community-based studies of insecticide-treated bednets, antimalarial chemoprophylaxis and insecticide residual spraying that reported the impact on childhood anaemia. Anaemia outcomes were standardized by conversion of packed cell volumes into Hb values assuming a fixed threefold difference, and by estimation of anaemia prevalences from mean Hb values by applying normal distributions. Determinants of impact were assessed in multivariate analysis. RESULTS: Across 29 studies, malaria control increased Hb among children by, on average, 0.76 g/dl [95% confidence interval (CI): 0.61-0.91], from a mean baseline level of 10.5 g/dl, after a mean of 1-2 years of intervention. This response corresponded to a relative risk for Hb < 11 g/dl of 0.73 (95% CI: 0.64-0.81) and for Hb < 8 g/dl of 0.40 (95% CI: 0.25-0.55). The anaemia response was positively correlated with the impact on parasitaemia (P = 0.005, P = 0.008 and P = 0.01 for the three outcome measures), but no relationship with the type or duration of malaria intervention was apparent. Impact on the prevalence of Hb < 11 g/dl was larger in sites with a higher baseline parasite prevalence. Although no age pattern in impact was apparent across the studies, some individual trials found larger impacts on anaemia in children aged 6-35 months than in older children. CONCLUSION: In malaria-endemic Africa, malaria control reduces childhood anaemia. Childhood anaemia may be a useful indicator of the burden of malaria and of the progress in malaria control.     

Fetal erythrocyte membrane lipids modification: preliminary observation of an early sign of compromised insulin sensitivity in offspring of gestational diabetic women.

AIMS: Intrauterine exposure to diabetes is a significant determinant of the development of obesity and early onset of Type 2 diabetes mellitus in the offspring. Both conditions are characterized by insulin resistance and the latter is associated with reduced membrane arachidonic and docosahexaenoic acids. Hence, we investigated if the membrane arachidonic and docosahexaenoic acids are depressed in the cord blood of babies born to women with gestational diabetes. METHODS: Cord (fetal) and maternal blood were obtained at delivery from control subjects (n = 33) and women with gestational diabetes (n = 40) and analysed for plasma triglycerides and cholinephosphoglycerides, and erythrocyte choline- and ethanolaminephosphoglycerides fatty acids. RESULTS: Babies of gestational diabetic mothers had reduced docosahexaenoic acid in the plasma (5.9 +/- 1.4 vs. 7.1 +/- 2.0, P < 0.01) and erythrocyte (4.0 +/- 2.2 vs. 5.4 +/- 2.9, P < 0.05) cholinephosphoglycerides. Moreover, the total omega-6 and omega-3 fatty acids of the erythrocyte cholinephosphoglycerides were significantly lower (P < 0.05) in these babies. A similar trend was observed in plasma triglycerides and erythrocyte ethanolaminephosphoglycerides. The maternal plasma triglycerides and erythrocyte ethanolaminephosphoglycerides fatty acids profile were not different between the two groups. However, there was a reduction in arachidonic acid and total omega-6 fatty acids in the erythrocyte cholinephosphoglycerides of the gestational diabetic women. CONCLUSION: The altered plasma and erythrocyte fatty acids in the cord blood of babies born to women with gestational diabetes suggests a perturbation in the maternal-fetal nutrient transport and/or fetal lipid metabolism.