Platelet antibody activity in malaria thrombocytopenia

To assess immune responses to malaria-induced thrombocytopenia, an haematologic and immunologic study was performed on 25 patients with imported malaria upon admission and 8 days after treatment. Thrombocytopenia (150 x 10(9)/litre) was detected in 19 cases (P. falciparum: 11 cases, P. ovale: 6 cases, P. vivax: 2 cases). No laboratory evidence of disseminated intravascular coagulation impairment was found in any of the patients. Bone marrow examination performed in 9 cases showed no abnormality in the megakaryocyte series. Platelet count was independent of circulating parasite levels (r = 0.27) and inversely related to the number of antibody binding sites (ABS) on platelets (r = -0.6, p. less than 0.01). The indirect Coombs test (r = -0.54; p less than 0.01) and IgG and IgE levels (p less than 0.02) gave similar findings. A statistical correlation was observed between the level of circulating immune complex and the number of ABS (r = 0.525, p less than 0.01). Thus malaria-induced thrombocytopenia seems to mainly involve IgG type antiplatelet antibody activity. Although they may be implicated in the binding of antibodies to platelets, circulating immune complexes do not appear to mediate thrombocytopenia.     

Serum levels of the proinflammatory cytokines interleukin-1 beta (IL-1beta), IL-6, IL-8, IL-10, tumor necrosis factor alpha, and IL-12(p70) in Malian children with severe Plasmodium falciparum malaria and matched uncomplicated malaria or healthy controls

Inflammatory cytokines play an important role in human immune responses to malarial disease. However, the role of these mediators in disease pathogenesis, and the relationship between host protection and injury remains unclear. A total of 248 cases of severe Plasmodium falciparum malaria among children aged 3 months to 14 years residing in Bandiagara, Mali, were matched to cases of uncomplicated malaria and healthy controls. Using modified World Health Organization criteria for defining severe malaria, we identified 100 cases of cerebral malaria (coma, seizure, and obtundation), 17 cases of severe anemia (hemoglobin, <5 g/dl), 18 cases combined cerebral malaria with severe anemia, and 92 cases with hyperparasitemia (asexual trophozoites, >500,000/mm3). Significantly elevated levels (given as geometric mean concentrations in picograms/milliliter) of interleukin-6 (IL-6; 485.2 versus 54.1; P = <0.001), IL-10 (1,099.3 versus 14.1; P = <0.001), tumor necrosis factor alpha (10.1 versus 7.7; P = <0.001), and IL-12(p70) (48.9 versus 31.3; P = 0.004) in serum were found in severe cases versus healthy controls. Significantly elevated levels of IL-6 (485.2 versus 141.0; P = <0.001) and IL-10 (1,099.3 versus 133.9; P = <0.001) were seen in severe malaria cases versus uncomplicated malaria controls. Cerebral malaria was associated with significantly elevated levels of IL-6 (754.5 versus 311.4; P = <0.001) and IL-10 (1,405.6 versus 868.6; P = 0.006) compared to severe malaria cases without cerebral manifestations. Conversely, lower levels of IL-6 (199.2 versus 487.6; P = 0.03) and IL-10 (391.1 versus 1,160.9; P = 0.002) were noted in children with severe anemia compared to severe malaria cases with hemoglobin at >5 g/dl. Hyperparasitemia was associated with significantly lower levels of IL-6 (336.6 versus 602.1; P = 0.002). These results illustrate the complex relationships between inflammatory cytokines and disease in P. falciparum malaria.     

Tolerance and efficacy of mefloquine as the first line treatment of uncomplicated P. falciparum malaria in children

INTRODUCTION: Given the national therapeutic guidelines in France, halofantrine represents the first line treatment of uncomplicated Plasmodium falciparum (P. falciparum) malaria in children. But several disadvantages exist using halofantrine in paediatrics. OBJECTIVES: The primary objective of this study is to evaluate the tolerance and the efficacy of mefloquine as the first line treatment of uncomplicated P. falciparum malaria in a paediatric emergency department. The secondary objective of the study is to evaluate whether symptomatic measures may improve the gastrointestinal tolerance of mefloquine. PATIENTS AND METHODS: This retrospective observational cohort study includes all the patients who have been treated for acute uncomplicated P. falciparum malaria in the paediatric emergency department of the Hospital Trousseau (Paris, France) in 2003. RESULTS: First line treatment was mefloquine in 35 children. Early vomiting occurred in 22 (63%) cases. All children responded to mefloquine therapy except two children who had persistent vomiting early after mefloquine therapy and required intravenous quinine. Those two children had initial vomiting. Light meal and metopimazine prophylaxis did not precede mefloquine intake in those two children. CONCLUSION: This study suggests that mefloquine treatment of uncomplicated P. falciparum malaria is effective and well tolerated in children. Furthermore, a light meal and metopimazine prophylaxis preceding mefloquine intake may improve its gastrointestinal tolerance.     

A molecular marker for chloroquine-resistant falciparum malaria

BACKGROUND: Chloroquine-resistant Plasmodium falciparum malaria is a major health problem, particularly in sub-Saharan Africa. Chloroquine resistance has been associated in vitro with point mutations in two genes, pfcrt and pfmdr 1, which encode the P. falciparum digestive-vacuole transmembrane proteins PfCRT and Pgh1, respectively. METHODS: To assess the value of these mutations as markers for clinical chloroquine resistance, we measured the association between the mutations and the response to chloroquine treatment in patients with uncomplicated falciparum malaria in Mali. The frequencies of the mutations in patients before and after treatment were compared for evidence of selection of resistance factors as a result of exposure to chloroquine. RESULTS: The pfcrt mutation resulting in the substitution of threonine (T76) for lysine at position 76 was present in all 60 samples from patients with chloroquine-resistant infections (those that persisted or recurred after treatment), as compared with a base-line prevalence of 41 percent in samples obtained before treatment from 116 randomly selected patients (P<0.001), indicating absolute selection for this mutation. The pfmdr 1 mutation resulting in the substitution of tyrosine for asparagine at position 86 was also selected for, since it was present in 48 of 56 post-treatment samples from patients with chloroquine-resistant infections (86 percent), as compared with a base-line prevalence of 50 percent in 115 samples obtained before treatment (P<0.001). The presence of pfcrt T76 was more strongly associated with the development of chloroquine resistance (odds ratio, 18.8; 95 percent confidence interval, 6.5 to 58.3) than was the presence of pfmdr 1 Y86 (odds ratio, 3.2; 95 percent confidence interval, 1.5 to 6.8) or the presence of both mutations (odds ratio, 9.8; 95 percent confidence interval, 4.4 to 22.1). CONCLUSIONS: This study shows an association between the pfcrt T76 mutation in P. falciparum and the development of chloroquine resistance during the treatment of malaria. This mutation can be used as a marker in surveillance for chloroquine-resistant falciparum malaria.     

Serum laminin in malaria.

AIM--To determine serum laminin concentrations in patients with uncomplicated Plasmodium falciparum malaria. METHODS--An enzyme linked immunosorbent assay (ELISA) was used to determine serum laminin concentrations in 54 patients with acute uncomplicated P falciparum malaria during and after treatment, and in 17 control subjects in Bangkok, Thailand. RESULTS--Raised concentrations of soluble laminin were observed in patients (mean (SD) concentration 628 (225) ng/ml), compared with normal controls (490 (116) ng/ml), during the acute phase of the disease. During treatment, serum laminin concentrations decreased and returned to normal within three days. Serum laminin concentrations were correlated with parasite counts before treatment, and with the serum concentration of soluble intercellular adhesion molecule-1 (ICAM-1), soluble E-selectin, and soluble tumour necrosis factor receptor at 55 kilodaltons. CONCLUSIONS--These findings are compatible with an increased production or release of laminin in P falciparum malaria, which could indicate a role for the subendothelial basement membrane in the pathogenesis of the disease.     

The gamma/delta T-cell response to Plasmodium falciparum malaria in a population in which malaria is endemic.

Frequencies and absolute numbers of peripheral gamma/delta T cells have been reported to increase after episodes of Plasmodium falciparum malaria in adults with limited or no previous malaria exposure. In contrast, little is known about the gamma/delta T-cell response to malaria in children from areas where malaria is endemic, who bear the burden of malaria-related morbidity and mortality. We investigated the gamma/delta T-cell response in 19 Ghanaian children from an area of hyperendemic, seasonal malaria transmission. The children presented with cerebral malaria (n = 7), severe malarial anemia (n = 5), or uncomplicated malaria (n = 7) and were monitored from admission until 4 weeks later. We found no evidence of increased frequencies of gamma/delta T cells in any of the patient groups, whereas one adult expatriate studied in Ghana and three adults admitted to the hospital in Copenhagen, Denmark, all with uncomplicated, primary P. falciparum malaria, showed increased gamma/delta T-cell frequencies similar to those previously reported. All patients had lowered absolute numbers of peripheral gamma/delta T cells at admission, changing to increased numbers by days 7 to 14 and then returning to normal levels. The study raises questions regarding age and degree of previous exposure as determinants of malaria-induced gamma/delta T-cell responses.     

Polymorphisms in interleukin-1beta and interleukin-1 receptor antagonist genes and malaria in Ghanaian children

We have investigated the possible associations between polymorphisms in two interleukin-1 (IL-1) genes and severity of Plasmodium falciparum malaria in Ghanaian children with cerebral malaria, severe anaemia or uncomplicated malaria and controls. There was no significant difference in genotype and allele frequencies in IL-1beta exon 5 or interleukin-1 receptor antagonist (IL-1ra) polymorphisms between the studied groups, suggesting that the two polymorphisms may not be involved in the pathogenesis of severe malaria. When parasitaemias in uncomplicated malaria patients were evaluated, a significantly higher level of parasitaemia was observed among carriers of IL-1beta A2 allele as compared with noncarriers of this allele (P = 0.01). The mean parasitaemia in an age-matched asymptomatic group did not reveal such associations. These data suggest that IL-1beta exon 5 allele 2 may play a possible role in the clinical outcome of uncomplicated malaria.     

Altered expression of human monocyte Fc receptors in Plasmodium falciparum malaria

The state of activation of human peripheral blood monocytes was examined by using a rosette assay that detects changes in Fc receptor expression. Monocytes from patients with uncomplicated Plasmodium falciparum malaria showed a significant increase in the number of rosettes relative to healthy controls. In addition, the monocytes from these patients were tested for their ability to phagocytose Candida albicans, but this ability did not differ from that of normal individuals. Finally, the monocytes from patients with cerebral malaria were also tested for Fc receptor expression. In contrast to the results from uncomplicated cases, the activity of the monocytes from these patients was no different from that of controls. We concluded that uncomplicated P. falciparum malaria caused an increase in monocyte Fc receptor expression which did not occur in cerebral malaria and that this difference in activation may be important in the pathogenesis of cerebral malaria.     

Strong association of a tumor necrosis factor-alpha promoter allele with cerebral malaria in Myanmar

To investigate the host genetic factors affecting the clinical course of falciparum malaria, polymorphism of the tumor necrosis factor-alpha (TNF-alpha) promoter region was analyzed in patients with cerebral malaria. Two hundred and forty-three Myanmar patients with falciparum malaria at Mae Sot Malaria clinic and Mae Sot General Hospital located at the border between Thailand and Myanmar, were included in this study. Among the patients (128 from Karen, 115 from Burma), 200 were uncomplicated and 43 had cerebral malaria. The TNF-alpha 5'- flanking region showed biallelic polymorphic sites at -238, -308, -857, -863, -1031, and there were 7 alleles (TNFP-A, B, C, D, M1, M4, M7) found in the patients from Myanmar. We found that the TNFP-D allele was significantly associated with cerebral malaria in the populations from Karen (Pc<0.0001, OR=124.86) and Burma (Pc<0.0001, OR=34.50). TNFP-D showed no significant linkage disequilibrium with any alleles of HLA-B or HLA-DRB1, suggesting that TNFP-D was primarily associated with cerebral malaria in Myanmar.     

Impact of human immunodeficiency virus infection in pregnant women on variant-specific immunity to malaria

Human immunodeficiency virus (HIV) increases susceptibility to Plasmodium falciparum infection, and this has most clearly been demonstrated in pregnant women. Variant surface antigens on the surfaces of erythrocytes infected with P. falciparum are major targets of protective immunity. We studied the impact of HIV infection on pregnant women's humoral immunity to variant surface antigens expressed by placental and pediatric isolates of P. falciparum. By flow cytometry, sera from HIV-infected women more frequently lacked antibodies to these antigens than sera from HIV-uninfected women. This difference was similar in magnitude for pediatric isolates (unadjusted odds ratio [OR] = 6.36; 95% confidence interval [CI] = 1.14, 35.32; P < 0.05) and placental isolates (unadjusted OR = 6.47; 95% CI = 0.75, 55.64; P < 0.10). We divided women into high and low responders on the basis of their antibody levels. After adjustment for CD4 count, maternal age, and gravidity, we found that HIV-infected women more frequently had low responses to both pediatric isolates (OR = 5.34; 95% CI = 1.23, 23.16; P = 0.025) and placental isolates (OR = 4.14; 95% CI = 1.71, 10.02; P = 0.002). The relative quantity of antibodies to both pediatric isolates (P = 0.035) and placental isolates (P = 0.005) was lower in HIV-infected women than in HIV-uninfected women. HIV infection has a broad impact on variant-specific immunity, which may explain the susceptibility of infected individuals to clinical malaria episodes.     

Pertinence of the 2000 WHO criteria in non-immune children with severe malaria in Dakar, Senegal

The relevance of World Health Organization (WHO) criteria for severe malaria has not been assessed in non-immune children. The objectives of this study were (i) to evaluate the significance of 1990 WHO definition reconsidered in 2000 on distribution and lethality of severe cases in children admitted with falciparum malaria, and (ii) to contribute to the study of relevance of the WHO severe criteria in Dakar, an hypoendemic area in Senegal. PATIENTS AND METHODS: The 1990 WHO criteria, respiratory distress and platelet counts were prospectively collected in 1997-99 from children admitted to H?pital Principal de Dakar, Senegal, with falciparum malaria diagnosed on a thick blood film. This method allowed also the definition of severe cases according to 2000 WHO criteria. RESULTS: Among 311 patients (median age: 8 years old), according to the 2000 WHO criteria, the frequency of severe malaria cases was increased by 23% (75% versus 52%) and case-fatality rates thereof were decreased by 5% (17% versus 12%) compared with 1990 WHO definition. One death occurred among cases defined as severe on admission only according to criteria modified by WHO in 2000. A multivariate logistic regression model identified several independent prognostic factors: cerebral malaria, hypoglycaemia, respiratory distress, renal failure, collapse, abnormal bleedings, pupillary abnormalities and thrombocytopaenia defined as a platelet count below 100,000/mm3. A significant association (p < 0.001) was observed between platelet count increase and consciousness level improvement, evaluated on day of first platelet count control (time from admission: 1-7 d). Among survivors, a lesser improvement in coma score was associated with a decrease in platelet counts (p < 0.04). CONCLUSIONS: The 1990 WHO criteria, which predicted death among malaria cases in children living under stable falciparum transmission, are relevant in this series of non-immune children living in a low and seasonal transmission. Nevertheless new WHO criteria showed poor prognostic significance. However, the 2000 WHO definition was highly sensitive to detect severe malaria cases. These findings should be considered for managing severe malaria in migrant children.     

Parasite virulence factors during falciparum malaria: rosetting, cytoadherence, and modulation of cytoadherence by cytokines.

To determine virulence factors of isolates of Plasmodium falciparum and the potential role of cytokines in cerebral malaria, 46 Malagasy patients presenting with cerebral (n = 10), severe (n = 10), and uncomplicated (n = 26) malaria were enrolled in a study. The capacity of 21 of 46 P. falciparum isolates to form rosettes in vitro and to adhere to human umbilical vein endothelial cells (HUVECs) that express intercellular adhesion molecule-1 receptors and to C32 amelanotic melanoma cells that express mainly CD36 receptors was investigated together with the effects of tumor necrosis factor alpha (TNF-alpha), granulocyte macrophage-colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-6 alone and in two-by-two combinations on the cytoadherence of infected erythrocytes to HUVECs. Plasma levels of these cytokines were also measured in the patients at admission. The percentage of rosette formation was higher for the isolates from patients with cerebral (n = 6; 19.5%) and severe (n = 6; 30.5%) malaria than for those from patients with uncomplicated malaria (n = 9; 5%) (P < 0.002). The cytoadherence properties of the isolates did not differ among the three groups whatever the target cell used, but adherence to melanoma cells was systematically higher than that to HUVECs. Adhesion to HUVECs was increased more after TNF-alpha stimulation than after GM-CSF, IL-3, or IL-6 stimulation (P < 0.01). Only the combination of TNF-alpha and IL-3 enhanced cytoadherence more than TNF-alpha used alone (P < 0.02). No difference in the modulation of cytoadherence by cytokines was found in relation to the severity of the disease. TNF-alpha and IL-6 levels in peripheral blood were higher in the patients with cerebral and severe malaria than in the patients with uncomplicated malaria (P < 0.005). Most of the patients' sera contained little or no IL-3 or GM-CSF. Our results challenge the role of intercellular adhesion molecule-1 as the principal receptor mediating the cytoadherence of P. falciparum-infected erythrocytes and contrast with data obtained in the murine model.     

Complexity and genetic diversity of<Emphasis Type="Italic"> Plasmodium falciparum</Emphasis> infections in young children living in urban areas of Central and West Africa

A site-based characterization of Plasmodium falciparum infections in children living in two malaria hyperendemic urban areas from West and Central Africa was undertaken. A total of 58 and 46 children with either asymptomatic infections or uncomplicated (symptomatic) malaria were recruited in Gabon and Benin, respectively. Parasite density, hematological factors, the genetic diversity of P. falciparum merozoite surface protein 2 (msp2) and the complexity of infections (mean number of P. falciparum genotypes per infected child) were used for this characterization. Gabonese children with uncomplicated malaria presented a higher mean axillary temperature (39.2 vs 38.6, P=0.004) and a higher geometric mean parasite density (30,538 vs 18,921, P<0.001) associated with a significantly lower hemoglobin level ( P<0.01). A higher degree of msp2 polymorphism and the complexity of P. falciparum infections were also observed in children from Gabon ( P<0.05). With a similar level of malaria transmission in both urban sites, these results suggest an impact of malaria control interventions on the dynamics of concurrent P. falciparum infections.     

High prevalence of co-factor independent anticardiolipin antibodies in malaria exposed individuals

Anticardiolipin antibodies (aCL) were investigated in 137 individuals chronically exposed to malaria and living in Africa and Asia. They belonged to several groups according to parasite (Plasmodium falciparum or vivax) and clinical manifestations (i.e. asymptomatic parasite carriers, acute uncomplicated attack or severe malaria episodes). aCL were measured in an enzyme immunoassay (ELISA) performed in the presence of either goat serum (aCLs) or gelatin (aCLg). In a group of 53 patients with autoimmune manifestations (i.e. antiphospholipid syndrome and/or lupus), detection of IgG but not IgM aCL was markedly reduced in the presence of gelatin. In malaria donors, high prevalence of serum co-factor-independent IgG and IgM were detected, and the presence of goat serum in the assay consistently decreased their detection. aCLg levels were found to be related to the clinical/endemic status of donors. IgG aCLg were found to be higher in asymptomatic P. falciparum carriers than in patients with uncomplicated acute or cerebral malaria. IgM aCLg were higher in the cerebral malaria group than in groups with uncomplicated acute malaria patients or asymptomatic individuals. Data suggest that using a serum co-factor independent, sensitive ELISA, aCL are commonly detected during malarial infections and related to malarial infection status.     

Mortality trends in falciparum malaria--effect of gender difference and pregnancy

Falciparum malaria in pregnancy is a significant health problem in India. Pregnant women constitute an important high risk group for malaria infection which may cause abortions, stillbirths, intra-uterine growth retardation (IUGR) and premature labour. In this hospital based study on 602 admitted patients of falciparum malaria which included 314 males, 243 non-pregnant females and 45 pregnant females, there was significantly increased mortality rate in females (18.4%) in comparison to males (7.64%, p < 0.001). The mortality rate was highly significant in pregnant females (37.77%) in comparison to non-pregnant females (14.81%) and males (7.64%; p < 0.001). Severe anaemia with Hb < 5 gm% was observed more commonly in pregnant patients (20.0%) in comparison to non-pregnant patients (4.11%). Incidence of malaria infection was more in primi gravida and second gravida. Pregnancy related complications in the form of preterm live births, intra-uterine death (IUD), still births and abortions were more in primi parous than multiparous patients. As the pregnancy is associated with increased incidence and adverse outcome of P.falciparum malaria infection, chemoprophylaxis should be made an integral part of antenatal care along with antianaemia therapy to reduce the risk of serious maternal and fetal complications.     

High levels of anti-phospholipid antibodies in uncomplicated and severe Plasmodium falciparum and in P. vivax malaria.

The majority (75%) of adult patients with uncomplicated Plasmodium falciparum and P. vivax malaria are positive for anti-phospholipid antibodies (aPLA) as demonstrated by ELISA using a panel of anionic and cationic phospholipids. The highest IgG and IgM binding was to the anionic phospholipids, phosphatidylserine (PS), phosphatidic acid (PA) and cardiolipin (CL), but excluding phosphatidylinositol (PI) to which only low antibody levels were found. Comparison of the mean IgG and IgM aPLA showed a trend for anti-PA > CL > PS > PC > PE > PI. Anti-PI levels were compared in two groups of African children, one group with non-severe and the other with severe (cerebral) falciparum malaria. Children with cerebral disease had significantly lower IgM anti-PI. The results are discussed with the view that serum-derived aPLA may have a role in 'anti-disease' immune responses. Their possible role in the opsonization and phagocytosis of parasitized erythrocytes and in thrombocytopenia is also considered.     

Invasion pathways and malaria severity in Kenyan Plasmodium falciparum clinical isolates

The invasion of erythrocytes by Plasmodium falciparum occurs through multiple pathways that can be studied in vitro by examining the invasion of erythrocytes treated with enzymes such as neuraminidase, trypsin, and chymotrypsin. We have studied the invasion pathways used by 31 Kenyan P. falciparum isolates from children with uncomplicated or severe malaria. Six distinct invasion profiles were detected, out of eight possible profiles. The majority of isolates (23 of 31) showed neuraminidase-resistant, trypsin-sensitive invasion, characteristic of the pathway mediated by an unknown parasite ligand and erythrocyte receptor "X." The neuraminidase-sensitive, trypsin-sensitive phenotype consistent with invasion mediated by the binding of parasite ligand erythrocyte binding antigen 175 to glycophorin A, the most common invasion profile in a previous study of Gambian field isolates, was seen in only 3 of 31 Kenyan isolates. No particular invasion profile was associated with severe P. falciparum malaria, and there was no significant difference in the levels of inhibition by the various enzyme treatments between isolates from children with severe malaria and those from children with uncomplicated malaria (P, >0.1 for all enzymes; Mann-Whitney U test). These results do not support the hypothesis that differences in invasion phenotypes play an important role in malaria virulence and indicate that considerable gaps remain in our knowledge of the molecular basis of invasion pathways in natural P. falciparum infections.     

Mannose-binding lectin is a disease modifier in clinical malaria and may function as opsonin for Plasmodium falciparum-infected erythrocytes

Variant alleles in the mannose-binding lectin (MBL) gene (mbl2) causing low levels of functional MBL are associated with susceptibility to different infections and are common in areas where malaria is endemic. Therefore, we investigated whether MBL variant alleles in 551 children from Ghana were associated with the occurrence and outcome parameters of Plasmodium falciparum malaria and asked whether MBL may function as an opsonin for P. falciparum. No difference in MBL genotype frequency was observed between infected and noninfected children or between children with cerebral malaria and/or severe malarial anemia and children with uncomplicated malaria. However, patients with complicated malaria who were homozygous for MBL variant alleles had significantly higher parasite counts and lower blood glucose levels than their MBL-competent counterparts. Distinct calcium-dependent binding of MBL to the membrane of P. falciparum-infected erythrocytes, which could be inhibited by mannose, was observed. Further characterization revealed that MBL reacted with a P. falciparum glycoprotein identical to the 78-kDa glucose-regulated stress protein of P. falciparum. MBL seems to be a disease modifier in clinical malaria and to function as an opsonin for erythrocytes invaded by P. falciparum and may thus be involved in sequestration of the parasite, which in turn may explain the association between homozygosity for MBL variant alleles and high parasite counts.     

The impact of malaria on common lipid parameters

No data are available in the literature to indicate whether low-level Plasmodium falciparum infections induce lipid parameter changes. We hypothesized that low-level P. falciparum infections induce significant changes in common lipid parameters. We retrospectively selected samples from a malaria prophylaxis study to measure the impact of sustained parasite clearance on common lipid parameters [total cholesterol (TChol), high-density lipoprotein (HDL)-cholesterol (HDL-c), low-density lipoprotein (LDL)-cholesterol (LDL-c) and triglycerides (TG)] in 47 apparently healthy schoolchildren whose P. falciparum parasitemia was initially below 1000/ microl. After parasite clearance, mean values were significantly increased for Tchol ( P<0.001) and HDL-c ( P<0.001), unlike LDL-c ( P=0.93); and TG were significantly decreased from the baseline ( P=0.004). No significant change was found in a control group. This is the first study showing significant lipid changes related to low-level P. falciparum infections. Further studies are needed to explore the relevance of this finding at the population level in hyperendemic malaria areas.     

Mefloquine treatment in infants and children with Plasmodium falciparum malaria: an efficient and well tolerated treatment

OBJECTIVES: The aim of this study was to evaluate the efficacy and tolerance of mefloquine treatment in children, especially in infants of less than 15 kg, in an endemic area of malaria (French Guiana). METHOD: This 5-years (1996-2000) retrospective study included 61 children aged 6 months to 16 years who had been treated with mefloquine for acute Plasmodium falciparum malaria. Twenty-six of these children weighted less than 15 kg. The efficiency of the treatment was evaluated using clinical and parasitic data that had been validated according to the criteria of the World Health Organization (WHO). Tolerance was compared with the data in the medical literature. RESULTS: None of the 59 patients who were given the treatment correctly presented signs of early therapeutic failure as defined by the WHO. Apyrexia was obtained in 48 h on average (CI 95%: 39-57; median: 36 h). The mean time required to obtain negative parasitism was 91 h (CI 95%: 80-101; median: 96 h) among the 51 patients in whom this was measured. Mild side effects were observed in 27.8% of the cases affecting mainly the digestive system. No differences were observed regarding efficacy or tolerance for children who weighed less than 15 kg. CONCLUSION: Mefloquine represents an efficient treatment for acute uncomplicated P. falciparum malaria in children and is well-tolerated even in infants.