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Biomedical subjects

B Lell

Publications and source records attributed to B Lell.

At least 19 recordsLinked to original sources
PubMed2002

Amodiaquine-artesunate versus amodiaquine for uncomplicated Plasmodium falciparum malaria in African children: a randomised, multicentre trial.

BACKGROUND: Increasing drug resistance limits the choice of efficacious chemotherapy against Plasmodium falciparum malaria in Africa. Amodiaquine still retains efficacy against P falciparum in many African countries. We assessed the safety, treatment efficacy, and effect on gametocyte carriage of adding artesunate to amodiaquine in three randomised trials in Kenya, Sénégal, and Gabon. METHODS: We enrolled 941 children (400 in Kenya, 321 in Sénégal, and 220 in Gabon) who were 10 years or older and who had uncomplicated P falciparum malaria. Patients were randomly assigned amodiaquine (10 mg/kg per day for 3 days) plus artesunate (4 mg/kg per day for 3 days) or amodiaquine (as above) and placebo (for 3 days). The primary endpoints were parasitological cure rates at days 14 and 28. Analysis was by intention to treat and by an evaluability method. FINDINGS: Both regimens were well tolerated. Six patients in the amodiaquine-artesunate group and five in the amodiaquine group developed early, drug-induced vomiting, necessitating alternative treatment. By intention-to-treat analysis, the day-14 cure rates for amodiaquine-artesunate versus amodiaquine were: 175/192 (91%) versus 140/188 (74%) in Kenya (D=16.7% [95% CI 9.3-24.1], p<0.0001), 148/160 (93%) versus 147/157 (94%) in Sénégal (-1.1% [-6.7 to 4.5], p=0.7), and 92/94 (98%) versus 86/96 (90%) in Gabon (8.3% [1.5-15.1], p=0.02). The corresponding rates for day 28 were: 123/180 (68%) versus 75/183 (41%) in Kenya (27.3% [17.5-37.2], p<0.0001), 130/159 (82%) versus 123/156 (79%) in Sénégal (2.9% [-5.9 to 11.7], p=0.5), and 80/94 (85%) versus 70/98 (71%) in Gabon (13.7% [2.2-25.2], p=0.02). Similar rates were obtained by evaluability analysis. INTERPRETATION: The combination of artesunate and amodiaquine improved treatment efficacy in Gabon and Kenya, and was equivalent in Sénégal. Amodiaquine-artesunate is a potential combination for use in Africa. Further investigations to assess the potential effect on the evolution of drug resistance, disease transmission, and safety of amodiaquine-artesunate are warranted.

Amodiaquine↗
PubMed2002

TNFalpha-308A associated with shorter intervals of Plasmodium falciparum reinfections.

A mutation at position -308 of the tumor necrosis factor alpha (TNF-308A) gene promoter has previously been associated with particular manifestations of infectious and non-infectious diseases. In a longitudinal study on malariological parameters in Gabon, TNF promoter variants of 98 children initially presenting with severe Plasmodium falciparum malaria, followed by a total of 504 reinfection events within 52 months, and 100 children initially presenting with mild malaria followed by a total of 342 reinfections were analyzed. Symptomatic P. falciparum reinfections occurred more quickly (median 11 weeks) in carriers of the TNF-308A allele, with severe malaria at enrollment, compared to carriers of other TNF promoter variants (median 16 weeks). The results show that this particular TNF promoter allele increases the risk of reinfection with the malaria parasite P. falciparum.

Animals↗
PubMed2001

Atopy and malaria.

The last decades have seen a dramatic rise in the prevalence of allergic diseases throughout the industrialised world. The "hygiene hypothesis" postulates that this is due to a reduced exposure to infections during childhood. A cohort study in children from Gabon gave us the unique opportunity to examine the relationship between exposure to P. falciparum and atopy. 91 children, who had been closely followed for an average of 5 years and of whom the exact incidence of malaria attacks was known, underwent a skin-prick test with mite antigen. 16 children (18%) had a positive reaction. Gender or age had no effect on the outcome of the test. However, those tested positive had had less infections and a lower incidence of malaria than children tested negative (p = 0.017). Survival analysis shows that children with a high exposure to P. falciparum were at lower risk of an atopic skin reaction (p = 0.001). We postulate that the low exposure to the malaria parasite contributes to the development of an imbalanced immune system with a subsequent higher reactivity to the allergen tested. Immuno-suppression is commonly seen during a malaria attack and this correlates positively with the level of anti-inflammatory cytokines such as interleukin-10. High exposure to parasite antigens might counterbalance pro-inflammatory immune reactions and thus protect against allergic diseases. A better understanding of the relationship between parasitic infection and allergy will help us to develop strategies to prevent allergic disease without being exposed to infectious diseases.

Adolescent↗
PubMed2001

Artesunate and praziquantel for the treatment of Schistosoma haematobium infections: a double-blind, randomized, placebo-controlled study.

Recently, artemisinin derivatives have been shown to be efficacious in chemoprophylaxis of and chemotherapy for Schistosoma japonicum and S. mansoni infections. Therefore, a double-blind, randomized, placebo-controlled study was carried out to investigate the efficacy and tolerability of artesunate plus placebo and the combination of artesunate and praziquantel in the treatment of S. haematobium infections in Gabon. The 300 infected schoolchildren included in the study were randomized to receive artesunate plus placebo (n=90), praziquantel plus placebo (n=90), artesunate and praziquantel (n=90), or only placebo (n=30). End points were efficacy, assessed as cure on day 56, and tolerability. All treatment regimens were well tolerated. The praziquantel plus placebo-treated group attained a cure rate of 73%, artesunate plus placebo a rate of 27%, the combination of artesunate and praziquantel a rate of 81%, and placebo alone a rate of 20%. In summary, earlier findings of efficacy of artemisinin derivitives against S. mansoni and S. japonicum could not be confirmed in S. haematobium infections.

Animals↗
PubMed2001

Effect of antipyretic drugs in children with malaria.

A comparison of different antipyretics in children with malaria showed a small effect of naproxen, but not of metamizol, on the reduction of fever peaks. Antipyretic treatment had no effect on fever clearance and therefore should be used cautiously in the treatment of malaria.

Analgesics, Non-Narcotic↗
PubMed2001

Plasmodium falciparum: in vitro growth inhibition by febrile temperatures.

Febrile episodes are the hallmark of malarial infection. We determined the inhibitory effect of febrile temperatures on the in vitro growth of Plasmodium falciparum. Parasites were cultured at various temperatures between 37 degrees C and 40 degrees C for 4 days. A logistic decrease in parasitaemia as a function of temperature was observed for continuous cultures. Incubation of synchronized cultures for different lengths of time during the parasite cycle showed a strong increase of growth inhibition with the maturing of parasites. Febrile temperatures inhibit parasite growth and long, high fevers during malaria may be beneficial for parasite clearance.

Animals↗
PubMed2001

Plasmodium falciparum transmission intensity and infection rates in children in Gabon.

Several factors can determine the outcome of a malarial infection. Studies on susceptibility or resistance to malarial infection can be confounded by differences in transmission. In the present study, the relationship between vector abundance and Plasmodium falciparum infection rate of Gabonese children was studied. Indoor human bait catches were conducted in the houses of two groups of children, those who had been found earlier to be either frequently (> 3 infections per year) or rarely (< 0.5 infections per year) infected with P. falciparum. The human biting rate was 12 and 31 bites per person per night during the dry and the rainy season, with 3% and 16% Anopheles, respectively. Anopheles gambiae and A. moucheti were found to be the only vectors involved in the transmission of malaria in this area. No significant difference in the abundance and the rate of P. falciparum infection of the Anopheles mosquitoes was found among children rarely or frequently infected. Differences in transmission cannot account for differences in infection rates in our study group. Hereditary and immunological factors seem to be the primary determinants for the outcome of malarial infection.

Animals↗
PubMed2001

Change in Plasmodium falciparum genotype during successive malaria episodes in Gabonese children.

Extensive polymorphism in the malaria parasite Plasmodium falciparum is one of the major obstacles to controlling the disease. With the aim of analysing the dynamics of P. falciparum inoculations, we investigated the parasite genotypes of successive malaria episodes. Polymerase chain reaction was performed on blood samples collected longitudinally from 31 children in Lambaréné, Gabon. The polymorphic regions of the merozoite surface antigens 1 and 2 were used as genetic markers. The data show that children in this area are exposed to many different P. falciparum strains. In a few cases, the same parasite genotypic pattern was observed in samples from two consecutive clinical attacks indicating probable recrudescences after therapy. In six cases the first successive infections with a particular merozoite surface antigen (MSA)-2 strain (3D7) were followed by infections with the other MSA-2 genotype (FC27). In all other cases the genetic characteristics of the parasite were different from one infection to the next, indicating that reinfection was caused by a new parasite strain.

Animals↗
PubMed2000

The circadian rhythm of body temperature is preserved during malarial fever.

Body temperature follows a circadian rhythm with a low around 6 a.m. and a peak about 12 hours later. The effect of fever on this endogenous oscillation is unknown. We obtained hourly measurements of the rectal temperature of 66 children with Plasmodium falciparum malaria. Even at febrile temperatures, the temperature followed a clear circadian rhythm. 33 patients (50%) had fever above 38 degrees C at 6 p.m. on the first day compared to only 9 (14%) at 6 a.m. the next morning. This considerable difference was also found on the second day of observation. Since in clinical practice antipyretics are often given above a certain fever threshold, the time of day should be taken into account when antipyretics are applied.

Body Temperature Regulation↗
PubMed2000

Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced interleukin-10.

BACKGROUND: Most of the effort directed at understanding the role infections have in preventing allergy has focused on bacteria and viruses and their ability to divert the immune system towards T-helper-1 responses and away from proallergic T-helper-2 responses. However, helminth infections, highly prevalent in large parts of the developing world, where allergy is uncommon, stimulate strong T-helper-2 responses. We investigated the influence of chronic helminth infections on the prevalence of atopy and aimed to understand the relation at a detailed immunological level. METHODS: 520 Gabonese schoolchildren were tested for skin reaction to house-dust mite and other allergens, for Schistosoma haematobium eggs in urine, and for microfilariae in blood samples. Total and mite-specific IgE antibodies were measured. A subsample selected on the basis of their skin test to house-dust mite received detailed immunological investigations. FINDINGS: Children with urinary schistosomiasis had a lower prevalence of a positive skin reaction to house-dust mite than those free of this infection (odds ratio 0.32 [95% CI 0.16-0.63]). The degree of sensitisation to house-dust mite could not explain this difference in skin-prick positivity. Schistosome-antigen-specific concentrations of interleukin-10 were significantly higher in infected children, and higher specific concentrations of this anti-inflammatory cytokine were negatively associated with the outcome of skin-test reactivity to mite (0.53 [0.30-0.96]). No association between polyclonal IgE antibodies and skin-test results was found. INTERPRETATION: The anti-inflammatory cytokine, interleukin-10, induced in chronic schistosomiasis, appears central to suppressing atopy in African children.

Adolescent↗
PubMed2000

HLA-DQB1*0501-restricted Th1 type immune responses to Plasmodium falciparum liver stage antigen 1 protect against malaria anemia and reinfections.

Protective immunity against Plasmodium falciparum requires constant exposure to the pathogen. T cell-mediated immune responses are induced by T cell epitopes of pre-erythrocytic stage antigens of P. falciparum and involve HLA-restricted CD4 and CD8 cells. Cytotoxic T cell responses to a conserved epitope of P. falciparum liver stage antigen (LSA) type 1 are restricted by the HLA class I allele Bw53. The role of HLA class II alleles in mediating cellular responses against P. falciparum LSA-1 has not yet been demonstrated. In a longitudinal study performed for >4 years, associations were found between the HLA class II allele DQB1*0501 and protection from malaria anemia and malarial reinfections in Gabonese children. Children carrying DQB1*0501 had a higher frequency of interferon-gamma responses to LSA-1 T cell epitopes, compared with noncarriers.

Alleles↗
PubMed2000

Plasma interleukin-10:Tumor necrosis factor (TNF)-alpha ratio is associated with TNF promoter variants and predicts malarial complications.

In individuals with severe malarial anemia, plasma levels of tumor necrosis factor (TNF)-alpha tend to exceed those of interleukin (IL)-10. In this study, IL-10:TNF plasma level ratios <1 were found to be a risk factor for both cerebral malaria and severe anemia (P=.009), whereas higher IL-10:TNF ratios were observed more frequently in hyperparasitemic individuals. When considering allelic variants of the TNF promoter in children with severe malaria, carriers of the wild type more frequently had an IL-10:TNF ratio >1 (P=.008). In contrast, individuals with a mutation at position -238 of the TNF promoter (TNF(-238A) and TNF(-376A/-238A)) consistently had lower IL-10 than TNF plasma levels (IL-10:TNF ratio <1; P=.003). Our results show that, in children with severe malaria, TNF promoter variants influence the balance of IL-10:TNF in the plasma, which, in turn, affects the outcome in terms of clinical complications.

Child↗
PubMed2000

Promoter variants of the human mannose-binding lectin gene show different binding.

Mannose-binding lectin (MBL) levels in the plasma of humans are highly variable. The level is influenced by gene mutations in exon1 and the promoter. Here we describe the distribution of three point mutations linked with a deletion in the MBL gene promoter in populations of Central Africa, Thailand, and Papua New Guinea. Among African children we find 20% with the wild-type allele, 53% are heterozygous, and 27% are homozygous for the mutation. In Thailand we find 65% with the wild-type allele, 33% are heterozygous, and 2% are homozygous for the variant. In Papua New Guinea the polymorphism is not found. The occurrence of the mutation was associated with MBL levels in the plasma (P = 0.043). Oligonucleotides derived from the variant promoter regions bind proteins differently according to their DNA sequence. The binding of proteins can be influenced by induction with interleukin-6.

Base Sequence↗
PubMed2000

Malaria chemoprophylaxis with tafenoquine: a randomised study.

BACKGROUND: Tafenoquine is an analogue of primaquine with an improved therapeutic and safety profile. It has a long half-life and activity against liver-stage malaria parasites, so may be useful for chemoprophylaxis. In this randomised, double-blind study we assessed the efficacy and safety of tafenoquine in different doses. METHODS: 2144 individuals aged 12-20 years living in Lambaréné, Gabon, an endemic area for Plasmodium falciparum malaria, were invited to take part. 535 attended, and 426 eligible participants were randomly assigned tafenoquine (250 mg, 125 mg, 62.5 mg, or 31.25 mg) or placebo daily for 3 days. 417 received initial curative treatment with halofantrine, and 410 completed the assigned prophylaxis regimen. During follow-up of 70 days, adverse events were recorded and thick blood smears were examined weekly. The primary and secondary endpoints were the number of individuals with positive blood smears by day 56 and day 77, respectively. Analyses were per-protocol. FINDINGS: Eight positive blood smears were recorded by day 56 (four/82 participants in the placebo group; four/79 tafenoquine 31.25 mg group). By day 77, 34 positive blood smears had been recorded (14/82 placebo; 16/79 tafenoquine 31.25 mg; three/86 tafenoquine 62.5 mg; one/79 tafenoquine 125 mg; none/84 tafenoquine 250 mg). Numbers of adverse events did not differ significantly between the treatment groups. INTERPRETATION: Tafenoquine is effective and well tolerated. It has the potential to replace currently used drugs for malaria chemoprophylaxis.

Adolescent↗
PubMed2000

A blinded, controlled trial of an ultrasound device as mosquito repellent.

Ultrasound emitting devices are used to repel mosquitoes. We tested the repelling properties of a commercially available ultrasound device in a domestic setting in Gabon. Devices emitting three different block frequencies ranging from 3 to 11 kHz were tested in a paired, cross-over blinded and placebo controlled trial during eighteen nights in nine pairs of houses. A total of 7485 mosquitoes (10% Anopheles, 62% Culex, 27% Mansonia and 1% Aedes) were caught, 23 per house per night. There was no significant difference in landing rate between the houses with ultrasound device and the houses with placebo for any species of mosquito. Thus the ultrasound device used was not effective against mosquitoes in this strictly controlled trial.

Animals↗
PubMed2000

Effect of alcohol on growth of Plasmodium falciparum.

The effect of ethanol on the in vitro growth of the malaria parasite Plasmodium falciparum was investigated. 17 mM (0.08%) and 85 mM (0.39%) ethanol were added to parasite cultures and growth was determined for six days. A significant growth inhibition for both ethanol concentrations was observed on each day. It reached 65% for 85 mM ethanol after six days of incubation. Malarial parasites are strongly inhibited by ethanol concentrations which are attainable by extensive alcohol consumption.

Africa↗
PubMed2000

Low interleukin-12 activity in severe Plasmodium falciparum malaria.

We compared interleukin-12 (IL-12) and other cytokine activities during and after an acute clinical episode in a matched-pair case-control study of young African children who presented with either mild or severe Plasmodium falciparum malaria. The acute-phase, pretreatment plasma IL-12 and alpha interferon (IFN-alpha) levels, as well as the acute-phase mitogen-stimulated whole-blood production capacity of IL-12, were significantly lower in children with severe rather than mild malaria. IL-12 levels, in addition, showed strong inverse correlations both with parasitemia and with the numbers of circulating malaria pigment-containing neutrophils. Acute-phase plasma tumor necrosis factor (TNF) and IL-10 levels were significantly higher in those with severe malaria, and the concentrations of both of these cytokines were positively correlated both with parasitemia and with the numbers of pigment-containing phagocytes in the blood. Children with severe anemia had the highest levels of TNF in plasma. In all the children, the levels in plasma and production capacities of all cytokines normalized when they were healthy and parasite free. The results indicate that severe but not mild P. falciparum malaria in young, nonimmune African children is characterized by down-regulated IL-12 activity, contrasting markedly with the up-regulation of both TNF and IL-10 in the same children. A combination of disturbed phagocyte functions resulting from hemozoin consumption, along with reduced IFN-gamma responses, may contribute to these differential effects.

Acute Disease↗