Intramuscular Artesunate for Severe Malaria in African Children: A Multicenter Randomized Controlled Trial.

BACKGROUND: Current artesunate (ARS) regimens for severe malaria are complex. Once daily intramuscular (i.m.) injection for 3 d would be simpler and more appropriate for remote health facilities than the current WHO-recommended regimen of five intravenous (i.v.) or i.m. injections over 4 d. We compared both a three-dose i.m. and a three-dose i.v. parenteral ARS regimen with the standard five-dose regimen using a non-inferiority design (with non-inferiority margins of 10%). METHODS AND FINDINGS: This randomized controlled trial included children (0.5-10 y) with severe malaria at seven sites in five African countries to assess whether the efficacy of simplified three-dose regimens is non-inferior to a five-dose regimen. We randomly allocated 1,047 children to receive a total dose of 12 mg/kg ARS as either a control regimen of five i.m. injections of 2.4 mg/kg (at 0, 12, 24, 48, and 72 h) (n = 348) or three injections of 4 mg/kg (at 0, 24, and 48 h) either i.m. (n = 348) or i.v. (n = 351), both of which were the intervention arms. The primary endpoint was the proportion of children with ≥ 99% reduction in parasitemia at 24 h from admission values, measured by microscopists who were blinded to the group allocations. Primary analysis was performed on the per-protocol population, which was 96% of the intention-to-treat population. Secondary analyses included an analysis of host and parasite genotypes as risks for prolongation of parasite clearance kinetics, measured every 6 h, and a Kaplan-Meier analysis to compare parasite clearance kinetics between treatment groups. A post hoc analysis was performed for delayed anemia, defined as hemoglobin ≤ 7 g/dl 7 d or more after admission. The per-protocol population was 1,002 children (five-dose i.m.: n = 331; three-dose i.m.: n = 338; three-dose i.v.: n = 333); 139 participants were lost to follow-up. In the three-dose i.m. arm, 265/338 (78%) children had a ≥ 99% reduction in parasitemia at 24 h compared to 263/331 (79%) receiving the five-dose i.m. regimen, showing non-inferiority of the simplified three-dose regimen to the conventional five-dose regimen (95% CI -7, 5; p = 0.02). In the three-dose i.v. arm, 246/333 (74%) children had ≥ 99% reduction in parasitemia at 24 h; hence, non-inferiority of this regimen to the five-dose control regimen was not shown (95% CI -12, 1; p = 0.24). Delayed parasite clearance was associated with the N86YPfmdr1 genotype. In a post hoc analysis, 192/885 (22%) children developed delayed anemia, an adverse event associated with increased leukocyte counts. There was no observed difference in delayed anemia between treatment arms. A potential limitation of the study is its open-label design, although the primary outcome measures were assessed in a blinded manner. CONCLUSIONS: A simplified three-dose i.m. regimen for severe malaria in African children is non-inferior to the more complex WHO-recommended regimen. Parenteral ARS is associated with a risk of delayed anemia in African children. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201102000277177.

Asymptomatic Plasmodium falciparum infection in children is associated with increased auto-antibody production, high IL-10 plasma levels and antibodies to merozoite surface protein 3.

BACKGROUND: Mechanisms of acquired protection to malaria in asymptomatic Plasmodium falciparum carriers are only partially understood. Among them, the role plays by the self-reactive antibodies has not been clarified yet. In this study, the relationship between repertoires of circulating self-reactive and parasite-specific immunoglobulin G (IgG), their correlation with cytokine levels, and their association with protection against malaria was investigated in asymptomatic Plasmodium falciparum-infected Gabonese children. METHODS: The diversity of P. falciparum-specific antibody repertoire was analysed using a protein micro-array immunoassay, the total auto-antibody repertoire by quantitative immunoblotting and circulating cytokine levels were measured by ELISA in endemic controls (EC) and P. falciparum-infected children from Gabon with asymptomatic (AM) or mild malaria (MM). The association of self- and parasite-specific antibody repertoires with circulating cytokines was evaluated using single linkage hierarchical clustering, Kruskal-Wallis tests and Spearman's rank correlation. RESULTS: Children with AM exhibited an IgG response to merozoite surface protein 3 (MSP3) but not to MSP1-19, although their levels of total P. falciparum-specific IgG were similar to those in the MM group. Moreover, the asymptomatic children had increased levels of autoantibodies recognising brain antigens. In addition, a correlation between IL-10 levels and parasite load was found in AM and MM children. These two groups also exhibited significant correlations between plasma levels of IL-10 and IFN-γ with age and with total plasma IgG levels. IL-10 and IFN-γ levels were also associated with auto-antibody responses in AM. CONCLUSIONS: Altogether, these results indicate that a self-reactive polyclonal response associated with increased IgG to MSP3 and high plasma levels of IL-10 and IFN-γ may contribute to protective immune mechanisms triggered in asymptomatic P. falciparum infection in Gabonese children.

Increase in malaria prevalence and age of at risk population in different areas of Gabon.

BACKGROUND: Following the deployment of new recommendations for malaria control according to the World Health Organization, an estimation of the real burden of the disease is needed to better identify populations at risk and to adapt control strategies. The aim of the present study was to estimate the clinical burden of malaria among febrile children aged less than 11 years, before and after six-year of deployment of malaria control strategies in different areas of Gabon. METHODS: Cross-sectional surveys were carried out in health care facilities at four locations: two urban areas (Libreville and Port-Gentil), one semi-urban area (Melen) and one rural area (Oyem), between 2005 and 2011. Febrile paediatric patients, aged less than 11 years old were screened for malaria using microscopy. Body temperature, history of fever, age, sex, and location were collected. RESULTS: A total of 16,831 febrile children were enrolled; 78.5% (n=13,212) were less than five years old. The rate of Plasmodium falciparum-infection was the lowest in Port-gentil (below 10%) and the highest at Oyem (above 35%). Between 2005 and 2008, malaria prevalence dropped significantly from 31.2% to 18.3%, followed by an increase in 2011 in Libreville (24.1%), Port-Gentil (6.5%) and Oyem (44.2%) (p<0.01). Median age among the infected patients increased throughout the study period reaching 84 (60-108) months in Libreville in 2011 (p<0.01). From 2008, at all sites, children older than five years were more frequently infected; the risk of being infected significantly increased with time, ranging from 0.37 to 1.50 in 2005 and from 2.03 to 5.10 in 2011 in this group (p<0.01). The risk of being P. falciparum-infected in children aged less than five years old significantly decreased from 2008 to 2011 (p<0.01). CONCLUSIONS: This study shows an increased risk of malaria infection in different areas of Gabon with over-five year-old children tending to become the most at-risk population, suggesting a changing epidemiology. Moreover, the heterogeneity of the malaria burden in the country highlights the importance of maintaining various malaria control strategies and redefining their implementation.

Sub-microscopic gametocyte carriage in febrile children living in different areas of Gabon.

BACKGROUND: Considering malaria prevalence declines in parts of sub-Saharan Africa, such as Gabon, identification of the human infectious reservoir is important for successful malaria control. Microscopic and sub-microscopic parasites contribute to malaria transmission. The aim of the present study was to evaluate the proportion of microscopic and sub-microscopic gametocyte carriers among febrile patients in two different areas of Gabon. METHODS: Samples from febrile children aged less than 11 years old were collected from February 2008 to January 2009 at two health centres of Gabon. Patients were screened for the presence of asexual Plasmodium falciparum parasites. Gametocyte carriage was determined by microscopy and QT-NASBA. RESULTS: Gametocytes were detected in 5.3% (n = 16/304) of children by microscopy compared to 45.7% (n = 139/304) by QT-Nasba. Sub-microscopic gametocyte carriage (ie microscopy negative and QT-Nasba positive) was found in 89.2% (n = 124/139) of patients. Among patients with microscopically detected trophozoites, the proportion of sub-microscopic gametocyte (SMG) carriers was 58.4% (n = 118/202) and 6% in samples from children with negative slides (p < 0.01). In Oyem, where malaria prevalence is three-fold higher than in Owendo, SMG carriage was more frequent (49.0% vs 32.6% in Owendo; p < 0.01). CONCLUSION: Sub-microscopic gametocytaemia is common among Gabonese febrile children. They might strongly contribute to maintain malaria transmission. However, further analysis of sub-microscopic parasite carriage among asymptomatic individuals will be helpful to better characterize malaria transmission.

Antenatal care visit attendance, intermittent preventive treatment and bed net use during pregnancy in Gabon.

BACKGROUND: The World Health Organization (WHO) recommends that intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) and insecticide treated bed nets (ITNs) must be provided during antenatal care (ANC) visits for malaria prevention during pregnancy. The aim of this study was to determine the level of ANC attendance and its relationship with IPTp-SP and bed net coverage in Gabonese pregnant women. METHODS: This was a cross-sectional survey performed in 2011 in sentinel sites for malaria: two ANC units (Melen and Owendo) and one delivery unit (CHL). A validated structured questionnaire was used to collect the following data: age, parity, history of the current pregnancy including gestational age at the interview, number of ANC visits already performed, date of first visit, use of malaria preventive measure and details on IPTp-SP administration. RESULTS: During the study, 1030 women were interviewed, 735 at their ANC visit and 295 at the delivery. Their median age was 24[20-29] years and 21.0% were primigravidae. More than 70.0% attended their first ANC visit during the second trimester. Among the 442 women who were at the end of their pregnancy, 71.5% had a correct attendance, at least four ANC visits, most frequently women with no education and older women; IPTp-SP was offered to 84.1% of them and 57.4% received at least two doses. The number of SP doses was correlated to the number of ANC visits. Bed net coverage was 59.0%, not associated with ANC attendance. Among the women with correct ANC attendance, only 49.5% had a complete IPTp-SP course associated with bed net use during pregnancy. In the site where SP administration was supervised, 80% had four ANC visits and 97.4% received a full 2-dose course of IPTp-SP. CONCLUSIONS: Despite a high level of correct ANC attendance in Gabon, the goal of 80% of women with 2-dose IPTp-SP during pregnancy is not achieved. Evaluations, training of health workers, as well as surveys from other areas of the country are needed to further measure the implementation and the impact of these strategies.

High levels of immunoglobulin E autoantibody to 14-3-3 epsilon protein correlate with protection against severe Plasmodium falciparum malaria.

Plasmodium falciparum infection generally induces elevated total plasma levels of immunoglobulins, some of which recognize self- or parasite-specific antigens. To our knowledge, we are the first to report high levels of functional immunoglobulin E (IgE) autoantibodies recognizing brain 14-3-3 protein ε in asymptomatic P. falciparum malaria. 14-3-3 ε protein belongs to a family of proteins that binds to CD81, a member of the tetraspanin superfamily elicited in hepatocyte invasion by sporozoites. Levels of expression of 14-3-3 ε protein were found to be increased in vivo and in vitro during Plasmodium yoelii and P. falciparum intrahepatic development. Collectively, these results indicate that self-reactive IgE is produced during malaria. In addition, the negative correlation between levels of self-reactive IgE to 14-3-3 ε protein and parasitemia in asymptomatic malaria due to P. falciparum supports a role for these IgE molecules in defense mechanisms, probably by interfering with development of liver-stage parasites through the CD81 pathway.

A simplified intravenous artesunate regimen for severe malaria.

BACKGROUND: We compared a conventional empirically derived regimen with a simplified regimen for parenteral artesunate in severe malaria. METHODS: This was a randomized, double-blind, placebo-controlled comparison to assess the noninferiority of a simplified 3-dose regimen (given at 0, 24, and 48 hours) compared with the conventional 5-dose regimen of intravenous artesunate (given at 0, 12, 24, 48, and 72 hours) in African children with Plasmodium falciparum malaria with a prespecified delta of 0.2. The total dose of artesunate in each group was 12 mg/kg. The primary end point was the proportion of children clearing ≥ 99% of their admission parasitemia at 24 hours. Safety data, secondary efficacy end points, and pharmacokinetics were also analyzed. RESULTS: In 171 children (per protocol), 78% of the recipients (95% confidence interval [CI], 69%-87%) in the 3-dose group achieved ≥ 99% parasite clearance 24 hours after the start of treatment, compared with 85% (95% CI, 77%-93%) of those receiving the conventional regimen (treatment difference, -7.2%; 95% CI, -18.9% to 4.4%). Dihydroartemisinin was cleared slightly more slowly in those children receiving the higher 3-dose regimen (7.4 vs 8.8 L/h for a 13-kg child; P 5 .008). CONCLUSIONS: Pharmacodynamic analysis suggests that 3 doses of artesunate were not inferior to 5 doses for the treatment of severe malaria in children. CLINICAL TRIALS REGISTRATION: NCT00522132.

Malaria transmission in Libreville: results of a one year survey.

BACKGROUND: In Gabon, vector transmission has been poorly studied. Since the implementation of the Roll Back malaria recommendations, clinical studies have shown a decline in the burden of malaria in Libreville, the capital city of Gabon. To better understand the transmission dynamic in Libreville, an entomological survey was conducted in five districts of the city. METHODS: Mosquitoes were sampled by human landing collection during 1 year in five districts of Libreville: Alibandeng, Beauséjour, Camp des Boys and Sotega. Mosquitoes were identified morphologically and by molecular methods. The Plasmodium falciparum circumsporozoïte indices were measured by ELISA, and the entomological inoculation rates (EIR) were calculated for all areas. Molecular assessments of pyrethroid knock down resistance (kdr) and of insensitive acetylcholinesterase resistance were conducted. RESULTS: A total of 57,531 mosquitoes were caught during 341 person-nights (161 person-nights indoor and 180 person-nights outdoor) among which, 4,223 were Anopheles gambiae s.l. The average Human Biting Rate fell from 15.5 bites per person during the rainy season to 4.7 during the dry season. The An. gambiae complex population was composed of An. gambiae s.s molecular form S (99.5%), Anopheles melas (0.3%) and An. gambiae s.s. form M (0.2%). Thirty-three out of 4,223 An. gambiae s.l. were found to be infected by P. falciparum (CSP index = 0.78%). The annual EIR was estimated at 33.9 infected bites per person per year ranging from 13 in Alibandeng to 88 in Sotega. No insensitive AChE mutation was identified but both kdr-w and kdr-e mutations were present in An. gambiae molecular form S with a higher frequency of the kdr-w allele (76%) than the kdr-e allele (23.5%). CONCLUSION: Malaria transmission in Libreville occurred mainly during the rainy season but also during the dry season in the five districts. Transmission level is high and seems to be very heterogeneous in the town. Interestingly, the highest EIR was recorded in the most central and urbanized quarter and the lowest in a peripheral area. The decrease of transmission usually seen from peri-urban areas to urban centers is probably more dependent of the socio-economic level of a quarter than of its location in the city. Urban malaria control programmes need to consider the socio economic level of an area rather than the location in the city in order to determine the areas most favourable to malaria transmission.

Complicated malaria and other severe febrile illness in a pediatric ward in Libreville, Gabon.

BACKGROUND: Although a substantial decline of Plasmodium falciparum infection is observed in Africa following implementation of new control strategies, malaria is still considered as the major cause of febrile illness in hospitalized African children. The present study was designed to assess the management of febrile illness and to determine the proportion of children with febrile illness hospitalized for primary diagnosis of malaria who had confirmed complicated malaria after implementation of new malaria control strategies in Libreville, Gabon. METHODS: Demographic, clinical and biological data from hospitalized children with fever or a history of fever, with a primary diagnosis of clinical malaria, aged less than 18 years old, who benefited from hematological measurements and microscopic malaria diagnosis, were recorded and analyzed during a prospective and observational study conducted in 2008 in the Centre Hospitalier de Libreville. RESULTS: A total of 418 febrile children were admitted at hospital as malaria cases. Majority of them (79.4%) were aged below five years. After medical examination, 168 were diagnosed and treated as clinical malaria and, among them, only 56.7% (n = 95) had Plasmodium falciparum positive blood smears. Age above five years, pallor, Blantyre Coma Score ≤2 and thrombocytopenia were predictive of malaria infection. Respiratory tract infections were the first leading cause of hospitalization (41.1%), followed by malaria (22.7%); co-morbidities were frequent (22%). Less than 5% of suspected bacterial infections were confirmed by culture. Global case fatality rate was 2.1% and 1% for malaria. Almost half (46%) of the children who received antimalarial therapy had negative blood smears. Likewise, antibiotics were frequently prescribed without bacteriological confirmation. CONCLUSIONS: The use of clinical symptoms for the management of children febrile illness is frequent in Gabon. Information, training of health workers and strengthening of diagnosis tools are necessary to improve febrile children care.

Phase I randomized dose-ascending placebo-controlled trials of ferroquine--a candidate anti-malarial drug--in adults with asymptomatic Plasmodium falciparum infection.

BACKGROUND: The development and spread of drug resistant Plasmodium falciparum strains is a major concern and novel anti-malarial drugs are, therefore, needed. Ferroquine is a ferrocenic derivative of chloroquine with proven anti-malarial activity against chloroquine-resistant and -sensitive P. falciparum laboratory strains. METHODS: Adult young male aged 18 to 45 years, asymptomatic carriers of P. falciparum, were included in two-dose escalation, double-blind, randomized, placebo-controlled Phase I trials, a single dose study and a multiple dose study aiming to evaluate oral doses of ferroquine from 400 to 1,600 mg. RESULTS: Overall, 54/66 patients (40 and 26 treated in the single and multiple dose studies, respectively) experienced at least one adverse event, 15 were under placebo. Adverse events were mainly gastrointestinal symptoms such as abdominal pain (16), diarrhoea (5), nausea (13), and vomiting (9), but also headache (11), and dizziness (5). A few patients had slightly elevated liver parameters (10/66) including two patients under placebo. Moderate changes in QTc and morphological changes in T waves were observed in the course of the study. However, no adverse cardiac effects with clinical relevance were observed. CONCLUSIONS: These phase I trials showed that clinically, ferroquine was generally well-tolerated up to 1,600 mg as single dose and up to 800 mg as repeated dose in asymptomatic young male with P. falciparum infection. Further clinical development of ferroquine, either alone or in combination with another anti-malarial, is highly warranted and currently underway.

[Parental administration of unprescribed antimalarial drugs to treat febrile children in Gabon]. / Usage des antipaludiques en automédication pour le traitement de la fièvre chez les enfants au Gabon.

Resistance by Plasmodium falciparum to antimalarial drugs has strongly hampered strategies for malaria control and elimination. Therefore, one of the goals of the World Health Organisation's new malaria control strategies is the rational and appropriate use of antimalarial drugs and in particular of artemisinin-based combination therapy (ACTs), currently used for the treatment of uncomplicated malaria; in order to delay the appearance of drug-resistant parasites. The unprescribed use of antimalarial drugs (self medication and parental administration to children) is a key component in the development of antimalarial drug resistance and must be controlled among patients living in malaria-endemic areas. The aim of our study was to estimate the frequency of this parental administration among febrile children and to identify the specific drugs used. Data were collected in two studies evaluating the proportion of malaria cases and the performance of rapid drug tests among febrile children seen in 2008-2009 at 3 hospitals, one in a rural area, one in an urban area, and the third in a semi-urban area. This parental medication administration was found among 21.4% of the 2543 children included in the studies. It was most common at the rural hospital (29%), which is also where malaria prevalence was highest (39%). Of the 548 children "medicated", 421, that is, almost 80%, were not infected. The antimalarial drugs used most frequently were ACTs (43.8%) and quinine (12%). In Gabon, as in other sub-Saharan countries, use of antimalarial drugs before consultation is common and is an obstacle to malaria control. Therefore, improving the rational use of these drugs by the population requires active outreach to the community about the risks of unprescribed medication.

[Trends in the prevalence of malaria and anemia at delivery in Libreville from 1995 to 2011]. / Infection plasmodiale et anémie chez des parturientes du Centre hospitalier de Libreville entre 1995 et 2011.

In 1995, 2005 and 2011, cross-sectional studies of 611 parturients at the Centre Hospitalier de Libreville in Gabon assessed the prevalence of maternal malaria and anaemia; two indicators of poor pregnancy outcomes. The prevalence of Plasmodium falciparum infection in maternal peripheral blood decreased from 25% in 2005 to 6% in 2011. Parasite density was significantly lower in 2005 (31 p/µL) than in 1995 (1,240 p/µL) or 2011 (35,055 p/µL). Anaemia prevalence was high (>50%) in 1995 and in 2005, but fell by more than 50% (24%) in 2011. After implementation of new malaria prevention strategies during pregnancy, the prevalence of both maternal peripheral P. falciparum infection and anaemia fell. Studies are necessary to assess the efficacy of these strategies and to seek other causes of anaemia.

Differential var gene expression in children with malaria and antidromic effects on host gene expression.

Among 62 children with mild malaria, cerebral malaria, or severe malarial anemia, we analyzed the transcription of different var gene types. There was no difference in parasitemia level or body temperature between groups. However, a significantly different expression pattern was observed in children with cerebral malaria, compared with that in patients in the other 2 groups: children with cerebral malaria had lower expression of the upsA subtype but higher expression of the upsB and upsC subtypes. Furthermore, expression of human genes responsive to tumor necrosis factor and hypoxia correlated with distinct ups types.

High prevalence of sulfadoxine/pyrimethamine-resistant alleles of Plasmodium falciparum isolates in pregnant women at the time of introduction of intermittent preventive treatment with sulfadoxine/pyrimethamine in Gabon.

OBJECTIVES: The frequency of dhfr and dhps point mutations was assessed in Plasmodium falciparum isolates from pregnant women in Libreville. METHODS: PCR-restriction fragment length polymorphism of polymorphic codons of the dhfr gene (51, 59 and 108) and the dhps gene (436, 437 and 540) was performed in matched peripheral and placental blood samples. RESULTS: The proportion of multiple mutations was high (98%), and was not different between women with and without a history of intermittent preventive treatment with sulfadoxine/pyrimethamine (IPTp/SP). The prevalence of triple dhfr mutation was 80%, and that of quadruple and quintuple mutations was 53% and 22%, respectively. The Glu540 mutation was present in two isolates. The concordance of resistant alleles in matched peripheral and placental isolates was >90% for both genes. CONCLUSIONS: These findings underline the need for a regular assessment of the relationship between the presence of resistant isolates and in vitro/in vivo IPTp/SP efficacy, and evaluation of an alternative drug.

Malaria transmission and insecticide resistance of Anopheles gambiae in Libreville and Port-Gentil, Gabon.

BACKGROUND: Urban malaria is a major health priority for civilian and militaries populations. A preliminary entomologic study has been conducted in 2006-2007, in the French military camps of the two mains towns of Gabon: Libreville and Port-Gentil. The aim was to assess the malaria transmission risk for troops. METHODS: Mosquitoes sampled by human landing collection were identified morphologically and by molecular methods. The Plasmodium falciparum circumsporozoïte (CSP) indexes were measured by ELISA, and the entomological inoculation rates (EIR) were calculated for both areas. Molecular assessments of pyrethroid knock down (kdr) resistance and of insensitive acetylcholinesterase resistance were conducted. RESULTS: In Libreville, Anopheles gambiae s.s. S form was the only specie of the An. gambiae complex present and was responsible of 9.4 bites per person per night. The circumsporozoïte index was 0.15% and the entomological inoculation rate estimated to be 1.23 infective bites during the four months period. In Port-Gentil, Anopheles melas (75.5% of catches) and An. gambiae s.s. S form (24.5%) were responsible of 58.7 bites per person per night. The CSP indexes were of 1.67% for An. gambiae s.s and 0.28% for An. melas and the EIRs were respectively of 1.8 infective bites per week and of 0.8 infective bites per week. Both kdr-w and kdr-e mutations in An. gambiae S form were found in Libreville and in Port-Gentil. Insensitive acetylcholinesterase has been detected for the first time in Gabon in Libreville. CONCLUSION: Malaria transmission exists in both town, but with high difference in the level of risk. The co-occurrence of molecular resistances to the main families of insecticide has implications for the effectiveness of the current vector control programmes that are based on pyrethroid-impregnated bed nets.

Immunoblot analysis of membrane antigens of Schistosoma mansoni, Schistosoma intercalatum, and Schistosoma haematobium against Schistosoma-infected patient sera.

Antigens present in aqueous n-butanolic extracts (BE) of Schistosoma mansoni (Venezuelan JL strain), Schistosoma intercalatum (Cameroon EDEA strain), and Schistosoma haematobium (Yemen strain) adult worm membranes were compared in immunoblot against sera of patients infected with S. mansoni, S. intercalatum, S. haematobium, Schistosoma japonicum, or Schistosoma mekongi looking for similarities (common antigens) and differences (species-specific antigens). About 17 S. mansoni BE polypeptides (M (r) approximately 8 to >80 kDa) were commonly recognized by S. mansoni-infected patient sera from Venezuela, Senegal, and Ethiopia. S. intercalatum-, S. haematobium-, or S. japonicum-infected sera were almost unreactive with S. mansoni BE. Nonetheless, S. mekongi-infected sera weakly cross-reacted with a approximately 10-15-kDa subset of S. mansoni BE. About 72.7% of S. intercalatum-infected patient sera reacted with a approximately 19-21-kDa complex in S. intercalatum BE and cross-reacted with a similar complex in S. haematobium BE. Conversely, all S. haematobium-infected patient sera reacted with a approximately 19-21-kDa complex in S. haematobium BE and cross-reacted with the approximately 19-21-kDa complex in S. intercalatum BE; S. mansoni- and S. japonicum-infected patient sera did not react with S. intercalatum or S. haematobium BE. Results showed the presence of a common membrane antigen between African schistosome species and species-specific antigens in S. mansoni BE that could be useful to discriminate between species and/or to detect Schistosoma infections.

[Epidemiology of parasitic diseases, hypereosinophilia, IgE from tropical and European parasitological origins]. / Epidémiologie des parasitoses, hyperéosinophilies sanguines et IgE d'origines parasitaires en milieux tempérés et tropicaux.

Etiologic investigations of hypereosinophilia, often accompanied by IgE elevation, depends on the patient's geographic origin and travel history. In France, helminth diseases are the only parasitoses associated with hypereosinophilia. Some, such as oxyurosis in children, are frequent but generally mild. More severe but less frequent infections include distomatoses, trichinellosis, taeniasis, echinococcosis and visceral larva migrans. Among subjects originating from or having travelled to tropical areas with poor hygiene, eosinophilia may be due to early intense polyparasitism and has little etiologic value. In Gabon, a warm, humid country in equatorial Africa, schoolchildren harbor an average of three different parasites capable of inducing hypereosinophilia or serum IgE elevation. These children's eosinophil counts start to rise at very young age, after weaning and contact with soil, and continue to increase rapidly until adulthood. Average values across all age groups are 1580 eosinophils/mm3 and 3300 kU IgE/L. Direct diagnosis of chronic parasitic infections is often possible in this setting, and specific treatments can be prescribed. In contrast, hypereosinophilia has less etiologic significance in patients originating from or having travelled to the tropics and who present to European parasitology units. Direct examination is rarely positive, and the etiologic diagnosis will thus be guided by epidemiologic, clinical and serologic findings. These findings are sometimes sufficient to initiate probabilistic treatment with albendazole, ivermectin and praziquentel.

The Lambaréné Organ Dysfunction Score (LODS) is a simple clinical predictor of fatal malaria in African children.

BACKGROUND: Plasmodium falciparum malaria accounts for >1 million deaths annually, mostly among young children in sub-Saharan Africa. Identifying those individuals who are likely to die is crucial. Several factors have been independently associated with death. Because malaria is a systemic disease, a quantitative score combining such risk factors may be superior. METHODS: We used both forward and backward stepwise logistic regression to select the best predictors of death, as evaluated for 23,890 African children with severe P. falciparum malaria. The study was conducted from December 2000 through May 2005 in 6 hospital-based research units (in Banjul in the Gambia, Blantyre in Malawi, Kilifi in Kenya, Kumasi in Ghana, and Lambaréné and Libreville in Gabon) in a network established to study severe malaria in African children (ie, the SMAC Network). RESULTS: The Lambaréné Organ Dysfunction Score (LODS) combines 3 variables: coma, prostration, and deep breathing. A LODS >0 (odd ratio, 9.6; 95% confidence interval, 8.0-11.4) has 85% sensitivity to predict death, and a LODS <3 is highly (98%) specific for survival. CONCLUSIONS: The LODS is a simple clinical predictor of fatal malaria in African children. This score provides accurate and rapid identification of children needing either referral or increased attention.

Multinormal in vitro distribution model suitable for the distribution of Plasmodium falciparum chemosusceptibility to doxycycline.

The distribution and range of 50% inhibitory concentrations (IC(50)s) of doxycycline were determined for 747 isolates obtained between 1997 and 2006 from patients living in Senegal, Republic of the Congo, and Gabon and patients hospitalized in France for imported malaria. The statistical analysis was designed to answer the specific question of whether Plasmodium falciparum has different phenotypes of susceptibility to doxycycline. A triple normal distribution was fitted to the data using a Bayesian mixture modeling approach. The IC(50) geometric mean ranged from 6.2 microM to 11.1 microM according to the geographical origin, with a mean of 9.3 microM for all 747 parasites. The values for all 747 isolates were classified into three components: component A, with an IC(50) mean of 4.9 microM (+/-2.1 microM [standard deviation]); component B, with an IC(50) mean of 7.7 microM (+/-1.2 microM); and component C, with an IC(50) mean of 17.9 microM (+/-1.4 microM). According to the origin of the P. falciparum isolates, the triple normal distribution was found in each subgroup. However, the proportion of isolates predicted to belong to component B was most important in isolates from Gabon and Congo and in isolates imported from Africa (from 46 to 56%). In Senegal, 55% of the P. falciparum isolates were predicted to be classified as component C. The cutoff of reduced susceptibility to doxycycline in vitro was estimated to be 35 microM.

Impact of Plasmodium falciparum infection on the frequency of moderate to severe anaemia in children below 10 years of age in Gabon.

BACKGROUND: Improving the understanding of childhood malarial anaemia may help in the design of appropriate management strategies. METHODS: A prospective observational study over a two-year period to assess the burden of anaemia and its relationship to Plasmodium falciparum infection and age was conducted in 8,195 febrile Gabonese children. RESULTS: The proportion of children with anaemia was 83.6% (n = 6830), higher in children between the ages of six and 23 months. Those under three years old were more likely to develop moderate to severe anaemia (68%). The prevalence of malaria was 42.7% and P. falciparum infection was more frequent in children aged 36-47 months (54.5%). The proportion of anaemic children increased with parasite density (p < 0.01). Most of infected children were moderately to severely anaemic (69.5%, p < 0.01). Infants aged from one to 11 months had a higher risk of developing severe malarial anaemia. In children over six years of age, anaemia occurrence was high (>60%), but was unrelated to P. falciparum parasitaemia. CONCLUSION: Malaria is one of the main risk factors for childhood anaemia which represents a public health problem in Gabon. The risk of severe malarial anaemia increases up the age of three years. Efforts to improve strategies for controlling anaemia and malaria are needed.