Falciparum Infection In Children Research Articles

Prevalence of Plasmodium falciparum infection in children under 15 years in two oil palm plantations in Aboisso, Côte d'Ivoire

Prevalence of Plasmodium falciparum infection in children under 15 years in two oil palm plantations in Aboisso, Côte d'Ivoire

Cytokine response in asymptomatic and symptomatic Plasmodium falciparum infections in children in a rural area of south-eastern Gabon.

Plasmodium falciparum is a parasite that causes asymptomatic or symptomatic malaria infections in humans depending on various factors. These infections are also a major cause of anemia in intertropical countries such as Gabon. Past studies have clearly demonstrated that inflammatory markers such as cytokines play a key role in the pathogenesis of malaria disease. However, the clinical manifestations of severe malaria vary according to the level of transmission and more information is needed to gain a better understanding of the factors involved. As such, the objective of this study was to investigate the circulating levels of nine cytokines in asymptomatic and symptomatic P. falciparum infections in Gabonese children and their roles in the pathogenesis of anemia. Blood samples were collected from 241 children aged 3 to 180 months in Lastourville, south-eastern Gabon. Diagnosis of P. falciparum infection was performed using Rapid Diagnosis Tests, microscopy and nested PCR. Levels in the plasma of the Th1 (IFN-γ, TNF-α, IL-6 and IL-12p70), Th17 (IL-17A and IL-22) and Th2 (IL-10, IL-4 and IL-13) cytokines were measured by ELISA. Data showed that IL-6, IFN-γ, IL-12p70, IL-10, and IL-13 levels were significantly higher in children with symptomatic P. falciparum infection compared to uninfected children. IL-10 levels were significantly higher in symptomatic children than in asymptomatic children, who had moderately increased levels compared to uninfected controls. Moreover, only IL-10 and IL-6 levels were significantly higher in children with severe malarial anemia compared to children with uncomplicated malaria who had significantly lower IL-10 levels than children with moderate malarial anemia. These data indicate that the progression of P. falciparum infection towards an advanced stage in children is accompanied by a significant increase in type Th1 and/or Th2 cytokines. These inflammatory mediators could serve as potential predictors of anemia for malaria patients.

Asymptomatic and sub-microscopic Plasmodium falciparum infection in children in the Mount Cameroon area: a cross-sectional study on altitudinal influence, haematological parameters and risk factors

BackgroundThe Mount Cameroon area has experienced a 57.2% decline in confirmed malaria cases between 2006 and 2013 with the implementation of different control measures but, the disease is still of public health concern. The objective of the study was to assess the burden of asymptomatic and sub-microscopic Plasmodium infection, altitudinal influence on it, their effect on haematological parameters as well as identify the risk factors of infection.MethodologyA cross-sectional community-based survey involving 1319 children of both sexes aged 6 months to 14 years was conducted between July 2017 and May 2018. Malaria parasitaemia was confirmed by Giemsa-stained microscopy, sub-microscopic Plasmodium infection by 18S mRNA using nested PCR and full blood count analysis was done using an auto haematology analyser.ResultsMalaria parasite, asymptomatic malaria parasitaemia and sub-microscopic Plasmodium infection and anaemia were prevalent in 36.4%, 34.0%, 43.8% and 62.3% of the children, respectively. The risk of having sub-microscopic Plasmodium infection was highest in children 5‒9 (OR = 3.13, P < 0.001) and 10‒14 years of age (OR = 8.18, P < 0.001), non-insecticide treated net users (OR = 1.69, P < 0.04) and those anaemic (OR = 9.01, P < 0.001). Children with sub-microscopic infection had a significantly lower mean haemoglobin (9.86 ± 1.7 g/dL, P < 0.001), red blood cell counts (4.48 ± 1.1 × 1012/L, P < 0.001), haematocrit (31.92%, P < 0.001), mean corpuscular haemoglobin concentration (313.25 ± 47.36, P = 0.035) and platelet counts (280.83 ± 112.62, P < 0.001) than their negative counterparts. Children < 5 years old (73.8%), having asymptomatic (69.8%) and sub-microscopic Plasmodium infection (78.3%) as well as resident in the middle belt (72.7%) had a higher prevalence of anaemia than their peers.ConclusionThe meaningful individual-level heterogeneity in the burden of asymptomatic and sub-microscopic Plasmodium infection in addition to its corollary on haematological variables among children in the different attitudinal sites of the Mount Cameroon Region accentuate the need for strategic context specific planning of malaria control and preventative measures.

Bayesian evaluation of the performance of three diagnostic tests for Plasmodium falciparum infection in a low-transmission setting in Kilifi County, Kenya.

Background: Central to the successful elimination of Plasmodium falciparum malaria, are tests with superior capability of diagnosing low-density parasitaemias. Empirical evidence on the performance of the commonly available diagnostics (light microscopy (LM), rapid diagnostic tests (RDT) and polymerase chain reaction (PCR)) is needed to better inform case management and surveillance activities within primary health care settings where elimination of falciparum malaria is targeted. The objective of this study was to estimate the sensitivity (Se) and specificity (Sp) and predictive values of LM, RDT and PCR tests for P. falciparum infection in children, while evaluating the effect of specific covariates on the accuracy of the tests. Methods: The study enrolled 1,563 children presenting with fever (axillary temperature ≥ 37.5 0C) to the Ngerenya dispensary, Kilifi County between March and December 2014. A Bayesian latent class model (BLCM) was fitted to the participants' diagnostic data obtained from blood samples that were screened for the presence of P. falciparum using the three tests. Results: The PCR assay registered a higher Se (97.6% [92.0; 99.7]) than LM (84.0% [74.8; 91.0]) but similar to RDT (92.2% [84.4; 97.0]). However, the assay showed a similar Sp (98.9% [98.2; 99.4]) to both RDT (99.4% [98.9; 99.7]) and LM (99.5% [99.0; 99.8]). Regarding predictive values, the tests yielded statistically similar estimates of positive and negative predictive values (PPV and NPV). A serial interpretation of the results of RDT and LM raised the PPVs and NPVs to >98%. Conclusions: LM and RDT afford high Se and Sp in symptomatic care-seeking children in this low P. falciparum prevalence setting. A serial combination of the tests assures high PPV and NPV estimates. These elements, coupled with the wide deployment and affordability of the tests, lend the tests useful for guiding clinical care and surveillance activities for P. falciparum within elimination settings.

Bayesian evaluation of the performance of three diagnostic tests for Plasmodium falciparum infection in a low-transmission setting in Kilifi County, Kenya

Background: Central to the successful elimination of Plasmodium falciparum malaria, are tests with superior capability of diagnosing low-density parasitaemias. Empirical evidence on the performance of the commonly available diagnostics (light microscopy (LM), rapid diagnostic tests (RDT) and polymerase chain reaction (PCR)) is needed to better inform case management and surveillance activities within primary health care settings where elimination of falciparum malaria is targeted. The objective of this study was to estimate the sensitivity (Se) and specificity (Sp) and predictive values of LM, RDT and PCR tests for P. falciparum infection in children, while evaluating the effect of specific covariates on the accuracy of the tests. Methods: The study enrolled 1,563 children presenting with fever (axillary temperature ≥ 37.50C) to the Ngerenya dispensary, Kilifi County between March and December 2014. A Bayesian latent class model (BLCM) was fitted to the participants’ diagnostic data obtained from blood samples that were screened for the presence of P. falciparum using the three tests. Results: The PCR assay registered a higher Se (97.6% [92.0; 99.7]) than LM (84.0% [74.8; 91.0]) but similar to RDT (92.2% [84.4; 97.0]). However, the assay showed a similar Sp (98.9% [98.2; 99.4]) to both RDT (99.4% [98.9; 99.7]) and LM (99.5% [99.0; 99.8]). Regarding predictive values, the tests yielded statistically similar estimates of positive and negative predictive values (PPV and NPV). A serial interpretation of the results of RDT and LM raised the PPVs and NPVs to &gt;98%. Conclusions: LM and RDT afford high Se and Sp in a low P. falciparum prevalence setting. A serial combination of the tests assures high PPV and NPV estimates. These elements, coupled with the wide deployment and affordability of the tests, lend the tests useful for guiding clinical care and surveillance activities for P. falciparum within elimination settings.

Bayesian evaluation of the performance of three diagnostic tests for Plasmodium falciparum infection in a low-transmission setting in Kilifi County, Kenya

Background: Central to the successful elimination of Plasmodium falciparum malaria, are tests with superior capability of diagnosing low-density parasitaemias. Empirical evidence on the performance of the commonly available diagnostics (light microscopy (LM), rapid diagnostic tests (RDT) and polymerase chain reaction (PCR)) is needed to better inform case management and surveillance activities within primary health care settings where elimination of falciparum malaria is targeted. The objective of this study was to estimate the sensitivity (Se) and specificity (Sp) and predictive values of LM, RDT and PCR tests for P. falciparum infection in children, while evaluating the effect of specific covariates on the accuracy of the tests. Methods: The study enrolled 1,563 children presenting with fever (axillary temperature ≥ 37.5 0C) to the Ngerenya dispensary, Kilifi County between March and December 2014. A Bayesian latent class model (BLCM) was fitted to the participants’ diagnostic data obtained from blood samples that were screened for the presence of P. falciparum using the three tests. Results: The PCR assay registered a higher Se (97.6% [92.0; 99.7]) than LM (84.0% [74.8; 91.0]) but similar to RDT (92.2% [84.4; 97.0]). However, the assay showed a similar Sp (98.9% [98.2; 99.4]) to both RDT (99.4% [98.9; 99.7]) and LM (99.5% [99.0; 99.8]). Regarding predictive values, the tests yielded statistically similar estimates of positive and negative predictive values (PPV and NPV). A serial interpretation of the results of RDT and LM raised the PPVs and NPVs to >98%. Conclusions: LM and RDT afford high Se and Sp in symptomatic care-seeking children in this low P. falciparum prevalence setting. A serial combination of the tests assures high PPV and NPV estimates. These elements, coupled with the wide deployment and affordability of the tests, lend the tests useful for guiding clinical care and surveillance activities for P. falciparum within elimination settings.

Role of genetic factors and ethnicity on the multiplicity of Plasmodium falciparum infection in children with asymptomatic malaria in Yaoundé, Cameroon

In this cross-sectional study, we investigated host genetic factors and ethnic variation in circulating Plasmodium falciparum merozoite surface protein 2 (msp-2) clones among children with asymptomatic malaria.Isolates from seventy two asymptomatic malaria children were used for genotyping block 3 of msp-2 gene by nested polymerase chain reaction (PCR). Sickle cell trait and glucose-6-phosphate dehydrogenase (G6PD) deficiency were analysed by restriction fragment length polymorphism of DNA products from PCR targeting codons 6 and 68 of the beta-globin (HBB) and G6PD genes respectively. ABO blood group was typed by agglutination method.A total of forty two msp-2 genotypes (20 for 3D7 and 22 for FC27) were detected for an average (standard error of mean) multiplicity of infection (MOI) of 2.45 (0.16). The MOI was statistically the same among the five identified ethnic groups (P = 0.83). The overall prevalence of sickle cell trait and G6PD deficiency were 12.50 % and 22.22 % respectively. MOI was similar between children with Hb AA and Hb AS genotypes (P = 0.42). MOI was significantly high among children with a mutant G6PD genotype (P = 0.017). MOI was significantly higher in blood group O than group A (P = 0.03).Our findings show that although ethnicity and sickle cell trait have no association with MOI, the association was observed with G6PD genotype and ABO group. The results suggest the need for extension and expansion of the current study in order to investigate the mechanisms involved.

Seasonal Variation in the Epidemiology of Asymptomatic Plasmodium falciparum Infections across Two Catchment Areas in Bongo District, Ghana.

Understanding the epidemiology of asymptomatic Plasmodium falciparum infections is critical for countries to move toward malaria elimination. Using different methods for parasite detection, we evaluated how seasonality, spatial location, and other factors affect the age-specific epidemiology of asymptomatic malaria in Bongo District, Ghana. Asymptomatic prevalence by microscopy decreased significantly from 42.5% at the end of the wet to 27.5% at the end of the dry season (P < 0.001). Using the 18S rRNA polymerase chain reactions (PCRs), all microscopy-negative samples were screened and prevalence of submicroscopic infections also decreased significantly from the wet (55.4%) to the dry (20.7%) season (P < 0.001). Combining detection methods, 74.4% and 42.5% of the population in the wet and dry seasons, respectively, had evidence of a P. falciparum infection. Interestingly in those > 20 years of age, we found evidence of infection in 64.3% of the population in the wet and 27.0% in the dry season. Using both microscopy and PCR, the asymptomatic P. falciparum reservoir peaks at the end of the wet season and infections in all age groups constitute the reservoir of malaria infection. At the end of the wet season, spatial heterogeneity in the prevalence and density of P. falciparum infections was observed between the two catchment areas surveyed in Bongo District. These results indicate that if elimination is to succeed, interventions will need to target not just P. falciparum infections in children but also in adults, and be implemented toward the end of the dry season in this area of West Africa.

Plasmodium falciparum Infection Status among Children with Schistosoma in Sub-Saharan Africa: A Systematic Review and Meta-analysis.

BackgroundIt has been suggested that Schistosoma infection may be associated with Plasmodium falciparum infection or related reduction in haemoglobin level, but the nature of this interaction remains unclear. This systematic review synthesized evidence on the relationship of S. haematobium or S. mansoni infection with the occurrence of P. falciparum malaria, Plasmodium density and related reduction in haemoglobin level among children in sub-Saharan Africa (SSA).Methodology/Principal findingsA systematic review in according with PRISMA guidelines was conducted. All published articles available in PubMed, Embase, Cochrane library and CINAHL databases before May 20, 2015 were searched without any limits. Two reviewers independently screened, reviewed and assessed all the studies. Cochrane Q and Moran’s I2 were used to assess heterogeneity and the Egger test was used to examine publication bias. The summary odds ratio (OR), summary regression co-efficient (β) and 95% confidence intervals (CI) were estimated using a random-effects model. Out of 2,920 citations screened, 12 articles (five cross-sectional, seven prospective cohort) were eligible to be included in the systematic review and 11 in the meta-analysis. The 12 studies involved 9,337 children in eight SSA countries. Eight studies compared the odds of asymptomatic/uncomplicated P. falciparum infection, two studies compared the incidence of uncomplicated P. falciparum infection, six studies compared P. falciparum density and four studies compared mean haemoglobin level between children infected and uninfected with S. haematobium or S. mansoni. Summary estimates of the eight studies based on 6,018 children showed a higher odds of asymptomatic/uncomplicated P. falciparum infection in children infected with S. mansoni or S. haematobium compared to those uninfected with Schistosoma (summary OR: 1.82; 95%CI: 1.41, 2.35; I2: 52.3%). The increase in odds of asymptomatic/uncomplicated P. falciparum infection among children infected with Schistosoma remained significant when subgroup analysis was conducted for S. haematobium (summary OR: 1.68; 95%CI: 1.18, 2.41; I2: 53.2%) and S. mansoni (summary OR: 2.15; 95%CI: 1.89, 2.46: I2: 0.0%) infection. However, the density of P. falciparum infection was lower in children co-infected with S. haematobium compared to those uninfected with Schistosoma (summary-β: -0.14; 95% CI: -0.24, -0.01; I2: 39.7%). The mean haemoglobin level was higher among children co-infected with S. haematobium and P. falciparum than those infected with only P. falciparum (summary-mean haemoglobin difference: 0.49; 95% CI: 0.04, 0.95; I2: 66.4%)Conclusions/SignificanceThe current review suggests S. mansoni or S. haematobium co-infection may be associated with increased prevalence of asymptomatic/uncomplicated P. falciparum infection in children, but may protect against high density P. falciparum infection and related reduction in haemoglobin level.

Severe anaemia associated with Plasmodium falciparum infection in children: consequences for additional blood sampling for research.

BackgroundPlasmodium falciparum infection may cause severe anaemia, particularly in children. When planning a diagnostic study on children suspected of severe malaria in sub-Saharan Africa, it was questioned how much blood could be safely sampled; intended blood volumes (blood cultures and EDTA blood) were 6 mL (children aged <6 years) and 10 mL (6–12 years). A previous review [Bull World Health Organ. 89: 46–53. 2011] recommended not to exceed 3.8 % of total blood volume (TBV). In a simulation exercise using data of children previously enrolled in a study about severe malaria and bacteraemia in Burkina Faso, the impact of this 3.8 % safety guideline was evaluated.MethodsFor a total of 666 children aged >2 months to <12 years, data of age, weight and haemoglobin value (Hb) were available. For each child, the estimated TBV (TBVe) (mL) was calculated by multiplying the body weight (kg) by the factor 80 (ml/kg). Next, TBVe was corrected for the degree of anaemia to obtain the functional TBV (TBVf). The correction factor consisted of the rate ‘Hb of the child divided by the reference Hb’; both the lowest (‘best case’) and highest (‘worst case’) reference Hb values were used. Next, the exact volume that a 3.8 % proportion of this TBVf would present was calculated and this volume was compared to the blood volumes that were intended to be sampled.ResultsWhen applied to the Burkina Faso cohort, the simulation exercise pointed out that in 5.3 % (best case) and 11.4 % (worst case) of children the blood volume intended to be sampled would exceed the volume as defined by the 3.8 % safety guideline. Highest proportions would be in the age groups 2–6 months (19.0 %; worst scenario) and 6 months–2 years (15.7 %; worst case scenario). A positive rapid diagnostic test for P. falciparum was associated with an increased risk of violating the safety guideline in the worst case scenario (p = 0.016).ConclusionsBlood sampling in children for research in P. falciparum endemic settings may easily violate the proposed safety guideline when applied to TBVf. Ethical committees and researchers should be wary of this and take appropriate precautions.

Within-host competition and drug resistance in the human malaria parasite Plasmodium falciparum.

Infections with the malaria parasite Plasmodium falciparum typically comprise multiple strains, especially in high-transmission areas where infectious mosquito bites occur frequently. However, little is known about the dynamics of mixed-strain infections, particularly whether strains sharing a host compete or grow independently. Competition between drug-sensitive and drug-resistant strains, if it occurs, could be a crucial determinant of the spread of resistance. We analysed 1341 P. falciparum infections in children from Angola, Ghana and Tanzania and found compelling evidence for competition in mixed-strain infections: overall parasite density did not increase with additional strains, and densities of individual chloroquine-sensitive (CQS) and chloroquine-resistant (CQR) strains were reduced in the presence of competitors. We also found that CQR strains exhibited low densities compared with CQS strains (in the absence of chloroquine), which may underlie observed declines of chloroquine resistance in many countries following retirement of chloroquine as a first-line therapy. Our observations support a key role for within-host competition in the evolution of drug-resistant malaria. Malaria control and resistance-management efforts in high-transmission regions may be significantly aided or hindered by the effects of competition in mixed-strain infections. Consideration of within-host dynamics may spur development of novel strategies to minimize resistance while maximizing the benefits of control measures.

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.

BackgroundMechanisms 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.MethodsThe 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.ResultsChildren 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.ConclusionsAltogether, 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0658-7) contains supplementary material, which is available to authorized users.

Metabolic Signature Profiling as a Diagnostic and Prognostic Tool in Pediatric Plasmodium falciparum Malaria.

Background. Accuracy in malaria diagnosis and staging is vital to reduce mortality and post infectious sequelae. In this study, we present a metabolomics approach to diagnostic staging of malaria infection, specifically Plasmodium falciparum infection in children. Methods. A group of 421 patients between 6 months and 6 years of age with mild and severe states of malaria with age-matched controls were included in the study, 107, 192, and 122, individuals, respectively. A multivariate design was used as basis for representative selection of 20 patients in each category. Patient plasma was subjected to gas chromatography-mass spectrometry analysis, and a full metabolite profile was produced from each patient. In addition, a proof-of-concept model was tested in a Plasmodium berghei in vivo model where metabolic profiles were discernible over time of infection. Results. A 2-component principal component analysis revealed that the patients could be separated into disease categories according to metabolite profiles, independently of any clinical information. Furthermore, 2 subgroups could be identified in the mild malaria cohort who we believe represent patients with divergent prognoses. Conclusions. Metabolite signature profiling could be used both for decision support in disease staging and prognostication.

A One-compartment Constant Rate Intravascular Infusion Model for the Evaluation of Increases in Hematocrit after Artemisinin-based Combination Treatments of Acute Falciparum Malaria in Children

Increases in hematocrit frequently follow successful treatment of uncomplicated falciparum infections in children, but there is no pharmacokinetic model for the analyses of the increases in hematocrit following artemisinin-based combination treatments (ACTs) in malarious children. A one-compartment constant rate intravascular infusion model (CRIVIM), which employed the principles of constant rate intravenous infusion of drugs (CRIVID), was used to evaluate the kinetics of the increases in hematocrit after artesunate-amodiaquine (AA) or artemether-lumefantrine (AL) treatments in 112 malarious children. The model assumed baseline hematocrit was zero, a constant rate increase in hematocrit from baseline following treatment, and it involved semi-logarithm plots of the difference between hematocrit at plateau and that at earlier times, against the corresponding times. Hematocrit reached a plateau in a median time of 28 days after treatment started. Mean plateau hematocrit was 6.7% (95%CI 5.9.-7.5) and was similar in AA- and AL- treated children [6.8% (95%CI 6-7.7), n = 81 v 6.3% (95%CI 4.9-7.7), n = 31, P = 0.56]. Times to plateau were significantly shorter and plateau hematocrit significantly lower in non-anemic compared to anemic children. Overall, declines from semi-logarithmic plots were monoexponential with mean half-time of hematocrit of 2.5 days (95%CI 2.2-2.8). Half-times were similar in AA and AL-treated children [2.4 days (95%CI 2.1-2.8) v 2.7 days (95%CI 2-3.3), P = 0.46], and were significantly shorter in anemic compared to non-anemic children [2.1 days (95%CI 1.8-2.4, n = 57) v 2.9 days (95%CI 2.4-3.5, n = 55), P = 0.01). Mean anemia recovery time was 13.8 days (95%CI 11.9 – 15.7). Bland-Altman analysis of 7 or 8 multiples of anaemia half-time and anaemia recovery times showed narrow limit of agreement with insignificant biases (P = 0.17 or 0.68, respectively). Steady state parameters were independent of baseline parasitemias. The one-compartment CRIVIM permits evaluation of increases in hematocrit following ACTs and may be used in observational and clinical studies in uncomplicated falciparum malaria.

Plasmodium falciparum infection during dry season: IgG responses to Anopheles gambiae salivary gSG6-P1 peptide as sensitive biomarker for malaria risk in Northern Senegal

BackgroundThe Northern part of Senegal is characterized by a low and seasonal transmission of malaria. However, some Plasmodium falciparum infections and malaria clinical cases are reported during the dry season. This study aims to assess the relationship between IgG antibody (Ab) responses to gSG6-P1 mosquito salivary peptide and the prevalence of P. falciparum infection in children during the dry season in the Senegal River Valley. The positive association of the Ab response to gSG6-P1, as biomarker of human exposure to Anopheles vector bite, and P. falciparum infectious status (uninfected, infected-asymptomatic or infected-symptomatic) will allow considering this biomarker as a potential indicator of P. falciparum infection risk during the dry season.MethodsMicroscopic examination of thick blood smears was performed in 371 and 310 children at the start (January) and at the end (June) of the dry season, respectively, in order to assess the prevalence of P. falciparum infection. Collected sera were used to evaluate IgG response to gSG6-P1 by ELISA. Association between parasitological and clinical data (infected-asymptomatic or infected-symptomatic) and the anti-gSG6-P1 IgG levels were evaluated during this period.ResultsThe prevalence of P. falciparum infection was very low to moderate according to the studied period and was higher in January (23.5%) compared to June (3.5%). Specific IgG response was also different between uninfected children and asymptomatic carriers of the parasite. Children with P. falciparum infection in the dry season showed higher IgG Ab levels to gSG6-P1 than uninfected children.ConclusionsThe results strengthen the hypothesis that malaria transmission is maintained during the dry season in an area of low and seasonal transmission. The measurement of IgG responses to gSG6-P1 salivary peptide could be a pertinent indicator of human malaria reservoir or infection risk in this particular epidemiological context. This promising immunological marker could be useful for the evaluation of the risk of P. falciparum exposure observed during dry season and, by consequences, could be used for the survey of potential pre-elimination situation.

Statins Decrease Neuroinflammation and Prevent Cognitive Impairment after Cerebral Malaria

Cerebral malaria (CM) is the most severe manifestation of Plasmodium falciparum infection in children and non-immune adults. Previous work has documented a persistent cognitive impairment in children who survive an episode of CM that is mimicked in animal models of the disease. Potential therapeutic interventions for this complication have not been investigated, and are urgently needed. HMG-CoA reductase inhibitors (statins) are widely prescribed for cardiovascular diseases. In addition to their effects on the inhibition of cholesterol synthesis, statins have pleiotropic immunomodulatory activities. Here we tested if statins would prevent cognitive impairment in a murine model of cerebral malaria. Six days after infection with Plasmodium berghei ANKA (PbA) mice displayed clear signs of CM and were treated with chloroquine, or chloroquine and lovastatin. Intravital examination of pial vessels of infected animals demonstrated a decrease in functional capillary density and an increase in rolling and adhesion of leukocytes to inflamed endothelium that were reversed by treatment with lovastatin. In addition, oedema, ICAM-1, and CD11b mRNA levels were reduced in lovastatin-treated PbA-infected mice brains. Moreover, HMOX-1 mRNA levels are enhanced in lovastatin-treated healthy and infected brains. Oxidative stress and key inflammatory chemokines and cytokines were reduced to non-infected control levels in animals treated with lovastatin. Fifteen days post-infection cognitive dysfunction was detected by a battery of cognition tests in animals rescued from CM by chloroquine treatment. In contrast, it was absent in animals treated with lovastatin and chloroquine. The outcome was similar in experimental bacterial sepsis, suggesting that statins have neuroprotective effects in severe infectious syndromes in addition to CM. Statin treatment prevents neuroinflammation and blood brain barrier dysfunction in experimental CM and related conditions that are associated with cognitive sequelae, and may be a valuable adjuvant therapeutic agent for prevention of cognitive impairment in patients surviving an episode of CM.

A direct comparison of real time PCR on plasma and blood to detect Plasmodium falciparum infection in children

BackgroundEstimation of Plasmodium falciparum parasitaemia can vary with the method used and time of sampling. Quantitative real time PCR (qPCR) on whole blood or plasma samples has previously been shown to be more sensitive than thick film microscopy. However the efficiencies of each method have not been compared using samples obtained from infants less than one year old.MethodsA multiple of statistical approaches were used to compare the performance of qPCR on whole blood or plasma to detect the 18 S ribosomal gene of P. falciparum in 548 samples from children aged 2.5 or 24 months. Parasite prevalence in matched samples was compared using Mcnemar’s test and agreement of positive results quantified as Kappa scores. Parasite prevalences between different age groups were compared by Fisher’s test. Results from analyses by thick film microscopy were also available from children at 24 months and their correlation to each qPCR method examined by the Spearman’s test. Finally the association of P. falciparum infection with the incidence of multiple malaria episodes from contact to 24 months of age was evaluated using negative binomial regression.ResultsThese analyses showed that qPCR from whole blood detected approximately 3-fold more cases of infection than plasma qPCR. Both qPCR methods agreed well with each other although qPCR from plasma had a greater agreement with microscopy (96.85%) than did qPCR from blood (69.7%). At 24 months the prevalence of infection detected by all methods was associated with anaemia (p < 0.05).ConclusionsThe data presented here demonstrates that low levels of parasitaemia are better detected by qPCR using parasite DNA from whole blood than from plasma. However plasma samples provide a viable substitute when parasite smears are unavailable.

Changes in the levels of cytokines, chemokines and malaria-specific antibodies in response to Plasmodium falciparum infection in children living in sympatry in Mali

BackgroundThe Fulani are known to be less susceptible to Plasmodium falciparum malaria as reflected by lower parasitaemia and fewer clinical symptoms than other sympatric ethnic groups. So far most studies in these groups have been performed on adults, which is why little is known about these responses in children. This study was designed to provide more information on this gap.MethodsCirculating inflammatory factors and antibody levels in children from the Fulani and Dogon ethnic groups were measured. The inflammatory cytokines; interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12p70, tumor necrosis factor (TNF) and the chemokines; regulated on activation normal T cell expressed and secreted (RANTES), monokine-induced by IFN-gamma (MIG), monocyte chemotactic protein (MCP)-1 and IFN-gamma-inducible protein (IP)-10 were measured by cytometric bead arrays. The levels of interferon (IFN)-alpha, IFN-gamma and malaria-specific antibodies; immunoglobulin (Ig) G, IgM and IgG subclasses (IgG1-IgG4) were measured by ELISA.ResultsThe results revealed that the Fulani children had higher levels of all tested cytokines compared to the Dogon, in particular IFN-gamma, a cytokine known to be involved in parasite clearance. Out of all the tested chemokines, only MCP-1 was increased in the Fulani compared to the Dogon. When dividing the children into infected and uninfected individuals, infected Dogon had significantly lower levels of RANTES compared to their uninfected peers, and significantly higher levels of MIG and IP-10 as well as MCP-1, although the latter did not reach statistical significance. In contrast, such patterns were not seen in the infected Fulani children and their chemokine levels remained unchanged upon infection compared to uninfected counterparts. Furthermore, the Fulani also had higher titres of malaria-specific IgG and IgM as well as IgG1-3 subclasses compared to the Dogon.ConclusionsTaken together, this study demonstrates, in accordance with previous work, that Fulani children mount a stronger inflammatory and antibody response against P. falciparum parasites compared to the Dogon and that these differences are evident already at an early age. The inflammatory responses in the Fulani were not influenced by an active infection which could explain why less clinical symptoms are seen in this group.

Control Using Genetically Modified Insects Poses Problems for Regulators

Control Using Genetically Modified Insects Poses Problems for Regulators

Assessment of exposure to Plasmodium falciparum transmission in a low endemicity area by using multiplex fluorescent microsphere-based serological assays

BackgroundThe evaluation of malaria transmission intensity is a crucial indicator for estimating the burden of malarial disease. In this respect, entomological and parasitological methods present limitations, especially in low transmission areas. The present study used a sensitive multiplex assay to assess the exposure to Plasmodium falciparum infection in children living in an area of low endemicity. In three Senegalese villages, specific antibody (IgG) responses to 13 pre-erythrocytic P. falciparum peptides derived from Lsa1, Lsa3, Glurp, Salsa, Trap, Starp, Csp and Pf11.1 proteins were simultaneously evaluated before (June), at the peak (September) and after (December) the period of malaria transmission, in children aged from 1 to 8 years.ResultsCompared to other antigens, a high percentage of seropositivity and specific antibody levels were detected with Glurp, Salsa1, Lsa3NR2, and Lsa1J antigens. The seropositivity increased with age for all tested antigens. Specific IgG levels to Glurp, Salsa1, Lsa3NR2, and Lsa1J were significantly higher in P. falciparum infected children compared to non-infected and this increase is significantly correlated with parasite density.ConclusionThe multiplex assay represents a useful technology for a serological assessment of rapid variations in malaria transmission intensity, especially in a context of low parasite rates. The use of such combined serological markers (i.e. Glurp, Lsa1, Lsa3, and Salsa) could offer the opportunity to examine these variations over time, and to evaluate the efficacy of integrated malaria control strategies.