Population genetics of Plasmodium falciparum within a malaria hyperendemic area

Parasitology ◽  
1991 ◽  
Vol 103 (1) ◽  
pp. 7-16 ◽  
Author(s):  
D. J. Conway ◽  
J. S. McBride
Keyword(s):  
Plasmodium Falciparum ◽  
The Gambia ◽  
Surface Proteins ◽  
Urban Region ◽  
Probable Number ◽  
Hyperendemic Area ◽  
Significant Difference ◽  
Genotype Diversity ◽  
Random Assortment ◽  
Exported Protein

Serotyping with monoclonal antibodies was used to estimate the number and frequencies of allelic variants of two merozoite surface proteins, MSP1 and MSP2, and an exported protein Exp-1, in a sample of 344 clinical isolates of Plasmodium falciparum from an urban region of The Gambia. Represented among the isolates were 36, 8 and 2 alleles of the MSP1, MSP2 and Exp-1 loci respectively. Relative frequencies of these alleles remained stable in the parasite population over the 2 years of the study. A computer program was used to calculate from the frequencies of individual alleles at the three loci, the probable number of different genotypes in samples from the population, assuming random assortment among the loci. No significant difference was found between the expected and the observed genotype diversity. It is concluded that recombination among unlinked loci is a common consequence of sexual reproduction of P. falciparum in The Gambia. Slightly lower genotype diversity was observed in each of two villages, which may be a consequence of smaller population size compared with the urban region.

scholarly journals Comparison of leucocyte profiles between healthy children and those with asymptomatic and symptomatic Plasmodium falciparum infections

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Diana Ahu Prah ◽  
Linda Eva Amoah ◽  
Matthew P. Gibbins ◽  
Yaw Bediako ◽  
Aubrey J. Cunnington ◽  
...  
Keyword(s):  
T Cells ◽  
Plasmodium Falciparum ◽  
Peripheral Blood ◽  
Parasite Load ◽  
Study Groups ◽  
Healthy Children ◽  
Peripheral Cell ◽  
Peripheral Blood Leucocyte ◽  
Cell Counts ◽  
Significant Difference

Abstract Background The immune mechanisms that determine whether a Plasmodium falciparum infection would be symptomatic or asymptomatic are not fully understood. Several studies have been carried out to characterize the associations between disease outcomes and leucocyte numbers. However, the majority of these studies have been conducted in adults with acute uncomplicated malaria, despite children being the most vulnerable group. Methods Peripheral blood leucocyte subpopulations were characterized in children with acute uncomplicated (symptomatic; n = 25) or asymptomatic (n = 67) P. falciparum malaria, as well as malaria-free (uninfected) children (n = 16) from Obom, a sub-district of Accra, Ghana. Leucocyte subpopulations were enumerated by flow cytometry and correlated with two measures of parasite load: (a) plasma levels of P. falciparum histidine-rich protein 2 (PfHRP2) as a proxy for parasite biomass and (b) peripheral blood parasite densities determined by microscopy. Results In children with symptomatic P. falciparum infections, the proportions and absolute cell counts of total (CD3 +) T cells, CD4 + T cells, CD8 + T cells, CD19 + B cells and CD11c + dendritic cells (DCs) were significantly lower as compared to asymptomatic P. falciparum-infected and uninfected children. Notably, CD15 + neutrophil proportions and cell counts were significantly increased in symptomatic children. There was no significant difference in the proportions and absolute counts of CD14 + monocytes amongst the three study groups. As expected, measures of parasite load were significantly higher in symptomatic cases. Remarkably, PfHRP2 levels and parasite densities negatively correlated with both the proportions and absolute numbers of peripheral leucocyte subsets: CD3 + T, CD4 + T, CD8 + T, CD19 + B, CD56 + NK, γδ + T and CD11c + cells. In contrast, both PfHRP2 levels and parasite densities positively correlated with the proportions and absolute numbers of CD15 + cells. Conclusions Symptomatic P. falciparum infection is correlated with an increase in the levels of peripheral blood neutrophils, indicating a role for this cell type in disease pathogenesis. Parasite load is a key determinant of peripheral cell numbers during malaria infections.

scholarly journals Interactions between Merozoite Surface Proteins 1, 6, and 7 of the Malaria Parasite Plasmodium falciparum

2006 ◽  
Vol 281 (42) ◽  
pp. 31517-31527
Author(s):  
Christian W. Kauth ◽  
Ute Woehlbier ◽  
Michaela Kern ◽  
Zeleke Mekonnen ◽  
Rolf Lutz ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Parasite ◽  
Surface Proteins ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

scholarly journals Erratum: CORRIGENDUM: Analyses of Interactions Between Heparin and the Apical Surface Proteins of Plasmodium falciparum

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Kyousuke Kobayashi ◽  
Ryo Takano ◽  
Hitoshi Takemae ◽  
Tatsuki Sugi ◽  
Akiko Ishiwa ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Surface Proteins ◽  
Apical Surface

scholarly journals 1241. PfSPZ Vaccine Administered by Direct Venous Inoculation to Prevent Plasmodium falciparum Malaria is as Safe as Normal Saline – a Meta-analysis of 12 Randomized Controlled Clinical Trials

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S639-S640
Author(s):  
L W Preston Church
Keyword(s):  
Plasmodium Falciparum ◽  
Random Effects ◽  
Normal Saline ◽  
Meta Analysis ◽  
Laboratory Data ◽  
Plasmodium Falciparum Malaria ◽  
Sub Saharan Africa ◽  
Sensitivity Analyses ◽  
Double Blind ◽  
Significant Difference

Abstract Background Sanaria’s PfSPZ Vaccine prevents Plasmodium falciparum (Pf) infection transmitted in the field and by controlled human malaria infection. Safety of PfSPZ Vaccine has been demonstrated in 12 randomized, double-blind, placebo-controlled trials (RCT) varying in regimen from 3 to 5 doses over 4 to 20 weeks and in size from 18 to 332 subjects in adults in the US and EU and 5-month to 65-year-olds in 5 countries in sub-Saharan Africa. This study was conducted to analyze solicited adverse event (AE) and laboratory data by random effects meta-analysis. Methods PfSPZ Vaccine is composed of radiation-attenuated, aseptic, purified, cryopreserved Pf sporozoites (SPZ) administered by direct venous inoculation (DVI). Normal saline (NS) is always the placebo. Data from all completed RCTs were included as either age > 18 years (n=598) or age 5 months to 17 years (n=641). Any subject receiving at least one dose was included. A random-effects model was used to study vaccine safety and I2 to evaluate heterogeneity. Analysis was performed for any systemic solicited AE and for the most frequently observed AEs and laboratory abnormalities. Sensitivity analyses were performed by removal of trials with zero events to evaluate potential bias. Results When examined individually, only 1 trial had a significant difference between PfSPZ Vaccine and NS for any AE (myalgias in adults). In the adult meta-analysis, there was no difference in the random effects risk ratios (RR) for having any vaccine-related AEs (1.40, 95% confidence interval (CI) 0.88-2.28), or for fever (0.75, 0.24-2.35), headache (1.23, 0.74-2.02), fatigue (0.72, 0.19-2.54), or myalgia (1.09, 0.26-4.68). In the pediatric meta-analysis there was no difference between the RR for PfSPZ Vaccine and NS for any AE (0.84, 0.59-1.18) or for fever (1.09, 0.44-2.69). No significant differences in the most common grade 2 or higher laboratory abnormalities – declines in hemoglobin, neutrophil or platelet count – were detected. Sensitivity analysis did not change the results. Conclusion There was no difference in risk for AEs or lab abnormalities between PfSPZ Vaccine and NS, indicating that PfSPZ Vaccine administered by DVI was extremely safe and well tolerated in 5-month- to 65-year-olds. Disclosures LW Preston Church, MD, FIDSA, Sanaria Inc. (Employee)

scholarly journals Epidemiological aspects of toxoplasmosis in schoolchildren residing in localities with urban or rural characteristics within the city of Rio de Janeiro, Brazil

1987 ◽  
Vol 82 (4) ◽  
pp. 475-482 ◽  
Author(s):  
Wilson J. S. Souza ◽  
Sergio G. Coutinho ◽  
Carlos Wilson G. Lopes ◽  
Carlos S. dos Santos ◽  
Nadia M. Neves ◽  
...  
Keyword(s):  
Rio De Janeiro ◽  
Junior High ◽  
Urban Region ◽  
Risk Of Infection ◽  
Urban Regions ◽  
Significant Difference ◽  
The City ◽  
Undercooked Meat

Immunofluorescence tests (IF) for toxoplasmosis were performed on a total of 608 schoolchildren in elementary and junior high grades. 166 being in the Bonsucesso district (an urban region of Rio de Janeiro) and 442 children from locations within the lowlands of Jacarepaguá (with rural characteristics). All the IF-IgM were nonreactive, whilst 416 schoolchildren (68.4%) were IF-IgG serum-reactive ([greater than or equal to] 1:16). The percentages of serum-reactives in Jacarepaguá were significantly higher than in Bonsucesso, both as regards the total number of schoolchildren (p < 0.001), as also when subdivided according to the age-grades from six to eight years (p < 0.001) or from twelve to fourteen (p < 0.05). Both in Jacarepaguá and in Bonsucesso, the prevalence of reactions in the 12 to 14 year age-grade was significantly greater than in the 6 to 8 year age-grade (p < 0.001 in both cases). Expressively larger prevalences of serum reactions were found in Jacarepaguá among schoolchildren who preferred eating raw or undercooked meat, as well as among those having cats as pets; this occurred equally in the 6 to 8 year and in the 12 to 14 year age-grades. In Bonsucesso, the only significant difference was in the 6 to 8 year age-grades that had cats as pets. Thus, it has been verified that the risk of infection is greater and more precocious in localities with rural characteristics than in urban regions.

scholarly journals How to induce protective humoral immunity against Plasmodium falciparum circumsporozoite protein

2022 ◽  
Vol 219 (2) ◽  
Author(s):  
Ilka Wahl ◽  
Hedda Wardemann
Keyword(s):  
Plasmodium Falciparum ◽  
Immune Responses ◽  
Vaccine Efficacy ◽  
Circumsporozoite Protein ◽  
Surface Proteins ◽  
Humoral Immune ◽  
Cell Responses ◽  
Humoral Immune Responses ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

The induction of protective humoral immune responses against sporozoite surface proteins of the human parasite Plasmodium falciparum (Pf) is a prime goal in the development of a preerythrocytic malaria vaccine. The most promising antibody target is circumsporozoite protein (CSP). Although PfCSP induces strong humoral immune responses upon vaccination, vaccine efficacy is overall limited and not durable. Here, we review recent efforts to gain a better molecular and cellular understanding of anti-PfCSP B cell responses in humans and discuss ways to overcome limitations in the induction of stable titers of high-affinity antibodies that might help to increase vaccine efficacy and promote long-lived protection.

scholarly journals The Effect of L2 Exposure Environment on Nnests’ Teaching Skills and Beliefs about EFL Learning Beyond the Class

2017 ◽  
Author(s):  
Arab World English Journal ◽  
Susilo Susilo ◽  
Bibit Suhatmady ◽  
Dyah Sunggingwati ◽  
Hany Farisa ◽  
...  
Keyword(s):  
Second Language ◽  
Foreign Language ◽  
T Test ◽  
Urban Region ◽  
Teaching Skills ◽  
Rural Region ◽  
Significant Difference ◽  
English Speaking ◽  
Native English Speaking Teachers ◽  
Efl Learning

The study aims at investigating the effect of second language (L2) exposure environment on NNESTs’ teaching skills and beliefs about EFL learning beyond the classroom. This is a survey for non-native English speaking teachers (NNESTs) of Indonesian Senior High Schools ( or in Indonesian terms ‘SMA’) from different L2 environments, namely: 1) urban-region exposure environment schools (n=40), and 2) rural-region exposure environment schools (n=40). There were two instruments used in the present study, i.e. 1) observation scaling checklist, and 2) questionnaire. The observation scaling checklist was used for assessing the respondents’ performance when they were teaching in class. Meanwhile, the questionnaire using a four-point Likert scale was used to elicit data. The researchers used a series of independent t-test to analyze the data. The result reveals that: 1) there is a significant difference between teaching skills of NNESTs from the urban region schools and those of NNESTs from rural region schools, t (78)= 19.499, p=0.000; and 2) there is a significant difference between beliefs about English as a foreign language (EFL learning beyond the classroom of the NNESTs from urban region schools and those of NNESTs from rural region schools, t (78)= - 4.925, p=0.000

scholarly journals Molecular characterization of Plasmodium falciparum PHISTb proteins as potential targets of naturally-acquired immunity against malaria

2020 ◽  
Vol 5 ◽  
pp. 136
Author(s):  
Tony I. Isebe ◽  
Joel L. Bargul ◽  
Bonface M. Gichuki ◽  
James M. Njunge ◽  
James Tuju ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
The Gambia ◽  
Antibody Responses ◽  
Transmission Intensity ◽  
Parasite Development ◽  
Natural Immunity ◽  
Malaria Transmission Intensity ◽  
Transmission Region ◽  
Antibody Levels

Background: Plasmodium falciparum causes the deadliest form of malaria in humans. Upon infection, the host’s infected red blood cells (iRBCs) are remodelled by exported parasite proteins in order to provide a niche for parasite development and maturation. Methods: Here we analysed the role of three PHISTb proteins Pf3D7_0532400, Pf3D7_1401600, and Pf3D7_1102500 by expressing recombinant proteins and evaluated antibody responses against these proteins using immune sera from malaria-exposed individuals from Kenya and The Gambia in Africa. Results: Our findings show that children and adults from malaria-endemic regions recognized the three PHISTb proteins. Responses against the PHISTb proteins varied with malaria transmission intensity in three different geographical sites in Kenya (Siaya and Takaungu) and The Gambia (Sukuta). Antibody responses against PHISTb antigens Pf3D7_1102500 and Pf3D7_1401600 were higher in Sukuta, a low transmission region in the Gambia, as compared to Siaya, a high transmission region in western Kenya, unlike Pf3D7_0532400. Anti-PHIST responses show a negative correlation between antibody levels and malaria transmission intensity for two PHIST antigens, Pf3D7_1102500 and Pf3D7_1401600. However, we report a correlation in antibody responses between schizont extract and Pf3D7_0532400 (p=0.00582). Acquisition of anti-PHIST antibodies was correlated with exposure to malaria for PHISTb protein Pf3D7_0532400 (p=0.009) but not the other PHIST antigens Pf3D7_1102500 and Pf3D7_1401600 (p=0.507 and p=0.15, respectively, CI=95%). Children aged below 2 years had the lowest antibody levels, but the responses do not correlate with age differences. Conclusions: Collectively, these findings provide evidence of natural immunity against PHISTb antigens that varies with level of malaria exposure and underscore potential for these parasite antigens as possible serological markers to P. falciparum infection aimed at contributing to malaria control through vaccine development.

scholarly journals Influence of Cytochrome P450 (CYP) 2C8 Polymorphisms on the Efficacy and Tolerability of Artesunate-Amodiaquine Treatment of Uncomplicated Plasmodium Falciparum Malaria in Zanzibar

2020 ◽  
Author(s):  
Leyre Pernaute-Lau ◽  
Ulrika Morris ◽  
Mwinyi Msellem ◽  
Andreas Mårtensson ◽  
Anders Björkman ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Cytochrome P450 ◽  
Randomized Clinical Trials ◽  
Plasmodium Falciparum Malaria ◽  
Serious Adverse Events ◽  
Cytochrome P450 2C8 ◽  
Significant Difference ◽  
Minor Alleles ◽  
Long Acting ◽  
Parasitological Response

Abstract Background The antimalarial drug amodiaquine, a commonly used long acting partner drug in artemisinin-based combination therapy, is metabolized to active desethyl-amodiaquine (DEAQ) by cytochrome P450 2C8 (CYP2C8). The CYP2C8 gene carries several polymorphisms including the more frequent minor alleles CYP2C8*2 and CYP2C8*3. These minor alleles have been associated with decreased enzymatic activity, slowing the amodiaquine biotransformation towards DEAQ. This study aimed to assess the influence of CYP2C8 polymorphisms on the efficacy and tolerability of artesunate-amodiaquine treatment for uncomplicated Plasmodium falciparum malaria in Zanzibar.Methods We analysed data from 618 children <5 years with uncomplicated P. falciparum malaria enrolled in two randomized clinical trials comparing artesunate-amodiaquine and artemether-lumefantrine in 2002-2005 in Zanzibar. CYP2C8*2 and CYP2C8*3 genotypes were determined by PCR-restriction fragment length polymorphism and assessed in relation to clinical data on treatment outcome and tolerance. Results The allele frequencies of CYP2C8*2 and CYP2C8*3 were 17.5% (95% CI 15.4-19.7%) and 2.7% (95% CI 1.8-3.7%), respectively. There was no significant difference in the proportion of subjects carrying either CYP2C8*2 or CYP2C8*3 alleles amongst those with reinfections (44.1 %; 95% CI 33.8-54.8) or those with recrudescent infections (48.3%; 95% CI 29.4-67.5), compared to those with adequate clinical and parasitological response (36.7 %; 95% CI 30.0-43.9) (P = 0.25 and P = 0.31, respectively). However, patients carrying either the CYP2C8*2 or CYP2C8*3 allele were significantly associated with increased occurrence of non-serious adverse events compare with CYP2C8 *1/*1 wildtype homozygotes (44.9%; 95% CI 36.1-54.0 versus 28.1%; 95% CI 21.9-35.0, respectively; P = 0.003). Conclusions CYP2C8 genotypes did not influence treatment efficacy directly, but the tolerability to ASAQ may be reduced in subjects carrying the CYP2C8*3 and CYP2C8*2 alleles. The importance of this non-negligible association with regards to amodiaquine-based malaria chemotherapy warrants further investigation.

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