scholarly journals Significant differences in FcγRIIa, FcγRIIIa and FcγRIIIb genes polymorphism and anti-malarial IgG subclass pattern are associated with severe Plasmodium falciparum malaria in Saudi children

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Amre Nasr ◽  
Ahmad Aljada ◽  
Osama Hamid ◽  
Hatim A. Elsheikh ◽  
Emad Masuadi ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Severe Malaria ◽  
Malaria Infection ◽  
Pcr Amplification ◽  
Plasmodium Falciparum Malaria ◽  
Enzyme Linked Immunosorbent Assay ◽  
Igg Subclass ◽  
Elisa Technique ◽  
Cellular And Humoral Immunity ◽  
The Impact

Abstract Background The FcγRs genotypes have been reported to play a key role in the defence against malaria parasites through both cellular and humoral immunity. This study aimed to investigate the possible correlation between FcγR (IIa, IIIa, and IIIb) genes polymorphism and the clinical outcome for anti‐malarial antibody response of Plasmodium falciparum infection among Saudi children. Methods A total of 600 volunteers were enrolled in this study, including 200 malaria-free control (MFC) subjects, 218 patients with uncomplicated malaria (UM) and 182 patients with severe malaria (SM). The FcγR genotypes were analysed using PCR amplification methods, and measurements of immunoglobulin were determined using enzyme-linked immunosorbent assay (ELISA) technique. Results The data revealed that the FcγRIIa-R/R131 showed a statistically significant association with SM patients when compared to UM patients. Furthermore, higher levels of IgG1, IgG2, and IgG4 were associated with the FcγRIIa-H/H131 genotype among UM patients. Although the FcγRIIa-F/V176 genotype was not associated with UM, it showed a significant association with severe malaria. Interestingly, the FcγRIIIa-V/V176 genotype offered protection against SM. Moreover, SM patients carrying the FcγRIIIa-F/F genotype showed higher levels of AMA-1-specific IgG2 and IgG4 antibodies. The FcγRIIIb-NA1/NA1 and FcγRIIIb-NA2/NA2 genotypes did not show significant differences between the UM and the MFC groups. However, the genotype FcγRIIIb-NA2/NA2 was statistically significantly associated with SM patients. Conclusions The data presented in this study suggest that the influence of the FcγRIIa-R/R131, FcγRIIIa-F/F176 and FcγRIIIb-NA2/NA2 genotypes are statistically significantly associated with SM patients. However, the FcγRIIa-H/H13 and FcγRIIIa-V/V176 genotypes have demonstrated a protective effect against SM when compared to UM patients. The impact of the FcyR (IIa, IIIa and IIIb) gene variants and anti-malaria IgG subclasses play an important role in susceptibility to malaria infection and disease outcome in Saudi children.

Significant Differences in FcγRIIa, FcγRIIa and FcγRIIIb Genes Polymorphism and Anti-malarial IgG Subclass Pattern are Associated with Severe Malaria in Saudi Children

2021 ◽  
Author(s):  
Amre Nasr ◽  
Ahmad Aljada ◽  
Osama Hamid ◽  
Hatim A. Elsheikh ◽  
Emad Masuadi ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Clinical Outcome ◽  
Severe Malaria ◽  
Malaria Infection ◽  
Pcr Amplification ◽  
Igg Subclass ◽  
Gene Variants ◽  
Disease Outcomes ◽  
Cellular And Humoral Immunity ◽  
Increased Susceptibility

Abstract Background: The FcyRs genotypes have been reported to play a key role in the defence against malaria parasites through both cellular and humoral immunity. This study aimed to investigate the possible correlation between FcγR (IIa, IIIa, and IIIb) genes polymorphism and the clinical outcome for anti‐malarial antibody response of Plasmodium falciparum infection among Saudi children. Material and methods: A 600 volunteers have been enrolled in this study, including 200 malaria-free control (MFC) subjects, 218 patients with uncomplicated malaria (UM) and 182 patients with severe malaria (SM). The FcγR genotypes was analysed using PCR amplification methods, and measurement of immunoglobulins were determine using ELISA. Results: The data revealed the FcγRIIa-R/R131 showed a statistically association with the increased susceptibility to SM when compared to UM patients. Furthermore, higher levels of IgG1, IgG2, and IgG4 were associated with the FcγRIIa-H/H131 genotypes among UM patients. Although the FcγRIIa-F/V176 genotype was not associated with UM, it showed a significant association with severe malaria. Interestingly, the FcγRIIa-V/V176 genotype was This study aimed to associated with protection against SM. Moreover, severe malaria patients carrying the FcγRIIa-F/F genotype showed higher levels of AMA-1-specific IgG2 and IgG4 antibodies. The FcγRIIIb NA1/NA1 and FcγRIIIb NA2/NA2 genotypes did not show significant differences between UM and the MFC. However, the genotype FcγRIIIb-NA2/NA2 was statistically associated with severe malaria. Conclusions: The data presented in this study strongly suggest the possible impact of FcyR (IIa, RIIIa and RIIIb) gene variants and anti-malaria IgG subclasses play a role in susceptibility to malaria infection and disease outcomes in Saudi children.

scholarly journals Maternally-derived Antibodies to Schizont Egress Antigen-1 and Protection of Infants From Severe Malaria

2018 ◽  
Vol 68 (10) ◽  
pp. 1718-1724 ◽  
Author(s):  
Jonathan D Kurtis ◽  
Dipak K Raj ◽  
Ian C Michelow ◽  
Sangshin Park ◽  
Christina E Nixon ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Cord Blood ◽  
Severe Malaria ◽  
Plasmodium Falciparum Malaria ◽  
First Year ◽  
Relative Resistance ◽  
Young Infants ◽  
Protective Antibodies ◽  
First Year Of Life ◽  
The Impact

AbstractBackgroundIn holoendemic areas, children suffer the most from Plasmodium falciparum malaria, yet newborns and young infants express a relative resistance to both infection and severe malarial disease (SM). This relative resistance has been ascribed to maternally-derived anti-parasite immunoglobulin G; however, the targets of these protective antibodies remain elusive.MethodsWe enrolled 647 newborns at birth from a malaria-holoendemic region of Tanzania. We collected cord blood, measured antibodies to Plasmodium falciparum Schizont Egress Antigen-1 (PfSEA-1), and related these antibodies to the risk of severe malaria in the first year of life. In addition, we vaccinated female mice with PbSEA-1, mated them, and challenged their pups with P. berghei ANKA parasites to assess the impact of maternal PbSEA-1 vaccination on newborns’ resistance to malaria.ResultsChildren with high cord-blood anti–PfSEA-1 antibody levels had 51.4% fewer cases of SM compared to individuals with lower anti–PfSEA-1 levels over 12 months of follow-up (P = .03). In 3 trials, pups born to PbSEA-1–vaccinated dams had significantly lower parasitemia and longer survival following a P. berghei challenge compared to pups born to control dams.ConclusionsWe demonstrate that maternally-derived, cord-blood anti–PfSEA-1 antibodies predict decreased risk of SM in infants and vaccination of mice with PbSEA-1 prior to pregnancy protects their offspring from lethal P. berghei challenge. These results identify, for the first time, a parasite-specific target of maternal antibodies that protect infants from SM and suggest that vaccination of pregnant women with PfSEA-1 may afford a survival advantage to their offspring.

scholarly journals Predictors of treatment failures of plasmodium falciparum malaria in Vietnam: a 4-year single‐centre retrospective study

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Minh Cuong Duong ◽  
Oanh Kieu Nguyet Pham ◽  
Phong Thanh Nguyen ◽  
Van Vinh Chau Nguyen ◽  
Phu Hoan Nguyen
Keyword(s):  
Plasmodium Falciparum ◽  
Treatment Failure ◽  
Severe Malaria ◽  
Falciparum Malaria ◽  
Control Strategies ◽  
Artemisinin Resistance ◽  
Plasmodium Falciparum Malaria ◽  
Molecular Technique ◽  
Drug Resistant ◽  
Public Health Burden

Abstract Background Drug-resistant falciparum malaria is an increasing public health burden. This study examined the magnitude of Plasmodium falciparum infection and the patterns and predictors of treatment failure in Vietnam. Methods Medical records of all 443 patients with malaria infection admitted to the Hospital for Tropical Diseases between January 2015 and December 2018 were used to extract information on demographics, risk factors, symptoms, laboratory tests, treatment, and outcome. Results More than half (59.8%, 265/443, CI 55.1–64.4%) of patients acquired Plasmodium falciparum infection of whom 21.9% (58/265, CI 17.1–27.4%) had severe malaria, while 7.2% (19/265, CI 4.6–10.9%) and 19.2% (51/265, CI 14.7–24.5%) developed early treatment failure (ETF) and late treatment failure (LTF) respectively. Among 58 patients with severe malaria, 14 (24.1%) acquired infection in regions where artemisinin resistance has been documented including Binh Phuoc (11 patients), Dak Nong (2 patients) and Gia Lai (1 patient). Under treatment with intravenous artesunate, the median (IQR) parasite half-life of 11 patients coming from Binh Phuoc was 3 h (2.3 to 8.3 h), two patients coming from Dak Nong was 2.8 and 5.7 h, and a patient coming from Gia Lai was 6.5 h. Most patients (98.5%, 261/265) recovered completely. Four patients with severe malaria died. Severe malaria was statistically associated with receiving treatment at previous hospitals (P < 0.001), hepatomegaly (P < 0.001) and number of inpatient days (P < 0.001). Having severe malaria was a predictor of ETF (AOR 6.96, CI 2.55–19.02, P < 0.001). No predictor of LTF was identified. Conclusions Plasmodium falciparum remains the prevalent malaria parasite. Despite low mortality rate, severe malaria is not rare and is a significant predictor of ETF. To reduce the risk for ETF, studies are needed to examine the effectiveness of combination therapy including parenteral artesunate and a parenteral partner drug for severe malaria. The study alerts the possibility of drug-resistant malaria in Africa and other areas in Vietnam, which are known as non-endemic areas of anti-malarial drug resistance. A more comprehensive study using molecular technique in these regions is required to completely understand the magnitude of drug-resistant malaria and to design appropriate control strategies.

scholarly journals The changing risk of Plasmodium falciparum malaria infection in Africa: 2000–10: a spatial and temporal analysis of transmission intensity

The Lancet ◽  
2014 ◽  
Vol 383 (9930) ◽  
pp. 1739-1747 ◽  
Author(s):  
Abdisalan M Noor ◽  
Damaris K Kinyoki ◽  
Clara W Mundia ◽  
Caroline W Kabaria ◽  
Jonesmus W Mutua ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Falciparum Malaria ◽  
Malaria Infection ◽  
Plasmodium Falciparum Malaria ◽  
Temporal Analysis ◽  
Transmission Intensity ◽  
Spatial And Temporal Analysis

Halofantrine efficacy in non-immune children with imported acute Plasmodium falciparum malaria Infection

2003 ◽  
Vol 163 (1) ◽  
pp. 22-24 ◽  
Author(s):  
Isabelle Hau ◽  
Sophie Seringe ◽  
Said Aberrane ◽  
France De La Rocque ◽  
Christophe Delacourt ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Falciparum Malaria ◽  
Malaria Infection ◽  
Plasmodium Falciparum Malaria

scholarly journals The Immunological Plasmodium falciparum Malaria Characteristics of Children in Tajikistan Republic

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Nighina M. Khodzhaeva ◽  
Alla M. Baranova ◽  
Anatoly K. Tokmalaev
Keyword(s):  
Plasmodium Falciparum ◽  
Humoral Immunity ◽  
Immunological Response ◽  
Epidemiological Data ◽  
Plasmodium Falciparum Malaria ◽  
Pathological Process ◽  
Adverse Outcomes ◽  
School Age Children ◽  
National Programme ◽  
Cellular And Humoral Immunity

The epidemiological situation in Tajikistan Republic deteriorated in the 1990s, when an influx of refugees from Afghanistan resulted in mass importation of Plasmodium vivax and Plasmodium falciparum malaria to Khatlon region. The National Programme of Malaria Control was successful and malaria transmission was interrupted in 2009. Background. The aim of this study was to investigate the mechanisms of immunological response in Tajik children with tropical Plasmodium falciparum malaria. Materials and Methods. We examined 124 patients with P. falciparum malaria at the age of 6 months up to 14 years that were hospitalized in Clinical Infectious Diseases Hospital in Dushanbe city and in Regional hospital of Khatlon region in the period 2000-2007. In most cases, they were school-age children (56%). The peak incidence was recorded in July-October. Verification of the diagnosis was based on clinical, epidemiological data, and the results of blood microscopy. In all patients, along with the standard, clinical, and laboratory tests, a number of indicators of the immune status were performed that include the T-immunity, the content of serum immunoglobulins of three main classes, the level of circulating immune complexes (CIC), C3 complement, and the concentration of key serum cytokines that have been studied in the dynamics of infectious process. Finding. The study of cellular and humoral immunity in patients with Plasmodium falciparum malaria is an obvious additional criterion in assessing the severity of infection. The imbalance of cytokine profile is an important pathogenic factor in the development of severe and recurrent forms of the disease, since the formation of a defective immune response to parasitic antigens contributes to adverse outcomes. Conclusions. Plasmodium falciparum malaria was characterized by depression of cellular and humoral immunity, the degree of which depended on the severity of the pathological process.

scholarly journals Multidose Priming and Delayed Boosting Improve PfSPZ Vaccine Efficacy against Heterologous P. falciparum Controlled Human Malaria Infection

2020 ◽  
Author(s):  
Kirsten E Lyke ◽  
Alexandra Singer ◽  
Andrea A Berry ◽  
Sharina Reyes ◽  
Sumana Chakravarty ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Vaccine Efficacy ◽  
Malaria Infection ◽  
Human Malaria ◽  
Group 4 ◽  
Controlled Human Malaria Infection ◽  
Group 3 ◽  
Group 2 ◽  
The Impact ◽  
Group 1

Abstract Background A live-attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) vaccine (PfSPZ Vaccine) has shown up to 100% protection against controlled human malaria infection (CHMI) using homologous parasites (same Pf strain as in the vaccine). Using a more stringent CHMI, with heterologous parasites (different Pf strain), we assessed the impact of higher PfSPZ doses, a novel multi-dose prime regimen, and a delayed vaccine boost upon vaccine efficacy. Methods Four groups of 15 healthy, malaria-naïve adults were immunized. Group (Grp) 1 received five doses of 4.5x10 5 PfSPZ (days 1, 3, 5, 7; week 16). Grps 2, 3 and 4 received three doses (weeks 0, 8, 16) with Gp 2 receiving 9.0×10 5/dose, Grp 3 receiving 18.0×10 5/dose, and Grp 4 receiving 27.0×10 5 for dose 1 and 9.0×10 5 for doses 2 and 3. VE was assessed by heterologous CHMI after 12 or 24 weeks. Volunteers not protected at 12 weeks were boosted prior to repeat CHMI at 24 weeks. Results At 12-week CHMI, 6/15 (40%) Group 1 (P=0.04), 3/15 (20%) Group 2 vs. 0/8 controls remained aparasitemic. At 24-week CHMI, 3/13 (23%) Group 3, 3/14 (21%) Group 4 vs. 0/8 controls remained aparasitemic (Groups 2-4, VE not significant). Post-boost, 9/14 (64%) vs. 0/8 controls remained aparasitemic (3/6 Group 1, P=0.025; 6/8 Group 2, P=0.002). Conclusions Four stacked, priming injections (multi-dose priming) showed 40% VE against heterologous CHMI, while dose escalation of PfSPZ using single dose priming was not significantly protective. Boosting unprotected subjects improved VE at 24 weeks to 64%.

scholarly journals PO 8590 COMPARATIVE ANALYSIS OF IGG RESPONSES TO RECOMBINANT Qβ PHAGE DISPLAYED MSP3 AND UBO5 IN DUAL HIV/MALARIA-CO-INFECTED ADULTS

2019 ◽  
Vol 4 (Suppl 3) ◽  
pp. A59.2-A59
Author(s):  
Godwin Nchinda ◽  
Abel Lissom ◽  
Herve Ouambo ◽  
Malachy I Okeke ◽  
Thibeau F Tchouangueu ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Malaria Infection ◽  
Study Participant ◽  
Transmission Intensity ◽  
Igg Subclass ◽  
Double Negative ◽  
Igg Antibody ◽  
Low Transmission ◽  
Malaria Transmission Intensity ◽  
The Impact

BackgroundImmunoglobulin G (IgG)-specific responses against Plasmodium falciparum merozoite antigens such as the merozoite surface protein 3 (MSP3) and UBO5 are known to play critical roles in parasitaemia control and protection from symptomatic illness. However, when there is intense perennial malaria transmission coupled with concurrent infection with the human immunodeficiency virus type 1 (HIV), knowledge of IgG antibody response profiles is limited.In this study we assessed the impact of dual HIV/malaria infections on IgG subclass responses to MSP3 (QβMSP3) and UBO5 (QβUB05) in individuals living in two areas of Cameroon differing in malaria transmission intensity.MethodsIgG and IgG subclass responses specific to either MSP3 or UBO5 were determined in plasma from study participant by ELISA. To improve reactivity with their respective antibodies the antigens were displayed upon the surface of the RNA coliphage Qβ.ResultsWe observed differences in antigen-specific IgG and IgG subclass responses which were dependent upon the antigen type, malaria transmission intensity, HIV infection, malaria infection and dual HIV/malaria infections. Individuals living in areas with high malaria transmission, had irrespective of HIV or malaria status significantly higher IgG responses to both antigens (p=0.0001 for QβMSP3, p=0.0001 for QβUB05) than their counterpart from areas with low transmission. When dual HIV/malaria infection is considered, significantly higher QβMSP3 specific IgG1 (p=0.0001) and IgG3 (p=0.04) responses in double-negative individuals was associated with protection against malaria in areas with low transmission. Superior QβUBO5 specific IgG1 responses (p=0.0001) in double-negative individuals were associated with protection in areas with high transmission in contrast to significantly higher IgG3 responses to QβUBO5 (p=0.0001) which were more relevant to protection in areas with low malaria transmission in the same population.ConclusionThus, understanding immune responses to QβUBO5 and QβMSP3 could facilitate the development of immunotherapeutic strategies suitable for areas differing in malaria transmission intensity.

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