RESUMO
Submicroscopic Plasmodium infections in pregnancy are common in endemic areas, and it is important to understand the impact of these low-level infections. Asymptomatic, chronic infections are advantageous for parasite persistence, particularly in areas where the optimal eco-epidemiological conditions for parasite transmission fluctuate. In chronic infections, the persistence of the antigenic stimulus changes the expression of immune mediators and promotes constant immune regulation, including increases in regulatory T cell populations. These alterations of the immune system could compromise the response to routine vaccination. This study aimed to evaluate the effect of submicroscopic plasmodial infection with P. falciparum and P. vivax during pregnancy on the immune response to the tetanus toxoid vaccine in Colombian women. Expression of different cytokines and mediators of immune regulation and levels of anti-tetanus toxoid (TT) immunoglobulin (Ig)G were quantified in pregnant women with and without submicroscopic plasmodial infection. The anti-TT IgG levels were significantly lower in the infected group compared with the uninfected group. The expression of interferon (IFN)-γ, tumour necrosis factor (TNF) and forkhead box protein 3 (FoxP3) was significantly higher in the infected group, while the expression of cytotoxic T lymphocyte antigen 4 (CTLA-4) and transforming growth factor (TGF)-ß was lower in the group of infected. In conclusion, submicroscopic Plasmodium infection altered the development of the immune response to the TT vaccine in Colombian pregnant women. The impact of Plasmodium infections on the immune regulatory pathways warrants further exploration.
Assuntos
Anticorpos Antibacterianos/sangue , Malária/imunologia , Plasmodium falciparum/fisiologia , Plasmodium vivax/fisiologia , Complicações Infecciosas na Gravidez/imunologia , Linfócitos T Reguladores/imunologia , Toxoide Tetânico/imunologia , Adolescente , Adulto , Doença Crônica , Colômbia , Citocinas/metabolismo , Feminino , Humanos , Imunidade Heteróloga , Gravidez , Vacinação , Adulto JovemRESUMO
Pregnancy-associated malaria (PAM) poses a threat to both the mother and fetus, increasing the risk of severe maternal anemia, fetal growth restriction and low birth weight infants. Two vaccines are currently in development to protect women from Plasmodium falciparum in pregnancy. Both vaccine constructs target the ID1-DBL2X domain of VAR2CSA, a protein expressed on the surface of infected erythrocytes (IEs) that mediates parasite sequestration in the placenta. Although development of an effective vaccine may be hampered by ID1-DBL2X polymorphisms expressed by field isolates, a recent study showed that genetic variation of this domain in South American parasite populations is much lower than in other geographical locations. This suggests that a recombinant vaccine designed to be efficacious in Africa and Asia is likely to be efficacious in South America. However, these studies did not include Colombian parasite populations in their analyses, which are known to be genetically distinct from other South American parasite populations due to their independent introduction from Africa. Therefore, we sought to determine the genetic variation of the ID1-DBL2X domain in Colombian parasites to assess the potential efficacy of the vaccine against PAM in this region. Through sequence analysis and population genetics, we show that there is a low degree of genetic variation amongst Colombian parasite populations and that a vaccine containing conserved antigen variants for worldwide populations is likely to be protective against PAM in Colombia. Our analysis also points towards an African origin for Colombian parasite populations, and suggests that their introduction into Colombia was a recurrent process encompassing multiple introduction events.
Assuntos
Variação Genética , Vacinas Antimaláricas/imunologia , Malária Falciparum/imunologia , Malária Falciparum/parasitologia , Plasmodium falciparum/genética , Plasmodium falciparum/imunologia , Adolescente , Adulto , Anticorpos Antiprotozoários/imunologia , Criança , Colômbia , Feminino , Genética Populacional , Genótipo , Humanos , Malária Falciparum/prevenção & controle , Pessoa de Meia-Idade , Testes de Neutralização , Filogenia , Plasmodium falciparum/classificação , Gravidez , Complicações Parasitárias na Gravidez/imunologia , Complicações Parasitárias na Gravidez/parasitologia , Complicações Parasitárias na Gravidez/prevenção & controle , Proteínas de Protozoários/imunologia , Adulto JovemRESUMO
In Colombia, Plasmodium resistance to antimalarials such as chloroquine and antifolates is a serious problem. As a result, the national Colombian health authorities are monitoring the efficacy of alternative drugs and schemes. The study of genetic polymorphisms related with drug resistance is required in the region. In vitro responses to chloroquine, quinine, mefloquine, amodiaquine, desethylamodiaquine, artesunate and dihydroartesunate were carried out by HRP ELISA. SNP analysis in Pfcrt and Pfmdr1 genes was performed by PCR-RFLP in 77 samples from the North West region of Colombia. In vitro resistance to chloroquine was high (74%), followed by mefloquine (30%) and desethylamodiaquine (30%). A positive correlation between the IC(50) of paired drugs was also detected. The allele Pfmdr1 N86 (wild) was present in 100% of the samples and 1246Y (mutant) in 92%. However, their presence did not correlate with in vitro drug resistance. Presence of the mutations K76T and N75E in Pfcrt was confirmed in all samples. Analysis of 4 codons (72, 74, 75 and 76) in pfcrt confirmed the presence of the haplotypes CMET in 91% and SMET in 9% of the samples.
Assuntos
Antimaláricos/farmacologia , Resistência a Medicamentos/genética , Proteínas de Membrana Transportadoras/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Plasmodium falciparum/efeitos dos fármacos , Polimorfismo de Nucleotídeo Único , Proteínas de Protozoários/genética , Amodiaquina/análogos & derivados , Amodiaquina/farmacologia , Animais , Cloroquina/farmacologia , Colômbia/epidemiologia , Humanos , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Mefloquina/farmacologia , Testes de Sensibilidade Parasitária , Plasmodium falciparum/genética , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de RestriçãoRESUMO
The population structure of Plasmodium falciparum has been widely studied in diverse epidemiological contexts, but emphasis has been made in regions with high and stable transmission. In order to establish the genetic structure of P. falciparum in areas of Colombia with different degree of endemicity, we studied 100 samples from malaria patients of two different municipalities. The frequency of multiclonal infection in these areas and the correlation with the endemicity were carried out by comparison of the amplified products from polymorphic segments of MSP-1, MSP-2, and GLURP genes. We found low size polymorphism of the studied genes: 1 MSP-1 allele, 3 MSP-2 alleles, and 4 GLURP alleles. We conclude that the P. falciparum population in the regions studied is genetically homogeneous.
Assuntos
Variação Genética , Malária Falciparum/parasitologia , Plasmodium falciparum/genética , Adolescente , Adulto , Alelos , Animais , Antígenos de Protozoários/genética , Criança , Colômbia/epidemiologia , Feminino , Humanos , Malária Falciparum/epidemiologia , Masculino , Proteína 1 de Superfície de Merozoito/genética , Polimorfismo Genético , Proteínas de Protozoários/genética , População RuralRESUMO
The horseradish peroxidase (HRP), a glycoprotein rich in mannose and N-acetylglucosamine residues has been used as a ligand to detect receptors for N-glycosidic linked oligosaccharides of glycoproteins in the human spermatozoon. Specific binding of HRP occurred to the membrane and the binding sites were visualized with 3,3'-diaminobenzidine-H2O2 (DAB-H2O2) reagent, and by fluorescence when the FITC-peroxidase was used. This specific binding was suppressed by alpha-D-methyl-mannoside and human chorionic gonadotropin, decreased by follicle stimulating and luteinizing hormones and slightly diminished by N-acetylglucosamine. The distribution of the N-linked oligosaccharide specific receptors for glycoproteins in the different zones of the membrane of the spermatozoon was determined by counting the spermatozoa labeled in those zones. The pattern of the distribution is similar to that found for N-linked oligosaccharides containing glycoproteins of the same membrane. The similarity of these distributions together with the general model for cell-to-cell recognition suggest that the sperm-egg interaction mechanism could consist of dual interactions by double binding receptors.