Novel regulatory SNPs in the promoter region of the TNFRSF18 gene in a Gabonese population

Parasites are accountable for driving diversity within immune gene families. We identified and investigated regulatory single nucleotide polymorphisms (SNPs) in the promoter regions of the tumor necrosis factor receptor superfamily member 18 (TNFRSF18) gene by direct sequencing in a group of male Gabonese individuals exposed to a wide array of parasitic diseases such as malaria, filariasis and schistosomiasis. Two new promoter variants were identified in 40 individuals. Both novel variants were heterozygous and were linked to SNP #rs3753344 (C/T), which has been described. One of the SNP variants (ss2080581728) was close to the general transcription factor site, the TATA box. We further validated these new promoter variants for their allelic gene expression using transient transfection assays. One new promoter variant with two base changes (C/T - ss2080581728/rs3753344) displayed an altered expression of the marker gene. Both novel variants remained less active at the non-induced state in comparison to the major allele. The allele frequencies observed in this study were consistent with data for other African populations. The detection and analysis of these human immune gene polymorphisms contribute to a better understanding of the interaction between host-parasite and expression of Treg activity.

Drug susceptibility of Plasmodium falciparum in the western Amazon region State of Acre, Brazil

Estudos de campo na Amazonia ocidental (Estado do Acre, Brasil) indicam que as 4-aminoquinolinas, assim como a sua combinacao com sulfadoxina-pirimetamina nao podem mais ser recomendadas para o tratamento e profilaxia das infeccoes pelo P. falciparum nesta regiao. A quinina permanece como droga efetiva quando usada corretamente. Entretanto, problemas podem surgir devido aos efeitos colaterais durante a sua aplicacao por periodo de 10 dias. Possibilidades de ultrapassar estes problemas combinando curto espaco de administracao da quinina com outras drogas estao no momento limitadas devido a falta de um composto associado adequado. Por esta razao, a combinacao quinina/clindamicina parece ser a terapeutica mais adequada para a malaria pelo P. falciparum. Nossos estudos in vitro sugerem que a mefloquina e outra alternativa efetiva para o tratamento da malaria falciparum nesta regiao da Amazonia.

Interaction of rheumatoid factor and Entamoeba histolytica

Testes para citotoxicidade e lise amebiana foram utilizados para deminstrar uma possível interaçäo entre o fator reumatóide e a Entamoeba histolytica. A atividade citotóxica amebiana foi inibida pela IgG antiameba de coelho purificada através de cromatografia. Constatou-se inibiçäo aumentada com IgG antiameba de coelho mais fator reumatóide. A mesma inibiçäo acentuada da atividade citotóxica amebiana pôde ser constatada quando se substituiu o fator reumatóide por sor humano normal, inativado pelo calor, como controle. Cerca de 50% de lise amebiana ocorreu quando as amebas foram misturadas com soro normal humano como fonte de complemento. A lise amebiana aumentou para 60% quando incubadas com soro humano normal, acrescido de anticorpos humanos antiameba. Nenum aumento adicional pode ser obtido pela adiçäo de fator reumatóide. Usando IgG antiameba de coelho em vez de anticorpos humanos, a proporçäo de lise näo aumentou. A incubaçäo de amebas com soro humano normal, IgG antiameba de coelho e fator reumatóide reduziu acentuadamente a lise amebiana. O fator reumatóide näo teve efeito na atividade citotóxica amebiana, nem na lise amebiana mediada pelo complemento in vitro

In vitro drug sensitivity of Plasmodium falciparum in Acre, Brazil

In Acre, the westernmost state of Brazil in the Amazon ragion, the sensitivity of Plasmodium falciparum to chloroquine, amodiaquine, mefloquine, quinine and uslfadozine/pyrimethamine was determined in vitro by the Rieckmann microtechnique. The study was performed between January and June 1987; the in vitro parasite responses to all antimalarial drugs were determined according to the recommendations of WHO. Of 83 isolates of P. falciparum, all were sensitive to mefloquine and of 87 isolated of P. falciparum, 84 (97 per cent) were sensitive to quinine. The EC50 for mefloquine was 0.27 umol/1 and for quinine 4.60 umol/1. In contrast, 65 of 89 (73 per cent) and 70 of 83 (84 per cent) isolates were resistant to amodiaquine was 0.34 umol/1 and for chloroquine 0.73 umol/1. Sulfadoxine /pyrimethamine resistance was seen in 23 of 25 (92 per cent) cases

These data clearly indicate that in the western part of the Amazon region the 4-aminoquinolines, as well as sulfadoxine/pyrimethamine, can no longer be recommended for the treatment of P. falciparum infections(AU)