Global genetic diversity of the Plasmodium vivax transmission-blocking vaccine candidate Pvs48/45.

BACKGROUND: Plasmodium vivax 48/45 protein is expressed on the surface of gametocytes/gametes and plays a key role in gamete fusion during fertilization. This protein was recently expressed in Escherichia coli host as a recombinant product that was highly immunogenic in mice and monkeys and induced antibodies with high transmission-blocking activity, suggesting its potential as a P. vivax transmission-blocking vaccine candidate. To determine sequence polymorphism of natural parasite isolates and its potential influence on the protein structure, all pvs48/45 sequences reported in databases from around the world as well as those from low-transmission settings of Latin America were compared. METHODS: Plasmodium vivax parasite isolates from malaria-endemic regions of Colombia, Brazil and Honduras (n = 60) were used to sequence the Pvs48/45 gene, and compared to those previously reported to GenBank and PlasmoDB (n = 222). Pvs48/45 gene haplotypes were analysed to determine the functional significance of genetic variation in protein structure and vaccine potential. RESULTS: Nine non-synonymous substitutions (E35K, Y196H, H211N, K250N, D335Y, E353Q, A376T, K390T, K418R) and three synonymous substitutions (I73, T149, C156) that define seven different haplotypes were found among the 282 isolates from nine countries when compared with the Sal I reference sequence. Nucleotide diversity (π) was 0.00173 for worldwide samples (range 0.00033-0.00216), resulting in relatively high diversity in Myanmar and Colombia, and low diversity in Mexico, Peru and South Korea. The two most frequent substitutions (E353Q: 41.9 %, K250N: 39.5 %) were predicted to be located in antigenic regions without affecting putative B cell epitopes or the tertiary protein structure. CONCLUSIONS: There is limited sequence polymorphism in pvs48/45 with noted geographical clustering among Asian and American isolates. The low genetic diversity of the protein does not influence the predicted antigenicity or protein structure and, therefore, supports its further development as transmission-blocking vaccine candidate.

Esclerosis Mesial temporal: Clinica, estudios paraclinicos y cirugia / Mesial temporal sclerosis a comprehensive approach

Se realiza una revisión no sistemática de los principales tópicos de la esclerosis mesial temporal. Su clínica en ocasiones precedida en años por crisis febriles, reaparece, en la adolescencia como una epilepsia evolutiva caracterizada por crisis parciales simples y complejas, en muchos casos con pobre respuesta al tratamiento farmacológico, lo cual hace a quien la presenta candidato a una cirugía, procedimiento que reduce (incluso elimina) el uso de antiepilépticos. Se revisan las principales manifestaciones clínicas y su importancia en cuanto a lateralidad y se analizan los principales métodos diagnósticos y se propone una evaluación prequirúrgica sistemática para los candidatos. Finalmente se discute el estudio de Ontario y sus implicaciones en el tratamiento quirúrgico de la epilepsia