RESUMO
Investigation of human genes under pathogen-driven selection as Plasmodium sp. has pinpointed genetic variants that participate in the adaptation to the environment and/or are related to severities of human diseases. The current study examined an example of an evolutionary trade-off in which genetic variants in the PKLR gene putatively selected for malaria resistance influence the susceptibility to mycobacterial diseases (leprosy and tuberculosis) in Brazilian population and Mozambique. A complete characterization of the biological effect of those risk variants may clarify the role of the PKLR gene in leprosy and tuberculosis. Deciphering the genetic basis of mycobacterial diseases has implications for the identification of true high-risk individuals in order to optimize screening strategies. Furthermore, the trade-off mechanism discussed in this work might occur in other central genes of immune response and biochemical pathways, controlling the susceptibility to other infectious diseases.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Piruvato Quinase/genética , Polimorfismo de Nucleotídeo Único , Malária/genética , Moçambique , Haplótipos , Brasil , Predisposição Genética para Doença , Frequência do GeneRESUMO
Quantitative plasma viral load (VL) at 1000 copies /mL was recommended as the threshold to confirm antiretroviral therapy (ART) failure by the World Health Organization (WHO). Because of ongoing challenges of using plasma for VL testing in resource-limited settings (RLS), especially for children, this study collected 717 DBS and paired plasma samples from children receiving ART ≥1 year in Mozambique and compared the performance of DBS using Abbott's VL test with a paired plasma sample using Roche's VL test. At a cut-off of 1000 copies/mL, sensitivity of DBS using Abbott DBS VL test was 79.9%, better than 71.0% and 63.9% at 3000 and 5000 copies/mL, respectively. Specificities were 97.6%, 98.8%, 99.3% at 1000, 3000, and 5000 copies/mL, respectively. The Kappa value at 1000 copies/mL, 0.80 (95% CI: 0.73, 0.87), was higher than 0.73 (95% CI: 0.66, 0.80) and 0.66 (95% CI: 0.59, 0.73) at 3000, 5000 copies/mL, respectively, also indicating better agreement. The mean difference between the DBS and plasma VL tests with 95% limits of agreement by Bland-Altman was 0.311 (-0.908, 1.530). Among 73 children with plasma VL between 1000 to 5000 copies/mL, the DBS results were undetectable in 53 at the 1000 copies/mL threshold. While one DBS sample in the Abbott DBS VL test may be an alternative method to confirm ART failure at 1000 copies/mL threshold when a plasma sample is not an option for treatment monitoring, because of sensitivity concerns between 1,000 and 5,000 copies/ml, two DBS samples may be preferred accompanied by careful patient monitoring and repeat testing.