Plasmodium falciparum protein kinase as a potential therapeutic target for antimalarial drugs development

@#Malaria is one of the most dangerous infectious diseases due to its high infection and mortality rates, especially in the tropical belt. Plasmodium falciparum (P. falciparum), the most virulent malaria parasite in humans, was recently reported to develop resistance against the final efficient antimalarial drug, artemisinin. Little is known about the resistance mechanisms, which further complicates the problem as a proper counteraction is unable to be taken. Hence, the understanding of drug mode of action and its molecular target is valuable knowledge that needs to be considered to develop the next generation of antimalarial drugs. P. falciparum protein kinase (Pf PK) is an attractive target for antimalarial chemotherapy due to its vital roles in all P. falciparum life stages. Moreover, overall structural differences and the presence of unique Pf PKs that are absent in human kinome, suggesting specific inhibition of Pf PK without affecting human cells is achievable. To date, at least 86 eukaryotic protein kinases have been identified in P. falciparum kinome, by which less than 40 were validated as potential targets at the erythrocytes stage. In this review, recent progress of the furthest validated Pf PKs; Pf Nek-1, Pf CDPK1, Pf CDPK4, Pf PKG, and Pf CLK-3 will be briefly discussed.

Clinical features and risk factors for HIV encephalopathy in children.

A prospective cohort study was conducted to determine the incidence of progressive encephalopathy (PE) and its associated clinical manifestations amongst a cohort of HIV infected children attending the HIV/AIDS clinic of the Pediatric Institute, Kuala Lumpur Hospital, Malaysia. Neurological and neurobehavioral assessments were performed in 55 children with HIV over a 24-month study period. Parameters assessed were physical and neurological assessments, CD4 counts, CD4 percentages, RNA viral loads and an IQ assessment at four monthly intervals. PE was diagnosed when patient developed at least one of the definitive criteria for PE based on the Consensus of Pediatric Neurology/Psychology Working Group, AIDS Clinical Trial 1996. The incidence of encephalopathy was 18.2% (n = 10) in 2002. All the patients had hepatosplenomegaly, lymphadenopathy, abnormal deep tendon reflexes and five had impairment in brain growth. The CD4 counts and CD4 percentages were more likely to be associated with PE compared to the non-PE group.