Dengue infection is endemic in South East Asia and parts of the Americas. Dengue hemorrhagic fever is characterized by vascular permeability, coagulation-disorders and thrombocytopenia, which can culminate in hypotension i.e. dengue shock syndrome. Hypopituitarism arising as a complication of dengue is extremely rare. Hemorrhagic pituitary apoplexy of pre-existing pituitary adenomas has been rarely reported in dengue. We describe an uncommon case of hypopituitarism in a dengue shock syndrome survivor without known pituitary adenoma. A 49 years old nulliparous lady (from Kuala Lumpur, Malaysia) presented with typical symptoms of hypocortisolism. Postural hypotension was evident with normal secondary sexual characteristics. Further history revealed that she survived an episode of dengue shock syndrome 6 years ago where premature menopause developed immediately after discharge, and subsequently insidious onset of multiple hormonal deficiencies indicative of panhypopituitarism. There were no neuro-ophthalmological symptoms suggestive of pituitary apoplexy during hospitalization for severe dengue. Magnetic resonance imaging of the pituitary 6 years later revealed an empty sella. Autoimmune screen and anti-thyroid peroxidase antibodies were negative. We describe a rare possible causative association of severe dengue with panhypopituitarism without known pituitary adenoma, postulating pituitary infarction secondary to hypotension (mimicking Sheehan’s syndrome), or a direct viral cytopathic effect. Subclinical pituitary apoplexy secondary to asymptomatic pituitary hemorrhage however cannot be excluded. Future research is required to determine the need for and timing of pituitary axis assessment among dengue shock syndrome survivors.

Entamoeba histolytica is the parasite responsible for amoebiasis, which can result in amoebic colitis or amoebic liver abscess. Metronidazole has been the conventional treatment for intestinal amoebiasis, but concerns regarding resistance have emerged due to the identification of resistance pathways in E. histolytica. This study investigates a novel anti-amoebic approach targeting the CDP-choline pathway. Inhibition studies were conducted using potential choline kinase (CK) inhibitors to inhibit the EhCK enzyme, and RNA interference was employed to knock down the EhCK gene. Km and Vmax of purified EhCK and hCKa2 proteins were determined by pyruvate kinase-lactate dehydrogenase (PK-LDH) coupled assay. The IC50 values for EhCK and hCKa2 were determined with several commercial CK inhibitors. Selected inhibitors were incubated with E. histolytica trophozoites for 48 hours to determine the EC50 for each inhibitor. Silencing of gene encoding EhCK was carried out using duplex siRNA and the gene expression level was measured by real-time qPCR. Based on the IC50 values, three of the inhibitors, namely CK37, flavopiridol and H-89 were more potent against EhCK than hCKa2. Trophozoites growth inhibition showed that only HDTAB, H-89 and control drug metronidazole could penetrate and induce cell death after 48-hour incubation. siRNA concentration of 10 µg/mL was used for the transfection of positive control GAPDH, EhCK, and non-targeting GFP siRNAs. RNAi experiment concluded with positive control GAPDH downregulated by 99% while the level of EhCK mRNA was downregulated by 47%. In this study, potential inhibitors of EhCK and siRNA have been identified, paving the way for further refinement and testing to enhance their potency against EhCK while sparing hCK. The utilization of these specific inhibitors and siRNA targeting EhCK represents a novel approach to impede the growth of E. histolytica by disrupting its phospholipid synthesis pathway.