Prevalence and Risk Factors of Intestinal Parasitism in Rural and Remote West Malaysia

Background: Intestinal parasitic infections (IPIs) have a worldwide distribution and have been identified as one of the most significant causes of illnesses and diseases among the disadvantaged population. In Malaysia, IPIs still persist in some rural areas, and this study was conducted to determine the current epidemiological status and to identify risk factors associated with IPIs among communities residing in rural and remote areas of West Malaysia. Methods/Findings: A total of 716 participants from 8 villages were involved, comprising those from 1 to 83 years old, 550 (76.8%) participants aged #12 years and 166 (23.2%) aged $13 years, and 304 (42.5%) male and 412 (57.5%) female. The overall prevalence of IPIs was high (73.2%). Soil-transmitted helminth (STH) infections (73.2%) were significantly more common compared to protozoa infections (21.4%) (p,0.001). The prevalence of IPIs showed an age dependency relationship, with significantly higher rates observed among those aged #12 years. Multivariate analysis demonstrated that participants aged #12 years (OR = 2.23; 95% CI = 1.45–3.45), low household income (OR = 4.93; 95% CI = 3.15–7.73), using untreated water supply (OR = 2.08; 95% CI = 1.36–3.21), and indiscriminate defecation (OR = 5.01; 95% CI = 3.30–7.62) were identified as significant predictors of IPIs among these communities. Conclusion: Essentially, these findings highlighted that IPIs are highly prevalent among the poor rural communities in West Malaysia. Poverty and low socioeconomic with poor environmental sanitation were indicated as important predictors of IPIs. Effective poverty reduction programmes, promotion of deworming, and mass campaigns to heighten awareness on health and hygiene are urgently needed to reduce IPIs

Prevalence and Risk Factors of Intestinal Parasitism in Rural and Remote West Malaysia

Intestinal parasitic infections (IPIs) are among the most prevalent human afflictions; these infections still have major impact on the socioeconomic and public health of the bottom billion of the world's poorest people. Although Malaysia has a thriving economy, IPIs are still very much prevalent and causing major health problems among the poor and in deprived communities especially in rural and remote areas. A comprehensive study is paramount to determine the current prevalent and factors closely linked to IPIs so that effective control measures can be instituted. In view of this, we conducted this study to provide detailed data of the existing status of IPIs among 716 participants living in rural and remote areas in Peninsular Malaysia. The establishment of such data is beneficial for the public health service to justify and facilitate the reassessment of control strategies and policies in terms of reducing intestinal parasitism. With effective control measures in place, these communities (especially children) will have a greater opportunity for a better future in terms of health and educational achievement and eventually will be at par socially and economically with urban communities in Malaysia

Discovery of a highly active anticancer analogue of cardamonin that acts as an inducer of caspase-dependent apoptosis and modulator of the mTOR pathway

Nineteen analogues of cardamonin were semi-synthesized and tested against A549 and HK1 cell lines. The analogues were fully characterized via IR and NMR analyses, while compound 19 (a Cu (II) complex of cardamonin) was further characterized via HRMS, ELEMENTAL ANALYSIS, TGA and UV-VIS spectroscopy. Results of the MTS cell viability assay showed that several derivatives possessed cytotoxic activities that were several-fold more potent than cardamonin. Compound 19 was the most potent analogue possessing IC50 values of 13.2 µM and 0.7 µM against A549 and HK1 cells, corresponding to a 5- and 32-fold increase in activity, respectively. Furthermore, the active analogues, especially 19, have generally demonstrated lower toxicity towards normal MRC5 cells. SAR analysis showed the importance of the ketone and alkene groups for bioactivity, while substituting cardamonin’s phenolic groups with more polar moieties resulted in activity enhancement. As part of the SAR study and further exploration of chemical space, the effect of metal coordination on cytotoxicity was also investigated, but it was only possible to successfully obtain the Cu (II) complex of cardamonin (19), and results showed that the metal ion enhanced activity. 19 was also able to significantly inhibit the migration of A549 and HK1 cells. Further studies have shown that the most active analogue, 19, induced DNA damage resulting in G2/M-phase cell-cycle arrest in both cell lines. These events further led to the induction of apoptosis by 19 via caspase-3/7 and caspase-9 activation, PARP cleavage and downregulation of Mcl-1 expression. Finally, 19 inhibited the expression levels of p-mTOR and p-4EBP1. These data indicated that 19 exerted its anticancer activity, at least in part, via inhibition of the mTOR signalling pathway

The effect of NAC on the inhibition of T cell proliferation mediated by z-FA-FMK is abolished by BSO.

<p>PBMCs (1 x 10⁶/ml) were stimulated with anti-CD3 (5 μg/ml) plus 50 μM z-FA-FMK in the presence or absence of NAC (5 mM) and BSO (0.5 mM) where indicated. BrdU incorporation was determined after 72 h as described in Materials and Methods. The relative incorporation of BrdU into control proliferation T cells (with anti-CD3 only) were normalised to 100%. Results are the mean ± SEM of at least three independent experiments. *,Significantly increased (p < 0.01) compared to z-FA-FMK; **Significantly decreased (p < 0.05) from z-FA-FMK + NAC.</p

Effect of GSH on the inhibition of CD25 and CD69 expression in activated T cells mediated by z-FA-FMK.

<p>PBMCs (1 x 10⁶/ml) were stimulated with anti-CD3 (5 μg/ml) plus 50 μM z-FA-FMK in the presence or absence of 5mM GSH. After 72 h, the cells were stained with FITC-conjugated anti-CD25 or PE-conjugated anti-CD69 before analysis using flow cytometry as described in Materials and Methods. The results are one representative from three independent experiments.</p

Effect of NAC and GSH on the inhibition of T cell proliferation mediated by z-FA-FMK.

<p>PBMCs (1 x 10⁶/ml) were stimulated with anti-CD3 (5 μg/ml) in the presence of 50 μM z-FA-FMK and varying concentrations of NAC (A) or GSH (B). BrdU incorporation was determined after 72 h as described in Materials and Methods. The relative incorporation of BrdU into control proliferation T cells (with anti-CD3 only) were normalised to 100%. Results are the mean ± SEM of at least three independent experiments. *,Significantly increased (p < 0.01) compared to z-FA-FMK + anti-CD3.</p

Effect of low molecular weight thiols on caspase-8 and -3 processing in z-FA-FMK-treated activated T cells.

<p>PBMCs (1 x 10⁶/ml) were stimulated with anti-CD3 (5 μg/ml) plus 50 μM z-FA-FMK in the presence or absence of antioxidants (5 mM). After 72 h, the cells were taken through a gradient density centrifugation using lymphoprep to obtain activated T cells. Whole cell lysates (20 μg protein) from activated T cells were resolved using 13% SDS-PAGE, transferred to nitrocellulose membrane and probed for caspase-8, caspase-3 and β-actin as described in Materials and Methods. The results are one representative of three independent experiments.</p

Effect of z-FA-FMK and other peptidyl methylketones on primary T cell proliferation.

<p>PBMCs (1 x 10⁶/ml) were stimulated with anti-CD3 (5 μg/ml) in the presence of various concentrations of z-FA-FMK analogues (A), different peptidyl FMKs (B), or different N-terminal groups (C) for 72 h. T cell proliferation was determined using BrdU incorporation as outlined in Materials and Methods. The relative incorporation of BrdU into control proliferation T cells (with anti-CD3 only) were normalised to 100%. The results are the means ± SEM from three separate donors. *,Significantly decreased (p < 0.01) from control.</p

Effect of low molecular weight thiols on the inhibition of T cell proliferation mediated by z-FA-FMK.

<p>PBMCs (1 x 10⁶/ml) were stimulated with anti-CD3 (5 μg/ml) plus 50 μM z-FA-FMK in the presence or absence of low molecular weight thiols (5 mM) or BSO (0.5 mM) where indicated. BrdU incorporation was determined after 72 h as described in Materials and Methods. The relative incorporation of BrdU into control proliferation T cells (with anti-CD3 only) were normalised to 100%. Results are the mean ± SEM of at least three independent experiments. *,Significantly increased (p < 0.01) compared to z-FA-FMK + anti-CD3.</p