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Fulltext Novel clones of Streptococcus pneumoniae causing invasive disease in Malaysia

Jefferies JM, Mohd Yusof MY, Devi Sekaran S, Clarke SC

PLoS One, 2014;9(6):e97912.
PMID: 24941079 DOI: 10.1371/journal.pone.0097912

Although Streptococcus pneumoniae is a leading cause of childhood disease in South East Asia, little has previously been reported regarding the epidemiology of invasive pneumococcal disease in Malaysia and very few studies have explored pneumococcal epidemiology using multilocus sequence typing (MLST). Here we describe serotype, multilocus sequence type (ST), and penicillin susceptibility of thirty pneumococcal invasive disease isolates received by the University of Malaya Medical Centre between February 2000 and January 2007 and relate this to the serotypes included in current pneumococcal conjugate vaccines. A high level of diversity was observed; fourteen serotypes and 26 sequence types (ST), (11 of which were not previously described) were detected from 30 isolates. Penicillin non-susceptible pneumococci accounted for 33% of isolates. The extent of molecular heterogeneity within carried and disease-causing Malaysian pneumococci remains unknown. Larger surveillance and epidemiological studies are now required in this region to provide robust evidence on which to base future vaccine policy.
Fulltext Effect of gelam honey on the oxidative stress-induced signaling pathways in pancreatic hamster cells

Batumalaie K, Zaman Safi S, Mohd Yusof K, Shah Ismail I, Devi Sekaran S, Qvist R

Int J Endocrinol, 2013;2013:367312.
PMID: 24324490 DOI: 10.1155/2013/367312

Background. Oxidative stress induced by reactive oxygen and nitrogen species is critically involved in the impairment of β -cell function during the development of diabetes. Methods. HIT-T15 cells were cultured in 5% CO2 and then preincubated with Gelam honey extracts (20, 40, 60, and 80 µg/mL) as well as quercetin (20, 40, 60, and 80 µM), prior to stimulation by 20 and 50 mM of glucose. Cell lysate was collected to determine the effect of honey extracts and quercetin on the stress activated NF- κ B, MAPK pathways, and the Akt (ser473) activated insulin signaling pathway. Results. HIT-T15 cells cultured under hyperglycemic conditions demonstrated insulin resistance with a significant increase in the levels of MAPK, NF- κ B, and IRS-1 serine phosphorylation (ser307); however, Akt expression and insulin contents are significantly decreased. Pretreatment with quercetin and Gelam honey extract improved insulin resistance and insulin content by reducing the expression of MAPK, NF- κ B, and IRS-1 serine phosphorylation (ser307) and increasing the expression of Akt significantly. Conclusion. Gelam honey-induced differential expression of MAPK, NF- κ B, IRS-1 (ser307), and Akt in HIT-T15 cells shows that Gelam honey exerts protective effects against diabetes- and hyperglycemia-induced oxidative stress by improving insulin content and insulin resistance.
Fulltext Lack of clinical manifestations in asymptomatic dengue infection is attributed to broad down-regulation and selective up-regulation of host defence response genes

Yeo AS, Azhar NA, Yeow W, Talbot CC, Khan MA, Shankar EM, et al.

PLoS One, 2014;9(4):e92240.
PMID: 24727912 DOI: 10.1371/journal.pone.0092240

Dengue represents one of the most serious life-threatening vector-borne infectious diseases that afflicts approximately 50 million people across the globe annually. Whilst symptomatic infections are frequently reported, asymptomatic dengue remains largely unnoticed. Therefore, we sought to investigate the immune correlates conferring protection to individuals that remain clinically asymptomatic.
Fulltext Feasibility of case-control and test-negative designs to evaluate dengue vaccine effectiveness in Malaysia

Nealon J, Lim WY, Moureau A, Linus Lojikip S, Junus S, Kumar S, et al.

Vaccine, 2019 09 16;37(39):5891-5898.
PMID: 31445770 DOI: 10.1016/j.vaccine.2019.07.083

BACKGROUND: The world's first dengue vaccine [Dengvaxia; Sanofi Pasteur] was licensed in 2015 and others are in development. Real-world evaluations of dengue vaccines will therefore soon be needed. We assessed feasibility of case control (CC) and test-negative (TN) design studies for dengue vaccine effectiveness by measuring associations between socio-demographic risk factors, and hospitalized dengue outcomes, in Malaysia.
METHODS: Following ethical approval, we conducted hospital-based dengue surveillance for one year in three referral hospitals. Suspected cases aged 9-25 years underwent dengue virological confirmation by RT-PCR and/or NS1 Ag ELISA at a central laboratory. Two age- and geography-matched hospitalized non-dengue case-controls were recruited for a traditional CC study. Suspected cases testing negative were test-negative controls. Socio-demographic, risk factor and routine laboratory data were collected. Logistic regression models were used to estimate associations between confirmed dengue and risk factors.
RESULTS: We recruited 327 subjects; 155 were suspected of dengue. The planned sample size was not met. 124 (80%) of suspected cases were dengue-confirmed; seven were assessed as severe. Three had missing RT-PCR results; the study recruited 28 test-negative controls. Only 172 matched controls could be recruited; 90 cases were matched with ≥1 controls. Characteristics of cases and controls were mostly similar. By CC design, two variables were significant risk factors for hospitalized dengue: recent household dengue contact (OR: 54, 95% CI: 7.3-397) and recent neighbourhood insecticidal fogging (OR: 2.1; 95% CI: 1.3-3.6). In the TN design, no risk factors were identified. In comparison with gold-standard diagnostics, routine tests performed poorly.
CONCLUSIONS: The CC design may be more appropriate than the TN design for hospitalized dengue vaccine effectiveness studies. Selection bias in case control selection could be minimized by protocol changes more easily than increasing TN design control numbers, because early-stage dengue diagnosis in endemic countries is highly specific. MREC study approval: (39)KKM/NIHSEC/P16-1334.
Fulltext Antibacterial effects of 18 medicinal plants used by the Khyang tribe in Bangladesh

Hossan MS, Jindal H, Maisha S, Samudi Raju C, Devi Sekaran S, Nissapatorn V, et al.

Pharm Biol, 2018 Dec;56(1):201-208.
PMID: 29529970 DOI: 10.1080/13880209.2018.1446030

CONTEXT: The resistance of bacteria to antibiotics is raising serious concern globally. Asian medicinal plants could improve the current treatment strategies for bacterial infections. The antibacterial properties of medicinal plants used by the Khyang tribe in Bangladesh have not been investigated.
OBJECTIVE: The present study examines the antibacterial properties of 18 medicinal plants used by the Khyang tribe in day-to-day practice against human pathogenic bacteria.
MATERIALS AND METHODS: Leaves, bark, fruits, seeds, roots and rhizomes from collected plants were successively extracted with hexane, ethyl acetate and ethanol. The corresponding 54 extracts were tested against six human pathogenic bacteria by broth microdilution assay. The antibacterial mode of actions of phytoconstituents and their synergistic effect with vancomycin and cefotaxime towards MRSA was determined by time-killing assay and synergistic interaction assay, respectively.
RESULTS AND DISCUSSION: Hexane extract of bark of Cinnamomum cassia (L.) J. Presl. (Lauraceae) inhibited the growth of MRSA, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii with MIC values below 100 µg/mL. From this plant, cinnamaldehyde evoked at 4 × MIC in 1 h an irreversible decrease of MRSA count Log10 (CFU/mL) from 6 to 0, and was synergistic with vancomycin for MRSA with fractional inhibitory concentration index of 0.3.
CONCLUSIONS: Our study provides evidence that the medicinal plants in Bangladesh have high potential to improve the current treatment strategies for bacterial infection.