Glycogen synthase kinase-3β inhibition improved survivability of mice infected with Burkholderia pseudomallei

The disease melioidosis, caused by the soil bacteria Burkholderia pseudomallei, often manifests as acute septicemia with high fatality. Glycogen synthase kinase-3β (GSK3β) plays a key role during the inflammatory response induced by bacteria. We used a murine model of acute melioidosis to investigate the effects of LiCl, a GSK3 inhibitor on experimental animal survivability as well as TNF-α, IL-1β, IFN-γ, IL-10 and IL-1Ra cytokine levels in blood, lung, liver and spleen of B. pseudomallei-infected mice. Our results showed that administration of 100 μg/g LiCl improved survivability of mice infected with 5 X LD50 of B. pseudomallei. Bacterial counts in spleen, liver and lungs of infected mice administered with LiCl were lower than non-treated controls. Our data also revealed that GSK3β is phosphorylated in the spleen, liver and lung of animals infected with B. pseudomallei. However in infected animals administered with LiCl, higher levels of pGSK3 were detected in the organs. Levels of proinflammatory cytokines (TNF-α, IL-1β and IFN-γ) and anti-inflammatory cytokines (IL-10 and IL-1Ra) in sera and organs tested were elevated significantly following B. pseudomallei infection. With GSK3β inhibition, pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β) were significantly decreased in all the samples tested whilst the levels of anti-inflammatory cytokines, IL-10 (spleen and lung) and IL-1Ra (spleen, liver and sera) were further elevated. This study represents the first report implicating GSK3β in the modulation of cytokine production during B. pseudomallei infection thus reiterating the important role of GSK3β in the inflammatory response caused by bacterial pathogens.

Seroprevalence of toxoplasmosis among migrant workers from different Asian countries working in Malaysia.

A serologic study of Toxoplasma antibodies among 501 foreign migrant workers in Malaysia was conducted in a plantation and detention camp. The highest prevalence rate of 46.2% was among Nepalese workers. Statistical analysis indicated the IgG positivity rate among local residents was significantly higher than the migrants studied (p < 0.05). The IgM positivity rate showed no significant difference between the two groups (p > 0.05). No significant difference in the prevalence rate was noted between the migrants and the local workers when grouped by agricultural and non-agricultural occupations (p > 0.05). The continuous introduction of these infections may influence the epidemiology and further compromise efforts in control and prevention. It is therefore important to monitor of non-notifiable diseases.

Anemia in remote interior communities in Sarawak, Malaysia.

A cross-sectional survey of 365 individuals, (51.9% males, 48.1% females; ages 5-85 years), from five remote interior communities in upper Rejang River basin Sarawak, Malaysia, found 24.4% were anemic. The range and mean of Hb concentration in male and female were: 7.2-17.0 mg/ml and 13.7 mg/ml and 7.9-15.7 mg/ml and 12.9 mg/ml respectively. Amongst the five tribes surveyed, the prevalence of anemia (range: 10.6-46.7%), was higher among the Penans (46.7%), Kenyahs (31.1%), Kajangs (27.8%) and Kayans (19.3%), than amongst the Ukits (10.6%). Anemia is more common among males >40 years and among adolescents and young reproductive females, as well as elderly females > 61 years old. Of the 83 anemic individuals, 6.0% and 3.6% had Trichuris trichiura or hookworm respectively; however there is no clear association with intestinal worm infection.

Intestinal parasitic infection among five interior communities at upper Rejang River, Sarawak, Malaysia.

Intestinal parasitic infection among five interior communities at Bakun Valley, upper Rejang River, Sarawak, Malaysia, was investigated as part of a public health impact assessment of the proposed US$ 3 billion Bakun Hydroelectric Project. Coproparasitological examination of 355 stool samples from 7 of 16 villages representing 5 of 7 tribes in the area revealed infection rate of 41%. A higher infection rate was found among the settled Kayans (56%) than the seminomadic Penans (29%). Infection rate was high (68%) among children less than 14 years old. Trichuris trichiura accounted for more than 90% of all infections; less common were Ascaris lumbricoides, hookworms and Strongyloides stercoralis. Polyparasitism was found in 8% of the individuals surveyed with dual infection due to T. trichiura and A. lumbricoides being more common than dual infection with T. trichiura and hookworm. Women had higher infection rates (57%) than men (33%).

Schistosomiasis malayensis-like infection among the Penan and other interior tribes (Orang Ulu) in upper Rejang River Basin Sarawak Malaysia.

A serosurvey of various indigenous interior tribes (Orang Ulu) in upper Rejang River Basin Sarawak Malaysia, the site of a multibillion Ringgit hydroelectric power project, found 6.8% of the individual surveyed were seropositive for schistosomiasis, as determined by ELISA method using the soluble egg antigen of Schistosoma malayensis Baling strain. In all age group, the seroprevalence rate is higher (9.5%) in males than in females (4.5%) except for the 31-40 age group. Seroprevalence of schistosomiasis was found to increase with age with the above 60 age group having the highest rate followed by the 31-40 age group. Seroprevalence rate among the tribes ranges from 4.1% among the Penan to 11.6% among the Kajang. There was no seroevidence of schistosomiasis among the Ukits. A snail survey found four snail species including Brotia species, the intermediate host of the lung fluke Paragonimus westermani, however no schistosome snail host was identified. Although schistosomiasis malayensis-like infection may be endemic in the area, its public health significance remains undetermined.

Rickettsial infection in five remote Orang Ulu villages in upper Rejang River, Sarawak, Malaysia.

People in 5 Orang Ulu villages in Sarawak, Malaysia were tested for rickettsial infection by Weil-Felix reaction and by indirect immunoperoxidase reaction. Of those surveyed 9.6% were positive for typhus. Of the positives, 3.8% were positive for tick typhus (7/11), scrub typhus (4/11) or endemic typhus (1/11). The incidence of typhus was higher among semi-nomadic Penans compared with the settled Kayans.

Enterobius vermicularis infection among children aged 1-8 years in a rural area in Malaysia.

The infection rate and relationship of enterobiasis with socio-economic status were determined in children aged 1-8 years, living in a rural area in Malaysia. Of the 178 subjects 40.4% were infected with Enterobius vermicularis. The distribution of enterobiasis among these children were analyzed in relation to age groups and sex. The rate of infection was significantly higher in older children (5-7 years). The association of enterobiasis with other factors studied such as number of persons per house, household income per months and mother's employment status were not significant. The sensitivity of three successive days anal swabs compared to a single swab was found to be statistically significant.

Prevalence of Enterobius vermicularis amongst adults living in hostels by six successive day examination.

The prevalence of Enterobius vermicularis in four groups of adults, all trainee public health inspectors or public health nurses, aged 18-35 years and all living in hostels on campus was studied. The modified scotch tape technique was used and the subjects were taught to do the examination on themselves to detect the presence of eggs over a period of 6 successive mornings. Each was given an elaborately illustrated diagram on how and when to take the samples and given demonstration in groups. The samples were examined by trained people. Most of the subjects took samples on 6 consecutive days. Of the 119 subjects who returned samples, the overall prevalence of E. vermicularis was 9.2% and this was thought to be high for this particular age group. This was due to the higher prevalence (19.4%) in one group, whereas in the others the range was 3.5-8.0%. Based on the samples returned on the first day none of the subjects were detected as having the infection. After examination on 3 successive days (109 subjects) 10.1% were found to be infected (chi 2 = 10.704; d. f. = 1) and after examination on 6 successive days (72 subjects) 13.9% were found to be infected (chi 2 = 3.026; d. f. = 1). There was no significance between examination over 3 successive days and 6 consecutive days (chi 2 = 0.296; d. f. = 1). There was no difference in the prevalence between males and females.(ABSTRACT TRUNCATED AT 250 WORDS)