The Effect of Three-Monthly Albendazole Treatment on Malarial Parasitemia and Allergy: A Household-Based Cluster-Randomized,Double-Blind,Placebo-Controlled Trial

Background

Helminth infections are proposed to have immunomodulatory activities affecting health outcomes either detrimentally or beneficially. We evaluated the effects of albendazole treatment, every three months for 21 months, on STH, malarial parasitemia and allergy.

Methods and Findings

A household-based cluster-randomized, double-blind, placebo-controlled trial was conducted in an area in Indonesia endemic for STH. Using computer-aided block randomization, 481 households (2022 subjects) and 473 households (1982 subjects) were assigned to receive placebo and albendazole, respectively, every three months. The treatment code was concealed from trial investigators and participants. Malarial parasitemia and malaria-like symptoms were assessed in participants older than four years of age while skin prick test (SPT) to allergens as well as reported symptoms of allergy in children aged 5–15 years. The general impact of treatment on STH prevalence and body mass index (BMI) was evaluated. Primary outcomes were prevalence of malarial parasitemia and SPT to any allergen. Analysis was by intention to treat. At 9 and 21 months post-treatment 80.8% and 80.1% of the study subjects were retained, respectively. The intensive treatment regiment resulted in a reduction in the prevalence of STH by 48% in albendazole and 9% in placebo group. Albendazole treatment led to a transient increase in malarial parasitemia at 6 months post treatment (OR 4.16(1.35–12.80)) and no statistically significant increase in SPT reactivity (OR 1.18(0.74–1.86) at 9 months or 1.37 (0.93–2.01) 21 months). No effect of anthelminthic treatment was found on BMI, reported malaria-like- and allergy symptoms. No adverse effects were reported.

Conclusions

The study indicates that intensive community treatment of 3 monthly albendazole administration for 21 months over two years leads to a reduction in STH. This degree of reduction appears safe without any increased risk of malaria or allergies.

Trial Registration

Controlled-Trials.com ISRCTN83830814     

Polypeptide binding specificities of Saccharomyces cerevisiae oligosaccharyltransferase accessory proteins Ost3p and Ost6p

Asparagine-linked glycosylation is a common and vital co- and post-translocational modification of diverse secretory and membrane proteins in eukaryotes that is catalyzed by the multiprotein complex oligosaccharyltransferase (OTase). Two isoforms of OTase are present in Saccharomyces cerevisiae, defined by the presence of either of the homologous proteins Ost3p or Ost6p, which possess different protein substrate specificities at the level of individual glycosylation sites. Here we present in vitro characterization of the polypeptide binding activity of these two subunits of the yeast enzyme, and show that the peptide-binding grooves in these proteins can transiently bind stretches of polypeptide with amino acid characteristics complementary to the characteristics of the grooves. We show that Ost6p, which has a peptide-binding groove with a strongly hydrophobic base lined by neutral and basic residues, binds peptides enriched in hydrophobic and acidic amino acids. Further, by introducing basic residues in place of the wild type neutral residues lining the peptide-binding groove of Ost3p, we engineer binding of a hydrophobic and acidic peptide. Our data supports a model of Ost3/6p function in which they transiently bind stretches of nascent polypeptide substrate to inhibit protein folding, thereby increasing glycosylation efficiency at nearby asparagine residues.     

En route to economical eco‐friendly solvent system in enhancing sustainable recovery of poly(3‐hydroxybutyrate‐co‐4‐hydroxybutyrate) copolymer

Separation of poly(3‐hydroxybutyrate‐co‐4‐hydroxybutyrate) [P(3HB‐co‐4HB)] from bacterial cell matter is a critical step in the downstream process with respect to material quality and eco‐balance as P(3HB‐co‐4HB) is widely used for biomedical applications. Therefore, an efficient and eco‐based extraction of P(3HB‐co‐4HB) using a combination of NaOH and Lysol in digesting the non‐polymeric cell material (NPCM) digestion is developed. The NaOH and Lysol show synergistic influence on the copolymer extraction at a high purity and recovery of 97 and 98 wt% respectively. The optimized cell digestion method was found applicable to a vast batch of cells containing copolymers from various 4HB monomer compositions. At the largest extraction volume of 100 L, P(3HB‐co‐4HB) with a purity of 89 wt% was extracted with a maximum recovery of 90 wt%. The method developed has also eliminated the cell pretreatment step. The extraction method developed in this research has not only produced an economic and efficient copolymer recovery but has also retained the copolymer quality, in term of its molecular weight and thermal properties. It demonstrates a practical and promising downstream processing method in recovering the copolymer effectively from the bacterial biomass.     

Eco-friendly methodology for efficient synthesis and scale-up of 2-ethylhexyl-p-methoxycinnamate using Rhizopus oryzae lipase and its biological evaluation

Lipase-mediated synthesis of phenolic acid esters is a green and economical alternative to current chemical methods. Octyl methoxycinnamate, an important UVB-absorbing compound, was synthesized by the esterification of p-methoxycinnamic acid with 2-ethyl hexanol using Rhizopus oryzae lipase. A molar ratio of 1:2 of p-methoxycinnamic acid and 2-ethyl hexanol was found to give an optimum yield using cyclo-octane (50 ml) as reaction solvent, at a temperature of 45 °C, and 750 U of lipase, resulting in a yield of 91.3 % in 96 h. This reaction was successfully scaled up to 400-ml reaction size where 88.6 %bioconversion was achieved. The synthesized compound was found to have superior antioxidant activity as compared to ascorbic acid. The synthesized compound also exhibited good antimicrobial activity against Escherichia coli, Klebsiella pneumonia, Salmonella typhi, Staphylococcus aures, Candida albicans (yeast), Aspergillus niger, Alternaria solani, and Fussarium oxysporum by well diffusion method in terms of zone of inhibitions (in mm).     

Contrasting genetic and morphological differentiation among geographical lineages of a stenotopic miniature rasborine,Boraras maculatus,in Peninsular Malaysia

The variability in the stenotopic miniature rasborine Boraras maculatus (Cypriniformes: Danionidae: Rasborinae) across acidic-water habitats of Peninsular Malaysia (PM) was investigated using two molecular markers (the mitochondrial cytochrome c oxidase subunit I [COI] gene and the nuclear rhodopsin gene), as well as morphological evidence. Molecular phylogenetic analyses revealed differentiation among populations of B. maculatus in PM with the distinction of four allopatric lineages. Each of them was recognized as a putative species by automatic species delimitation methods. These lineages diverged from each other between 7.4 and 1.9 million years ago. A principal component analysis (PCA) was conducted to examine the multivariate variation in 11 morphometric measurements among three of these lineages. PCA results showed a significant overlap in morphological characteristics among these lineages. Additionally, a photograph-based machine learning approach failed to fully differentiate these lineages, suggesting limited morphological differentiation. B. maculatus represents a case of morphological stasis in a stenotopic miniature species. Strong habitat preference, coupled with long-term habitat fragmentation, may explain why each lineage of B. maculatus has a restricted distribution and did not disperse to other regions within and outside of PM, despite ample possibilities when the Sunda shelf was emerged and drained by large paleodrainages for most of the past 7 million years. The conservation status of B. maculatus and its peat swamp habitats are discussed, and it is concluded that peat swamps comprise several evolutionary units. Each of these units is considered a conservation unit and deserves appropriate protection.     

Genetic diversity of the tire track eel Mastacembelus favus in Southeast Asia inferred from microsatellite markers

Ichthyological Research - The tire track eel, Mastacembelus favus, is an economically important freshwater fish in mainland Southeast Asia. Understanding the spatial population structure is...     

A comparative genomic analysis of the alkalitolerant soil bacterium Bacillus lehensis G1

Bacillus lehensis G1 is a Gram-positive, moderately alkalitolerant bacterium isolated from soil samples. B. lehensis produces cyclodextrin glucanotransferase (CGTase), an enzyme that has enabled the extensive use of cyclodextrin in foodstuffs, chemicals, and pharmaceuticals. The genome sequence of B. lehensis G1 consists of a single circular 3.99 Mb chromosome containing 4017 protein-coding sequences (CDSs), of which 2818 (70.15%) have assigned biological roles, 936 (23.30%) have conserved domains with unknown functions, and 263 (6.55%) have no match with any protein database. Bacillus clausii KSM-K16 was established as the closest relative to B. lehensis G1 based on gene content similarity and 16S rRNA phylogenetic analysis. A total of 2820 proteins from B. lehensis G1 were found to have orthologues in B. clausii, including sodium–proton antiporters, transport proteins, and proteins involved in ATP synthesis. A comparative analysis of these proteins and those in B. clausii and other alkaliphilic Bacillus species was carried out to investigate their contributions towards the alkalitolerance of the microorganism. The similarities and differences in alkalitolerance-related genes among alkalitolerant/alkaliphilic Bacillus species highlight the complex mechanism of pH homeostasis. The B. lehensis G1 genome was also mined for proteins and enzymes with potential viability for industrial and commercial purposes.     

Risk Factors Associated with the Development of Atopic Sensitization in Indonesia

Background

The prevalence of allergic diseases has increased not only in high income but also in low-to-middle income countries. However, risk factors for their development are still not well established, particularly in the latter.

Objective

To assess prevalence and identify risk factors for sensitization to two major inhalant allergens among children from semi-urban and rural areas in Indonesia.

Method

A cross-sectional survey was performed among 1,674 school children aged 5–15 years old. Information on potential risk factors and reported allergic symptoms were obtained by questionnaire. Helminth infections were assessed. Skin prick tests (SPT) were performed, total IgE as well as allergen-specific IgE for house dust mite (HDM) and cockroach were measured.

Result

The prevalence of allergic skin sensitization to both aeroallergens was significantly higher in the semi-urban than in the rural area. However, serum IgE against HDM and cockroach as well as total IgE were significantly lower in semi-urban than in rural children. In the semi-urban area, there was a significant positive association between SPT to HDM and higher paternal education but a negative one with hookworm infection. The risk factors linked to cockroach sensitization were different: being of a farmer offspring and lacking access to piped water were associated with an increased risk for a positive SPT to cockroach. No significant associations between measured risk factors and having a positive SPT were found in the rural area.

Conclusion

Sensitization to HDM and cockroach is common in Indonesia, more often translating into a positive SPT in the semi-urban than in the rural setting. Whereas high paternal education and low hookworm infection were associated with increased risk of SPT to HDM, we were surprised to find parameters of lower SES were identified as risk factor for cockroach SPT.