Displaying publications 61 - 79 of 79 in total

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  1. Fulltext Aporphine alkaloids from the leaves of Phoebe grandis (Nees) Mer. (Lauraceae) and their cytotoxic and antibacterial activities
    Omar H, Hashim NM, Zajmi A, Nordin N, Abdelwahab SI, Azizan AH, et al.
    Molecules, 2013 Jul 29;18(8):8994-9009.
    PMID: 23899833 DOI: 10.3390/molecules18088994
    The oxoaporphine alkaloid lysicamine (1), and three proaporphine alkaloids, litsericinone (2), 8,9,11,12-tetrahydromecambrine (3) and hexahydromecambrine A (4) were isolated from the leaves of Phoebe grandis (Nees) Merr. (Lauraceae). Compounds 2 and 3 were first time isolated as new naturally occurring compounds from plants. The NMR data for the compounds 2-4 have never been reported so far. Compounds 1 and 2 showed significant cytotoxic activity against a MCF7 (human estrogen receptor (ER+) positive breast cancer) cell line with IC₅₀ values of 26 and 60 µg/mL, respectively. Furthermore, in vitro cytotoxic activity against HepG2 (human liver cancer) cell line was evaluated for compounds 1-4 with IC₅₀ values of 27, 14, 81 and 20 µg/mL, respectively. Lysicamine (1) displayed strong antibacterial activity against Bacillus subtilis (B145), Staphylococcus aureus (S1434) and Staphylococus epidermidis (a clinically isolated strain) with inhibition zones of 15.50 ± 0.57, 13.33 ± 0.57 and 12.00 ± 0.00 mm, respectively. However, none of the tested pathogenic bacteria were susceptible towards compounds 2 and 3.
  2. Fulltext Effects of one-year supplementation with Phyllanthus niruri on fibrosis score and metabolic markers in patients with non-alcoholic fatty liver disease: A randomized, double-blind, placebo-controlled trial
    Abu Hassan MR, Hj Md Said R, Zainuddin Z, Omar H, Md Ali SM, Aris SA, et al.
    Heliyon, 2023 Jun;9(6):e16652.
    PMID: 37313177 DOI: 10.1016/j.heliyon.2023.e16652
    BACKGROUND AND PURPOSE: and purpose: Non-alcoholic fatty liver disease (NAFLD) is a significant global health concern with limited pharmacotherapy options. This study aimed to evaluate the effectiveness of a standardized extract of Phyllanthus niruri in mild-to-moderate NAFLD.

    MATERIALS AND METHODS: This was a 12-month randomized controlled trial, in which adults with a controlled attenuation parameter (CAP) score >250 dB/m and a fibrosis score <10 kPa were randomly assigned to receive a standardized P. niruri extract at a dose of 3,000 mg daily (n = 112) or a placebo (n = 114). The primary outcomes were changes in CAP score and liver enzyme levels, while the secondary outcomes were changes in other metabolic parameters. The analysis was performed on an intention-to-treat basis.

    RESULTS: After 12 months, there was no significant difference in the change of CAP score between the intervention and control groups (-15.05 ± 36.76 dB/m vs. -14.74 ± 41.08 dB/m; p = 0.869). There was also no significant difference in the changes of liver enzyme levels between the two groups. However, the intervention group showed a significant reduction in fibrosis score, which was not observed in the control group (-0.64 ± 1.66 kPa versus 0.10 ± 1.61 kPa; p = 0.001). No major adverse events were reported in either group.

    CONCLUSION: This study showed that P. niruri did not significantly reduce CAP score and liver enzyme levels in patients with mild-to-moderate NAFLD. However, a significant improvement in fibrosis score was observed. Further research is needed to determine its clinical benefits at different dosages for NAFLD treatment.

  3. Association between ABCB1 polymorphism and response to sodium valproate treatment in Malaysian epilepsy patients
    Haerian BS, Lim KS, Tan HJ, Mohamed EH, Tan CT, Raymond AA, et al.
    Epileptic Disord, 2011 Mar;13(1):65-75.
    PMID: 21388909 DOI: 10.1684/epd.2011.0419
    Over-expression of P-glycoprotein, encoded by the ABCB1 gene, is proposed to be involved in resistance to antiepileptic drugs in about 30% of patients with epilepsy. Here, we investigated the possible association between ABCB1 polymorphisms and sodium valproate (VPA) treatment in Malaysian epilepsy patients. Genotypes were assessed in 249 drug-resistant and 256 drug-responsive Malaysian patients for C1236T, G2677T/A, and C 5T polymorphisms in the ABCB1 gene. No genotypes, alleles, or haplotypes were associated with the response to VPA in either the overall group or Chinese, Indian, and Malay subgroups. Our data suggest that C1236T, G2677T/A, and C3435T polymorphisms in the ABCB1 gene do not contribute to the response to VPA in patients with epilepsy.
  4. Onchocerca takaokai n. sp. (Nematoda: Filarioidea) in Japanese wild boars (Sus scrofa leucomystax): Description and molecular identification of intradermal females
    Uni S, Fukuda M, Agatsuma T, Bain O, Otsuka Y, Nakatani J, et al.
    Parasitol Int, 2015 Dec;64(6):493-502.
    PMID: 26165205 DOI: 10.1016/j.parint.2015.07.001
    Human zoonotic onchocercosis is caused by Onchocerca dewittei japonica, parasitic in wild boars (Sus scrofa leucomystax) in Japan. Previously, microfilariae longer than those of Onchocerca dewittei japonica were observed in skin snips from wild boars during the study of O. dewittei japonica. Moreover, the third-stage larvae (L3) of these longer microfilariae were obtained from the blackfly Simulium bidentatum after experimental injections. Based on morphometric and molecular studies, similar L3 were found in blackflies during fieldwork in Oita, Japan. However, except for O. dewittei japonica, adult worms of Onchocerca have not been found in wild boars. In this study, we discovered adult females of a novel Onchocerca species in the skin of a wild boar in Oita, and named it Onchocerca takaokai n. sp. Females of this new species had longer microfilariae and differed from O. dewittei japonica in terms of their morphological characteristics and parasitic location. The molecular characteristics of the cytochrome c oxidase subunit 1 and 12S rRNA genes of the new species were identical to those of the longer microfilariae and L3 previously detected, but they differed from those of O. dewittei japonica at the species level. However, both species indicated a close affinity among their congeners and Onchocerca ramachandrini, parasitic in the warthog in Africa, was basal in the Suidae cluster of the 12S rRNA tree.
  5. Fulltext Neurodevelopmental effects of childhood malnutrition: A neuroimaging perspective
    Galler JR, Bringas-Vega ML, Tang Q, Rabinowitz AG, Musa KI, Chai WJ, et al.
    Neuroimage, 2021 05 01;231:117828.
    PMID: 33549754 DOI: 10.1016/j.neuroimage.2021.117828
    Approximately one in five children worldwide suffers from childhood malnutrition and its complications, including increased susceptibility to inflammation and infectious diseases. Due to improved early interventions, most of these children now survive early malnutrition, even in low-resource settings (LRS). However, many continue to exhibit neurodevelopmental deficits, including low IQ, poor school performance, and behavioral problems over their lifetimes. Most studies have relied on neuropsychological tests, school performance, and mental health and behavioral measures. Few studies, in contrast, have assessed brain structure and function, and to date, these have mainly relied on low-cost techniques, including electroencephalography (EEG) and evoked potentials (ERP). The use of more advanced methods of neuroimaging, including magnetic resonance imaging (MRI) and functional near-infrared spectroscopy (fNIRS), has been limited by cost factors and lack of availability of these technologies in developing countries, where malnutrition is nearly ubiquitous. This report summarizes the current state of knowledge and evidence gaps regarding childhood malnutrition and the study of its impact on neurodevelopment. It may help to inform the development of new strategies to improve the identification, classification, and treatment of neurodevelopmental disabilities in underserved populations at the highest risk for childhood malnutrition.
  6. Bioaccumulation of zinc in edible tropical vegetables in Peninsular Malaysia and its human health risk assessment based on various ethnicities in Malaysia
    Wong KW, Yap CK, Yaacob A, Nulit R, Omar H, Aris AZ, et al.
    Environ Sci Pollut Res Int, 2021 Mar 22.
    PMID: 33751349 DOI: 10.1007/s11356-021-13361-3
    Along with the growing utilization of zinc (Zn) and Zn-containing nanoparticles in various industries, Zn ecotoxicological evaluation on human food supply is necessary even though Zn is generally considered safe and rarely concentrated ecotoxicologically. This study aimed to investigate the bioaccumulation of Zn in 18 species of vegetables (seven leafy, nine fruity vegetables and one species each of tuber and legume) collected from two farming sites in the west coast of Peninsular Malaysia. A human health risk assessment (HHRA) was also conducted. In addition to HHRA based on the general population, HHRA based on each major ethnic group of the Malaysian society was also determined considering that the food consumption pattern would definitely be varied across ethnicities and age groups (children and adults). The study results showed that Zn concentrations were significantly higher (p < 0.05) in leafy vegetables than in other types of vegetables. However, the target hazard quotient (THQ) values were all found to be < 1.0. Therefore, based on the Malaysian ethnicities and age groups with their respective vegetable consumption patterns, the results indicated insignificant noncarcinogenic human health risk of Zn via oral consumption of vegetables by the Malaysian population. As a metric of measurement of HHRA, a comparison of THQ values could yield previously unreported insights into HHRA differences among the compared populations. A comparison of THQ values among the consumer groups indicated higher HHR for Chinese Malaysians and children due to their higher vegetable consumption and lower body weight, respectively. A comparison the Zn intakes of all the consumer groups with the recommended nutrient intakes indicated that the oral consumption of the vegetable species collected in this study would not result in Zn-related hazards and would not be able to fulfil the Zn dietary need of the individual consumer.
  7. Intraoperative blood loss and blood transfusion requirement among liver transplant recipients: A national single-center experience 2020
    Yusop MF, Tahir NM, Azim SMSS, Kamaruzaman AA, Hata NRM, Kugaan A, et al.
    Asian J Transfus Sci, 2023;17(2):251-255.
    PMID: 38274975 DOI: 10.4103/ajts.ajts_38_21
    BACKGROUND: Liver transplantation (LT) is a complicated surgical procedure with high risk for massive intraoperative blood loss due to pre-existing coagulopathy, portosystemic shunts with collateral circulations, and splenomegaly. The transfusion service will direct most of their resources toward LT programs with great impact on cost. The purpose of this study was to evaluate single center transfusion strategies and to identify the risk factors associated with the intraoperative blood loss and blood transfusion.

    METHODS: The study includes 18 patients who underwent LT at Hospital Selayang between January 2020 and December 2020. Retrospective analysis of data included preoperative assessment of coagulopathy, intraoperative blood loss, and blood component transfusion.

    RESULTS: The mean age in the study group was 36.4 ± 12.68 years. The mean intraoperative blood loss was 4450 ± 1646 ml requiring 4.17 ± 3.3 packed red blood cell (PRBC) units, 7.56 ± 5.5 platelet units, and 9.50 ± 6.0 fresh-frozen plasma units. The independent risk factor for high blood loss (HBL) group was lower preoperative platelet count and it is statistically significant (P = 0.024). The HBL group is associated with higher usage of PRBC (P = 0.024) and platelet units (P = 0.031) and it is statistically significant. The length of stay (LOS) in intensive care unit (ICU) averaging 8.6 ± 4.95 days, and there is no significant differences comparing the HBL and LBL group (P = 0.552). The mortality <90 days for all recipients was 22.2%.

    CONCLUSION: The preoperative platelet count for is the most important factor associated with HBL in LT procedure. The usage of PRBC and platelet units was statistically higher in the HBL group. Comparing HBL and LBL patients, there is no difference in terms of the LOS in ICU postoperatively. A larger sample size would be needed in view of relatively small sample size.

  8. Fulltext Redescription, molecular characterisation and Wolbachia endosymbionts of Mansonella (Tupainema) dunni (Mullin & Orihel, 1972) (Spirurida: Onchocercidae) from the common treeshrew Tupaia glis Diard & Duvaucel (Mammalia: Scandentia) in Peninsular Malaysia
    Mat Udin AS, Uni S, Rodrigues J, Martin C, Junker K, Agatsuma T, et al.
    Curr Res Parasitol Vector Borne Dis, 2024;5:100154.
    PMID: 38193019 DOI: 10.1016/j.crpvbd.2023.100154
    The genus Mansonella Faust, 1929 includes 29 species, mainly parasites of platyrrhine monkeys in South America and anthropoid apes in Africa. In Malaysia, Mansonella (Tupainema) dunni (Mullin & Orihel, 1972) was described from the common treeshrew Tupaia glis Diard & Duvaucel (Scandentia). In a recent classification of the genus Mansonella, seven subgenera were proposed, with M. (Tup.) dunni as a monotypic species in the subgenus Tupainema. In this study, we collected new material of M. (Tup.) dunni from common treeshrews in Peninsular Malaysia and redescribed the morphological features of this species. We found that M. (Tup.) dunni differs from M. (Cutifilaria) perforata Uni et al., 2004 from sika deer Cervus nippon (Cetartiodactyla) in Japan, with regards to morphological features and predilection sites in their respective hosts. Based on multi-locus sequence analyses, we examined the molecular phylogeny of M. (Tup.) dunni and its Wolbachia genotype. Species of the genus Mansonella grouped monophyletically in clade ONC5 and M. (Tup.) dunni was placed in the most derived position within this genus. Mansonella (Tup.) dunni was closely related to M. (M.) ozzardi (Manson, 1897) from humans in Central and South America, and most distant from M. (C.) perforata. The calculated p-distances between the cox1 gene sequences for M. (Tup.) dunni and its congeners were 13.09% for M. (M.) ozzardi and 15.6-16.15% for M. (C.) perforata. The molecular phylogeny of Mansonella spp. thus corroborates their morphological differences. We determined that M. (Tup.) dunni harbours Wolbachia endosymbionts of the supergroup F genotype, in keeping with all other Mansonella species screened to date.
  9. Fulltext Anti-ulcerogenic effect of methanolic extracts from Enicosanthellum pulchrum (King) Heusden against ethanol-induced acute gastric lesion in animal models
    Nordin N, Salama SM, Golbabapour S, Hajrezaie M, Hassandarvish P, Kamalidehghan B, et al.
    PLoS One, 2014;9(11):e111925.
    PMID: 25379712 DOI: 10.1371/journal.pone.0111925
    A natural source of medicine, Enicosanthellum pulchrum is a tropical plant which belongs to the family Annonaceae. In this study, methanol extract from the leaves and stems of this species was evaluated for its gastroprotective potential against mucosal lesions induced by ethanol in rats. Seven groups of rats were assigned, groups 1 and 2 were given Tween 20 (10% v/v) orally. Group 3 was administered omeprazole 20 mg/kg (10% Tween 20) whilst the remaining groups received the leaf and stem extracts at doses of 150 and 300 mg/kg, respectively. After an additional hour, the rats in groups 2-7 received ethanol (95% v/v; 8 mL/kg) orally while group 1 received Tween 20 (10% v/v) instead. Rats were sacrificed after 1 h and their stomachs subjected to further studies. Macroscopically and histologically, group 2 rats showed extremely severe disruption of the gastric mucosa compared to rats pre-treated with the E. pulchrum extracts based on the ulcer index, where remarkable protection was noticed. Meanwhile, a significant percentage of inhibition was shown with the stem extract at 62% (150 mg/kg) and 65% (300 mg/kg), whilst the percentage with the leaf extract at doses of 150 and 300 mg/kg was 63% and 75%, respectively. An increase in mucus content, nitric oxide, glutathione, prostaglandin E2, superoxide dismutase, protein and catalase, and a decrease in malondialdehyde level compared to group 2 were also obtained. Furthermore, immunohistochemical staining of groups 4-7 exhibited down-regulation of Bax and up-regulation of Hsp70 proteins. The methanol extract from the leaves and the stems showed notable gastroprotective potential against ethanol.
  10. Zoonotic infection with Onchocerca dewittei japonica in an 11-year-old boy in Kansai Region, Western Honshu, Japan
    Uni S, Fukuda M, Ogawa K, Lim YA, Agatsuma T, Bunchom N, et al.
    Parasitol Int, 2017 Oct;66(5):593-595.
    PMID: 28648713 DOI: 10.1016/j.parint.2017.06.006
    An 11-year-old boy living in Otsu City, Shiga Prefecture, Kansai Region, Western Honshu, Japan had zoonotic onchocercosis. The patient developed a painful swelling on the little finger of his left hand. The worm detected in the excised mass had external transverse ridges but did not have inner striae in the cuticle. On the basis of the parasite's histopathological characteristics, the causative agent was identified as a female Onchocerca dewittei japonica (Spirurida: Onchocercidae). The species of the filarial parasite was confirmed by sequencing the cox1 gene of the parasite. The Japanese wild boar Sus scrofa leucomystax is a definitive host for O. dewittei japonica, which is then transmitted by blackflies as the vector to humans. The current case described occurred in the Kansai Region, Western Honshu, where such infections were previously not reported.
  11. Description and molecular characteristics of Morishitium polonicum malayense Urabe, Nor Hashim & Uni, n. subsp. (Trematoda: Cyclocoelidae) from the Asian glossy starling, Aplonis panayensis strigata (Passeriformes: Sturnidae) in Peninsular Malaysia
    Urabe M, Nor Hashim NE, Uni S, Iwaki T, Abdullah Halim MR, Marzuki ME, et al.
    Parasitol Int, 2020 Jun;76:102074.
    PMID: 32057926 DOI: 10.1016/j.parint.2020.102074
    We describe Morishitium polonicum malayense n. subsp. from Asian glossy starlings (Aplonis panayensis strigata) (Horsfield, 1821) (Passeriformis: Sturnidae) caught in Malaysia. The trematodes had parasitized the air sacs and the thoracic and body cavities of 40 out of 67 (59.7%) birds examined. The specimens each had an oral sucker, a postpharyngeal genital pore, and tandem testes, but lacked a ventral sucker. The morphological characteristics of our specimens were similar to those of M. polonicum polonicum (Machalska, 1980) from Poland. However, the anterior extremity of vitelline follicles of the present specimens sometimes extended to the level of pharynx. The oral sucker width, oral sucker width/pharynx width ratio, and intertesticular space metrics differed from those of M. p. polonicum. The maximum-likelihood trees based on the cytochrome c oxidase subunit I (COI) and the internal transcribed spacer 2 (ITS2) sequences indicated that the species from the present study formed a sister group with M. p. polonicum from the Czech Republic. The p-distances of COI and ITS2 sequences between the present specimens and M. p. polonicum from the Czech Republic were 6.9-7.5% and 0.6%, respectively. These genetic divergences indicate the border for intra- or interspecific variation of digeneans. The definitive host species and geographical distribution of the current specimens were distinct from those of M. p. polonicum from Europe. We thus concluded that the present specimens are ranked as a new subspecies of M. polonicum, namely M. polonicum malayense n. subsp.
  12. Fulltext Genetic Diversity and Phylogeography of Thottapalayam thottimvirus (Hantaviridae) in Asian House Shrew (Suncus murinus) in Eurasia
    Kikuchi F, Aoki K, Ohdachi SD, Tsuchiya K, Motokawa M, Jogahara T, et al.
    Front Cell Infect Microbiol, 2020;10:438.
    PMID: 32974220 DOI: 10.3389/fcimb.2020.00438
    Murid and cricetid rodents were previously believed to be the principal reservoir hosts of hantaviruses. Recently, however, multiple newfound hantaviruses have been discovered in shrews, moles, and bats, suggesting a complex evolutionary history. Little is known about the genetic diversity and geographic distribution of the prototype shrew-borne hantavirus, Thottapalayam thottimvirus (TPMV), carried by the Asian house shrew (Suncus murinus), which is widespread in Asia, Africa, and the Middle East. Comparison of TPMV genomic sequences from two Asian house shrews captured in Myanmar and Pakistan with TPMV strains in GenBank revealed that the Myanmar TPMV strain (H2763) was closely related to the prototype TPMV strain (VRC66412) from India. In the L-segment tree, on the other hand, the Pakistan TPMV strain (PK3629) appeared to be the most divergent, followed by TPMV strains from Nepal, then the Indian-Myanmar strains, and finally TPMV strains from China. The Myanmar strain of TPMV showed sequence similarity of 79.3-96.1% at the nucleotide level, but the deduced amino acid sequences showed a high degree of conservation of more than 94% with TPMV strains from Nepal, India, Pakistan, and China. Cophylogenetic analysis of host cytochrome b and TPMV strains suggested that the Pakistan TPMV strain was mismatched. Phylogenetic trees, based on host cytochrome b and cytochrome c oxidase subunit I genes of mitochondrial DNA, and on host recombination activating gene 1 of nuclear DNA, suggested that the Asian house shrew and Asian highland shrew (Suncus montanus) comprised a species complex. Overall, the geographic-specific clustering of TPMV strains in Asian countries suggested local host-specific adaptation. Additional in-depth studies are warranted to ascertain if TPMV originated in Asian house shrews on the Indian subcontinent.
  13. Fulltext Description and molecular characterisation of Pelecitus copsychi Uni, Mat Udin & Martin n. sp. (Nematoda: Onchocercidae) from the white-rumped shama Copsychus malabaricus (Scopoli) (Passeriformes: Muscicapidae) of Pahang, Malaysia
    Uni S, Mat Udin AS, Tan PE, Rodrigues J, Martin C, Junker K, et al.
    Curr Res Parasitol Vector Borne Dis, 2022;2:100078.
    PMID: 36589876 DOI: 10.1016/j.crpvbd.2022.100078
    Species of the genus Pelecitus Railliet & Henry, 1910 the most widely distributed avian filariae in Africa and South America. Zoonotic cases in humans were reported in South America. While investigating the filarial fauna of wild animals in Malaysia, we discovered an undescribed filaria from the swollen footpad of the left leg of Copsychus malabaricus (Scopoli) in Pahang, Peninsular Malaysia. Adults of both sexes have a corkscrew-shaped body. Based on comparison of their morphological characteristics (i.e. pre-oesophageal cuticular ring distinct, oesophagus divided, vulva protuberant and situated at the level of anterior half of oesophagus, spicules strongly sclerotized and left spicule with broad blade) with other Pelecitus species, they are here described as Pelecitus copsychi Uni, Mat Udin & Martin n. sp. Multi-locus sequence analyses based on seven genes (12S rDNA, cox1, 18S rDNA, 28S rDNA, MyoHC, rbp1 and hsp70) were performed to determine the phylogenetic position of the new species. The calculated p-distance between the cox1 gene sequences for P. copsychi n. sp. and Pelecitus fulicaeatrae (Diesing, 1861) was 14.1%. Intraspecific genetic variation between two individuals of the new species was 0.4%. In both the Bayesian inference and maximum-likelihood trees, P. copsychi n. sp. was positioned in the second clade of ONC5, containing three genera of the subfamily Dirofilariinae (Foleyella Seurat, 1917, Pelecitus and Loa Stiles, 1905). Immunostaining and molecular analyses remained negative for the presence of Wolbachia endosymbionts. Our findings corroborate the division of the subfamily Dirofilariinae into ONC3 with Dirofilaria Railliet & Henry, 1911 and ONC5 with Pelecitus.
  14. Blood gene signature for early hepatocellular carcinoma detection in patients with chronic hepatitis B
    Omar H, Lim CR, Chao S, Lee MM, Bong CW, Ooi EJ, et al.
    J Clin Gastroenterol, 2015 Feb;49(2):150-7.
    PMID: 25569223 DOI: 10.1097/MCG.0000000000000112
    Up to 25% of chronic hepatitis B (CHB) patients eventually develop hepatocellular carcinoma (HCC), a disease with poor prognosis unless detected early. This study identifies a blood-based RNA biomarker panel for early HCC detection in CHB.
  15. Fulltext Morphological and molecular characteristics of Malayfilaria sofiani Uni, Mat Udin & Takaoka n. g., n. sp. (Nematoda: Filarioidea) from the common treeshrew Tupaia glis Diard & Duvaucel (Mammalia: Scandentia) in Peninsular Malaysia
    Uni S, Mat Udin AS, Agatsuma T, Saijuntha W, Junker K, Ramli R, et al.
    Parasit Vectors, 2017 Apr 20;10(1):194.
    PMID: 28427478 DOI: 10.1186/s13071-017-2105-9
    BACKGROUND: The filarial nematodes Wuchereria bancrofti (Cobbold, 1877), Brugia malayi (Brug, 1927) and B. timori Partono, Purnomo, Dennis, Atmosoedjono, Oemijati & Cross, 1977 cause lymphatic diseases in humans in the tropics, while B. pahangi (Buckley & Edeson, 1956) infects carnivores and causes zoonotic diseases in humans in Malaysia. Wuchereria bancrofti, W. kalimantani Palmieri, Pulnomo, Dennis & Marwoto, 1980 and six out of ten Brugia spp. have been described from Australia, Southeast Asia, Sri Lanka and India. However, the origin and evolution of the species in the Wuchereria-Brugia clade remain unclear. While investigating the diversity of filarial parasites in Malaysia, we discovered an undescribed species in the common treeshrew Tupaia glis Diard & Duvaucel (Mammalia: Scandentia).

    METHODS: We examined 81 common treeshrews from 14 areas in nine states and the Federal Territory of Peninsular Malaysia for filarial parasites. Once any filariae that were found had been isolated, we examined their morphological characteristics and determined the partial sequences of their mitochondrial cytochrome c oxidase subunit 1 (cox1) and 12S rRNA genes. Polymerase chain reaction (PCR) products of the internal transcribed spacer 1 (ITS1) region were then cloned into the pGEM-T vector, and the recombinant plasmids were used as templates for sequencing.

    RESULTS: Malayfilaria sofiani Uni, Mat Udin & Takaoka, n. g., n. sp. is described based on the morphological characteristics of adults and microfilariae found in common treeshrews from Jeram Pasu, Kelantan, Malaysia. The Kimura 2-parameter distance between the cox1 gene sequences of the new species and W. bancrofti was 11.8%. Based on the three gene sequences, the new species forms a monophyletic clade with W. bancrofti and Brugia spp. The adult parasites were found in tissues surrounding the lymph nodes of the neck of common treeshrews.

    CONCLUSIONS: The newly described species appears most closely related to Wuchereria spp. and Brugia spp., but differs from these in several morphological characteristics. Molecular analyses based on the cox1 and 12S rRNA genes and the ITS1 region indicated that this species differs from both W. bancrofti and Brugia spp. at the genus level. We thus propose a new genus, Malayfilaria, along with the new species M. sofiani.

  16. Fulltext Description, molecular characteristics and Wolbachia endosymbionts of Onchocerca borneensis Uni, Mat Udin & Takaoka n. sp. (Nematoda: Filarioidea) from the Bornean bearded pig Sus barbatus Müller (Cetartiodactyla: Suidae) of Sarawak, Malaysia
    Uni S, Mat Udin AS, Agatsuma T, Junker K, Saijuntha W, Bunchom N, et al.
    Parasit Vectors, 2020 Feb 06;13(1):50.
    PMID: 32028994 DOI: 10.1186/s13071-020-3907-8
    BACKGROUND: The genus Onchocerca Diesing, 1841 includes species of medical importance, such as O. volvulus (Leuckart, 1893), which causes river blindness in the tropics. Recently, zoonotic onchocercosis has been reported in humans worldwide. In Japan, O. dewittei japonica Uni, Bain & Takaoka, 2001 from wild boars is a causative agent for this zoonosis. Many filarioid nematodes are infected with Wolbachia endosymbionts which exhibit various evolutionary relationships with their hosts. While investigating the filarial fauna of Borneo, we discovered an undescribed Onchocerca species in the bearded pig Sus barbatus Müller (Cetartiodactyla: Suidae).

    METHODS: We isolated Onchocerca specimens from bearded pigs and examined their morphology. For comparative material, we collected fresh specimens of O. d. dewittei Bain, Ramachandran, Petter & Mak, 1977 from banded pigs (S. scrofa vittatus Boie) in Peninsular Malaysia. Partial sequences of three different genes (two mitochondrial genes, cox1 and 12S rRNA, and one nuclear ITS region) of these filarioids were analysed. By multi-locus sequence analyses based on six genes (16S rDNA, ftsZ, dnaA, coxA, fbpA and gatB) of Wolbachia, we determined the supergroups in the specimens from bearded pigs and those of O. d. dewittei.

    RESULTS: Onchocerca borneensis Uni, Mat Udin & Takaoka n. sp. is described on the basis of morphological characteristics and its genetic divergence from congeners. Molecular characteristics of the new species revealed its close evolutionary relationship with O. d. dewittei. Calculated p-distance for the cox1 gene sequences between O. borneensis n. sp. and O. d. dewittei was 5.9%, while that between O. d. dewittei and O. d. japonica was 7.6%. No intraspecific genetic variation was found for the new species. Wolbachia strains identified in the new species and O. d. dewittei belonged to supergroup C and are closely related.

    CONCLUSIONS: Our molecular analyses of filarioids from Asian suids indicate that the new species is sister to O. d. dewittei. On the basis of its morphological and molecular characteristics, we propose to elevate O. d. japonica to species level as O. japonica Uni, Bain & Takaoka, 2001. Coevolutionary relationships exist between the Wolbachia strains and their filarial hosts in Borneo and Peninsular Malaysia.

  17. Fulltext Assessing the impact of simplified HCV care on linkage to care amongst high-risk patients at primary healthcare clinics in Malaysia: a prospective observational study
    Markby J, Shilton S, Sem X, Chan HK, Md Said R, Siva S, et al.
    BMJ Open, 2021 Dec 24;11(12):e055142.
    PMID: 34952885 DOI: 10.1136/bmjopen-2021-055142
    INTRODUCTION: To achieve the elimination of hepatitis C virus (HCV), substantial scale-up in access to testing and treatment is needed. This will require innovation and simplification of the care pathway, through decentralisation of testing and treatment to primary care settings and task-shifting to non-specialists. The objective of this study was to evaluate the feasibility and effectiveness of decentralisation of HCV testing and treatment using rapid diagnostic tests (RDTs) in primary healthcare clinics (PHCs) among high-risk populations, with referral of seropositive patients for confirmatory viral load testing and treatment.

    METHODS: This observational study was conducted between December 2018 and October 2019 at 25 PHCs in three regions in Malaysia. Each PHC was linked to one or more hospitals, for referral of seropositive participants for confirmatory testing and pretreatment evaluation. Treatment was provided in PHCs for non-cirrhotic patients and at hospitals for cirrhotic patients.

    RESULTS: During the study period, a total of 15 366 adults were screened at the 25 PHCs, using RDTs for HCV antibodies. Of the 2020 (13.2%) HCV antibody-positive participants, 1481/2020 (73.3%) had a confirmatory viral load test, 1241/1481 (83.8%) were HCV RNA-positive, 991/1241 (79.9%) completed pretreatment assessment, 632/991 (63.8%) initiated treatment, 518/632 (82.0%) completed treatment, 352/518 (68.0%) were eligible for a sustained virological response (SVR) cure assessment, 209/352 (59.4%) had an SVR cure assessment, and SVR was achieved in 202/209 (96.7%) patients. A significantly higher proportion of patients referred to PHCs initiated treatment compared with those who had treatment initiated at hospitals (71.0% vs 48.8%, p<0.001).

    CONCLUSIONS: This study demonstrated the effectiveness and feasibility of a simplified decentralised HCV testing and treatment model in primary healthcare settings, targeting high-risk groups in Malaysia. There were good outcomes across most steps of the cascade of care when treatment was provided at PHCs compared with hospitals.

  18. Fulltext Efficacy and safety of ravidasvir plus sofosbuvir in patients with chronic hepatitis C infection without cirrhosis or with compensated cirrhosis (STORM-C-1): interim analysis of a two-stage, open-label, multicentre, single arm, phase 2/3 trial
    Andrieux-Meyer I, Tan SS, Thanprasertsuk S, Salvadori N, Menétrey C, Simon F, et al.
    Lancet Gastroenterol Hepatol, 2021 Jun;6(6):448-458.
    PMID: 33865507 DOI: 10.1016/S2468-1253(21)00031-5
    BACKGROUND: In low-income and middle-income countries, affordable direct-acting antivirals are urgently needed to treat hepatitis C virus (HCV) infection. The combination of ravidasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, and sofosbuvir has shown efficacy and safety in patients with chronic HCV genotype 4 infection. STORM-C-1 trial aimed to assess the efficacy and safety of ravidasvir plus sofosbuvir in a diverse population of adults chronically infected with HCV.

    METHODS: STORM-C-1 is a two-stage, open-label, phase 2/3 single-arm clinical trial in six public academic and non-academic centres in Malaysia and four public academic and non-academic centres in Thailand. Patients with HCV with compensated cirrhosis (Metavir F4 and Child-Turcotte-Pugh class A) or without cirrhosis (Metavir F0-3) aged 18-69 years were eligible to participate, regardless of HCV genotype, HIV infection status, previous interferon-based HCV treatment, or source of HCV infection. Once daily ravidasvir (200 mg) and sofosbuvir (400 mg) were prescribed for 12 weeks for patients without cirrhosis and for 24 weeks for those with cirrhosis. The primary endpoint was sustained virological response at 12 weeks after treatment (SVR12; defined as HCV RNA <12 IU/mL in Thailand and HCV RNA <15 IU/mL in Malaysia at 12 weeks after the end of treatment). This trial is registered with ClinicalTrials.gov, number NCT02961426, and the National Medical Research Register of Malaysia, NMRR-16-747-29183.

    FINDINGS: Between Sept 14, 2016, and June 5, 2017, 301 patients were enrolled in stage one of STORM-C-1. 98 (33%) patients had genotype 1a infection, 27 (9%) had genotype 1b infection, two (1%) had genotype 2 infection, 158 (52%) had genotype 3 infection, and 16 (5%) had genotype 6 infection. 81 (27%) patients had compensated cirrhosis, 90 (30%) had HIV co-infection, and 99 (33%) had received previous interferon-based treatment. The most common treatment-emergent adverse events were pyrexia (35 [12%]), cough (26 [9%]), upper respiratory tract infection (23 [8%]), and headache (20 [7%]). There were no deaths or treatment discontinuations due to serious adverse events related to study drugs. Of the 300 patients included in the full analysis set, 291 (97%; 95% CI 94-99) had SVR12. Of note, SVR12 was reported in 78 (96%) of 81 patients with cirrhosis and 153 (97%) of 158 patients with genotype 3 infection, including 51 (96%) of 53 patients with cirrhosis. There was no difference in SVR12 rates by HIV co-infection or previous interferon treatment.

    INTERPRETATION: In this first stage, ravidasvir plus sofosbuvir was effective and well tolerated in this diverse adult population of patients with chronic HCV infection. Ravidasvir plus sofosbuvir has the potential to provide an additional affordable, simple, and efficacious public health tool for large-scale implementation to eliminate HCV as a cause of morbidity and mortality.

    FUNDING: National Science and Technology Development Agency, Thailand; Department of Disease Control, Ministry of Public Health, Thailand; Ministry of Health, Malaysia; UK Aid; Médecins Sans Frontières (MSF); MSF Transformational Investment Capacity; FIND; Pharmaniaga; Starr International Foundation; Foundation for Art, Research, Partnership and Education; and the Swiss Agency for Development and Cooperation.

  19. Fulltext A collective statement in support of saving pangolins
    Choo SW, Chong JL, Gaubert P, Hughes AC, O'Brien S, Chaber AL, et al.
    Sci Total Environ, 2022 Jun 10;824:153666.
    PMID: 35176378 DOI: 10.1016/j.scitotenv.2022.153666
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