Displaying publications 1 - 20 of 163 in total

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  1. Yong HS, Song SL, Eamsobhana P, Goh SY, Lim PE
    Acta Trop, 2015 Dec;152:157-164.
    PMID: 26348256 DOI: 10.1016/j.actatropica.2015.09.001
    Angiostrongylus cantonensis is a zoonotic parasite that causes eosinophilic meningitis in humans. Earlier work on its mitochondrial genome was based on long polymerase chain reaction method. To date, only the mitogenome of the isolates from China has been studied. We report here the complete mitogenome of the Thailand isolate based on next generation sequencing and compare the genetic diversity with other isolates. The mitogenome of the Thailand isolate (13,519bp) is longer than those of the China isolates (13,497-13,502bp). Five protein-coding genes (atp6, cox1, cox2, cob, nad2) show variations in length among the isolates. The stop codon of the Thailand isolate differs from the China and Taiwan isolates in 4 genes (atp6, cob, nad2, nad6). Additionally, the Thailand isolate has 4 incomplete T stop codon compared to 3 in the China and Taiwan isolates. The control region is longer in the Thailand isolate (258bp) than the China (230-236bp) and Taiwan (237bp) isolates. The intergenic sequence between nad4 and cox1 genes in the Thailand isolate lacks 2bp (indels) at the 5'-end of the sequence as well as differs at 7 other sites compared to the China and Taiwan isolates. In the Thailand isolate, 18 tRNAs lack the entire TΨC-arm, compared to 17 in the China isolate and 16 in the Taiwan isolate. Phylogenetic analyses based on 36 mt-genes, 12 PCGs, 2 rRNA genes, 22 tRNA genes and control region all indicate closer genetic affinity between the China and Taiwan isolates compared to the Thailand isolate. Based on 36 mt-genes, the inter-isolate genetic distance varies from p=3.2% between China and Taiwan isolates to p=11.6% between Thailand and China isolates. The mitogenome will be useful for population, phylogenetics and phylogeography studies.
  2. Yong HS, Song SL, Eamsobhana P, Lim PE
    Acta Trop, 2016 May 17;161:33-40.
    PMID: 27207134 DOI: 10.1016/j.actatropica.2016.05.002
    Angiostrongylus malaysiensis is a nematode parasite of various rat species. When first documented in Malaysia, it was referred to as A. cantonensis. Unlike A. cantonensis, the complete mitochondrial genome of A. malaysiensis has not been documented. We report here its complete mitogenome, its differentiation from A. cantonensis, and the phylogenetic relationships with its congeners and other Metastrongyloid taxa. The whole mitogenome of A. malaysiensis had a total length of 13,516bp, comprising 36 genes (12 PCGs, 2 rRNA and 22 tRNA genes) and a control region. It is longer than that of A. cantonensis (13,509bp). Its control region had a long poly T-stretch of 12bp which was not present in A. cantonensis. A. malaysiensis and A. cantonensis had identical start codon for the 12 PCGs, but four PCGs (atp6, cob, nad2, nad6) had different stop codon. The cloverleaf structure for the 22 tRNAs was similar in A. malaysiensis and A. cantonensis except the TΨC-arm was absent in trnV for A. malaysiensis but present in A. cantonensis. The Angiostrongylus genus was monophyletic, with A. malaysiensis and A. cantonensis forming a distinct lineage from that of A. costaricensis and A. vasorum. The genetic distance between A. malaysiensis and A. cantonensis was p=11.9% based on 12 PCGs, p=9.5% based on 2 rRNA genes, and p=11.6% based on 14 mt-genes. The mitogenome will prove useful for studies on phylogenetics and systematics of Angiostrongylus lungworms and other Metastrongyloid nematodes.
  3. Yong HS, Eamsobhana P, Lim PE, Razali R, Aziz FA, Rosli NS, et al.
    Acta Trop, 2015 Aug;148:51-7.
    PMID: 25910624 DOI: 10.1016/j.actatropica.2015.04.012
    Angiostrongylus cantonensis is a bursate nematode parasite that causes eosinophilic meningitis (or meningoencephalitis) in humans in many parts of the world. The genomic data from A. cantonensis will form a useful resource for comparative genomic and chemogenomic studies to aid the development of diagnostics and therapeutics. We have sequenced, assembled and annotated the genome of A. cantonensis. The genome size is estimated to be ∼260 Mb, with 17,280 genomic scaffolds, 91X coverage, 81.45% for complete and 93.95% for partial score based on CEGMA analysis of genome completeness. The number of predicted genes of ≥300 bp was 17,482. A total of 7737 predicted protein-coding genes of ≥50 amino acids were identified in the assembled genome. Among the proteins of known function, kinases are the most abundant followed by transferases. The draft genome contains 34 excretory-secretory proteins (ES), a minimum of 44 Nematode Astacin (NAS) metalloproteases, 12 Homeobox (HOX) genes, and 30 neurotransmitters. The assembled genome size (260 Mb) is larger than those of Pristionchus pacificus, Caenorhabditis elegans, Necator americanus, Caenorhabditis briggsae, Trichinella spiralis, Brugia malayi and Loa loa, but smaller than Haemonchus contortus and Ascaris suum. The repeat content (25%) is similar to H. contortus. The GC content (41.17%) is lower compared to P. pacificus (42.7%) and H. contortus (43.1%) but higher compared to C. briggsae (37.69%), A. suum (37.9%) and N. americanus (40.2%) while the scaffold N50 is 42,191. This draft genome will facilitate the understanding of many unresolved issues on the parasite and the disorder it causes.
  4. Yong HS, Eamsobhana P, Song SL, Prasartvit A, Lim PE
    Acta Trop, 2015 Aug;148:66-71.
    PMID: 25930187 DOI: 10.1016/j.actatropica.2015.04.020
    Angiostrongylus cantonensis is an important emerging zoonotic parasite causing human eosinophilic meningitis (or meningoencephalitis) in many parts of the world. To-date there is only a single study using mitochondrial cytochrome b (CYTB) gene to determine its genetic structure in eight geographical localities in Thailand. The present study examined the molecular phylogeography of this rat lungworm and its phylogenetic relationship with congeners using CYTB gene marker. A total of 15 CYTB haplotypes was found in 37 sequences from 14 geographical localities (covering north, west, east, central and south regions) in Thailand. These CYTB haplotypes were distinct from those of A. cantonensis for China and Hawaii. In Thailand, some CYTB haplotypes appeared to be confined to specific geographical localities. The partial CYTB DNA nucleotide sequences separated unequivocally the A. cantonensis isolates of Thailand, China and Hawaii as well as the congeners Angiostrongylus malaysiensis, A. costaricensis and Angiostrongylus vasorum, with A. malaysiensis grouped with A. cantonensis and A. costaricensis grouped with A. vasorum. Likewise the congeners of Metastrongylus and Onchocerca genera could also be clearly differentiated. The present study added two new definitive hosts (Bandicota savilei and Rattus losea) and three new localities (Mae Hong Son in the north, Tak in the west, and Phang Nga in the south) for A. malaysiensis in Thailand, indicating its wide occurrence in the country. Three CYTB haplotypes were found in the Thailand samples of A. malaysiensis. In addition to differentiation of congeners, CYTB gene marker could be used for determining the genetic diversity of a given population/taxon.
  5. Yap MK, Fung SY, Tan KY, Tan NH
    Acta Trop, 2014 May;133:15-25.
    PMID: 24508616 DOI: 10.1016/j.actatropica.2014.01.014
    The proteome of Naja sumatrana (Equatorial spitting cobra) venom was investigated by shotgun analysis and a combination of ion-exchange chromatography and reverse phase HPLC. Shotgun analysis revealed the presence of 39 proteins in the venom while the chromatographic approach identified 37 venom proteins. The results indicated that, like other Asiatic cobra venoms, N. sumatrana contains large number of three finger toxins and phospholipases A2, which together constitute 92.1% by weight of venom protein. However, only eight of the toxins can be considered as major venom toxins. These include two phospholipases A2, three neurotoxins (two long neurotoxins and a short neurotoxin) and three cardiotoxins. The eight major toxins have relative abundance of 1.6-27.2% venom proteins and together account for 89.8% (by weight) of total venom protein. Other venom proteins identified include Zn-metalloproteinase-disintegrin, Thaicobrin, CRISP, natriuretic peptide, complement depleting factors, cobra venom factors, venom nerve growth factor and cobra serum albumin. The proteome of N. sumatrana venom is similar to proteome of other Asiatic cobra venoms but differs from that of African spitting cobra venom. Our results confirm that the main toxic action of N. sumatrana venom is neurotoxic but the large amount of cardiotoxins and phospholipases A2 are likely to contribute significantly to the overall pathophysiological action of the venom. The differences in toxin distribution between N. sumatrana venom and African spitting cobra venoms suggest possible differences in the pathophysiological actions of N. sumatrana venom and the African spitting cobra venoms, and explain why antivenom raised against Asiatic cobra venom is not effective against African spitting cobra venoms.
  6. Ya'cob Z, Takaoka H, Pramual P, Low VL, Sofian-Azirun M
    Acta Trop, 2016 Jan;153:57-63.
    PMID: 26476394 DOI: 10.1016/j.actatropica.2015.10.007
    To investigate the breeding habitat preference of black flies, a comprehensive black fly survey was conducted for the first time in Peninsular Malaysia. Preimaginal black flies (pupae and larvae) were collected manually from 180 stream points encompassing northern, southern, central and east coast of the Peninsular Malaysia. A total of 47 black fly species were recorded in this study. The predominant species were Simulium trangense (36.7%) and Simulium angulistylum (33.3%). Relatively common species were Simulium cheongi (29.4%), Simulium tani (25.6%), Simulium nobile (16.2%), Simulium sheilae (14.5%) and Simulium bishopi (10.6%). Principal Component Analysis (PCA) of all stream variables revealed four PCs that accounted for 69.3% of the total intersite variance. Regression analysis revealed that high species richness is associated with larger, deeper, faster and higher discharge streams with larger streambed particles, more riparian vegetation and low pH (F=22.7, d.f.=1, 173; P<0.001). Relationship between species occurrence of seven common species (present in >10% of the sampling sites) was assessed. Forward logistic regression analysis indicated that four species were significantly related to the stream variables. S. nobile and S. tani prefer large, fast flowing streams with higher pH, large streambed particles and riparian trees. S. bishopi was commonly found at high elevation with cooler stream, low conductivity, higher conductivity and more riparian trees. In contrast, S. sheilae was negatively correlated with PC-2, thus, this species commonly found at low elevation, warmer stream with low conductivity and less riparian trees. The results of this study are consistent with previous studies from other geographic regions, which indicated that both physical and chemical stream conditions are the key factors for black fly ecology.
  7. Ya'cob Z, Takaoka H, Low VL, Sofian-Azirun M
    Acta Trop, 2018 Sep;185:110-114.
    PMID: 29709632 DOI: 10.1016/j.actatropica.2018.04.029
    Simulium (Simulium) hackeri Edwards, 1928 of the Simulium variegatum species-group from Malaysia was described initially based on the female specimen from Cameron Highlands, Pahang. In the present study, the pupa and larva of this species are described for the first time. Their morphological characters resemble those of the Simulium variegatum species-group by having six gill filaments per side, abdomen with dorsal spine-combs at least on segments 7 and 8, cocoon with wall-pocket shaped and with or without an anterodorsal projection. Postgenal cleft of the larva medium-sized, rarely small, ventral papillae small or absent. The DNA barcode of this species is also reported herein.
  8. Ya'cob Z, Takaoka H, Low VL, Sofian-Azirun M
    Acta Trop, 2017 May;169:133-141.
    PMID: 28185824 DOI: 10.1016/j.actatropica.2017.02.005
    A black fly species of the Simulium feuerborni species-group of Simulium (Nevermannia) from Cameron Highland, Peninsular Malaysia, previously regarded as S. feuerborni Edwards, originally described from East Java, is described as Simulium pairoti sp. nov. based on complete life stages. High intraspecific variations in the arrangement of the six pupal gill filaments, length of the stalk of the ventral paired filaments, and length of the anterodorsal projection of the cocoon, are noted in this species. This new species is readily distinguished from its congeners by having the characters of male genitalia with simple lamellate ventral plate, short inwardly-twisted styles, several parameral hooks, and a simple narrow median sclerite. Morphological data reported herein plus the chromosomal and molecular data presented elsewhere support S. pairoti as a novel pseudocryptic species.
  9. Ya'cob Z, Takaoka H, Low VL, Sofian-Azirun M
    Acta Trop, 2017 Mar;167:31-39.
    PMID: 27986545 DOI: 10.1016/j.actatropica.2016.12.009
    In recent decades, the numbers of cryptic taxa have increased significantly with current progress in DNA barcoding, yet, most of these cryptic taxa have not been formally named and recognized as valid species. To address this issue, we provide a guide for applying the procedure of describing new cryptic species in the family Simuliidae. Simulium (Simulium) vanluni from Pahang, Peninsular Malaysia, previously treated as S. nobile De Meijere, is described as a new species by using an integrated morpho-taxonomical and genetic approach. This new species is morphologically identical to S. nobile from Java and S. kiuliense Smart & Clifford from Borneo, but their distinctiveness is supported by an expanded multigene phylogeny analysis.
  10. Ya'cob Z, Takaoka H, Low VL, Tan TK, Sofian-Azirun M
    Acta Trop, 2019 May;193:66-70.
    PMID: 30807749 DOI: 10.1016/j.actatropica.2019.02.023
    Simulium (Gomphostilbia) aziruni Takaoka, Hashim & Chen was described initially based only on a pupa and a mature larva collected from Peninsular Malaysia. Herein, we describe the morphological characters of the female of S. aziruni for the first time. It resembles those of the other members of the Simulium gombakense species-group by the genital fork with a distinct projection directed medioposteriorly from each arm and claw with a large basal tooth. Cytochrome c oxidase I (COI) barcoding analysis indicates that S. aziruni is the sister species of S. maleewongae, but both are distantly separated by a genetic distance of 4.9%.
  11. Ya'cob Z, Takaoka H, Low VL, Sofian-Azirun M
    Acta Trop, 2018 Jun;182:1-3.
    PMID: 29453951 DOI: 10.1016/j.actatropica.2018.02.007
    Simulium (Simulium) rasuli sp. nov. is described from two females collected by a Malaise trap in Genting Highlands, Peninsular Malaysia. This new species is placed in the Simulium christophersi species-group of the subgenus Simulium. The female of this new specie is characterized by the scutum with three longitudinal vittae, dark legs, claw with a small subbasal tooth, and ovipositor valve triangular with its inner margin nearly straight. This new species is distinguished in the female from all the six named species of the species-group by the entirely brownish-black femora and tibiae.
  12. Wong WK, Foo PC, Olivos-Garcia A, Noordin R, Mohamed Z, Othman N, et al.
    Acta Trop, 2017 Aug;172:208-212.
    PMID: 28506795 DOI: 10.1016/j.actatropica.2017.05.017
    Crude soluble antigen (CSA) produced from Entamoeba histolytica trophozoite is conventionally used for serodiagnosis of invasive amoebiasis. However, high background seropositivities by CSA-assay in endemic areas complicate the interpretation of positive result in clinical settings. Instead, incorporating a second assay which indicates active or recent infection into the routine amoebic serology could possibly complement the limitations of CSA-assay. Hence, the present study aimed to evaluate the diagnostic efficacies of indirect ELISAs using CSA and excretory-secretory antigen (ESA) for serodiagnosis of amoebic liver abscess (ALA). Reference standard for diagnosis of ALA at Hospital Universiti Sains Malaysia is based on clinical presentation, radiological imaging and positive indirect haemagglutination assay (titer ≥256). Five groups of human serum samples collected from the hospital included Group I - ALA diagnosed by the reference standard and pus aspirate analysis using real-time PCR (n=10), Group II - ALA diagnosed by the reference standard only (n=41), Group III - healthy control (n=45), Group IV - other diseases control (n=51) and Group V - other infectious diseases control (n=31). For serodiagnosis of ALA serum samples (Group I and II), CSA-ELISA showed sensitivities of 100% for both groups, while ESA-ELISA showed sensitivities of 100% and 88%, respectively. For serodiagnosis of non-ALA serum samples (Group III, IV and V), CSA-ELISA showed specificities of 91%, 75% and 100%, respectively; while ESA-ELISA showed specificities of 96%, 98% and 100%, respectively. Indirect ELISAs using CSA and ESA have shown distinct strength for serodiagnosis of ALA, in terms of sensitivity and specificity, respectively. In conclusion, parallel analysis by both assays improved the overall efficacies of amoebic serology as compared to either single assay.
  13. Wong MTJ, Anuar NS, Noordin R, Tye GJ
    Acta Trop, 2023 Mar;239:106796.
    PMID: 36586174 DOI: 10.1016/j.actatropica.2022.106796
    It has been tested and proven that vaccination is still the best strategy to combat infectious diseases. However, to date, there are still no vaccines against human soil-transmitted helminthic diseases, despite their high prevalence globally, particularly in developing countries and rural areas with tropical climates and poor sanitation. The development of vaccines against helminths is riddled with obstacles. Helminths have a complex life cycle, multiple stages within the same host with stage-specific antigen expression, and the ability to regulate host immune reactions to evade the immune response. These elements contribute to the main challenge of helminthic vaccines: the identification of effective vaccine candidates. Therefore, this article reviews the current progress and potential future direction of soil-transmitted helminthic vaccines, particularly against Trichuris trichiura, Ascaris lumbricoides, Strongyloides stercoralis, Necator americanus and Ancylostoma duodenale. The study design employed was a systematic review, using qualitative meta-summary synthesis. Preclinical studies and clinical trials on the development of protein subunit vaccines against the five soil-transmitted helminths were searched on PubMed and Scopus. Effectiveness was indicated by a reduction in worm burden or larval output, an increase in specific IgG levels, or an increase in cytokine production. Our findings show that only the hookworm vaccine against N. americanus is in the clinical trial phase, while the rest is still in exploratory research and pre-clinical development phase.
  14. Wong MTJ, Anuar NS, Noordin R, Tye GJ
    Acta Trop, 2024 Mar;251:107122.
    PMID: 38246399 DOI: 10.1016/j.actatropica.2024.107122
    Strongyloidiasis, caused by the nematode Strongyloides stercoralis, remains a threat to global public health, and a vaccine would be useful to control the disease, especially in developing countries. This study aimed to evaluate the efficacy of recombinant proteins, A133 and Ss-IR, as potential vaccine candidates against strongyloidiasis by investigating the humoral and cellular immune responses in immunized mice. Respective antigens were adjuvanted with Complete Freund's Adjuvant (prime) and Incomplete Freund's Adjuvant (boost) and administered intraperitoneally (prime) and subcutaneously (boost) to female BALB/c mice. For antigen-only doses, only antigens were injected without adjuvants. Altogether, 1 prime dose, 4 booster doses, and 2 antigen-only doses were administered successively. ELISAs were conducted to assess the antibody responses, along with flow cytometry and cytokine ELISA to elucidate the cellular immune responses. Results showed that A133 and Ss-IR induced the production of IgG1 and IgG2a, with A133 generating more robust IgG2a responses than Ss-IR. Flow cytometry findings indicated that effector CD8+T-cells and memory B-cells activity were upregulated significantly for A133 only, whereas cytokine ELISA demonstrated that a Th1/Th2/Th17 mixed cell responses were triggered upon vaccination with either antigen. This preliminary study illustrated the good potential of recombinant A133 and Ss-IR as vaccine candidates against S. stercoralis. It provided information on the probable immune mechanism involved in host defence and the elicitation of protection against S. stercoralis.
  15. Win SY, Chel HM, Hmoon MM, Htun LL, Bawm S, Win MM, et al.
    Acta Trop, 2020 Dec;212:105719.
    PMID: 32976841 DOI: 10.1016/j.actatropica.2020.105719
    Village chicken production, a traditional, small-scale, and extensive backyard poultry industry, has been profitable for local farmers in Myanmar. However, there is scanty information available concerning the infection of these chickens with avian pathogens, including haemoprotozoan parasites. In the present study, we provide the first report of microscopic detection and molecular identification of Leucocytozoon and Plasmodium parasites from seven different areas of Myanmar. Leucocytozoon gametocytes were detected in 17.6% (81/461) of the blood smears from village chickens. The nested polymerase chain reaction (PCR) for targeting Leucocytozoon mitochondrial cytochrome b (cyt b) genes had a 17.6% positive rate. Although the positive rate of nested PCR targeting Plasmodium/Haemoproteus cyt b was 34.3%, the PCR protocol was observed to possibly amplify DNA of a certain species of Leucocytozoon. There were no obvious clinical signs in the infected birds. Statistical analysis of the microscopic detection and PCR detection rates using the age and sex of birds as internal factors revealed that the statistical significances differed according to the study area. The sequencing of 32 PCR products obtained from each study area revealed infection by Leucocytozoon caulleryi in three birds, Leucocytozoon sabrazesi in two birds, Leucocytozoon schoutedeni in two birds, Leucocytozoon sp. in eighteen birds, and Plasmodium juxtanucleare in seven birds; however, Haemoproteus infection was not detected. While L. sabrazesi was detected in chickens from the central region of Myanmar, the other haemosporidians were detected in those from different areas. In the haplotype analysis, we detected 17 haemosporidian cyt b haplotypes, including two for L. caulleryi, one for L. sabrazesi, two for L. schoutedeni, nine for Leucocytozoon sp., and three for P. juxtanucleare. Phylogenetic analysis of the cyt b haplotypes revealed a considerably close genetic relationship among chicken haemosporidians detected in Myanmar, Thailand, and Malaysia. These results indicate that well-recognized widespread species of chicken Leucocytozoon and Plasmodium are distributed nationwide in Myanmar, providing new insights into the ecosystem and control strategies of haemosporidian parasites in domesticated chickens in Myanmar.
  16. Whittaker MA, Naing C, Tung WS, Aung HH, Wah MJ
    Acta Trop, 2023 Oct 20.
    PMID: 37866729 DOI: 10.1016/j.actatropica.2023.107049
    Lymphatic filariasis is a public health problem and targeted for global elimination. WHO recommends mass drug administration to interrupt transmission of the parasites involved. There are concerns that transmission interruption may be difficult in areas of zoonotic filarial infections. This study aimed to estimate the pooled prevalence of zoonotic brugian filariasis, and to compare the pooled prevalence of brugian filariasis in human and animal populations in the same area based on available studies. A comprehensive literature search was conducted in health-related electronic databases (PubMed, Ovid MEDLINE, Index Medicus, google scholar). A random-effect meta-analysis of the pooled overall prevalence of filariasis in animal populations was conducted. Sixteen studies from four different Asian countries were identified. Studies were conducted most frequently in Thailand (n = 7), followed by Malaysia (n = 5), India (n = 3), and Sri Lanka (n = 1). Regardless of animal group, the pooled overall prevalence of animal Brugia infections was 13% (95%CI: 7-21%, I2:98%, 16 studies). On stratification, the pooled overall prevalence in the animal population was 19% (95%CI: 1-50%, I2: 99%, 3 studies) in India, 8% (95%CI: 2-7%, I2: 97%, 5 studies) in Malaysia, and 13% (95%CI: 7-20%, I2: 94%, 7 studies) in Thailand. The prevalence in the animal population was 17% (95%CI: 13-21%, 1 study) in Sri Lanka. The pooled overall prevalence of Brugia malayi was 13% (95%CI: 7-21%, I2:98%, 12 studies), while for Brugia pahangi this was 12% (95%CI: 7-19%, I2:86%, 7 studies). Regardless of animal group, geographic area, or diagnostic test, the prevalence of B. malayi was consistently high. On stratification by animal category, the pooled overall prevalence was 10% (95%CI: 6-14%, I2:92%, 13 studies) in cats, 12% (95%CI: 2-28%, I2: 99%, 6 studies) in dogs, and 55% (95%CI: 47-63%, 1 study) in leaf-eating monkeys. The findings show the extent of zoonotic Brugiainfections in domestic cats and dogs, suggesting that these animals are potential reservoirs for human brugian filariasis in the study countries. To substantiate this with more accuracy, future well designed whole genomic sequencing of individual mf collected from humans and B. malayi infected animals in the same area are needed.
  17. Walvekar S, Anwar A, Anwar A, Sridewi N, Khalid M, Yow YY, et al.
    Acta Trop, 2020 Nov;211:105618.
    PMID: 32628912 DOI: 10.1016/j.actatropica.2020.105618
    Acanthamoeba spp. are free living amoeba (FLA) which are widely distributed in nature. They are opportunistic parasites and can cause severe infections to the eye, skin and central nervous system. The advances in drug discovery and modifications in the chemotherapeutic agents have shown little improvement in morbidity and mortality rates associated with Acanthamoeba infections. The mechanism-based process of drug discovery depends on the molecular drug targets present in the signaling pathways in the genome. Synthetic libraries provide a platform for broad spectrum of activities due to their desired structural modifications. Azoles, originally a class of synthetic anti-fungal drugs, disrupt the fungal cell membrane by inhibiting the biosynthesis of ergosterol through the inhibition of cytochrome P450 dependent 14α-lanosterol, a key step of the sterol pathway. Acanthamoeba and fungi share the presence of similar sterol intermediate, as ergosterol is also the major end-product in the sterol biosynthesis in Acanthamoeba. Sterols present in the eukaryotic cell membrane are one of the most essential lipids and exhibit important structural and signaling functions. Therefore, in this review we highlight the importance of specific targeting of ergosterol present in Acanthamoebic membrane by azole compounds for amoebicidal activity. Previously, azoles have also been repurposed to report antimicrobial, antiparasitic and antibacterial properties. Moreover, by loading the azoles into nanoparticles through advanced techniques in nanotechnology, such as physical encapsulation, adsorption, or chemical conjugation, the pharmacokinetics and therapeutic index of the drugs can be significantly improved. The current review proposes an important strategy to target Acanthamoeba using synthetic libraries of azoles and their conjugated nanoparticles for the first time.
  18. Vythilingam I, Chan ST, Shanmugratnam C, Tanrang H, Chooi KH
    Acta Trop, 2005 Oct;96(1):24-30.
    PMID: 16076459
    A study was carried out from July 2001 until January 2003 in the Kinabatangan area of Sabah, part of Borneo island, where malaria used to be mesoendemic. Vector surveys determined that Plasmodium falciparum was the predominant species and Anopheles balabacensis the primary vector. Malaria cases have dropped drastically over the years but P. falciparum is still predominant. In the present study, Anopheles donaldi was the predominant species and was positive for sporozoites. Although An. balabacensis was present, none were infective. An. donaldi bite more outdoors than indoors and have a peak biting time from 18:00 to 19:00 h when most people are still out of their homes. An integrated malaria control programme along with area development has helped in the control of malaria and its vector.
  19. Tran L, Radwan I, Minh LHN, Low SK, Hashan MR, Gomaa MD, et al.
    Acta Trop, 2021 Jan 06.
    PMID: 33421421 DOI: 10.1016/j.actatropica.2021.105823
    BACKGROUND AND OBJECTIVES: Modulation of the immune reaction is essential in the development of various diseases, including dengue's "Cytokine Tsunami", an increase in vascular permeability with concomitant severe vascular leakage. We aim to identify the role of T-helper (Th) cells, Th2 and Th7, with their related cytokines in dengue pathogenesis.

    MATERIAL AND METHODS: Nine electronic databases and manual search were applied to detect available publications. A meta-analysis using a fixed- or random-effect model was performed to measure standardized mean difference (SMD) with 95% confidence interval (CI). The National Institute of Health (NIH) tools for observational cohort, cross-sectional, and case-control studies were used to examine the risk of bias. The protocol was recorded in PROSPERO with CRD42017060230.

    RESULTS: A total of 38 articles were found including 19 case-control, 11 cross-sectional and 8 prospective cohort studies. We indicated that Th2 cytokines (IL-4, IL-6, IL-8) and Th17 cytokine (IL-17) in dengue patients were notably higher than in a healthy control group in acute phase (SMD = 1.59, 95% CI [0.68, 2.51], p = 0.001; SMD = 1.24, 95% CI [0.41, 2.06], p = 0.003; SMD = 1.13, 95% CI [0.61, 1.66], p<0.0001; SMD = 1.74, 95% CI [0.87, 2.61], p<0.0001), respectively.

    CONCLUSIONS: This study provides evidence of the significant roles of IL-4, IL-6, IL-8, IL-10 and IL-17 in the pathogenesis of developing a severe reaction in dengue fever. However, to fully determine the association of Th cytokines with dengue, it is necessary to perform further studies to assess kinetic levels during the duration of the illness.

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