Displaying publications 141 - 160 of 173 in total

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  1. Chong ETJ, Neoh JWF, Lau TY, Lim YA, Chua KH, Lee PC
    Acta Trop, 2018 May;181:35-39.
    PMID: 29409854 DOI: 10.1016/j.actatropica.2018.01.018
    Malaria is a notorious disease which causes major global morbidity and mortality. This study aims to investigate the genetic and haplotype differences of Plasmodium knowlesi (P. knowlesi) isolates in Malaysian Borneo and Peninsular Malaysia based on the molecular analysis of the cytochrome b (cyt b) gene. The cyt b gene of 49 P. knowlesi isolates collected from Sabah, Malaysian Borneo and Peninsular Malaysia was amplified using PCR, cloned into a commercialized vector and sequenced. In addition, 45 cyt b sequences were retrieved from humans and macaques bringing to a total of 94 cyt b gene nucleotide sequences for phylogenetic analysis. Genetic and haplotype analyses of the cyt b were analyzed using MEGA6 and DnaSP ver. 5.10.01. The haplotype genealogical linkage of cyt b was generated using NETWORK ver. 4.6.1.3. Our phylogenetic tree revealed the conservation of the cyt b coding sequences with no distinct cluster across different geographic regions. Nucleotide analysis of cyt b showed that the P. knowlesi isolates underwent purifying selection with population expansion, which was further supported by extensive haplotype sharing between the macaques and humans from Malaysian Borneo and Peninsular Malaysia in the median-joining network analysis. This study expands knowledge on conservation of the zoonotic P. knowlesi cyt b gene between Malaysian Borneo and Peninsular Malaysia.
  2. Engku Nur Syafirah EAR, Nurul Najian AB, Foo PC, Mohd Ali MR, Mohamed M, Yean CY
    Acta Trop, 2018 Jun;182:223-231.
    PMID: 29545156 DOI: 10.1016/j.actatropica.2018.03.004
    Cholera, caused by Vibrio cholerae is a foodborne disease that frequently reported in food and water related outbreak. Rapid diagnosis of cholera infection is important to avoid potential spread of disease. Among available diagnostic platforms, loop-mediated isothermal amplification (LAMP) is regarded as a potential diagnostic tool due to its rapidity, high sensitivity and specificity and independent of sophisticated thermalcycler. However, the current LAMP often requires multiple pipetting steps, hence is susceptible to cross contamination. Besides, the strict requirement of cold-chain during transportation and storage make its application in low resource settings to be inconvenient. To overcome these problems, the present study is aimed to develop an ambient-temperature-stable and ready-to-use LAMP assay for the detection of toxigenic Vibrio cholerae in low resource settings. A set of specific LAMP primers were designed and tested against 155 V. cholerae and non-V. cholerae strains. Analytical specifity showed that the developed LAMP assay detected 100% of pathogenic V. cholerae and did not amplified other tested bacterial strains. Upon testing against stool samples spiked with toxigenic V. cholerae outbreak isolates, the LAMP assay detected all of the spiked samples (n = 76/76, 100%), in contrast to the conventional PCR which amplified 77.6% (n = 59/76) of the tested specimens. In term of sensitivity, the LAMP assay was 100-fold more sensitive as compared to the conventional PCR method, with LOD of 10 fg per μL and 10 CFU per mL. Following lyophilisation with addition of lyoprotectants, the dry-reagent LAMP mix has an estimated shelf-life of 90.75 days at room temperature.
  3. Low GK, Ogston SA, Yong MH, Gan SC, Chee HY
    Acta Trop, 2018 Jun;182:237-245.
    PMID: 29545158 DOI: 10.1016/j.actatropica.2018.03.014
    BACKGROUND: Since the introduction of 2009 WHO dengue case classification, no literature was found regarding its effect on dengue death. This study was to evaluate the effect of 2009 WHO dengue case classification towards dengue case fatality rate.

    METHODS: Various databases were used to search relevant articles since 1995. Studies included were cohort and cross-sectional studies, all patients with dengue infection and must report the number of death or case fatality rate. The Joanna Briggs Institute appraisal checklist was used to evaluate the risk of bias of the full-texts. The studies were grouped according to the classification adopted: WHO 1997 and WHO 2009. Meta-regression was employed using a logistic transformation (log-odds) of the case fatality rate. The result of the meta-regression was the adjusted case fatality rate and odds ratio on the explanatory variables.

    RESULTS: A total of 77 studies were included in the meta-regression analysis. The case fatality rate for all studies combined was 1.14% with 95% confidence interval (CI) of 0.82-1.58%. The combined (unadjusted) case fatality rate for 69 studies which adopted WHO 1997 dengue case classification was 1.09% with 95% CI of 0.77-1.55%; and for eight studies with WHO 2009 was 1.62% with 95% CI of 0.64-4.02%. The unadjusted and adjusted odds ratio of case fatality using WHO 2009 dengue case classification was 1.49 (95% CI: 0.52, 4.24) and 0.83 (95% CI: 0.26, 2.63) respectively, compared to WHO 1997 dengue case classification. There was an apparent increase in trend of case fatality rate from the year 1992-2016. Neither was statistically significant.

    CONCLUSIONS: The WHO 2009 dengue case classification might have no effect towards the case fatality rate although the adjusted results indicated a lower case fatality rate. Future studies are required for an update in the meta-regression analysis to confirm the findings.

  4. Takaoka H, Srisuka W, Van Lun Low, Saeung A
    Acta Trop, 2018 Jun;182:271-284.
    PMID: 29551392 DOI: 10.1016/j.actatropica.2018.03.019
    Five new species of black flies, Simulium (Gomphostilbia) chiangraiense, S. (G.) huaikaeoense, S. (G.) khaokhoense, S. (G.) maeklangense, and S. (G.) pamiangense, are described based on adults, pupae and mature larvae from Thailand. These five species are similar to one another and are placed in the S. decuplum subgroup of the S. batoense species-group by having the male fore coxae darkened, ventral plate flat and transverse; pupal gill with 10 short filaments; and larval postgenal cleft deep approaching or reaching the posterior margin of the hypostoma. Simulium (G.) chiangraiense sp. nov. and S. (G.) pamiangense sp. nov. differ from the three other new species by the much longer pupal gill filaments and darkened dorsal surface of abdominal segments 1 and 2. Taxonomic notes are provided to distinguish these five new species from five other related species. The phylogenetic positions of these new species in the S. decuplum subgroup are presented based on the mitochondrial COI gene. Simulium (G.) pamiangense sp. nov. and S. (G.) huaikaeoense sp. nov. are highly similar to each other genetically, showing a sister relationship, though they are clearly different morphologically. On the contrary, S. (G.) khaokhoense sp. nov. is distantly positioned from S. (G.) huaikaeoense nov., though it is almost indistinguishable morphologically from the latter.
  5. Tao Y, Shen C, Zhang Y, Zhao X, Leow CY, Wu J, et al.
    Acta Trop, 2023 Feb;238:106783.
    PMID: 36455636 DOI: 10.1016/j.actatropica.2022.106783
    BACKGROUND: The scale-up of zoonoses prevention control and eradication in China, coupled with numerous academic articles in Chinese journals has led to the development of new tools and strategies aimed at further consolidating parasite control goals. As a result, there is a growing need for an up-to-date understanding of the research progress and prevention and control experience of parasitic diseases in China.

    METHODS: To understand the research status of schistosomiasis and toxoplasmosis in China, academic articles published in Chinese journals from 1980 to 2021 were retrieved from China National Knowledge Infrastructure (CNKI) and Wanfang databases. The Bibliographic Items Co-occurrence Matrix Builder (BICOMB) software was used to extract and analyze the keyword frequencies. The 'K/A ratio' as the frequency of a keyword that occurred in all the articles within a certain time stage was calculated to compare the popularity of the same keyword in different time stages. Keyword co-occurrence network maps were constructed by VOSviewer software.

    RESULTS: A total of 18,508 articles in the research field of Schistosoma and 13,289 articles in the field of Toxoplasma gondii were included. Results in both fields showed some similarities: the annual number of articles presented an increasing trend before entering the 21st century and decreased rapidly in recent years. Two opposite changing trends of keyword frequency could be observed in the K/A ratio analysis: the K/A ratios of 'Surveillance' and 'Infection' continuously increased over time, while those of 'Schistosoma mansoni' and 'Mesenteric lymph nodes' decreased. The diversification of keyword co-occurrence networks could be observed in the co-occurrence network maps.

    CONCLUSIONS: This bibliometric analysis reveals trends in research themes in the fields of Schistosoma and Toxoplasma gondii from 1980 to 2021, presenting China's experience such as a high degree of government involvement and multidisciplinary participation in schistosomiasis and toxoplasmosis control and elimination.

  6. Ong SQ, Pauzi MBM, Gan KH
    Acta Trop, 2022 Jul;231:106447.
    PMID: 35430265 DOI: 10.1016/j.actatropica.2022.106447
    Mosquito-borne diseases are emerging and re-emerging across the globe, especially after the COVID19 pandemic. The recent advances in text mining in infectious diseases hold the potential of providing timely access to explicit and implicit associations among information in the text. In the past few years, the availability of online text data in the form of unstructured or semi-structured text with rich content of information from this domain enables many studies to provide solutions in this area, e.g., disease-related knowledge discovery, disease surveillance, early detection system, etc. However, a recent review of text mining in the domain of mosquito-borne disease was not available to the best of our knowledge. In this review, we survey the recent works in the text mining techniques used in combating mosquito-borne diseases. We highlight the corpus sources, technologies, applications, and the challenges faced by the studies, followed by the possible future directions that can be taken further in this domain. We present a bibliometric analysis of the 294 scientific articles that have been published in Scopus and PubMed in the domain of text mining in mosquito-borne diseases, from the year 2016 to 2021. The papers were further filtered and reviewed based on the techniques used to analyze the text related to mosquito-borne diseases. Based on the corpus of 158 selected articles, we found 27 of the articles were relevant and used text mining in mosquito-borne diseases. These articles covered the majority of Zika (38.70%), Dengue (32.26%), and Malaria (29.03%), with extremely low numbers or none of the other crucial mosquito-borne diseases like chikungunya, yellow fever, West Nile fever. Twitter was the dominant corpus resource to perform text mining in mosquito-borne diseases, followed by PubMed and LexisNexis databases. Sentiment analysis was the most popular technique of text mining to understand the discourse of the disease and followed by information extraction, which dependency relation and co-occurrence-based approach to extract relations and events. Surveillance was the main usage of most of the reviewed studies and followed by treatment, which focused on the drug-disease or symptom-disease association. The advance in text mining could improve the management of mosquito-borne diseases. However, the technique and application posed many limitations and challenges, including biases like user authentication and language, real-world implementation, etc. We discussed the future direction which can be useful to expand this area and domain. This review paper contributes mainly as a library for text mining in mosquito-borne diseases and could further explore the system for other neglected diseases.
  7. Ahmed U, Manzoor M, Qureshi S, Mazhar M, Fatima A, Aurangzeb S, et al.
    Acta Trop, 2023 Mar;239:106824.
    PMID: 36610529 DOI: 10.1016/j.actatropica.2023.106824
    Pathogenic A. castellanii and N. fowleri are opportunistic free-living amoebae. Acanthamoeba spp. are the causative agents of granulomatous amebic encephalitis (GAE) and amebic keratitis (AK), whereas Naegleria fowleri causes a very rare but severe brain infection called primary amebic meningoencephalitis (PAM). Acridinone is an important heterocyclic scaffold and both synthetic and naturally occurring derivatives have shown various valuable biological properties. In the present study, ten synthetic Acridinone derivatives (I-X) were synthesized and assessed against both amoebae for anti-amoebic and cysticidal activities in vitro. In addition, excystation, encystation, cytotoxicity, host cell pathogenicity was also performed in-vitro. Furthermore, molecular docking studies of these compounds with three cathepsin B paralogous enzymes of N. fowleri were performed in order to predict the possible docking mode with pathogen. Compound VII showed potent anti-amoebic activity against A. castellanii with IC50 53.46 µg/mL, while compound IX showed strong activity against N. fowleri in vitro with IC50 72.41 µg/mL. Compounds II and VII showed a significant inhibition of phenotypic alteration of A. castellanii, while compound VIII significantly inhibited N. fowleri cysts. Cytotoxicity assessment showed that these compounds caused minimum damage to human keratinocyte cells (HaCaT cells) at 100 µg/mL, while also effectively reduced the cytopathogenicity of Acanthamoeba to HaCaT cells. Moreover, Cathepsin B protease was investigated in-silico as a new molecular therapeutic target for these compounds. All compounds showed potential interactions with the catalytic residues. These results showed that acridine-9(10H)-one derivatives, in particular compounds II, VII, VIII and IX hold promise in the development of therapeutic agents against these free-living amoebae.
  8. 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.
  9. Srisuka W, Takaoka H, Aupalee K, Saeung A
    Acta Trop, 2023 Feb;238:106790.
    PMID: 36473597 DOI: 10.1016/j.actatropica.2022.106790
    The female, male, pupa and mature larva of Simulium (Simulium) poolpholi sp. nov. collected from a large and seasonal stream in northeastern Thailand are described. This new species is placed in the S. striatum species-group by the female sternite 8 concave posteromedially in form of the inverted-U shape, ovipositor valve with a ventrally produced process along its inner margin, male ventral plate saddle-shaped, style with a basal protuberance, and pupal gill with 10 filaments. It is morphologically similar to S. (S.) phraense Takaoka, Srisuka & Saeung from northern Thailand by lacking annular ridges on the surface of pupal gill filaments but it is distinguished from the latter species by the arrangement of pupal gill filaments. Molecular analysis using the fast-evolving nuclear big zinc finger (BZF) gene shows that S. (S.) poolpholi sp. nov. formed a distinct clade, being separated from the seven other Thai species of this species-group by a genetic distance of 1.84-4.55%. Our discovery increases the number of species in the S. striatum species-group in Thailand to nine.
  10. Lai MY, Lau YL
    Acta Trop, 2020 May 15;208:105511.
    PMID: 32422380 DOI: 10.1016/j.actatropica.2020.105511
    In this study, recombinase polymerase amplification (RPA) combined with SYBR Green I was developed for the detection of Plasmodium knowlesi. Positive samples were indicated with a green color while negative samples were orange. To increase the efficiency of amplification, an interval mixing step of samples after 3 to 6 min incubation was recommended. Different sets of reaction volumes from 6.25 to 50 µL were tested and the results indicated no differences in detection. RPA's combination with SYBR Green I is fast and easy to perform, hence this method is suitable for use in resource-limited settings.
  11. Rizwan M, Ali S, Javid A, von Fricken ME, Rashid MI
    Acta Trop, 2023 Jul;243:106940.
    PMID: 37160189 DOI: 10.1016/j.actatropica.2023.106940
    Bartonella can infect a variety of mammals including humans and has been detected in the Americas, Europe, Africa, and Asia. Roughly two-thirds of identified Bartonella species are found and maintained in rodent reservoirs, with some of these species linked to human infections. Rodents (N=236) were caught from the Sahiwal division of Punjab, Pakistan and tested for Bartonella using PCR targeting gltA and rpoB genes, followed by sequencing of rpoB-positive samples. Genetic relatedness to other published Bartonella spp. rpoB gene sequences were examined using BLAST and phylogenetic analysis. Overall, 7.62% (18/236) of rodents were positive for both gltA and rpoB fragments. Rattus rattus and R. norvegicus had 7.94% (12/151) and 7.05% (6/85) positivity rates for Bartonella DNA, respectively. Phylogenetic analysis revealed a close relatedness between Bartonella spp. from Pakistan to Bartonella spp. from China, Nepal, and Malaysia. This study is the first reported detection of Bartonella spp. in R. rattus and R. norvegicus from the Sahiwal area of Punjab, Pakistan.
  12. Srisuka W, Takaoka H, Aupalee K, Saeung A
    Acta Trop, 2023 Aug;244:106947.
    PMID: 37196907 DOI: 10.1016/j.actatropica.2023.106947
    A new black fly species, Simulium (Gomphostilbia) wijiti, is described based on adult females, males, pupal exuviae and mature larvae from Mae Hong Son Province, Thailand. This new species is placed in the Simulium ceylonicum species-group. It is distinguished from four Thai members of the S. ceylonicum species-group [S. (G.) curtatum Jitklang et al., S. (G.) pangsidaense Takaoka, Srisuka & Saeung, S. (G.) sheilae Takaoka & Davies, and S. (G.) trangense Jitklang et al.], in the female by the short to medium long sensory vesicle; in the male by the large number of upper-eye (large) facets in 15 vertical columns and 15 or 16 horizontal rows; in the pupa by the dorsum of abdominal segments darkened; and in the larva by the antenna as long as or slightly shorter than the stem of the labral fan (longer than the stem of the labral fan in four other species). Phylogenetic analysis based on the COI gene sequences revealed that this new species is genetically closely related to S. leparense of the S. ceylonicum species-group, but is clearly separated from the latter species, and also from the three Thai related species (S. curtatum, S. sheilae and S. trangense) of the same species-group with interspecific genetic distances ranging from 9.65% to 12.67%. This is the fifth member of the S. ceylonicum species-group recorded from Thailand.
  13. 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.
  14. Narapakdeesakul D, Pengsakul T, Kaewparuehaschai M, Thongsahuan S, Moonmake S, Lekcharoen P, et al.
    Acta Trop, 2023 Dec;248:107030.
    PMID: 37742788 DOI: 10.1016/j.actatropica.2023.107030
    Despite the natural occurrences of human infections by Plasmodium knowlesi, P. cynomolgi, P. inui, and P. fieldi in Thailand, investigating the prevalence and genetic diversity of the zoonotic simian malaria parasites in macaque populations has been limited to certain areas. To address this gap, a total of 560 long-tailed macaques (Macaca fascicularis) and 20 southern pig-tailed macaques (M. nemestrina) were captured from 15 locations across 10 provinces throughout Thailand between 2018 and 2021 for investigation of malaria, as were 15 human samples residing in two simian-malaria endemic provinces, namely Songkhla and Satun, who exhibited malaria-like symptoms. Using PCR techniques targeting the mitochondrial cytb and cox1 genes coupled with DNA sequencing, 40 long-tailed macaques inhabiting five locations had mono-infections with one of the three simian malaria species. Most of the positive cases of macaque were infected with P. inui (32/40), while infections with P. cynomolgi (6/40) and P. knowlesi (2/40) were less common and confined to specific macaque populations. Interestingly, all 15 human cases were mono-infected with P. knowlesi, with one of them residing in an area with two P. knowlesi-infected macaques. Nucleotide sequence analysis showed a high level of genetic diversity in P. inui, while P. cynomolgi and P. knowlesi displayed limited genetic diversity. Phylogenetic and haplotype network analyses revealed that P. inui in this study was closely related to simian and Anopheles isolates from Peninsular Malaysia, while P. cynomolgi clustered with simian and human isolates from Asian countries. P. knowlesi, which was found in both macaques and humans in this study, was closely related to isolates from macaques, humans, and An. hackeri in Peninsular Malaysia, suggesting a sylvatic transmission cycle extending across these endemic regions. This study highlights the current hotspots for zoonotic simian malaria and sheds light on the genetic characteristics of recent isolates in both macaques and human residents in Thailand.
  15. Ahmed U, Sivasothy Y, Khan KM, Khan NA, Wahab SMA, Awang K, et al.
    Acta Trop, 2023 Dec;248:107033.
    PMID: 37783284 DOI: 10.1016/j.actatropica.2023.107033
    Acanthamoeba castellanii is an opportunistic free-living amoeba (FLA) pathogen which can cause fatal central nervous system (CNS) infection, granulomatous amoebic encephalitis (GAE) and potentially blinding ocular infection, Acanthamoeba keratitis (AK). Acanthamoeba species remain a challenging protist to treat due to the unavailability of safe and effective therapeutic drugs and their ability to protect themselves in the cyst stage. Natural products and their secondary metabolites play a pivotal role in drug discovery against various pathogenic microorganisms. In the present study, the ethyl acetate extract of Myristica cinnamomea King fruit was evaluated against A. castellanii (ATCC 50492), showing an IC50 of 45.102 ± 4.62 µg/mL. Previously, the bio-guided fractionation of the extract resulted in the identification of three active compounds, namely Malabaricones (A-C). The isolated and thoroughly characterized acylphenols were evaluated for their anti-amoebic activity against A. castellanii for the first time. Among tested compounds, Malabaricone B (IC50 of 101.31 ± 17.41 µM) and Malabaricone C (IC50 of 49.95 ± 6.33 µM) showed potent anti-amoebic activity against A. castellanii trophozoites and reduced their viability up-to 75 and 80 %, respectively. Moreover, both extract and Malabaricones also significantly (p < 0.05) inhibit the encystation and excystation of A. castellanii, while showed minimal toxicity against human keratinocyte cells (HaCaT cells) at lower tested concentrations. Following that, the explanation of the possible mechanism of action of purified compounds were assessed by detection of the state of chromatin. Hoechst/PI 33342 double staining showed that necrotic cell death occurred in A. castellanii trophozoites after 8 h treatment of Malabaricones (A-C). These findings demonstrate that Malabaricones B and C could serve as promising therapeutic options against A. castellanii infections.
  16. Kwak ML, Hitch AT, Borthwick SA, Low DHW, Markowsky G, McInnes D, et al.
    Acta Trop, 2023 Oct;246:106992.
    PMID: 37543183 DOI: 10.1016/j.actatropica.2023.106992
    The Asian rodent tick (Ixodes granulatus) occurs throughout much of Asia, it frequently bites humans, and zoonotic pathogens, such as Borrelia burgdorferi (sensu lato) and Rickettsia honei, have been detected within it. Unfortunately, the ecology of I. granulatus remains poorly known, including drivers of its abundance and the interaction ecology with its sylvatic hosts. To elucidate the ecology of this medically important species, the habitat preferences of I. granulatus were assessed in Singapore and Malaysia. Ixodes granulatus showed strong associations with old forest habitats, though across different age classes of old forest there was limited variation in abundance. Ixodes granulatus was absent from other habitats including young forest, scrubland, and parks/gardens. Within its sylvatic rodent hosts, a range of factors were found to be statistically significant predictors of I. granulatus load and/or infestation risk, including sex and body condition index. Male rodents were significantly more likely to be infested and to have higher loads than females, similarly, animals with a lower body condition index were significantly more likely to be infested. Proactive public health efforts targeted at preventing bites by this tick should carefully consider its ecology to minimise ecological overlap between humans and I. granulatus.
  17. Sangsri R, Choowongkomon K, Tuntipaiboontana R, Sugaram R, Boondej P, Sudathip P, et al.
    Acta Trop, 2023 Dec;248:107016.
    PMID: 37683820 DOI: 10.1016/j.actatropica.2023.107016
    BACKGROUND: The 2022 malaria WHO reported around 4000 P. knowlesi infections in the South-East Asia region. In the same period, 72 positive cases were reported by the Department of Disease Control in Thailand, suggesting a persistent infection. Little is known about dihydrofolate reductase (pkdhfr) and dihydropteroate synthase (pkdhps), putative antimalarial resistance markers for P. knowlesi. The relevant amplification and sequencing protocol are presently unavailable. In this study, we developed a protocol for amplifying and evaluating pkdhps mutations. The haplotype pattern of pkdhfr-pkdhps in Thai isolates was analyzed, and the effects of these pkdhps mutations were predicted by using a computer program.

    METHODS: Pkdhps were amplified and sequenced from 28 P. knowlesi samples collected in 2008 and 2020 from nine provinces across Thailand. Combining pkdhfr sequencing data from previous work with pkdhps data to analyze polymorphisms of pkdhfr and pkdhps haplotype. Protein modeling and molecular docking were constructed using two inhibitors, sulfadoxine and sulfamethoxazole, and further details were obtained through analyses of protein-ligand interactions by using the Genetic Optimisation for Ligand Docking program. A phylogenetic tree cluster analysis was reconstructed to compare the P. knowlesi Malaysia isolates.

    RESULTS: Five nonsynonymous mutations in the pkdhps were detected outside the equivalence of the binding pocket sites to sulfadoxine and sulfamethoxazole, which are at N391S, E421G, I425R, A449S, and N517S. Based on the modeling and molecular docking analyses, the N391S and N517S mutations located close to the enzyme-binding pocket demonstrated a different docking score and protein-ligand interaction in loop 2 of the enzyme. These findings indicated that it was less likely to induce drug resistance. Of the four haplotypes of pkdhfr-pkdhps, the most common one is the R34L pkdhfr mutation and the pkdhps quadruple mutation (GRSS) at E421G, I425R, A449S, and N517S, which were observed in P. knowlesi in southern Thailand (53.57%). Based on the results of neighbor-joining analysis for pkdhfr and pkdhps, the samples isolated from eastern Thailand displayed a close relationship with Cambodia isolates, while southern Thailand isolates showed a long branch separated from the Malaysian isolates.

    CONCLUSIONS: A new PCR protocol amplification and evaluation of dihydropteroate synthase mutations in Knowlesi (pkdhps) has been developed. The most prevalent pkdhfr-pkdhps haplotypes (53.57%) in southern Thailand are R34L pkdhfr mutation and pkdhps quadruple mutation. Further investigation requires additional phenotypic data from clinical isolates, transgenic lines expressing mutant alleles, or recombinant proteins.

  18. Lim ASS, Tan KY, Tan CH
    Acta Trop, 2024 Feb;250:107099.
    PMID: 38097152 DOI: 10.1016/j.actatropica.2023.107099
    Snakebite envenoming (SBE) is a priority Neglected Tropical Disease listed by the World Health Organization. South Asia is heavily affected, and virtually all countries in the region import polyvalent antivenom products from India for clinical use. The imported antivenoms, however, have suboptimal effectiveness due to geographical venom variation. Recently, a domestic bivalent product, named Pakistani Viper Antivenom (PVAV) has been developed specifically for Pakistani vipers, Echis carinatus sochureki and Daboia russelii. As a bivalent viperid antivenom, it is unknown yet if PVAV exhibits higher immunological binding and neutralization activities against viper venoms from distant locales compared with polyvalent antivenoms manufactured in India. This study thus examined the preclinical efficacy of PVAV against venoms of Western Russell's Vipers and Saw-scaled Viper subspecies from selected locales in the Indian subcontinent. PVAV generally outperformed the commonly used VINS polyvalent antivenom (VPAV, manufactured in India) in binding toward venoms, and showed superior or comparable neutralization efficacy against the venom procoagulant and hemorrhagic effects of Saw-scaled Vipers as well as Russell's Vipers from Pakistan and Sri Lanka. Based on normalized potency values, PVAV is far more potent than VPAV in neutralizing the lethality of all viper venoms, except that of the Indian Russell's Viper. The study shows conserved antigenicity of toxins responsible for major toxicity across these viperid venoms, and suggests the feasible production of a viper-specific antivenom with higher potency and broader geographical utility for the region.
  19. Hew YX, Ya'cob Z, Chen CD, Lau KW, Sofian-Azirun M, Muhammad-Rasul AH, et al.
    Acta Trop, 2024 Feb;250:107097.
    PMID: 38097150 DOI: 10.1016/j.actatropica.2023.107097
    Mitochondrial cytochrome c oxidase subunit I (COI) sequences were utilized to infer the population genetic structure of Simulium (Gomphostilbia) atratum De Meijere, an endemic simulid species to Indonesia. Both median-joining haplotype network and maximum-likelihood tree revealed two genetic lineages (A and B) within the species, with an overlap distribution in Lombok, which is situated along Wallace's line. Genetic differentiation and gene flow with varying frequencies (FST = 0.02-0.967; Nm = 0.01-10.58) were observed between populations of S. (G.) atratum, of which population pairs of different lineages showed high genetic differentiation. Notably, the high genetic distance of up to 5.92 % observed within S. (G.) atratum in Lombok was attributed to the existence of two genetically distinct lineages. The co-occurrence of distinct lineages in Lombok indicated that Wallace's line did not act as faunistic border for S. (G.) atratum in the present study. Moreover, both lineages also exhibited unimodal distributions and negative values of neutrality tests, suggesting a pattern of population expansion. The expansion and divergence time estimation suggested that the two lineages of S. (G.) atratum diverged and expanded during the Pleistocene era in Indonesia.
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