Displaying publications 21 - 40 of 44 in total

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  1. Hawkes FM, Manin BO, Cooper A, Daim S, R H, Jelip J, et al.
    Sci Rep, 2019 Nov 20;9(1):17510.
    PMID: 31745193 DOI: 10.1038/s41598-019-53744-8
    An amendment to this paper has been published and can be accessed via a link at the top of the paper.
  2. Daim S, Barnad E, Johnny V, Suleiman M, Jikal M, Chua TH, et al.
    Clin Case Rep, 2020 Jan;8(1):171-175.
    PMID: 31998510 DOI: 10.1002/ccr3.2584
    In endemic regions, include melioidosis in the routine differential diagnosis of neonates with respiratory distress, and consider early empirical ceftazidime treatment for neonates with worsening respiratory distress.
  3. Aung TS, Gintarong T, Balingi DB, Emran A, Thein TT, Chua TH
    Trop Biomed, 2020 Mar 01;37(1):58-65.
    PMID: 33612718
    An outbreak of dengue in Kudat, northern Sabah in 2016-2017 provided an opportunity to investigate the circulating serotypes of dengue viruses of cases at Hospital Kudat. Between September 2016 and December 2017, a total of 156 dengue positive sera (tested positive by either NS1 antigen, or IgM and IgG antibody rapid test) were collected from dengue patients who had acute fever and showed signs and symptoms suggestive of dengue. RNA was extracted from the sera using QIAamp RNA Blood Mini Kit, and molecular amplification was performed using one-step RT-PCR kit, followed by nested PCR using HotStart Taq master mix kit with the primers of the dengue C-prM gene. There were 81 (52%) male and 75 (48%) female cases. The age group with the highest number of cases was the 10-19 years old, while the youngest infected was 8 months old and the oldest was 83 years old. RT-PCR results showed 88 sera dengue positive, 48 infected with a single serotype while another 40 with multiple serotypes. All four DENV serotypes were co-circulating during the outbreak period and DENV-1 was predominant. Molecular analysis also indicated 69.2%, 50.0%, 51.9% and 48.9% respectively of the NS1, IgM, IgG and IgM and IgG positive sera were RT-PCR positive for dengue. High number of cases were seen in December 2016, February and May 2017. The dengue outbreak might be related to switching of predominant serotype from DENV 4 to DENV 1.
  4. Vythilingam I, Chua TH, Liew JWK, Manin BO, Ferguson HM
    Adv Parasitol, 2021;113:131-189.
    PMID: 34620382 DOI: 10.1016/bs.apar.2021.08.005
    Plasmodium knowlesi, a simian malaria parasite of great public health concern has been reported from most countries in Southeast Asia and exported to various countries around the world. Currently P. knowlesi is the predominant species infecting humans in Malaysia. Besides this species, other simian malaria parasites such as P. cynomolgi and P. inui are also infecting humans in the region. The vectors of P. knowlesi and other Asian simian malarias belong to the Leucosphyrus Group of Anopheles mosquitoes which are generally forest dwelling species. Continual deforestation has resulted in these species moving into forest fringes, farms, plantations and human settlements along with their macaque hosts. Limited studies have shown that mosquito vectors are attracted to both humans and macaque hosts, preferring to bite outdoors and in the early part of the night. We here review the current status of simian malaria vectors and their parasites, knowledge of vector competence from experimental infections and discuss possible vector control measures. The challenges encountered in simian malaria elimination are also discussed. We highlight key knowledge gaps on vector distribution and ecology that may impede effective control strategies.
  5. Stanis CS, Song BK, Chua TH, Lau YL, Jelip J
    Turk J Med Sci, 2016 Jan 05;46(1):207-18.
    PMID: 27511356 DOI: 10.3906/sag-1411-114
    BACKGROUND/AIM: Malaria is a major public health problem, especially in the Southeast Asia region, caused by 5 species of Plasmodium (P. falciparum, P. vivax, P. malariae, P. ovale, and P. knowlesi). The aim of this study was to compare parasite species identification methods using the new multiplex polymerase chain reaction (PCR) against nested PCR and microscopy.

    MATERIALS AND METHODS: Blood samples on filter papers were subject to conventional PCR methods using primers designed by us in multiplex PCR and previously designed primers of nested PCR. Both sets of results were compared with microscopic identification.

    RESULTS: Of the 129 samples identified as malaria-positive by microscopy, 15 samples were positive for P. falciparum, 14 for P. vivax, 6 for P. knowlesi, 72 for P. malariae, and 2 for mixed infection of P. falciparum/P. malariae. Both multiplex and nested PCR identified 12 P. falciparum single infections. For P. vivax, 9 were identified by multiplex and 12 by nested PCR. For 72 P. malariae cases, multiplex PCR identified 58 as P. knowlesi and 10 as P. malariae compared to nested PCR, which identified 59 as P. knowlesi and 7 as P. malariae.

    CONCLUSION: Multiplex PCR could be used as alternative molecular diagnosis for the identification of all Plasmodium species as it requires a shorter time to screen a large number of samples.

  6. Grignard L, Shah S, Chua TH, William T, Drakeley CJ, Fornace KM
    J Infect Dis, 2019 11 06;220(12):1946-1949.
    PMID: 31418017 DOI: 10.1093/infdis/jiz397
    To determine the presence and species composition of malaria infections, we screened a subset of samples collected during a cross-sectional survey in Northern Sabah, Malaysia using highly sensitive molecular techniques. Results identified 54 asymptomatic submicroscopic malaria infections, including a large cluster of Plasmodium falciparum and 3 P. knowlesi infections. We additionally identified 2 monoinfections with the zoonotic malaria Plasmodium cynomolgi, both in individuals reporting no history of forest activities or contact with macaques. Results highlight the need for improved surveillance strategies to detect these infections and determine public health impacts.
  7. Davidson G, Speldewinde P, Manin BO, Cook A, Weinstein P, Chua TH
    Ecohealth, 2024 Feb 27.
    PMID: 38411846 DOI: 10.1007/s10393-024-01675-w
    Anthropogenic changes to forest cover have been linked to an increase in zoonotic diseases. In many areas, natural forests are being replaced with monoculture plantations, such as oil palm, which reduce biodiversity and create a mosaic of landscapes with increased forest edge habitat and an altered micro-climate. These altered conditions may be facilitating the spread of the zoonotic malaria parasite Plasmodium knowlesi in Sabah, on the island of Borneo, through changes to mosquito vector habitat. We conducted a study on mosquito abundance and diversity in four different land uses comprising restored native forest, degraded native forest, an oil palm estate and a eucalyptus plantation, these land uses varying in their vegetation types and structure. The main mosquito vector, Anopheles balabacensis, has adapted its habitat preference from closed canopy rainforest to more open logged forest and plantations. The eucalyptus plantations (Eucalyptus pellita) assessed in this study contained significantly higher abundance of many mosquito species compared with the other land uses, whereas the restored dipterocarp forest had a low abundance of all mosquitos, in particular, An. balabacensis. No P. knowlesi was detected by PCR assay in any of the vectors collected during the study; however, P. inui, P. fieldi and P. vivax were detected in An. balabacensis. These findings indicate that restoring degraded natural forests with native species to closed canopy conditions reduces abundance of this zoonotic malarial mosquito vector and therefore should be incorporated into future restoration research and potentially contribute to the control strategies against simian malaria.
  8. Frias L, Manin BO, Guerrero-Sánchez S, Sipangkui S, Chua TH
    Parasitology, 2024 Feb;151(2):181-184.
    PMID: 38167272 DOI: 10.1017/S0031182023001257
    In this study, we report the occurrence of echinostomatid eggs in feces of wildlife, domestic animals and humans frequenting the forest–oil palm plantation interface in the Kinabatangan (Sabah, Malaysia), and discuss potential implications for public health. Using microscopy, we detected echinostomatid eggs in six host species, including Asian palm civets (Paradoxurus hermaphroditus [13/18]), leopard cats (Prionailurus bengalensis [3/4]), long-tailed macaques (Macaca fascicularis [1/10]), domestic dogs [3/5] and cats [1/1], and humans [7/9]. Molecular analysis revealed a close genetic proximity of civet echinostomatids to Artyfechinostomum malayanum, a zoonotic parasite of public health relevance. The intermediate hosts for A. malayanum have been reported in at least 3 districts in Sabah, suggesting that all the necessary elements required for the completion of the parasite's life cycle are present. Our findings point at the presence of zoonotic trematodes in an area with high human–wildlife interaction and highlight the potential public and animal health concern of zoonotic trematode infection in the context of Southeast Asia's rapidly changing ecosystems.
  9. Frias L, Hasegawa H, Stark DJ, Lynn MS, Nathan SK, Chua TH, et al.
    PMID: 30619706 DOI: 10.1016/j.ijppaw.2018.11.009
    Lemuricola (Protenterobius) nycticebi is the only pinworm species known to infect strepsirrhine primates outside Africa, and the only pinworm species yet described in slow lorises. Here, we provided a detailed morphological comparison of female and male worms, and a first description of fourth-stage larvae collected from free-living slow lorises (Nycticebus menagensis) in Sabah, Malaysian Borneo. Using mitochondrial and nuclear markers, we also reconstructed the species' phylogenetic relationship with other pinworms infecting primates. Both morphological and molecular results indicated a distinct association between L. (P.) nycticebi and its host. However, while taxonomy identified this species as a member of the Lemuricola clade and grouped pinworms infecting lemurs and slow lorises together, phylogenetic reconstruction split them, placing L. (P.) nycticebi within the Enterobius clade. Our results suggest that L. (P.) nycticebi may represent a different taxon altogether, and that it is more closely related to pinworm species infecting Old World primates outside Madagascar. Pongobius pongoi (Foitová et al., 2008) n. comb. is also proposed.
  10. Lau SM, Vythilingam I, Doss JI, Sekaran SD, Chua TH, Wan Sulaiman WY, et al.
    Trop Med Int Health, 2015 Oct;20(10):1271-80.
    PMID: 26094839 DOI: 10.1111/tmi.12555
    To determine the effectiveness of using sticky traps and the NS1 dengue antigen kit for the surveillance of Aedes mosquitoes for dengue control.
  11. Lau SM, Chua TH, Sulaiman WY, Joanne S, Lim YA, Sekaran SD, et al.
    Parasit Vectors, 2017 Mar 21;10(1):151.
    PMID: 28327173 DOI: 10.1186/s13071-017-2091-y
    BACKGROUND: Dengue remains a serious public health problem in Southeast Asia and has increased 37-fold in Malaysia compared to decades ago. New strategies are urgently needed for early detection and control of dengue epidemics.

    METHODS: We conducted a two year study in a high human density dengue-endemic urban area in Selangor, where Gravid Ovipositing Sticky (GOS) traps were set up to capture adult Aedes spp. mosquitoes. All Aedes mosquitoes were tested using the NS1 dengue antigen test kit. All dengue cases from the study site notified to the State Health Department were recorded. Weekly microclimatic temperature, relative humidity (RH) and rainfall were monitored.

    RESULTS: Aedes aegypti was the predominant mosquito (95.6%) caught in GOS traps and 23% (43/187 pools of 5 mosquitoes each) were found to be positive for dengue using the NS1 antigen kit. Confirmed cases of dengue were observed with a lag of one week after positive Ae. aegypti were detected. Aedes aegypti density as analysed by distributed lag non-linear models, will increase lag of 2-3 weeks for temperature increase from 28 to 30 °C; and lag of three weeks for increased rainfall.

    CONCLUSION: Proactive strategy is needed for dengue vector surveillance programme. One method would be to use the GOS trap which is simple to setup, cost effective (below USD 1 per trap) and environmental friendly (i.e. use recyclable plastic materials) to capture Ae. aegypti followed by a rapid method of detecting of dengue virus using the NS1 dengue antigen kit. Control measures should be initiated when positive mosquitoes are detected.

  12. Frias L, Hasegawa H, Chua TH, Sipangkui S, Stark DJ, Salgado-Lynn M, et al.
    Int J Parasitol, 2021 10;51(11):925-933.
    PMID: 33862059 DOI: 10.1016/j.ijpara.2021.03.003
    Parasites are important components of ecosystems, influencing trophic networks, competitive interactions and biodiversity patterns. Nonetheless, we are not nearly close to disentangling their complex roles in natural systems. Southeast Asia falls within global areas targeted as most likely to source parasites with zoonotic potential, where high rates of land conversion and fragmentation have altered the circulation of wildlife species and their parasites, potentially resulting in altered host-parasite systems. Although the overall biodiversity in the region predicts equally high, or even higher, parasite diversity, we know surprisingly little about wild primate parasites, even though this constitutes the first step towards a more comprehensive understanding of parasite transmission processes. Here, we characterise the gastrointestinal helminth parasite assemblages of a community of Bornean primates living along the Kinabatangan floodplain in Sabah (Malaysian Borneo), including two species endemic to the island. Through parasitological analyses, and by using several measures of parasite infection as proxies for parasite diversity and distribution, we show that (i) most parasite taxonomic groups are not limited to a single host, suggesting a greater flexibility for habitat disturbance, (ii) parasite infracommunities of nocturnal primates differ from their diurnal counterparts, reflecting both phylogenetic and ecological constraints, and (iii) soil-transmitted helminths such as whipworm, threadworm and nodule worm are widespread across the primate community. This study also provides new parasite records for southern pig-tailed macaques (Macaca nemestrina), silvered langurs (Trachypithecus cristatus) and Western tarsiers (Cephalopachus bancanus) in the wild, while adding to the limited records for the other primate species in the community. Given the information gap regarding primate-parasite associations in the region, the information presented here should prove relevant for future studies of parasite biodiversity and infectious disease ecology in Asia and elsewhere.
  13. Selvarajoo S, Liew JWK, Chua TH, Tan W, Zaki RA, Ngui R, et al.
    Sci Rep, 2022 01 12;12(1):571.
    PMID: 35022501 DOI: 10.1038/s41598-021-04643-4
    Dengue remains a major public threat and existing dengue control/surveillance programs lack sensitivity and proactivity. More efficient methods are needed. A cluster randomized controlled trial was conducted for 18 months to determine the efficacy of using a combination of gravid oviposition sticky (GOS) traps and dengue non-structural 1 (NS1) antigen for early surveillance of dengue among Aedes mosquito. Eight residential apartments were randomly assigned into intervention and control groups. GOS traps were placed at the intervention apartments weekly to trap Aedes mosquitoes and these tested for dengue NS1 antigen. When dengue-positive pool was detected, the community were notified and advised to execute protective measures. Fewer dengue cases were recorded in the intervention group than the control. Detection of NS1-positive mosquitoes was significantly associated with GOS Aedes index (rs = 0.68, P 
  14. Chan YL, Patterson CL, Priest JW, Stresman G, William T, Chua TH, et al.
    Front Public Health, 2022;10:924316.
    PMID: 36388287 DOI: 10.3389/fpubh.2022.924316
    BACKGROUND: Infectious diseases continue to burden populations in Malaysia, especially among rural communities where resources are limited and access to health care is difficult. Current epidemiological trends of several neglected tropical diseases in these populations are at present absent due to the lack of habitual and efficient surveillance. To date, various studies have explored the utility of serological multiplex beads to monitor numerous diseases simultaneously. We therefore applied this platform to assess population level exposure to six infectious diseases in Sabah, Malaysia. Furthermore, we concurrently investigated demographic and spatial risk factors that may be associated with exposure for each disease.

    METHODS: This study was conducted in four districts of Northern Sabah in Malaysian Borneo, using an environmentally stratified, population-based cross-sectional serological survey targeted to determine risk factors for malaria. Samples were collected between September to December 2015, from 919 villages totaling 10,100 persons. IgG responses to twelve antigens of six diseases (lymphatic filariasis- Bm33, Bm14, BmR1, Wb123; strongyloides- NIE; toxoplasmosis-SAG2A; yaws- Rp17 and TmpA; trachoma- Pgp3, Ct694; and giardiasis- VSP3, VSP5) were measured using serological multiplex bead assays. Eight demographic risk factors and twelve environmental covariates were included in this study to better understand transmission in this community.

    RESULTS: Seroprevalence of LF antigens included Bm33 (10.9%), Bm14+ BmR1 (3.5%), and Wb123 (1.7%). Seroprevalence of Strongyloides antigen NIE was 16.8%, for Toxoplasma antigen SAG2A was 29.9%, and Giardia antigens GVSP3 + GVSP5 was 23.2%. Seroprevalence estimates for yaws Rp17 was 4.91%, for TmpA was 4.81%, and for combined seropositivity to both antigens was 1.2%. Seroprevalence estimates for trachoma Pgp3 + Ct694 were 4.5%. Age was a significant risk factors consistent among all antigens assessed, while other risk factors varied among the different antigens. Spatial heterogeneity of seroprevalence was observed more prominently in lymphatic filariasis and toxoplasmosis.

    CONCLUSIONS: Multiplex bead assays can be used to assess serological responses to numerous pathogens simultaneously to support infectious disease surveillance in rural communities, especially where prevalences estimates are lacking for neglected tropical diseases. Demographic and spatial data collected alongside serosurveys can prove useful in identifying risk factors associated with exposure and geographic distribution of transmission.

  15. Byrne I, Aure W, Manin BO, Vythilingam I, Ferguson HM, Drakeley CJ, et al.
    Sci Rep, 2021 Jun 03;11(1):11810.
    PMID: 34083582 DOI: 10.1038/s41598-021-90893-1
    Land-use changes, such as deforestation and agriculture, can influence mosquito vector populations and malaria transmission. These land-use changes have been linked to increased incidence in human cases of the zoonotic malaria Plasmodium knowlesi in Sabah, Malaysian Borneo. This study investigates whether these associations are partially driven by fine-scale land-use changes creating more favourable aquatic breeding habitats for P. knowlesi anopheline vectors. Using aerial remote sensing data, we developed a sampling frame representative of all land use types within a major focus of P. knowlesi transmission. From 2015 to 2016 monthly longitudinal surveys of larval habitats were collected in randomly selected areas stratified by land use type. Additional remote sensing data on environmental variables, land cover and landscape configuration were assembled for the study site. Risk factor analyses were performed over multiple spatial scales to determine associations between environmental and spatial variables and anopheline larval presence. Habitat fragmentation (300 m), aspect (350 m), distance to rubber plantations (100 m) and Culex larval presence were identified as risk factors for Anopheles breeding. Additionally, models were fit to determine the presence of potential larval habitats within the areas surveyed and used to generate a time-series of monthly predictive maps. These results indicate that land-use change and topography influence the suitability of larval habitats, and may partially explain the link between P. knowlesi incidence and deforestation. The predictive maps, and identification of the spatial scales at which risk factors are most influential may aid spatio-temporally targeted vector control interventions.
  16. Wong ML, Chua TH, Leong CS, Khaw LT, Fornace K, Wan-Sulaiman WY, et al.
    PLoS Negl Trop Dis, 2015;9(10):e0004135.
    PMID: 26448052 DOI: 10.1371/journal.pntd.0004135
    BACKGROUND: The simian malaria parasite Plasmodium knowlesi is emerging as a public health problem in Southeast Asia, particularly in Malaysian Borneo where it now accounts for the greatest burden of malaria cases and deaths. Control is hindered by limited understanding of the ecology of potential vector species.

    METHODOLOGY/PRINCIPAL FINDINGS: We conducted a one year longitudinal study of P. knowlesi vectors in three sites within an endemic area of Sabah, Malaysia. All mosquitoes were captured using human landing catch. Anopheles mosquitoes were dissected to determine, oocyst, sporozoites and parous rate. Anopheles balabacensis is confirmed as the primary vector of. P. knowlesi (using nested PCR) in Sabah for the first time. Vector densities were significantly higher and more seasonally variable in the village than forest or small scale farming site. However An. balabacensis survival and P. knowlesi infection rates were highest in forest and small scale farm sites. Anopheles balabacensis mostly bites humans outdoors in the early evening between 1800 to 2000 hrs.

    CONCLUSIONS/SIGNIFICANCE: This study indicates transmission is unlikely to be prevented by bednets. This combined with its high vectorial capacity poses a threat to malaria elimination programmes within the region.

  17. Hambali NL, Mohd Noh M, Paramasivam S, Chua TH, Hayati F, Payus AO, et al.
    Front Public Health, 2020;8:584552.
    PMID: 33304877 DOI: 10.3389/fpubh.2020.584552
    Interleukin 6 (IL-6) is one of the markers of immune system activation indicating existent infection and inflammation. We present here a case of a 55-year-old male COVID-19 patient with an unusual high level of interleukin 6 (IL-6). Further investigation revealed he had hepatocellular carcinoma (HCC) with underlying hepatitis B. He did not present with respiratory symptoms although a baseline chest x-ray showed changes, and the patient was categorized as Class 3A of COVID-19. Routine investigations proceeded with high-resolution computed tomography and IL-6 to monitor for progression to severe COVID-19. Notably, there was a high IL-6 level but other parameters did not show he was in severe COVID-19. In this report, we conclude that elevated IL-6 level in a COVID-19 patient is not necessarily associated with severe COVID-19.
  18. Wong ML, Ahmed MA, Sulaiman WYW, Manin BO, Leong CS, Quan FS, et al.
    Infect Genet Evol, 2019 09;73:26-32.
    PMID: 30999059 DOI: 10.1016/j.meegid.2019.04.010
    We explored and constructed haplotype network for simian malaria species: Plasmodium knowlesi, P. cynomolgi and P. inui aiming to understand the transmission dynamics between mosquitoes, humans and macaques. Mosquitoes were collected from villages in an area where zoonotic malaria is prevalent. PCR analysis confirmed Anopheles balabacensis as the main vector for macaque parasites, moreover nearly 60% of the mosquitoes harboured more than one Plasmodium species. Fragments of the A-type small subunit ribosomal RNA (SS rRNA) amplified from salivary gland sporozoites, and equivalent sequences obtained from GenBank were used to construct haplotype networks. The patterns were consistent with the presence of geographically distinct populations for P. inui and P. cynomolgi, and with three discrete P. knowlesi populations. This study provides a preliminary snapshot of the structure of these populations, that was insufficient to answer our aim. Thus, collection of parasites from their various hosts and over time, associated with a systematic analysis of a set of genetical loci is strongly advocated in order to obtain a clear picture of the parasite population and the flow between different hosts. This is important to devise measures that will minimise the risk of transmission to humans, because zoonotic malaria impedes malaria elimination.
  19. Fornace KM, Alexander N, Abidin TR, Brock PM, Chua TH, Vythilingam I, et al.
    Elife, 2019 10 22;8.
    PMID: 31638575 DOI: 10.7554/eLife.47602
    Human movement into insect vector and wildlife reservoir habitats determines zoonotic disease risks; however, few data are available to quantify the impact of land use on pathogen transmission. Here, we utilise GPS tracking devices and novel applications of ecological methods to develop fine-scale models of human space use relative to land cover to assess exposure to the zoonotic malaria Plasmodium knowlesi in Malaysian Borneo. Combining data with spatially explicit models of mosquito biting rates, we demonstrate the role of individual heterogeneities in local space use in disease exposure. At a community level, our data indicate that areas close to both secondary forest and houses have the highest probability of human P. knowlesi exposure, providing quantitative evidence for the importance of ecotones. Despite higher biting rates in forests, incorporating human movement and space use into exposure estimates illustrates the importance of intensified interactions between pathogens, insect vectors and people around habitat edges.
  20. Fornace KM, Zorello Laporta G, Vythilingham I, Chua TH, Ahmed K, Jeyaprakasam NK, et al.
    Lancet Infect Dis, 2023 Dec;23(12):e520-e532.
    PMID: 37454671 DOI: 10.1016/S1473-3099(23)00298-0
    Simian malaria from wild non-human primate populations is increasingly recognised as a public health threat and is now the main cause of human malaria in Malaysia and some regions of Brazil. In 2022, Malaysia became the first country not to achieve malaria elimination due to zoonotic simian malaria. We review the global distribution and drivers of simian malaria and identify priorities for diagnosis, treatment, surveillance, and control. Environmental change is driving closer interactions between humans and wildlife, with malaria parasites from non-human primates spilling over into human populations and human malaria parasites spilling back into wild non-human primate populations. These complex transmission cycles require new molecular and epidemiological approaches to track parasite spread. Current methods of malaria control are ineffective, with wildlife reservoirs and primarily outdoor-biting mosquito vectors urgently requiring the development of novel control strategies. Without these, simian malaria has the potential to undermine malaria elimination globally.
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