Displaying publications 41 - 60 of 164 in total

Abstract:
Sort:
  1. Brown R, Chua TH, Fornace K, Drakeley C, Vythilingam I, Ferguson HM
    PLoS Negl Trop Dis, 2020 09;14(9):e0008617.
    PMID: 32886679 DOI: 10.1371/journal.pntd.0008617
    The zoonotic malaria parasite, Plasmodium knowlesi, is now a substantial public health problem in Malaysian Borneo. Current understanding of P. knowlesi vector bionomics and ecology in Sabah comes from a few studies near the epicentre of human cases in one district, Kudat. These have incriminated Anopheles balabacensis as the primary vector, and suggest that human exposure to vector biting is peri-domestic as well as in forest environments. To address the limited understanding of vector ecology and human exposure risk outside of Kudat, we performed wider scale surveillance across four districts in Sabah with confirmed transmission to investigate spatial heterogeneity in vector abundance, diversity and infection rate. Entomological surveillance was carried out six months after a cross-sectional survey of P. knowlesi prevalence in humans throughout the study area; providing an opportunity to investigate associations between entomological indicators and infection. Human-landing catches were performed in peri-domestic, farm and forest sites in 11 villages (3-4 per district) and paired with estimates of human P. knowlesi exposure based on sero-prevalence. Anopheles balabacensis was present in all districts but only 6/11 villages. The mean density of An. balabacensis was relatively low, but significantly higher in farm (0.094/night) and forest (0.082/night) than peri-domestic areas (0.007/night). Only one An. balabacensis (n = 32) was infected with P. knowlesi. Plasmodium knowlesi sero-positivity in people was not associated with An. balabacensis density at the village-level however post hoc analyses indicated the study had limited power to detect a statistical association due low vector density. Wider scale sampling revealed substantial heterogeneity in vector density and distribution between villages and districts. Vector-habitat associations predicted from this larger-scale surveillance differed from those inferred from smaller-scale studies in Kudat; highlighting the importance of local ecological context. Findings highlight potential trade-offs between maximizing temporal versus spatial breadth when designing entomological surveillance; and provide baseline entomological and epidemiological data to inform future studies of entomological risk factors for human P. knowlesi infection.
  2. Blasdell KR, Morand S, Perera D, Firth C
    PLoS Negl Trop Dis, 2019 02;13(2):e0007141.
    PMID: 30811387 DOI: 10.1371/journal.pntd.0007141
    Although leptospirosis is traditionally considered a disease of rural, agricultural and flooded environments, Leptospira spp. are found in a range of habitats and infect numerous host species, with rodents among the most significant reservoirs and vectors. To explore the local ecology of Leptospira spp. in a city experiencing rapid urbanization, we assessed Leptospira prevalence in rodents from three locations in Malaysian Borneo with differing levels of anthropogenic influence: 1) high but stable influence (urban); 2) moderate yet increasing (developing); and 3) low (rural). A total of 116 urban, 122 developing and 78 rural rodents were sampled, with the majority of individuals assigned to either the Rattus rattus lineage R3 (n = 165) or Sundamys muelleri (n = 100). Leptospira spp. DNA was detected in 31.6% of all rodents, with more urban rodents positive (44.8%), than developing (32.0%) or rural rodents (28.1%), and these differences were statistically significant. The majority of positive samples were identified by sequence comparison to belong to known human pathogens L. interrogans (n = 57) and L. borgpetersenii (n = 38). Statistical analyses revealed that both Leptospira species occurred more commonly at sites with higher anthropogenic influence, particularly those with a combination of commercial and residential activity, while L. interrogans infection was also associated with low forest cover, and L. borgpetersenii was more likely to be identified at sites without natural bodies of water. This study suggests that some features associated with urbanization may promote the circulation of Leptospira spp., resulting in a potential public health risk in cities that may be substantially underestimated.
  3. Supali T, Djuardi Y, Bradley M, Noordin R, Rückert P, Fischer PU
    PLoS Negl Trop Dis, 2013;7(12):e2586.
    PMID: 24349595 DOI: 10.1371/journal.pntd.0002586
    The lymphatic filarial parasite Brugia timori occurs only in eastern Indonesia where it causes high morbidity. The absence of an animal reservoir, the inefficient transmission by Anopheles mosquitoes and the high sensitivity to DEC/albendazole treatment make this species a prime candidate for elimination by mass drug administration (MDA).
  4. Murphy A, Rajahram GS, Jilip J, Maluda M, William T, Hu W, et al.
    PLoS Negl Trop Dis, 2020 05;14(5):e0007504.
    PMID: 32392222 DOI: 10.1371/journal.pntd.0007504
    In South East Asia, dengue epidemics have increased in size and geographical distribution in recent years. We examined the spatiotemporal distribution and epidemiological characteristics of reported dengue cases in the predominantly rural state of Sabah, in Malaysian Borneo-an area where sylvatic and urban circulation of pathogens are known to intersect. Using a public health data set of routinely notified dengue cases in Sabah between 2010 and 2016, we described demographic and entomological risk factors, both before and after a 2014 change in the clinical case definition for the disease. Annual dengue incidence rates were spatially variable over the 7-year study period from 2010-2016 (state-wide mean annual incidence of 21 cases/100,000 people; range 5-42/100,000), but were highest in rural localities in the western districts of the state (Kuala Penyu, Nabawan, Tenom and Kota Marudu). Eastern districts exhibited lower overall dengue rates, although a high proportion of severe (haemorrhagic) dengue cases (44%) were focused in Sandakan and Tawau. Dengue incidence was highest for those aged between 10 and 29 years (24/100,000), and was slightly higher for males compared to females. Available vector surveillance data indicated that during large outbreaks in 2015 and 2016 the mosquito Aedes albopictus was more prevalent in both urban and rural households (House Index of 64%) than Ae. aegypti (15%). Demographic patterns remained unchanged both before and after the dengue case definition was changed; however, in the years following the change, reported case numbers increased substantially. Overall, these findings suggest that dengue outbreaks in Sabah are increasing in both urban and rural settings. Future studies to better understand the drivers of risk in specific age groups, genders and geographic locations, and to test the potential role of Ae. albopictus in transmission, may help target dengue prevention and control efforts.
  5. Cheng Q, Jing Q, Spear RC, Marshall JM, Yang Z, Gong P
    PLoS Negl Trop Dis, 2017 Jun;11(6):e0005701.
    PMID: 28640895 DOI: 10.1371/journal.pntd.0005701
    Dengue is a fast spreading mosquito-borne disease that affects more than half of the population worldwide. An unprecedented outbreak happened in Guangzhou, China in 2014, which contributed 52 percent of all dengue cases that occurred in mainland China between 1990 and 2015. Our previous analysis, based on a deterministic model, concluded that the early timing of the first imported case that triggered local transmission and the excessive rainfall thereafter were the most important determinants of the large final epidemic size in 2014. However, the deterministic model did not allow us to explore the driving force of the early local transmission. Here, we expand the model to include stochastic elements and calculate the successful invasion rate of cases that entered Guangzhou at different times under different climate and intervention scenarios. The conclusion is that the higher number of imported cases in May and June was responsible for the early outbreak instead of climate. Although the excessive rainfall in 2014 did increase the success rate, this effect was offset by the low initial water level caused by interventions in late 2013. The success rate is strongly dependent on mosquito abundance during the recovery period of the imported case, since the first step of a successful invasion is infecting at least one local mosquito. The average final epidemic size of successful invasion decreases exponentially with introduction time, which means if an imported case in early summer initiates the infection process, the final number infected can be extremely large. Therefore, dengue outbreaks occurring in Thailand, Singapore, Malaysia and Vietnam in early summer merit greater attention, since the travel volumes between Guangzhou and these countries are large. As the climate changes, destroying mosquito breeding sites in Guangzhou can mitigate the detrimental effects of the probable increase in rainfall in spring and summer.
  6. Rajamanikam A, Isa MNM, Samudi C, Devaraj S, Govind SK
    PLoS Negl Trop Dis, 2023 Mar;17(3):e0011170.
    PMID: 36989208 DOI: 10.1371/journal.pntd.0011170
    Whilst the influence of intestinal microbiota has been shown in many diseases such as irritable bowel syndrome, colorectal cancer, and aging, investigations are still scarce on its role in altering the nature of other infective organisms. Here we studied the association and interaction of Blastocystis sp. and human intestinal microbiota. In this study, we investigated the gut microbiome of Blastocystis sp.-free and Blastocystis sp. ST3-infected individuals who are symptomatic and asymptomatic. We tested if the expression of phenotype and pathogenic characteristics of Blastocystis sp. ST3 was influenced by the alteration of its accompanying microbiota. Blastocystis sp. ST3 infection alters bacterial composition. Its presence in asymptomatic individuals showed a significant effect on microbial richness compared to symptomatic ones. Inferred metagenomic findings suggest that colonization of Blastocystis sp. ST3 could contribute to the alteration of microbial functions. For the first time, we demonstrate the influence of bacteria on Blastocystis sp. pathogenicity. When Blastocystis sp. isolated from a symptomatic individual was co-cultured with bacterial suspension of Blastocystis sp. from an asymptomatic individual, the parasite demonstrated increased growth and reduced potential pathogenic expressions. This study also reveals that Blastocystis sp. infection could influence microbial functions without much effect on the microbiota diversity itself. Our results also demonstrate evidence on the influential role of gut microbiota in altering the characteristics of the parasite, which becomes the basis for the contradictory findings on the parasite's pathogenic role seen across different studies. Our study provides evidence that asymptomatic Blastocystis sp. in a human gut can be triggered to show pathogenic characteristics when influenced by the intestinal microbiota.
  7. Tomashek KM, Wills B, See Lum LC, Thomas L, Durbin A, Leo YS, et al.
    PLoS Negl Trop Dis, 2018 10;12(10):e0006497.
    PMID: 30286085 DOI: 10.1371/journal.pntd.0006497
    Dengue is a major public health problem worldwide. Although several drug candidates have been evaluated in randomized controlled trials, none has been effective and at present, early recognition of severe dengue and timely supportive care are used to reduce mortality. While the first dengue vaccine was recently licensed, and several other candidates are in late stage clinical trials, future decisions regarding widespread deployment of vaccines and/or therapeutics will require evidence of product safety, efficacy and effectiveness. Standard, quantifiable clinical endpoints are needed to ensure reproducibility and comparability of research findings. To address this need, we established a working group of dengue researchers and public health specialists to develop standardized endpoints and work towards consensus opinion on those endpoints. After discussion at two working group meetings and presentations at international conferences, a Delphi methodology-based query was used to finalize and operationalize the clinical endpoints. Participants were asked to select the best endpoints from proposed definitions or offer revised/new definitions, and to indicate whether contributing items should be designated as optional or required. After the third round of inquiry, 70% or greater agreement was reached on moderate and severe plasma leakage, moderate and severe bleeding, acute hepatitis and acute liver failure, and moderate and severe neurologic disease. There was less agreement regarding moderate and severe thrombocytopenia and moderate and severe myocarditis. Notably, 68% of participants agreed that a 50,000 to 20,000 mm3 platelet range be used to define moderate thrombocytopenia; however, they remained divided on whether a rapid decreasing trend or one platelet count should be case defining. While at least 70% agreement was reached on most endpoints, the process identified areas for further evaluation and standardization within the context of ongoing clinical studies. These endpoints can be used to harmonize data collection and improve comparability between dengue clinical trials.
  8. Shepard DS, Undurraga EA, Betancourt-Cravioto M, Guzmán MG, Halstead SB, Harris E, et al.
    PLoS Negl Trop Dis, 2014 Nov;8(11):e3306.
    PMID: 25412506 DOI: 10.1371/journal.pntd.0003306
    Dengue presents a formidable and growing global economic and disease burden, with around half the world's population estimated to be at risk of infection. There is wide variation and substantial uncertainty in current estimates of dengue disease burden and, consequently, on economic burden estimates. Dengue disease varies across time, geography and persons affected. Variations in the transmission of four different viruses and interactions among vector density and host's immune status, age, pre-existing medical conditions, all contribute to the disease's complexity. This systematic review aims to identify and examine estimates of dengue disease burden and costs, discuss major sources of uncertainty, and suggest next steps to improve estimates. Economic analysis of dengue is mainly concerned with costs of illness, particularly in estimating total episodes of symptomatic dengue. However, national dengue disease reporting systems show a great diversity in design and implementation, hindering accurate global estimates of dengue episodes and country comparisons. A combination of immediate, short-, and long-term strategies could substantially improve estimates of disease and, consequently, of economic burden of dengue. Suggestions for immediate implementation include refining analysis of currently available data to adjust reported episodes and expanding data collection in empirical studies, such as documenting the number of ambulatory visits before and after hospitalization and including breakdowns by age. Short-term recommendations include merging multiple data sources, such as cohort and surveillance data to evaluate the accuracy of reporting rates (by health sector, treatment, severity, etc.), and using covariates to extrapolate dengue incidence to locations with no or limited reporting. Long-term efforts aim at strengthening capacity to document dengue transmission using serological methods to systematically analyze and relate to epidemiologic data. As promising tools for diagnosis, vaccination, vector control, and treatment are being developed, these recommended steps should improve objective, systematic measures of dengue burden to strengthen health policy decisions.
  9. Shepard DS, Undurraga EA, Halasa YA
    PLoS Negl Trop Dis, 2013;7(2):e2055.
    PMID: 23437406 DOI: 10.1371/journal.pntd.0002055
    BACKGROUND: Dengue poses a substantial economic and disease burden in Southeast Asia (SEA). Quantifying this burden is critical to set policy priorities and disease-control strategies.

    METHODS AND FINDINGS: We estimated the economic and disease burden of dengue in 12 countries in SEA: Bhutan, Brunei, Cambodia, East-Timor, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, Thailand, and Viet Nam. We obtained reported cases from multiple sources--surveillance data, World Health Organization (WHO), and published studies--and adjusted for underreporting using expansion factors from previous literature. We obtained unit costs per episode through a systematic literature review, and completed missing data using linear regressions. We excluded costs such as prevention and vector control, and long-term sequelae of dengue. Over the decade of 2001-2010, we obtained an annual average of 2.9 million (m) dengue episodes and 5,906 deaths. The annual economic burden (with 95% certainty levels) was US$950m (US$610m-US$1,384m) or about US$1.65 (US$1.06-US$2.41) per capita. The annual number of disability-adjusted life years (DALYs), based on the original 1994 definition, was 214,000 (120,000-299,000), which is equivalent to 372 (210-520) DALYs per million inhabitants.

    CONCLUSION: Dengue poses a substantial economic and disease burden in SEA with a DALY burden per million inhabitants in the region. This burden is higher than that of 17 other conditions, including Japanese encephalitis, upper respiratory infections, and hepatitis B.

  10. Bray DP, Yaman K, Underhilll BA, Mitchell F, Carter V, Hamilton JG
    PLoS Negl Trop Dis, 2014 Dec;8(12):e3316.
    PMID: 25474027 DOI: 10.1371/journal.pntd.0003316
    BACKGROUND: The sand fly Phlebotomus argentipes is arguably the most important vector of leishmaniasis worldwide. As there is no vaccine against the parasites that cause leishmaniasis, disease prevention focuses on control of the insect vector. Understanding reproductive behaviour will be essential to controlling populations of P. argentipes, and developing new strategies for reducing leishmaniasis transmission. Through statistical analysis of male-female interactions, this study provides a detailed description of P. argentipes courtship, and behaviours critical to mating success are highlighted. The potential for a role of cuticular hydrocarbons in P. argentipes courtship is also investigated, by comparing chemicals extracted from the surface of male and female flies.

    PRINCIPAL FINDINGS: P. argentipes courtship shared many similarities with that of both Phlebotomus papatasi and the New World leishmaniasis vector Lutzomyia longipalpis. Male wing-flapping while approaching the female during courtship predicted mating success, and touching between males and females was a common and frequent occurrence. Both sexes were able to reject a potential partner. Significant differences were found in the profile of chemicals extracted from the surface of males and females. Results of GC analysis indicate that female extracts contained a number of peaks with relatively short retention times not present in males. Extracts from males had higher peaks for chemicals with relatively long retention times.

    CONCLUSIONS: The importance of male approach flapping suggests that production of audio signals through wing beating, or dispersal of sex pheromones, are important to mating in this species. Frequent touching as a means of communication, and the differences in the chemical profiles extracted from males and females, may also indicate a role for cuticular hydrocarbons in P. argentipes courtship. Comparing characteristics of successful and unsuccessful mates could aid in identifying the modality of signals involved in P. argentipes courtship, and their potential for use in developing new strategies for vector control.

  11. Muh F, Kim N, Nyunt MH, Firdaus ER, Han JH, Hoque MR, et al.
    PLoS Negl Trop Dis, 2020 06;14(6):e0008323.
    PMID: 32559186 DOI: 10.1371/journal.pntd.0008323
    Malaria is caused by multiple different species of protozoan parasites, and interventions in the pre-elimination phase can lead to drastic changes in the proportion of each species causing malaria. In endemic areas, cross-reactivity may play an important role in the protection and blocking transmission. Thus, successful control of one species could lead to an increase in other parasite species. A few studies have reported cross-reactivity producing cross-immunity, but the extent of cross-reactive, particularly between closely related species, is poorly understood. P. vivax and P. knowlesi are particularly closely related species causing malaria infections in SE Asia, and whilst P. vivax cases are in decline, zoonotic P. knowlesi infections are rising in some areas. In this study, the cross-species reactivity and growth inhibition activity of P. vivax blood-stage antigen-specific antibodies against P. knowlesi parasites were investigated. Bioinformatics analysis, immunofluorescence assay, western blotting, protein microarray, and growth inhibition assay were performed to investigate the cross-reactivity. P. vivax blood-stage antigen-specific antibodies recognized the molecules located on the surface or released from apical organelles of P. knowlesi merozoites. Recombinant P. vivax and P. knowlesi proteins were also recognized by P. knowlesi- and P. vivax-infected patient antibodies, respectively. Immunoglobulin G against P. vivax antigens from both immune animals and human malaria patients inhibited the erythrocyte invasion by P. knowlesi. This study demonstrates that there is extensive cross-reactivity between antibodies against P. vivax to P. knowlesi in the blood stage, and these antibodies can potently inhibit in vitro invasion, highlighting the potential cross-protective immunity in endemic areas.
  12. Han JH, Cho JS, Ong JJY, Park JH, Nyunt MH, Sutanto E, et al.
    PLoS Negl Trop Dis, 2020 Jul;14(7):e0008202.
    PMID: 32645098 DOI: 10.1371/journal.pntd.0008202
    Plasmodium vivax is the most widespread and difficult to treat cause of human malaria. The development of vaccines against the blood stages of P. vivax remains a key objective for the control and elimination of vivax malaria. Erythrocyte binding-like (EBL) protein family members such as Duffy binding protein (PvDBP) are of critical importance to erythrocyte invasion and have been the major target for vivax malaria vaccine development. In this study, we focus on another member of EBL protein family, P. vivax erythrocyte binding protein (PvEBP). PvEBP was first identified in Cambodian (C127) field isolates and has subsequently been showed its preferences for binding reticulocytes which is directly inhibited by antibodies. We analysed PvEBP sequence from 316 vivax clinical isolates from eight countries including China (n = 4), Ethiopia (n = 24), Malaysia (n = 53), Myanmar (n = 10), Papua New Guinea (n = 16), Republic of Korea (n = 10), Thailand (n = 174), and Vietnam (n = 25). PvEBP gene exhibited four different phenotypic clusters based on the insertion/deletion (indels) variation. PvEBP-RII (179-479 aa.) showed highest polymorphism similar to other EBL family proteins in various Plasmodium species. Whereas even though PvEBP-RIII-V (480-690 aa.) was the most conserved domain, that showed strong neutral selection pressure for gene purifying with significant population expansion. Antigenicity of both of PvEBP-RII (16.1%) and PvEBP-RIII-V (21.5%) domains were comparatively lower than other P. vivax antigen which expected antigens associated with merozoite invasion. Total IgG recognition level of PvEBP-RII was stronger than PvEBP-RIII-V domain, whereas total IgG inducing level was stronger in PvEBP-RIII-V domain. These results suggest that PvEBP-RII is mainly recognized by natural IgG for innate protection, whereas PvEBP-RIII-V stimulates IgG production activity by B-cell for acquired immunity. Overall, the low antigenicity of both regions in patients with vivax malaria likely reflects genetic polymorphism for strong positive selection in PvEBP-RII and purifying selection in PvEBP-RIII-V domain. These observations pose challenging questions to the selection of EBP and point out the importance of immune pressure and polymorphism required for inclusion of PvEBP as a vaccine candidate.
  13. Park JH, Kim MH, Sutanto E, Na SW, Kim MJ, Yeom JS, et al.
    PLoS Negl Trop Dis, 2022 Jun;16(6):e0010492.
    PMID: 35737709 DOI: 10.1371/journal.pntd.0010492
    Plasmodium vivax is the most widespread cause of human malaria. Recent reports of drug resistant vivax malaria and the challenge of eradicating the dormant liver forms increase the importance of vaccine development against this relapsing disease. P. vivax reticulocyte binding protein 1a (PvRBP1a) is a potential vaccine candidate, which is involved in red cell tropism, a crucial step in the merozoite invasion of host reticulocytes. As part of the initial evaluation of the PvRBP1a vaccine candidate, we investigated its genetic diversity and antigenicity using geographically diverse clinical isolates. We analysed pvrbp1a genetic polymorphisms using 202 vivax clinical isolates from six countries. Pvrbp1a was separated into six regions based on specific domain features, sequence conserved/polymorphic regions, and the reticulocyte binding like (RBL) domains. In the fragmented gene sequence analysis, PvRBP1a region II (RII) and RIII (head and tail structure homolog, 152-625 aa.) showed extensive polymorphism caused by random point mutations. The haplotype network of these polymorphic regions was classified into three clusters that converged to independent populations. Antigenicity screening was performed using recombinant proteins PvRBP1a-N (157-560 aa.) and PvRBP1a-C (606-962 aa.), which contained head and tail structure region and sequence conserved region, respectively. Sensitivity against PvRBP1a-N (46.7%) was higher than PvRBP1a-C (17.8%). PvRBP1a-N was reported as a reticulocyte binding domain and this study identified a linear epitope with moderate antigenicity, thus an attractive domain for merozoite invasion-blocking vaccine development. However, our study highlights that a global PvRBP1a-based vaccine design needs to overcome several difficulties due to three distinct genotypes and low antigenicity levels.
  14. Moyes CL, Henry AJ, Golding N, Huang Z, Singh B, Baird JK, et al.
    PLoS Negl Trop Dis, 2014 Mar;8(3):e2780.
    PMID: 24676231 DOI: 10.1371/journal.pntd.0002780
    BACKGROUND: The simian malaria parasite, Plasmodium knowlesi, can cause severe and fatal disease in humans yet it is rarely included in routine public health reporting systems for malaria and its geographical range is largely unknown. Because malaria caused by P. knowlesi is a truly neglected tropical disease, there are substantial obstacles to defining the geographical extent and risk of this disease. Information is required on the occurrence of human cases in different locations, on which non-human primates host this parasite and on which vectors are able to transmit it to humans. We undertook a systematic review and ranked the existing evidence, at a subnational spatial scale, to investigate the potential geographical range of the parasite reservoir capable of infecting humans.

    METHODOLOGY/PRINCIPAL FINDINGS: After reviewing the published literature we identified potential host and vector species and ranked these based on how informative they are for the presence of an infectious parasite reservoir, based on current evidence. We collated spatial data on parasite occurrence and the ranges of the identified host and vector species. The ranked spatial data allowed us to assign an evidence score to 475 subnational areas in 19 countries and we present the results on a map of the Southeast and South Asia region.

    CONCLUSIONS/SIGNIFICANCE: We have ranked subnational areas within the potential disease range according to evidence for presence of a disease risk to humans, providing geographical evidence to support decisions on prevention, management and prophylaxis. This work also highlights the unknown risk status of large parts of the region. Within this unknown category, our map identifies which areas have most evidence for the potential to support an infectious reservoir and are therefore a priority for further investigation. Furthermore we identify geographical areas where further investigation of putative host and vector species would be highly informative for the region-wide assessment.

  15. Cong Y, Lentz MR, Lara A, Alexander I, Bartos C, Bohannon JK, et al.
    PLoS Negl Trop Dis, 2017 04;11(4):e0005532.
    PMID: 28388650 DOI: 10.1371/journal.pntd.0005532
    Nipah virus (NiV) is a paramyxovirus (genus Henipavirus) that emerged in the late 1990s in Malaysia and has since been identified as the cause of sporadic outbreaks of severe febrile disease in Bangladesh and India. NiV infection is frequently associated with severe respiratory or neurological disease in infected humans with transmission to humans through inhalation, contact or consumption of NiV contaminated foods. In the work presented here, the development of disease was investigated in the African Green Monkey (AGM) model following intratracheal (IT) and, for the first time, small-particle aerosol administration of NiV. This study utilized computed tomography (CT) and magnetic resonance imaging (MRI) to temporally assess disease progression. The host immune response and changes in immune cell populations over the course of disease were also evaluated. This study found that IT and small-particle administration of NiV caused similar disease progression, but that IT inoculation induced significant congestion in the lungs while disease following small-particle aerosol inoculation was largely confined to the lower respiratory tract. Quantitative assessment of changes in lung volume found up to a 45% loss in IT inoculated animals. None of the subjects in this study developed overt neurological disease, a finding that was supported by MRI analysis. The development of neutralizing antibodies was not apparent over the 8-10 day course of disease, but changes in cytokine response in all animals and activated CD8+ T cell numbers suggest the onset of cell-mediated immunity. These studies demonstrate that IT and small-particle aerosol infection with NiV in the AGM model leads to a severe respiratory disease devoid of neurological indications. This work also suggests that extending the disease course or minimizing the impact of the respiratory component is critical to developing a model that has a neurological component and more accurately reflects the human condition.
  16. Lara A, Cong Y, Jahrling PB, Mednikov M, Postnikova E, Yu S, et al.
    PLoS Negl Trop Dis, 2019 06;13(6):e0007454.
    PMID: 31166946 DOI: 10.1371/journal.pntd.0007454
    The ability to appropriately mimic human disease is critical for using animal models as a tool for understanding virus pathogenesis. In the case of Nipah virus (NiV), infection of humans appears to occur either through inhalation, contact with or consumption of infected material. In two of these circumstances, respiratory or sinusoidal exposure represents a likely route of infection. In this study, intermediate-size aerosol particles (~7 μm) of NiV-Malaysia were used to mimic potential routes of exposure by focusing viral deposition in the upper respiratory tract. Our previous report showed this route of exposure extended the disease course and a single animal survived the infection. Here, analysis of the peripheral immune response found minimal evidence of systemic inflammation and depletion of B cells during acute disease. However, the animal that survived infection developed an early IgM response with rapid development of neutralizing antibodies that likely afforded protection. The increase in NiV-specific antibodies correlated with an expansion of the B cell population in the survivor. Cell-mediated immunity was not clearly apparent in animals that succumbed during the acute phase of disease. However, CD4+ and CD8+ effector memory cells increased in the survivor with correlating increases in cytokines and chemokines associated with cell-mediated immunity. Interestingly, kinetic changes of the CD4+ and CD8bright T cell populations over the course of acute disease were opposite from animals that succumbed to infection. In addition, increases in NK cells and basophils during convalescence of the surviving animal were also evident, with viral antigen found in NK cells. These data suggest that a systemic inflammatory response and "cytokine storm" are not major contributors to NiV-Malaysia pathogenesis in the AGM model using this exposure route. Further, these data demonstrate that regulation of cell-mediated immunity, in addition to rapid production of NiV specific antibodies, may be critical for surviving NiV infection.
  17. Kar SK, Dwibedi B, Das BK, Agrawala BK, Ramachandran CP, Horton J
    PLoS Negl Trop Dis, 2017 Oct;11(10):e0005631.
    PMID: 29059186 DOI: 10.1371/journal.pntd.0005631
    BACKGROUND: Once interruption of transmission of lymphatic filariasis is achieved, morbidity prevention and management becomes more important. A study in Brugia malayi filariasis from India has shown sub-clinical lymphatic pathology with potential reversibility. We studied a Wuchereria bancrofti infected population, the major contributor to LF globally.

    METHODS: Children aged 5-18 years from Odisha, India were screened for W. bancrofti infection and disease. 102 infected children, 50 with filarial disease and 52 without symptoms were investigated by lymphoscintigraphy and then randomized to receive a supervised single oral dose of DEC and albendazole which was repeated either annually or semi-annually. The lymphatic pathology was evaluated six monthly for two years.

    FINDINGS: Baseline lymphoscintigraphy showed abnormality in lower limb lymphatics in 80% of symptomatic (40/50) and 63·5% (33/52) of asymptomatic children. Progressive improvement in baseline pathology was seen in 70·8, 87·3, 98·6, and 98·6% of cases at 6, 12, 18, and 24 months follow up, while in 4·2, 22·5, 47·9 and 64·8%, pathology reverted to normal. This was independent of age (p = 0·27), symptomatic status (p = 0·57) and semi-annual/bi-annual dosing (p = 0·46). Six of eleven cases showed clinical reduction in lymphedema of legs.

    INTERPRETATION: A significant proportion of a young W. bancrofti infected population exhibited lymphatic pathology which was reversible with annual dosage of DEC and albendazole. This provides evidence for morbidity prevention & treatment of early lymphedema. It can also be used as a tool to improve community compliance during mass drug administration.

    TRIAL REGISTRATION: ClinicalTrials.gov No CTRI/2013/10/004121.

  18. Isa A, Loke YK, Smith JR, Papageorgiou A, Hunter PR
    PLoS Negl Trop Dis, 2013;7(9):e2401.
    PMID: 24086777 DOI: 10.1371/journal.pntd.0002401
    BACKGROUND: Dengue fever is endemic in Malaysia, with frequent major outbreaks in urban areas. The major control strategy relies on health promotional campaigns aimed at encouraging people to reduce mosquito breeding sites close to people's homes. However, such campaigns have not always been 100% effective. The concept of self-efficacy is an area of increasing research interest in understanding how health promotion can be most effective. This paper reports on a study of the impact of self-efficacy on dengue knowledge and dengue preventive behaviour.

    METHODS AND FINDINGS: We recruited 280 adults from 27 post-outbreak villages in the state of Terengganu, east coast of Malaysia. Measures of health promotion and educational intervention activities and types of communication during outbreak, level of dengue knowledge, level and strength of self-efficacy and dengue preventive behaviour were obtained via face-to-face interviews and questionnaires. A structural equation model was tested and fitted the data well (χ(2) = 71.659, df = 40, p = 0.002, RMSEA = 0.053, CFI = 0.973, TLI = 0.963). Mass media, local contact and direct information-giving sessions significantly predicted level of knowledge of dengue. Level and strength of self-efficacy fully mediated the relationship between knowledge of dengue and dengue preventive behaviours. Strength of self-efficacy acted as partial mediator in the relationship between knowledge of dengue and dengue preventive behaviours.

    CONCLUSIONS: To control and prevent dengue outbreaks by behavioural measures, health promotion and educational interventions during outbreaks should now focus on those approaches that are most likely to increase the level and strength of self-efficacy.

  19. Ramli SR, Moreira GMSG, Zantow J, Goris MGA, Nguyen VK, Novoselova N, et al.
    PLoS Negl Trop Dis, 2019 01;13(1):e0007131.
    PMID: 30677033 DOI: 10.1371/journal.pntd.0007131
    BACKGROUND: Leptospirosis is the most common zoonotic disease worldwide. The diagnostic performance of a serological test for human leptospirosis is mainly influenced by the antigen used in the test assay. An ideal serological test should cover all serovars of pathogenic leptospires with high sensitivity and specificity and use reagents that are relatively inexpensive to produce and can be used in tropical climates. Peptide-based tests fulfil at least the latter two requirements, and ORFeome phage display has been successfully used to identify immunogenic peptides from other pathogens.

    METHODOLOGY/PRINCIPAL FINDINGS: Two ORFeome phage display libraries of the entire Leptospira spp. genomes from five local strains isolated in Malaysia and seven WHO reference strains were constructed. Subsequently, 18 unique Leptospira peptides were identified in a screen using a pool of sera from patients with acute leptospirosis. Five of these were validated by titration ELISA using different pools of patient or control sera. The diagnostic performance of these five peptides was then assessed against 16 individual sera from patients with acute leptospirosis and 16 healthy donors and was compared to that of two recombinant reference proteins from L. interrogans. This analysis revealed two peptides (SIR16-D1 and SIR16-H1) from the local isolates with good accuracy for the detection of acute leptospirosis (area under the ROC curve: 0.86 and 0.78, respectively; sensitivity: 0.88 and 0.94; specificity: 0.81 and 0.69), which was close to that of the reference proteins LipL32 and Loa22 (area under the ROC curve: 0.91 and 0.80; sensitivity: 0.94 and 0.81; specificity: 0.75 and 0.75).

    CONCLUSIONS/SIGNIFICANCE: This analysis lends further support for using ORFeome phage display to identify pathogen-associated immunogenic peptides, and it suggests that this technique holds promise for the development of peptide-based diagnostics for leptospirosis and, possibly, of vaccines against this pathogen.

  20. Arham AF, Amin L, Mustapa MAC, Mahadi Z, Yaacob M, Ibrahim M
    PLoS Negl Trop Dis, 2021 Jun;15(6):e0009493.
    PMID: 34185785 DOI: 10.1371/journal.pntd.0009493
    Outdoor Residual Spraying (ORS) technique is a complementary preventive measure for dengue. The alarming number of dengue cases in Malaysia requires an alternative method to control dengue besides the traditional method such as fogging. However, the introduction of new technologies depends on social acceptance. Therefore, this study was important to determine the factors that influence stakeholders' attitudes towards the ORS and the moderating factor. A validated instrument was used to randomly interview 399 respondents representing two stakeholder groups which consist of scientists, and the public in Klang Valley, Malaysia. The findings revealed that the stakeholders claimed to have a high degree of religiosity, a high level of trust in the key players, perceived ORS as having high benefits, and displayed highly positive attitudes towards the ORS. The attitudes model towards the ORS model was developed using the SmartPLS software version. The perceived benefit was endorsed as the most important direct predictor of attitudes towards the ORS (ß = 0.618, P<0.001), followed by trust in the key players (ß = 0.151, P<0.001). It is also interesting to note that religiosity served as a moderator for the association between perceived benefit (ß = 0.075, P = 0.024) and perceived risk (ß = 0.114, P = 0.006) with attitudes towards the ORS. The identified predictor factors of stakeholders' attitudes toward the ORS and the moderating factor can serve as indicators for social acceptance of ORS in developing countries. These indicators can help the policymakers in decision making to implement this technique.
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links