Displaying publications 81 - 100 of 163 in total

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  1. Lim JT, Dickens BSL, Chew LZX, Choo ELW, Koo JR, Aik J, et al.
    PLoS Negl Trop Dis, 2020 10;14(10):e0008719.
    PMID: 33119609 DOI: 10.1371/journal.pntd.0008719
    An estimated 105 million dengue infections occur per year across 120 countries, where traditional vector control is the primary control strategy to reduce contact between mosquito vectors and people. The ongoing sars-cov-2 pandemic has resulted in dramatic reductions in human mobility due to social distancing measures; the effects on vector-borne illnesses are not known. Here we examine the pre and post differences of dengue case counts in Malaysia, Singapore and Thailand, and estimate the effects of social distancing as a treatment effect whilst adjusting for temporal confounders. We found that social distancing is expected to lead to 4.32 additional cases per 100,000 individuals in Thailand per month, which equates to 170 more cases per month in the Bangkok province (95% CI: 100-242) and 2008 cases in the country as a whole (95% CI: 1170-2846). Social distancing policy estimates for Thailand were also found to be robust to model misspecification, and variable addition and omission. Conversely, no significant impact on dengue transmission was found in Singapore or Malaysia. Across country disparities in social distancing policy effects on reported dengue cases are reasoned to be driven by differences in workplace-residence structure, with an increase in transmission risk of arboviruses from social distancing primarily through heightened exposure to vectors in elevated time spent at residences, demonstrating the need to understand the effects of location on dengue transmission risk under novel population mixing conditions such as those under social distancing policies.
  2. 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).
  3. Olliaro P, Fouque F, Kroeger A, Bowman L, Velayudhan R, Santelli AC, et al.
    PLoS Negl Trop Dis, 2018 02;12(2):e0005967.
    PMID: 29389959 DOI: 10.1371/journal.pntd.0005967
    BACKGROUND: Research has been conducted on interventions to control dengue transmission and respond to outbreaks. A summary of the available evidence will help inform disease control policy decisions and research directions, both for dengue and, more broadly, for all Aedes-borne arboviral diseases.

    METHOD: A research-to-policy forum was convened by TDR, the Special Programme for Research and Training in Tropical Diseases, with researchers and representatives from ministries of health, in order to review research findings and discuss their implications for policy and research.

    RESULTS: The participants reviewed findings of research supported by TDR and others. Surveillance and early outbreak warning. Systematic reviews and country studies identify the critical characteristics that an alert system should have to document trends reliably and trigger timely responses (i.e., early enough to prevent the epidemic spread of the virus) to dengue outbreaks. A range of variables that, according to the literature, either indicate risk of forthcoming dengue transmission or predict dengue outbreaks were tested and some of them could be successfully applied in an Early Warning and Response System (EWARS). Entomological surveillance and vector management. A summary of the published literature shows that controlling Aedes vectors requires complex interventions and points to the need for more rigorous, standardised study designs, with disease reduction as the primary outcome to be measured. House screening and targeted vector interventions are promising vector management approaches. Sampling vector populations, both for surveillance purposes and evaluation of control activities, is usually conducted in an unsystematic way, limiting the potentials of entomological surveillance for outbreak prediction. Combining outbreak alert and improved approaches of vector management will help to overcome the present uncertainties about major risk groups or areas where outbreak response should be initiated and where resources for vector management should be allocated during the interepidemic period.

    CONCLUSIONS: The Forum concluded that the evidence collected can inform policy decisions, but also that important research gaps have yet to be filled.

  4. Hussin A, Nor Rahim MY, Dalusim F, Shahidan MA, Nathan S, Ibrahim N
    PLoS Negl Trop Dis, 2023 Oct;17(10):e0011696.
    PMID: 37844130 DOI: 10.1371/journal.pntd.0011696
    INTRODUCTION: Melioidosis is a deadly endemic disease in northern Australia and Southeast Asia, including Sabah, Malaysia, which is caused by the bacterium Burkholderia pseudomallei. It contributes to high fatality rates, mainly due to misdiagnosis leading to the wrong treatment being administered to the patients. Local epidemiology and data on clinical features could assist clinicians during diagnosis and treatment. However, these details are still scarce, particularly in Sabah.

    METHODS: A retrospective study of 246 culture-confirmed melioidosis cases in Queen Elizabeth Hospital, Sabah, Malaysia was performed between 2016 and 2018. The epidemiological data and clinical and laboratory findings were extracted and analysed.

    RESULTS: The annual incidence of culture-confirmed melioidosis cases was estimated to be 4.97 per 100,000 people. The mean age of the patients was 50±15 years. Males and members of the Kadazan-Dusun ethnic group accounted for the majority of the melioidosis cases. The odds ratio analysis indicated that bacteraemic melioidosis in this region was significantly associated with fever (76%), and patients having at least one underlying illness (43%), including diabetes mellitus (32%). Sixty-eight patients (28%) succumbed to melioidosis. Contrary to what is known regarding factors that promote bacteraemic melioidosis, neither patients with fever nor patients with at least one comorbid disease, including diabetes mellitus, were significantly associated with death from melioidosis. There was no statistically significant difference between patients without comorbidities (24, 27%) and those with at least one comorbid disease (26, 25%), including diabetes mellitus (18, 23%). The odds ratios indicate that melioidosis mortality in this region is related to patients showing respiratory organ-associated symptoms (29%), bacteraemia (30%), and septic shock (47%). Burkholderia pseudomallei isolates in this study were highly susceptible to ceftazidime (100%), imipenem (100%), and trimethoprim-sulfamethoxazole (98%).

    CONCLUSIONS: Information obtained from this study can be used by clinicians to recognise individuals with the highest risk of acquiring melioidosis, estimate an accurate prognosis, and provide effective treatment for melioidosis patients to reduce death from melioidosis.

  5. Nwameme A, Dako-Gyeke P, Asampong E, Allotey P, Reidpath DD, Certain E, et al.
    PLoS Negl Trop Dis, 2023 Mar;17(3):e0011139.
    PMID: 36961830 DOI: 10.1371/journal.pntd.0011139
    The Special Programme for Research and Training in Tropical Diseases developed a massive open online course (MOOC) on implementation research with a focus on infectious diseases of poverty (IDPs) to reinforce the explanation of implementation research concepts through real case studies. The target MOOC participant group included public health officers, researchers and students. By reshaping institutions and building resilience in communities and systems, implementation research will allow progress towards universal health coverage and sustainable development goals. This study evaluates learners' knowledge in implementation research after completing the MOOC using anonymous exit survey responses. Of the almost 4000 enrolled in the two sessions of the MOOC in 2018, about 30% completed all five modules and the assessments, and were awarded certificates. The majority of the participants were early to mid-career professionals, under the age of 40, and from low- and middle-income countries. They were slightly more likely to be men (56%) with a Bachelor or a Master's degree. Participants were public health researchers (45%), public health officers (11%) or students (11%). On completion of the course, an exit survey revealed that 80.9% of respondents indicated significant improvement to strong and very strong implementation research knowledge. This evaluation clearly shows the usefulness of the MOOC on implementation research for reaching out to field researchers and public health practitioners who are facing problems in the implementation of control programmes in low- and middle-income countries.
  6. 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.
  7. William T, Rahman HA, Jelip J, Ibrahim MY, Menon J, Grigg MJ, et al.
    PLoS Negl Trop Dis, 2013;7(1):e2026.
    PMID: 23359830 DOI: 10.1371/journal.pntd.0002026
    BACKGROUND: The simian parasite Plasmodium knowlesi is a common cause of human malaria in Malaysian Borneo and threatens the prospect of malaria elimination. However, little is known about the emergence of P. knowlesi, particularly in Sabah. We reviewed Sabah Department of Health records to investigate the trend of each malaria species over time.

    METHODS: Reporting of microscopy-diagnosed malaria cases in Sabah is mandatory. We reviewed all available Department of Health malaria notification records from 1992-2011. Notifications of P. malariae and P. knowlesi were considered as a single group due to microscopic near-identity.

    RESULTS: From 1992-2011 total malaria notifications decreased dramatically, with P. falciparum peaking at 33,153 in 1994 and decreasing 55-fold to 605 in 2011, and P. vivax peaking at 15,857 in 1995 and decreasing 25-fold to 628 in 2011. Notifications of P. malariae/P. knowlesi also demonstrated a peak in the mid-1990s (614 in 1994) before decreasing to ≈ 100/year in the late 1990s/early 2000s. However, P. malariae/P. knowlesi notifications increased >10-fold between 2004 (n = 59) and 2011 (n = 703). In 1992 P. falciparum, P. vivax and P. malariae/P. knowlesi monoinfections accounted for 70%, 24% and 1% respectively of malaria notifications, compared to 30%, 31% and 35% in 2011. The increase in P. malariae/P. knowlesi notifications occurred state-wide, appearing to have begun in the southwest and progressed north-easterly.

    CONCLUSIONS: A significant recent increase has occurred in P. knowlesi notifications following reduced transmission of the human Plasmodium species, and this trend threatens malaria elimination. Determination of transmission dynamics and risk factors for knowlesi malaria is required to guide measures to control this rising incidence.

  8. Alhoot MA, Wang SM, Sekaran SD
    PLoS Negl Trop Dis, 2011 Nov;5(11):e1410.
    PMID: 22140591 DOI: 10.1371/journal.pntd.0001410
    Dengue infection ranks as one of the most significant viral diseases of the globe. Currently, there is no specific vaccine or antiviral therapy for prevention or treatment. Monocytes/macrophages are the principal target cells for dengue virus and are responsible for disseminating the virus after its transmission. Dengue virus enters target cells via receptor-mediated endocytosis after the viral envelope protein E attaches to the cell surface receptor. This study aimed to investigate the effect of silencing the CD-14 associated molecule and clathrin-mediated endocytosis using siRNA on dengue virus entry into monocytes.
  9. Rasli R, Cheong YL, Che Ibrahim MK, Farahininajua Fikri SF, Norzali RN, Nazarudin NA, et al.
    PLoS Negl Trop Dis, 2021 Mar;15(3):e0009205.
    PMID: 33755661 DOI: 10.1371/journal.pntd.0009205
    BACKGROUND: In Malaysia, dengue remains a top priority disease and usage of insecticides is the main method for dengue vector control. Limited baseline insecticide resistance data in dengue hotspots has prompted us to conduct this study. The present study reports the use of a map on the insecticide susceptibility status of Aedes aegypti and Aedes albopictus to provide a quick visualization and overview of the distribution of insecticide resistance.

    METHOD AND RESULTS: The insecticide resistance status of Aedes populations collected from 24 dengue hotspot areas from the period of December 2018 until June 2019 was proactively monitored using the World Health Organization standard protocol for adult and larval susceptibility testing was conducted, together with elucidation of the mechanisms involved in observed resistance. For resistance monitoring, susceptibility to three adulticides (permethrin, deltamethrin, and malathion) was tested, as well as susceptibility to the larvicide, temephos. Data showed significant resistance to both deltamethrin and permethrin (pyrethroid insecticides), and to malathion (organophosphate insecticide) in all sampled Aedes aegypti populations, while variable resistance patterns were found in the sampled Aedes albopictus populations. Temephos resistance was observed when larvae were tested using the diagnostic dosage of 0.012mg/L but not at the operational dosage of 1mg/L for both species.

    CONCLUSION: The present study highlights evidence of a potential threat to the effectiveness of insecticides currently used in dengue vector control, and the urgent requirement for insecticide resistance management to be integrated into the National Dengue Control Program.

  10. Manin BO, Ferguson HM, Vythilingam I, Fornace K, William T, Torr SJ, et al.
    PLoS Negl Trop Dis, 2016 Oct;10(10):e0005064.
    PMID: 27741235 DOI: 10.1371/journal.pntd.0005064
    In recent years, the primate malaria Plasmodium knowlesi has emerged in human populations throughout South East Asia, with the largest hotspot being in Sabah, Malaysian Borneo. Control efforts are hindered by limited knowledge of where and when people get exposed to mosquito vectors. It is assumed that exposure occurs primarily when people are working in forest areas, but the role of other potential exposure routes (including domestic or peri-domestic transmission) has not been thoroughly investigated.
  11. Naing C, Whittaker MA, Nyunt Wai V, Mak JW
    PLoS Negl Trop Dis, 2014 Aug;8(8):e3071.
    PMID: 25121491 DOI: 10.1371/journal.pntd.0003071
    BACKGROUND: Plasmodium vivax is one of the major species of malaria infecting humans. Although emphasis on P. falciparum is appropriate, the burden of vivax malaria should be given due attention. This study aimed to synthesize the evidence on severe malaria in P. vivax infection compared with that in P. falciparum infection.
    METHODS/PRINCIPAL FINDINGS: We searched relevant studies in electronic databases. The main outcomes required for inclusion in the review were mortality, severe malaria (SM) and severe anaemia (SA). The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale. Overall, 26 studies were included. The main meta-analysis was restricted to the high quality studies. Eight studies (n = 27490) compared the incidence of SM between P. vivax infection and P. falciparum mono-infection; a comparable incidence was found in infants (OR: 0.45, 95% CI:0.04-5.68, I2:98%), under 5 year age group (OR: 2.06, 95% CI: 0.83-5.1, I2:83%), the 5-15 year-age group (OR: 0.6, 95% CI: 0.31-1.16, I2:81%) and adults (OR: 0.83, 95% CI: 0.67-1.03, I2:25%). Six studies reported the incidences of SA in P. vivax infection and P. falciparum mono-infection; a comparable incidence of SA was found among infants (OR: 3.47, 95%:0.64-18.94, I2: 92%), the 5-15 year-age group (OR:0.71, 95% CI: 0.06-8.57, I2:82%). This was significantly lower in adults (OR:0.75, 95% CI: 0.62-0.92, I2:0%). Five studies (n = 71079) compared the mortality rate between vivax malaria and falciparum malaria. A lower rate of mortality was found in infants with vivax malaria (OR:0.61, 95% CI:0.5-0.76, I2:0%), while this was comparable in the 5-15 year- age group (OR: 0.43, 95% CI:0.06-2.91, I2:84%) and the children of unspecified-age group (OR: 0.77, 95% CI:0.59-1.01, I2:0%).
    CONCLUSION: Overall, the present analysis identified that the incidence of SM in patients infected with P. vivax was considerable, indicating that P. vivax is a major cause of SM. Awareness of the clinical manifestations of vivax malaria should prompt early detection. Subsequent treatment and monitoring of complications can be life-saving.
  12. Jamil H, Din MFU, Tahir MJ, Saqlain M, Hassan Z, Khan MA, et al.
    PLoS Negl Trop Dis, 2022 Dec;16(12):e0010988.
    PMID: 36480553 DOI: 10.1371/journal.pntd.0010988
    BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) continues to pose a serious threat to the fragile healthcare system of Pakistan with a continuous increase of morbidity and mortality. The present study aimed to assess the knowledge, attitudes, and practices regarding CCHF among general people who resided in Pakistan.

    METHODS: An online cross-sectional survey design was applied, and a convenience sampling technique was used to recruit 1039 adult people from Pakistan. Data were collected from September 08 to October 12, 2021. The questionnaire consisted of a total of 32 questions in four parts assessing socio-demographics, as well as knowledge, attitudes, and practices regarding CCHF. All statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS), and logistic regression analyses were performed to determine the factors associated with good knowledge, positive attitudes, and good practices.

    RESULTS: Alarmingly, 51.5% of participants heard about CCHF infection before administering the survey. Among these, 20.2%, 33.3%, and 48.2% of the study participants had demonstrated good knowledge, positive attitudes, and good practices, respectively. Binary logistic regression analysis revealed that education and income status had a significant impact on knowledge and attitudes (p<0.05). Similarly, the mean attitude scores differed significantly by age, education, and income status (p<0.05).

    CONCLUSIONS: The findings reflected inadequate levels of knowledge, attitudes, and practices regarding CCHF among general people in Pakistan which may regard as lower than expected. As CCHF is a highly contagious disease, it's urgent to initiate a comprehensive approach to handle the situation before it spreads further in Pakistan.

  13. Boey K, Shiokawa K, Rajeev S
    PLoS Negl Trop Dis, 2019 08;13(8):e0007499.
    PMID: 31398190 DOI: 10.1371/journal.pntd.0007499
    BACKGROUND: The role of rodents in Leptospira epidemiology and transmission is well known worldwide. Rats are known to carry different pathogenic serovars of Leptospira spp. capable of causing disease in humans and animals. Wild rats (Rattus spp.), especially the Norway/brown rat (Rattus norvegicus) and the black rat (R. rattus), are the most important sources of Leptospira infection, as they are abundant in urban and peridomestic environments. In this study, we compiled and summarized available data in the literature on global prevalence of Leptospira exposure and infection in rats, as well as compared the global distribution of Leptospira spp. in rats with respect to prevalence, geographic location, method of detection, diversity of serogroups/serovars, and species of rat.

    METHODS: We conducted a thorough literature search using PubMed without restrictions on publication date as well as Google Scholar to manually search for other relevant articles. Abstracts were included if they described data pertaining to Leptospira spp. in rats (Rattus spp.) from any geographic region around the world, including reviews. The data extracted from the articles selected included the author(s), year of publication, geographic location, method(s) of detection used, species of rat(s), sample size, prevalence of Leptospira spp. (overall and within each rat species), and information on species, serogroups, and/or serovars of Leptospira spp. detected.

    FINDINGS: A thorough search on PubMed retrieved 303 titles. After screening the articles for duplicates and inclusion/exclusion criteria, as well as manual inclusion of relevant articles, 145 articles were included in this review. Leptospira prevalence in rats varied considerably based on geographic location, with some reporting zero prevalence in countries such as Madagascar, Tanzania, and the Faroe Islands, and others reporting as high as >80% prevalence in studies done in Brazil, India, and the Philippines. The top five countries that were reported based on number of articles include India (n = 13), Malaysia (n = 9), Brazil (n = 8), Thailand (n = 7), and France (n = 6). Methods of detecting or isolating Leptospira spp. also varied among studies. Studies among different Rattus species reported a higher Leptospira prevalence in R. norvegicus. The serovar Icterohaemorrhagiae was the most prevalent serovar reported in Rattus spp. worldwide. Additionally, this literature review provided evidence for Leptospira infection in laboratory rodent colonies within controlled environments, implicating the zoonotic potential to laboratory animal caretakers.

    CONCLUSIONS: Reports on global distribution of Leptospira infection in rats varies widely, with considerably high prevalence reported in many countries. This literature review emphasizes the need for enhanced surveillance programs using standardized methods for assessing Leptospira exposure or infection in rats. This review also demonstrated several weaknesses to the current methods of reporting the prevalence of Leptospira spp. in rats worldwide. As such, this necessitates a call for standardized protocols for the testing and reporting of such studies, especially pertaining to the diagnostic methods used. A deeper understanding of the ecology and epidemiology of Leptospira spp. in rats in urban environments is warranted. It is also pertinent for rat control programs to be proposed in conjunction with increased efforts for public awareness and education regarding leptospirosis transmission and prevention.

  14. Philip N, Bahtiar Affendy N, Ramli SNA, Arif M, Raja P, Nagandran E, et al.
    PLoS Negl Trop Dis, 2020 Mar;14(3):e0008197.
    PMID: 32203511 DOI: 10.1371/journal.pntd.0008197
    BACKGROUND: Leptospirosis, commonly known as rat-urine disease, is a global but endemic zoonotic disease in the tropics. Despite the historical report of leptospirosis in Malaysia, the information on human-infecting species is limited. Determining the circulating species is important to understand its epidemiology, thereby to strategize appropriate control measures through public health interventions, diagnostics, therapeutics and vaccine development.

    METHODOLOGY/PRINCIPLE FINDINGS: We investigated the human-infecting Leptospira species in blood and serum samples collected from clinically suspected leptospirosis patients admitted to three tertiary care hospitals in Malaysia. From a total of 165 patients, 92 (56%) were confirmed cases of leptospirosis through Microscopic Agglutination Test (MAT) (n = 43; 47%), Polymerase Chain Reaction (PCR) (n = 63; 68%) or both MAT and PCR (n = 14; 15%). The infecting Leptospira spp., determined by partial 16S rDNA (rrs) gene sequencing revealed two pathogenic species namely Leptospira interrogans (n = 44, 70%) and Leptospira kirschneri (n = 17, 27%) and one intermediate species Leptospira wolffii (n = 2, 3%). Multilocus sequence typing (MLST) identified an isolate of L. interrogans as a novel sequence type (ST 265), suggesting that this human-infecting strain has a unique genetic profile different from similar species isolated from rodents so far.

    CONCLUSIONS/SIGNIFICANCE: Leptospira interrogans and Leptospira kirschneri were identified as the dominant Leptospira species causing human leptospirosis in Central Malaysia. The existence of novel clinically important ST 265 (infecting human), that is different from rodent L. interrogans strains cautions reservoir(s) of these Leptospira lineages are yet to be identified.

  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. 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.

  17. Williams HF, Mellows BA, Mitchell R, Sfyri P, Layfield HJ, Salamah M, et al.
    PLoS Negl Trop Dis, 2019 01;13(1):e0007041.
    PMID: 30695027 DOI: 10.1371/journal.pntd.0007041
    Snakebite is a major neglected tropical health issue that affects over 5 million people worldwide resulting in around 1.8 million envenomations and 100,000 deaths each year. Snakebite envenomation also causes innumerable morbidities, specifically loss of limbs as a result of excessive tissue/muscle damage. Snake venom metalloproteases (SVMPs) are a predominant component of viper venoms, and are involved in the degradation of basement membrane proteins (particularly collagen) surrounding the tissues around the bite site. Although their collagenolytic properties have been established, the molecular mechanisms through which SVMPs induce permanent muscle damage are poorly understood. Here, we demonstrate the purification and characterisation of an SVMP from a viper (Crotalus atrox) venom. Mass spectrometry analysis confirmed that this protein is most likely to be a group III metalloprotease (showing high similarity to VAP2A) and has been referred to as CAMP (Crotalus atrox metalloprotease). CAMP displays both collagenolytic and fibrinogenolytic activities and inhibits CRP-XL-induced platelet aggregation. To determine its effects on muscle damage, CAMP was administered into the tibialis anterior muscle of mice and its actions were compared with cardiotoxin I (a three-finger toxin) from an elapid snake (Naja pallida) venom. Extensive immunohistochemistry analyses revealed that CAMP significantly damages skeletal muscles by attacking the collagen scaffold and other important basement membrane proteins, and prevents their regeneration through disrupting the functions of satellite cells. In contrast, cardiotoxin I destroys skeletal muscle by damaging the plasma membrane, but does not impact regeneration due to its inability to affect the extracellular matrix. Overall, this study provides novel insights into the mechanisms through which SVMPs induce permanent muscle damage.
  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. Kingsley PV, Leader M, Nagodawithana NS, Tipre M, Sathiakumar N
    PLoS Negl Trop Dis, 2016 12;10(12):e0005182.
    PMID: 28005910 DOI: 10.1371/journal.pntd.0005182
    BACKGROUND: Melioidosis is a tropical infectious disease associated with significant mortality due to early onset of sepsis.

    OBJECTIVE: We sought to review case reports of melioidosis from Malaysia.

    METHODS: We conducted a computerized search of literature resources including PubMed, OVID, Scopus, MEDLINE and the COCHRANE database to identify published case reports from 1975 to 2015. We abstracted information on clinical characteristics, exposure history, comorbid conditions, management and outcome.

    RESULTS: Overall, 67 cases were reported with 29 (43%) deaths; the median age was 44 years, and a male preponderance (84%) was noted. Forty-one cases (61%) were bacteremic, and fatal septic shock occurred in 13 (19%) within 24-48 hours of admission; nine of the 13 cases were not specifically treated for melioidosis as confirmatory evidence was available only after death. Diabetes mellitus (n = 36, 54%) was the most common risk factor. Twenty-six cases (39%) had a history of exposure to contaminated soil/water or employment in high-risk occupations. Pneumonia (n = 24, 36%) was the most common primary clinical presentation followed by soft tissue abscess (n = 22, 33%). Other types of clinical presentations were less common-genitourinary (n = 5), neurological (n = 5), osteomyelitis/septic arthritis (n = 4) and skin (n = 2); five cases had no evidence of a focus of infection. With regard to internal foci of infection, abscesses of the subcutaneous tissue (n = 14, 21%) was the most common followed by liver (18%); abscesses of the spleen and lung were the third most common (12% each). Seven of 56 males were reported to have prostatic abscesses. Mycotic pseudoaneurysm occurred in five cases. Only one case of parotid abscess was reported in an adult. Of the 67 cases, 13 were children (≤ 18 years of age) with seven deaths; five of the 13 were neonates presenting primarily with bronchopneumonia, four of whom died. Older children had a similar presentation as adults; no case of parotid abscess was reported among children.

    CONCLUSIONS: The clinical patterns of cases reported from Malaysia are consistent for the most part from previous case reports from South and Southeast Asia with regard to common primary presentations of pneumonia and soft tissue abscesses, and diabetes as a major risk factor. Bacteremic melioidosis carried a poor prognosis and septic shock was strong predictor of mortality. Differences included the occurrence of: primary neurological infection was higher in Malaysia compared to reports outside Malaysia; internal foci of infection such as abscesses of the liver, spleen, prostate, and mycotic pseudoaneurysms were higher than previously reported in the region. No parotid abscess was reported among children. Early recognition of the disease is the cornerstone of management. In clinical situations of community-acquired sepsis and/or pneumonia, where laboratory bacteriological confirmation is not possible, empirical treatment with antimicrobials for B. pseudomallei is recommended.

  20. Perumal Samy R, Stiles BG, Sethi G, Lim LHK
    PLoS Negl Trop Dis, 2017 May;11(5):e0004738.
    PMID: 28493905 DOI: 10.1371/journal.pntd.0004738
    This review briefly summarizes the geographical distribution and clinical impact of melioidosis, especially in the tropics. Burkholderia pseudomallei (a gram-negative bacterium) is the major causative agent for melioidosis, which is prevalent in Singapore, Malaysia, Thailand, Vietnam, and Northern Australia. Melioidosis patients are increasingly being recognized in other parts of the world. The bacteria are intrinsically resistant to many antimicrobial agents, but prolonged treatment, especially with combinations of antibiotics, may be effective. Despite therapy, the overall case fatality rate of septicemia in melioidosis remains significantly high. Intracellular survival of the bacteria within macrophages may progress to chronic infections, and about 10% of patients suffer relapses. In the coming decades, melioidosis will increasingly afflict travelers throughout many global regions. Clinicians managing travelers returning from the subtropics or tropics with severe pneumonia or septicemia should consider acute melioidosis as a differential diagnosis. Patients with open skin wounds, diabetes, or chronic renal disease are at higher risk for melioidosis and should avoid direct contact with soil and standing water in endemic regions. Furthermore, there are fears that B. pseudomallei may be used as a biological weapon. Technological advancements in molecular diagnostics and antibiotic therapy are improving the disease outcomes in endemic areas throughout Asia. Research and development efforts on vaccine candidates against melioidosis are ongoing.
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