Displaying publications 1 - 20 of 44 in total

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  1. Lee JH, Hammoud DA, Cong Y, Huzella LM, Castro MA, Solomon J, et al.
    J Infect Dis, 2020 05 11;221(Suppl 4):S419-S430.
    PMID: 31687756 DOI: 10.1093/infdis/jiz502
    Nipah virus (NiV) is an emerging virus associated with outbreaks of acute respiratory disease and encephalitis. To develop a neurological model for NiV infection, we exposed 6 adult African green monkeys to a large-particle (approximately 12 μm) aerosol containing NiV (Malaysian isolate). Brain magnetic resonance images were obtained at baseline, every 3 days after exposure for 2 weeks, and then weekly until week 8 after exposure. Four of six animals showed abnormalities reminiscent of human disease in brain magnetic resonance images. Abnormalities ranged from cytotoxic edema to vasogenic edema. The majority of lesions were small infarcts, and a few showed inflammatory or encephalitic changes. Resolution or decreased size in some lesions resembled findings reported in patients with NiV infection. Histological lesions in the brain included multifocal areas of encephalomalacia, corresponding to known ischemic foci. In other regions of the brain there was evidence of vasculitis, with perivascular infiltrates of inflammatory cells and rare intravascular fibrin thrombi. This animal model will help us better understand the acute neurological features of NiV infection and develop therapeutic approaches for managing disease caused by NiV infection.
  2. Jusof FF, Lim CK, Aziz FN, Soe HJ, Raju CS, Sekaran SD, et al.
    J Infect Dis, 2022 Nov 28;226(11):1964-1973.
    PMID: 35767283 DOI: 10.1093/infdis/jiac273
    BACKGROUND: The resolution or aggravation of dengue infection depends on the patient's immune response during the critical phase. Cytokines released by immune cells increase with the worsening severity of dengue infections. Cytokines activate the kynurenine pathway (KP) and the extent of KP activation then influences disease severity.

    METHODS: KP metabolites and cytokines in plasma samples of patients with dengue infection (dengue without warning signs [DWS-], dengue with warning signs [DWS+], or severe dengue) were analyzed. Cytokines (interferon gamma [IFN-ɣ], tumor necrosis factor, interleukin 6, CXCL10/interferon-inducile protein 10 [IP-10], interleukin 18 [IL-18], CCL2/monocyte chemoattractant protein-1 [MCP-1], and CCL4/macrophage inflammatory protein-1beta [MIP-1β] were assessed by a Human Luminex Screening Assay, while KP metabolites (tryptophan, kynurenine, anthranilic acid [AA], picolinic acid, and quinolinic acid) were assessed by ultra-high-performance liquid chromatography and Gas Chromatography Mass Spectrophotometry [GCMS] assays.

    RESULTS: Patients with DWS+ had increased activation of the KP where kynurenine-tryptophan ratio, anthranilic acid, and picolinic acid were elevated. These patients also had higher levels of the cytokines IFN-ɣ, CXCL10, CCL4, and IL-18 than those with DWS-. Further receiver operating characteristic analysis identified 3 prognostic biomarker candidates, CXCL10, CCL2, and AA, which predicted patients with higher risks of developing DWS+ with an accuracy of 97%.

    CONCLUSIONS: The data suggest a unique biochemical signature in patients with DWS+. CXCL10 and CCL2 together with AA are potential prognostic biomarkers that discern patients with higher risk of developing DWS+ at earlier stages of infection.

  3. Yong MY, Lee SC, Ngui R, Lim YA, Phipps ME, Chang LY
    J Infect Dis, 2020 05 11;221(Suppl 4):S370-S374.
    PMID: 32392323 DOI: 10.1093/infdis/jiaa085
    Nipah virus (NiV) outbreak occurred in Malaysia in 1998. The natural host reservoir for NiV is Pteropus bats, which are commonly found throughout Malaysia. Humans become infected when NiV spills over from the reservoir species. In this study, NiV serosurveillance in Peninsular Malaysia, particularly among the indigenous population, was performed. The collected samples were tested for presence of NiV antibodies using a comparative indirect enzyme-linked immunosorbent assay based on the recombinant NiV nucleocapsid (rNiV-N) protein. We found that 10.73% of the participants recruited in this study had antibodies against rNiV-N, suggesting possible exposure to NiV.
  4. Yaiw KC, Crameri G, Wang L, Chong HT, Chua KB, Tan CT, et al.
    J Infect Dis, 2007 Sep 15;196(6):884-6.
    PMID: 17703419
    Tioman virus, a relatively new paramyxovirus, was isolated from fruit bats (Pteropus species) on Tioman Island, Malaysia, in 2001. The objective of this study was to determine the prevalence of antibodies to T. virus in island inhabitants, by use of comparative ELISA and serum neutralization assays. Of the 169 human sera analyzed, 5 (approximately 3.0%) were positive for T. virus, by comparative ELISA. Of these 5 sera, 3 (1.8% of the total) had neutralizing antibodies against T. virus, suggesting previous infection of this study population by this virus or a similar virus.
  5. Nealon J, Taurel AF, Yoksan S, Moureau A, Bonaparte M, Quang LC, et al.
    J Infect Dis, 2019 Jan 09;219(3):375-381.
    PMID: 30165664 DOI: 10.1093/infdis/jiy513
    Background: Japanese encephalitis virus (JEV) is a zoonotic, mosquito-borne flavivirus, distributed across Asia. Infections are mostly mild or asymptomatic, but symptoms include neurological disorders, sequelae, and fatalities. Data to inform control strategies are limited due to incomplete case reporting.

    Methods: We used JEV serological data from a multicountry Asian dengue vaccine study in children aged 2-14 years to describe JEV endemicity, measuring antibodies by plaque reduction neutralization test (PRNT50).

    Results: A total 1479 unvaccinated subjects were included. A minimal estimate of pediatric JEV seroprevalence in dengue-naive individuals was 8.1% in Indonesia, 5.8% in Malaysia, 10.8% in the Philippines, and 30.7% in Vietnam, translating to annual infection risks varying from 0.8% (in Malaysia) to 5.2% (in Vietnam). JEV seroprevalence and annual infection estimates were much higher in children with history of dengue infection, indicating cross-neutralization within the JEV PRNT50 assay.

    Conclusions: These data confirm JEV transmission across predominantly urban areas and support a greater emphasis on JEV case finding, diagnosis, and prevention.

  6. Chew MH, Arguin PM, Shay DK, Goh KT, Rollin PE, Shieh WJ, et al.
    J Infect Dis, 2000 May;181(5):1760-3.
    PMID: 10823780
    During 10-19 March 1999, 11 workers in 1 of 2 Singaporean abattoirs developed Nipah-virus associated encephalitis or pneumonia, resulting in 1 fatality. A case-control study was conducted to determine occupational risk factors for infection. Case patients were abattoir A workers who had anti-Nipah IgM antibodies; control subjects were randomly selected abattoir A workers who tested negative for anti-Nipah IgM. All 13 case patients versus 26 (63%) of 41 control subjects reported contact with live pigs (P=.01). Swine importation from Malaysian states concurrently experiencing a Nipah virus outbreak was banned on 3 March 1999; on 19 March 1999, importation of Malaysian pigs was banned, and abattoirs were closed. No unusual illnesses among pigs processed during February-March were reported. Contact with live pigs appeared to be the most important risk factor for human Nipah virus infection. Direct contact with live, potentially infected pigs should be minimized to prevent transmission of this potentially fatal zoonosis to humans.
  7. Rapmund G
    J Infect Dis, 1984 Mar;149(3):330-8.
    PMID: 6425420
    The rickettsial disease of man found only in Asia is mite-borne (scrub) typhus, caused by Rickettsia tsutsugamushi. Unique to southern Japan is a little-known human mononucleosis-like disease caused by Rickettsia sennetsu. In 1981 and 1982, there was a remarkable resurgence in the number of reported cases of mite-borne typhus in Japan after some years of virtual absence. Recent studies of R sennetsu have resulted in its reclassification to the genus Ehrlichia, members of which until now have been exclusively pathogens of animals. The historical background of ecologic investigations, in Malaysia and elsewhere, of these two developments suggest directions for future research.
  8. Govindasamy G, Barber BE, Ghani SA, William T, Grigg MJ, Borooah S, et al.
    J Infect Dis, 2016 May 1;213(9):1476-82.
    PMID: 26671886 DOI: 10.1093/infdis/jiv746
    Plasmodium knowlesicauses severe malaria, but its pathogenesis is poorly understood. Retinal changes provide insights into falciparum malaria pathogenesis but have not been studied in knowlesi malaria.
  9. Prasad AN, Woolsey C, Geisbert JB, Agans KN, Borisevich V, Deer DJ, et al.
    J Infect Dis, 2020 05 11;221(Suppl 4):S436-S447.
    PMID: 32022850 DOI: 10.1093/infdis/jiz613
    BACKGROUND: The henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), are capable of causing severe and often lethal respiratory and/or neurologic disease in animals and humans. Given the sporadic nature of henipavirus outbreaks, licensure of vaccines and therapeutics for human use will likely require demonstration of efficacy in animal models that faithfully reproduce the human condition. Currently, the African green monkey (AGM) best mimics human henipavirus-induced disease.

    METHODS: The pathogenic potential of HeV and both strains of NiV (Malaysia, Bangladesh) was assessed in cynomolgus monkeys and compared with henipavirus-infected historical control AGMs. Multiplex gene and protein expression assays were used to compare host responses.

    RESULTS: In contrast to AGMs, in which henipaviruses cause severe and usually lethal disease, HeV and NiVs caused only mild or asymptomatic infections in macaques. All henipaviruses replicated in macaques with similar kinetics as in AGMs. Infection in macaques was associated with activation and predicted recruitment of cytotoxic CD8+ T cells, Th1 cells, IgM+ B cells, and plasma cells. Conversely, fatal outcome in AGMs was associated with aberrant innate immune signaling, complement dysregulation, Th2 skewing, and increased secretion of MCP-1.

    CONCLUSION: The restriction factors identified in macaques can be harnessed for development of effective countermeasures against henipavirus disease.

  10. Hegde ST, Lee KH, Styczynski A, Jones FK, Gomes I, Das P, et al.
    J Infect Dis, 2024 Mar 14;229(3):733-742.
    PMID: 37925626 DOI: 10.1093/infdis/jiad467
    Nipah virus Bangladesh (NiVB) is a bat-borne zoonosis transmitted between people through the respiratory route. The risk posed by related henipaviruses, including Hendra virus (HeV) and Nipah virus Malaysia (NiVM), is less clear. We conducted a broad search of the literature encompassing both human infections and animal models to synthesize evidence about potential for person-to-person spread. More than 600 human infections have been reported in the literature, but information on viral shedding was only available for 40 case-patients. There is substantial evidence demonstrating person-to-person transmission of NiVB, and some evidence for NiVM. Less direct evidence is available about the risk for person-to-person transmission of HeV, but animals infected with HeV shed more virus in the respiratory tract than those infected with NiVM, suggesting potential for transmission. As the group of known henipaviruses continues to grow, shared protocols for conducting and reporting from human investigations and animal experiments are urgently needed.
  11. Grau GE, Mackenzie CD, Carr RA, Redard M, Pizzolato G, Allasia C, et al.
    J Infect Dis, 2003 Feb 1;187(3):461-6.
    PMID: 12552430
    The pathogenesis of fatal cerebral malaria (CM) is not well understood, in part because data from patients in whom a clinical diagnosis was established prior to death are rare. In a murine CM model, platelets accumulate in brain microvasculature, and antiplatelet therapy can improve outcome. We determined whether platelets are also found in cerebral vessels in human CM, and we performed immunohistopathology for platelet-specific glycoprotein, GPIIb-IIIa, on tissue from multiple brain sites in Malawian children whose fatal illness was severe malarial anemia, CM, or nonmalarial encephalopathy. Platelets were observed in 3 locations within microvessels: between malaria pigment and leukocytes, associated with malaria pigment, or alone. The mean surface area of platelet staining and the proportion of vessels showing platelet accumulation were significantly higher in patients with CM than in those without it. Platelet accumulation occurs in the microvasculature of patients with CM and may play a role in the pathogenesis of the disease.
  12. Barber BE, Bird E, Wilkes CS, William T, Grigg MJ, Paramaswaran U, et al.
    J Infect Dis, 2015 Apr 1;211(7):1104-10.
    PMID: 25301955 DOI: 10.1093/infdis/jiu562
    BACKGROUND: Plasmodium knowlesi is the commonest cause of malaria in Malaysia, but little is known regarding infection during pregnancy.
    METHODS: To investigate comparative risk and consequences of knowlesi malaria during pregnancy, we reviewed (1) Sabah Health Department malaria-notification records created during 2012-2013, (2) prospectively collected data from all females with polymerase chain reaction (PCR)-confirmed malaria who were admitted to a Sabah tertiary care referral hospital during 2011-2014, and (3) malaria microscopy and clinical data recorded at a Sabah tertiary care women and children's hospital during 2010-2014.
    RESULTS: During 2012-2013, 774 females with microscopy-diagnosed malaria were notified, including 252 (33%), 172 (20%), 333 (43%), and 17 (2%) with Plasmodium falciparum infection, Plasmodium vivax infection, Plasmodium malariae/Plasmodium knowlesi infection, and mixed infection, respectively. Among females aged 15-45 years, pregnancy was reported in 18 of 124 (14.5%), 9 of 93 (9.7%), and 4 of 151 (2.6%) P. falciparum, P. vivax, and P. malariae/P. knowlesi notifications respectively (P = .002). Three females with knowlesi malaria were confirmed as pregnant: 2 had moderate anemia, and 1 delivered a preterm low-birth-weight infant. There were 17, 7, and 0 pregnant women with falciparum, vivax, and knowlesi malaria, respectively, identified from the 2 referral hospitals.
    CONCLUSIONS: Although P. knowlesi is the commonest malaria species among females in Sabah, P. knowlesi infection is relatively rare during pregnancy. It may however be associated with adverse maternal and pregnancy outcomes.
    KEYWORDS: Plasmodium knowlesi; malaria; maternal anemia; pregnancy; preterm delivery
  13. 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.
  14. Naing C, Whittaker MA, Tanner M
    J Infect Dis, 2020 10 29;222(Suppl 8):S717-S725.
    PMID: 33119095 DOI: 10.1093/infdis/jiaa335
    BACKGROUND: Myanmar is a premalaria elimination country with artemisinin-resistant malaria. A strategy for transmission control is focused on vulnerable groups such as mobile and migrant populations (MMPs), and includes improving access to insecticide-treated bed nets in the Myanmar artemisinin resistance containment (MARC) zones using multisectoral approaches (MSA).

    METHODS: This narrative systematic review addressed MSAs targeted to MMPs in Myanmar for malaria prevention. We searched relevant studies in electronic databases and present the narrative findings in 4 domains: stakeholder groups, net coverage and utilization, social determinates, and facilitators/barriers.

    RESULTS: Nine studies were included. The review identified stakeholders involved in intersectoral collaboration. Net ownership was higher than utilization rates in the MARC zones and rates remained below the WHO recommended target of 100%. There was inadequate description of roles and responsibilities for implementation and on channels of communication within the partnerships and with the Government.

    CONCLUSIONS: Findings show that interventions to distribute treated bed nets were supported by the multiple stakeholders. Due to the design of the primary studies, analysis of the added value of intersectoral collaboration was limited. More attention must be paid to designing studies to document and evaluate the contributions and outcomes of intersectoral collaboration.

  15. Mulders MN, Lipskaya GY, van der Avoort HG, Koopmans MP, Kew OM, van Loon AM
    J Infect Dis, 1995 Jun;171(6):1399-405.
    PMID: 7769273
    The genomic relationships of wild poliovirus type 1 strains recently isolated in Europe, the Middle East, and the Indian subcontinent was analyzed by automated amplicon sequencing of the VP1/2A junction region of the genome. Four major genotypes of poliovirus type 1 were found to circulate. Two genotypes were found predominantly in Eastern Europe, one of these in the Caucasian Region and the other in countries bordering the Black Sea. A third genotype circulated mainly in Egypt. The fourth and largest genotype circulated in the largest geographic area. Strains belonging to this genotype could be found in countries as far apart as Malaysia and Ukraine. Considerable genetic variation was observed among strains isolated in Egypt, Pakistan, and India, where poliovirus is endemic. Strains belonging to all four genotypes circulated in Pakistan. Data confirm the extent of poliovirus circulation in certain regions, stressing the need for intensification of vaccination in these regions.
  16. Jessie K, Fong MY, Devi S, Lam SK, Wong KT
    J Infect Dis, 2004 Apr 15;189(8):1411-8.
    PMID: 15073678
    Dengue viral antigens have been demonstrated in several types of naturally infected human tissues, but little is known of whether these same tissues have detectable viral RNA. We studied tissue specimens from patients with serologically or virologically confirmed dengue infections by immunohistochemistry (IHC) and in situ hybridization (ISH), to localize viral antigen and RNA, respectively. IHC was performed on specimens obtained from 5 autopsies and 24 biopsies and on 20 blood-clot samples. For ISH, antisense riboprobes to the dengue E gene were applied to tissue specimens in which IHC was positive. Viral antigens were demonstrated in Kupffer and sinusoidal endothelial cells of the liver; macrophages, multinucleated cells, and reactive lymphoid cells in the spleen; macrophages and vascular endothelium in the lung; kidney tubules; and monocytes and lymphocytes in blood-clot samples. Positive-strand viral RNA was detected in the same IHC-positive cells found in the spleen and blood-clot samples. The strong, positive ISH signal in these cells indicated a high copy number of viral RNA, suggesting replication.
  17. Crane M, Avihingsanon A, Rajasuriar R, Velayudham P, Iser D, Solomon A, et al.
    J Infect Dis, 2014 Sep 1;210(5):745-51.
    PMID: 24585898 DOI: 10.1093/infdis/jiu119
    We investigated the relationship between microbial translocation, immune activation, and liver disease in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) coinfection. Lipopolysaccharide (LPS), soluble CD14, CXCL10, and CCL-2 levels were elevated in patients with HIV/HBV coinfection. Levels of LPS, soluble CD14, and CCL-2 declined following receipt of HBV-active combination antiretroviral therapy (cART), but the CXCL10 level remained elevated. No markers were associated with liver disease severity on liver biopsy (n = 96), but CXCL10, interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor α, and interferon γ (IFN-γ) were all associated with elevated liver enzyme levels during receipt of HBV-active cART. Stimulation of hepatocyte cell lines in vitro with IFN-γ and LPS induced a profound synergistic increase in the production of CXCL10. LPS may contribute to liver disease via stimulating persistent production of CXCL10.
  18. Xu X, Smith CB, Mungall BA, Lindstrom SE, Hall HE, Subbarao K, et al.
    J Infect Dis, 2002 Nov 15;186(10):1490-3.
    PMID: 12404167
    Reassortant influenza A viruses bearing the H1 subtype of hemagglutinin (HA) and the N2 subtype of neuraminidase (NA) were isolated from humans in the United States, Canada, Singapore, Malaysia, India, Oman, Egypt, and several countries in Europe during the 2001-2002 influenza season. The HAs of these H1N2 viruses were similar to that of the A/New Caledonia/20/99(H1N1) vaccine strain both antigenically and genetically, and the NAs were antigenically and genetically related to those of recent human H3N2 reference strains, such as A/Moscow/10/99(H3N2). All 6 internal genes of the H1N2 reassortants examined originated from an H3N2 virus. This article documents the first widespread circulation of H1N2 reassortants on 4 continents. The current influenza vaccine is expected to provide good protection against H1N2 viruses, because it contains the A/New Caledonia/20/99(H1N1) and A/Moscow/10/99(H3N2)-like viruses, which have H1 and N2 antigens that are similar to those of recent H1N2 viruses.
  19. Oyong DA, Wilson DW, Barber BE, William T, Jiang J, Galinski MR, et al.
    J Infect Dis, 2019 11 06;220(12):1950-1961.
    PMID: 31419296 DOI: 10.1093/infdis/jiz407
    BACKGROUND: Complement-fixing antibodies are important mediators of protection against Plasmodium falciparum malaria. However, complement-fixing antibodies remain uncharacterized for Plasmodium vivax malaria. P. vivax merozoite surface protein 3α (PvMSP3α) is a target of acquired immunity and a potential vaccine candidate.

    METHODS: Plasma from children and adults with P. vivax malaria in Sabah, Malaysia, were collected during acute infection, 7 and 28 days after drug treatment. Complement-fixing antibodies and immunoglobulin M and G (IgM and IgG), targeting 3 distinctive regions of PvMSP3α, were measured by means of enzyme-linked immunosorbent assay.

    RESULTS: The seroprevalence of complement-fixing antibodies was highest against the PvMSP3α central region (77.6%). IgG1, IgG3, and IgM were significantly correlated with C1q fixation, and both purified IgG and IgM were capable of mediating C1q fixation to PvMSP3α. Complement-fixing antibody levels were similar between age groups, but IgM was predominant in children and IgG3 more prevalent in adults. Levels of functional antibodies increased after acute infection through 7 days after treatment but rapidly waned by day 28.

    CONCLUSION: Our study demonstrates that PvMSP3α antibodies acquired during P. vivax infection can mediate complement fixation and shows the important influence of age in shaping these specific antibody responses. Further studies are warranted to understand the role of these functional antibodies in protective immunity against P. vivax malaria.

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