Displaying publications 21 - 40 of 44 in total

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  1. Mounts AW, Kaur H, Parashar UD, Ksiazek TG, Cannon D, Arokiasamy JT, et al.
    J Infect Dis, 2001 Mar 1;183(5):810-3.
    PMID: 11181159 DOI: 10.1086/318822
    During 1998-1999, an outbreak of Nipah virus encephalitis occurred in Malaysia. To assess the possibility of nosocomial transmission, 338 health care workers (HCWs) exposed and 288 HCWs unexposed to outbreak-related patients were surveyed, and their serum samples were tested for anti-Nipah virus antibody. Needlestick injuries were reported by 12 (3%) HCWs, mucosal surface exposure to body fluids by 39 (11%), and skin exposure to body fluids by 89 (25%). No encephalitis occurred in either group. Three exposed and no unexposed HCWs tested positive by EIA for IgG antibodies. It is likely that these 3 were false positives; no IgM response occurred, and the serum samples were negative for anti-Nipah virus neutralizing antibodies. The risk of nosocomial transmission of Nipah virus appears to be low; however, given the high case-fatality rate and the presence of virus in respiratory secretions and urine of some patients, standard and droplet infection-control practices should be maintained with these patients.
  2. 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.
  3. Mollerup S, Asplund M, Friis-Nielsen J, Kjartansdóttir KR, Fridholm H, Hansen TA, et al.
    J Infect Dis, 2019 09 13;220(8):1312-1324.
    PMID: 31253993 DOI: 10.1093/infdis/jiz318
    BACKGROUND: Viruses and other infectious agents cause more than 15% of human cancer cases. High-throughput sequencing-based studies of virus-cancer associations have mainly focused on cancer transcriptome data.

    METHODS: In this study, we applied a diverse selection of presequencing enrichment methods targeting all major viral groups, to characterize the viruses present in 197 samples from 18 sample types of cancerous origin. Using high-throughput sequencing, we generated 710 datasets constituting 57 billion sequencing reads.

    RESULTS: Detailed in silico investigation of the viral content, including exclusion of viral artefacts, from de novo assembled contigs and individual sequencing reads yielded a map of the viruses detected. Our data reveal a virome dominated by papillomaviruses, anelloviruses, herpesviruses, and parvoviruses. More than half of the included samples contained 1 or more viruses; however, no link between specific viruses and cancer types were found.

    CONCLUSIONS: Our study sheds light on viral presence in cancers and provides highly relevant virome data for future reference.

  4. Barber BE, Grigg MJ, Piera K, Amante FH, William T, Boyle MJ, et al.
    J Infect Dis, 2019 09 26;220(9):1435-1443.
    PMID: 31250022 DOI: 10.1093/infdis/jiz334
    BACKGROUND: Anemia is a major complication of vivax malaria. Antiphosphatidylserine (PS) antibodies generated during falciparum malaria mediate phagocytosis of uninfected red blood cells that expose PS and have been linked to late malarial anemia. However, their role in anemia from non-falciparum Plasmodium species is not known, nor their role in early anemia from falciparum malaria.

    METHODS: We measured PS immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies in Malaysian patients with vivax, falciparum, knowlesi, and malariae malaria, and in healthy controls, and correlated antibody titres with hemoglobin. PS antibodies were also measured in volunteers experimentally infected with Plasmodium vivax and Plasmodium falciparum.

    RESULTS: PS IgM and IgG antibodies were elevated in patients with vivax, falciparum, knowlesi, and malariae malaria (P < .0001 for all comparisons with controls) and were highest in vivax malaria. In vivax and falciparum malaria, PS IgM and IgG on admission correlated inversely with admission and nadir hemoglobin, controlling for parasitemia and fever duration. PS IgM and IgG were also increased in volunteers infected with blood-stage P. vivax and P. falciparum, and were higher in P. vivax infection.

    CONCLUSIONS: PS antibodies are higher in vivax than falciparum malaria, correlate inversely with hemoglobin, and may contribute to the early loss of uninfected red blood cells found in malarial anemia from both species.

  5. 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.
  6. Fornace KM, Nuin NA, Betson M, Grigg MJ, William T, Anstey NM, et al.
    J Infect Dis, 2016 Mar 01;213(5):784-7.
    PMID: 26433222 DOI: 10.1093/infdis/jiv475
    Although asymptomatic carriage of human malaria species has been widely reported, the extent of asymptomatic, submicroscopic Plasmodium knowlesi parasitemia is unknown. In this study, samples were obtained from individuals residing in households or villages of symptomatic malaria cases with the aim of detecting submicroscopic P. knowlesi in this population. Four published molecular assays were used to confirm the presence of P. knowlesi. Latent class analysis revealed that the estimated proportion of asymptomatic individuals was 6.9% (95% confidence interval, 5.6%-8.4%). This study confirms the presence of a substantial number of asymptomatic monoinfections across all age groups; further work is needed to estimate prevalence in the wider community.
  7. Zhang R, Suwanarusk R, Malleret B, Cooke BM, Nosten F, Lau YL, et al.
    J Infect Dis, 2016 Jan 1;213(1):100-4.
    PMID: 26136472 DOI: 10.1093/infdis/jiv358
    Recent clinical trials revealed a surprisingly rapid clearance of red blood cells (RBCs) infected with malaria parasites by the spiroindolone KAE609. Here, we show that ring-stage parasite-infected RBCs exposed to KAE609 become spherical and rigid, probably through osmotic dysregulation consequent to the disruption of the parasite's sodium efflux pump (adenosine triphosphate 4). We also show that this peculiar drug effect is likely to cause accelerated splenic clearance of the rheologically impaired Plasmodium vivax- and Plasmodium falciparum-infected RBCs.
  8. 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
  9. Kang WT, Vellasamy KM, Chua EG, Vadivelu J
    J Infect Dis, 2015 Mar 1;211(5):827-34.
    PMID: 25165162 DOI: 10.1093/infdis/jiu492
    OBJECTIVES: The bsa locus of Burkholderia pseudomallei encodes several proteins that are components of the type III secretion system (TTSS). BipC was postulated as one of the TTSS-3 effector proteins, but its role in the pathogenesis of B. pseudomallei infection is not well understood. Thus, the aim of this study was to determine its role(s) in the virulence of B. pseudomallei pathogenesis.
    METHODS: A bipC TTSS-3-deficient strain of B. pseudomallei and complemented strains were generated to assess the role of BipC as a type III translocation apparatus. Human cell lines and a mouse model of melioidosis were used for in vitro and in vivo assays, respectively.
    RESULTS: A significant 2-fold reduction was demonstrated in the percentage of adherence, invasion, intracellular survival, and phagosomal escape of the bipC mutant. Interestingly, microscopic studies have shown that BipC was capable of delayed B. pseudomallei actin-based motility. The virulence of the mutant strain in a murine model of melioidosis demonstrated that the bipC mutant was less virulent, compared with the wild type.
    CONCLUSION: The results suggested that BipC possesses virulence determinants that play significant roles in host cell invasion and immune evasion.
    KEYWORDS: BipC; Burkholderia pseudomallei; host cell invasion; type III secretion system; type III translocation apparatus; virulence
  10. Parashar UD, Sunn LM, Ong F, Mounts AW, Arif MT, Ksiazek TG, et al.
    J Infect Dis, 2000 May;181(5):1755-9.
    PMID: 10823779
    An outbreak of encephalitis affecting 265 patients (105 fatally) occurred during 1998-1999 in Malaysia and was linked to a new paramyxovirus, Nipah, that infected pigs, humans, dogs, and cats. Most patients were pig farmers. Clinically undetected Nipah infection was noted in 10 (6%) of 166 community-farm controls (persons from farms without reported encephalitis patients) and 20 (11%) of 178 case-farm controls (persons from farms with encephalitis patients). Case patients (persons with Nipah infection) were more likely than community-farm controls to report increased numbers of sick/dying pigs on the farm (59% vs. 24%, P=.001) and were more likely than case-farm controls to perform activities requiring direct contact with pigs (86% vs. 50%, P=.005). Only 8% of case patients reported no contact with pigs. The outbreak stopped after pigs in the affected areas were slaughtered and buried. Direct, close contact with pigs was the primary source of human Nipah infection, but other sources, such as infected dogs and cats, cannot be excluded.
  11. 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.
  12. 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.
  13. Lubis IND, Wijaya H, Lubis M, Lubis CP, Divis PCS, Beshir KB, et al.
    J Infect Dis, 2017 Apr 01;215(7):1148-1155.
    PMID: 28201638 DOI: 10.1093/infdis/jix091
    Background: As Indonesia works toward the goal of malaria elimination, information is lacking on malaria epidemiology from some western provinces. As a basis for studies of antimalarial efficacy, we set out to survey parasite carriage in 3 communities in North Sumatera Province.

    Methods: A combination of active and passive detection of infection was carried out among communities in Batubara, Langkat, and South Nias regencies. Finger-prick blood samples from consenting individuals of all ages provided blood films for microscopic examination and blood spots on filter paper. Plasmodium species were identified using nested polymerase chain reaction (PCR) of ribosomal RNA genes and a novel assay that amplifies a conserved sequence specific for the sicavar gene family of Plasmodium knowlesi.

    Results: Of 3731 participants, 614 (16.5%) were positive for malaria parasites by microscopy. PCR detected parasite DNA in samples from 1169 individuals (31.3%). In total, 377 participants (11.8%) harbored P. knowlesi. Also present were Plasmodium vivax (14.3%), Plasmodium falciparum (10.5%) and Plasmodium malariae (3.4%).

    Conclusions: Amplification of sicavar is a specific and sensitive test for the presence of P. knowlesi DNA in humans. Subpatent and asymptomatic multispecies parasitemia is relatively common in North Sumatera, so PCR-based surveillance is required to support control and elimination activities.

  14. Barber BE, Grigg MJ, William T, Piera KA, Boyle MJ, Yeo TW, et al.
    J Infect Dis, 2017 06 15;215(12):1908-1917.
    PMID: 28863470 DOI: 10.1093/infdis/jix193
    Background: In populations pauci-immune to malaria, risk of severe malaria increases with age. This is particularly apparent in Plasmodium knowlesi malaria. However, pathophysiological mechanisms underlying knowlesi malaria, and of the age-related increase in risk of severe malaria in general, are poorly understood.

    Methods: In Malaysian patients aged ≥12 years with severe (n = 47) and nonsevere (n = 99) knowlesi malaria, severe (n = 21) and nonsevere (n = 109) falciparum malaria, and healthy controls (n = 50), we measured parasite biomass, systemic inflammation (interleukin 6 [IL-6]), endothelial activation (angiopoietin-2), and microvascular function, and evaluated the effects of age.

    Results: Plasmodium knowlesi parasitemia correlated with age (Spearman's correlation coefficient [rs] = 0.36; P < .0001). In knowlesi malaria, IL-6, angiopoietin-2, and microvascular dysfunction were increased in severe compared to nonsevere disease, and all correlated with age, independent of parasitemia. In falciparum malaria, angiopoietin-2 increased with age, independent of parasite biomass (histidine-rich protein 2 [HRP2]). Independent risk factors for severe malaria included parasitemia and angiopoietin-2 in knowlesi malaria, and HRP2, angiopoietin-2, and microvascular dysfunction in falciparum malaria.

    Conclusions: Parasite biomass, endothelial activation, and microvascular dysfunction are associated with severe disease in knowlesi malaria and likely contribute to pathogenesis. The association of each of these processes with aging may account for the greater severity of malaria observed in older adults in low-endemic regions.

  15. Escaffre O, Hill T, Ikegami T, Juelich TL, Smith JK, Zhang L, et al.
    J Infect Dis, 2018 10 05;218(10):1602-1610.
    PMID: 29912426 DOI: 10.1093/infdis/jiy357
    Background: Nipah virus (NiV) is a paramyxovirus (genus Henipavirus) that can cause severe respiratory illness and encephalitis in humans. Transmission occurs through consumption of NiV-contaminated foods, and contact with NiV-infected animals or human body fluids. However, it is unclear whether aerosols derived from aforesaid sources or others also contribute to transmission, and current knowledge on NiV-induced pathogenicity after small-particle aerosol exposure is still limited.

    Methods: Infectivity, pathogenicity, and real-time dissemination of aerosolized NiV in Syrian hamsters was evaluated using NiV-Malaysia (NiV-M) and/or its recombinant expressing firefly luciferase (rNiV-FlucNP).

    Results: Both viruses had an equivalent pathogenicity in hamsters, which developed respiratory and neurological symptoms of disease, similar to using intranasal route, with no direct correlations to the dose. We showed that virus replication was predominantly initiated in the lower respiratory tract and, although delayed, also intensely in the oronasal cavity and possibly the brain, with gradual increase of signal in these regions until at least day 5-6 postinfection.

    Conclusion: Hamsters infected with small-particle aerosolized NiV undergo similar clinical manifestations of the disease as previously described using liquid inoculum, and exhibit histopathological lesions consistent with NiV patient reports. NiV droplets could therefore play a role in transmission by close contact.

  16. 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.

  17. 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.

  18. Kua KP, Chongmelaxme B, Lee SWH
    J Infect Dis, 2023 Feb 14;227(4):471-482.
    PMID: 35512129 DOI: 10.1093/infdis/jiac179
    BACKGROUND: Tuberculosis is one of the leading causes of mortality worldwide from an infectious disease. This review aimed to investigate the association between prior cytomegalovirus infection and tuberculosis disease.

    METHODS: Six bibliographic databases were searched from their respective inception to 31 December 2021. Data were pooled using random-effects meta-analysis.

    RESULTS: Of 5476 identified articles, 15 satisfied the inclusion criteria with a total sample size of 38 618 patients. Pooled findings showed that individuals with cytomegalovirus infection had a higher risk of tuberculosis disease compared to those not infected with cytomegalovirus (odds ratio [OR], 3.20; 95% confidence interval [CI], 2.18-4.70). Age was the only covariate that exerted a significant effect on the result of the association. Meta-analysis of risk estimates reported in individual studies showed a marked and significant correlation of cytomegalovirus infection with active tuberculosis (adjusted hazard ratio, 2.92; 95% CI, 1.34-4.51; adjusted OR, 1.14; 95% CI, .71-1.57). A clear dose-response relation was inferred between the levels of cytomegalovirus antibodies and the risks of tuberculosis events (OR for high levels of cytomegalovirus antibodies, 4.07; OR for medium levels of cytomegalovirus antibodies, 3.58).

    CONCLUSIONS: The results suggest an elevated risk of tuberculosis disease among individuals with a prior cytomegalovirus infection.

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