Displaying publications 21 - 40 of 87 in total

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  1. Fulltext Genetic characterization of Zika virus strains: geographic expansion of the Asian lineage
    Haddow AD, Schuh AJ, Yasuda CY, Kasper MR, Heang V, Huy R, et al.
    PLoS Negl Trop Dis, 2012;6(2):e1477.
    PMID: 22389730 DOI: 10.1371/journal.pntd.0001477
    Zika virus (ZIKV) is a mosquito-borne flavivirus distributed throughout much of Africa and Asia. Infection with the virus may cause acute febrile illness that clinically resembles dengue fever. A recent study indicated the existence of three geographically distinct viral lineages; however this analysis utilized only a single viral gene. Although ZIKV has been known to circulate in both Africa and Asia since at least the 1950s, little is known about the genetic relationships between geographically distinct virus strains. Moreover, the geographic origin of the strains responsible for the epidemic that occurred on Yap Island, Federated States of Micronesia in 2007, and a 2010 pediatric case in Cambodia, has not been determined.
    Matched MeSH terms: Zika Virus Infection/epidemiology; Zika Virus Infection/virology*; Zika Virus/classification*; Zika Virus/genetics*; Zika Virus/isolation & purification
  2. Zika virus, a cause of fever in Central Java, Indonesia
    Olson JG, Ksiazek TG, Suhandiman, Triwibowo
    Trans R Soc Trop Med Hyg, 1981;75(3):389-93.
    PMID: 6275577
    In 1977 and 1978 selected in-patients at the Tegalyoso Hospital, Klaten, Indonesia who had recent onsets of acute fever were serologically studied for evidence for alphavirus and flavivirus infections. A brief clinical history was taken and a check list of signs and symptoms was completed on admission. Acute and convalescent phase sera from 30 patients who showed evidence that a flavivirus had caused their illnesses were tested for neutralizing antibodies to several flaviviruses which occur in South-east Asia. Paired sera from seven patients demonstrated a fourfold rise in antibody titre from acute to convalescent phase. The most common clinical manifestations observed in this series of patients included high fever, malaise, stomach ache, dizziness and anorexia. None of the seven patients had headache or rash despite the fact that headache and rash had been associated with two of the three previously studied. The onsets of illness clustered toward the end of the rainy season when populations of Aedes aegypti, a probable vector in Malaysia, were most abundant.
    Matched MeSH terms: Zika Virus Infection/complications; Zika Virus Infection/epidemiology*; Zika Virus/immunology; Zika Virus/isolation & purification*
  3. Fulltext Functional Genomics and Immunologic Tools: The Impact of Viral and Host Genetic Variations on the Outcome of Zika Virus Infection
    Yun SI, Song BH, Frank JC, Julander JG, Olsen AL, Polejaeva IA, et al.
    Viruses, 2018 08 11;10(8).
    PMID: 30103523 DOI: 10.3390/v10080422
    Zika virus (ZIKV) causes no-to-mild symptoms or severe neurological disorders. To investigate the importance of viral and host genetic variations in determining ZIKV infection outcomes, we created three full-length infectious cDNA clones as bacterial artificial chromosomes for each of three spatiotemporally distinct and genetically divergent ZIKVs: MR-766 (Uganda, 1947), P6-740 (Malaysia, 1966), and PRVABC-59 (Puerto Rico, 2015). Using the three molecularly cloned ZIKVs, together with 13 ZIKV region-specific polyclonal antibodies covering nearly the entire viral protein-coding region, we made three conceptual advances: (i) We created a comprehensive genome-wide portrait of ZIKV gene products and their related species, with several previously undescribed gene products identified in the case of all three molecularly cloned ZIKVs. (ii) We found that ZIKV has a broad cell tropism in vitro, being capable of establishing productive infection in 16 of 17 animal cell lines from 12 different species, although its growth kinetics varied depending on both the specific virus strain and host cell line. More importantly, we identified one ZIKV-non-susceptible bovine cell line that has a block in viral entry but fully supports the subsequent post-entry steps. (iii) We showed that in mice, the three molecularly cloned ZIKVs differ in their neuropathogenicity, depending on the particular combination of viral and host genetic backgrounds, as well as in the presence or absence of type I/II interferon signaling. Overall, our findings demonstrate the impact of viral and host genetic variations on the replication kinetics and neuropathogenicity of ZIKV and provide multiple avenues for developing and testing medical countermeasures against ZIKV.
    Matched MeSH terms: Zika Virus Infection/genetics*; Zika Virus Infection/virology; Zika Virus/genetics*; Zika Virus/physiology
  4. Baicalein and baicalin as Zika virus inhibitors
    Oo A, Teoh BT, Sam SS, Bakar SA, Zandi K
    Arch Virol, 2019 Feb;164(2):585-593.
    PMID: 30392049 DOI: 10.1007/s00705-018-4083-4
    At present, there is no effective antiviral agent for Zika virus (ZIKV), an arbovirus that is known for its teratogenic effects on newborns. Baicalein and baicalin were found to be capable of downregulating ZIKV replication up to 10 hours postinfection, while prophylactic effects were evident in pre-treated cells. Baicalein exhibited its highest potency during intracellular ZIKV replication, whereas baicalin was most effective against virus entry. Our in silico interaction assays predicted that both compounds exhibited the strongest binding affinities towards ZIKV NS5, while the virus envelope glycoprotein was the least likely target protein. These findings serve as a crucial platform for further in-depth studies to decipher the underlying anti-ZIKV mechanism(s) of each compound.
    Matched MeSH terms: Zika Virus Infection; Zika Virus
  5. Monitoring Changes in Human Umbilical Vein Endothelial Cells upon Viral Infection Using Impedance-Based Real-Time Cell Analysis
    Wong JE, Zainal N, AbuBakar S, Tan KK
    J Vis Exp, 2023 May 05.
    PMID: 37212555 DOI: 10.3791/64887
    Endothelial cells line the inner surface of all blood and lymphatic vessels, creating a semi-permeable barrier regulating fluid and solute exchange between blood or lymph and their surrounding tissues. The ability of a virus to cross the endothelial barrier is an important mechanism that facilitates virus dissemination in the human body. Many viruses are reported to alter endothelial permeability and/or cause endothelial cell barrier disruption during infection, which is able to cause vascular leakage. The current study describes a real-time cell analysis (RTCA) protocol, using a commercial real-time cell analyzer to monitor endothelial integrity and permeability changes during Zika virus (ZIKV) infection of the human umbilical vein endothelial cells (HUVECs). The impedance signals recorded before and after ZIKV infection were translated to cell index (CI) values and analyzed. The RTCA protocol allows the detection of transient effects in the form of cell morphological changes during a viral infection. This assay could also be useful for studying changes in the vascular integrity of HUVECs in other experimental setups.
    Matched MeSH terms: Zika Virus Infection*
  6. Fulltext Application of medical information system to identify dengue outbreak factors: Insights from a hyperendemic city in Malaysia
    Keat-Chuan Ng C, Linus-Lojikip S, Mohamed K, Hss AS
    Int J Med Inform, 2023 Sep;177:105162.
    PMID: 37549500 DOI: 10.1016/j.ijmedinf.2023.105162
    BACKGROUND: Dengue is widespread globally, but it is more severe in hyperendemic regions where the virus, its vectors, and its human hosts naturally occur. The problem is particularly acute in cities, where outbreaks affect a large human population living in a wide array of socio-environmental conditions. Controlling outbreaks will rely largely on systematic data collection and analysis approaches to uncover nuances on a city-by-city basis due to the diversity of factors.

    OBJECTIVE: The main objective of this study is to consolidate and analyse the dengue case dataset amassed by the e-Dengue web-based information system, developed by the Ministry of Health Malaysia, to improve our epidemiological understanding.

    METHODS: We retrieved data from the e-Dengue system and integrated a total of 18,812 cases from 2012 to 2019 (8 years) with meteorological data, geoinformatics techniques, and socio-environmental observations to identify plausible factors that could have caused dengue outbreaks in Ipoh, a hyperendemic city in Malaysia.

    RESULTS: The rainfall trend characterised by a linearity of R2 > 0.99, termed the "wet-dry steps", may be the unifying factor for triggering dengue outbreaks, though it is still a hypothesis that needs further validation. Successful mapping of the dengue "reservoir" contact zones and spill-over diffusion revealed socio-environmental factors that may be controlled through preventive measures. Age is another factor to consider, as the platelet and white blood cell counts in the "below 5" age group are much greater than in other age groups.

    CONCLUSIONS: Our work demonstrates the novelty of the e-Dengue system, which can identify outbreak factors at high resolution when integrated with non-medical fields. Besides dengue, the techniques and insights laid out in this paper are valuable, at large, for advancing control strategies for other mosquito-borne diseases such as malaria, chikungunya, and zika in other hyperendemic cities elsewhere globally.

    Matched MeSH terms: Zika Virus*
  7. A graphene-based dengue immunosensor using plant-derived envelope glycoprotein domain III (EDIII) as the novel probe antigen
    Siew QY, Tan SH, Pang EL, Loh HS, Tan MTT
    Analyst, 2021 Mar 21;146(6):2009-2018.
    PMID: 33523052 DOI: 10.1039/d0an02219e
    The envelope glycoprotein domain III (EDIII) of dengue virus (DENV) has been recognised as the antigenic region responsible for receptor binding. In the present work, we have proposed a novel immunosensor constructed on a graphene-coated screen-printed carbon electrode (SPCE) using plant-derived EDIII as the probe antigen to target DENV IgG antibodies. The developed immunosensor demonstrated high sensitivity towards DENV IgG within a wide linear working range (125-2000 ng mL-1) under the optimised sensing conditions. The limit of detection was determined to be 22.5 ng mL-1. The immunosensor also showed high specificity towards DENV IgG, capable of differentiating DENV IgG from the antibodies of other infectious diseases including the similarly structured Zika virus (ZIKV). The ability of the immunosensor to detect dengue antibodies in serum samples was also verified by conducting tests on mouse serum samples. The proposed immunosensor was able to provide a binary (positive/negative) response towards the serum samples comparable to the conventional enzyme-linked immunosorbent assay (ELISA), indicating promising potential for realistic applications.
    Matched MeSH terms: Zika Virus Infection*; Zika Virus*
  8. Zika virus modulates blood-brain barrier of brain microvascular endothelial cells
    Ismail AA, Mahboob T, Samudi Raju C, Sekaran SD
    Trop Biomed, 2019 Dec 01;36(4):888-897.
    PMID: 33597462
    Zika virus (ZIKV) is a mosquito-borne Flaviviruses. ZIKV is known to cause birth defect in pregnant women, especially microcephaly in the fetus. Hence, more study is required to understand the infection of Zika virus towards human brain microvascular endothelial cells (MECs). In this study, brain MECs were infected with ZIKV at MOI of 1 and 5 in vitro. The changes in barrier function and membrane permeability of ZIKV-infected brain MECs were determined using electric cell-substrate impedance sensing (ECIS) system followed by gene expression of ZIKV-infected brain MECs at 24 hours post infection using one-color gene expression microarray. The ECIS results demonstrated that ZIKV infection enhances vascular leakage by increasing cell membrane permeability via alteration of brain MECs barrier function. This was further supported by high expression of proinflammatory cytokine genes (lnc-IL6-2, TNFAIP1 and TNFAIP6), adhesion molecules (CERCAM and ESAM) and growth factor (FIGF). Overall, findings of this study revealed that ZIKV infection could alter the barrier function of brain MECs by altering adhesion molecules and inflammatory response.
    Matched MeSH terms: Zika Virus Infection/pathology*; Zika Virus Infection/virology; Zika Virus
  9. Zika virus infection and Guillain-Barré syndrome: a review focused on clinical and electrophysiological subtypes
    Uncini A, Shahrizaila N, Kuwabara S
    J Neurol Neurosurg Psychiatry, 2017 03;88(3):266-271.
    PMID: 27799296 DOI: 10.1136/jnnp-2016-314310
    In 2016, we have seen a rapid emergence of Zika virus-associated Guillain-Barré syndrome (GBS) since its first description in a French-Polynesian patient in 2014. Current evidence estimates the incidence of GBS at 24 cases per 100 000 persons infected by Zika virus. This will result in a sharp rise in the number of GBS cases worldwide with the anticipated global spread of Zika virus. A better understanding of the pathogenesis of Zika-associated GBS is crucial to prepare us for the current epidemic. In this review, we evaluate the existing literature on GBS in association with Zika and other flavivirus to better define its clinical subtypes and electrophysiological characteristics, demonstrating a demyelinating subtype of GBS in most cases. We also recommend measures that will help reduce the gaps in knowledge that currently exist.
    Matched MeSH terms: Zika Virus Infection/epidemiology; Zika Virus/isolation & purification
  10. Fulltext Host immune response against DENV and ZIKV infections
    Sekaran SD, Ismail AA, Thergarajan G, Chandramathi S, Rahman SKH, Mani RR, et al.
    Front Cell Infect Microbiol, 2022;12:975222.
    PMID: 36159640 DOI: 10.3389/fcimb.2022.975222
    Dengue is a major public health concern, affecting almost 400 million people worldwide, with about 70% of the global burden of disease in Asia. Despite revised clinical classifications of dengue infections by the World Health Organization, the wide spectrum of the manifestations of dengue illness continues to pose challenges in diagnosis and patient management for clinicians. When the Zika epidemic spread through the American continent and then later to Africa and Asia in 2015, researchers compared the characteristics of the Zika infection to Dengue, considering both these viruses were transmitted primarily through the same vector, the Aedes aegypti female mosquitoes. An important difference to note, however, was that the Zika epidemic diffused in a shorter time span compared to the persisting feature of Dengue infections, which is endemic in many Asian countries. As the pathogenesis of viral illnesses is affected by host immune responses, various immune modulators have been proposed as biomarkers to predict the risk of the disease progression to a severe form, at a much earlier stage of the illness. However, the findings for most biomarkers are highly discrepant between studies. Meanwhile, the cross-reactivity of CD8+ and CD4+ T cells response to Dengue and Zika viruses provide important clues for further development of potential treatments. This review discusses similarities between Dengue and Zika infections, comparing their disease transmissions and vectors involved, and both the innate and adaptive immune responses in these infections. Consideration of the genetic identity of both the Dengue and Zika flaviviruses as well as the cross-reactivity of relevant T cells along with the actions of CD4+ cytotoxic cells in these infections are also presented. Finally, a summary of the immune biomarkers that have been reported for dengue and Zika viral infections are discussed which may be useful indicators for future anti-viral targets or predictors for disease severity. Together, this information appraises the current understanding of both Zika and Dengue infections, providing insights for future vaccine design approaches against both viruses.
    Matched MeSH terms: Zika Virus Infection*; Zika Virus*
  11. Fulltext Susceptibility of Aedes albopictus, Ae. aegypti and human populations to Ross River virus in Kuala Lumpur, Malaysia
    Fu JYL, Chua CL, Abu Bakar AS, Vythilingam I, Wan Sulaiman WY, Alphey L, et al.
    PLoS Negl Trop Dis, 2023 Jun;17(6):e0011423.
    PMID: 37307291 DOI: 10.1371/journal.pntd.0011423
    BACKGROUND: Emerging arboviruses such as chikungunya and Zika viruses have unexpectedly caused widespread outbreaks in tropical and subtropical regions recently. Ross River virus (RRV) is endemic in Australia and has epidemic potential. In Malaysia, Aedes mosquitoes are abundant and drive dengue and chikungunya outbreaks. We assessed risk of an RRV outbreak in Kuala Lumpur, Malaysia by determining vector competence of local Aedes mosquitoes and local seroprevalence as a proxy of human population susceptibility.

    METHODOLOGY/PRINCIPAL FINDINGS: We assessed oral susceptibility of Malaysian Ae. aegypti and Ae. albopictus by real-time PCR to an Australian RRV strain SW2089. Replication kinetics in midgut, head and saliva were determined at 3 and 10 days post-infection (dpi). With a 3 log10 PFU/ml blood meal, infection rate was higher in Ae. albopictus (60%) than Ae. aegypti (15%; p<0.05). Despite similar infection rates at 5 and 7 log10 PFU/ml blood meals, Ae. albopictus had significantly higher viral loads and required a significantly lower median oral infectious dose (2.7 log10 PFU/ml) than Ae. aegypti (4.2 log10 PFU/ml). Ae. albopictus showed higher vector competence, with higher viral loads in heads and saliva, and higher transmission rate (RRV present in saliva) of 100% at 10 dpi, than Ae. aegypti (41%). Ae. aegypti demonstrated greater barriers at either midgut escape or salivary gland infection, and salivary gland escape. We then assessed seropositivity against RRV among 240 Kuala Lumpur inpatients using plaque reduction neutralization, and found a low rate of 0.8%.

    CONCLUSIONS/SIGNIFICANCE: Both Ae. aegypti and Ae. albopictus are susceptible to RRV, but Ae. albopictus displays greater vector competence. Extensive travel links with Australia, abundant Aedes vectors, and low population immunity places Kuala Lumpur, Malaysia at risk of an imported RRV outbreak. Surveillance and increased diagnostic awareness and capacity are imperative to prevent establishment of new arboviruses in Malaysia.

    Matched MeSH terms: Zika Virus Infection*; Zika Virus*
  12. Fulltext Entomological Surveillance Associated with Human Zika Cases in Miri Sarawak, Malaysia
    Ali R, Azmi RA, Wasi Ahmad N, Abd Hadi A, Muhamed KA, Rasli R, et al.
    Am J Trop Med Hyg, 2020 May;102(5):964-970.
    PMID: 32228777 DOI: 10.4269/ajtmh.19-0339
    Two confirmed human cases of Zika virus (ZIKV) were reported in the district of Miri, Sarawak, in 2016. Following that, a mosquito-based ZIKV surveillance study was conducted within 200-m radius from the case houses. Mosquito surveillance was conducted using five different methods, that is, biogents sentinel mosquito (BG) sentinel trap, modified sticky ovitrap, resting catch, larval surveillance, and conventional ovitrap. A total of 527 and 390 mosquito samples were obtained from the case houses in two localities, namely, Kampung Lopeng and Taman Shang Ri La, Miri, Sarawak, respectively. All mosquitoes collected were identified, which consisted of 11 species. Aedes albopictus, both the adult and larval stages, was the dominant species. Resting catch method obtained the highest number of adult mosquitoes (67%), whereas ovitrap showed the highest catch for larval mosquitoes (84%). Zika virus was detected in both adults and larvae of Ae. albopictus together with adults of Culex gelidus, and Culex quinquefasciatus using the real-time reverse transcriptase polymerase chain reaction (PCR) technique. It was noteworthy that Ae. albopictus positive with ZIKV were caught and obtained from four types of collection method. By contrast, Cx. gelidus and Culex quinquefasciatus adults collected from sticky ovitraps were also found positive with ZIKV. This study reveals vital information regarding the potential vectors of ZIKV and the possibility of transovarian transmission of the virus in Malaysia. These findings will be essentials for vector control program managers to devise preparedness and contingency plans of prevention and control of the arboviral disease.
    Matched MeSH terms: Zika Virus Infection/etiology; Zika Virus Infection/epidemiology*; Zika Virus Infection/transmission
  13. Fulltext Diagnosis and management of Guillain-Barré syndrome in ten steps
    Leonhard SE, Mandarakas MR, Gondim FAA, Bateman K, Ferreira MLB, Cornblath DR, et al.
    Nat Rev Neurol, 2019 Nov;15(11):671-683.
    PMID: 31541214 DOI: 10.1038/s41582-019-0250-9
    Guillain-Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots that is usually triggered by infections. The incidence of GBS can therefore increase during outbreaks of infectious diseases, as was seen during the Zika virus epidemics in 2013 in French Polynesia and 2015 in Latin America. Diagnosis and management of GBS can be complicated as its clinical presentation and disease course are heterogeneous, and no international clinical guidelines are currently available. To support clinicians, especially in the context of an outbreak, we have developed a globally applicable guideline for the diagnosis and management of GBS. The guideline is based on current literature and expert consensus, and has a ten-step structure to facilitate its use in clinical practice. We first provide an introduction to the diagnostic criteria, clinical variants and differential diagnoses of GBS. The ten steps then cover early recognition and diagnosis of GBS, admission to the intensive care unit, treatment indication and selection, monitoring and treatment of disease progression, prediction of clinical course and outcome, and management of complications and sequelae.
    Matched MeSH terms: Zika Virus Infection/diagnosis; Zika Virus Infection/epidemiology; Zika Virus Infection/therapy
  14. Zika Virus Infection: Current Concerns and Perspectives
    Maharajan MK, Ranjan A, Chu JF, Foo WL, Chai ZX, Lau EY, et al.
    Clin Rev Allergy Immunol, 2016 Dec;51(3):383-394.
    PMID: 27236440
    The Zika virus outbreaks highlight the growing importance need for a reliable, specific and rapid diagnostic device to detect Zika virus, as it is often recognized as a mild disease without being identified. Many Zika virus infection cases have been misdiagnosed or underreported because of the non-specific clinical presentation. The aim of this review was to provide a critical and comprehensive overview of the published peer-reviewed evidence related to clinical presentations, various diagnostic methods and modes of transmission of Zika virus infection, as well as potential therapeutic targets to combat microcephaly. Zika virus is mainly transmitted through bites from Aedes aegypti mosquito. It can also be transmitted through blood, perinatally and sexually. Pregnant women are advised to postpone or avoid travelling to areas where active Zika virus transmission is reported, as this infection is directly linked to foetal microcephaly. Due to the high prevalence of Guillain-Barre syndrome and microcephaly in the endemic area, it is vital to confirm the diagnosis of Zika virus. Zika virus infection had been declared as a public health emergency and of international concern by the World Health Organisation. Governments and agencies should play an important role in terms of investing time and resources to fundamentally understand this infection so that a vaccine can be developed besides raising awareness.
    Matched MeSH terms: Zika Virus Infection/diagnosis*; Zika Virus Infection/drug therapy; Zika Virus Infection/transmission; Zika Virus Infection/virology*; Zika Virus/physiology*
  15. Fulltext A reverse transcription loop-mediated isothermal amplification for broad coverage detection of Asian and African Zika virus lineages
    Teoh BT, Chin KL, Samsudin NI, Loong SK, Sam SS, Tan KK, et al.
    BMC Infect Dis, 2020 Dec 11;20(1):947.
    PMID: 33308203 DOI: 10.1186/s12879-020-05585-4
    BACKGROUND: Early detection of Zika virus (ZIKV) infection during the viremia and viruria facilitates proper patient management and mosquito control measurement to prevent disease spread. Therefore, a cost-effective nucleic acid detection method for the diagnosis of ZIKV infection, especially in resource-deficient settings, is highly required.

    METHODS: In the present study, a single-tube reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed for the detection of both the Asian and African-lineage ZIKV. The detection limit, strain coverage and cross-reactivity of the ZIKV RT-LAMP assay was evaluated. The sensitivity and specificity of the RT-LAMP were also evaluated using a total of 24 simulated clinical samples. The ZIKV quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay was used as the reference assay.

    RESULTS: The detection limit of the RT-LAMP assay was 3.73 ZIKV RNA copies (probit analysis, P ≤ 0.05). The RT-LAMP assay detected the ZIKV genomes of both the Asian and African lineages without cross-reacting with other arthropod-borne viruses. The sensitivity and specificity of the RT-LAMP assay were 90% (95% CI = 59.6-98.2) and 100% (95% CI = 78.5-100.0), respectively. The RT-LAMP assay detected ZIKV genome in 9 of 24 (37.5%) of the simulated clinical samples compared to 10 of 24 (41.7%) by qRT-PCR assay with a high level of concordance (κ = 0.913, P 

    Matched MeSH terms: Zika Virus Infection/diagnosis*; Zika Virus Infection/epidemiology*; Zika Virus Infection/virology; Zika Virus/classification*; Zika Virus/genetics*
  16. Fulltext Serological Evidence of Zika Virus Infection in Febrile Patients and Healthy Blood Donors in Sabah, Malaysian Borneo, 2017-2018
    Ngwe Tun MM, Mori D, Sabri SB, Kugan O, Shaharom SB, John J, et al.
    Am J Trop Med Hyg, 2021 Nov 22;106(2):601-606.
    PMID: 34814105 DOI: 10.4269/ajtmh.21-0802
    Several Zika virus (ZIKV) seroprevalence studies have been conducted in Africa, Asia, Oceania, the Americas, and the Caribbean. However, studies on ZIKV seroprevalence are limited in Malaysia though several studies have shown that the disease is endemic in the Malaysian state of Sabah. To evaluate the seroprevalence of ZIKV infection, 818 serum samples were collected from febrile patients and healthy blood donors from the Kudat and Kota Kinabalu districts in Sabah from 2017 to 2018. They were screened for ZIKV infection by IgM and IgG ELISA, and positive ZIKV IgM samples were subjected to a 90% neutralization test for confirmation. Twenty-four (6% [95% CI 4 to 8]) confirmed and two (0.5% [95% CI 0.13 to 1.8]) probable ZIKV infections were detected among 400 febrile illness patients. Of 418 healthy blood donor samples, six (1.4% [95% CI 0.65 to 3]) were determined as confirmed ZIKV infections and six (1.4% [95% CI 0.65 to 3]) indicated probable ZIKV infection. This is the first study on the seroprevalence of ZIKV infections among patients and healthy blood donors in Sabah. Compared with previous studies in Malaysia, this study shows that the incidence of ZIKV infection has increased. It also suggests that a sero-surveillance system is essential to determine the circulation of ZIKV in Sabah, Malaysia.
    Matched MeSH terms: Zika Virus Infection/blood*; Zika Virus Infection/diagnosis*; Zika Virus Infection/epidemiology; Zika Virus Infection/prevention & control; Zika Virus/immunology
  17. Fulltext Vector competence of Aedes aegypti, Culex tarsalis, and Culex quinquefasciatus from California for Zika virus
    Main BJ, Nicholson J, Winokur OC, Steiner C, Riemersma KK, Stuart J, et al.
    PLoS Negl Trop Dis, 2018 Jun;12(6):e0006524.
    PMID: 29927940 DOI: 10.1371/journal.pntd.0006524
    Zika virus (ZIKV) has emerged since 2013 as a significant global human health threat following outbreaks in the Pacific Islands and rapid spread throughout South and Central America. Severe congenital and neurological sequelae have been linked to ZIKV infections. Assessing the ability of common mosquito species to transmit ZIKV and characterizing variation in mosquito transmission of different ZIKV strains is important for estimating regional outbreak potential and for prioritizing local mosquito control strategies for Aedes and Culex species. In this study, we evaluated the laboratory vector competence of Aedes aegypti, Culex quinquefasciatus, and Culex tarsalis that originated in areas of California where ZIKV cases in travelers since 2015 were frequent. We compared infection, dissemination, and transmission rates by measuring ZIKV RNA levels in cohorts of mosquitoes that ingested blood meals from type I interferon-deficient mice infected with either a Puerto Rican ZIKV strain from 2015 (PR15), a Brazilian ZIKV strain from 2015 (BR15), or an ancestral Asian-lineage Malaysian ZIKV strain from 1966 (MA66). With PR15, Cx. quinquefasciatus was refractory to infection (0%, N = 42) and Cx. tarsalis was infected at 4% (N = 46). No ZIKV RNA was detected in saliva from either Culex species 14 or 21 days post feeding (dpf). In contrast, Ae. aegypti developed infection rates of 85% (PR15; N = 46), 90% (BR15; N = 20), and 81% (MA66; N = 85) 14 or 15 dpf. Although MA66-infected Ae. aegypti showed higher levels of ZIKV RNA in mosquito bodies and legs, transmission rates were not significantly different across virus strains (P = 0.13, Fisher's exact test). To confirm infectivity and measure the transmitted ZIKV dose, we enumerated infectious ZIKV in Ae. aegypti saliva using Vero cell plaque assays. The expectorated plaque forming units PFU varied by viral strain: MA66-infected expectorated 13±4 PFU (mean±SE, N = 13) compared to 29±6 PFU for PR15-infected (N = 13) and 35±8 PFU for BR15-infected (N = 6; ANOVA, df = 2, F = 3.8, P = 0.035). These laboratory vector competence results support an emerging consensus that Cx. tarsalis and Cx. quinquefasciatus are not vectors of ZIKV. These results also indicate that Ae. aegypti from California are efficient laboratory vectors of ancestral and contemporary Asian lineage ZIKV.
    Matched MeSH terms: Zika Virus Infection/epidemiology; Zika Virus Infection/transmission*; Zika Virus Infection/virology; Zika Virus/genetics; Zika Virus/physiology*
  18. Fulltext Current concerns and perspectives on Zika virus co-infection with arboviruses and HIV
    Rothan HA, Bidokhti MRM, Byrareddy SN
    J Autoimmun, 2018 05;89:11-20.
    PMID: 29352633 DOI: 10.1016/j.jaut.2018.01.002
    Dissemination of vector-borne viruses, such as Zika virus (ZIKV), in tropical and sub-tropical regions has a complicated impact on the immunopathogenesis of other endemic viruses such as dengue virus (DENV), chikungunya virus (CHIKV) and human immunodeficiency virus (HIV). The consequences of the possible co-infections with these viruses have specifically shown significant impact on the treatment and vaccination strategies. ZIKV is a mosquito-borne flavivirus from African and Asian lineages that causes neurological complications in infected humans. Many of DENV and CHIKV endemic regions have been experiencing outbreaks of ZIKV infection. Intriguingly, the mosquitoes, Aedes Aegypti and Aedes Albopictus, can simultaneously transmit all the combinations of ZIKV, DENV, and CHIKV to the humans. The co-circulation of these viruses leads to a complicated immune response due to the pre-existence or co-existence of ZIKV infection with DENV and CHIKV infections. The non-vector transmission of ZIKV, especially, via sexual intercourse and placenta represents an additional burden that may hander the treatment strategies of other sexually transmitted diseases such as HIV. Collectively, ZIKV co-circulation and co-infection with other viruses have inevitable impact on the host immune response, diagnosis techniques, and vaccine development strategies for the control of these co-infections.
    Matched MeSH terms: Zika Virus Infection/immunology; Zika Virus Infection/epidemiology*; Zika Virus/physiology*
  19. Attitudes towards Zika screening and vaccination acceptability among pregnant women in Malaysia
    Wong LP, Alias H, Hassan J, AbuBakar S
    Vaccine, 2017 10 13;35(43):5912-5917.
    PMID: 28886944 DOI: 10.1016/j.vaccine.2017.08.074
    The aim of this study was to examine the willingness of pregnant women to have prenatal screening for the Zika virus (ZIKV). Secondly, the study also assessed the acceptability of a hypothetical Zika vaccination and its association with the health belief model (HBM) constructs. A cross-sectional study was conducted from 4th October to 11th November 2016, among pregnant women who attended antenatal care at the University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia. The majority (81.8%) was willing to be tested for ZIKV and 78% felt that their spouse would be willing to be tested for ZIKV. A total of 94% expressed a willingness to receive a Zika vaccination if available. The participants expressed high perceived benefits of a ZIKV vaccination. Although many have a high perception of the severity of ZIKV, the proportion with a strong perception of their susceptibility to ZIKV was low. In the multivariate analysis of all the HBM constructs, cue-to-action, namely physician recommendation (odds ratio [OR]=2.288; 95% confidence interval [CI] 1.093-4.793) and recommendation from friends or relatives (OR=4.030; 95% CI 1.694-9.587), were significantly associated with a willingness to be vaccinated against ZIKV. The favourable response to a Zika vaccination implies that more research attention has to be given to develop a vaccine against ZIKV. Should the vaccine be available in the future, publicity and healthcare providers would play a vital role in ensuring vaccine uptake among pregnant women.
    Matched MeSH terms: Zika Virus Infection/immunology*; Zika Virus Infection/prevention & control*; Zika Virus/immunology*
  20. Fulltext Resveratrol affects Zika virus replication in vitro
    Mohd A, Zainal N, Tan KK, AbuBakar S
    Sci Rep, 2019 10 04;9(1):14336.
    PMID: 31586088 DOI: 10.1038/s41598-019-50674-3
    Zika virus (ZIKV) infection is a serious public health concern. ZIKV infection has been associated with increased occurrences of microcephaly among newborns and incidences of Guillain-Barré syndrome among adults. No specific therapeutics or vaccines are currently available to treat and protect against ZIKV infection. Here, a plant-secreted phytoalexin, resveratrol (RES), was investigated for its ability to inhibit ZIKV replication in vitro. Several RES treatment regimens were used. The ZIKV titers of mock- and RES-treated infected cell cultures were determined using the focus-forming assay and the Zika mRNA copy number as determined using qRT-PCR. Our results suggested that RES treatment reduced ZIKV titers in a dose-dependent manner. A reduction of >90% of virus titer and ZIKV mRNA copy number was achieved when infected cells were treated with 80 µM of RES post-infection. Pre-incubation of the virus with 80 µM RES showed >30% reduction in ZIKV titers and ZIKV mRNA copy number, implying potential direct virucidal effects of RES against the virus. The RES treatment reduced >70% virus titer in the anti-adsorption assay, suggesting the possibility that RES also interferes with ZIKV binding. However, there was no significant decrease in ZIKV titer when a short-period of RES treatment was applied to cells before ZIKV infection (pre-infection) and after the virus bound to the cells (virus internalization inhibition), implying that RES acts through its continuous presence in the cell cultures after virus infection. Overall, our results suggested that RES exhibited direct virucidal activity against ZIKV and possessed anti-ZIKV replication properties, highlighting the need for further exploration of RES as a potential antiviral molecule against ZIKV infection.
    Matched MeSH terms: Zika Virus Infection/drug therapy*; Zika Virus Infection/virology; Zika Virus/drug effects*; Zika Virus/physiology
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