scholarly journals Encephalitis in Thailand: A Neglected Disease Increasingly Caused by Enterovirus

2021 ◽  
Vol 6 (3) ◽  
pp. 117
Author(s):  
Pasin Hemachudha ◽  
Sininat Petcharat ◽  
Soawapak Hinjoy ◽  
Abhinbhen W. Saraya ◽  
Thiravat Hemachudha

From 2013 to 2018, the Thai Red Cross Emerging Infectious Disease–Health Science Center (TRC-EID-HS), in collaboration with the Department of Disease Control (DDC) and the Ministry of Public Health (MOPH) Thailand, conducted encephalitis surveillance. A total of 1700 cerebrospinal fluid (CSF) samples from patients with encephalitis were tested by a predesigned multiplex PCR. Diagnosis was made in 318 cases (18.7%), 86 (27%) of which were caused by Epstein–Barr virus (EBV), 55 (17.3%) by enteroviruses (EV), 36 (11.3%) by varicella–zoster virus (VZV), 31 (9.7%) by cytomegalovirus (CMV), 25 (7.8%) by herpes simplex virus type 1 (HSV-1), and 20 (6.3%) by human herpesvirus 6 (HHV-6). Results were compared with 3099 CSF samples from patients with encephalitis collected between 2002 to 2012, which were tested by specific PCR assays. Diagnosis was made in 337 (10.9%) of these cases, and 91 (27%) were CMV, 79 (23.4%) were VZV, 72 (21.4%) were EBV, 39 (11.6%) were EVs, 39 (11.6%) were HSV-1, 33 (9.8%) were HSV-2, and 2 (0.6%) were Dengue virus (DENV). The change in the pattern toward EVs as a major cause of viral encephalitis was unexpected, and a change in viral neurotropism may be responsible.

2009 ◽  
Vol 53 (12) ◽  
pp. 5251-5258 ◽  
Author(s):  
Mark N. Prichard ◽  
Debra C. Quenelle ◽  
Caroll B. Hartline ◽  
Emma A. Harden ◽  
Geraldine Jefferson ◽  
...  

ABSTRACT A series of 4′-thionucleosides were synthesized and evaluated for activities against orthopoxviruses and herpesviruses. We reported previously that one analog, 5-iodo-4′-thio-2′-deoxyuridine (4′-thioIDU), exhibits good activity both in vitro and in vivo against two orthopoxviruses. This compound also has good activity in cell culture against many of the herpesviruses. It inhibited the replication of herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus with 50% effective concentrations (EC50s) of 0.1, 0.5, and 2 μM, respectively. It also inhibited the replication of human cytomegalovirus (HCMV) with an EC50 of 5.9 μM but did not selectively inhibit Epstein-Barr virus, human herpesvirus 6, or human herpesvirus 8. While acyclovir-resistant strains of HSV-1 and HSV-2 were comparatively resistant to 4′-thioIDU, it retained modest activity (EC50s of 4 to 12 μM) against these strains. Some ganciclovir-resistant strains of HCMV also exhibited reduced susceptibilities to the compound, which appeared to be related to the specific mutations in the DNA polymerase, consistent with the observed incorporation of the compound into viral DNA. The activity of 4′-thioIDU was also evaluated using mice infected intranasally with the MS strain of HSV-2. Although there was no decrease in final mortality rates, the mean length of survival after inoculation increased significantly (P < 0.05) for all animals receiving 4′-thioIDU. The findings from the studies presented here suggest that 4′-thioIDU is a good inhibitor of some herpesviruses, as well as orthopoxviruses, and this class of compounds warrants further study as a therapy for infections with these viruses.


1999 ◽  
Vol 37 (4) ◽  
pp. 950-953 ◽  
Author(s):  
Sophie Minjolle ◽  
C. Michelet ◽  
I. Jusselin ◽  
M. Joannes ◽  
F. Cartier ◽  
...  

We used a novel type of primer system, a system that uses stair primers, in which the primer sequences are based on consensus sequences in the DNA polymerase gene of herpesvirus to detect herpesviruses by PCR. A single PCR in a single tube detected the six major herpesviruses that infect the central nervous system: herpes simplex virus type 1 (HSV-1), and type 2 (HSV-2), cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella-zoster virus (VZV), and human herpesvirus 6 (HHV-6). We used the technique to analyze 142 cerebrospinal fluid (CSF) samples that had been stored at −80°C and compared the results with those obtained previously for the same samples by standard, targeted PCR. Four hundred one targeted PCR tests had been run with the 142 samples to detect HSV-1, HSV-2, CMV, and VZV; screening for EBV and HHV-6 was not prescribed when the samples were initially taken. Eighteen CSF samples tested positive by classic targeted PCR. The herpesvirus consensus PCR detected herpesviruses in 37 samples, including 3 samples with coinfections and 17 viral isolates which were not targeted. Two samples identified as infected by the targeted PCR tested negative by the consensus PCR, and eight samples that tested positive by the consensus PCR were negative by the targeted PCR. One hundred three samples scored negative by both the targeted and the consensus PCRs. This preliminary study demonstrates the value of testing for six different herpesviruses simultaneously by a sensitive and straightforward technique rather than screening only for those viruses that are causing infections as suggested by clinical signs.


2014 ◽  
Vol 7 (2) ◽  
pp. 109-118
Author(s):  
Jana Blaškovičová ◽  
Ján Labuda

Abstract Genomics is a branch of bioanalytical chemistry characterized as the study of the genome structure and function. Genome represents the complete set of chromosomal and extrachromosomal genes of an organism, a cell, an organelle or a virus. There are at least five from eight species of herpesviruses commonly widespread among humans, Herpes simplex virus type 1 and 2, Varicella zoster virus, Epstein-Barr virus and Cytomegalovirus. Human gammaherpesviruses can cause serious diseases including B-cell lymphoma and Kaposi’s sarcoma. Diagnostics and study of the herpesviruses is directly dependent on the development of modern analytical methods able to detect and determine the presence and evolution of herpesviral particles/ genomes. Diagnostics and genomic characterization of human herpesvirus species is based on bioanalytical methods such as polymerase chain reaction (PCR), DNA sequencing, gel electrophoresis, blotting and others. The progress in analytical approaches in the herpesvirus genomics is reviewed in this article.


2019 ◽  
Vol 39 (03) ◽  
pp. 369-382 ◽  
Author(s):  
Tehmina Bharucha ◽  
Catherine F. Houlihan ◽  
Judith Breuer

AbstractThere are over 200 herpesvirus species, of which 10 affect humans. Each of these 10 herpesviruses has a unique clinical syndrome, but common to all is their ability to cause infection and pathology in the central nervous system. In this article, we discuss the epidemiology, clinical presentation, diagnostic modalities, treatment, sequelae, and availability of vaccination of each of the following herpesviruses: herpes simplex virus 1 and 2, varicella zoster virus, human cytomegalovirus, human herpesvirus 6A, 6B, and 7, Epstein–Barr virus, human herpesvirus 8, and simian herpesvirus B.


2005 ◽  
Vol 49 (3) ◽  
pp. 1039-1045 ◽  
Author(s):  
Earl R. Kern ◽  
Nicole L. Kushner ◽  
Caroll B. Hartline ◽  
Stephanie L. Williams-Aziz ◽  
Emma A. Harden ◽  
...  

ABSTRACT We have reported previously that methylenecyclopropane analogs of nucleosides have excellent activity against certain members of the herpesvirus family. A second generation, the 2,2-bis-hydroxymethyl derivatives, were synthesized, and 18 compounds were tested for activity in vitro against herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), human and murine cytomegalovirus (HCMV and MCMV), varicella-zoster virus (VZV), and Epstein-Barr virus (EBV). Selected analogs were also evaluated against human herpesvirus type 6 (HHV-6) and HHV-8. None of the 18 compounds had activity against HSV-1 or HSV-2, but four were active against VZV by plaque reduction (PR) assay at 50% effective concentration (EC50) levels of ≤50 μM. Six of the 18 compounds were active against HCMV by cytopathic effect or PR assays with EC50s of 0.5 to 44 μM, and all were active against MCMV by PR (0.3 to 54 μM). Four of the compounds were active against EBV by enzyme-linked immunosorbent assay (<0.3 to 4.4 μM). Four compounds with CMV activity were also active against HHV-6A and HHV-6B (0.7 to 28 μM), and three compounds were active against HHV-8 (5.5 to 16 μM). One of these, ZSM-I-62, had particularly good activity against CMV, HHV-6, and HHV-8, with EC50s of 0.7 to 8 μM. Toxicity was evaluated in adherent and nonadherent cells, and minimal cytotoxicity was observed. Mechanism of action studies with HCMV suggested that these compounds are phosphorylated by the ppUL97 phosphotransferase and are potent inhibitors of viral DNA synthesis. These results indicate that at least one of these compounds may have potential for use in treating CMV and other herpesvirus infections in humans.


2014 ◽  
Vol 58 (8) ◽  
pp. 4328-4340 ◽  
Author(s):  
Natacha Coen ◽  
Sophie Duraffour ◽  
Kazuhiro Haraguchi ◽  
Jan Balzarini ◽  
Joost J. van den Oord ◽  
...  

ABSTRACTThe emergence of drug-resistant herpesviruses represents a significant problem in clinical practice, primarily in immunocompromised patients. Furthermore, effective antiviral therapies against gammaherpesvirus-associated diseases are lacking. Here, we present two thiothymidine derivatives, KAY-2-41 and KAH-39-149, with different spectra of antiviral activity from those of the reference antiherpetic drugs, showing inhibitory activities against herpes simplex virus, varicella-zoster virus (VZV), and particularly against Epstein-Barr virus, with high selectivityin vitro. While KAY-2-41- and KAH-39-149-resistant herpesviruses were found to harbor mutations in the viral thymidine kinase (TK), these mutations conferred only low levels of resistance to these drugs but high levels to other TK-dependent drugs. Also, antiviral assays in HeLa TK-deficient cells showed a lack of KAY-2-41 and KAH-39-149 activities against herpes simplex virus 1 (HSV-1) and HSV-2 TK-deficient mutants. Furthermore, enzymatic TK assays showed the ability of HSV-1 TK, VZV TK, and cellular TK1 and TK2 to recognize and phosphorylate KAY-2-41 and KAH-39-149. These results demonstrate that the compounds depend on both viral and host TKs to exert antiviral activity. Additionally, the antiviral efficacy of KAH-39-149 proved to be superior to that of KAY-2-41 in a mouse model of gammaherpesvirus infection, highlighting the potential of this class of antiviral agents for further development as selective therapeutics against Epstein-Barr virus.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S736-S736
Author(s):  
Melissa R Gitman ◽  
Michael D Nowak ◽  
Allison Navis ◽  
Emilia Mia. Sordillo

Abstract Background Syndromic molecular panels enable rapid diagnosis and optimized management of infections with significant morbidity and mortality, but may be overused without clear guidelines. A recent report indicated there was little clinical suspicion of infection in up to 1/3 of cases for which a FILMARRAY® Meningitis/Encephalitis Panel (ME Panel, bioMérieux) was ordered. We recently implemented the ME Panel in our multicenter health system. We assessed ME Panel use for the 6-month period following test implementation. Methods A testing algorithm was developed, vetted with our system-wide Infectious Diseases (ID) and Neuro-ID Services, and used as the basis for the education of the Emergency Medicine, Internal Medicine, Hospitalist, Pediatric, and Critical Care Medicine Services. Algorithm elements were embedded in the electronic medical record (EMR). Lab records and EMRs were reviewed for all patients tested by ME Panel or cerebrospinal (CSF) culture. Lab results, baseline demographic and underlying medical history, and results of singleplex viral PCR CSF tests and the multiplex NY State Encephalitis PCR Panel (NYS Panel, Wadsworth Laboratory, Albany, NY) were recorded. ME Panel results were compared with other findings. Results 115 ME Panels were performed, with 5 (4%) positives [1 N.meningitidis, 1 H.influenzae, 1 cytomegalovirus (CMV), 1 Herpes simplex virus type 1 (HSV1), and 1 varicella zoster virus (VZV)]. Other findings were consistent with true infection for the N. meningitis, HSV and VZV; the CMV was likely reactivation. Significance of the H. influenzae was unclear. There were 830 CSF cultures, with 38 (4%) positive; 5 of the 38 were ME Panel targets. 29 NYS Panels were sent [1 positive each for Human Herpesvirus 6 (HHV6) and Epstein Barr Virus (EBV)]. Finally, 7 singleplex PCRs were positive [5 HSV, 1 CMV and 1 HHV6], including one negative by ME Panel. Conclusion We did not find ME Panel overuse; rather, we found several cases for which the ME Panel could have given a more rapid diagnosis. We did identify areas for improvement in test ordering, such as minimizing duplicate testing (e.g., singleplex PCR) A multi-disciplinary approach engaging stakeholders in the lab, ID and Neuro-ID can assist appropriate test utilization and diagnostic stewardship. Disclosures All authors: No reported disclosures.


2005 ◽  
Vol 49 (9) ◽  
pp. 3724-3733 ◽  
Author(s):  
Stephanie L. Williams-Aziz ◽  
Caroll B. Hartline ◽  
Emma A. Harden ◽  
Shannon L. Daily ◽  
Mark N. Prichard ◽  
...  

ABSTRACT Cidofovir (CDV) is an effective therapy for certain human cytomegalovirus (HCMV) infections in immunocompromised patients that are resistant to other antiviral drugs, but the compound is not active orally. To improve oral bioavailability, a series of lipid analogs of CDV and cyclic CDV (cCDV), including hexadecyloxypropyl-CDV and -cCDV and octadecyloxyethyl-CDV and -cCDV, were synthesized and found to have multiple-log-unit enhanced activity against HCMV in vitro. On the basis of the activity observed with these analogs, additional lipid esters were synthesized and evaluated for their activity against herpes simplex virus (HSV) types 1 and 2, human cytomegalovirus, murine cytomegalovirus, varicella-zoster virus (VZV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and HHV-8. Using several different in vitro assays, concentrations of drug as low as 0.001 μM reduced herpesvirus replication by 50% (EC50) with the CDV analogs, whereas the cCDV compounds were generally less active. In most of the assays performed, the EC50 values of the lipid esters were at least 100-fold lower than the EC50 values for unmodified CDV or cCDV. The lipid analogs were also active against isolates that were resistant to CDV, ganciclovir, or foscarnet. These results indicate that the lipid ester analogs are considerably more active than CDV itself against HSV, VZV, CMV, EBV, HHV-6, and HHV-8 in vitro, suggesting that they may have potential for the treatment of infections caused by a variety of herpesviruses.


2018 ◽  
Vol 80 (5-6) ◽  
pp. 229-235 ◽  
Author(s):  
Agata Czarnowska ◽  
Katarzyna Kapica-Topczewska ◽  
Olga Zajkowska ◽  
Renata Świerzbińska ◽  
Monika Chorąży ◽  
...  

Background: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system that leads to inflammation, demyelination and neurodegeneration. Viral aetiology has been suspected to be an MS trigger for a long time, and herpesviruses (HSs) are among the potential pathogens involved. Objectives: The present investigation aims to detect the presence of antibodies against the herpes simplex virus (HSV), varicella-zoster virus, Epstein-Barr virus (EBV), human cytomegalovirus (CMV) and human herpesvirus 6 (HHV6) in the serum of MS patients and control individuals in north-eastern Poland. Method: Plasma was collected from 141 MS patients and 44 blood donors who served as the control group. These individuals were assessed for the presence of antibodies using an enzyme-linked immunosorbent assay. Results: The statistical analysis showed a higher probability of EBV (p = 0.037, OR 4.359) and HHV6 (p = 0.020, OR 3.343) antibody presence in patients with MS compared to that in the control group. In the MS patient group, the prevalence of CMV IgG antibodies was significantly higher in females (p = 0.025). Patients who tested positive for anti-EBV IgG were diagnosed 7.9 years earlier than patients who tested negative for anti-EBV IgG (p = 0.048). Conclusions: The study showed that MS patients in north-eastern Poland were more likely to be seropositive for EBV and HHV6 than healthy individuals. Further work should be undertaken in other regions of Poland and other European countries with particular attention paid to testing seropositivity in all HSs, particularly in the MS patient population, to evaluate the impact of HSs on MS patients in different environments.


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