Enterovirus and Parechovirus meningitis in children: a review of the epidemiology, diagnostic challenges, and significance of on-site CSF virology tests in tropical paediatric patients’ care

Enteroviruses and Parechoviruses are increasingly recognized as the cause of aseptic meningitis, especially in the paediatric age group. However, because of indistinguishable clinical features with bacterial meningitis, many clinicians cannot make a clear distinction in disease presentation, and a large number of cases go undiagnosed. Although polymerase chain reaction is the current standard diagnostic approach, it takes many hours or days to get a result and these tests are not available at primary and secondary levels of care in many resource-poor countries. Furthermore, diagnosis is often difficult in children due to nonspecific cellular and biochemical cerebrospinal fluid findings. Some affected children may develop neurologic or/and systemic complications, resulting in prolonged hospital admission, increasing the risk of avoidable deaths, and healthcare expenditures. This review focuses on epidemiology, presentation, and diagnosis of Enterovirus and Parechovirus meningitis, highlighting the challenges in diagnosis and the potential roles of on-site CSF virology tests in improving the quality of paediatric patient’s care. The information provided should help early case detection, thereby ensuring avoidance of unnecessary antibiotics, minimal complications, a short period of hospital stays, and a reduction in healthcare-associated costs. Keywords: Aseptic meningitis; Enterovirus; Parechovirus; Diagnostic challenge; On-site virology test; Children   FrenchTitle: Méningite à Entérovirus et Parechovirus chez les enfants: un examen de l’épidémiologie, des défis diagnostiques et de l’importance du tests virologique sur site du LCR dans les soins aux patients pédiatriques tropicaux   Les entérovirus et les parechovirus sont de plus en plus reconnus comme la cause de la méningite aseptique, en particulier dans le groupe d'âge pédiatrique. Cependant, en raison des caractéristiques cliniques indiscernables de la méningite bactérienne, de nombreux cliniciens ne peuvent pas faire une distinction claire dans la présentation de la maladie, et un grand nombre de cas ne sont pas diagnostiqués. Bien que la réaction en chaîne par polymérase soit l'approche diagnostique standard actuelle, il faut plusieurs heures ou jours pour obtenir un résultat et ces tests ne sont pas disponibles aux niveaux de soins primaires et secondaires dans de nombreux pays pauvres en ressources. En outre, le diagnostic est souvent difficile chez les enfants en raison de découvertes non spécifiques du liquide céphalo-rachidien cellulaire et biochimique. Certains enfants atteints peuvent développer des complications neurologiques ou systémiques, entraînant une hospitalisation  prolongée, augmentant le risque de décès évitables et les dépenses de santé. Cette revue se concentre sur l'épidémiologie, la présentation et le diagnostic de la méningite à entérovirus et parechovirus, mettant en évidence les défis du diagnostic et les rôles potentiels des tests virologiques sur place dans le LCR dans  l'amélioration de la qualité des soins aux patients pédiatriques. Les informations fournies devraient contribuer à la détection précoce des cas, garantissant ainsi d'éviter les antibiotiques inutiles, des complications minimales, une courte période d'hospitalisation et une réduction des coûts associés aux soins de santé. Mots clés: méningite aseptique; Entérovirus; Parechovirus; Défi diagnostique; Test de virologie sur place;  Enfant

Establishment of national primary immunodeficiency network, requisite of health organization and final stage of polio eradication: Review article

Primary immunodeficiency diseases (PIDs) is a diverse group of diseases, characterized by a defect in the immune system. These patients are susceptible to recurrent respiratory infections, gastrointestinal problems, autoimmune diseases, and malignancies. In most cases, patients with primary immunodeficiency disorders have genetic defects and are monogenic disorders that follow a simple Mendelian inheritance, however, some PIDs recognize a more complex polygenic origin. Overall, almost 70 to 90 percent of patients with primary immunodeficiency are undiagnosed. Given that these patients are exposing to respiratory infectious agents and some live-attenuated vaccines, thus they have a high risk to some clinical complications. The administration of oral polio vaccine in patients with PIDs especially can increase the possibility of acute flaccid paralysis. These patients will excrete the poliovirus for a long time through their feces, even though they are not paralyzed. Long-term virus proliferation in the vaccinated individuals causes a mutation in the poliovirus and creates a vaccine-derived polioviruses (VDPVs), which is a major challenge to the final stages of the worldwide eradication of polio. To increase the diagnosis and identification of patients with immunodeficiency and carrying out a national plan for screening patients with immunodeficiency from the fecal excretion of the poliovirus, a possible polio epidemic can be prevented during post-eradication. Development of laboratory facilities in provincial and city centers, improvement of communications among physicians regarding medical consultation and establishment of referring systems for patients by national network lead to improve status of diagnosis and treatment of patients with primary immunodefiicencies. In this context, launching and activating the national network of immunodeficiency diseases is essential for improving the health of children and reducing the cost of the health system of the country. A national network of immunodeficiency can lead to increase awareness of physiciansregarding primary immunodeficiency disorders, improve collaboration among physicians about genetic consultation and establish a practical referral system in Iran that resultsin increased diagnosis and improve treatment of patients with primary immunodeficiency disorders. © 2020 Tehran University of Medical Sciences. All rights reserved

Efficient inhibition of human immunodeficiency virus replication using novel modified microRNA-30a targeting 3'-untranslated region transcripts

RNA interference (RNAi)-based gene therapy is currently considered to be a combinatorial anti-human immunodeficiency virus-1 (HIV-1) therapy. Although arti­ficial polycistronic microRNAs (miRs) can reduce HIV-1 escape mutant variants, this approach may increase the risk of side effects. The present study aimed to optimize the efficiency of anti-HIV RNAi gene therapy in order to reduce the cell toxicity induced by multi-short hairpin RNA expression. An artificial miR-30a-3'-untranslated region (miR-3'-UTR) obtained from a single RNA polymerase II was used to simultaneously target all viral transcripts. The results of the present study demonstrated that HIV-1 replication was signifi­cantly inhibited in the cells with the miR-3'-UTR construct, suggesting that miR-3'-UTR may serve as a promising tool for RNAi-based gene therapy in the treatment of HIV-1. © 2016, Spandidos Publications. All Rights Reserved

Patients with primary immunodeficiencies are a reservoir of poliovirus and a risk to polio eradication

ABSTARCT: Immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) have been isolated from primary immunodeficiency (PID) patients exposed to oral poliovirus vaccine (OPV). Patients may excrete poliovirus strains for months or years; the excreted viruses are frequently highly divergent from the parental OPV and have been shown to be as neurovirulent as wild virus. Thus, these patients represent a potential reservoir for transmission of neurovirulent polioviruses in the post-eradication era. In support of WHO recommendations to better estimate the prevalence of poliovirus excreters among PIDs and characterize genetic evolution of these strains, 635 patients including 570 with primary antibody deficiencies and 65 combined immunodeficiencies were studied from 13 OPV-using countries. Two stool samples were collected over 4 days, tested for enterovirus, and the poliovirus positive samples were sequenced. Thirteen patients (2%) excreted polioviruses, most for less than 2 months following identification of infection. Five (0.8%) were classified as iVDPVs (only in combined immunodeficiencies and mostly poliovirus serotype 2). Non-polio enteroviruses were detected in 30 patients (4.7%). Patients with combined immunodeficiencies had increased risk of delayed poliovirus clearance compared to primary antibody deficiencies. Usually, iVDPV was detected in subjects with combined immunodeficiencies in a short period of time after OPV exposure, most for less than 6 months. Surveillance for poliovirus excretion among PID patients should be reinforced until polio eradication is certified and the use of OPV is stopped. Survival rates among PID patients are improving in lower and middle income countries, and iVDPV excreters are identified more frequently. Antivirals or enhanced immunotherapies presently in development represent the only potential means to manage the treatment of prolonged excreters and the risk they present to the polio endgame. Keywords: Poliovirus eradication, Immunodeficiency-associated vaccine-derived polioviruses, Oral poliovirus vaccine, Humoral immunodeficiency, Combined immunodeficiency, Primary immunodeficienc

Association between circulating rotavirus genotypes and histo-blood group antigens in the children hospitalized with acute gastroenteritis in Iran

Rotaviruses are the dominant cause of severe acute gastroenteritis in children under 5 years of age. Previous studies showed that some children are less susceptible to rotavirus gastroenteritis. It has been shown that this resistance depends on the rotavirus genotype and also human histo-blood group antigens (HBGAs), which works as a receptor for rotavirus surface protein (VP4). The present study aimed to evaluate the human genetic susceptibility to rotavirus gastroenteritis in Iran and to obtain a comparative analysis between rotavirus gastroenteritis and secretor or Lewis status in case and control groups in the Iranian population. The study was performed on fecal specimens from 108 children with acute rotavirus gastroenteritis from 2015 to 2017. A total of 50 fecal specimens from children with acute gastroenteritis of unknown etiology were also used as a control group. After the genotyping of positive rotavirus cases and human HBGAs by Sanger sequencing, the phylogenetic tree analysis showed that all rotavirus strains from Iran belonged to PII. The most common genotype was P8 (n = 102; 94.4%), while the remaining belonged to P4 (n = 3; 2.8%) and P6 (n = 3; 2.8%) genotypes. The P8 genotype was found to be associated with secretor and Lewis positive status (p <.05). © 2021 Wiley Periodicals LL

First Report of Respiratory Syncytial Virus and Human Metapneumovirus Co-Infection in a 2-Year-Old Kawasaki Patient in Iran

Background: Respiratory virus infections in children are a leading cause of morbidity and mortality worldwide. Methods: A total of 897 clinical specimens were collected from February 2007 to January 2008 and transported to the Na&amp;shy;tional Influenza Center. Two hundred and two samples belonged to children under the age of six from 897 specimens, de&amp;shy;scribed above, were selected. Then they were tested for influenza virus types and subtypes by real time PCR assay subse&amp;shy;quently, the specimens were tested for RSV and hMPV by hemi-nested multiplex PCR and parainfluenza viruses type 1-4 by hemi-nested multiplex PCR and adenovirus by hemi-nested PCR. Results: The throat swab was taken from the Kawasaki case with the history of chicken`s contact. The specimen was tested for all influenza subtypes especially H5N1 and the results were negative. Meanwhile PCR was done for screening of other respira&amp;shy;tory viruses that results came out positive for RSV and hMPV. Conclusion: In the present study, we demonstrated the possibility to detect dual infection caused by RSV and hMPV, but be&amp;shy;cause of the extravagant pattern of this case, more investigation is suggested specially on Kawasaki patients

Prevalence of human herpesvirus-8 among HIV-infected patients, intravenous drug users and the general population in Iran

Studies looking at the frequency of human herpesvirus-8 (HHV-8) among Iranian blood donors have produced conflicting results. The aim of this study was to investigate the prevalence of HHV-8 DNA by using polymerase chain reaction methods among 168 healthy individuals, 60 intravenous drug users and 100 HIV-infected patients from Iran. The prevalence of HHV-8 was significantly higher among intravenous drug users (13.3) compared with the general population (3.6; P�0.017). The HHV-8 genome was mostly detected among intravenous drug users who displayed high-risk sexual behaviours. Moreover, the HHV-8 genome was also detected in 8 of HIV-infected patients. The present study findings support the likelihood that the transmission of HHV-8 is via a sexual route in the Iranian population. Journal compilation © CSIRO 2016

First report of human parvovirus 4 detection in Iran

Parvovirus 4 (PARV4) is an emerging and intriguing virus that currently received many attentions. High prevalence of PARV4 infection in high-risk groups such as HIV infected patients highlights the potential clinical outcomes that this virus might have. Molecular techniques were used to determine both the presence and the genotype of circulating PARV4 on previously collected serum samples from 133 HIV infected patients and 120 healthy blood donors. Nested PCR was applied to assess the presence of PARV4 DNA genome in both groups. PARV4 DNA was detected in 35.3 of HIV infected patients compared to 16.6 healthy donors. To genetically characterize the PARV4 genotype in these groups, positive samples were randomly selected and subjected for sequencing and phylogenetic analysis. All PARV4 sequences were found to be genotype 1 and clustered with the reference sequences of PARV4 genotype 1. © 2016 Wiley Periodicals, Inc