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Fulltext Inhibition of enterovirus 71 infection by antisense octaguanidinium dendrimer-conjugated morpholino oligomers

Tan CW, Chan YF, Quah YW, Poh CL

Antiviral Res, 2014 Jul;107:35-41.
PMID: 24769243 DOI: 10.1016/j.antiviral.2014.04.004

Enterovirus 71 (EV-71) infections are generally manifested as mild hand, foot and mouth disease, but have been reported to cause severe neurological complications with high mortality rates. Treatment options remain limited due to the lack of antivirals. Octaguanidinium-conjugated morpholino oligomers (vivo-MOs) are single-stranded DNA-like antisense agents that can readily penetrate cells and reduce gene expression by steric blocking of complementary RNA sequences. In this study, inhibitory effects of three vivo-MOs that are complementary to the EV-71 internal ribosome entry site (IRES) and the RNA-dependent RNA polymerase (RdRP) were tested in RD cells. Vivo-MO-1 and vivo-MO-2 targeting the EV-71 IRES showed significant viral plaque reductions of 2.5 and 3.5 log10PFU/ml, respectively. Both vivo-MOs reduced viral RNA copies and viral capsid expression in RD cells in a dose-dependent manner. In contrast, vivo-MO-3 targeting the EV-71 RdRP exhibited less antiviral activity. Both vivo-MO-1 and 2 remained active when administered either 4h before or within 6h after EV-71 infection. Vivo-MO-2 exhibited antiviral activities against poliovirus (PV) and coxsackievirus A16 but vivo-MO-1 showed no antiviral activities against PV. Both the IRES-targeting vivo-MO-1 and vivo-MO-2 inhibit EV-71 RNA translation. Resistant mutants arose after serial passages in the presence of vivo-MO-1, but none were isolated against vivo-MO-2. A single T to C substitution at nucleotide position 533 was sufficient to confer resistance to vivo-MO-1. Our findings suggest that IRES-targeting vivo-MOs are good antiviral candidates for treating early EV-71 infection, and vivo-MO-2 is a more favorable candidate with broader antiviral spectrum against enteroviruses and are refractory to antiviral resistance.

Matched MeSH terms: Poliovirus/drug effects
Fulltext A Cross-Sectional Survey of Healthcare Workers on the Knowledge and Attitudes towards Polio Vaccination in Pakistan

Khan MU, Ahmad A, Aqeel T, Akbar N, Salman S, Idress J

PLoS One, 2015;10(11):e0142485.
PMID: 26559184 DOI: 10.1371/journal.pone.0142485

INTRODUCTION: Pakistan accounts for 85.2% of the total polio cases reported worldwide. Healthcare workers (HCWs) are an integral part of immunization campaigns and source of education for the general public. This study aimed to assess the knowledge and attitudes towards polio vaccination among HCWs providing immunisation and education to general public in Quetta and Peshawar divisions of Pakistan.
METHODS: A cross-sectional survey of 490 HCWs was conducted in two major referral public teaching hospitals of Quetta and Peshawar divisions. During February to April, 2015, a random sample of 490 HCWs was invited to participate in this study. Knowledge and attitudes were assessed by using self-administered, anonymous and pretested questionnaire. Descriptive and logistic regression analyses were used to express the results.
RESULTS: A total of 468 participants responded to the questionnaire, giving a response rate of 95.5%. Overall, participants demonstrated good knowledge and positive attitudes towards polio vaccination. The mean knowledge score of HCWs about polio was 13.42 ± 2.39 (based on 18 knowledge questions) while the mean attitude score was 28.75 ± 5.5 (based on 9 attitudes statements). Knowledge gaps were identified about the incubation period of poliovirus (19.5%), management issues (31.9%), use of polio vaccine in mild illnesses (34.7%) and the consequences of the polio virus (36.9%). The majority of participants agreed that all children should be vaccinated for polio (95.1%), while reservations were noted about the need of a booster (38.9%), and sterility issues associated with polio vaccines (43.6%). Internet (n = 167, 37%) and Posters (n = 158, 35%) were the main sources used by HCWs to educate themselves about polio.
CONCLUSION: Participants in this study had good knowledge and positive attitudes towards polio vaccination. Although the data are indicative of gaps in the knowledge of HCWs, the findings may not be generalized to other hospitals in Pakistan.

Matched MeSH terms: Poliovirus Vaccines/immunology*
Challenges to health workers and their opinions about parents' refusal of oral polio vaccination in the Khyber Pakhtoon Khawa (KPK) province, Pakistan

Khan TM, Sahibzada MU

Vaccine, 2016 Apr 19;34(18):2074-81.
PMID: 26993330 DOI: 10.1016/j.vaccine.2016.03.008

A qualitative study design was adapted to explore the challenges faced by health workers (HWs) during the polio health campaign. In addition, HWs' opinions about the factors causing parents to refuse oral polio vaccination (OPV) were also explored. Four focus group discussions (FGDs) were held (from 1st January 2015-31st March 2015) with the HWs who participated in the OPV campaigns in the polio red zones of Khyber Pakhtoon Khawa (KPK) province of Pakistan, namely Kohat (FG 1), Domel and Bannu (FG 2), Hangoo (FG 3), and Peshawar (FG 4). A total of N=42 HWs (10-11 in each FG) agreed to participate in this study. Overall, HWs disclosed that public attitude and harsh behaviour towards the HWs and security threats are the two main challenges they face. Common issues hindering parents' willingness to vaccinate their children against OPV are: OPV is seen as haram and not permitted in Islam, it is said to contain the blood of pigs (Khinzir) and monkeys, and parents are afraid that it is done to induce sterility among their children. HWs also shared that parents have a strong belief in the conspiracies that are associated with OPV, i.e. the USA and CIA, are spying on us and our government is helping them to achieve their agenda. Furthermore, HWs revealed that frequent visits may further strengthen parents' perceptions and make them more resistant to OPV. The common side effects of OPV reported by parents were mainly gastro-intestinal problems and in some cases mild to moderate fever with some respiratory symptoms. There is a great need to improve the logistics and facilities for HWs assisting in vaccination programmes. Furthermore, it is necessary to improve education, so people understand the basic concept of revaccination and booster doses, thereby assisting in creating a basic understanding of vaccinations, which may trigger changes in attitudes and make people believe in the benefits of OPV rather than following the conspiracies that lead them to refuse it.

Matched MeSH terms: Poliovirus Vaccine, Oral/administration & dosage*
Enterovirus-Specific Anti-peptide Antibodies

Poh CL, Kirk K, Chua HN, Grollo L

Methods Mol Biol, 2015;1348:341-50.
PMID: 26424285 DOI: 10.1007/978-1-4939-2999-3_29

Enterovirus 71 (EV-71) is the main causative agent of hand, foot, and mouth disease (HFMD) which is generally regarded as a mild childhood disease. In recent years, EV71 has emerged as a significant pathogen capable of causing high mortalities and severe neurological complications in large outbreaks in Asia. A formalin-inactivated EV71 whole virus vaccine has completed phase III trial in China but is currently unavailable clinically. The high cost of manufacturing and supply problems may limit practical implementations in developing countries. Synthetic peptides representing the native primary structure of the viral immunogen which is able to elicit neutralizing antibodies can be made readily and is cost effective. However, it is necessary to conjugate short synthetic peptides to carrier proteins to enhance their immunogenicity. This review describes the production of cross-neutralizing anti-peptide antibodies in response to immunization with synthetic peptides selected from in silico analysis, generation of B-cell epitopes of EV71 conjugated to a promiscuous T-cell epitope from Poliovirus, and evaluation of the neutralizing activities of the anti-peptide antibodies. Besides neutralizing EV71 in vitro, the neutralizing antibodies were cross-reactive against several Enteroviruses including CVA16, CVB4, CVB6, and ECHO13.

Matched MeSH terms: Poliovirus
Poliomyelitis in Malaysia: two confirmed cases after 6 years without polio

Ismail HI, Lal M

Ann Trop Paediatr, 1993;13(4):339-43.
PMID: 7506880

Poliomyelitis in Malaysia has not been reported since 1986. We report two cases of poliomyelitis in non-immunized children whose parents, though relatively educated, opted not to vaccinate their children for socio-cultural reasons. This recent trend may interfere with our attempts to eradicate poliomyelitis globally by the year 2000. The clinical features, pathophysiology and differential diagnosis are discussed.

Matched MeSH terms: Poliovirus Vaccine, Inactivated