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Pediatric HIV Infection and Decreased Prevalence of OPV Point Mutations Linked to Vaccine-associated Paralytic Poliomyelitis.

ABSTRACT: Background:Mutations associated with prolonged replication of the attenuated polioviruses found in oral poliovirus vaccine (OPV) can lead to vaccine-derived poliovirus (VDPV) and cause paralysis indistinguishable from that caused by wild poliovirus. In response, the World Health Organization has initiated the transition to exclusive use of inactivated poliovirus vaccine (IPV), with OPV administration in cases of outbreak. However, it is currently unclear how IPV-only vaccination, well known to provide humoral but not mucosal immunity, will impact the development of paralysis causing OPV variants. Children infected with human immunodeficiency virus (HIV) have been documented to show decreased mucosal immunity following OPV vaccination. Thus, HIV-infected children vaccinated with OPV may serve as proxy for children with IPV-only vaccination. Methods:We conducted a prospective study of Zimbabwean infants receiving OPV as part of their routine vaccination schedule. Stool samples collected from OPV-vaccinated children serially until age 24 months were tested for OPV serotypes using a real-time polymerase chain reaction protocol that quantifies the amount of mutant OPV variants found in each sample. Results:Out of 2130 stool samples collected from 402 infants 365 stool samples were OPV positive: 313 from 212 HIV-noninfected (HIV-) infants and 52 from 34 HIV-infected (HIV+) infants. HIV- infants showed significantly higher proportions of OPV mutants when compared to HIV+ infants. Conclusions:HIV infection is associated with a reduced proportion of OPV vaccine associated paralytic polio mutants. These results suggest that OPV administered to individuals previously vaccinated only with IPV will show decreased propensity for OPV mutations.

SUBMITTER: Halpern MS

PROVIDER: S-EPMC6206102 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Pediatric HIV Infection and Decreased Prevalence of OPV Point Mutations Linked to Vaccine-associated Paralytic Poliomyelitis.

Halpern Meira S MS Altamirano Jonathan J Maldonado Yvonne Y

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20181001 suppl_1

<h4>Background</h4>Mutations associated with prolonged replication of the attenuated polioviruses found in oral poliovirus vaccine (OPV) can lead to vaccine-derived poliovirus (VDPV) and cause paralysis indistinguishable from that caused by wild poliovirus. In response, the World Health Organization has initiated the transition to exclusive use of inactivated poliovirus vaccine (IPV), with OPV administration in cases of outbreak. However, it is currently unclear how IPV-only vaccination, well kn ...[more]

PMID: 30376083

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Project description:Abstract Background The live vaccines bacille Calmette-Guérin (BCG) and measles vaccine have beneficial nonspecific effects (NSEs) reducing mortality, more than can be explained by prevention of tuberculosis or measles infection. Live oral polio vaccine (OPV) will be stopped after polio eradication; we therefore reviewed the potential NSEs of OPV. Methods OPV has been provided in 3 contexts: (1) coadministration of OPV and diphtheria-tetanus-pertussis (DTP) vaccine at 6, 10, and 14 weeks of age; (2) at birth (OPV0) with BCG; and (3) in OPV campaigns (C-OPVs) initiated to eradicate polio infection. We searched PubMed and Embase for studies of OPV with mortality as an outcome. We used meta-analysis to obtain the combined relative risk (RR) of mortality associated with different uses of OPV. Results First, in natural experiments when DTP was missing, OPV-only compared with DTP + OPV was associated with 3-fold lower mortality in community studies (RR, 0.33 [95% confidence interval {CI}, .14–.75]) and a hospital study (RR, 0.29 [95% CI, .11–.77]). Conversely, when OPV was missing, DTP-only was associated with 3-fold higher mortality than DTP + OPV (RR, 3.23 [95% CI, 1.27–8.21]). Second, in a randomized controlled trial, BCG + OPV0 vs BCG + no OPV0 was associated with 32% (95% CI, 0–55%) lower infant mortality. Beneficial NSEs were stronger with early use of OPV0. Third, in 5 population-based studies from Guinea-Bissau and Bangladesh, the mortality rate was 24% (95% CI, 17%–31%) lower after C-OPVs than before C-OPVs. Conclusions There have been few clinical polio cases reported in this century, and no confounding factors or bias would explain all these patterns. The only consistent interpretation is that OPV has beneficial NSEs, reducing nonpolio child mortality. Oral polio vaccine is associated with beneficial nonspecific effects in relation to its current use as a birth dose, as 3 infant doses coadministered with diphtheria-tetanus-pertussis vaccine, and as a campaign vaccine delivered to all children <5 years of age.

Project description:Four cases of acute flaccid paralysis caused by slightly evolved (Sabin-like) vaccine polioviruses of serotype 2 were registered in July to August 2010 in an orphanage of Biysk (Altai Region, Russia). The Biysk cluster of vaccine-associated paralytic poliomyelitis (VAPP) had several uncommon, if not unique, features. (i) Until this outbreak, Sabin-like viruses (in distinction to more markedly evolved vaccine-derived polioviruses [VDPVs]) were reported to cause only sporadic cases of VAPP. Consequently, VAPP cases were not considered to require outbreak-type responses. However, the Biysk outbreak completely blurred the borderline between Sabin-like viruses and VDPVs in epidemiological terms. (ii) The outbreak demonstrated a very high disease/infection ratio, apparently exceeding even that reported for wild polioviruses. The viral genome structures did not provide any substantial hints as to the underlying reason(s) for such pathogenicity. (iii) The replacement of intestinal poliovirus lineages by other Sabin-like lineages during short intervals after the disease onsets was observed in two patients. Again, the sequences of the respective genomes provided no clues to explain these events. (iv) The polioviruses isolated from the patients and their contacts demonstrated a striking heterogeneity as well as rapid and uneven evolution of the whole genomes and their parts, apparently due to extensive interpersonal contacts in a relatively small closed community, multiple bottlenecking, and recombination. Altogether, the results demonstrate several new aspects of pathogenicity, epidemiology, and evolution of vaccine-related polioviruses and underscore several serious gaps in understanding these problems.The oral poliovirus vaccine largely contributed to the nearly complete disappearance of poliovirus-caused poliomyelitis. Being generally safe, it can, in some cases, result in a paralytic disease. Two types of such outcomes are distinguished: those caused by slightly diverged (Sabin-like) viruses on the one hand and those caused by significantly diverged VDPVs on the other. This classification is based on the number of mutations in the viral genome region encoding a viral structural protein. Until now, only sporadic poliomyelitis cases due to Sabin-like polioviruses had been described, and in distinction from the VDPV-triggered outbreaks, they did not require broad-scale epidemiological responses. Here, an unusual outbreak of poliomyelitis caused by a Sabin-like virus is reported, which had an exceptionally high disease/infection ratio. This outbreak blurred the borderline between Sabin-like polioviruses and VDPVs both in pathogenicity and in the kind of responses required, as well as underscoring important gaps in understanding the pathogenicity, epidemiology, and evolution of vaccine-derived polioviruses.

Project description:BACKGROUND: Nigeria is one of the major African countries in which incidences of polio infection persist in spite of several eradication efforts. The preponderance of paralytic poliomyelitis particularly in the northern part of Nigeria raises the question as to whether parents of children affected with polio know how polio is contracted and spread, whether having a disabled child affects the parents' attitude towards these children, and what they believe about poliomyelitis in view of their socio-cultural and belief system in the sub-region. Zamfara State, in the north-west of Nigeria is one of the endemic areas where resistance to the global campaign on polio eradication was very high. Therefore this study was conducted to investigate the knowledge, attitudes and beliefs of parents/primary caregivers of children affected with paralytic poliomyelitis in Zamfara State. METHODS: This study is a cross-sectional survey in which the multistage probability sampling technique was used to randomly select two local government areas in Zamfara State where consenting parents/primary caregivers of children with paralytic poliomyelitis were purposively selected. The knowledge, attitudes and beliefs of parents were assessed with the aid of a 4-part 52-item structured researcher administered questionnaire and the data obtained were analyzed. RESULTS: Two hundred and seventeen parents/primary caregivers participated in the study. One hundred and forty-two, (65.4%) reported good, 51 (23.8%) reported fair, while 24 (11%) of participants reported poor knowledge of paralytic poliomyelitis. More respondents 120 (55.3%) showed a positive attitude towards children with paralytic poliomyelitis. Younger age (P=0.016) and paid employment (P=0.020) were positively associated with good knowledge of paralytic poliomyelitis. Female gender (P=0.020), higher educational level (P=0.015), being employed (P=0.010) and having from middle to high household income (P=0.016) were positively associated with a positive attitude toward children with paralytic poliomyelitis. Most respondents showed a reasonable belief over the cause of their children's condition rather than the erroneous traditional belief that paralytic poliomyelitis is caused by spirit forces. CONCLUSIONS: It is of great concern that the good knowledge, positive attitude and reasonable belief by parents/primary caregivers about paralytic poliomyelitis observed in this study did not play a prominent role in preventing susceptibility of children in north-west Nigeria to paralytic poliomyelitis. It is imperative that Nigerian policy makers should device more strategic measures toward the prevention of paralytic poliomyelitis in this sub region.

Dataset Information

Pediatric HIV Infection and Decreased Prevalence of OPV Point Mutations Linked to Vaccine-associated Paralytic Poliomyelitis.

Publications

Pediatric HIV Infection and Decreased Prevalence of OPV Point Mutations Linked to Vaccine-associated Paralytic Poliomyelitis.

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