Multiple Independent Emergences of Type 2 Vaccine-Derived Polioviruses during a Large Outbreak in Northern Nigeria

Multiple Independent Emergences of Type 2 Vaccine-Derived Polioviruses during a Large Outbreak in Northern Nigeria
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DOI:
10.1128/jvi.02954-12
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发表时间:
2013-05-01
影响因子:
5.4
通讯作者:
Kew, Olen
Kew, Olen
中科院分区:
医学2区
文献类型:
--
作者:
Burns, Cara C.;Shaw, Jing;Kew, Olen

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自2005年以来,北方尼日利亚发生了与2型循环疫苗衍生脊髓灰质炎病毒(cVDPV 2)相关的大规模脊髓灰质炎疫情,三价口服脊髓灰质炎病毒疫苗(tOPV)的免疫覆盖率一直很低。对2005年至2011年报告的403例病例中每例病例分离株的P1/衣壳区序列进行系统发育分析,将此次疫情分解为23个独立的2型疫苗衍生脊髓灰质炎病毒(VDPV 2)紧急事件,其中至少7个建立了循环谱系群。据估计,一次出现的病毒(谱系组2005-8; 361株分离株)已传播6年以上。主要cVDPV 2谱系组的群体在2009年初迅速扩大,在2009年中期两轮tOPV后急剧下降,并在2011年再次逐渐扩大。Sabin 2型口服脊髓灰质炎病毒疫苗株减毒的两个主要决定因素(5 '-非翻译区[5'-UTR]中的A(481)和VP 1-Ile(143))在所有VDPV 2分离株中均被替换;大多数A(481)5 '-UTR替换通过与其他肠道病毒重组发生。代表不同谱系组的cVDPV 2分离株具有与野生脊髓灰质炎病毒无法区分的生物学特性,包括在神经元衍生的HEK 293细胞中的有效生长、在人类和PVR-Tg 21转基因小鼠中引起麻痹性疾病的能力、温度敏感表型的丧失以及持续人与人传播的能力。我们根据脊髓灰质炎病例数和2型野生脊髓灰质炎病毒感染的麻痹病例与感染比率估计,疫情期间发生了类似于70万例cVDPV 2感染。在尼日利亚北方检测到多起同时发生的cVDPV 2型暴发,突出表明在发展中国家,随着tOPV使用覆盖率低,出现cVDPV的风险。
Since 2005, a large poliomyelitis outbreak associated with type 2 circulating vaccine-derived poliovirus (cVDPV2) has occurred in northern Nigeria, where immunization coverage with trivalent oral poliovirus vaccine (tOPV) has been low. Phylogenetic analysis of P1/capsid region sequences of isolates from each of the 403 cases reported in 2005 to 2011 resolved the outbreak into 23 independent type 2 vaccine-derived poliovirus (VDPV2) emergences, at least 7 of which established circulating lineage groups. Virus from one emergence (lineage group 2005-8; 361 isolates) was estimated to have circulated for over 6 years. The population of the major cVDPV2 lineage group expanded rapidly in early 2009, fell sharply after two tOPV rounds in mid-2009, and gradually expanded again through 2011. The two major determinants of attenuation of the Sabin 2 oral poliovirus vaccine strain (A(481) in the 5'-untranslated region [5'-UTR] and VP1-Ile(143)) had been replaced in all VDPV2 isolates; most A(481) 5'-UTR replacements occurred by recombination with other enteroviruses. cVDPV2 isolates representing different lineage groups had biological properties indistinguishable from those of wild polioviruses, including efficient growth in neuron-derived HEK293 cells, the capacity to cause paralytic disease in both humans and PVR-Tg21 transgenic mice, loss of the temperature-sensitive phenotype, and the capacity for sustained person-to-person transmission. We estimate from the poliomyelitis case count and the paralytic case-to-infection ratio for type 2 wild poliovirus infections that similar to 700,000 cVDPV2 infections have occurred during the outbreak. The detection of multiple concurrent cVDPV2 outbreaks in northern Nigeria highlights the risks of cVDPV emergence accompanying tOPV use at low rates of coverage in developing countries.